TOBACCO SMOKING AS A COPING MECHANISM IN PSYCHIATRIC PATIENTS:
PSYCHOLOGICAL, BEHAVIORAL AND PHYSIOLOGICAL INVESTIGATIONS
A Research Proposal
PHASE II'
1984 1985
Dr. Verner J. Knott
Royal Ottawa Hospital
March, 19R4
--J
BATCo document for Province of British Columbia 15 April 1999

TOBACCO SMOKING AS A COPING MECHANISM IN PSYCHIATRIC PATIENTS:
PSYCHOLOGICAL, BEHAVIORAL AND PHYSIOLOGICAL INVESTIGATIONS
Z
PHASE II
Dr. V. Knott
SUMMARY
This research proposal is focussed on the motivational mechanisms underlyin
excessive tobacco use in psychiatric patients. To some extent, resolution of th s
relationship is clarified by examining the characteristics of smokers and smoking
effects in normal populations. A review of the tobacco literature indicates that
in general smokers tend to exhibit personality and physiological profiles indicative
of hyper-arousal and responsivity and report that they smoke to reduce hyper-
arousal and responsivity. As experimental studies support the contention that
tobacco 'normalizes' excessive activation in smokers and as anxiety patients
exhibit extreme high-arousal-responsivity profiles, it is hypothesized that their
excessive tobacco use is a coping mechanism aimed at inhibiting the intrusivenes
of disruptive and excessive arousal upon ongoing physiological, behavioural and
cognitive processes. In order co examine possible tobacco-induced normalization
of arousal deficits in anxiety patients, schizophrenics and depressives, two
psychophysiological investigations are outlined which are aimed at examining,
(a) the effects of smoking abstinence and, (b) changes in smoking behaviors and
their impact during treatment progression in relation to a phasic electroence-
phalographic (EEG) based measure - the contingent negative variation (CNV) . The
choice of CNV is based on its proven sensitivity to diagnostic categories, smoker
vs non-smoker differences, tobacco effects and arousal processes. In addition to.
there studies a third (c) non-physiological investigation is outlined wh is
aimed at examining the relationship of smoker/non-smoker status and degree of
smoking in psychiatric patients to treatment outcome.
t
U-4
L..P4
co
BATCo document for Province of British Columbia 15 April 1999

C 0 N T E N T S
A. Background Summary
1. Tobacco Smoking: Emotionality, Mental Impairment .2
and Psychiatric Status
2. Tobacco Smoking; Biological Trait-State Factors 2
as Critical Motivational Elements
3. Clinical Anxiety: Psychophysiological Defect t5
in Arousal Processes
4. Tobacco Smoking: An Adaptive Tool for Regulation .7
of Arousal Processes
(a) Psychological Effects 7
(b) Behavioral Effects .8
(c) Physiological Effects 11
(d) Neurophysiological Effects 14
B. (a) Conclusions 15
(b) Objectives & Hypotheses 16
C. Slow Cortical EEG Potentials: A Psychophysiological I6a
Paradigm for the Study of Tobacco Smoking and Arousal
Processes in Psychiatric Patients
D. Method
1. Study 1: Effects of Smoking Abstinence on Symptomatology 2,0
and Psychiological Behavioral and Psychophysiological
Functioning in Psychiatric Patients and Normal Controls
2. Study II, Changes in Smoking Patterns and Their Effects 24
in Psychiatric Patients From Admission Through to
Discharge from Treatment
3. Study III: Smoking Status of Psychiatric Patients and 25
its Relationship to Treatment Outcome
E. References
-ch.
co
BATCo document for Province of British Columbia 15 April 1999

Tobacco Smoking As A --oping Mcchanism In Psychiatric Patients-
Psychological, Behavioral and Physiological Investigations
r
Verner J. Knott, D. Phil - 4
A. Background Sunmary
1. Tobacco Smoking: Emotionality, Mental Impairment and PsychiatrIc Statusl
Over the past two decades there has been a number of studies which have-
attempted to delineate the relationship between smoking and emotionality and
mental health in normal populations (Eysenck, 1980). A major focus of these
studies has been the relationship between smoking and personality Keith specif ic
interest on neuroticism (anxiety). Although inconsistencies are apparent, the
outcome of these studies on individual differences tend to indicate that
smokers are characterized by higher neuroticism scores on personality tests
than non-smokers (Matarazzo & Saslow, 1960; Eysenck, 1973; 1980; Kozlowski, !
1978) and on average there seems to be a positive correlation between anxiety
and the degree of smoking within the smoking population (eq. Thomas, 1978) t.
As with other studies and other variables however, whenever differences are
reported between smokers and non-smokers, it is usually impossible to deter.-Line
whether the differences reflect the consequences of smoking or possibly have
a causal relationship to smoking behavior. This objection applies to a lesser
extent to studies on child smokers and to studies where personality asses+e7 ts
were obtained prior to smoking onset. Powell, Stewart and Grylls (1979) examined
neuroticism along with a number of other dimensions on a sample of 608 middle-
class children between 7 and 16 years of age. More than half of the boys and
girls had tried smoking cigarettes by the age of 15 years. Of the children.
who tried, they were found to be particularly high on neuroticisn, as well-as
extroversion and psychopathy dimensions. The authors concluded that this
pattern is identical to that of children who are anxious and misbehave and do
not conform in a general sense. Similar studies exist to indicate that rebellious-
ness and antisocial traits were correlated with smoking in children and persisted
into adult smoking (Jamison, 1978; Steword & Livson, 1966). Cherry and
the' data
Kiernan's (1978) longitudinal study is of narticular interest in that kr
pertains to personality dimensions pro-dating the smoking habit for those 'who,
took up smoking after 16 years of age. It is clear from their data, that those
who are to become smokers are more neurotic, less stable and more, extroverted
than those who do not. Cherry & Kiernan's (197B) findings that young people with
high neufoticism scores were more likely to start Smoking than r.ore stal---le
adolescents is supported both by ' (1970) study which indicated that
situations of "nervous irritation" %..-ere co-%-..on occasions for smok.ing among'
adolescents and adults, and by Henderson, Le-wis and Howell and Roynar's (1981)
findings with a secondary school population where a significant positive , iI
association was found between the probability of a neurotic disorder and use
of tobacco.
UQ
co
N..)
BATCo document for Province of British Columbia 16 April 1999

-2-
Although this literature definitely supports a relationship
between anxiety and tobacco use in normal populations, relatively fc%,r
investigations have examined relationship between psychiatric impairment I
and smoking behavior. Lidenthal, Myers and Pepper's (1972) stands alone as
a clinical attempt to relate smoking behavior to psychological impairment
(as assessed by a me status exam) and subsequent changes in smoking
behavior as a result of life crises. Here, several significant-findings were
observed: (a) the more psychologically impaired an individual, the more
likely he is to report smoking' often and the less likely he is to report
himself as a non-smoker compared with someone who is psychologically
unimpaired; (b) at times of crises, increases in smoking are directly relateld
to psychological impairment; (c) as the number of crises increase, the
relationship between changes in smoking psychological impairment is
strengthened. These authors concluded that their data supported the notion
that smoking served as an adaptive behavior for coping with life's exigencies.
The relationship between smoking and psychiatric impairment is further
supported by Parr's (1963) observations an psychiatric inpatients with
diagnoses of anxiety and depression. Here, a greater incidence of kmokers
t
and very heavy smokers was observed in patients relative to the national i
average. Also observed was a change in desire to smoke on admission, with
half the patients reporting afi increased "need" for tobacco. Parr's (1963)
report is strongly buttressed by Salmons and Sims' (1981) study on smoking
profiles of patients admitted for neuroses. Here, neurotic patient's %-.ere f ind
more likely to be smokers, to have started at an earlier age, to be heavier!
smokers and to smoke more deeply than normal controls.
In summary then, their tends to be a strong relationship, perhaps causative,
between anxiety and tobacco use in both normal populations and in populatiol.1s
diagnosed as psychiatrically ill. But to establish this relationship does
not explain the critical motivational mechanisms and processes which initia e
and maintain it.
2. Tobacco Smoking: Biological Trait-State Factors as Critical Notivationall
Elements
Although it is generally stated that social and psychological factors are
responsible for the initiation of smoking, it is clear that no sharp line divides
the biological from the psychological and sociological. The kinds of inner
emotions that people experience in relation to environmental conditions and:
events is at the same time an expression of both psychological and biological
factors. These emotions and the environmental situations that are perceivedi
as rewarding or aversive will determine, at least in part, a wide variety of
behaviors including one's response to cigarette smoke (Jaffe and Jarvik, 1976).
individual differences in personality- and particularly in orientation
towards the kiftd of psychological rewards offered by smoking are idercdz
to be of paramount importance in determining both smoker/non-smoker statuszand
type of smoking behavior.
co
BATCo document for Province of British Columbia 15 April 1999

-3-
Urnat then is the nature of these rcwards and what arc their basis? Thorq
is a growing consensus that organismic-dispositional factors contribute,to.the
development of the smoking habit but as to I a I extent such organismic factors
can be attributed to genetic biological influences as opposed to acquired
influences is as yet unclear (Battig, 1980). The emphasis an organismic trait
and state factors in influencing smoking behavior has been expressed in i
varying degrees by a number of researchers. In attempting to extract meaning
from their highly variable data on students, McArthur, Waldron and Dickinson
(1958) hypothesized 11 ... that starting to smoke is largely brought about bi
one's social environment but that reactions to smoking ... seem to depend @n
good part on the personal needs that the newly established habit is able tO
gratify (p. 272) Seltzer (1962) paraphrased these observations in biogenettic
terms: "Rather than a superficial habit overlaid indiscriminately !upon various
persons, smoking appears to be a response to a wide variety of personality and
behavioral characteristics which have their origin, in part, in the biologic
and genetic make-up of the individual (p. 43) - " Dunn (1973) made similar I
references to organismic variables with specific references to early experimenta-
tion with cigarettes: "... it is likely that we shall ultimately find that the
critical mechanisms involved in smoking require the synergistic presence of some
other factor, such as anxiety or possibly some constitutionally determined
reactivity. The observation that only about half of those who try smoking
cigarettes go on to take up the habit certainly suggests so;re king of interaction
process. Smoking apparently is not sufficiently pleasurable among the
disinterested half of the tryers for the aversiveness of smoking to be overridden.
Smoke is smoke - whether its inhalation is pleasurable is dependeqI upon what
the individual brings to the situation... Whether or not the tota. experien.be
is judged by the smokers as positive or negative might in tine prove to be
associated with biochemical, endocrinological, or neurophysiological variables
which are either constitutionally fixed or shaped by experience pr,ior to initial
experimentation with tobacco smoke (p. 101-102) .
The average pack-a-day smoker takes B-10 puffs per cigarette and absorbs
approximately 50-150 ug of nicotine per puff. Each dose of nicotine reaches:
the brain within 7 seconds and exerts widespread and varied central and periphe-
ral nervous sytem effects (both stimulation and depression, all of which ar6
potential reinforcers) , via its capacity to af f ect the actions of and release of
-important neurochemical transmitters (Russell, 1976). For the average srzkor
the behavior is reinforced approximately 50-70 thousand times a year and this
consumption level would tend to suggest that organismic factors of a markedly
compelling nature are operative in the inception and persistence of smoking;
behavior. While environmental cues and contingency factors play a crucial iole
in tobacco usage, a comprehensive analysis of smoking also must take into ;
consideration the effects of tobacco in relation to organismic variables. The
mode of interaction between a pharmacological agent and ongoing organismic state
is of critical importance therapeutically but its study has also proved
valuable in furthering an understanding of target physiological systems by the
known actions of such psychoactive drugs (Irwin, 1968) - A similar approach can
be taken in tobacco research, namely to detarnine tobacco's effects on the
C=)
CC)
BATCo document for Province of British Columbia 15 April 1999

-4-
organism, taking into consideration ongoing states, so as to elucidate
possible mechanisms and sought for effects by the individual. Nicotine, as
a chemical, does not affect behavior directly but rather interacts with
other chemicals at a cellular level to produce changes in tissue, brgan a4
systemic functioning. The resulting alteration in physiological state then i
determines the limits and manner by which the individual copes and Interacts
with his environment- Thijs the mode of action r)f nic.0tine at the biochemical and
physiological levels may provide useful information of its possible dissimilar
effects in smokers and non-smokers that may result in differential behavioral
patterns of consumption. The issue is raised as to whether smokers
and in particu lar smokers with high anxiety levels, are unique in their
reasons for selection of and response to tobacco and hence consume this
substance in an effort at modifying or manipulating a target system
(ok systems). Their consumption therefore would have ultimately
behavioral consequences that alter and possibly increase coping capabilities
(Mills, 1978). Such an interpretation of tobacco usage has an obvious teleallo-
gical flavor insofar as it presupposes that smoking serves at least a potentially
adaptive purpose. As will be elaborated upon more fully later, there is some
indication that this may indeed be the case for some smokers.
If, as pointed out earlier, the organismic state is an important determinant
of tobacco consumption, then it remains to be elucidated as to what target
physiological system or systems the person seeks to modify and toward what
altered state the Individual is striving: Irwin (1968) summarised some of the
more salient organismic conditions from psychopharmacological studies. All of
the factors - including wakefulness, arousal, activity, endurance, biosociil
drives, set, responsiveness to stimuli, information processing and autonomic,
neurophysiological and endocrine functioning have been investigated in tobacco
research and have been suggested as reasons for consumption at one time ori
another (Dunn, 1973).
A person who voluntarily takes a drug often does so with the ikention of
altering one or more of the organismic variables mentioned above. The point
I
to be made here is that the motivation for and effect sought can vary between
individuals and serve diverse functions in a given person in different sit ations.
This fact is of paramount importance in the study of smoking motivation.
First, it emphasizes multiple causality in the onset of the habit and illus 'trates
how consideration of organismic states precludes unidimensional etiological
mechanisms as explanations for all smokers. A second point is that in addition
to motivational needs and sought for altered organismic states that tobacco: can
induce, another factor for tobacco use may be intrinsic physiological disturbance
that is rectified by tobacco. Thus a pre-smoker person who is defective in one
aspect of physiological functioning may see), tobacco with essentially medi6al
intent, much as a person with adrenocortical insufficiency craves salt (Wilkens
and Richter. 1940). Thus, the study of tobacco consumption must incorporate into
a comprehensive explanatory system in understanding of the state of the
organism which under appropriate environmental circumstances icues and
contingencies) leads to experimentation and repeated use of tobacco by an
CZ)
CO
BATCo document for Province of British Columbia 15 April 1999

individual for its perceived and/or real effects in modifying coping capacity
through its mediating action on target physiological systems.
3. Clinical Anxiety: Psychophysiological Deficit in Arousal Processes
From the preceeding discussion it is ac arent that the motivation for
using tobacco can vary between individuals, and that tobacco may possess
unique adaptive coping effects for certain individuals whose organismic
state dispositionally distinguishes them frc-.w other. In vie%,7 of the strong:
relationship between anxiety and smoking, the issue is raised as to whether
anxiety is unique with respect to any one or more organismic variables. Oi the
limitless number of organismic variables that can lead to physiological and
behavioral disruption (and this possible use of tobacco) the concept of
disturbed arousal has probably received the most attention in the study of-
anxiety. The concept of arousal is central to psychophysiological theories
of psychopathology (Alexander, 1973). At the behavioral level, it is concep-
tualised as a continuum ranging from sleep to drowsiness and inalertness to
normal awakening and on to heightened emotional states and finally extreme
emotions such as panic, rage and disorganised behavior. According to
arousal theory (Duffy, 1962; Malmo, 1959), there is an inverted U-relation@hip
betwoin mental efficiency and arousal. At low arousal levels the organism may
be inattentive and easily distracted, and poor perf ormance is 'probably associated
with slowing dot.. of cortical processes. At somewhat higher optimal arousal levels,
the organism's resources are mobilized, full attention is given to the task-,
and it performs to the best of its abilities.Still higher, excessive levels of
arousal are associated with excessive tension and intense emotions; the decline
in performance and mental efficiency probably reflecting impaired cortical
control of selectivity of responses.
To a great extent, arousal level is determined by the impact of external
stimuli on central nervous system structures, and the literature here has
concentrated on interactions between subcortical structures of the reticular
formation and limbic system in controlling and regulating response iivity to
environmental stimuli(Routeenberg, 1968). Eysenck (1967), Zuckerman (1.69
and Petrie (1967) each have attempted to tie together the various hypotheses
concerning arousal level and mental functioning in theories which can best!
be formed "optimal levels of stimulation." The key proposition of these theories
is that every individual has a characteristic optimal level of stimulatia and
arousal for efficient cognitive and motor activity and subjective well be`i9
and tolerance. Thus, individuals differ with regard to their stimulus need
and tolerance.
Psychophysiology, the non-invasive recording of bioclectric signals from
autonomic, central and somatic systems has had a long and useful history in
.pact (Duffy, 1973; Malmo, 1973) .
monitoring arousal levels and stimulus im
The clinical'applications of psychophysiological tcchnicues has spanned a
variety of disorders (Lader, 1975a; Fowles, 1975) and disturbances in
arousal mcchanisms have been implicated in a variety of psychopathological;
CD
co
01%
BATCo document for Province of British Columbia 15 April 1999

conditions ranging from childhood disorders, to anxie@ty, depression, psychopat@y
and schizophrenia (van Praag, Lader, Rafaelsen and Sachar, 1980). Lader (1975a$
1975b, and 1980) has provided recent and comprehensive reviews of the;psycho-
physiological research on anxiety in normals and in patients and it would be
both presumptions and beyond the scope of this section to present the numerous;
findings. As an alternative, the two frequent major deficits in arousal
processes will be briefly summarized and in some cases illustrated by'a specif@c
study:
(a). There appear to be no qualitative psychophysiological distinctions
between anxiety in normal populations and clinical anxiety, merely differences:
in degree- Thus, the physiological changes accompanying the experimental
induction of anxiety in normal controls resemble those found spontaneously
in anxious patients. Anxiety is a normal physiological emotion which @4e all
experience in appropriate stress situations and it quickly subsides. Clinical
anxiety is defined as physiological arousal which is 'more severe, more persistent,
or more pervasive than the individual is accustomed to and can bear. Almost
all studies suggest that clinically anxious patients are in resting state of
overalertness, overarousal and overpreparedness. This has been shown for
peripheral autonomic measures such as skin conductance and heart rate, somatic'
variables like EMG, and central correlates such as EEG and event related
potentials (ERPs). Moreover, the more anxious the patient, the higher his
physiological activity, and clinical improvement is associated with a lessening
of his arousal.
(b). The second physiological attribute which now seems well established i&
the impairment of adaptation and slowing of habituation which accompanies
clinical anxiety. The process of habituation is man's most effective neans of
coping with overstimulation. %-.Ihen bombarded wiib too many, too strong or too
frequent stimuli, the response of the nervous system gradually weakens - the
stimuli loose their impact and the reactions diminish, the physiological arous.al
effects become less intense and feelings of distress and anxiety fade. Lader dnd
Wing's C1966) original electrodermal work with anxiety patients significantly i i
demonstrates this arousal disturbance. Three aspects of skin conductance proved
to be the most sensitive parameters.,Firstly, the change in skin conductance
throughout a standard stimulation procedure provided some measure of the
adaptation of the patient to that sitmulation procedure. Secondly, as@ the
stimulation procedure consisted of a series of twenty identical stimuli, the
decrement in responses of the subject with repetition of the stimuli yielded a@n
estimate of habituation. Finally, spontaneous responses, occurring in the tracings
were counted: these are abrupt increases in conductance resembling responses
but occurring in the absence of external stimuli. Paticnts with anxiety statel
were found to adapt less, habituate less and had more fluctuations then
normal controls; these differences were lessened but not abolished by treatin
the patients with. sedative drugs. Additional studies by Lader and colleagues
Mader. 1967; Bond, James and Lader, 1974; Chattopadhyay. Bond amid Lader, 1975)
confirmed abnormal electrodermal responsivity and further studies on heart rate
co
BATCo document for Province of British Columbia 16 April 1999

-7-
(Hart, 1974). blood pressure Malmo,- Shagass and HC 1951), blood flow
(Kelly, 196G) , pupidography (Rubin, 1964). electroinyography (Goldstein, 1964)
and EEG responsivity (Shagass, 1955)have indicated hyper-responsibity and I
of adaptation to stimuli in anxiety patients.
Having oliserved a relationship between clinical anxiety and smoking, an
arousal disturbances and anxiety, it is reasonable to suggest thatitobacco
induced alterations in arousal processes may be a critical clement in patients
motivation to smoke. The subsequent induced change is presumably from an
$.aberrant" state to a more "normal" one and this change is translated into
a psychologically rewarding experience. Thus within this frame of reference,
physiological processes are translated into psychological reactivities on
which the principles of the reward conditioning paradigm are fully operati
This may be conceptualized as a psychophysiological paradigm. under these
T-
circumstances each successive rewarding experience (arousal alterations) I
strengthens the conditioned response (smoking) and the habit develops. Given
tha anxiety patients are susceptible individuals, the question still arises
Why specifically do they smoke? Clues to the reasons why smokers, and more :
specifically anxious smokers, smoke have been obtained by investigating the
acute effects of tobacco inhalation on psychological, behavioral and
physiological functioning.
4. Tobacco Smoking: An Adaptive Tool for Regulation of Arousal Processes
(a). Psychological Effects
A key to the understanding of smoking behavior is to be fo-ind in the
management of affect. if you ask smokc rs why they smoke, overwhelmingly th 4y
respond in sedational terms. In a study by Meyer, Friedman and Lazersfeld 1973) ,
smokers were asked, 'Why do you smoke?". The question could be interpreted
historically (How did you get started smoking?) or instru.mentally (What dol
you get out of smoking?). Of 126 respondents, 76 interpreted the question i
instrumentally. Of this group, 64% answered in sedational terms, that is, With
such replies as, "It relaxes me,' "It calms me down,' and so on. lot a single
respondent answered in terms that could be coded--&$ indicating arousal ,
such as "It stimulates me, ' or 'It bucks me up." And these are typical I
Ague (1973) asked smokers to fill in a Mood Adjective Check List before and
after smoking a cigarette at different times of the day. Although there we re
interactions with time of day and test conditions, in general smoking was
found to increase feeling of relaxation and decrease feelings of Aggressio ,
anxiety and tension. These effects were greatest for hIgh nicotine@cigarcttds.
Tomkins (19 0 2) has classified a number of types of smokers in the 'smoking @opula-
tion. Many of the smokers are "negative affect" or sedative smokers. They itno-ne
when the negative affect (distress, anger, worry, fear, shame, contempt, cic.)
gets to a certain intensity or when they feel that negative affect is incr'asing
CD
LN
CC)
i co
BATCo document for Province of British Columbia 15 April 1999

to a high level or indeed when they anticipate negative affect will increasd in
the near future. Russell, Peto and Patel (1974) found that many smokers repdrt
smoking when anxious or angry; the proportions were 74% of hospital workers'
93% of patients at a smoking clinic and 88% of a group of universi y studen S
(Warburton and Wesnes, 1978).
The outcome of these studies strongly parallel the findings on Individual
differences which were discussed earlier and which indicated that smokers t4nd
to be characterized by higher neuraticism (anxiety) scores on personality tests
than non-smokers. A common picture of smoking as a stress reducer @merges from
these studies. Mills (1978) has discussed the possible role of to o as al '
coping mechanism in high-arousal situations and there is a growing consensu*
tobacco functions as a psychological tool in the attenuation of stress (Ste It ney,
1979, 1980). Warburton and Wesnes (1979) have suggested that tobacco (nicot ne) ,
like anxiolytics acts as a negative reinforcer by reducing the unpleasant
emotional experience of anxiety/arousal provoked by the internal or exte
environment. Anxiolytics, however, do not exhibit similar biochemical or
electrophysiologIcal actions as nitocine and furthermore, anxiolytics are of
little aid in smoking cessation- in an attempt to elucidate specific mechanisms
of action, a great deal of research has focussed on behavioral and physiological
concommitants of tobacco-induced stress reduction.
(b). Behavioral Effects
Studies on the effects of cigarette smoking on human performance r
suggest that nicotine and smoking may enhance behavioral efficiency on senspri-
motor and cognitive functions by increasing arousal. Improvements @n sensor@motor
tasks following smoking or oral ingestion of nicotine tablets have been I
repeatedly observed in long-term vigilance and signal detection tasks which!
in Kahneman's (1973) terms, require sustained mental effort (Frankenhauser
Myrsten, Post and Johansson, 1971; Mangan and Golding, 1978; Tong, Leigh,
Campbell and Smith, 1977; Wesnes and Warburton, 1978; Hyr-sten and Andersson,
1978; Waller and Levander, 1980). These improvements are considerable if
comparisons are made between deprived smokers and non-deprived smokers.
Typical non-smoker performances, however, usually lie between these two extremes.
Both Battig (1980) and Stepney (1979) have commented that kt-is difficult t@
interpret these results as the observed differences may be attributed to a
performance reduction caused by nicotine deprivation, to a performance improvement
induced by the administration of nicotine, or to both of them, Indications that
improvement may actually reflect on nicotine-enhancement effect is@ seen in i I
Heimstra, Fallesen, Kinsley and Warner's (1980) study which made uise of nicotine
tablets and found improvements in the performance of non-smokers as well. Studies
on cognitive functioning, or more specifically learning and memory, have indicated
that smoking exerts adverse effects on short-term memory and improves long-term
retention as measured by delayed recall (Andersson and Post. 1974; Andersson,
1975; Myrten amd Andersson, 1978; Williams, 1980).
C,
co
BATCo document for Province of British Columbia 15 April 1999

As studies on learning and arousal agree that high arousal during o
leads to improved ultimate memory (Kleinsmith and Kaplan, 1963; Berlyne, BcFsa I
Hamacher and Koeing, 1966; Walker and Tarte, 1963) but leads to detrimental
effects on immediate recall, the results of the above tobacco-learning studies
were interpreted on the basis of the arousal-increasing properties Of smok@-ng.
Although this proposed general arousal mechanism seems to be an adequate I
hypothesis for them tobacco-induced performance changes, an altardative second-
order interpretation based on Easterbrook's (1959) data suggest t@at increA@se
arousal may function by narrowing the focus of attention (i.e., stlbjccts
sample a smaller range of potentially distracting, irrelevant external and
internal stimuli and focus siectively on relevant stimuli). This increased
ability to attend selectively to certain relevant aspects of the stimulus field
while simultaneously inhibiting response to other aspects of the field may
account for Andersson and Hockey's (1975) findings that smoking rc@duces thi
incidental learning of irrelevant stimulus material. The results imply thaq-
attentional processes are affected by cigarette smoking in the same way as-..by
other arousal-increasing events. Easterbrook's hypothesis, proposing that @he
range of cues are reduced in states of high arousal, was supported by these
findings. This increased selectivity of attention by tobacco may well bc the
basis of the frequent reports by smokers that smoking improves their concentra-
tion and that not smoking results in extreme difficulty in concentration.
As with the cognitive studies, tobacco-induced improvement in vigilance per 'formance
has frequently been interpreted within arousal theory, and indeed there is a
solid body of data supporting relationship between arousal and vigilance
(Mackworth, 1969; Tong, Henderson and Chipperfield, 1980). Hom-ever, this data
may also be interpreted specifically within an attentional framework as
Mangan and Golding's (197B) results indicated conclusively that sm'O"Zing
improves vigilance performance by decreasing the subjects errors o :f commisAon
(false positive) rather than by improving his detection rate.
The notion that the attraction of tobacco may lie in its ability to screen or
block out disruptive, distracting effects of irrelevant input on ongoing ta -sks
and performance has been forwarded by a number of researchers (Dunn, XVS4. .Ynott,
1978;, 1979; Warburton and Ilesnes, 1978, 1979; Wesnes and Warburton, 1978)
empirical basis for this approach is based in part on studies which have shw.,-n
that tobacco does not appear to have any consistent effect on short-term I
performance proficiency under conditions conducive to good per (Dunn, 1978;
Stepney, 1979), but it does seem to offer an advantage under conditions likely
to interfere with performance. Initial support is forthcoming fro.-.1 studies @. ich
shot-., that nicotine reduced the distractibility on the Stroop task (Wesnes and
t
Warburton, 1978) and that tobacco s-making counteracts the decrement in reacl ion
time performance observed under distracting noise conditions (Tong Knott,
McGraw and Leigh, 1974) .
BATCo document for Province of British Columbia 15 April 1999

-lo-
in contrast, to Warburton and Wesnes (1979) who emphasize the impact of
tobacco on performance as being an enhancement of signal or relevant target
information, due to increased arousal, both Dunn (1978) and Knott (1978, 19ig)
have emphasized the inhibitory role of nicotine and tobacco in dampening doi;n
the impact of hyper-arousal responsivity on task performance induced by
disruptive, distracting input. An initial study by Dunn (1978) on the disru,
p
effects of frustration on anger and performance proficiency in a c:nplex
perceptual-motor task supported this notion. Here, smokers and non-@-smokers
displayed the same increases 'in anger, but the performance proficiency scorqs
of the smokers were significantly superior to the scores of both prived a d
non-smokers during the anger-induced period. In Dunn's word's, " .. the smoker
is unwittingly triggering a physiological response sequence w,hen Ae smoYes (which
has the effect at the psychological level of improving his coping Efficiency
in face of otherwise disruptive influences... I aLm suggesting @ hat @ . . the ,
subjects emotional or affective arousal had reached a level such ai to impair
ongoing task performance and that the arousal did in fact impair t@e performance
of the non-smoking and placebo subjects. The smoking subjects, however, weri
invoking protective physiological mechanisms that had the psychological ef
of insulating ongoing performance from the disruptive influence of excessiv
arousal. Smoking may be having a negative or inhibitory effect upo@ the intru-
siveness of excessive affective arousal upon ongoing behavior (p. 22)." This data
is to a great extent supported by studies which clearly sho-.,, that nicotine
can play a significant part in reducing'the disruptive effects of stress
(electric shock) on behavior in animals (Stepney, 1979, 1980).
Recently, based on his electrocortical findings which suggested.that tobacco
normalized" central nervous system activity of smokers to a level. coi-nperable to
that of non-smokers (Knott, and Venables, 1977, 1978), a "filtcr model" Wa
proposed by Knott (1978, 1979) to relate the relative attentional deficits in
deprived smokers and improvement by tobacco to the frequently reported
sedational or stress-reducing effects of smoking (Gilbert, 1979) . @he dell,
hypothesized that (a) relative to non-s=kers, smokers deprived of@tobacco
exhibit an inefficient central filtering mechanism for gating out irrelevant,
distracting stimuli and experience input more readily and more.strong ly a4
as a result are characterized by a distressed state of relative stimulus overload
inappropriate for efficient performance and (b) the attraction of tobacco
smoking may lie in its ability to normalize control of stimulus input thereby
relieving distress and improving performance and subjective well-being. The:
filter model runs parallel to findings of greater irritability to intense
stimulation and reduced pain thresholds, i.e., greater sensitivity to pain,%
observed in smokers relative to non-smokers and subsequent increasing pain
thresholds and decreases in stimulus irritability following smoking 9 pain
1973; Schzchter, 1973, 1978vSeltzar, Friedman, Siegelaub and Collon, 1974):.
Initial behavioral support for smoker vs non-smoker differences on susceptibility
to distractiorLeffects was observed by Knott's (1980) finding that, high intensity
auditory noise significantly impaired smokers performance on a. choice reaction
time task but had no effect on non-smokers. A subsequent (1901a) study further
indicated that female smokers, who have been reported to have their greatest
"lo
BATCo document for Province of British Columbia 16 April 1999

distraction induced deterioration in choice reaction. Although this data ir.
colored by possible secondary phenomena such as long-term tobacco effects
and influences of deprivation, they may be suggestive of predispositional
factors relating to the onset of the smoking habit.
(c). Physiological Effects
All of the evidence from the performance studies provide strong support
for the notion that tobacco smoking reduces perceived stress by inhibiting
indiscrimate arousal responses to disruptions by internal and external input.
This neat picture is complicated, however, by what is probably time least i
equivocal, best establish4d fact about the physiological consequences of smoking-
namely that it seems to lead to widespread increases in nervous system ar Sal
with the most obvious alternations being exhibited within the peripheral
autonomic nervous system. Larson, Haag and Silvette (1961) have il emarked at
there are so many peripheral effects of nicotine that the centra marked
seem to be obscured. Similarly, the Surgeon General's Report (196.4) shoured
that "smoking 1 to 2 cigarettes causes in most persons, both smo%ers and non-
smokers, an increase in resting heart rates of 15 to 25 beats pa@ minute, a
rise in blood pressure of 10 to 20 tm-n fig systolic and 5 to 15 mra Hg distolic,
and an increase in cardiac output of about 0. 5 1/r.in/sq.m (p. 318) . " In s4ort,
there are a host of transient increases in physiological resrons@s to s'no e
inhalation and they include elevated heart rate, elevated corona,v flow, I
elevated blood sugar level, lower cutaneous temperature in the I
increased blood flow'in skeletal musculature, a reactive release of adren Ain
and alterations in electrical potential patterns of the brain (Dunn, 1973)., all-
of which are customarily associated with increased states of arousal or activa-
tion or emotionality. As theories of emotion view increased autonomic arousal
as an essential component of emotional processes, and as tobacco increases
physiological arousal yet frequently reduces behavioral effects 6f arousal
and self-report measure, an intriguing paradox pervades the motivational
literature. Recently, there have been an increasing ntunber of studies and!
theories (Gilbert, 1979; Schachter, 1973) that pertain to the resolution of
these apparently contradictory findings and there is a general picture emerging
%,.hich indicates physiological evidence for tobacco induced arousal reduction
as apparent in specific electrophysiological measures and eliciting this
response it is important to look at the effects of nicotine, not in isolation,
but in conjunction with the situation in which the nicotine is administirid,
and also in relation to the personality of the subject. The combination oi
these three factors (amount of nicotine taken in, arousal-producing situations
and low or high-arousal organism) determines the outcome of any tobacco experiment.
Neurophysiological stodies in animals are in general agreement that the'
effects of small and medium dose of nicotine on the central nervous sv e MNS)
-St 7al phase
are biphasic, there being a marked sequential effect, with a primary arou
being followed by a secondary depression effect on electrocorticograms (Schaepp"
19G7; Goldstein, Beck and m.undschenk, 1967). ,here is also evidence that 'While
small dose of nicotine increase arousal, larger doses r.,.ay decrease arousni.
Thus, Armitagc, Hall and Sellers (I ID rig) found that doses of 2 Ing/kg everylthirty
seconds for twenty minutes, given intravenously to cats, caused danynchro,iza-
tion of the electrocardiogram indicating cortical activation, and an increase in
BATCo document for Province of British Columbia 16 April 1999

- 1 2 -
the release of cortical acetylcholine. However, a larger dose given less
I mg/kg every minute for twenty minutes) caused sometimes an
increase and sometimes a decrease in cortical activity, such changes being
accompanied by an increase or a decrease in cortical acetylcholine output. On
this basis and on the basis of the previously discussed distraction based
stress hypothesis, one would expect that the artinn of tobacco or nicotine on
the human EEG should mimic the action of anxiolytics but the electrophysiolplgical
evidence does not strongly support this notion. in a pioneering comparison bf
nicotine and an anxiolytic (Murphree, Pfeiffer and Price, 1967), the means @a.d
variance for the total energy.increased across the spectrum of EEG I
the anxiolytic while there was a general reduction in means and variance
across the whole spectrum for nicotine. It was concluded that the
nicotine changes were more typical of a stimulant drug than an anti-anxiety
compound. Subsequent EEG studies, reviewed by Conrin (1980) have for the most
part focussed on B-12 Hz alpha activity and are in general agreement that il
tobacco smoking increases the dominant alpha frequency. Knott and es @(1977)
observed a "normalizing" effect of tobacco inhalation on dominant I,frequenc
Analysis of pre-smoking activity revealed a slower dominant frequency an
deprived smokers relative to non-smokers and non-deprived smokers @nd the
immediate effect of smoking was to increase dominant smokers and - I
smokers. Instead of relating these findings to an arousal phenome a, Knott @and
Venables cited a solid body of literature which suggested that dolinant alpha
frequency reflected a CNS scanning or gating process involved in sitimulus-intput
and in cognitive processing (Lykkan, 1975). As this tobacco-induced shift in
EEG frequency may reflect improved cortical scanning and speed of cognitive
processing, the authors suggested that smokers may smoke in order to achi e the
psychological state of increased vigilance and attention associated with t s
shift. On this basis it would seem that this repeatable shift in dominant
frequency induced by smoking may have particular functional significance i
relation to both the distraction hypothesis discussed earlier and in relation to
predisposing electrophysiological factors to the smoking habit. The dominant
rhythm appears to reflect CNS maturation, appearing at 3 or 4 months of ag6
at 3-4 Hz and increases to the adult frequency of about 10 Hz at about 10 ars
of age. This rhythm, although responsive to static factors, under normal Ylle
circumstances remains constant day in and day out and month by month
(Lindsley and Rugenstein, 1937). Is it possible, that the slower rhythm 'In
deprived smokers represents a delayed CNS maturation, and hence a relatively
inherent perceptual deficit which may "set-up" a need or perdisposition for
tobacco (or some other substance or activity) which is readily available av
can specifically alter the rhythm at any given time?
As it is reasonable to suppose that the satisfaction of tobraccd smoking Js
ultimately dependent upon cerebral events, a number of studies have focussed on
the measurement phasic potentials which sensory stimuli evoke (ERps) in the cortex
as a way of studying cerebral processes. The initial study by Hall, Rappaport,
Hopkins and Gr.if (1973) on visual evoked potentials showed that tobacco
smoking increased amplitudes of late components (more than 80 ms after
stimulus onset), changes which are consistent with the contention that
tobacco increases arousal. Later studies by Friedman, Goldberg, Horvath ancl,
Meares (1974), and Friedman and Meares (1980) suggested that the tobacco
effect may be modality specific, increasing late components of the visual evoked
-FIJI.
\0
BATCo document for Province of British Columbia 15 April 1999

-1 3-
potential. The reduction in late auditory evoked potc@tial components isof
interest in that Knott (1980) had shown that the performance of mokers ai
compared to non-smokers, was significantly more affected by high intensit'
noise. Knott and Venables (1978) observed a "normalizing" effect of toba4co
smoking on visual cortical evoked responses in that deprived smokers evidenced
faster latencies and larger amplitudes (11.2. more sensitive) than both non-
smokers and deprived smokers who exhibited comparable responsiveness. Th4
authors suggested that a possible attraction of tobacco smoking may lie in
its ability to function as a "chemical stimulus filter" thereby reducing 1
the distracting effect of irrelevant, adverse stimuli on I efficiency
and emotional tonus. Complimentary results are provided by Vasquez and
Toman's (1967) observation of a decrease in late ERP amplitudes during i
smoking, an increase during abstinence. These evoked potential studies
received some support from an animal investigation by Pradhan and Guha (19 76)
who recorded from the auditory cortex of cats and observed that the initiail
effect of smoking dosages of nicotine (12.5 rg/kO 'reduced both anplitude'.and
area measures of late COMDOnents of the auditory evoked response. This appeared
to be an apparent selective effect as nicotine produced general CNS excitation
at the same time.
.A number of additional electrophysiological studies have provided sun rt for
. PO
the notion that tobacco dampens CNIS responsivity to stimuli input and therefore
they are of particular interest for the distraction hypothesis. Friedman.:
Horvath and Meares (1974) and Mangan ana Golding (1978) found that tobacco
smoking increases the speed of habituation of CNS (alpha blocking) and ANS
(skin conductance responses) responding to repeated presentations of high' -
intensity auditory stimulation. These authors suggested that a possible ed!IS
of reinforcement of tobacco smoking nay lie in its ability to stinulate AS
inhibitory mechanisms (without simultaneous reductions in CNS exditatory ocesses)
Sory in,
resulting in the "screening out' of irrelevant and irritating se I 4t
into consciousness. in this regard, it is interesting to note Mangan and
Golding's (1978) observation that inhibition of momentary spontancous imbalances
in autonomic arousal may be a physiological basis of tobacco ind ced improvement
in vigilance performance. During their vigilance task, it was =ed im, th@ 'at
false positives occurred most often immediately following a Spontaneous skin
U'= - r
conductance fluctuation. As smoking reduced both spontaneous fl tuations: tand false
positives they inferred that performance improvement was due to ..t-he increa ed stabi-
lity of the autonomic arousal system. The possibility that Smokers nay eXibit
greater autonomic responsivity than non-smokers was confirmed by Knott (19 -80) who
observed that smokers exhibited significantly higher resting skin.conductance levels
!I
faster response laten@:;es, large response amplitudes and significantly fas@er and
larger cardiac accelerations to a high intensity auditory rt . Pore recently
Knott (1981b) has observed that female smokers relative to male smokers and female a
male non-smokers, exhibit significantly higher resting skin conductance levels and
larger skin conductance responses to high intensity auditory stimuli. Thip is in li
with a previously discussed study which indicated that female smokers exhibit a rare
frequent craving in high arousal/anxiety situations. One may predict from.
BATCo document for Province of British Columbia 16 April 1999

-14 -
the above studies that under conditions of stress and overload, high ncuroticism
scoring subjects should benefit more from smoking than low neuroticism sco@inq
subjects. Studies by Kucek (1975) and Warburton and Wesnes (1978) ibear this
out. In the former study, subjects were tested in an experiment under conditions
of information overload and smoking had a beneficial affect on th@: perforatince
neurotic subjects. In the Warburton and Wesnes study, an attentional vigilance
task was employed and it was found that smoking helped high N scoring subjects,
but not low N scoring subjects. The correlation between improvement and
neuroticism was 0.68 which indicates the importance of personality in
evaluating the effects of smoking on performance and stress reduction.
Finally, an additional target physiological system implicated in to Lac cj -
induced stress reduction is skeletal muscle activity. A number of1studies .ave
reported on the effects of nicotine and tobacco smoking on skeletal muscle tone
in men. Webster (1964) reported a short-lived reduction in muscular tensi0q
in spastic patients after smoking a single cigarette and Domino's (1973)
study showed a significant reduction of the patellar tendon reflex (knee jerk)
and associated electromyographic (EMG) musculature following tobacco smoki
and oral administration of nicotine arousal. Hutchinson and Enley (1973) 1 1
established that deprived smokers shooed an increased frequency and force of
spontaneous masseler MG contractions and found that 5mg of nicotine in water
decreased the frequency and force of masseter EMG jaw contractions to intense
auditory stimuli in both smokers and non-smokers. This consistent picture is
disturbed, however by Fagerstrom and Gotestam's (1977) study which showed that
resting EMG activity of the trapezium neck muscle increased during tobaccot
smoking. One must conclude that nicotine, or at least tobacco smoking of
varying nicotine content, has biphasic effects as far ar E..,:G activity is
concerned. Stimulant and depressant effects seem to be dependent on both tle
site of recording and whether or not one is focussing on tonic or phasic
components.
(d). Neurophysiological Effects
up to this point, the neurophysiological mechanisms relevant to the proposal
filter model have not been discussed, and although at this stage of resear, h
it is recognized that discussion is purely speculative, some recent nouro y-
siological research is worth mentioning. Jasper (1958) and other a
(Demetrescu and Denietrescu, (1962) have implicated the reticular formation in
controlling selective responsiveness to significant stimuli by preventing
general alerting actions to all incoming stimuli and this focus Parallels
the findings of investigations which found significant effects of:nicotine:
on this CNS site (Domino, 1967). However, as with recent empirical data which
has focussed on the role of the limbic system in the control of attention,-,
neurophysiclogical investigations of nicotine action have also attributed the
ef of nblotine to changes exerted by the limbic system. Here,: employing
(Bhattac@aryi and Gol4stain,
electrophysiological measures, Nelsen and colleagues
1970; Nelson, Pelley and Goldstein, 1973) have provided evidence that the
CN
\0
BATCo document for Province of British Columbia 15 April 1999

hippocampal limbic system is a major target area for nicotine, in that c6rtical
activity under nicotine treatment is controlled sr-are by the hippocampus
than by the reticular formation- Based on Routtenberg's (1968) hypot he that
hippocampal activity inhibits the reticular formation, Nelsen (.1974) hy thesized
that the neurophysiological mechanisms underlying nicotine-seeking behavior
lies in its ability to counteract inappropriate responding by the reticular
formation, by its (nicotine) action on the limbic system. support for this
hypothesis was observed in their animal investigation in which @icotine '
treatment was found to counteract decreased performance in selective att6tion
which was induced by electrical stimulation of the reticular formation. Pn
this basis, these authors suggest that a possible motivation underlying
smoking behavior is its ability to reduce reticular excitation 'which isi
manifested in a hyper-stimulated anxious state inappropriate for effective
behavior and to engender what might be considered a state of useful behavioral
arousal. In relation to the filter model, it is interesting to speculate here
whether the often reported relaxation smoking is related to inappropriate
reticular hippocampal filtering or inappropriate hippocampal limbic control
of reticular filtering (or both) in deprived smokers relative to nonsmokers.
B. Summary, Rationale & objectives of Proposal
A
The approach of this paper has been to examine the possible role o'.
organismic trait and state factors in relation to the high frequency of
tobacco use in psychiatric patients diagnosed with clinical anxiety. 11ore
specifically, the issue raised in this review was whether anxiety patien ts
exhibit specific arousal factors which reinforce repeated use of tobaccdc for
its perceived and/or real effects in modifying abnormal physiological and
behavioral systems. In general. the tobacco literature which relied primarily
on studies focusing on the acute effects of smoking, supported an arousa I1
interpretation in that:
1. in general, smokers tend to exhibit personality profiles indicative
of physiological hyper-arousal and hyper-rcsponsivity; I
2. in general, smokers report that they smoke to reduce hyper-arouslal
and responsivity and experimental studies sup ort the contention that tobacco
reduces both behavioral and subjective measures of arousal; T
3. in general, and in particular for smokers assessed as exhibiting'
high-arousal profiles, tobacco smoking exhibits a negative inhibitory effect
upon the intrusiveness of disruptive and excessive arousal upon ongoing
physiological, behavioral and cognitive processes.
t
czar
C.-4
'IO
ON
BATCo document for Province of British Columbia 16 April 1999

hippocampal limbic system is a major target area for nicotine, in that coriical
activity under nicotine treatment is controlled more by the hippocampus
than by the reticular formation. Based on Routtenberg's (1968) hypothesis @hat
hippocampal activity inhibits the reticular formation, Nelsen (1974) hypothesized
that the neurophysiological mechanisms underlying nicotine-seeking behavior
lies in its ability to counteract inappropriate responding by the reticular
formation, by its (nicotine) action on the linthic system. Support for-this
hypothesis was observed in their animal investigation in which nicotine
treatment was found to counteract decreased performance in selective attention
which was induced by electrical stimulation of the reticular formation. On@,
this basis, those authors suggest that a possible motivation underlying
smoking behavior is its ability to reduce reticular excitation W@ich is
manifested in a hyper-stimulated anxious state inappropriate foxi effective
behavior and to engender what might be considered a state of useful behavi ral
@O
arousal. In relation to the filter model, it is interesting to speculate here
whether the often reported relaxation smoking is related to inappropriate
reticular hippocampal filtering or inappropriate h-,ppocampal- I control
of reticular filtering (or both) in deprived smokers relative to non-smokers.
13. (a) Conclusions
The approach of this paper has been to examine the possible role of
organismic trait and state factors in relation to the high frequency of
tobacco use in psychiatric patients diagnosed with clinical anxii@ty. More
specifically, the issue raised in this review was v.-hether anxiety patient
exhibit specific arousal factors which reinforce repeated use of tobacco for
its perceived and/or real effects in modifying abnormal physiological and
behavioral systems. In general, the tobacco literature which relied prim ly
on studies focusing on the acute effects of smoking, supported an arousal
interpretation in that:
1. 'n general, smokers tend to exhibit personality profiles indicatilie
of physiological hyper-arousal and hyper-responsivity;
2. in general, smokers report that they smoke to reduce hyper-arousal
and responsivity and experimental studies support the contention that tobacco
reduces-both behavioral and subjective measures of arousal;
J. in general, and in particular for smokers assessed as exhibiting
high-arousal profiles, tobacco smoking exhibbits a negative inhibitory t
upon the intrusiveness of disruptive and excessive arousal upon itory eff
physiological, behavioral and cognitive processes.
4
^J
\0
BATCo document for Province of British Columbia 16 April 1999

16
In addition to the tobacco literature, a portion of this' K
been aimed at presenting available evidence which may be indicative 6f disturbances
of arousal processes in patients diagnosed with clinical anxiety. Fkom the s6dies
cited, it appears that although no specific target physiological sysqem can b
complicated in smoking motivation, it appears that a host of CNS and ANS irrequlari-
ties in the directions of hyper-arousal and hyper-respansivity ma exist in anxiety
patients and thus may play a role in the onset and maintenance of the habit. :
Integrally linked with tnis picture is the concept of defective filtering whiA
implies certain characteristics of the patients' attentional style that tends ,to
augment the intensity and impact of input both from the internal and external -;world.
For patients with this type of dysfunction the attraction of ninotine seems obivious.
The mechanism of action of nicotine that has been proposed is not the same as f
negative reinforcement. Negative reinforcement occurs when a drug terminates @or
reduces a negative affect. Thus an anxiolytic is taken during aversive event I in
order to avoid them. Alcoholics seem to drink for this reason. In 6ontrast,, icotine
enables the patient to confront his problems and perhaps overcome them. Thus 'we
would paraphrase nicotine's action by saying that nicotine is a drug of ccynf ra 'tat ion
and not escapism. a sharpening drug not a blunting drug. In this way it is a -@unique
anti-anxiety compound. It increases clarity of thought by enhancing filtering
processes as a consequence of its action on physiological systems and therebyidecreases
distraction from disruptive input of internal and external sources (Warburton :.and Wesnes,
1979).
In summary, the general trend toward hyper-arousal and hyper-responsivityin
anxiety patients supports the contention that high-frequency tobacco-use in these
individuals may be interpreted as a coping behavior aimed at "normalization" qf
arousal processes.
(b) Objectives & Hypotheses:
To investigate psychophysiological parameters of tobacco smoking in patiepts
diagnosed with clinical anxiety. In addition, psychophysiological parameters of
tobacco smoking will also be examined in patients with diagnoses of depression and
schizophrenia in view of the anecdotal evidence of high tobacco consumption i ' these
two disorders and in view of the role of arousal disturbances which seem to be
underlying these psychopathologies (Spohn and Patterson, 1980; Christie, Little
and Gordon, 1980; Perris, 1980). Studies will focus on these specific questi 'Ts:
I. To what extent is psychiatric symptomatology and related psych ogical,
behavioral and psychophysiological functioning altered during smoking abstinence?
One might hypothesize here that relative to normal controls, all measures will;,
increase in degree of abnormality and will subsequently improve/normalize during
non-abstinence periods.
II. To what extent do the smoking behaviors (and their effects on
psychological behavioral and psychophysiological functioning) of psychiatric
patients change from admission through to discharge from treatment? One migh
hypothesize here that relative to treatment termination where illness seve
is reduced, the'greater need for coping during the severe illness period at
admission will be reflected in more intensive smoking behaviors and a ; greater
normalization impact on functioning.
U1
X.-
cc
BATCo document for Province of British Columbia 15 April 1999

16a
111, To what extent is smokf-r/non-smoker status and d gree of smoking
of psychiatric patients related to treatment outcome? One might hypothesize
here that smokers, with the additional coping mechanism, would exhibit a gr6ater
and quicker degree of clinical improvement relative to non-smoker,patients @nd
that treatment improvement would be positively related to degree (if smokin
in smoking patients.
C. Slow Cortical EEG Potentials: A Psychophysiological Paradigm for the
study of Tobacco Smoking and Arousal Processes in Psychiatric Patients
The contingent negative variation (CNV) is a small scalp-recorded negative
potential which slowly builds up between a warning signal and an imperative..
r I
signal (such as in a standard fore period reaction time task) eql4ring the:
subject to carry out some response, usually a motor response such s pressi@g
a button. This slow cortical potential occurs in an expectancy sitation is
sometimes referred to as an expectancy wave. Tecce, Savignano-Bom, man and @I
Cole (1978) have proposed that two processes of arousal and attention become
coupled under drug administration, such that over increase in attentional
demand will increase arousal, but an over increase in arousal will reduce
attentiveness and so attenuate optimal CNV development. The function of
self regulated drug administration such as smoking is thus presumably to adl ust
this distraction-arousal coupling to an optimal level according to task I
demand. As Ashton and Watson (1970) and Ashton, Savage, Telford, Thompson and
Watson (1972) have shown that situational stress radically affects smoking
strategies ( i.e. , increases puff frequency and thus nicotine dosage) this
theory would predict that individuals differing in arousal levels would adjust
their smoking parameters accordingly (e.g. puff frequency, duration, volume'
etc)-so as to bring CNV development to an optimal level. Studies on CNV,
tobacco and individual differences have on the whole supported this content Ion
and failure to take into account personality differences may have been the
basis for the non-significant tobacco effect an CNV observed by Knott and
Venables (1980). The initial study by Ashton, Millman, Telford and Thompson
(1974) showed that individuals high in cortical arousal (in tr overt s)
exhibited consistent CNV amplitude reductions (depression) following tobacco
smoking while individuals rated low in cortical arousal (extroverts) showed:
consistent increases in CNV amplitude (stimulation) following smoking. Estimates
of nicotine intake (such as puff volume, frequency. butt analysis) indicate
that extroverts took in more nicotine than introverts. Subjects who said el ey
were relaxed by cigarette smoking tended to show a diminished CNV and these
C-D
(,n
L.^J
BATCo document for Province of British Columbia 16 April 1999

17
results parallel reports of a greater desire to smoke for tranquilizaiion and
stress-reduction in introverts (Gilbert, 1980). Subsequent studies by Ashton,
Marsh, Millman, Rawlins, Telford and Thompson, (1978) on effects of intravenous
injections of various smoking dose of nicotine on the CNV produced a 4ose-resp se
relationship in which smaller doses were found to have a stimulant effect and
large doses a depressant one. On commenting cm these findings, St crnqiy (1979)
stated that smoking is capable of producing either stimulant or depressant CNS
effects, depending on the smoker's environment and the dose of nicotine taken,
and that the point at which the nicotine dose crosses over from havi4 a stimu
lant effect to having a depressant one is within the range of do th it can be
obtained from a cigarette. This would give the smoker an 0 ose useful too
for arousal control. The notion that smokers may use cigarettes demands of a ;
specific environment is supported by a study by Myrsten, Andersson, Frnakenhaeuiser
and Elgerot (1975). Here, smokers who self-reported their strongest need to
smoke under low-arousal conditions (low-arousal smokers) performed and felt
better when smoking under laboratory tasks of low complexity and smokers who
self-reported their strongest need to smoke under high-arousal conditions (high-
arousal smokers), performed and felt better when smoking under laboratory tasks'
of high complexity.
As with extraversion-introversion, one may predict from the above studies
that under conditions of stress and overload, high neuroticism scoring subjects,
should benefit more from smoking than low neu-roticism scoring subjects,. Studiel
by Kucek (1975) and Warburton and Wesnes (19@8) bear this out. In the@ former
study, subjects were tested in an experiment under conditions of infor-mat ion
overload and smoking had a beneficial effect an the performance of neu@ 'rot ic
subjects. In the Warburton and Wesnes study, an attentional vigilance task was
employed and it was found that smoking helped high N scoring subjects, but not
low N scoring subjects. The correlation between improvement and neuroticism
was 0.68 which indicates the importance of personality in evaluating the effect
of smoking on performance and stress reduction.
The sensitivity of the CNV to tobacco/nicotine and to distraction-arousal
variations makes it a promising covert response measure for research into
smoking motivation, particularly in psychiatric patients where arousal distract on
deficits are not readily apparent to the clinician or to the patient. 'The CNV
paradigm seems to be particularly appropriate for investigations of tobacco
smoking in anxiety patients, as both experimentally induced anxiety (Knott and
Peters, 1974) and distraction (Blowers, 1977; Tecce, Savignano-Bowman
(-,4
Ln
BATCo document for Province of British Columbia 15 April 1999

elford and Thompson
Venables (1980). The initial study by Ashton, Millman, T
(1974) showed that individual-S high in cortical arousal (introverts)
exhibited consistent CNv amplitude reductions (depression) follow@ng tobacco
smoking while individuals rated low in cortical arousal (extroverts)
showed consistent increases in CNV amplitude (stimulation) following
smoking. Estimates of nicotine intake (such as puff volume, frequency,-
butt analysis) indicated that extroverts took in more nicotine tha:n introvqlrts.
Subjects who said they were relaxed by cigarette smoking tended io show a:
:ire to
diminished CNV and these results parallel reports of a greater der
smoke for tranquilization and stress-reduction in introverts (Gil)ert, 198p.
Subsequent studies by Ashton, Marsh, Millman, Rawlins, Telford ani Thompsoq,
(1978) on effects of intravenous injections of various smoking do;e of nic4tine
on the CNV produced a dose-response relationship in which smaller,doses were
found to have a stimulant effect and large doses a depressant.oneL On commenting
on these findings, Stepney (1979) stated that smoking is capable of producing
either stimulant or depressant CNS effects, depending on the smoker's environment
and the dose of nicotine taken, and that the point at which the nicotine d6se
crosses over from having a stimulant effect to having a depressant one is I
within the range of dose that-can be obtained from a cigarette. This would-
give the smoker an extremely useful tool for arousal control. The notion that
smokers may use cigarettes demands of a specific environment is su y
.pported
a study by Hyrsten, Andersson, Frankenhaeuser and Elgerot (1975).IHere,
smokers who self-reported their strongest need to smoke under low-arousali
conditions (low-arousal smokers) performed and felt better when smoking under
laboratory tasks of low complexity and smokers who self-reported,their
strongest need to smoke under high-arousal conditions (high-arousil smokeri),
performed and felt better when smoking under laboratory tasks of Aigh complexity.
As with extraversion-introversion one may predict from the above studies
that under conditions of stress and overload, high neuroticism scoring subjects
should benefit more from. smoking than low neuroticism scoring subjects. Stlidies
by Kucek (1975) and Warburton and Wesnes (1978) bear this out. In the former
study, subjects were tested in an experiment under conditions of information
overload and smoking had a beneficial effect on the performance of neurotij
subjects. In the Warburton-En-W Vesnes study, an attentional. vigilance task!was
employed and it was found that smoking helped high N scoring subjects, butf
not low N scoring subjects. The correlation between improvement and neuroticism
was 0.68 which indicates the importance of personality in evaluating the
effects of smoking on performance and stress reduction.
The sensitivity of the CNV to tobacco/nicotine and to distraction-
arousal variations makes it a promising covert response measure for rescardh
into smoking motivation, particularly in psychiatric patients where arousal
distraction deficits are not readily apparent to the clinician or 'to tho 11
patient. The CNV paradigm seems to be particularly appropriate for investigations
of to@acco smoking in anxiety patients, as both experimentally induced anxiety
(Knott and Peters, 1974) and distraction (Blowers, 1977; Tecce, Savignano-9.0;,--man
(-n
L@N
BATCo document for Province of BritiSh Columbia 15 April 1999

_19-
and f4einbresso, 1976) have been shown to reduce CWN amplitude and slot'
reaction time and neurotic patients have been shown to exhibit smaller CNVZ
amplitudes and greater reductions under distraction conditions than normal!
controls (McCallum and Walter, 1968).
The CNV has also been examined in depressive patients and theke appearl
to be consistency in the findings that CN%1 amplitudes are approximately 50t
smaller in depressed patients than in healthy controls (Timsit-Berthier
Koninckx,'Dargent, Fontaine and Dongier, 1970; Small and Small, 1971; Gredko,
Bolz and Hermann, 1980). In addition, depressive patients seem tp be dist@n-
guished by a failure of the resolutions of negative wave to borderline following
the reaction time response to the imperative stimulus. This post 7imperatiire
negative variation (PINVI has been observed to be higher in depressives
particularly under conditions of uncontrollability (Bolz and Gredko, 1980)'
The PINV has also been shown to have promising potential as a diagnostic
tool for schizophrenia. The research of Dongier and Timsit-Derthier and t@eir
colleagues (Dongier, 1976; Dongier, Dubrovsky and Engelsmann,-197R; Bachneff
and Engelsmann, 1980; Timsit-Berthier, Delaunoy and Rousseau, 1976) Documents
that patients suffering from psychopathological disorders (above all schizophrenia
J
show a-reduced C.NV and a prolonged PIXV. According to Dongier and colleagpes,
a PIWV was observed in nearly 95% of patients diagnosed as suffering from pcute
schizophrenia; in healthy human subjects a prolonged PIW-1 is only,'found in'10 to
is%.
the waAing
Aside from CNIV amplitude, PIN%Y and sensory evoked responses to
and imperative stimuli, an additional. attractive feature of this paradigm. is the
elicitation of two apparently functionally different CNIV con-concnts under iong
preparatory intervals (greater than 4 secs). The two CNV components have @een
tentatively related to assenting and preparatory functions of in f rmation Processing
respectively (Neerts and Lung, 1973; Loveless and Sandford, 1974)rand their have
been shown to be differentially sensitive to individual differences in arousal
and to tobacco smoking (O'Connor, 1982). The erRoloyment of lonq:foreparioa
intervals in a CNV paradigm would appear to offer an additiona I a dvantage @s it
would allow monitoring of the slow, time locked heart rate deceleration response
which occurs just prior to the imperative signal (Chase, Grahan. and Grahaq, 1968).
Although the functional significance of this heart rate responseiis still Peing
debated, reaction time speed has been negatively correlated withicardiac celer-
ation (i.e., greater deceleration associated with faster reaction .times) 2d as
such there is a general tendency to relate this psychological response to
information processing operations of attention and intake-rejection (Dunca,n-
Johnson, and Coles, 197S).
In summary, the a4ioution of the long forcperiod CNV paradigm -,---ould se# to
be-advantageaus in examining smoking motivation in psychiatric patients for
several reasonL. which include: sensitivity to tobacco/nicoti4ie effects; scnsiti-
vity to arousal-distraction variations; sensitivity to various psychiatri disorders.
Ln
BATCo document for Province of BritiSh Columbia 15 April 1999

20
In addition, the long foreperiod CNV paradigm allows for the examination of a
pattern of responsivity across a variety of response measures which include:
sensory evoked responses to warning and imperative stimuli; orienting and
preparatory components of CNV; resolution (PINV) of CNV processes; cardiovascular
deceleration responses and additional autonomic (e.g. electrodecimal)-and
somatic (e.g. electromyographic) responsivity; and finally, the behavioral measure
of reaction time itself.
D. Method
1. Study I: Effects of Smoking Abstinence an Symptomatology and Psychiological
Behavioral and Psychoohysiological Functioning in Psychiatric Patients and:
Normal Controls
a) Subjects:
The subjects will consist of 2 main groups, psychiatric patients and
normal volunteer controls. Psychiatric patients will include samples gr up)
of admitted in-patients, diagnosed according to ICD-9 criteria, as haying suffered
from a disorder of depression (endogenous, unipolar, receiving anti-depressant:;
medication) anxiety (generalized, receiving benzodiazepine medication) or schizophrenia
(under control by long-acting neuroleptics) which required treatment at the ROH.
In-patients will selected in order to increase monitoring and control of smoking
abstinence periods. Selection of patients for the study will occur during the' id-
point of their treatment regime. An attempt will be made to match patient grotips
on both duration of illness and time since last episode so as to make comparisons
between the various disorders. Patients with neurologic disorders and or acute
medical conditions which might interfere with the task of the study will be
screened from the study. Twenty habitual smokers and 20 non-smokers will be
sampled from each of the 3 diagnostic populations. Smokers will be defined as
those who have smoked cigarettes for at least 5 years, are smoking 10 or more
cigarettes/day, are presently inhaling. An attempt will be made to match patient
groups on duration of illness by equaling for number of hospitalizations. tota@
years of treatment etc. so as to make comparisons across the various disorders
Medication status, both past and present will be assessed for all patients in
all studies in order to examine possible relationships-and-interactions with
elactrophysiological data.
Normal volunteers will consist of 20 smokers defined above. These will be
selected from the staff of the ROH. Normal volunteers will be matched with
patients for age, sex and social class index will be matched with patient smokers
on smoking cfiaracteristics (i.e., no. of cigs/day/ smoking history, etc.) To bek'
included in the study, controls will have to meet the following criteria: no h story
of psychiatric treatment in themselves or in any of their Ist degree relatives 0
known neurologic disorder and no acute medical condition which would interfere th
task performance or interpretation of the study.
C=)
-curb
BATCo document for Province of British Columbia 15 April 1999

21
b) Study Design:
All subjects will attend the laboratory for two separate testing se sions,
separated by two days. For one session (Non-Abstinence) subjects Hill be ailowed
to smoke as usual up until the test time between 9 - 11 a.m. For the second
session (Abstinence) subjects will be asked to abstain from tobacco for thei
complete day (24 hours) preceding the test session. To ensure abstinence, is
maintained, expired alveolar CO air samples will be collected throughout thl@
preceeding test day (up until test time) at 2-hour intervals. Subjects
exhibiting excessive levels during the abstinence period will be screened fTom
the study. Half of the subjects in each group will start with the Abstinence
session first and the remaining half will start with the Non-Abstinence sesiion.
In addition to the questionnaires to be completed by each subject during the
laboratory sessions (see below), patient's ward behavior during Abstinent aAd
Non-Abstinent periods, will be rated by staff nurses employing the Nurses'
Observation Scale for In-patient Evaluation (NOSIE).
All subjects on having signed a consent form for participation in the study,
will complete a smoking history questionnaire; a smoking motives questionnaire;
a drug use questionnaire; and an Eysinck Personality questionnaire. ?I
c) Laboratory Design and Procedure:
Psychophysiological recordings in each session will focus n,CNVs ler
two conditions - distraction and no distration. Half of the subjects in each
group will start with the 'distraction' condition and the remaining half will
start with the 'no distraction' condition. Both conditions will be presented
at one session between 9:00 - 11:00 a.m. and all smokers will be asked to
refrain from smoking 11:00 p.m. the night before the session up until the time
they reach the laboratory. Upon reaching the laboratory, expired alveolar 6rbon
monoxide (CO) will be checked and subjects with excessive levels will be screened
from the study. Subjects will also be asked to refrain from coffee and tea, one
hour prior to the test sessions.
Upon arriving at the laboratory subjects will be screened for CO levels and
then administered self-rating questionnaires which will include- a cigarette
craving' questionnaire; a subjectives stress-arousal questionnaire; Zung
Depression questionnaire; Zung Anxiety Questionnaire and Hopkins Symptom Check
List. Following CO, questionnaires and application of electrodes, subjects:
will be instructed as to the nature of the CNV-reaction time task and will @e
allowed practice trials until 5 successive Lrials are completed. Opposite the
subject (distance: 2m) there will be a fixation point for the eyes, to limit
eye movements. The subjects will be instructed to refrain from movement an@
blinking during stimulus presentation.
All testing will take place in a sound-attenuated, electrically shielded
chamber with'a one-way viewing mirror which is immediately adjacent to the 1,
experimental control room housing the polygraphic, computer and associated 1
stimulus equipment. All tests will be taken with the subjects sitting in an
easy-chair with reduced room lighting and relatively constant temperatures.,
C=>
BATCo document for Province of British Columbia 15 April 1999

22
Before starting, subjects will be familiarized with the apparatus and procedure
and will be reassured that it will be harmless and painless, and will be tald
of their right to terminate participation at any time. Prior to their sess@ion
all subjects will have signed informed consent forms.
d) CNV Stimuli:
The basic stimulus procedure will be that of a constant fdreperiod simple
reaction-time paradigm. The preparatory stimulus (first stimulus on Sl)
consisted of a brief tone (50 msec, 1000 Hz. 70 dbA, 20 msec riseiand decay)
presented binaurally through earphones. The second imperative stimulus (S2) will
be a 9reen flash projected 2 m from the subject's eyes at an approximate angle
of 25 from the horizontal and standing at eye level. Sl-S2 intervals will be
4.0 sec and stimulus generation will be controlled by a Ficolet P@thfinder
EEC - Evoked Potential processor. Upon presentation of the S2 sti, 'mulus, subjects
will be required to respond by releasing the index finger of theirs dominantihand
from a 'home key' and pressing a 'response key' which terminates the S2 stimulus.
Reaction times will be monitored by a Lafayette Reaction Time Est*ator (Mohel
63017). Each subject will receive 16 trials per condition and inter-trial 4nterval
will vary from 15-20 sec.
e) Distracting Stimuli:
Distracting stimuli will be presented in the auditory modality (through
earphones) and will consist of 90 dbA. .1 msec clicks presented ati irregular
intervals of 500-2400 msec. In the distraction condition, click presentations
will begin 20 sec before the first trial and end immediately following the S2
stimulus of the 16th trial. Stimuli will be generated from a Grass auditors
click-time stimulator (Model SIO CTCM) and timing will be controlled by a
Cromemco Z2D microprocessor.
f) Recording Apparatus:
Nicolet Pathfinder amplifiers will be used to record EEG (CHv) and electro-
culogram (EOG) signals. The EEG will be recorded from Fz, Cz and Pz sites Jrith
linked earlobes (Al, A2) as reference. The EOG will be recorded from a Y' above
the left supra-orbital ridge and 1j" below the left infra-orbital ridge in I G@___
with the pupil. Electrodes will be Beckman Na-NalCl standard miniature types.
The time constant for EEG and EOC recordings will be 10 sec and the high frequency
cut-off will be 100 Hz (50% amplitude reduction) with 12 dB per oci ave roll'off.
Sensitivity will be set at 50uv/cm. Analog to digital conversions ( sampling,
every 16 msec) and time locked averaging of SI-S2 trials will be carried ou@ on-line
by the Nicolet Pathfinder and trials with EOG exceeding 50uv will be screened
from the final average.
Auditory evoked potentials (AEPs) to the distracting stimuli (from the same
receding sites) will be recorded from Biodata EEG amplifiers with low-and-high
frequency filters set at .16 and 100 Hz and sensitivity at 50uv/cm. 17 Croliemco
Z2D software signal averaging program will carry out analog to-digital conversions
(sampling every 2 msec) and complete the final average on line. Trials wit@ EOG
artifact exceeding 50 uv will be screened from the final average.
@N
BATCo document for Province of BritiSh Columbia 15 April 1999

2 3
Electromyographic (EMG) activity will be recorded using a bipolar montage
(using Beckman Na-NaICI miniature electrodes) from the forearm extensors o4. the
non-dominant hand. EMG signals will be amplified by a Beckman 9852A EMG cc6plex
with filter settings at 5 Hz - 2000 Hz and sensitivity at 50 uv/cm. The Crl'amemco
Z2D software will perform time-locked SI-S2 average integration on EMG signals.
Heart rate (HR) activity will be recorded form-s standard Lea@ II
_Positiion
(RA-LL) using Beckman electrodes and a Beckman 9857 cardiotachometer which gives
HR on a sec by sec basis.
Electrodermal skin conductance (SC) activity will be recorded -with miniature
Beckman electrodes placed on the mid-portion of the first 2 finger' of the
non-dominant hand. A 0.5% Na Cl electrolyte will be employed. Skin conductance
activity will be amplified by a Beckman 9844 constant voltage skin conductance
coupler with sensitivity set at .05 uhmos/cm.
f) Data Reduction:
CNV averages will be "normalized" about a 1-sec baseline preceding I.
CNV parameters scored were: 'O' wave amplitude of the CNV, which was defineo
as a point of maximal negativity during 400-750 msec post SI; 'E' @Jwave amplitude
which was defined as a peak amplitude in 100 msec proceeding S2; PINV, the
time from onset of S2 to next base-line cross. In-&addition to these measures,
HI and F2 auditory evoked potentials to SI (amplitude and latency)@and NI ap'd
P2 visual evoked potentials were analysed. Auditory HI is defined as the mbst
negative peak 75-150 msec post SI and P2 is the most positive peak 180-250 @hsec
past SI. Visual Nl is defined as the most negative peak 75-140 msec post SI and
P2 is the most positive peak between 105-250 msec post S2.
Parameters scored on AEPs to distracting stimuli will be limited to PI. !Nl,
P2, N2 components. N1 and P2 are as described above, and PI is the most positive
peak between 40-70 ms post stimulus and N2 is the most negative peak after 225
msec. Latency and amplitude measures will be scored.
Scoring of averaged integrated EMG activity will be limited toithe absolute
level prior to SI and to the difference in integrated E24G activity. between pre-
S2 and pre-SI.
Heart rate scoring will focus on resting level defined as the mean of the
10 beats pre-Sl and on maximum deceleration defined as the difference between
resting level pre-Sl and the minlyn- HR at the beat just prior to S2 onset.
In additi.on, maximum HR acceleration. defined as the highest beat 0-10 secsi
post S2 (expressed as a difference relative to baseline) will be examined.
Each of these response measures will be averaged across trials.
Scoring of skin conductance activity will focus on: -total non-specifict
response deffned as responses equal to or exceeding .05 uhmos between 10 sees
post S2 of a trial up to SI, beginning 10 sec post S2 of trial-1; skin conductance
level defined as the average (over 16 trials) resting level just prior to Sl;
skin conductance response pre-S2 defined as the difference between skin conauc-@
tance pre-SI and pre-S2; maximum skin conductance response post S2 defined As the
-post S2(::@
difference between pre-Sl skin conductance and maximum conductance O-IO sec,
CN
BATCo document for Province of BritiSh Columbia 15 April 1999

- 24
h) Data Analysis:
Each of the scored components for CNV, AEPs, EMG, HR and SC (incl 9
eact ion time), will be submitted to a split-plot 4 (Groups) x 2 (Smokingutstinence-
on-Abstinence) x 2 (No Distraction-Distraction) analysis of variance (ANOMA) with
etween group variables and one within group variable. Correlation coe-f
-ill be run on each measure with respect to symptomatology 3s assessed by s
;elf-report ratings on a recent drug-trial and/or as assessed by the presepleviou
;elf-report ratings acquired in the laboratory. If indicated, multivariate
uialysis procedures will be employed.
2. Study II: Changes in Smoking Patterns and Their Effects in Psychiatric:
Patients From Admission Through to Dischar;
_ge from Treatment
a) Subjects, Design and Procedure:
As in Study 1. subjects will consist of 3 groups (n -20) of psychialic
in-patients (diagnosed as anxiety, depression, schizophrenic disorders) and a
group (n- 2 0) of normal volunteers, all smokers fitting the criteria described
previously. Patients will be assessed on two separate occasions,-once within
the first 3 days of admission and once within 3 days prior to discharge. Oh
t
each occasion, patients will attend the laboratory at 9:00 a.m. after having I
abstained from tobacco overnight and CNVs and associated elect-rophysiology ill
be examined under distraction and non-distraction conditions, both before aild
immediately after a 1-hour smoking period while completing questionnaires
identical as those stated in study I, each patient's smoking pattern will be
observed through a one-way mirror and a video-recording system. @he target!
behaviours which will be monitored include: (1) cigarette frequency - number of
cigarettes lit during the 45-minute period f*119wing the strikinglof the fi@'rst
match; (2) inter-cigarette-interval - amount of time from the termination of the i
first cigarette to the beginning of the second cigarette; (3) puff frequency per
cigarette - number of times lit cigarette contacts smoker's lips; (4) percentage
of tobacco burned - grams of tobacco burned divided by grams of tobacco in unlit i
cigarette; (5) cigarette duration - time elapsed between lighting of a cigarette
and putting it out in the ashtray; (6) inter-puff-interval - amount of time
elapsing between each puff of each cigarette; (7) puff duration - amount of time
lit cigarette was in contact with the subject's lips and 'flaring'. CO samples
will be collected before and after smoking. Total number of cigarettes smoked/
day will also be recorded for each patient on each of the two target days. iin
addition, CO samples will be collected at 2-hour intervals on each target day.
This will be assessed by having patients deposit their butts in a collection bag
on each day.
Twenty non-smokers, matched ofr age, sex and social class will be selec ed
from the ROH staff and assessed on the same parameters on two separate sessions.
Attempts will be made to match inter-session intervals with those observed @-n
patients.
C=l
BATCo document for Province of British Columbia 15 April 1999

2 5
b) CNV Stimuli: as in Study I
c) Distracting Stimuli: as in Study I
d) Recording Apparatus: as in Study I
e) Data Reduction: as in Study I
f) Data Analysis:
Each dependent measure will be submitted to a 4 (Group) x 2 (Session) A6VA
and will be allowed through with appropriate a priori and past cT-tests.
Study III: Smoking Status of Psychiatric Patients and its Relationship to
Treatment Outcome
a) Subjects, Design and Procedures:
Samples of anxiety patients, depressive patients and schizophrenics.
(ranging from n - 60/group) who have entered and completed a clinical drug trial
within the last 2 years will be the subject population. The drug trials in C- I Li de
the following: (a) Dose Ranging Study of Bromazepamin Generalized Anxiety Disorders;
(b) A Double-Blind Placebo Controlled Randomised Comparative Study of Fluvbxamine
and Tmipramine in In-patients with Primary Depression and (c) A Comparison; of
Haloperidol and Fluphenaz ine in the Treatment of Chronic Schizoph. ic son 0
Symptom severity and treatment outcome data is available from case record fprms or
patient charts. When smoking status is not available, patients will be contacted
by telephone or mail in order to assess smoking characteristics. Patients in each
group will be divided into 4 categories; non-smoker (as defined in Study 1) ; light
smoker (up to 10 cigs/day); moderate smoker (up to 2'5 cigs/day); heavy smoker
(greater than 25 cigs/day). Treatment outcome scores will be assessed by examining
"difference scores" on clinically rated and self-reported Symptom scales.
b) Data Analysis:
A one-way, 4 level (Smoker Category) ANOVA will be applied to each treatment
outcome score for each of the drug trials. Within each drug trial, treatment outcome
scores will be correlated with smoking characteristics such as number of ye rs
smoking. number of cigarettes/day etc.
(_^J
co
BATCo document for Province of British Columbia 16 April 1999

REFERENCES
ACUE. C.: Smoking Patterns, nicotine intake at different times of day: and
changes in two cardiovascular variables while smoking cigarettes
Psychopharmacologia, 30, 135-144,.1973.
ALEXANDER, A.A.: Psychophysiological concept of psycopathology. In: N!
Greenfield, R. Sternback (Eds.), 925-964, New York, Holt, Rineha5lt
and Winston. 1972.
ANDERSSON, K.: Effects of cigarette smoking on learning and retention
Psychopharmacologia, 41, 1-5, 1975.
ANDERSSON, K. and HOCKEY, G.: Effects of cigarette smoking on incidental
memory. Reports from the Department of Psychology, University o
Stockholm, no. 455, 1975.
ANDERSSON, K. and POST, B.: Effects of cigarette smoking on verbal ra
learning and physiological arousal. Scandinavian Journal of
Psychology, 15, 263-267, 1974.
ARMITAGE, A., HALL, C. and SELLERS, C.: Effects of nicotine on
electrocortical activity and acetylcholine release from the cot
cerebral cortex. British Journal of Pharmacology, 35, 157-160,
1969.
ASHTON, H., MARSH, U., MI J., RAWLINS, M., TELFORD, R. and
THOMPSON, J.: The use of event-relared slow potentials of the brhin
as a means to analyse the effects of cigarette smoking and nI CC)
in humans. In: Smot,@_Ing Behaviour, Physiological and Psychological
Influences, R. Thornton (Ed.), 54-68, New York, Churchill
Livingstone, 1978.
ASHTON, H., MILLMAN, J. E., TELFORD, R. and THOMPSON, J. W. : Stimulant ank
depressant effects of cigarette smoking on brain activity in man..
British Journal of Pharmacology, 48, 715-717.
ASHTON, H. and WATSON, D.: Puffing frequency and nicotine Intake in
cigarette smokers. British Hadical Journal, 19 ' 679-631 t 1970.
BACHNEFF, S.A. and ENGELSWN.: Contingent negative variation, postiop ra
tive, negative variation, and psychopathology. Biological
Psychiatry, 15(2), 323-327, 1980.
BATT IC, K.: The smoking habit and psychopharmacological effects of
nicotine. Activ. Nerv. Sup. (Praha) 22, 274-288, 1980.
BERLYNE, D., BORSA, D., HAMACHER, J., KOEING, I.' Paired associate
learning and the time of arousal. Journal of Experimental
Psychology, 72, 1-6, 1977.
BHATTACHARYA, I. and GOLDSTEIN, L.., Influence of active and chronic
nicotine administration on intra- and inter-structural relationships
of the electrical activity in the rabbit brain. NeuropharmacologX,
9, 109-118. 1970.
BLOWERS; G. H. : The CNV: An electrocortical sign of attention or arousal?
Ps7chologia, 20(4), 206-215, 1977.
BOLZ, J., GREDKO, H. and HEIMANN, H.:_GSR,.AEP and CNV in depressed
patients and healthy controls. f-a Human Evoked Potentials, Le
D. and Callaway, E. (Eds.), Plenum Press, New York, p.448. I I
BOND, A.J.,-JAMES, D.C. and LADER, M.H.: Physiological and psychological
measures in anxious patients. Psychol. Med. 4, 364-373. 1974.
C]LkSF, W. C. I GRAHAM, F. K. and GLXHAM, D.T.: Components of HR response iri
anticipation of reaction time and exercise tasks. Journal of
Experimental Psychology, 76, 642-648, 1968.
BATCo document for Province of British Columbia 15 April 1999

CUATTOPADHYAY, P.Y., BOND, A.J. and LADER, H.H.., Characteristics of
galvanic skin response in anxiety states. Journal of Psychiat.
Res., 12. 265-270, 1975.
,CHERRY, N. and KIERNAN, K.: A longitudinal study of smoking and
personality, In: Smoking Behaviour: Physiological and
Psychological Influences, R. Thornton (Ed.), 12-18, Edinburgh,
Churchill Linvingstone, 1978.
CHRISTEE, N.J., LITTLE, B.C. and CORDON, A.M. Peripheral Indices of
Depressive states. In: H.H. Van Praag, 11-I.H., Lader, O.J.,
Rafaelsen, E.j., Sachar (Eds.), New Yer!:, Marcel Dekker, Inc., 1980.
Handbook of Biological Psychiatry. Part II. Brain Mechanisms
Abnormal Behavior - Psychophysiology.
CONRIN, J. The EEG effects of tobacco smoking--a review. Clinical
Electroencaphalography. 11, 4, 180-187, 1980.
DEMETILISCU, R. and DEMETRESCU, M. Ascending inhibition and activation
from the lower brain stemt the influence of pontine reticular
stiwilation on thalaoocortical evoked potentials in the rat.
Electroencephalography and Clinical Neurophysiology, 14, 602-620,
1962.
DOMINO, E.: Electroencephalographic and behavioral arousal effects of
small doses of nicotine: a neuropsychopharmacological study. Annals
of the New York Academy of Science, 142, 216-244, 1967.
DOMINO, E. Neuropsychopharmacology of nicotine and tobacco sm.3king. In:
Smokina Behaviors: Motives and Incentives. W.L. Dunn (Ed.), Ne-w
York, John Wiley & Sons, 1973.
DONGIER, K. Event-related slow potentials: recent data on clinicl
significance of CNV and PINV. Research Communications in
Ps;chology, Psychiatry and Behavior, l(l), 1976.
DONGIER, M., DUBROVSKY, E. and ENGELS'_Lk.%N, F. Event-related slow
potentials in psychiatry. In: Shagass, C., Gershon, S. and I
Friedhoff, A. (Eds.) Psychopathology and Brain Dysfunction. -New
York: Raven Press, 1977.
DUFFY, E. Activation and Behavior. few York: Wiley, 1962.
DUFFEY, E. Activation. In: Handbook- of Psychophysiology, N. Creenfield
and R. Sternback (Eds.), New York, Holt, Rinehart and Winston, Inc.,;
1972.
DUNCAN-JOHNSON, C. and COLES, H. Heart rate and disjunctive reaction
time: The effects of discrimination requirements. Journal of
Experimental Psychology, 103(6). 1160-1168. 1974.
DUNQN, W.: Experimental methods and conceptual models as applied to the
tudy of motivation in cigarette smoking. In: Smoking Behavior:
r,
motives and Incentives. W. Dunn (Ed.), 93-111, Washington,,D.C.' z
Winston and Sons, 1973.
DUNN, W. : Smoking as a possible inhibitor of arousal. In: Behavioural
Effa@ts of Nicotine, K. Batti- (Ed.), 12-25, Basal, S. Karger, 1978.i
EASTERBROCK, J.: The effect of emotLon on cue utilization and the
orgnnization of behaviour. Psychologi!:al Review, 66, 183-201. 1959.1t
EYSENCK, A.: The Biolocgical Basis Of Personality. Springfield: C.C.
Thomas, 11967.
EYStNCK, H.: nd the Maintenance of the Sooking Habit. In:
Personality a
Smoking Behaviour: Motives and Incentives. W. Dunn (Ed.) 113-146,
Washington, D.C., Winston & Sons, 1973. C=)
EYSENCK, H.: The Causcs and Efects of Smokin.g. Great Britain, @!aurice
Temple Smith, Ltd., 1980-
.L
BATCo document for Province of BritiSh Columbia 15 April 1999

FACERSTROM, K. and GOTESTM, K.: Increase in muscle Conus after tobacco
smoking. Addictive Behaviors, 2, 203-206, 1977.
FOWLES, D.C. (Ed.) Clinical Applications of Psychophysiology. New York-:
Columbia University Press, 1974.
FRANUNHAUSER, M., HYRSTEN, A., POST, B., JOILANSSON, G.: Behavioral and
physiological effects of cigarette smoking in a monotonous Si
Psychopharmacologia, 22, 1-7, 197f.-
FRIEDMAN, J., GOLDBERG, J., HORVATH, T., and ',IEARES,R.: The effect of
tobacco smoking on evoked potentials. Clinical Experimental
Pharmacology and Physiology, 1, 3, 249-58, 1974.
FRIEDHAN, J., HORVATH, T. and MEARES, R.: Tobacco smoking and a stimulus
barrier. Nature, 248, 455, 1974.
FRIEDMAN, J. and MEARES, R.: Smoking and cortical evoked potentials: an
opposite effect on auditory and visual systems. Clinical and
Experimental Pharmacology and Physiology, 7, 609-615, 1980.
GILBERT, D.: Paradoxical tranquilizing and emotion-reducing effects of
nicotine. Psychological Bulletin, 86, 643-661, 1979.
GILBERT, D.: Extraversion and self-reported reason for and times of urge:
for smoking. Addictive Behaviors, 5, 97-99, 1980.
GOLDSTEIN, J. B. Physiological responses in anxious women patients'. A
study of autonomic activity and muscle tension. Arch. Gen.
Psychiatry, 10, 382-383.
GOLDSTEIN, L., BECK, R. and HUNDSCHENK, D.: Effects of nicotine upon I
cortical activity of the rabbit brain: quantitative analysis.
Annals of the New York Academy- of Sciences. 142, 130-180, 1967.
GREDKO, H., BOLTZ. J. and HFI',L-'LXN, H.: Evoked potentials, expectancy wave
and skin resistance in depressed patients and healthy controls.
Pharmakopsychiatrie 13:91-101, 1980.
HALL. R., RAPPAPORT, M., HOPKINS, H. and GRIFFIN, R.,: Tobacco and evoked
potential. Sciences, 180, 212-214, 19 73. 11
HART, J.: Physiological responses of anxious and normal subjects to
simple signal and non-signal auditory stimuli. Psychophysiology,
11(4), 443-451, 1974.
HEIMSTRA, N., FALLESEN, J., KINSLEY, S. and WARNER, N.: The effects of
deprivation of cigarette smoking on psychomotor performance.
Ergonomics, 23, 1047-1055, 1980.
HENDERSON, S., LEWIS, I.C., HOWELL, R.H. and ROYNER, K.J.: rental Health
and the use of alcohol, tobacco, analgesics and vitamins in a
secondary school population. Acta. Psychiatrica Scandinavia, 63,
186-189, 1981.
HUTCHINSON, R. and EMLEY, G.: Effects of nicotine on avoidance,
conditioned suppression and aggression response measures in animals:,
and men. In: Smoking Behaviour: Motives and Incentives. W. Dttnn
(Ed.), 171-196, Washington, Winston and Sons, 1973.
IRWIN, S.: Rational ramework for the development, evaluation and-use of I
psychoactive drugs. American Journal of Psychiatry, 124, 1-19, i
1968.
JAFFE, J. and JARVIK, M.: Tobacco use and tobacco use disorder. In
Psychopharmacology: A Generation of Progress. 1665-1677. Raven
Press, New York, 1978.
JAMISON, R.: ,Personality, antisocial behaviour and risk perception in
adolescents. London: University of London, unpublished Ph.D.
thesis, 1978.
JASPER, H.: Reticular Formation of the Brain, London. Churchill
Livingstone. 1958.
BATCo document for Province of British Columbia 15 April 1999

KAHNEKAN, D.: Attention and Effort. Englewood Cliffs: Prentice-Hall,
1973.
KELLY, D.H.W.(1966): Measurement of anxiety by forearm blood flow.
British Hournal of Psychiatry 112, @89-798.
KLEINSMITH, L. and KAPLAN, S.: Paired associate learning as a function o@
arousal and interpolated interval. Journal of Experimental
Psychology, 65, 190-193, 1963.
KNOTT, V.: Smoking, EEC and input regulation in smokers and non-smokers.
In: Smoking Behavior: Physiological and Psychological Influences,
R. Thornton (Ed.), 115-130, Edinburgh, Churchill Livingstone, 1978. i:
KNOTT, V.: Psychophysiological correlates of s=okers and non-smokers'
studies on cortical, autonomic and behavioral responsivity. In:
Electrophysiological Effects of Nicotine, A. RAmond, C. Inaid
(Eds.), 99-116, Amsterdam, Elsevier, 1979.
KNOTT, V.: Reaction time, noise, distraction and autonomic responsivity
in smokers and non-smokers. Perceptual and Motor S',-ills, 50,
1271-1280, 1980.
KNOTT, V.: Reaction time, distraction and sex differences in smokers and
non-smokers, 1981a (In preparation).
KNOTT, V.: Electrodermal reactivity to high intensity stimuli: sex
differences in smokers and nonsmokers, 1981b (In preparation).
KNOTT, V. and PETERS, J.: Changes in CNV amplitude with progressive
induction of stress as a function of sex. Electroencephalography
and Clinical Neurophysiology, 1974. 36:47-51.
KNOTT, V. and 11E.N.A.BLES, P.: EEG alpha correlatas of non-s=okarrs, s@rcokarrs,
smoking and smoking deprivation. Psychophysiology, 14, 1507156,
1977.
KNOTT, V. and VENABLES, P.: Stimulus intensity control and the cortical
evoked response in smokers and nonsmokers. Psychophysiology, 15,
186-192, 1978.
KNOTT, V. and VEN&BLES, P.: Separate and combined effects of alcohol and
tobacco on the amplitude of the contingent negative variation.
Psychopharmacolo.ay, 70, 167-172, 1930.
KOZLOWSKI, L.: Psychosocial influences on cigarette smoking. In: National
Institute on Drug Abuse Research 26. N. Krasnegor (Ed.), Rockville,
Maryland, Department of health. Education and Welfare, 1979.
KUCEK, P.: Effect of smoking on performance underload. Studia
Psychologia, 17, 204-212, 1975.
LADER, M.H.: Palmar skin conductance measures in anxiety and photic
states. J. Psychosom. Res. 11, 271-281, 1967.
logy of anxious and depressed patients. In:
LADER, H.H.:The psychophysio
Clinical Applications of Psychophysiology, Fowles, D.F. (Ed.) 12-41,
New York, Columbia University Press, 1975b.
LADER, M.H.: The psychophysiology of anxiety. In: Handbook of Biological
Psy@hiatry Part 11 Brain Mechanisms and Abnormal
Behavior--psychophysiology, H. Van Pruag, M. Lader, 0. Rafaelsen, E.
Sacher (Eds.), New York and Basel, Narcel Dekker, Inc., 1930.
LADeR, ti.11. and WTNG, L.: Physiological Heasuras, Sedative Drugs, and
Morbid 6nxiety. Oxford University Press, London, 1966.
tal and
LARSON, P.S., HAAG, H.B., and SILVETTF, H. Tobacco: Experimen
clinical studies. Baltimore: Williams & 1.1ilkins. 1961.
LIDENTRAL, J., HYEkS, J., and PEPPER, M.: Smoking, psychological status
. Social Sciences and 'iedicine 6. 533-591. 1972,
and stress C=)
BATCo document for Province of BritiSh Columbia 15 April 1999

LINDSLEY, D., and RUBENSTEIN, B.: Relationship between brain potentials
and some other physiological variables. Proceedings of the Society
of Experimental Biology and Medicine 35, 558-563, 1937.
LOVELESS, N.E. and SANFORD, A.J.: Effects of age on the contingent
negative variation and preparatory set In a reaction-time task.
Journal of Gerontology, 29, 52-63, 1974.
LYKKEN, D.: Psychometric applications of the EEG. In: Clinical
Applications of Psychophysiology, D. Fowles (Ed.) 139-166, New York,
Columbia Unversity Press, 1975.
RACkWORTH, J.: Vigilance and Habituation. Middlesex, Penguism, 1969.
MAL40, R.B.: Activation: A neurophysiological dimension. Psychological
Review, 66, 367-386, 1959..
MAL-110, R.B.: Overview. In: Handbook of Psychophysiology, N. Greenfield
and R. Sternback (Eds.), New York, Holt, Rinehart and Winston, Inc.,
1972.
MALMO, R.B., SKAGASS, C. and HESL&M, R.M.: Blood pressure response to
repeated brief stress in psychoneurosis: A study of adaptation.
-179, 1951.
Can. Journal of Psychology, 5, 167
MATARZZO, J., SASLOW, C.: Psychological and related characteristics of
smokers and non-smokers. Psychological Bulletin, 57, 493-513, 1960.
MANGAN, C., GOLDING, J.: An enhancement model of smoking maintenance.
In: Smoking Behaviour: Physiological and Psychological Influences.
R. Thornton (Ed.), 87-114, New York: CHurchill Livingstone, 1978.
MCARTHUR, C., WALDRON, E., DICKINSON, J.: The Psychology of Smoking.
Journal of Abnormal Psycholoe, 57, 267-275, 1958
MCCALLUK, W.C. and WALTER, W.G.: The effects of attention and distraction
on the contingent negative variation'in normal and neurotic
subjects. Electroencephalography and clinical neurophysiology, 25,
319-329, 1968.
MCKEUNELL, A.: Smoking motivation factors. British Journal of Social and
Clinical Psychology, 9, B-22, 1970.
MEYER, A., FRIED,%Vul?, L., LAZER.FELD, P.: Motivational conflicts
engendered by the ongoing discussion of cigarette smoking. In:
Smoking Behaviour; Motive and Incentives, W. Dunn (Ed.): 243:-254,
Winston and Sons, Washington, 1973.
MILLS, I.: Coping Mechanism@; in the Brain. In: Smoking Behavior
Physiological and Psychological Influences, R. Thorton, (Ed.)!. 1-11.
Churchill Livingstone, Edinburgh, 1978.
HURPHREE, H.. PFEIFFER, C. and PRICE, L.: Electroencephalographic changes
in man following smoking. Annals of the New York Academy of
Sciences, 142, 245-260, 1967.
MYRSTEN, A., ANDERSON. K.: Effects of cigarette smoking on human
performance. In: Smoking Behavior: Physiological and Psychological
Influences. R. Thornton (Ed.), 156-167, New York: Churchill
Livingstone, 1978.
MYRSTEN, A., ANDERSSON, K., FRANKENHAEUSER, M. and ELCEROT, A.: Immediate
effects of cigarette smoking as related to different smoking habits.
Perceptual and Motor Skills, 40, 515-523, 1975.
NELSON, J.:' Neurophysiological and Benavioral consequences of chronic
nicotine treatment. In: 'Drug Addiction Vol. 3. Neurobiology and
Influences on Behavior. J. Singh aud H. Lal (Eds.), 375-336, New
York, Stratton Intercontinental, 1974.
NELSON, J., PELLEY, K. and GOLDSTEIN, L.: Chronic nicotine treatment in
rats: 2. 'Electroencephlographic amplitude and variability -changes
occurring betwuen and within structures. Rcsearch Communications in
Chemical Pathology and Pharmacology. 5, 764-704, 1973.
BATCO document for Province of BritiSh Columbia 16 April 1999

NESBITT, P.: Smoking, physiological arousal and emotional response.
Journal of Personality and Social Psychology. 25, 137-144, 1973.
O'CONNOR, K.: Individual differences in the effect of smoking on
frontal-cencral distribution of the CNV: Some observations on
smokers' control of attentional behaviour. Person. indiv. Diff., 3.
-235, 1982.
271
PARR, D. Smoking and psychiatric patients. British 'medical Journal, p.
1611-1612, 1963.
PERRIS, C.: Central measures of depression. In: Handbook of Biological
Psychiatry, Part It Brain Mechanisms and Abnormal
Behavior--Psychaphysiology. New York, "tarcel Dekker, Inc., 1980.
PETRIE, A.: Individuality in Fain and Suffering. Chicago, Chicago
University Press, 1967.
POWELL, C., STEWART, R., GRYLLS, D.: The personality of young smokers.
British Journal of Addiction, 74, 311-315, 1979.
PRADRAN, S., and BUCA, D.: Studies on gross behavior and electrical
activity of the brain during various environmental and
pharmacological states. Research Communications in Psychology,
Psychiatry, and Behavior, 1, 257-268, 1976.
ROUTTEMBERG, A.: The two arousal hypotheses: Reticular formation and
limbic. system. Psychological Review 35, 51-80, 1968.
RUBIN, L.S.: Autonomic dysfunction as a concomitant of neurotic
behaviour. J. Nerv. 1-lent. Dis., 138, 358-574, 1964.
RUSSELL, M.: Tobacco smoking and nicotine dependence. In: Recent
Advances in alcohol and Drug Problems, Vol. III, R. Gibbins'(Ed.)
1-47, New York: V11ey S Sons, 1976.
RUSSELL, M., PETRO, J., PATEL, V.: The classification of smoking by
factorial structures of motives. Journal of the Poyal Statistical
Secrety, 137, 313-346, 1974. 9
SALXONS, P. and SI.MS, A.: Smoking profiles of patients admitted for
neurosis. Brit. J. Psychiat., 139, 43-46, 19S1.
SCILIXTER, S. : Ne3bitts paradox. In: Smoking Behavior: Xatives and
Intentives. W. Dunn (Ed.), 147-155, New York, Winston and Sons,
1973.
SCHACTER, S.: Pharmacological and psychological determinants of smoking.
In: Smoking Behaviour: Physiological and Psychological Influences.
R. Thornton (Ed.), New York, Churchill Livingstone, 1978.
scHAzoPPI, v.-. -Effects of nicotine administration to the cat's lower brain
stem upon electroencephalographic. and autonomic system. Anals of
-49,
the New York Academy of Science, 142, 40 19 67.
SELTZER, C.: Why people smoke. Atlantic Monthly, 211, 41-43, 1962.
SELTZER. S., FRIEDMN, G., SIECELAUU, A., and COLLEN, M.: Smoking habits it
and pain tolerance. Archives of Environmental Health, 24, 170-172,
1974.
SIMASS, C.: Differentiation betwee- anxiety and depression by the
photically activated electroencephalogram. Am.J.Psychiatry 112,
41-4G, 1955.
SMALL, J.G. and SUALL, I.F.: Contingent ncyntivc variation (C%V)
correlation with psychiatric diagnosis. Arch. Cen. Psychiat., 25,
550-554.
SPOHN, II.E. and PATTERSON. T. Recent stufli.:.s of psychaphysiology in J
schizophrenfa. In: Snecial. Peport: Schivoptircnia, 1980. National I
Institute of Mental Heillch. S. VeiLh and I.. Xasher (Fds.).
Vapartment of Ht.-alch and Iturian Sorvicc-:;, 1980. Ln
LJ_4
BATCo document for Province of BritiSh Columbia 15 April 1999

STEPNEY, R.: Smoking as a psychological tool. Bulletin of the British
Psychological Society. 32., 341-345, 1979.
STEPNEY, R.: Smoking behaviour: A psychology of the cigarette habit.
British Journal of Diseases of the Chest, 74, 325-344, 1980.
STEWARD, L. and LIVSQN, N.: Smoking and rebelliousness. Journal of
Consulting Psychology, 30, 225-229, 1966.
TEECE, J., SAV IC J. and COLE, J.: Drug effects on CKV and,;y
blinks: the distraction arousal hypothesis. In: Psychopharmacolo
A generation of Progress, M. Lipton, A. Dimaccio, K. Killman (Eds. ) I
745, New York Raven, 1978.
TEECE, J., SAVIGNANO-BOWMMI, J. and '&11EINBF_ESSO,D.: Contingent negative
variation and the distraction-arousal hypothesis.
Electroancephalography and Clinical Neurophysiology,41.277-286, 197
THOMAS, C.: Personality differences between smokers and non-smokers,
Maryland State Medical Journal, 114, 84-87, 1978.
TIKSIT-BERTHIER, H., DEUUNCY, J. and ROUSSEAU, J.: Some problems and
tentative solutions to questions raised by slow potential 'changes it,
psychiatry. In: McCallum, W. and Knott, J. (Eds. ) The Responsive
Braid. Bristol: Wright, 1976.
TIMSIT-BERTHIER, H., KON I NCKX, N., DARGENT, J., FONTAIA, O., and DONGIER,
M.: Variations contingents nfigatives en psychiatric.
Electroencephalog. Clin. Neurophysiol., 2B, 41-47, 1970.
TOMKINS, S.: Psychological model for smoking behavior. American journa
of Public health, 56, 17-20, 1962.
TONG, J., HENDERSON, P. and CRIPPERIFIELD, B.: Effects of ethanol -and
tobacco on auditory vigilance performance. Addictive Behaviour, 5
153-158, 1980.
TONG, J., KNOTT, V., MCGRAW, D. and LEIGH, C.: Smoking and human
experimental psychology. Bulletin of the British Psychological
Society, 27, 533-538, 1974.
TONG, J., LEIGH, G. CAUPBELL, J. and SMITH, D.: Tobacco smoking,
personality and sex factors in auditory vigilance performance.
British Journal of Psychology, 68, 365-370, 1977.
U.S. Public Health Service. Smoking and health: Report of the Advisory
Committee to the Surgeon General of the Public Health Service.
(USPHS Publication 'No. 1103) Washington, D.C.: U.S. Government
Printing Office, 1964.
VAN PRAAC, H.M., LADER, M.H., RAFAELSEN, O.J. and SACHAR, E.J.: Handbook'
of Biological Psychiatry Part 11 Brain Mechanisms and Abnormal
Behavior-Psychophysiology. 'New York. Marcel Dekker, Inc.. 1980.
VASQUEZ, A., and TOMAN, J.: Some interactions of nicotine with other
drugs upon central nervous system function. Annals of the New Yor
Academy of Sciences, 142, 209-215, 1967. i 0 J
WALKER, E. and TARTE, R.: Memory storage as a function of arousal and
time with homogenous and heterogenous lists. Journal ofVerbal
Learning and Verbal Behaviour, 2. 113-119, 1963.
WALLER. D. and LEVANDER, S.: Smoking and vigilance. I i
70, 131-136, 1980.
ft g and
WARBURTON D. and WESNES, K.: Individual differences in smok in
'%. 'In: R. Thornton (Ed.) Smoking Behaviour:
attentional performance.
Physiological and Psychological Influences. London. Churchill-
Livingston, 1978.
BATCo document for Province of British Columbia 15 April 1999

WARiURTON, D. and WESNES, K.: The role of electrocortical arousal in the
smoking habit: electrophysiological. effects of nicotine, A. Rfimond,
S. Enaid (Eds.), 183-199,,Amsterdam: Elsevier, 1979.
WEBSTER, D.: The dynamic quantitation of spacticity with automated
integrals of passive motion resistance. Clinical Pharmacology and
Therapeutics, 5, 900-908, 1974.
WEERTS, T.C. and 1ANG, P.J.: The effectof eye fixation and stimulus and
response location on the contingent negative variation (CNV),
Biological Psychology, 2, 1-19, 1973.
WESNES, K. and WARBURTON, D.: The effects of cigarette smoking and
nicotine tablets upon human attention. In: Smoking Behavior:
Physiological and Psychological Influences. R. Thornton (Ed.),
131-147. New York: Churchi.11 Livingstone, 1978.
WILLUMS, D.: Effects of cigarette smoking on immediate memory and
performance in different kinds of smokers. British Journal of
Psychology, 7, 83-90, 1980.
ZUCKERMAN, M., PERSKY, H. and CURTIS, C.C.: !L-lationships among anxiety,
depression, hostility and autonomic variables. J. Nerv. Ment.
Dis., 146, 481-487.
t
U14
BATCo document for Province of BritiSh Columbia 15 April 1999