Download Effort and Cognition in Depression - Research

Effort and
Robert M.
Cognition in Depression
Cohen, MD, PhD; Herbert Weingartner, PhD; Sheila
A.
performance and cognitive function were examined
depressed patients and controls. Increasing severity of
depression was strongly associated with decrements in performance in both motor and memory tasks. Greatest depressionrelated impairment was found on those cognitive and motor
tasks that required sustained effort. We discuss these results in
terms of a generalized deficit in the central motivational state of
depressed individuals.
(Arch Gen Psychiatry 1982;39:593-597)
\s=b\ Motor
in
changes frequently
Cogni
t
i
v
e
Laboratory
depressed patients
accompany the mood disturbances that characterize the affective disorders.12
show a
observations of
positive correlation between the degree of memory impairment and the intensity of depression.35 However, the
mechanisms and structure of cognitive changes in depression remain poorly understood2 (R.M. Cohen, MD, PhD, et
al, unpublished data, May 1978). The difficulties are due
both to a lack of systematic exploration of depressionrelated cognitive mechanisms and the uncertainties in our
understanding of unimpaired cognition.
These latter uncertainties arise in part from a failure of
staging theories of information processing to adequately
differentiate the components of memory and learning, eg,
attention, short-term memory, long-term memory, retrieval, and memory consolidation.618 In place of staging theories, new strategies have emerged that emphasize the
context for processing an event, the characteristics of the
to-be-remembered stimuli, and the elaborateness of the
operations performed by the subjects as determinants of
whether an event is memorable.1922 This "single trace"
conceptualization of information processing has been
increasingly useful and productive in the study of learning
and memory.
Within this theoretical framework, investigators have
devised strategies for manipulating the activity or effort
required of experimental subjects to successfully complete
cognitive tasks. Specific cognitive operations are classified
somewhere along the continuum between active and passive.10,2325 Passive or automatic operations are defined in
part by their capacity to be carried on simultaneously with
little cost in their performance. In contrast, tasks that
involve effort or active processing require some sustained
motivation, are more easily disrupted, and are not independent of other operations that also require effort. As
currently conceptualized by some researchers in this area,
automatic processes appear to be "wired in" and species
specific, whereas effortful processing appears to involve
more individual variation between and within subjects.
This distinction between effortful and passive or automatic processing of information may be used to conceptualize
strategies for defining the cognitive impairments in
Accepted for publication Aug 24, 1981.
From the Clinical Neuropharmacology Branch (Drs Cohen and Murphy),
the Laboratory of Psychology and Psychopathology (Dr Weingartner and
Ms Smallberg), and the Biological Psychiatry Branch (Dr Pickar), National
Institute of Mental Health, Bethesda, Md.
Reprint requests to Clinical Neuropharmacology Branch, National Institute of Mental Health, Bethesda, MD 20205 (Dr Cohen).
Smallberg; David Pickar, MD; Dennis L. Murphy, MD
depression. For example, the degree of arousal and mood
state are considered influential determinants primarily of
effortful processing.
Both social-learning theory and cognitive-behavioral
theory have considered the mechanisms by which reinforcement, drive, and motivation might mediate environmental or stimulus-specific performance so as to produce
behavioral decrements in depressed individuals.26"31
Although changes in these conceptually related variables,
particularly in drive and motivation, have been observed in
depression, few attempts have been made to systematically
explore and integrate these findings with specific memory
deficits. In this study, we examined whether a general
deficit in the central motivational state in depression could
account for the memory impairments observed in depression. We proposed that the depressive's reduced capacity to
integrate external stimuli with appropriate behavioral
response,
result in
or
the maintenance of such
a
response, would
increasing decrement in his cognitive performance as the effort required of him increased. To test this
hypothesis, a simple motor task was devised that would
provide a measure of effort that was relatively independent of both intrinsic motor strength and cognitive processing. The subjects of the motor task would also be
expected to perform a simple memory task requiring little
motor activity. The two tests would permit direct comparisons between individual (motor) effort and cognitive
performance.
an
SUBJECTS AND METHODS
Subjects
Subjects
for the
study consisted of normal volunteers (mean
age, 37.2 years; SD, 15.5 years; range, 19 to 53 years) and patients
with affective disorders (mean age, 33.2 years; SD, 11.7 years;
range, 20 to 50 years) living on a research unit at the Clinical
Center of the National Institutes of Health, Bethesda, Md. Two of
the volunteers were also housed on the same unit during the
period of the study. The remainder of the volunteers were chosen
from among the nonprofessional staff of the institution. All
subjects had at minimum completed a high school education.
Educational levels of volunteers and patients were roughly comparable. The diagnosis of major affective illness in each of the
patients was made on the basis of Research Diagnostic Criteria,32
with the aid of the Schedule for Affective Disorders and Schizophrenia." Two female patients reached criteria for bipolar II
subtype. All other patients were of the unipolar subtype and in
varying stages of their illness during testing. During the threemonth study interval, all patients who were drug free for at least
three weeks as part of a placebo period were asked to participate.
Each subject was fully informed as to the nature and purpose of
the experimental tasks and gave his informed consent to participate. The patients received a weekly Hamilton Depression Scale
rating by a physician, and were rated twice a day by the nursing
staff utilizing the Bunney-Hamburg 15-point ward rating scale.34
Beck Depression Inventories were obtained from patients weekly,
and each subject completed a Profile of Mood State (POMS) prior
to each motor test.35 Motor tests were administered in the
mornings and memory tests in the early afternoon.
Procedure
For the motor task, each subject was instructed to squeeze a
dynamometer, which had been placed on a table in front of him, as
hard as he could, first with his right hand and then with his left.
Downloaded from www.archgenpsychiatry.com on December 22, 2010
Following the recording of each peak response in kilograms, the
subject was requested to squeeze the dynamometer again. This
time, the subject was informed that he was only to squeeze hard
enough to reach half his previous maximum, and then to maintain
this pressure for as long as possible. To accomplish this, since he
was unable to view his own performance, he was instructed to
slowly increase the pressure he was exerting until the tester
informed him that he had reached half his peak response and then
to maintain this squeeze as long as he could. Sustained time was
measured from the point the subject reached half his maximum
and ended when the observed hand pressure dipped 5% below the
half-maximum mark.
The memory task used equivalent lists of 40 trigrams. Each
trigram or nonsense syllable consisted of three different consonants, eg, MXP. Trigrams were chosen and controlled for pronouncibility, meaningfulness, and frequency of occurrence. The choice
of trigrams as stimuli, or target items for learning and recall, was
predicated on the fact that subjects had to be tested frequently
with material that was easily forgotten and would not be likely to
produce either facilitating or inhibiting effects with repeated
usage. Also, comparative performance on this task has been
evaluated in samples of unimpaired subjects ranging in age from
19 to 52 years. These evaluations have provided normative findings for this study as well as other investigations, including
drug-induced impairments in learning and memory.3* As the task
was performed, the subject was instructed that the experimenter
would read aloud a single trigram. At one of five (0, 3, 6, 9, or 18 s)
different times (randomized for order) after trigram presentation,
he was asked to recall the trigram. After recall of the first, a
second trigram was presented in this manner (eight trigrams for
each recall interval), until all 40 of the trigrams on the list for that
day's trial had been presented and recall attempted. As a short
distractor task designed to prevent rehearsal during the intervals
between presentation and recall, the subject was instructed to
count backwards from 200 by threes. Test scores consisted of the
number of trigrams recalled at each interval, with a score of 8
reflecting a perfect performance for that interval.
The study was originally designed to measure both intersubject
and intrasubject changes in motor and memory performances as
related to mood shifts. However, based on clinical judgment and
confirmed by our objective assessments of mood state, no subjects
in the study showed substantial mood change while drug free. It
was therefore possible to collect all of each subject's performances
on the motor and memory tasks as well as the corresponding
ratings for the entire period and average them to obtain a single
mean value for each subject. This avoided the introduction of any
bias as a result of variable subject participation. First sessions
were taken as practice and eliminated from further analysis. A
total of 80 memory and motor tests were obtained from the 11
individuals in the depressed patient group while drug free, and 11
from the five individuals in the normal control population. No
subject was tested more frequently than once every two days. As
expected, no trend was observed for change in any individual
subject across his motor and memory tasks during the period of
testing.
F ratios obtained for both linear regressions and analyses of
variance (ANOVAs) were judged significant whenever the corresponding P value was equal to or less than .05.
RESULTS
Initial evaluation made use of straight-line regression
analyses of variables derived from the behavioral ratings,
motor, and memory performances. Further evaluation
used an ANOVA model in which subjects were categorized
into groups of severely depressed patients (five women,
aged 19, 31, 34, 53, and 60), moderately depressed patients
(three women, aged 21 [bipolar II], 24, and 53), euthymic
patients (one woman [bipolar II], aged 56; two men, aged 23
and 35), and normal controls (four women, aged 20, 33, 38,
and 50; one man, aged 25). The total population for all the
statistical analyses was 16, with the exception of comparisons that used the Hamilton or Beck rating scales. As
normal subjects did not receive these more clinically
oriented and symptom-based scales, their total population
was
11.
Correlational Analysis
The consistency of the patient behavioral ratings was
underscored by the significant correlations between the
subjective and objective rating scales, eg, the POMS
Depression Scale (POMS-D) with the Hamilton (r .92,
P .001) and Beck (r .97, P .0001), and the Beck with
the Hamilton (r = .92, P .001). As they were so highly
correlated, it is possible to report correlations between
mood and motor and memory performances in terms of the
POMS-D as representative of the data as a whole. The
motor tasks also demonstrated similar consistency. Lefthand and right-hand peak responses were significantly
correlated (r .95, P .0001), as were left-hand and righthand sustained performances (r .77, P .0004). A somewhat lower correlation was found for right-hand peak with
right-hand sustained response (r .65, P .006), while
left-hand peak vs left-hand sustained response was not
significantly correlated (r .45, P .08).
All behavioral ratings had significant negative relationships with respect to motor performance. The POMS-D
was significantly negatively correlated with peak motor
responses (right hand, r —.63, P .009; left hand,
r
—.56, P .02) and even more highly negatively correlated with sustained motor performance (right hand,
r
-.66, P .006; left hand, r -.73, P .001). Similar
correlations were obtained with the Beck and Hamilton
depression scales.
Next, the relationship between mood and memory performance was examined. Memory performance was
observed to be inversely related to the behavioral rating
scales. The POMS-D ratings were significantly negatively
correlated with the number of words recalled immediately
(r -.82, P .0001), at 3 s (r -.77, P .0005), at 6 s
(r -.75, P .0007), at 9 s (r -.53, P .035), and at 18 s
(r —.76, P .0006). Again, the other depression rating
scales yielded similar negative correlations.
Finally, motor and memory performance were contrasted. Performance on all motor tasks was positively
correlated with the number of trigrams recalled at each
recall interval, with correlation coefficients ranging from
.42 to .72 and with corresponding significance probabilities
of .1 to .002. In general, highest correlations with recall
were observed for right- and left-hand sustained motor
performances; for example, when recall at the longest
interval was correlated with right- and left-hand peak
motor responses and right- and left-hand sustained motor
responses, correlations of .56, .49, .66, and .62 were
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
=
obtained, respectively.
Subgroup Analysis
Table 1 summarizes the mood data for the subjects as
they were divided into groups of normal, euthymic, moderately depressed, and severely depressed subjects on the
basis of the POMS-D scale. As a reflection of the meaningfulness of this division, one-way ANOVA using the Hamilton, Beck, and POMS-D scales as dependent variables
demonstrated significant group differences (F[2,7] 13.08,
P<.01; f[2,6] 54.3, P < .001; i^[3,12] 63.3, P < .001,
respectively). Significance was not observed for right- and
left-hand peak motor performances across the four subject
groups, although a trend was evident (right-hand peak,
F[Z,IZ\ 2.7, P .09; left-hand peak, F[3,12] 2.2,
P .14). However, significant differences among groups
were found for sustained motor performance (right hand,
^[3,12] 21.58, P<.001; left hand, ^[3,12] 7.54,
P .004), and memory performance (i^[3,12] 10.82,
P .001) (Table 2).
These findings of a reduction in the sustained motor
=
=
=
=
=
=
=
=
=
=
Downloaded from www.archgenpsychiatry.com on December 22, 2010
=
=
performance according to severity of depression ratings
are particularly striking in that the output of effort for
each individual would be expected to be a function of both
peak and time. Despite the reduction in peak, the
depressed subjects still cannot hold at half maximum as
long as normal subjects. As for the memory tests, there
was as expected a significant time effect, ie, number of
words recalled
sure and recall
was
was
decreased as the time between expoincreased (.F[4,48] 28, P < .0001). In
=
Table 1. Depression Scale Ratings for Patients With
Affective Disorders and Normal Controls*
—
Profile of
Mood State
Hamilton
Beck
Depression
Depression
Subscale
Scale
Depression
Inventory
8.5 ± 1.5
11.1 ±5.8
Depressed patients
Euthymic
(N 3)
(6.3-10.5)
(5.3-16.9)
(2.0-6.7)
Moderate
21.5 ± 1.6
21.9 ± 7.8
20.3 ± 7.1
=
(N
=
3)
(20-24)
Severe
(N
=
(N
=
'Mean
(10-40)
5)
(10-30)
44.6 ± 4.4
52 ± 4.0
44.9 ± 2.3
(40-52.8)
(38-56.8)
Normal controls
4.4 ± 2.3
(39.7-46)
7.5 ± 2.7
(2.5-14.5)
5)
values ±
•
o
SEM;
ranges
indicated in
are
parentheses.
Normal Controls
Euthymic Patients
Moderately Depressed Patients
Severely Depressed Patients
9
12
Delay in Recall, s
recall
of
information
in depressed patients.
Delayed
Table 2.— Motor and
addition, a significant group-time interaction effect was
found (F[12,48] 1.99, P .047). As evident in the Figure,
it is the severely depressed subjects' performance that
most rapidly decreases with time of recall as compared
with the other three groups.
=
COMMENT
The results demonstrate deficits in the motor and cognitive performance of depressed patients that appear to be
proportionate to depression severity. On the motor task,
depressed patients had both a reduced capacity to exert
maximally and an inability to sustain their half-maximal
hand squeeze as measured by our dynamometer procedure.
On the memory task, the depressed patients recalled fewer
trigrams at all recall intervals. The impairment on both
motor and cognitive tasks appeared to be most noticeable
on those subtasks that required greater sustained effort.
For example, increasing the length of time over which a
subject must retain three consonants in memory before
recall would be expected to increase the effort required of
the successful subject. Thus, the observed increase in recall
deficit in depression with increasing time is consistent
with the hypothesis of an enhanced deficit in the depressive subject on those tasks requiring the greatest effort.
Several objections might be raised as to the generalizability of these observations. The first is that the findings
result from studies predominantly in female subjects, eg,
there are no men in the severely depressed group. The
second is the potential long-term effects of psychotropic
medications that the patients may have been receiving
before their drug-free period. Third, the data are based on
group phenomena only, with a small number of subjects. In
support of generalizability, we had, in fact, tested one
severely depressed man (POMS-D score, 60; Beck score, 57;
Hamilton score, 54); however, because we were unable to
obtain memory data from a drug-free period, he was not
included in the analysis. His data do, however, support the
notion of a decrease in effort; six motor trials averaged a
right-hand peak of 39 kg, left-hand peak of 26 kg, a
right-hand sustained response of 3.0 s, and a left-hand
sustained response of 2.0 s. In addition, we have had more
than an equal number of motor and memory tasks completed by patients while receiving drugs, and although the
number of drugs were sufficiently diverse as to preclude
detailed statistical analysis, there was no trend for any of
the patients receiving tricyclic antidepressant drugs to
have shifts in either their memory or motor performances
when no mood response was evident. Finally, we have
recently retested one patient from the severely depressed
group who has had a considerable clinical improvement
while receiving nortriptyline hydrochloride. As expected,
Memory Performances by Patients With Affective Disorders and Normal Controls*
Force Exerted by
Duration of HalfMaximal Response,
Subjects, kg
,-,
Right-hand Peak
Depressed patients
Euthymic
(N 3)_42.2
=
=
(N
=
Left-hand Sustained
No. of
Trisyllables Recalledt
±
16.4_17.2
±
2.7_24.5
±
0.7_7.02
± 0.91
3)_25.0
±
0.8_19.3
±
1.7_9.4
±
1.7_17.9
±
7.8_6.19
± 0.59
5)_22.2
±
1.0_19.8
±
0.9_9.5
±
2.0_8.4
±
2.0_3.89
± 0.96
Normal controls
*Mean
Right-hand Sustained
15.7_35.6
Severe
(N
Left-hand Peak
s
,->-,
±
=
Moderate
(N
=
5)
42.2 ± 8.5
35.3 ± 6.7
25.1 ± 1.4
28.6 ± 3.1
values ± SEM.
tDerived by averaging number of trigrams recalled at each time interval (0, 3, 6, 9, and 18 s).
Downloaded from www.archgenpsychiatry.com on December 22, 2010
6.44 ± 0.29
her
performance on both the
strikingly improved.
memory and motor tasks
We therefore believe that these results support the
hypothesis of a general deficit in the capacity to maintain
effort as an important component for the understanding of
the cognitive and other behavioral changes that take place
during depression.
Studies of Model States
This "lack of effort" on the part of depressed patients
has been frequently observed by clinicians, who have noted
their increased dependency, indecisiveness, and avoidance
of responsibility as part of a general picture of motivational change. So striking are these changes that they are
sometimes accorded a central role in models of depressive
illness, eg, Schmale and Engel's3739 conservation withdrawal or "giving up—given up" and Miller and Seligman's30
"learned helplessness" animal model. The latter model
deserves detailed attention in view of our own results and
the extensive behavioral and neurochemical investigations
associated with the model.
The Miller and Seligman hypothesis is based on a body
of work in which animals demonstrated deficits in their
performance and learning of active avoidance behavior
after inescapable but not escapable shock. The original
investigators proposed that the animals had learned the
concept that nothing they did mattered.40'41 Subsequent
work in other species, however, has cast considerable doubt
as to the necessity of postulating a mediating cognitive
concept to explain the deficits observed.
For example, Weiss et al42-43 in recent reviews have
offered an alternative explanation in which the stressinduced physiological changes result in a problem with
"motor activation" that accounts for the observed performance deficits. Consistent with their hypothesis, deficits depend on the amount of motor effort required in the
active avoidance paradigm. On the neurochemical level,
the effects have been proposed to depend on the reduction
in brain catecholamine levels demonstrated to follow
inescapable shock.4447 As expected, then, these specific
behavioral effects have been mimicked, enhanced, or alleviated experimentally by drug treatment. Dopamine
antagonists, catecholamine blocking agents (eg, FLA 63,
alpha methylparatyrosine) or increasing cholinergic activity have been demonstrated to exacerbate the syndrome,
and levodopa or cholinergic antagonists antagonize these
effects.48 Most importantly, prior escape training leads to
resistance to the drug- or stress-induced effects. These
observations find their parallel in the cognitive depression
literature. Levodopa and amphetamine enhance memory
performance in depressives.3-49 Practice of otherwise effortful processes would be expected to move cognitive processes along the continuum toward the automatic end of the
spectrum, making them less susceptible to changes in
central motivational state.2324'50-51 Particularly striking in
terms of the maintenance of effort concept are the observations that affected animals often show normal performance on initial trials but fall off when responses are
measured over additional trials.48
Considerable additional evidence exists to link these
changes in catecholamine pathways to affective pathological mood states and with motivation, arousal, reinforcement, and learning in animals.5256 Other transmitters and
hormones (eg, opioid-like peptides, corticotropin, vasopressin, cortisol), however, have also been implicated in memory processes and mood changes.5760 Therefore, which
specific pathways are associated with the specific motivational and cognitive changes observable in depression still
remain to be determined. Furthermore, whether these
observed motor effects in animals originate from a more
general problem involving the reinforcement, motivational
areas that would be expected to be actively involved in the
maintenance and initiation of all behavior, as is suggested
by the "learned helplessness" hypothesis, is at present
unknown.
Observations in Depressed Patients
In this context, however, the observations in the
depressed patient population take on additional significance. Cognitive performance in general requires little
motor activation or effort, and simple motor tasks require
little in the way of cognitive process. If the decrements in
performance of both motor and cognitive functions in
depression show a close relationship, as we have observed,
the most parsimonious explanation would be one based on
a single deficit in the area of the central motivational
state.
For example, in the specific case of memory tasks, which
require the recall of words, there is evidence to support the
hypothesis of an initial automatic activation process
resulting from a word being read aloud.23 However, many
of the alternative strategies or responses that are normally activated to obtain the goal of memorizing specific types
of materials are unobservable and even subjectively unappreciated. All of these tasks would be expected to require
extended effort and therefore be affected by arousal and
mood.
Observations on the importance of these encoding processes in impaired and unimpaired cognition must, however, rely on indirect measurements of their participation in
observable memory performance change resulting from
the manipulation of stimuli. For example, Weingartner et
al61 recently established a differential response of
depressed patients to the varying task requirements of
memorizing lists that varied in organization. Depressed
subjects perform essentially as normal subjects for highly
clustered and organized material, but fall off sharply when
more effortful encoding strategies are required. As predicted by this model, depressed and nondepressed college
students perform equally well on frequency estimates, but
depressed patients perform less advantageously when
mnemonic activities such as semantic processing are
involved.23 Depressed patients also show a greater deficit
in free recall in comparison with cued recall, the former
task requiring probably greater depth of processing and
therefore effort in learning and/or a greater effort in the
use of a more complex retrieval strategy.
CONCLUSIONS
These findings raise considerable doubt as to the reasonableness of hypothesizing specific memory deficits in
depression separable from the general deficits of motivation, drive, and attention. Rather, wherever one might look
in terms of cognitive deficiencies, regardless of stage or
process (eg, attention, short-term memory, long-term
memory, consolidation, retrieval), one is likely to find
factors susceptible to deficit in the depressive patient, if
one is free to vary the requirements of the tasks in such a
manner as to increase the complexity and therefore the
effort required of the subject. Consequently, the study of
the specific memory deficits in depression may disclose
important information about the more general problems of
initiation and maintenance of behavior in the depressive
state. In addition, such study may serve to demonstrate the
specific sites for the physiologic and neurochemical substrata influencing the interaction of the central motivational state with the specific processes that are part of
memory. However, it must be emphasized that the specific
Downloaded from www.archgenpsychiatry.com on December 22, 2010
a unifying single deficit in the area of the
central motivational state for depression is only one of
many alternative hypotheses that could reasonably be
hypothesis pool? J Exp Soc Psychol
hypothesis of
Learned helplessness
proposed
32. Spitzer RL, Endicott J, Robins E: Research Diagnostic Criteria:
Rationale and reliability. Arch Gen Psychiatry 1978;35:773-782.
33. Endicott J, Spitzer RL: A diagnostic interview: The Schedule for
Affective Disorders and Schizophrenia. Arch Gen Psychiatry 1978;35:837-
explain depression-associated performance
to
decrements.
Eberhard H. Uhlenhuth, MD, discussed with
ment and cognition.
us
the
subjects of reinforce-
References
Depressive neurosis, in Arieti S, Brody E (eds): American
Handbook of Psychiatry. New York, Basic Books Inc, 1974, vol 2, pp
1. Beck AT:
61-90.
2. Miller
WR:
Psychological deficit in depression. Psychol Bull
1975;82:238-260.
3. Henry GM, Weingartner H, Murphy DL: Influence of affective states
and psychoactive drugs on verbal learning and memory. Am J Psychiatry
1973;130:966-971.
4. Sternberg DE, Jarvik ME: Memory functions in depression. Arch Gen
Psychiatry 1976;33:219-224.
Stromgren LS: The influence of depression on memory. Acta Psychiatr
Scand 1977;56:109-128.
6. Cherkin A: Retrograde amnesia: Impaired memory consolidation or
impaired retrieval. Commun Behav Biol 1970;5:183-190.
7. Gold PE, McGaugh JL: A single-trace, two-process view of memory
storage processes, in Deutsch D, Deutsch JA (eds): Short-term Memory.
New York, Academic Press Inc, 1975, pp 356-378.
8. Kinsbourne M, Wood F: Short-term memory processes and the amnesic syndrome, in Deutsch D, Deutsch JA (eds): Short-term Memory. New
York, Academic Press Inc, 1975, pp 257-291.
9. Lewis DJ: Sources of experimental amnesia. Psychol Rev 1969;76:461\x=req-\
5.
472.
10. Lewis DJ:
Psychobiology of active and inactive memory. Psychol Bull
1979;86:1054-1083.
11. Miller RR, Springer AD: Amnesia, consolidation, and retrieval.
Psychol Rev 1973;80:69-79.
12. Reitman JS: Without surreptitious rehearsal, information in short\x=req-\
term memory decays. J Verb Learning Verb Behav 1974;13:365-377.
13. Shulman HG: Encoding and retention of semantic phonemic information in short-term memory. J Verb Learning Verb Behav 1970;9:499-508.
14. Shulman HG: Semantic confusion errors in short-term memory.
J Verb Learning Verb Behav 1972;11:221-227.
15. Spear NE: Retrieval of memory in animals. Psychol Rev 1973;80:163\x=req-\
194.
16. Weiskrantz L, Warrington EK: The problem of the amnesic syndrome
in man and animals, in Isaacson RL, Pribram KH (eds): The Hippocampus.
New York, Plenum Press, 1975, vol 2, pp 411-441.
17. Wicklegren WA: The long and the short of memory, in Deutsch D,
Deutsch JA (eds): Short-term Memory. New York, Academic Press Inc, 1975,
pp 41-63.
18. Wicklegren WA: More on the long and short of memory, in Deutsch D,
Deutsch JA (eds): Short-term Memory. New York, Academic Press Inc, 1975,
pp 65-72.
19. Craik RIM, Lockhart RS: Levels of processing: A framework for
memory research. J Verb Learning Verb Behav 1972;11:671-684.
20. Hyde TS, Jenkins TS: Recall of words as a function of semantic,
graphic, and syntactic orienting tasks. J Verb Learning Verb Behav
1973;12:417-480.
21. Tulving E, Thomson DM: Encoding specificity and retrieval processes
in episodic memory. Psychol Rev 1973;80:352-373.
22. Tulving E, Watkins MJ: Structure of memory traces. Psychol Rev
1975;87:261-275.
23. Hasher
L, Zacks RT: Automatic and effortful processes in memory.
J Exp Psychol 1979;108:356-388.
24. Shiffrin RM, Schneider W: Controlled and automatic human information processing: II. Perceptual learning, automatic attending and a general
theory. Psychol Rev 1977;84:127-190.
25. Schneider W, Shiffrin RM: Controlled and automatic human information processing: I. Detection, search and attention. Psychol Rev 1977;84:1\x=req-\
66.
26. Bandura A:
Self-efficacy: Toward a unifying theory of behavioral
change. Psychol Rev 1977;84:191-215.
27. Beck AT: Depression: Clinical, Experimental and Theoretical Aspects.
Hagerstown, Md, Harper & Row Publishers Inc, 1967.
28. Lewinsohn PM, Youngren MA, Grosscup SJ: Reinforcement and
depression, in DePue R (ed): The Psychobiology of the Depressive Disorders:
Implications for the Effects of Stress. New York, Academic Press Inc, 1979,
pp 291-316.
29. Miller WR, Seligman MEP: Depression and the perception of reinforcement. J Abnorm Psychol 1973;82:62-73.
30. Miller WR, Seligman MEP: Depression and learned helplessness in
man.
J Abnorm
Psychol 1975;84:228-238.
Learning impairment following insoluble problems:
31. Peterson C:
or
altered
1978;14:53-68.
844.
34. Bunney WE Jr, Hamburg DA: Methods for reliable longitudinal
observation of behavior. Arch Gen Psychiatry 1963;9:280-294.
35. Guy W: ECDEU Assessment Manual for Psychopharmacology. Dept
of Health, Education, and Welfare publication 76-338 1976.
36. Caine ED, Weingartner H, Ludlow CL, et al: Qualitative analysis of
scopolamine induced amnesia. Psychopharmacology 1981;74:74-80.
37. Engel GL, Schmale AH: Conservation withdrawal: A primary regulatory complex. Bull Menninger Clin 1968;37:355-365.
38. Engel GL, Schmale AH: Conservation withdrawal: A primary regulatory process for organismic homeostasis: Psychology, emotion and psychosomatic illness. Ciba Found Symp 1972;8:57-75.
39. Schmale AM: Giving up as a final common pathway to changes in
health. Adv Psychosom Med 1972;8:20-40.
40. Overmier TB, Seligman MEP: Effects of inescapable shock on subsequent escape and avoidance learning. J Comp Physiol Psychol 1967;63:28-
33.
41.
Seligman MEP, Maier SF: Failure to escape traumatic shock. J Exp
Psychol 1967;74:1-9.
42. Weiss JM, Glazer HI, Pohorecky LA: Coping behavior and neurochemical changes: An alternative explanation for the original 'learned
helplessness' experiments, in Serban GH, Kling A (eds): Animal Models in
Human Psychobiology. New York, Plenum Press, 1976, pp 141-173.
43. Weiss JM, Glazer HI, Pohorecky LA, et al: Coping behavior and
stress-induced studies of the role of brain catecholamines, in DePue R (ed):
The Psychobiology of the Depressive Disorders: Implications for the Effects
of Stress. New York, Academic Press Inc, 1979, pp 125-176.
44. Stone EA: Stress and catecholamines, in Friedhoff AJ (ed): Catecholamines and Behavior. New York, Plenum Press, 1975, vol 2, pp 31-72.
45. Anisman H: Time dependent variations in anxiety motivated behaviors: Non-associated effects of cholinergic and catecholaminergic activity.
Psychol Rev 1975;82:359-385.
46. Anisman H: Neurochemical changes elicited by states: Behavioral
correlates, in Anisman H, Bignami G (eds): Psychopharmacology ofAversively Motivated Behavior. New York, Plenum Press, 1978, pp 119-171.
47. Weiss JM, Glazer HI, Pohorecky LA, et al: Effects of chronic exposure
to Stressors on avoidance—escape behavior and on brain norepinephrine.
Psychol Med 1975;37:522-533.
48. Anisman H, Remington G, Sklar LS: Effect of inescapable shock on
subsequent escape performance: Catecholaminergic and cholinergic mediation of response initiation and maintenance. Psychopharmacology
1979;61:107-124.
49. Reus VI, Silberman E, Post RM, et al: d-Amphetamine: Effects on
memory in a depressed population. Biol Psychiatry 1979;13:345-356.
50. LaBerge D: Attention and the measurement of perceptual learning.
Memory and Cognition 1973;1:268-276.
51. LaBerge D, Samuels SJ: Toward a theory of automatic information
processing in reading. Cognitive Psychol 1974;6:293-323.
52. Gorelick DA, Bozewicz TR, Bridger WH: The role of catecholamines
in animal learning and memory, in Friedhoff AJ (ed): Catecholamines and
Behavior. New York, Plenum Press, 1975, vol 2, pp 1-30.
53. Kety SF: The biogenic amines in the central nervous system: Their
possible roles in arousal, emotion and learning, in Schmitt FO (ed): The
Neurosciences: The Second Study Program. New York, Rockefeller Press,
1970,
pp 324-336.
Murphy DL, Redmond DE: The catecholamines: Possible role in
affect, mood and emotional behavior in man and animals, in Friedhoff AJ
(ed): Catecholamines and Behavior. New York, Plenum Press, 1975, pp
54.
73-117.
55. Schildkraut JT: The catecholamine hypothesis of affective disorders,
in Lipton MA, DiMascio A, Killam KF (eds): Psychopharmacology: A
Generation of Progress. New York, Raven Press, 1978, pp 1223-1234.
56. Wise RA: Catecholamine theories of reward: A critical review. Brain
Res 1978;152:215-247.
57. Rigter H, van Riezen H: Hormones and memory, in Lipton MA,
DiMascio A, Killam KF (eds): Psychopharmacology: A Generation of
Progress. New York, Raven Press, 1978, pp 667-689.
58. Roberts D, Fibiger H: Evidence for interactions between central
noradrenergic neurons and adrenal hormones and memory. Pharmacol
Biochem Behav 1977;7:191-194.
59. Stein L, Belluzzi JD: Brain endorphins and the sense of well-being: A
psychobiological hypothesis, in Costa E, Trabucchi M (eds): The Endorphins: Advances in Biochemical Psychopharmacology. New York, Raven
Press, 1978, vol 18, pp 299-311.
60. Zornetzer SE: Neurotransmitter modulation and memory: A new
neuropharmacologic phrenology, in Lipton MA, DiMascio A, Killam KF
(eds): Psychopharmacology: A Generation of Progress. New York, Raven
Press, 1978, pp 637-649.
61. Weingartner L, Cohen RM, Murphy DL, et al: Cognitive processes in
depression. Arch Gen Psychiatry 1981;38:42-47.
Downloaded from www.archgenpsychiatry.com on December 22, 2010