ArticlePDF AvailableLiterature Review

Abstract and Figures

The authors summarize current knowledge regarding the psychomotor symptoms of depression. Findings from the objective quantification of psychomotor symptoms are reviewed, and methodological issues are considered. The contemporary empirical literature regarding the diagnostic, prognostic, and potential pathophysiologic significance of psychomotor symptoms is summarized. It has been repeatedly shown that depressed patients differ from normal and psychiatric comparison groups with regard to objectively quantified gross motor activity, body movements, speech, and motor reaction time. Course of illness, diurnal variation, medication status, sex, and age are associated with agitation and retardation and should be controlled when one is studying psychomotor symptoms. Psychomotor symptoms in depression may have unique significance. They have high discriminative validity, may be the only symptoms of depression that distinguish depression subtypes, and are predictive of good response to tricyclic antidepressants. Results of brain imaging and biochemical studies link depression and motor symptoms to abnormalities in the basal ganglia and basal ganglia/thalamo-cortical circuits. The investigation of psychomotor disturbance in depression is specifically consistent with neo-Kraepelinian standards for the study of psychiatric disorders. Our current knowledge of psychomotor symptoms is conceptually obscure, yet a large body of evidence specifies their manifestation and supports their significance. Identifying the incidence of abnormal motor behaviors in depressed patients and assessing the component processes that accompany and determine their manifestation may be important advances in the study of psychomotor symptoms in depression.
Content may be subject to copyright.
Am J Psychiatry 154:1, January 1997
Special Article
Psychomotor Symptoms of Depression
Christina Sobin, Ph.D., and Harold A. Sackeim, Ph.D.
Objective: The authors summarize current knowledge regarding the psychomotor symp-
toms of depression.
Method: Findings from the objective quantification of psychomotor symp-
toms are reviewed, and methodological issues are considered. The contemporary empirical
literature regarding the diagnostic, prognostic, and potential pathophysiologic significance of
psychomotor symptoms is summarized.
Results: It has been repeatedly shown that depressed
patients differ from normal and psychiatric comparison groups with regard to objectively
quantified gross motor activity, body movements, speech, and motor reaction time. Course of
illness, diurnal variation, medication status, sex, and age are associated with agitation and
retardation and should be controlled when one is studying psychomotor symptoms. Psycho-
motor symptoms in depression may have unique significance. They have high discriminative
validity, may be the only symptoms of depression that distinguish depression subtypes, and
are predictive of good response to tricyclic antidepressants. Results of brain imaging and
biochemical studies link depression and motor symptoms to abnormalities in the basal ganglia
and basal ganglia/thalamo-cortical circuits.
Conclusions: The investigation of psychomotor
disturbance in depression is specifically consistent with neo-Kraepelinian standards for the
study of psychiatric disorders. Our current knowledge of psychomotor symptoms is concep-
tually obscure, yet a large body of evidence specifies their manifestation and supports their
significance. Identifying the incidence of abnormal motor behaviors in depressed patients and
assessing the component processes that accompany and determine their manifestation may be
important advances in the study of psychomotor symptoms in depression.
(Am J Psychiatry 1997; 154:4–17)
He is apparently unable to move and express himself
freely. This very circumstance, that the answers come
slowly, even on matters of indifference, shows that in this
patient we have not to deal with a fear of expressing himself
but with some general obstacle to the utterance of speech.
Indeed, not only speech but all action of the will is extremely
difficult to him . . . . The disturbance must be essentially
confined to the accomplishment of voluntary movements.
This constraint is by far the most obvious clinical feature of
the disease and compared with this, the sad, oppressed
mood has but little prominence.
—Kraepelin (1)
raepelin’s evocative description of his patient’s psy-
chomotor symptoms echoed the observations of
the earliest psychiatric writers, including Aretaeus of
Cappadocia, Hippocrates, Caelius Aurelianus, and Plu-
tarch (2, 3), and psychomotor disturbance continues to
be regarded as an essential feature of major depressive
disorder. Objectively measured motor behavior, includ-
ing gross motor activity, discrete body movements,
speech, and motor reaction time, have been shown to re-
liably differentiate depressed patients from psychiatric
and normal comparison groups. From a nosologic per-
spective, psychomotor disturbance remains a principal
symptom category in contemporary classification sys-
tems. Of 16 symptom domains, only psychomotor dis-
turbance was included in all of the 10 diagnostic systems
that defined criteria for the melancholic subtype (4). Fur-
thermore, evidence suggests that psychomotor symptoms
may have unique prognostic and, perhaps, pathophysi-
ologic significance. However, explicit definitions of psy-
chomotor phenomena remain elusive. The term is com-
Received Feb. 5, 1996; revision received June 17, 1996; accepted
July 1, 1996. From the Department of Psychiatry, College of Physi-
cians and Surgeons, Columbia University, and the New York State
Psychiatric Institute, New York. Address reprint requests to Dr. So-
bin, The Rockefeller University, 1230 York Ave., Box 313, New
York, NY 10021.
Supported in part by grants from the National Association for Re-
search on Schizophrenia and Depression Young Investigators Pro-
gram and NIMH grants MH-35636 and MH-47739.
4 Am J Psychiatry 154:1, January 1997
monly applied to virtually any observable manifestation
of slowing (retardation) or increased activity (agitation)
during a depressed state (DSM-IV), and many have ob-
served that our knowledge of psychomotor symptoms is
seriously limited and awaits major methodologic and
theoretical development (5–8). Thus, a central purpose of
this review is to examine our accumulated knowledge
and promote the development of an informed definition
of psychomotor symptoms in depression.
We begin with a review of studies that have objec-
tively quantified the manifestation of psychomotor
symptoms in the domains of gross motor activity, dis-
crete body movements, speech, and motor reaction
time. These results provide an empirical foundation for
considering the nature of psychomotor symptoms and
raise important issues regarding their measurement. Us-
ing results of studies that have assessed psychomotor
functioning in depression through clinical ratings, we
review the diagnostic, prognostic, and possible patho-
physiologic significance of psychomotor symptoms. We
conclude with a summary of alternative strategies for
expanding our understanding of the significance of psy-
chomotor symptoms in depression.
Studies that have objectively measured the individual
manifestations of psychomotor symptoms in depressed
patients have found that depressed patients differ from
psychiatric and normal comparison groups with regard
to gross motor activity level, movements of the limbs,
trunk, and head, speech, and motor reaction time (table
1). These studies provide a foundation for conceptualiz-
ing the manifestation of motor symptoms in depression.
Gross Motor Activity
Among the methods of quantifying psychomotor re-
tardation and agitation, perhaps none is as intuitively
TABLE 1. Summary of Key Findings From Unidimensional Studies of the Manifestations of Psychomotor Abnormalities in Depressed Patients
Variable Finding for Subjects Compared Reference for Study
Gross motor activity
Amount of 24-hour activity Bipolar, depressed < normal comparison 9, 10
Bipolar, manic > normal comparison 10
Amount of activity between midnight and 7:00 a.m. Depressed, unipolar/bipolar > schizophrenic 11
Percent of total activity between midnight and 7:00 a.m. Depressed, unipolar/bipolar > schizophrenic 11
Activity level variability Depressed, unipolar/bipolar < schizophrenic 11
Amount of 24-hour activity Bipolar, depressed < unipolar, depressed 9, 12
Body movements
Duration and frequency
Self-touching Depressed > normal comparison 13
Eye contact Depressed < normal comparison 13
Smiling Depressed < normal comparison 13
Eyebrow movement Depressed < normal comparison 13
Self-touching Depressed > schizophrenic 13
Small head movements Depressed > schizophrenic 13
Frequency of large head movements Depressed > schizophrenic 13
Duration of eye contact Depressed < schizophrenic 13
Speech pause time Depressed > normal comparison 14–17
Depressed with retardation > normal comparison 11
Depressed without retardation normal comparison 11
Pause time at speech initiation Depressed > normal comparison 17
Fundamental frequency change rate Depressed < normal comparison 18
Fundamental frequency variability Depressed < normal comparison 14, 16–20
Rate of diphthong production (articulation) Depressed < normal comparison 5
Parkinson’s disease < normal comparison 5
Depressed Parkinson’s disease 5
Speech pause time Depressed > psychiatric comparison 5
Unipolar > bipolar 15
Motor response time
Decision time and motor response time Depressed > normal comparison 21–28
Central processing component of decision time
Depressed > normal comparison 21–28
Simple reaction time Psychotically depressed > normal comparison 29
Nonpsychotically depressed normal comparison 29
Decision time and motor response time Depressed with retardation > normal comparison 21
Motor response time Depressed with retardation > depressed with agitation 21
Depressed with agitation > normal comparison 21
Melancholic depressed > normal comparison 30
Nonmelancholic depressed > normal comparison 30
Decision time Melancholic depressed > normal comparison 30
Nonmelancholic depressed normal comparison 30
Total reaction time variability Depressed < schizophrenic 29
Through peripheral initiation of motor response.
Am J Psychiatry 154:1, January 1997 5
apparent as continuous activity monitoring. Unlike
other techniques, measurement of motor activity over a
24-hour period captures the diurnal variation that is
fundamental to human behavior. Motor activity has
been measured with telemetric and nontelemetric wrist-
watch-like devices that transform large arm movements
into electronic impulses for storage in solid-state mem-
ory. High correspondence of the activity data with
changes in patients’ activities, as well as with staff ob-
servations of activity levels and ratings of mood state,
has substantiated the validity of this method (31, 32).
High between-patient variability and differences in ac-
tivity regimentation across inpatient wards led to the
recommendation that the relative distribution of activ-
ity during a 24-hour period be examined also (11).
Thus, variables in the studies of gross motor activity
include the total number of movements in a 24-hour
period and ratios of daytime activity levels to levels dur-
ing nighttime hours as well.
Depressed bipolar inpatients have manifested low ac-
tivity levels relative to normal comparison groups (9,
10), whereas patients in the manic phase have shown
elevated levels (10). In the only comparison of 24-hour
motor activity in which a psychiatric comparison group
was used (11), drug-free schizophrenic inpatients and
depressed inpatients (12 unipolar and five bipolar)
differed in the absolute amount and distribution of
their activity levels. The depressed patients exhibited a
greater amount of activity between midnight and 7:00
a.m. and had a greater percentage of their total 24-hour
activity during these nighttime hours. Furthermore, the
schizophrenic patients had greater temporal variability
in their activity levels.
Research that compared the activity levels of pa-
tients with subtypes of depression demonstrated that
unipolar patients had higher motor activity levels than
bipolar depressed patients (9, 12). Studies have also
shown that 24-hour activity levels covaried with changes
in clinical state. Kupfer and Foster (33) reported
that as the mood of a 54-year-old psychotic woman
with unipolar depression resolved, her gross motor ac-
tivity decreased by 25% during daytime hours and by
50% during nighttime hours. In contrast, Post et al.
(32), in a single-case study of a rapid-cycling bipolar
patient, found that motor changes occurred primarily
during daytime hours and preceded gradually the more
abrupt onset of mood change, suggesting the potential
clinical value of tracking shifts in motor activity in bi-
polar patients. In one of the largest studies completed
to date (9), 25 bipolar patients had less motor activity
in their depressed state than in their euthymic and
manic states. These changes were found to occur during
daytime but not nighttime hours.
Thus, bipolar depressed patients have been found to
differ from normal comparison groups in absolute lev-
els of 24-hour motor activity. During depressed phases,
their activity is decreased, and during manic phases it is
increased. The 24-hour gross motor activity of unipolar
depressed inpatients is greater than that of schizo-
phrenic patients and bipolar depressed patients, and
unipolar depressed inpatients are more active during
nighttime hours. Furthermore, 24-hour motor activity
may be a sensitive measure of mood change within cy-
cling and recovering mood disorder patients. Unipolar
depressed patients may have increased gross motor ac-
tivity, the resolution of which is most apparent during
nighttime hours, while bipolar patients have decreased
gross motor activity, the resolution of which may be
most apparent during daytime hours.
Movements of the Head, Torso, and Limbs
Naturalistic observation through videotaped ratings
offers a method for determining the individual move-
ments that together may constitute agitation or retarda-
tion in depressed patients. In one of the only studies of
its kind, Jones and Pansa (13) videotaped medication-
free depressed and schizophrenic patients (ICD-9 crite-
ria) and a normal comparison group during a 10-min-
ute interview session and during the presentation of
visual stimuli with moderate emotional content. They
examined facial gestures, head movements, looking be-
havior, and self-touching behavior. The depressed pa-
tients were found to differ from the normal comparison
group in the duration and frequency of self-touching
(increased), direct eye contact with the interviewer (de-
creased), smiling (decreased), and eyebrow movement
(decreased). When compared to the schizophrenic pa-
tients, the depressed patients had more frequent and
longer small movements of the head, more frequent
large movements of the head, more frequent body
touching, and shorter duration of eye contact with the
interviewer and toward visual stimuli. Thus, the behav-
iors that differentiated the depressed patients from both
the psychiatric group and the normal comparison
group included increased frequency of body touching
and diminished eye contact.
Results from one of the only studies to examine mul-
tiple manifestations of psychomotor symptoms within de-
pressed patients suggested that motor retardation and
agitation are likely to be multidimensionally manifested.
Ulrich and Harms (8) factor analyzed the videotape-based
ratings of nonverbal behaviors of 47 patients with endo-
genous depression (ICD-9 criteria). A retardation factor
and two agitation factors emerged. The loadings of 0.75
and above on the retardation factor included those for
reduced eye movements, reduced facial expression, con-
stricted posture, low voice amplitude, diminished pros-
ody, and shortened speaking time. The first agitation fac-
tor was characterized as “gross motor restlessness” and
included postural restlessness, brief repetitive body
touching, and continuous hand-to-head touching. The
second agitation factor was characterized as “constricted
restlessness” and included constricted posture, postural
restlessness, and continuous hand-to-hand movements.
As with any factor analytic results, high factor loadings
do not necessarily indicate the behaviors that will co-oc-
cur within individual patients (34, 35). These findings
await replication and determination of their covariation
with clinical judgments of agitation and retardation.
6 Am J Psychiatry 154:1, January 1997
The complex motor act that results in speech has long
been considered a valuable objective measure of psycho-
motor retardation in depression (14, 15). In addition to
paucity of speech, the motor-retarded depressed pa-
tient may show slowed responses, monotonic phrases,
and poor articulation. Among the temporal characteristics
of speech, the amount of time between utterances (speech
pause time) while a person is engaged in a simple counting
task has been shown to correlate with global psychomotor
retardation, as measured by the Widlocher Retardation
Rating Scale (36). It has been shown that depressed pa-
tients have increased speech pause time during an auto-
matic counting task (14–16) and during a clinical inter-
view (17) when compared to normal comparison groups.
Greden et al. (16) contrasted the speech pause time of 36
unipolar and bipolar depressed subjects with that of 19
nondepressed psychiatric control subjects (eight schizo-
phrenic, three demented, two phobic, one with Briquet’s
disorder, three with other psychiatric disorder as defined
by the Research Diagnostic Criteria [RDC], and two with
no psychiatric diagnosis). Speech pause time was longer
only among the depressed patients, regardless of subtype.
Inconsistent results have emerged, however, in the
comparison of bipolar and unipolar depressed patients.
While Greden et al. (16) reported that the speech pause
time of unipolar and bipolar patients did not differ,
Hoffman et al. (15) reported that only unipolar, and
not bipolar, depressed patients had increased speech
pause time relative to a normal comparison group. This
is the opposite of what would be predicted by results
from gross motor activity studies and could suggest that
the mechanisms underlying speech delay are inde-
pendent of those responsible for reduced gross motor
activity. In the only demonstration of the association
between clinically rated motor retardation and speech,
these same unipolar and bipolar patients were re-
grouped according to their retardation scores on the
Widlocher scale (36). Only those with retardation dif-
fered from the normal comparison group in speech
pause time (15). Nilsonne (17) has further suggested
that the speech delay characteristic of depressed pa-
tients may occur specifically in the initiation of re-
sponses to interviewers’ questions.
Differences between depressed and normal compari-
son groups have also been shown in the variables meas-
uring aspects of fundamental frequency (mean vocal
pitch). In one study (18), depressed patients had a re-
duced rate of change and less variability in mean vocal
pitch when compared to a group of normal subjects.
Flint et al. (5) compared the articulation characteristics
of 30 motor-retarded depressed patients, 30 nonde-
pressed and nondemented patients with Parkinson’s
disease, and 31 normal subjects. Second formant tran-
sition (speed of diphthong production) and voice onset
time (time between consonant production and the fol-
lowing vowel) were decreased, while spirantization
(voice noise or “leakage”) was increased in the patients
with major depression compared to the normal group.
The patients with Parkinson’s disease had similarly de-
creased second formant transition and voice onset time,
but they did not differ from the normal comparison
group on spirantization. There were no significant dif-
ferences between the patients with major depression
and those with Parkinson’s disease on any of the articu-
lation measures.
Alterations in speech among depressed patients have
been repeatedly shown to be externally valid. Both
speech slowing and reduced prosody have been found
to have a high correlation (14, 19) with a validated psy-
chomotor retardation rating scale (36). Nilsonne (17)
reported a high correlation between clinical ratings of
retardation and both slowed speech initiation and re-
duced pitch variability. Global depression scores also
have been found to be associated with these same
speech measures (14, 16, 19). The predictive validity of
increased speech pause time and decreased pitch var-
iability has been suggested by their change to more
normal values when depressed patients return to a eu-
thymic state (14, 16, 20, 37). At the same time, data
indicating the discriminative validity of pause time,
pitch variability, and altered articulation for retarded
and nonretarded depressed patients are limited.
Motor Speed
The speed with which patients execute a discrete mo-
tor act has also been used as an objective measure of
psychomotor retardation. Earlier investigators simply
timed the completion of a task, such as card sorting,
with a stopwatch (38). However, reaction time repre-
sents a combination of cognitive and motor processes.
The attempt to assess evaluative or decision processes
before the execution of a motor response separately
from motor speed is unique to the field of reaction time
research, and in this way, researchers have tried to iden-
tify the “functional basis” of motor retardation in de-
pression (39). Thus, while some researchers have used
a simple key press task, many have used the “fixed
foreperiod” paradigm. In this method, a trial begins
when the subject presses a “home” key with the domi-
nant index finger. A timer starts as a visual, auditory,
or tactile stimulus is presented and stops when the sub-
ject lifts his or her finger from the home key en route to
the appropriate “choice” key. When the first timer
stops, a second timer starts, and it stops when the sub-
ject presses the choice key. The time between stimulus
presentation and release of the home key has been in-
terpreted as decision time, and the time required to
reach the decision key has been considered the motor
response time. Decision time, motor response time, and
total reaction time, assessed with the fixed foreperiod
paradigm, decrease after pharmacologic treatment of
depression and subsequent symptom remission (40),
suggesting that these measures are an objective gauge of
depression-related phenomena.
The separation of decision and motor response com-
ponents has been advantageous. In the one study to
compare clinically assessed, medication-free, retarded
Am J Psychiatry 154:1, January 1997 7
and agitated depressed inpatients and a normal com-
parison group (21), only motor response time distin-
guished the agitated depressed patients from the re-
tarded depressed patients and the normal comparison
group. The retarded depressed patients were found to
be slower than the normal comparison group with re-
gard to both decision time and motor response time.
Another valuable finding to emerge from the separation
of response components concerns the relationship be-
tween them. Within normal comparison groups, deci-
sion and motor response times are independent (22–24,
41), while for female depressed subjects, decision and
motor response times were found to be correlated, sug-
gesting that these processes may become linked during
depression (25). However, the separation of decision
and motor response components has added little to our
understanding of the differences in motor speed be-
tween depressed patients and normal comparison
groups. Both components are slower in depressed pa-
tients, as compared to normal groups, in response to
visual, auditory, and tactile stimuli in both simple and
choice paradigms (21–28). Similarly perhaps, the sepa-
ration of decision and motor reaction times has not en-
hanced the differentiation of depressed and schizo-
phrenic patients with regard to motor speed (42–44),
although patients with depressive disorder have been
shown to be less variable in their total reaction time
than schizophrenic patients (29).
The separation of decision and motor response times
by means of the fixed foreperiod paradigm has also
been criticized for its underlying assumption that cog-
nitive and motor processes are distinct, sequentially oc-
curring components of performance (30). The instruc-
tion to subjects that movement should not occur until a
final choice has been made is fundamental in this
method, and low mean error rates are typically re-
ported as confirmation that a final choice decision was
made before movement. In fact, a decision process that
continues during the initiation and execution of move-
ment may not necessarily result in error, and it may
accurately reflect an efficient interaction of cognitive
and motor processes. Borrowing from the cognitive
psychology literature (45), Cornell et al. (30) assessed
cognitive slowing during a reaction time task by hold-
ing constant the motor demand while varying the cog-
nitive complexity; motor slowing was assessed by hold-
ing constant the cognitive complexity and varying the
motor demand. It was suggested that comparisons of
the reaction times of patients and a group of normal
subjects under low and high demand conditions could
potentially reveal deficits in each component process
among the patient groups. Cornell et al. found that mel-
ancholic and nonmelancholic depressed patients dif-
fered from the normal comparison group with regard
to motor slowing, while only the melancholic depressed
patients differed from the normal subjects with regard
to cognitive slowing.
While the reaction time literature offers one strategy
for controlling cognitive factors in the study of motor
disturbance in depression, ultimately, new strategies
will be needed to assess the central processing deficits
associated with motor agitation and retardation. Infor-
mation-processing models that accommodate the inter-
play of motor and cognitive functions have been pro-
posed (46) and may provide a useful direction for
further study.
Studies of the individual manifestations of psycho-
motor disturbance in depression offer many interesting
clues to their nature. From an experimental perspective,
these results also suggest comparisons for future studies
and factors that should be controlled in examining mo-
tor agitation and retardation. Several manifestations of
psychomotor disturbance in depression have been
shown to differentiate depressed patients from normal
subjects. These include amount of 24-hour gross motor
activity; duration and frequency of body movements
such as self-touching, eye contact, smiling, and eyebrow
movement; speech pause time, voice pitch, and articu-
lation; and reaction time. Fewer studies, however, have
demonstrated the specificity of these motor distur-
bances to depressed patients. Results to date suggest
that depressed patients have increased self-touching, in-
creased head movements, and decreased eye contact
when compared to schizophrenic patients. Depressed
patients have been shown to have increased speech
pause time as compared to a mixed group of nonde-
pressed psychiatric control subjects, and depressed pa-
tients have been shown to have less variability in their
total reaction time across trials. However, motor dis-
turbance is known to occur in many psychiatric disor-
ders. Motor deficits have been a key feature in studies
of negative-symptom schizophrenia (47, 48), and mo-
tor restlessness has been described in studies of anxiety
disorder (49, 50). Whether the retardation in depres-
sion is behaviorally equivalent to the retardation char-
acteristic of negative-symptom schizophrenia, however,
has not been studied. Similarly, the nervous restlessness
that is clinically observed in anxious patients may or
may not mimic the agitation observed in patients with
agitated depression. Studies that compare the specific
motor components of clinically assessed retardation
and agitation in different psychiatric groups are needed
before the specificity of psychomotor disturbance to de-
pression can be understood.
The data reviewed suggest that whether a patient is
retarded or agitated or both may depend on whether
the lifetime course of illness is unipolar or bipolar. In
addition, the high rates of overlap in depression and
anxiety syndromes (51, 52) and the possible influence
of this comorbidity on the manifestation of motor
symptoms suggest that the presence of secondary disor-
ders and lifetime course of illness should also be ascer-
tained when one is studying psychomotor symptoms.
Retardation and agitation are not mutually exclusive.
Reduced looking and decreased facial expression are
8 Am J Psychiatry 154:1, January 1997
often coupled with gross motor restlessness and in-
creased hand movements (8, 13), especially in patients
with severe depression. Thus, instruments used for
identifying and measuring retardation and agitation
must be designed to accommodate the presence of
either or both, and clinical raters must be trained to
consider them independently.
Research on the abnormalities of circadian rhythms
in depressed patients suggests that controlling the time
of day of testing is also essential in studies of the psy-
chomotor symptoms in depression. Peaks and lows in
motor activity, as well as in urinary norepinephrine me-
tabolites (3-methoxy-4-hydroxyphenylglycol [MHPG])
and oral temperature, were found to be advanced by
1–3 hours in bipolar patients when compared to normal
subjects (10). More recently, Piletz et al. (53) suggested
that the phase advance phenomenon was associated
more strongly with agitated than retarded depression,
and with first as compared to subsequent depressive
episodes. Furthermore, the variability of circadian
peaks and lows was found to be increased in depressed
patients as compared to normal subjects. In a demon-
stration of the profound effect of diurnal variation on
motor reaction time, Moffoot et al. (54) reported that
the decision time and movement time of melancholic
depressed patients were slower than the times in a nor-
mal comparison group during morning but not evening
hours, and while the afternoon performance of the mel-
ancholic patients improved, the performance of the
comparison group diminished.
In addition, both sex and age may be determinants of
the manifestation of psychomotor symptoms. Males
have been found to have more retardation than females,
while females have been found to have more agitation
than males (55–57). With regard to age, depressed pa-
tients under 40 years are more likely to have motor re-
tardation, while patients over age 40 are more likely to
have motor agitation (55, 57). This association may
warrant special examination. The loss of subcortical
neurons and subsequent reduction of dopamine-synthe-
sizing enzymes, which are characteristic of normal ag-
ing (58), might predict the opposite. Because sedation
can be a side effect of heterocyclic antidepressants, and
agitation can be a side effect of the unicyclics and selec-
tive serotonin reuptake inhibitors, controlling medica-
tion status is essential in the design of motor behavior
Finally, the significance of psychomotor symptoms
across the full spectrum of depressive disorders, and
their association with illness severity, must eventually
be addressed. The only study to examine the association
between severe depressive symptoms and motor distur-
bance (55) reported that in three groups of depressed
inpatients stratified according to the presence of motor
agitation or motor retardation or the absence of motor
symptoms, those with motor retardation were more
likely to be psychotic than were those with motor agi-
tation. This may indirectly suggest that global sever-
ity is associated with motor-retarded but not motor-
agitated depression. Obviously, however, the question
awaits further analysis. Methods for objectively meas-
uring minor manifestations of endogenous depression
have rarely been applied in nosologic studies. Psycho-
motor disturbance, one of the only objectively measur-
able symptoms of endogenous depression, may be a
reasonable starting point for such an endeavor. While
particular features of endogenous depression, such as
psychomotor disturbance, have long been recognized as
features of psychotic depression (59, 60), it has not yet
been determined whether these features occur only in
cases of severe depression. The possibility of a mild
form of endogenous depression with psychomotor dis-
turbance, similar to the “endogenomorphic” depres-
sion described by Klein (61), should not be ruled out.
Despite the many advances in the objective assess-
ment of psychomotor symptoms in depression, studies
examining their diagnostic significance derive from
clinical judgment and single-item ratings. In these stud-
ies, psychomotor disturbance was evaluated with items
describing global agitation and/or retardation. As sug-
gested above, objective assessment has indicated that
motor agitation and retardation can be manifested in
multiple motor domains. It is not known which mani-
festations of psychomotor disturbance result in a posi-
tive single-item clinical rating of agitation or retarda-
tion, whether most patients simultaneously experience
more than one motor disturbance, and whether the dif-
ferent manifestations of motor disturbance are equally
apparent to observing clinicians.
Historically, psychomotor symptoms contributed im-
portantly to the evolving nosology of depression sub-
types. Early studies sought to isolate the clinical differ-
ences between psychotic and neurotic patients. Linear
discriminant function analysis was used to optimize
separation of these “known” subgroups, and it was re-
peatedly found that psychomotor symptoms provided
the strongest differentiation. In a study of 391 psychotic
and 250 neurotic depressed patients diagnosed accord-
ing to ICD-7 criteria (62), discriminant function analy-
sis indicated that of 60 symptoms and course descrip-
tors, delusions and psychomotor symptoms were the
most robust subtype discriminators. In a later study of
115 psychotic and 63 neurotic inpatients (63), the high-
est loadings of the 32 symptoms assessed were for audi-
tory hallucinations (0.92), agitation (0.77), and delu-
sions (0.70). Feeling motorically slowed (as assessed on
the Present State Examination [PSE]) had the next high-
est loading (0.50), but it is interesting that observed mo-
tor retardation (PSE behavior rating) had one of the low-
est loadings. In another comparison of psychotic (N=
65) and neurotic (N=39) inpatients, Fleiss (64) found
that motor retardation, agitation, and somatic com-
plaints best discriminated the psychotic group. In the
only analysis to include a rating of global symptom se-
verity, Bhrolchain et al. (65) found that global severity
Am J Psychiatry 154:1, January 1997 9
and motor retardation best distinguished 73 psychotic
female inpatients from 41 neurotic female outpatients.
The presumption in earlier studies was that a particu-
lar subtyping distinction, psychotic versus neurotic,
was valid, and the most discriminating symptom fea-
tures were identified. Later studies did not precategor-
ize patient subgroups and instead attempted to identify
depression subtypes by analyzing the factor structure of
presenting symptoms. These studies suggested that psy-
chomotor symptoms were among the strongest indica-
tors of the melancholic/endogenous subtype. In a com-
prehensive review of factor analytic studies, Nelson and
Charney (7) observed that 11 of 12 reports that evalu-
ated psychomotor retardation found that this symptom
loaded on the melancholic/endogenous factor at 0.50 or
higher, with the exception reporting a factor loading of
0.40. Of the 20 depressive symptoms considered, psy-
chomotor retardation had the highest and the most con-
sistent (positive) loadings on the melancholic/endo-
genous factor. More recent reviews of this literature (4,
66) concluded the same.
The frequency with which a given symptom occurs
within patients can further indicate its diagnostic sig-
nificance relative to other aspects of a given syndrome.
The close examination of a symptom that rarely occurs
may add little to our understanding of a diagnostic syn-
drome, while a symptom that occurs in virtually every
case will not contribute to the differentiation of syn-
drome subtypes. Unfortunately, relatively few recent
studies have reported and compared symptom rates
within depressed patients. A literature search revealed
only six such studies, and in these, the presence or ab-
sence of symptoms was determined by clinical interview
and the rating of single-symptom items (table 2). In gen-
eral, the frequency of psychomotor symptoms falls ap-
proximately within the range of the frequency of other
symptoms of depression, suggesting that they are not so
rare as to be nosologically insignificant. Perhaps not
surprisingly, “marked” psychomotor symptoms have
been found to occur with considerably less frequency
than moderate manifestations. Young et al. (69), in an
analysis of the symptoms of a mixed unipolar/bipolar
group of 788 patients meeting definite RDC for major
depressive disorder found that marked psychomotor
symptoms (agitation or retardation) occurred in only
11.8% of the patients. However, in contrast to the
more moderate psychomotor symptoms, the discrimi-
native sensitivity of marked psychomotor symptoms to
DSM-III-defined melancholia was high, although their
absence did not always indicate a nonmelancholic sub-
type. Accurately assessing the severity of psychomotor
symptoms may be critical in determining their diagnos-
tic discriminative power.
In two studies that examined symptom rates across
diagnostic subtypes, large differences were indicated.
One pre-DSM-III study that used the psychotic/neurotic
distinction (65) suggested that psychotic patients were
more likely to manifest retardation than were neurotic
depressed patients. When bipolar, unipolar, and reac-
tive depressed patients were compared (71), the bipolar
patients appeared to manifest more psychomotor dys-
function than the unipolar and reactive patients. Retar-
dation was more common among the depressed bipolar
patients than the depressed unipolar patients, while the
unipolar patients were more likely than the bipolar pa-
tients to manifest agitation. The rates of no other de-
pressive symptoms differed as greatly across subtypes
of depression. In a study that was designed to examine
TABLE 2. Symptom Rates in Studies of Depression
Patients With Major Depression
et al. Mendels
Nelson and Charney (71)
Bhrolchain et al.
(65) (N=114)
Symptom N % N % N % N % N % N % N % N % N %
Any psychomotor disturbance 62 58 531 67 7 100 20 69 14 35
Retardation 44 46 25 50 6 86 10 34 10 25 45 73 15 31
Agitation 44 46 2 29 11 38 4 10
“Marked” motor symptoms 93 12
Sleep disturbance 98 92 55 58 590 75 32 64 5 71 29 100 33 83 43 69 27 55
Appetite disturbance 86 80 49 52 555 70 7 100 28 97 36 90 50 81 31 63
Decreased energy 93 87 71 75 3 43 14 48 13 33
Loss of interest/pleasure 75 70 78 82 763 97 7 100 29 100 32 80
Guilt/self-reproach 29 31 601 76 25 50 0 0 13 45 2 5
Concentration disturbance 78 73 71 75 6 86 26 90 14 35
Suicidal ideation/intent 74 69 55 58 5 71 15 52 33 83
DSM-III-R diagnosis; mean age=33 years (SD=10); 67% female; 100% psychiatric emergency room intake patients.
DSM-III diagnosis; mean age=49 years (SD=19); 72% female; 100% inpatients; 3% bipolar, 3% schizoaffective.
DSM-III/RDC diagnosis; mean age=38.7 years (SD=14.5); 59% female; 77% inpatients; 66% endogenous/melancholic.
Clinical diagnosis; 100% inpatients; 38% endogenous.
RDC diagnosis; mean age=37 years; 82% female; 100% acute inpatients.
Present State Examination diagnosis; age range=18–65 years; 100% female; 59% inpatients.
10 Am J Psychiatry 154:1, January 1997
the frequency of depressive symptoms and their diag-
nostic value (67), unlike other neurovegetative symp-
toms (including appetite loss, sleep disturbance, and
loss of energy), psychomotor symptoms were reported
least frequently (19%) by patients not meeting criteria
for a major depressive episode, suggesting that psycho-
motor symptoms may have high discriminative validity.
Determining the specificity of these symptoms to major
depression, however, will require studies that examine
and compare their specific manifestations within differ-
ent diagnostic groups.
Thus, psychomotor symptoms, as judged by clinical
ratings, are among the most frequently occurring symp-
toms associated with the melancholic subtype. They are
infrequently reported by patients not meeting criteria
for major depressive disorder, and unlike other neuro-
vegetative symptoms, they appear to discriminate among
depression subtypes. Evidence suggests that bipolar de-
pressed patients may be more likely to manifest retar-
dation than unipolar depressed patients, while unipolar
patients may be more likely to manifest agitation than
bipolar patients. At the same time, the specificity of re-
tardation and agitation to depressive disorder awaits
further examination.
Of the symptoms associated with depression, psycho-
motor retardation may be the most consistently predic-
tive of good response to tricyclic antidepressants (72).
Overall et al. (73) reported that among 77 psychotically
depressed inpatients subtyped as either anxious, hos-
tile, or motor-retarded, only the motorically disturbed
patients responded to imipramine. Downing and Rick-
els (74) reported that among 95 moderately depressed
outpatients treated with amitriptyline by general prac-
titioners, psychomotor symptoms were predictive of re-
sponse. White and White (75) found that psychomotor
retardation, as well as depressed mood and weight loss
as assessed by the Hamilton Depression Rating Scale,
predicted superior response to tranylcypromine in 58
depressed inpatients.
The results of studies that have objectively measured
specific manifestations of psychomotor symptoms also
lend support for their predictive value. Ranelli and Mil-
ler (76) compared the baseline speech and motor move-
ments of unipolar depressed inpatients, diagnosed ac-
cording to the RDC, who were responders (N=8) and
nonresponders (N=10) to amitriptyline and of a normal
comparison group (N=18). Speech pause time and du-
ration of head aversions were greater in the unipolar
depressed patients who responded to amitriptyline as
compared to the nonresponders and the normal sub-
jects. Depressed nonresponders had increased body
touching and postural changes as compared to the nor-
mal group. Global clinical ratings of agitation and re-
tardation were not examined. However, to the extent
that the objective measures of delayed speech and in-
creased body movement were a manifestation of retar-
dation and agitation, respectively, the results of clinical
rating and objective studies together suggest that mo-
tor-retarded depressed patients may have a superior re-
sponse, and motor-agitated depressed patients may
have an inferior response, to at least some forms of anti-
depressant treatment.
In contrast, the results of studies that examined the
predictive value of motor symptoms in depression with
regard to outcome after ECT have been inconsistent.
Early studies reported strong positive associations be-
tween psychomotor symptoms in the context of melan-
cholic depression and good response to ECT (70, 77).
More recently, Avery and Silverman (55) examined the
response to ECT of depressed inpatients subgrouped
according to the presence of either agitation or retarda-
tion or the absence of motor symptoms. While all of the
patients with motor impairment had a superior re-
sponse to ECT when compared to the patients with no
motor symptoms, the patients with retardation alone
had a slower and poorer response to ECT than the pa-
tients with agitation alone. Strian et al. (78) also re-
ported superior response to ECT in agitated depressed
patients as opposed to retarded depressed patients.
Results from studies comparing real and sham ECT
are inconsistent regarding the prognostic value of psy-
chomotor symptoms in ECT. Brandon et al. (79) in-
itially reported that among 77 depressed inpatients, re-
tardation and/or delusions predicted increased efficacy
of real as opposed to sham ECT. Agitation was not con-
sidered. Buchan et al. (80) combined the reported data
from the Northwick Park study (81, 82) and the Leices-
tershire study (79) and found that the combination of
delusions and retardation led to the greatest response to
ECT. It was concluded that real ECT was not more ef-
fective than simulated treatment for patients without
retardation or delusions. Again, the role of agitation
was not considered. In contrast, O’Leary et al. (83) re-
ported that in a group of 44 depressed inpatients, real
ECT was of greater benefit than sham treatment for all
patients, including those without retardation and delu-
sions. Similarly, in a recent analysis comparing the
treatment response of 148 patients meeting the RDC
and DSM-IV criteria for major depressive disorder (84),
neither agitation, retardation, nor psychosis predicted
superior response to effective versus ineffective forms of
ECT. Thus, there is evidence to suggest that motor re-
tardation may predict superior response, and agitation
may predict poorer response, to some types of anti-
depressant medication, but that the prognostic value of
these symptoms with regard to ECT is uncertain.
A collection of provocative findings suggest that mo-
tor symptoms in major depression may indicate con-
comitant abnormalities in specific structures and path-
ways of the brain. It has frequently been reported that
Am J Psychiatry 154:1, January 1997 11
patients with basal ganglia diseases, characterized by
motor dysfunction and dopaminergic abnormalities,
such as Parkinson’s disease (85), supranuclear palsy
(86), Huntington’s disease (87), Meige’s disease (88,
89), Wilson’s disease (90, 91), and basal ganglia calci-
fication (92), manifest high rates of mood disorders.
These findings are not intuitive and have led some
authors to propose that the well-defined neuropathol-
ogy of specific basal ganglia diseases may provide a use-
ful model for investigating the pathophysiology of
mood disorders (93).
The results of other investigations have linked both
behavioral apathy, or “frontal lobe” syndrome, and de-
pression to abnormalities in the structures of the basal
ganglia and in the parallel segregated circuits that con-
nect the basal ganglia to the prefrontal and anterior cin-
gulate cortex (94). For example, a review of case re-
ports of 240 patients with lesions of the caudate,
putamen, and/or globus pallidus (95) revealed that an
apathy syndrome—characterized by the loss of initia-
tive, spontaneous thought, and emotional responsiv-
ity—was the most common behavioral disturbance,
with particular overrepresentation in patients with cau-
date lesions. Dystonia was the most frequent motor
syndrome reported among all of the patients and was
most prominent in patients with lesions of the putamen
and globus pallidus. Starkstein et al. (96) reported that
poststroke mood disorders were more frequent and se-
vere among patients with left-side caudate lesions, as
compared to poststroke patients with right-side caudate
or thalamic lesions. Citing the finding that lesions in the
basal ganglia/anterior cingulate circuit are strongly as-
sociated with the clinical presentation of poststroke
mania, these authors suggested that the functioning of
this pathway may be both negatively influenced by le-
sions of the caudate through which it passes and funda-
mental to the modulation of mood. Similarly, a review
of findings from patients with specific basal ganglia/
thalamo-cortical circuit damage (97) suggested that be-
havioral syndromes unique to each pathway were iden-
tifiable. In particular, while disordered movement was
indicative of lesions in the caudate nucleus, apathy syn-
dromes were linked to lesions of the basal ganglia/ante-
rior cingulate circuit. Finally, Laplane et al. (98) studied
eight patients with bilateral basal ganglia lesions re-
stricted to the area of the lentiform nucleus (putamen
and globus pallidus). PET findings revealed hypo-
metabolism of the lateral prefrontal cortex, the cortical
area innervated by the dorsolateral prefrontal basal
ganglia/thalamo-cortical circuit. More generally, the
parallel, segregated circuits of the basal ganglia, each
with connectivity to distinct brain areas, may explain
the fact that comparable basal ganglia lesions result in
different clinical manifestations, including either motor
symptoms, an apathy or mood syndrome, or both.
Laplane et al. hypothesized that psychiatric disorders
such as major depression may be associated with struc-
tural or functional anomalies of the dorsolateral pre-
frontal basal ganglia circuit.
Brain imaging studies provide supporting evidence
for basal ganglia and basal ganglia/thalamo-cortical
circuit abnormalities in major depression. Magnetic
resonance imaging studies in depressed inpatients have
revealed an increase in basal ganglia lesions among eld-
erly depressed patients (99) and an excess of hyperin-
tensities in the basal ganglia, as well as in deep white
matter regions containing basal ganglia/thalamo-corti-
cal circuit fibers, among both elderly and nonelderly
depressed patients (100–104). Depressed patients have
been found to have decreased volume of the putamen
nuclei (105) and caudate nucleus (106) when compared
to control subjects matched on age and sex. While Ayl-
ward et al. (107) did not replicate these volumetric find-
ings, in their data there was a trend toward reduced
caudate, putamen, and globus pallidus volumes among
female bipolar subjects as compared to female control
Functional imaging studies also lend support for ab-
normalities in basal ganglia structures and in brain ar-
eas innervated by basal ganglia/thalamo-cortical pro-
jections in depressed patients. A decreased metabolic
rate in the caudate nucleus (108–111) and a left-side
decrease in caudate blood flow (112) have been re-
ported. Decreased regional cerebral blood flow (CBF)
in the anterior cingulate region (113, 114) and de-
creased glucose metabolism in the left dorsolateral pre-
frontal cortex (113–117) have been reported. Reduced
glucose metabolism in the temporal cortex of depressed
patients (114, 118), an area innervated by the same ba-
sal ganglia/thalamo-cortical loop as that which projects
to the anterior cingulate region, has also been reported.
Surprisingly few studies have attempted to relate
symptom features of major depression—in particular,
motor disturbance—to the patterns of functional defi-
cits. Thus, a link between specific areas of deficit and
symptom expression has not been clearly established.
One exception has been the work of Mayberg et al.
(119). Using single photon emission computed to-
mography, they compared subjects with severe depres-
sion to an age-matched normal group. Decreases in
CBF were found in paralimbic regions, including the
inferior frontal, anterior cingulate, and anterior tempo-
ral cortex. When the associations between psychiatric
symptoms and perfusion were examined, only clinically
rated psychomotor slowing was correlated with perfu-
sion levels, and this occurred in all three regions of hy-
poperfusion. Another exception has been the work of
Bench et al. (120). High scores on a symptom-derived
psychomotor retardation factor were associated with
reduced regional CBF in the left dorsolateral prefrontal
cortex and left angular gyrus. Increased blood flow in
the cingulate cortex and inferior parietal lobe corre-
lated with a psychomotor agitation factor. Similarly,
Liddle et al. (121) found a reduction of regional CBF in
the dorsolateral prefrontal cortex of schizophrenic pa-
tients with psychomotor poverty. Studies of response
selection in the absence of extrinsic information have
suggested that activation of the dorsolateral prefrontal
cortex is associated with intrinsically generated, willful
behavior (122), and it has been proposed that psycho-
12 Am J Psychiatry 154:1, January 1997
motor retardation reflects a volitional disturbance com-
mon to both schizophrenia and depression that results
from dorsolateral prefrontal cortex dysfunction (123).
Given that segregated basal ganglia projections inner-
vate the dorsolateral prefrontal cortex, the anterior cin-
gulate region, and the lateral temporal lobe, this propo-
sition is consistent with a theory of depression which
posits that abnormalities in basal ganglia/thalamo-cor-
tical circuitry may underlie some of its clinical manifes-
tations (119).
It is well established that the striatum receives a pri-
mary serotonergic projection from the dorsal raphe nu-
cleus (124). In addition, more than 80% of the dopa-
mine in the brain is produced in the basal ganglia (125).
Thus, despite the fact that psychobiological studies of
depression have focused primarily on noradrenaline
and serotonin abnormalities, it is not surprising that
preclinical studies of atypical antidepressants have
aroused new interest in the complex interdependency
between the serotonergic and dopaminergic systems
(126–128). These studies might also suggest that abnor-
malities of the basal ganglia or basal ganglia/thalamo-
cortical circuitry in some depressed patients indicate
dopaminergic dysfunction modulated by concomitant
serotonergic abnormalities. Several studies have sug-
gested that abnormal dopamine levels occur in some
depressed patients (129). Studies have reported in-
creased CSF dopamine levels in depressed patients as
compared to normal groups (130, 131). It has also been
reported that CSF homovanillic acid (HVA), a dopa-
mine metabolite, is lowered in depressed patients com-
pared to normal groups (132) and, more specifically, in
melancholic as compared to nonmelancholic depressed
patients and a normal group (133). Furthermore, it has
been suggested that the nature of abnormalities in pe-
ripheral catecholamine concentrations may be a func-
tion of symptom features. Decreased HVA levels have
been shown to be associated with increased motor re-
tardation (134), while reduced plasma HVA has been
shown to be related to increased extrapyramidal symp-
toms in a mixed group of patients with Alzheimer’s dis-
ease, Parkinson’s disease, or major depressive disorder
(135). MHPG, a norepinephrine metabolite, has been
reported to have a curvilinear relationship with psycho-
motor retardation and anxiety in depressed patients
(136). Finally, Maes et al. (137) reported that the 24-
hour urinary excretion of norepinephrine, adrenaline,
and dopamine was positively correlated with middle in-
somnia, while MHPG excretion was negatively associ-
ated with somatic anxiety and hypochondriasis. To the
extent that the latter symptoms are associated with psy-
chomotor agitation, these findings may suggest that in-
creased catecholamine turnover contributes to the de-
pressive symptoms of motorically agitated patients. In
contrast, decreased dopamine turnover may be associ-
ated with psychomotor retardation.
Positive findings regarding the catecholamine meta-
bolites have been described here; however, many stud-
ies have failed to replicate these results. In addition, the
metabolite research has been criticized for focusing on
presynaptic and synaptic action, while giving little at-
tention to postsynaptic events (138). Ultimately, the
conclusions that can be drawn from metabolite studies
may be limited. Treatment efficacy studies with de-
pressed patients, however, may offer collateral evidence
of an association between dopaminergic abnormalities
and depressive symptom manifestation. Rampello et al.
(139), testing a dopaminergic hypothesis for retarded
depression, used a double-blind, placebo-controlled de-
sign and found that the clinical improvement in psycho-
motor-retarded depressed patients paralleled the dopa-
minetic specificity of the antidepressants administered,
which included amineptine, minaprine, and clomipra-
mine. Furthermore, double-blind, placebo-controlled
studies examining the antidepressant effects of dopa-
mine agonists, including
L-deprenyl (140), bupropion
(141, 142), and nomifensine (143, 144), have demon-
strated substantial antidepressant effects.
Interpretation of these provocative findings awaits
further research. Results of studies in the 1990s (126–
128) suggest that exclusive focus on either the seroto-
nergic or dopaminergic transmitter system will neces-
sarily lead to incomplete and misleading conclusions.
Furthermore, enhanced delineation and improved as-
sessment of psychomotor symptoms will undoubtedly
strengthen the investigation of their pathophysiologic
Use of psychomotor symptoms as a focus of research
is specifically consistent with neo-Kraepelinian stand-
ards for the study of psychiatric disorders (145). These
symptoms are objectively observable and are measur-
able with the use of advanced technology that yields
data appropriate for statistical analysis, and substantial
progress has been made in identifying the complex
neuroanatomical pathways and processes that combine
to produce motor acts (146). Depressed patients have
been shown to differ from normal and psychiatric com-
parison groups in gross motor activity, discrete body
movements, speech characteristics, and motor speed.
Studies of psychomotor symptoms have demonstrated
that course of illness, time of day, medication status,
sex, and age are factors that influence the expression of
psychomotor symptoms. Furthermore, it has been sug-
gested that agitation and retardation are not mutually
exclusive and should be measured as independently
varying phenomena. Evidence also suggests that psy-
chomotor symptoms have special diagnostic, prognos-
tic, and possibly pathophysiologic significance.
At the same time, a consideration of these results il-
luminates gaps in our understanding of psychomotor
phenomena in depression. Historical and contempo-
rary descriptions have suggested that motor retardation
and agitation are manifested in multiple motor do-
mains, yet studies that objectively measure psychomo-
tor symptoms tend to focus on only a single manifesta-
tion of agitation or retardation, and diagnostic studies
Am J Psychiatry 154:1, January 1997 13
have been based primarily on the presence or absence
of single-symptom items. Unidimensional studies can
incorrectly subgroup patients whose motor dysfunction
is not manifested in the measured domain. Clinical rat-
ings can miss patients whose psychomotor manifesta-
tions occur over time (24-hour gross motor activity) or
at a particular time of day (motor reaction time) or are
too subtle to rate reliably (diminished pitch variability
in the speaking voice). Few studies have objectively
measured these multiple manifestations within de-
pressed patients. Thus, we do not know which of these
abnormalities constitute the necessary and sufficient
components of motor retardation or motor agitation in
depression. Determining the extent to which motor be-
havior per se contributes to psychomotor phenomena
in depression will also be essential to the further study
of these symptoms.
As research on the psychomotor symptoms of depres-
sion progresses, many additional issues will inform our
understanding of their nature. For example, very little
is known regarding the course of psychomotor symp-
toms within and across episodes of depression. Few
studies have examined psychomotor symptoms in de-
pression from a developmental perspective, and rates
of motor symptoms in depressed children have not
been reported. Furthermore, while normal aging results
in altered dopamine production and motor system
changes, the interaction of age and depressive illness is
not obvious, as suggested by the increased rates of agi-
tation among elderly depressed persons (55).
Thus, while psychomotor symptoms have been stud-
ied intensively from unidimensional and symptom-
based perspectives, there remains substantial concep-
tual uncertainty regarding the nature of the deficits that
give rise to psychomotor symptoms. The term “psycho-
motor” itself reflects our lack of knowledge regarding
the contribution of component processes that we sus-
pect may be involved (30, 46). Identifying the incidence
of psychomotor symptoms within depressed patients,
in addition to assessing the component processes that
precede and accompany motor disturbance, may yield
the methods necessary for the identification of more ho-
mogeneous subgroups of patients, a fuller interpreta-
tion of past studies of psychomotor manifestations in
depression, and, perhaps, new hypotheses regarding the
pathophysiologic significance of psychomotor symp-
toms in depression.
1. Kraepelin E: Lectures on Clinical Psychiatry (1904). New York,
Hafner, 1968
2. Zilboorg G: A History of Medical Psychology. New York, Nor-
ton, 1944
3. Whitwell JR: Historical Notes on Psychiatry. London, Lewis,
4. Rush AJ, Weissenburger JE: Melancholic symptom features and
DSM-IV. Am J Psychiatry 1994; 151:489–498
5. Flint AJ, Black SE, Campbell-Taylor I, Gailey GF, Levinton C:
Abnormal speech articulation, psychomotor retardation, and
subcortical dysfunction in major depression. J Psychiatr Res
1993; 27:309–319
6. Greden JF: Psychomotor monitoring: a promise being fulfilled? J
Psychiatr Res 1993; 27:285–287
7. Nelson JC, Charney DS: The symptoms of major depressive ill-
ness. Am J Psychiatry 1981; 138:1–13
8. Ulrich G, Harms K: A video analysis of the nonverbal behaviour
of depressed patients before and after treatment. J Affect Disord
1985; 9:63–67
9. Wolff EA III, Putnam FW, Post RM: Motor activity and affective
illness: the relationship of amplitude and temporal distribution
to changes in affective state. Arch Gen Psychiatry 1985; 42:288–
10. Wehr TA, Muscettola G, Goodwin FK: Urinary 3-methoxy-4-
hydroxyphenylglycol circadian rhythm: early timing (phase-ad-
vance) in manic-depressives compared with normal subjects.
Arch Gen Psychiatry 1980; 37:257–263
11. Foster FG, Kupfer DJ: Psychomotor activity as a correlate of de-
pression and sleep in acutely disturbed psychiatric inpatients.
Am J Psychiatry 1975; 132:928–931
12. Kupfer DJ, Weiss BL, Foster G, Detre TP, McPartland R: Psycho-
motor activity in affective states. Arch Gen Psychiatry 1974; 30:
13. Jones IH, Pansa M: Some nonverbal aspects of depression and
schizophrenia occurring during the interview. J Nerv Ment Dis
1979; 167:402–409
14. Szabadi E, Bradshaw CM, Besson JA: Elongation of pause-time
in speech: a simple, objective measure of motor retardation in
depression. Br J Psychiatry 1976; 129:592–597
15. Hoffmann GM, Gonze JC, Mendlewicz J: Speech pause time as
a method for the evaluation of psychomotor retardation in de-
pressive illness. Br J Psychiatry 1985; 146:535–538
16. Greden JF, Albala AA, Smokler IA, Gardner R, Carroll BJ: Speech
pause time: a marker of psychomotor retardation among endog-
enous depressives. Biol Psychiatry 1981; 16:851–859
17. Nilsonne A: Speech characteristics as indicators of depressive ill-
ness. Acta Psychiatr Scand 1988; 77:253–263
18. Hardy P, Jouvent R, Widlocher D: Speech pause time and the
retardation rating scale for depression: towards a reciprocal vali-
dation. J Affect Disord 1984; 6:123–127
19. Nilsonne A: Acoustic analysis of speech variables during depres-
sion and after improvement. Acta Psychiatr Scand 1987; 76:
20. Kuny S, Stassen HH: Speaking behavior and voice sound charac-
teristics in depressive patients during recovery. J Psychiatr Res
1993; 27:289–307
21. Lapierre YD, Butter HJ: Agitated and retarded depression: a
clinical psychophysiological evaluation. Neuropsychobiology
1980; 6:217–223
22. Weiss AD: The location of reaction time change with sex, moti-
vation and age. J Gerontol 1965; 20:60–64
23. Welford AT: Fundamentals of Skill. London, Methuen, 1968
24. Danev SG, DeWinter CR, Wartna GF: On the relation between
reaction and motion times on a choice reaction task. Acta Psy-
chol (Amst) 1971; 55:188–197
25. Knott V, Lapierre L, Griffiths L, de Lugt D, Bakish D: Event-re-
lated potentials and selective attention in major depressive ill-
ness. J Affect Disord 1991; 23:43–48
26. Weckowicz TE, Tam CN, Mason J, Bay KS: Speed in test per-
formance in depressed patients. J Abnorm Psychol 1978; 87:
27. Bruder G, Yozawitz A, Berenhaus I, Sutton S: Reaction time fa-
cilitation in affective psychotic patients. Psychol Med 1980; 10:
28. Bulbena A, Berrios GE: Cognitive function in the affective disor-
ders: a prospective study. Psychopathology 1993; 26:6–12
29. Schwartz F, Carr AC, Munich RL, Glauber S, Lesser B, Murray
J: Reaction time impairment in schizophrenia and affective ill-
ness: the role of attention. Biol Psychiatry 1989; 25:540–548
30. Cornell DG, Suarez R, Berent S: Psychomotor retardation in mel-
ancholic and nonmelancholic depression: cognitive and motor
components. J Abnorm Psychol 1984; 93:150–157
31. Kupfer DJ, Detre TP, Foster G, Tucker GJ, Delgado J: The appli-
cation of Delgado’s telemetric mobility recorder for human stud-
ies. Behav Biol 1972; 7:585–590
14 Am J Psychiatry 154:1, January 1997
32. Post RM, Stoddard FJ, Gillin JC, Buchsbaum MS, Runkle DC,
Black KE, Bunney WE Jr: Alterations in motor activity, sleep,
and biochemistry in a cycling manic-depressive patient. Arch
Gen Psychiatry 1977; 34:470–477
33. Kupfer DJ, Foster FG: Sleep and activity in a psychotic depres-
sion. J Nerv Ment Dis 1973; 156:341–348
34. Maxwell R: Multivariate statistical methods and classification
problems. Br J Psychiatry 1971; 119:121–127
35. Kendell RE: The classification of depressions: a review of con-
temporary confusion. Br J Psychiatry 1976; 129:15–28
36. Widlocher DJ: Psychomotor retardation: clinical, theoretical and
psychometric aspects. Psychiatr Clin North Am 1983; 6:7–43
37. Nilsonne A, Sundberg J, Ternstrom S, Askenfelt A: Measuring
the rate of change of voice fundamental frequency in fluent
speech during mental depression. J Acoust Soc Am 1988; 83:
38. Hemsley DR: Attention and information processing in schizo-
phrenia. Br J Soc Clin Psychol 1976; 15:199–209
39. Judd LL: Effect of lithium on mood, cognition, and personality
function in normal subjects. Arch Gen Psychiatry 1979; 36:860–866
40. Ghozlan A, Widlocher D: Decision time and movement time in
depression: differential effects of practice before and after clini-
cal improvement. Percept Mot Skills 1989; 68:187–192
41. Henry FM: Reaction time-movement correlations. Percept Mot
Skills 1961; 12:63–66
42. Bohannon WE, Strauss ME: Reaction-time crossover in psychi-
atric outpatients. Psychiatry Res 1983; 9:17–22
43. Levinson DF: Skin conductance orienting response in unmedi-
cated RDC schizophrenic, schizoaffective, depressed, and con-
trol subjects. Biol Psychiatry 1991; 30:663–683
44. Williams RM, Hemsley DR: Choice reaction time performance
in hospitalized schizophrenic patients and depressed patients.
Eur Arch Psychiatry Neurol Sci 1986; 236:169–173
45. Posner MI, Boies SJ, Eichelman WH, Taylor RL: Retention of
visual and name codes of single letters. J Exp Psychol 1969; 79:
46. Smith MJ, Brebion G, Banquet JP, Allilaire JF: Experimental evi-
dence for two dimensions of cognitive disorders in depressives. J
Psychiatr Res 1994; 28:401–411
47. Chatterjee A, Chakos M, Koreen A, Geisler S, Sheitman B, Wo-
erner M, Kane JM, Alvir J, Lieberman JA: Prevalence and clinical
correlates of extrapyramidal signs and spontaneous dyskinesia
in never-medicated schizophrenic patients. Am J Psychiatry
1995; 152:1724–1729
48. Cuesta MJ, Peralta V: Are positive and negative symptoms rele-
vant to cross-sectional diagnosis of schizophrenic and schizoaf-
fective patients? Compr Psychiatry 1995; 36:353–361
49. Ball SG, Buchwald AM, Waddell MT, Shekhar A: Depression
and generalized anxiety symptoms in panic disorder: implica-
tions for comorbidity. J Nerv Ment Dis 1995; 183:304–308
50. Marten PA, Brown TA, Barlow DH, Borkovec TD, Shear MK,
Lydiard RB: Evaluation of the ratings comprising the associated
symptom criterion of DSM-III-R generalized anxiety disorder. J
Nerv Ment Dis 1993; 181:676–682
51. Rickels K, Schweizer E: The treatment of generalized anxiety dis-
order in patients with depressive symptomatology. J Clin Psy-
chiatry 1993; 54(Jan suppl):20–23
52. Hecht H, von Zerssen D, Krieg C, Possl J, Wittchen HU: Anxiety
and depression: comorbidity, psychopathology, and social func-
tioning. Compr Psychiatry 1989; 30:420–433
53. Piletz JE, DeMet E, Gwirtsman HE, Halaris A: Disruption of
circadian MHPG rhythmicity in major depression. Biol Psychia-
try 1994; 35:830–842
54. Moffoot AP, O’Carroll RE, Bennie J, Carroll S, Dick H, Ebmeier
KP, Goodwin GM: Diurnal variation of mood and neuropsycho-
logical function in major depression with melancholia. J Affect
Disord 1994; 32:257–269
55. Avery D, Silverman J: Psychomotor retardation and agitation in
depression: relationship to age, sex and response to treatment. J
Affect Disord 1984; 7:67–76
56. Hamilton M: Development of a rating scale for primary depres-
sive illness. Br J Soc Clin Psychol 1967; 6:278–296
57. Winokur G, Morrison J, Clancy J, Crowe R: The Iowa 500: fa-
milial and clinical findings favor two kinds of depressive illness.
Compr Psychiatry 1973; 14:99–106
58. Goldman J, Cote L: Aging of the brain: dementia of the Alzhei-
mer’s type, in Principles of Neural Science, 3rd ed. Edited by
Kandel ER, Schwartz JH, Jessell TM. Norwalk, Conn, Appleton
& Lange, 1991, pp 974–983
59. Kay DW, Garside RF, Beamish P, Roy JR: Endogenous and neu-
rotic syndromes of depression: a factor analytic study of 104
cases: clinical features. Br J Psychiatry 1969; 115:377–388
60. Mendels J, Cochrane C: The nosology of depression: the endo-
genous-reactive concept. Am J Psychiatry 1968; 124(May sup-
61. Klein DF: Endogenomorphic depression: a conceptual and termi-
nological revision. Arch Gen Psychiatry 1974; 31:447–454
62. Kendell RE: The Classification of Depressive Illness: Maudsley
Monograph 18. London, Oxford University Press, 1968
63. Kendell RE, Gourlay J: The clinical distinction between psy-
chotic and neurotic depression. Br J Psychiatry 1970; 117:257–260
64. Fleiss JL: Classification of the depressive disorders by numerical
typology. J Psychiatr Res 1972; 9:141–153
65. Bhrolchain MN, Brown GW, Harris TO: Psychotic and neurotic
depression, 2: clinical characteristics. Br J Psychiatry 1979; 134:
66. Parker G, Hadzi-Pavlovic D, Boyce P: Endogenous depression as
a construct: a quantitative analysis of the literature and a study
of clinician judgements. Aust NZ J Psychiatry 1989; 23:357–368
67. Buchwald AM, Rudick-Davis D: The symptoms of major depres-
sion. J Abnorm Psychol 1993; 102:197–205
68. Miller KB, Nelson JC: Does the dexamethasone suppression test
relate to subtypes, factors, symptoms, or severity? Arch Gen Psy-
chiatry 1987; 44:769–774
69. Young MA, Scheftner WA, Klerman GL, Andreasen NC, Hirsch-
feld RM: The endogenous subtype of depression: a study of its
internal construct validity. Br J Psychiatry 1986; 148:257–267
70. Mendels J: Electroconvulsive therapy and depression, part 3: a
method for prognosis. Br J Psychiatry 1965; 111:687–690
71. Nelson JC, Charney DS: Primary affective disorder criteria and
the endogenous-reactive distinction. Arch Gen Psychiatry 1980;
72. Joyce PR, Paykel ES: Predictors of drug response in depression.
Arch Gen Psychiatry 1989; 46:89–99
73. Overall JE, Hollister LE, Johnson M, Pennington V: Nosology of
depression and differential response to drugs. JAMA 1966; 195:
74. Downing RW, Rickels K: Predictors of amitriptyline response in
out-patient depressives. J Nerv Ment Dis 1972; 154:248–263
75. White K, White J: Tranylcypromine: patterns and predictors of
response. J Clin Psychiatry 1986; 47:380–382
76. Ranelli CJ, Miller RE: Behavioral predictors of amitriptyline re-
sponse in depression. Am J Psychiatry 1981; 138:30–34
77. Carney MW, Roth P, Garside RI: The diagnosis of depressive
syndromes and the prediction of ECT response. Br J Psychiatry
1965; 111:659–674
78. Strian F, Albert W, Klicpera C: Course of depressive mood and
psychomotor activation in endogenous depression. Arch Psychi-
atr Nervenkr 1979; 227:193–206
79. Brandon S, Cowley P, McDonald C, Neville P, Palmer R, Well-
stood-Eason S: Electroconvulsive therapy: results in depressive
illness from the Leicestershire trial. BMJ Clin Res 1984; 288:22–
80. Buchan H, Johnstone E, McPherson K, Palmer RL, Crow TJ,
Brandon S: Who benefits from electroconvulsive therapy? com-
bined results of the Leicester and Northwick Park trials. Br J
Psychiatry 1992; 160:355–359
81. Johnstone EC, Deakin JF, Lawler P, Frith CD, Stevens M, Mc-
Pherson K, Crow TJ: The Northwick Park electroconvulsive
therapy trial. Lancet 1980; 2:1317–1320
82. Clinical Research Centre Division of Psychiatry: The Northwick
Park ECT trial: predictors of response to real and simulated
ECT. Br J Psychiatry 1984; 144:227–237
83. O’Leary D, Gill D, Gregory S, Shawcross C: Which depressed
patients respond to ECT? the Nottingham results. J Affect Dis-
ord 1995; 33:245–250
Am J Psychiatry 154:1, January 1997 15
84. Sobin C, Prudic J, Devanand DP, Nobler MS, Sackeim HA: Who
responds to electroconvulsive therapy? a comparison of effec-
tive and ineffective forms of treatment. Br J Psychiatry 1996;
85. Cummings JL: Depression and Parkinson’s disease: a review.
Am J Psychiatry 1992; 149:443–454
86. Albert ML, Feldman RG, Willis AL: The “subcortical demen-
tia” of progressive supranuclear palsy. J Neurol Neurosurg Psy-
chiatry 1974; 37:121–130
87. Jeste DV, Karson CN, Wyatt RJ: Movement disorders and psy-
chopathology, in Neuropsychiatric Movement Disorders. Ed-
ited by Jeste DV, Wyatt RJ. Washington, DC, American Psychi-
atric Press, 1984, pp 119–150
88. Jankovic J, Ford J: Blepharospasm and orofacial-cervical dys-
tonia: clinical and pharmacological findings in 100 patients.
Ann Neurol 1983; 13:402–411
89. Tolosa ES, Lai C: Meige disease: striatal dopaminergic prepon-
derance. Neurology 1979; 29:1126–1130
90. Akil M, Schwartz JA, Dutchak D, Yuzbasiyan-Gurkan V,
Brewer GJ: The psychiatric presentations of Wilson’s disease. J
Neuropsychiatry Clin Neurosci 1991; 3:377–382
91. Dening TR, Berrios GE: Wilson’s disease: a longitudinal study
of psychiatric symptoms. Biol Psychiatry 1990; 28:255–265
92. Trautner RJ, Cummings JL, Read SL, Benson DF: Idiopathic
basal ganglia calcification and organic mood disorder. Am J
Psychiatry 1988; 145:350–353
93. Peyser CE, Folstein SE: Huntington’s disease as a model for
mood disorders. Mol Chem Neuropathol 1990; 12:99–119
94. Alexander GE, DeLong MR, Strick PL: Parallel organization of
functionally segregated circuits linking basal ganglia and cortex.
Ann Rev Neurosci 1986; 9:357–381
95. Bhatia KP, Marsden CD: The behavioural and motor conse-
quences of focal lesions of the basal ganglia in man. Brain 1994;
96. Starkstein SE, Robinson RG, Berthier ML, Parikh RM, Price
TR: Differential mood changes following basal ganglia vs tha-
lamic lesions. Arch Neurol 1988; 45:725–730
97. Cummings JL: Frontal-subcortical circuits and human behav-
ior. Arch Neurol 1993; 50:873–880
98. Laplane D, Levasseur M, Pillon B, Dubois B, Baulac M, Ma-
zoyer B, Tran Dinh S, Sette G, Danze F, Baron JC: Obsessive-
compulsive and other behavioural changes with bilateral basal
ganglia lesions: a neuropsychological, magnetic resonance im-
aging and positron tomography study. Brain 1989; 112:699–
99. Coffey CE, Figiel GS, Djang WT, Weiner RD: Subcortical hy-
perintensity on magnetic resonance imaging: a comparison of
normal and depressed elderly subjects. Am J Psychiatry 1990;
100. Dupont RM, Jernigan TL, Gillin JC, Butters N, Delis DC, Hes-
selink JR: Subcortical signal hyperintensities in bipolar patients
detected by MRI. Psychiatry Res 1987; 21:357–358
101. Figiel GS, Krishnan KR, Rao VP, Doraiswamy M, Ellinwood
EH Jr, Nemeroff CB, Evans D, Boyko O: Subcortical hyperin-
tensities on brain magnetic resonance imaging: a comparison of
normal and bipolar subjects. J Neuropsychiatry Clin Neurosci
1991; 3:18–22
102. Hickie I, Scott E, Mitchell P, Wilhelm K, Austin MP, Bennett B:
Subcortical hyperintensities on magnetic resonance imaging:
clinical correlates and prognostic significance in patients with
severe depression. Biol Psychiatry 1995; 37:151–160
103. Krishnan KRR, Goli V, Ellinwood EH, France RD, Blazer DG,
Nemeroff CB: Leukoencephalopathy in patients diagnosed as
major depressive. Biol Psychiatry 1988; 23:519–522
104. McDonald WM, Krishnan KRR, Doraiswamy PM, Blazer DG:
Occurrence of subcortical hyperintensities in elderly subjects
with mania. Psychiatry Res Neuroimaging 1991; 40:211–220
105. Husain MM, McDonald WM, Doraiswamy PM, Figiel GS, Na
C, Escalone PR, Boyko OB, Nemeroff CB, Krishnan KRR: A
magnetic resonance imaging study of putamen nuclei in major
depression. Psychiatry Res Neuroimaging 1991; 40:95–99
106. Krishnan KRR, McDonald WM, Escalone PR, Doraiswamy
PM, Na C, Husain MM, Figiel GS, Boyko OB, Ellinwood EH,
Nemeroff CB: Magnetic resonance imaging of the caudate
nucleus in depression. Arch Gen Psychiatry 1992; 49:553–
107. Aylward EH, Roberts-Twillie JV, Barta PE, Kumar AJ, Harris
GJ, Geer M, Peyser CE, Pearlson GD: Basal ganglia volumes
and white matter hyperintensities in patients with bipolar dis-
order. Am J Psychiatry 1994; 151:687–693
108. Baxter LR, Phelps ME, Mazziotta JC, Schwartz JM, Gerner RH,
Selin CE, Sumida RM: Cerebral metabolic rates for glucose in
mood disorders. Arch Gen Psychiatry 1985; 42:441–447
109. Buchsbaum MS, Wu J, DeLisi LE, Holcomb H, Kessler R, John-
son J, King AC, Hazlett E, Langston K, Post RM: Frontal cortex
and basal ganglia metabolic rates assessed by positron emission
tomography with [18F]2-deoxyglucose in affective illness. J Af-
fect Disord 1986; 10:137–152
110. Drevets WC, Raichle ME: Neuroanatomical circuits in depres-
sion: implications for treatment mechanisms. Psychopharmacol
Bull 1992; 28:261–274
111. Hagman JO, Buchsbaum MS, Wu JC, Rao SJ, Reynolds CA,
Blinder BJ: Comparison of regional cerebral brain metabolism
in bulimia nervosa and affective disorder assessed with positron
emission tomography. J Affect Disord 1990; 19:153–162
112. Mayberg HS, Jeffery PJ, Wagner HN, Simpson SG: Regional
cerebral blood flow in patients with refractory unipolar depres-
sion measured with Tc-99m HMPAO SPECT. J Nucl Med
1991; 32(suppl):951
113. Bench CJ, Friston KJ, Brown RG, Scott L, Frackowiak RSJ, Do-
lan RJ: The anatomy of melancholia: abnormalities of regional
cerebral blood flow in major depression. Psychol Med 1992;
114. Ketter TA, Andreason PJ, George MS, Post RM, DeLisi LE,
Uhde TW, Cohen R, Buchsbaum MS: Blunted cerebral blood
flow response to procaine in mood disorders, in New Re-
search Program and Abstracts of the 146th Annual Meeting of
the American Psychiatric Association. Washington, DC, APA,
115. Baxter LR, Schwartz JM, Phelps ME, Mazziotta JC, Guze BH,
Selin CE, Gerner RH, Sumida RM: Reduction of prefrontal cor-
tex metabolism common to three types of depression. Arch Gen
Psychiatry 1989; 46:243–250
116. Cohen RM, Semple WE, Gross M, Nordahl TE, King AC, Pick-
ar D, Post RM: Evidence for common alterations in cerebral
glucose metabolism in major affective disorders and schizophre-
nia. Neuropsychopharmacology 1989; 2:241–254
117. Martinot J-L, Hardy P, Feline A, Huret J-D, Mazoyer B, Attar-
Levy D, Pappata S, Syrota A: Left prefrontal glucose hypo-
metabolism in the depressed state: a confirmation. Am J Psy-
chiatry 1990; 147:1313–1317
118. Post RM, DeLisi LE, Holcomb HH, Uhde TW, Cohen R, Buchs-
baum MS: Glucose utilization in the temporal cortex of affec-
tively ill patients: positron emission tomography. Biol Psychia-
try 1987; 22:545–553
119. Mayberg HS, Lewis PJ, Regenold W, Wagner HN Jr: Paralimbic
hypoperfusion in unipolar depression. J Nucl Med 1994; 35:
120. Bench CJ, Friston KJ, Brown RG, Frackowiak RS, Dolan RJ:
Regional cerebral blood flow in depression measured by posi-
tron emission tomography: the relationship with clinical dimen-
sions. Psychol Med 1993; 23:579–590
121. Liddle PF, Friston KJ, Frith CD, Hirsch SR, Jones T, Frackowiak
RS: Patterns of cerebral blood flow in schizophrenia. Br J Psy-
chiatry 1992; 160:179–186
122. Goldman-Rakic PS: Circuitry of primate prefrontal cortex and
regulation of behaviour by representational memory, in Hand-
book of Physiology—The Nervous System, V. Edited by
Mountcastle VB, Plum F, Geiger SR. Bethesda, Md, American
Physiological Society, 1987, pp 373–417
123. Dolan RJ, Bench CJ, Brown RG, Scott LC, Friston KJ, Frack-
owiak RS: Regional cerebral blood flow abnormalities in de-
pressed patients with cognitive impairment. J Neurol Neuro-
surg Psychiatry 1992; 55:768–773
124. Martin J: Neuroanatomy Text and Atlas. Norwalk, Conn, Ap-
pleton & Lange, 1989
16 Am J Psychiatry 154:1, January 1997
125. Carllson A: The occurrence, distribution and physiological role
of catecholamines in the nervous system. Pharmacol Rev 1959;
126. Meltzer HY: The importance of serotonin-dopamine interac-
tions in the action of clozapine. Br J Psychiatry Suppl 1992;
127. Meltzer HY, Nash JF: Effects of antipsychotic drugs on seroto-
nin receptors. Pharmacol Rev 1991; 42:587–604
128. Moghaddam B, Bunney BS: Acute effects of typical and atypical
antipsychotic drugs on the release of dopamine from prefrontal
cortex, nucleus acumbens, and striatum of the rat: an in vivo
microdialysis study. J Neurochem 1990; 54:1755–1760
129. Brown AS, Gershon S: Dopamine and depression. J Neural
Transm 1993; 91:75–109
130. Gjerris A, Werdelin L, Rafaelsen OJ, Alling C, Christensen NJ:
CSF dopamine increased in depression: CSF dopamine, norad-
renaline and their metabolites in depressed patients and in con-
trols. J Affect Disord 1987; 13:279–286
131. Gjerris A: Do concentrations of neurotransmitters in lumbar
CSF reflect cerebral dysfunction in depression? Acta Psychiatr
Scand Suppl 1988; 345:21–24
132. Reddy PL, Khanna S, Subhash MN, Channabasavanna SM,
Rao BS: CSF amine metabolites in depression. Biol Psychiatry
1992; 31:112–118
133. Roy A, Pickar D, Linnoila M, Doran AR, Ninan P, Paul SM:
Cerebrospinal fluid monoamine and monoamine metabolite
concentrations in melancholia. Psychiatry Res 1985; 15:281–
134. Markianos M, Alevizos B, Hatzimanolis J, Stefanis C: Effects
of monoamine oxidase A inhibition on plasma biogenic amine
metabolites in depressed patients. Psychiatry Res 1994; 52:259–
135. Wolfe N, Katz DI, Albert ML, Almozlino A, Durso R, Smith
MC, Volicer L: Neuropsychological profile linked to low dopa-
mine: in Alzheimer’s disease, major depression, and Parkinson’s
disease. J Neurol Neurosurg Psychiatry 1990; 53:915–917
136. Carr V, Edwards J, Prior M: Urinary MHPG, platelet 3H-imip-
ramine binding and symptomatology in depression: an explora-
tory study of clinical heterogeneity. Biol Psychiatry 1988; 23:
137. Maes M, Meltzer HY, Suy E, Minner B, Calabrese J, Cosyns P:
Sleep disorders and anxiety as symptom profiles of sympatho-
adrenal system hyperactivity in major depression. J Affect Dis-
ord 1993; 27:197–207
138. Nair NP, Sharma M: Neurochemical and receptor theories of
depression. Psychiatr J Univ Ottawa 1989; 14:328–341
139. Rampello L, Nicoletti G, Raffaele R: Dopaminergic hypothesis
for retarded depression: a symptom profile for predicting thera-
peutical responses. Acta Psychiatr Scand 1991; 84:552–554
140. Kabins D, Gershon S: Potential applications for monoamine
oxidase B inhibitor. Dementia 1990; 1:323–348
141. Rudorfer MV, Golden RN, Potter WZ: Second-generation an-
tidepressants. Psychiatr Clin North Am 1984; 7:519–534
142. Goodnick PJ, Extein IL: Bupropion and fluoxetine in depressive
subtypes. Ann Clin Psychiatry 1989; 1:119–122
143. Goldstein BJ, Brauzer B, Kentsmith D, Rosenthal S, Charalam-
pous KD: Double-blind placebo-controlled multicenter evalu-
ation of the efficacy and safety of nomifensine in depressed out-
patients. J Clin Psychiatry 1984; 45:52–55
144. Feighner JP, Merideth CH, Claghorn JL: Multicenter placebo-
controlled evaluation of nomifensine treatment in depressed
outpatients. J Clin Psychiatry 1984; 45(4, part 2):47–51
145. Klerman GL: The evolution of a scientific nosology, in Schizo-
phrenia: Science and Practice. Edited by Shershow JC. Cam-
bridge, Mass, Harvard University Press, 1978, pp 99–121
146. Ghez C: Voluntary movement, in Principles of Neural Science,
3rd ed. Edited by Kandel ER, Schwartz JH, Jessell TM. Nor-
walk, Conn, Appleton & Lange, 1991, pp 626–646
Am J Psychiatry 154:1, January 1997 17
... Clinical outcomes following ischemic stroke in patients with depression manifest in various forms, including ambulation, which is relevant in the assessment of treatment outcomes [1]. Ambulatory behavior is known to be modulated by emotions and has long been recognized as an integral sign of depression [2], and can predict the course of the disease [3,4]. Alterations in the ambulatory status are well-known as clinically observable phenomena of depressed patients [5]. ...
... These alterations may be linked to abnormalities in the motor pathways that may also lead to alterations of ambulatory patterns in depressed patients [6]. Several studies [7][8][9][10] provide evidence that an improvement or lack of improvement in the ambulatory status of patients with depression is relevant for evaluation of course and treatment response [3,4,11]. After stroke, more than 60% of survivors present with a reduced ambulatory status [12,13]. ...
Background. Specific clinical risk factors that may be associated with ambulatory outcome following thrombolysis therapy in ischemic stroke patients with pre-stroke depression is not fully understood. This was investigated. Methods. Multivariate analyses were performed to identify predictors of functional ambulatory outcomes. Patient demographics and clinical risk factors served as predictive variables, while improvement or no improvement in ambulatory outcome was considered as the primary outcome. Results. A total of 595 of these patients received rtPA of which 310 patients presented with pre-stroke depression, 217 had no improvement in functional outcome, while 93 patients presented with an improvement in functional outcome. Carotid artery stenosis (OR= 11.577, 95% CI, 1.281 – 104.636, P=0.029) and peripheral vascular disease (OR= 18.040, 95% CI, 2.956-110.086, P=0.002) were more likely to be associated with an improvement in ambulation. Antihypertensive medications (OR= 7.810, 95% CI, 1.401 –43.529, P=0.019),previous TIA (OR= 0.444, 95% CI, 0.517 –0.971, P=0.012), and congestive heart failure (OR= 0.217, 95% CI, 0.318 –0.402, P=0.030) were associated with a no improvement in ambulation. Conclusion. After adjustment for covariates, more clinical risk factors were associated with no improvement when compared with improvement in functional outcome following thrombolysis therapy in an acute ischemic stroke population with pre-stroke depression.
... Actigraphy data is obtained using a compact, lightweight, and affordable device with longterm data storage capability that only requires wearing a wrist/waist band with minor intervention (periodic charging). 185,[195][196][197] Even though actigraphy has been used to evaluate sleep-wake changes for nearly half a century, a more modern and promising application in recent years involves its automated measures of circadian motor activity rhythms with date-time stamps. 198 With the growing popularity of wearable technology, the use of actigraphy devices with valid measures of motor activity has become widespread and the data have become easily accessible. ...
... 13 Through the objective measures of motor activity, actigraphy can be used to detect early improvement in depression that can predict remission from antidepressant treatment. 80,185,196,201 However, to our knowledge, no study to date has used actigraphy early in treatment to assess initial antidepressant response to conventional MDD treatments. Assessing response in the first week of treatment may be especially important because the initial effect of antidepressants may occur by the end of the first week of treatment. ...
No biomarkers for antidepressant efficacy in major depressive disorder (MDD) are available that can reduce patient suffering and healthcare costs from ineffective trials. This dissertation examined such biomarkers using modalities such as pretreatment neuroimaging including structural magnetic resonance imaging (sMRI), positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG), magnetic resonance spectroscopy (MRS) and actigraphy. The data came from a double-blind, randomized, placebo-controlled antidepressant trial in participants with MDD whose depression severity was quantified before, after one week and after eight weeks of treatment. The most promising neuroimaging biomarkers were detected from pretreatment PET/MRS (n=60) data using machine learning with a split of 67% for training and cross-validation, and 33% for testing. The training data underwent Synthetic Minority Over-sampling Technique and outlier removal using OneClassSVM, before being used in the eXtreme Gradient Boosting (XGBoost) algorithm to predict remission following eight weeks of treatment. The hyperparameters including subsampling, tree depth, number of trees and L1 and L2 regularization were optimized using GridSearchCV with 3 repetitions of stratified 10-fold cross-validation. In the test set, this model showed 62% sensitivity and 92% specificity with 77% weighted accuracy. Pretreatment metabolism of left hippocampus was the most predictive of all features. In addition, cost-effective measures of motor activity related to circadian rhythm (CR), recorded using actigraphy devices, were collected from 40 participants during this trial. Parametric measures of average of CR (midline estimating statistic of rhythm, MESOR), amplitude, circadian quotient (CQ: amplitude/MESOR) and time of peak activity (acrophase) were obtained by applying cosinor analysis. Nonparametric measures including the average activity over 10 most and 5 least active hours were extracted along with intradaily variability and interdaily stability. These actigraphy measures from the first week of treatment did not predict depression severity after eight weeks of treatment. However, each percent improvement in depression from baseline during first week was associated with lower CQ (48.78 units) during that week (p<0.05). The findings suggest that any predictive value gained from 60 minutes of pretreatment neuroimaging can save patients from weeks of ineffective trials. Moreover, motor activity can be valuable for remotely monitoring patients with limited access to mental health care.
... Even though NSS have been most thoroughly investigated in schizophrenia, increased NSS have also been reported in obsessive compulsive disorder (Hollander et al. 2005;Tumkaya et al. 2012), borderline personality disorder (De la Fuente et al. 2006), post-traumatic stress disorder (Gurvits et al. 1993(Gurvits et al. , 2000(Gurvits et al. , 2006 and MDD (Cox and Ludwig 1979b;Baldwin et al. 2005). NSS in unipolar depression have so far received little attention, despite the fact that psychomotor retardation is a core feature of depression (Sobin and Sackeim 1997) and part of DSM-V criteria for MDD diagnosis. While much research has focused on potential cognitive side effects of ECT (Semkovska and McLoughlin 2010), NSS had hitherto never been studied longitudinally in MDD patients receiving ECT. ...
Full-text available
The significance of neurological soft signs (NSS) in major depressive disorder (MDD) remains unclear and the stability of NSS in relation to antidepressant treatment has never been investigated. We hypothesized that NSS are relatively stable trait markers of MDD. We thus predicted that patients show more NSS than healthy controls, irrespective of illness duration and antidepressant treatment. To test this hypothesis, NSS were assessed in chronically depressed, medicated MDD patients before (n = 23) and after (n = 18) a series of electroconvulsive therapy (ECT). In addition, NSS were assessed once in acutely depressed, unmedicated MDD patients (n = 16) and healthy controls (n = 20). We found that both chronically depressed, medicated MDD patients and acutely depressed, unmedicated MDD patients showed more NSS than healthy controls. The degree of NSS in both patient groups did not differ. Importantly, we found no change in NSS after on average eleven sessions of ECT. Thus, the manifestation of NSS in MDD seems to be independent of illness duration and pharmacological and electroconvulsive antidepressant treatment. From a clinical perspective, our findings corroborate the neurological safety of ECT.
... The primary motor cortex (M1) initiates and controls voluntary movements and contributes to motor learning. Although motor symptoms are known to occur in psychiatric disorders like major depression (Sobin and Sackeim 1997), M1 was previously not a region associated with stress effects. By in vivo imaging of M1, we detected a persistent reduction of dendritic spines and disturbed spine dynamics of excitatory neurons upon CSDS, which lasted up to 23 days ). ...
Full-text available
Neuropsychiatric disorders, such as major depression, anxiety disorders, and post-traumatic stress disorder, tend to be long-term conditions in whose development and maintenance stress are central pathogenic factors. Translational mouse models are widely used in neuropsychiatric research, exploiting social and non-social stressors to investigate the mechanisms underlying their detrimental effects. However, most studies focus on the short-term consequences of chronic stress, whereas only a few are interested in the long-term course. This is counterintuitive given the human conditions that preclinical models are designed to mimic. In this review, we have summarized the limited work to date on long-term effects of chronic stress in mice models. First, the different models are presented and a definition of short- vs. long-term sequelae is proposed. On this basis, behavioral, endocrine, and vegetative effects are addressed before examining data on cellular and molecular alterations in the brain. Finally, future directions for research on the long-term effects of stress are discussed.
... Clinicians classify depressed speech as monotonous, boring and listless (Sobin & Sackeim, 1997). The emotional state of depressive patients affects the acoustic quality of speech (Cummins et al., 2015). ...
Full-text available
Early intervention for depression could provide a means to reducing the disease burden, but there is a lack of objective diagnostic methods. This study investigated automatic depression classification on a speech dataset of 85 healthy controls (51 females and 34 males) and 85 depressed patients (53 females and 32 males). Considering that there are obvious differences in the performance of different types of speech features, we propose a radius-incorporated localized multiple kernel learning (trLMKL) algorithm for detecting depression in speech to make the best use of speech features. To improve the classification accuracy, we combine the information of both the margin and the radius of the MEB to learn the gating model parameters in our algorithm. Furthermore, we do not directly incorporate the radius of the MEB, but incorporate the trace of the total scattering matrix of training data. This method can avoid the time cost of calculating the radius at each iteration and decrease the computational complexity. Comprehensive experiments were carried out on our depressed speech dataset and 10 UCI datasets. Our algorithm achieved better classification performance overall than SimpleMKL and LMKL, and it was efficient at detecting depression, indicating its potential for use as a diagnostic method for depression.
... Speech affected by depression is often subjectively characterised in clinical settings by decreases in verbal activity, decreases in utterance length, a reduction in speech rate and an increase in long silent pauses [9,10,11,12]. Speech has many properties which make it an attractive candidate for use in an automated screening tool; it can be measured cheaply, remotely, non-invasively and non-intrusively [13]. On the other side, previous studies have already shown that depression also has an effect on the language used by affected individuals [14]. ...
Background: Previous studies suggested an association between functional alteration of the amygdala and typical major depressive disorder (MDD) symptoms. Examining whether and how the interaction between the amygdala and regions/functional networks is altered in patients with MDD is important for understanding its neural basis. Methods: Resting-state functional magnetic resonance imaging data were recorded from 67 patients with MDD and 74 age- and sex-matched healthy controls (HCs). A framework for large-scale network analysis based on seed mappings of amygdala sub-regions, using a multi-connectivity-indicator strategy (cross-correlation, total interdependencies (TI), Granger causality (GC), and machine learning), was employed. Multiple indicators were compared between the two groups. The altered indicators were ranked in a supporting-vector machine-based procedure and associated with the Hamilton Rating Scale for Depression scores. Results: The amygdala connectivity with the default mode network and ventral attention network regions was enhanced and that with the somatomotor network, dorsal frontoparietal network, and putamen regions in patients with MDD was reduced. The machine learning analysis highlighted altered indicators that were most conducive to the classification between the two groups. Limitations: Most patients with MDD received different pharmacological treatments. It is difficult to illustrate the medication state's effect on the alteration model because of its complex situation. Conclusion: The results indicate an unbalanced interaction model between the amygdala and functional networks and regions essential for various emotional and cognitive functions. The model can help explain potential aberrancy in the neural mechanisms that underlie the functional impairments observed across various domains in patients with MDD.
Background: Automatic diagnosis of depression based on speech can complement mental health treatment methods in the future. Previous studies have reported that acoustic properties can be used to identify depression. However, few studies have attempted a large-scale differential diagnosis of patients with depressive disorders using acoustic characteristics of non-English speakers. Objective: This study proposes a framework for automatic depression detection using large-scale acoustic characteristics based on the Korean language. Methods: We recruited 153 patients who met the criteria for major depressive disorder and 165 healthy controls without current or past mental illness. Participants' voices were recorded on a smartphone while performing the task of reading predefined text-based sentences. Three approaches were evaluated and compared to detect depression using data sets with text-dependent read speech tasks: conventional machine learning models based on acoustic features, a proposed model that trains and classifies log-Mel spectrograms by applying a deep convolutional neural network (CNN) with a relatively small number of parameters, and models that train and classify log-Mel spectrograms by applying well-known pretrained networks. Results: The acoustic characteristics of the predefined text-based sentence reading automatically detected depression using the proposed CNN model. The highest accuracy achieved with the proposed CNN on the speech data was 78.14%. Our results show that the deep-learned acoustic characteristics lead to better performance than those obtained using the conventional approach and pretrained models. Conclusions: Checking the mood of patients with major depressive disorder and detecting the consistency of objective descriptions are very important research topics. This study suggests that the analysis of speech data recorded while reading text-dependent sentences could help predict depression status automatically by capturing the characteristics of depression. Our method is smartphone based, is easily accessible, and can contribute to the automatic identification of depressive states.
Psychotic depression has a high rate of relapse. The study aims were to identify a prediction model of risk of relapse of psychotic depression and examine whether predictors moderated the effect of treatment on relapse. One hundred and twenty-six men and women aged 18-85 years, who experienced sustained remission or near-remission of psychotic depression with sertraline plus olanzapine, participated in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse (NCT01427608). Cox regression analyses were performed to identify significant predictors of relapse and to model the combined role of significant predictors. Concordance statistic was calculated to determine the accuracy of the best fit multivariable models in predicting relapse. Finally, interaction terms were tested for each significant predictor to examine whether they moderated the effect of treatment on risk of relapse. Lifetime number of depressive episodes, severity of residual depressive symptoms at the time of randomization, and psychomotor disturbance both at acute enrollment when participants were depressed and at the time of randomization predicted risk of relapse. Multivariable models had 69-70% accuracy in predicting relapse. Psychomotor disturbance was associated with increased risk of relapse in the sertraline plus olanzapine group compared with sertraline plus placebo, whereas the other predictors did not moderate the effect of treatment on relapse. Future research is needed to determine whether a combination of clinical and biological variables can further increase the accuracy of prediction of relapse of psychotic depression.
The clinical characteristics of 70 patients included in the Northwick Park ECT trial of real against simulated ECT were analysed to identify predictors of response to the two treatments. The initial agitated/deluded/retarded substratification, the initial assessment of delusions by PSE, the individual items and factors derived from the Hamilton depression scale were all evaluated, together with six scales previously held to predict response to ECT and the individual items of these scales. The limited size of the sample does not allow firm conclusions, but the most significant and only consistent predictor of response to real ECT appeared to be the presence of delusions. The features of 'endogenous depression' did not in themselves appear to predict response to real ECT. The findings are discussed in relation to the viewpoint that delusional depression may be a specific entity which is relatively resistant to tricyclic antidepressants but responsive to electroconvulsive shock.
• Cerebral metabolic rates for glucose were examined in patients with unipolar depression (N=11), bipolar depression (N=5), mania (N=5), bipolar mixed states (N =3), and in normal controls (N = 9) using positron emission tomography and fluorodeoxyglucose F 18. All subjects were studied supine under ambient room conditions with eyes open. Bipolar depressed and mixed patients had supratentorial whole brain glucose metabolic rates that were significantly lower than those of the other comparison groups. The whole brain metabolic rates for patients with bipolar depression increased going from depression or a mixed state to a euthymic or manic state. Patients with unipolar depression showed a significantly lower ratio of the metabolic rate of the caudate nucleus, divided by that of the hemisphere as a whole, when compared with normal controls and patients with bipolar depression.
Under two experimental conditions the relation between the reaction time (RT) and the motion time (MT) in a choice reaction task was studied. In a condition ‘without time stress’ RT and MT turned out to be directly proportional, whereas in the ‘time stress’ condition RT and MT were inversely related. From these observations it was inferred that under ‘time stress’ Ss are able to compensate a long RT by means of a short MT. In a second experiment it was shown that the compensation is made consciously: Ss being aware of relatively small fluctuations in their RT adapt consciously the complexity of a required motor response to the length of a given RT in order to finish the total reaction in time.
Monoamine oxidase inhibitors (MAOIs) are not only effective antidepressants, but also have several other applications. Yet, they are infrequently used as a result of their potential to cause toxic side effects such as tyramine-induced hypertensive crisis (cheese effect). A resurgence of interest in MAOIs followed the finding of two forms of MAO. This resulted from the development of drugs that selectively inhibit the metabolism of serotonin and norepinephrine (MAO-A) or dopamine and phenethylamine (MAO-B). MAO-B is the predominant MAO found in the human brain. Theoretically, selective MAO-B inhibition can enhance brain MAO levels while leaving intestinal MAO-A intact, thus bypassing the cheese effect, L-deprenyl is the most extensively studied MAO-B inhibitor. At low doses, it is very selective for MAO-B and is not associated with the cheese effect. At higher doses, it is virtually nonselective. L-deprenyl enhances the effect of L-dopa on Parkinson's disease and may retard its natural progression. Although studies have found L-deprenyl to be an effective antidepressant only at nonselective doses, certain subtypes of depression may respond to selective doses. Also, evidence suggests that L-deprenyl has a positive effect on the general function and cognitive abilities of Alzheimer patients. Studies to date, including those showing a significant increase in the life span of rats following L-deprenyl use have led to the speculation that L-deprenyl may not only treat or retard degenerative diseases and acute brain insults, but may prove to be the first antiaging medication. Several other potential applications of MAO-B inhibitors include panic, ADHD, sexual dysfunction, and PTSD. It remains unclear what role MAO-B inhibition plays in the various therapeutic effects of L-deprenyl. Other potential mechanisms are discussed.Copyright © 1990 S. Karger AG, Basel
Monoamine oxidase inhibitors (MAOIs) are not only effective antidepressants, but also have several other applications. Yet, they are infrequently used as a result of their potential to cause toxic side effects such as tyramine-induced hypertensive crisis (cheese effect). A resurgence of interest in MAOIs followed the finding of two forms of MAO. This resulted from the development of drugs that selectively inhibit the metabolism of serotonin and norepinephrine (MAO-A) or dopamine and phenethylamine (MAO-B). MAO-B is the predominant MAO found in the human brain. Theoretically, selective MAO-B inhibition can enhance brain MAO levels while leaving intestinal MAO-A intact, thus bypassing the cheese effect, L-deprenyl is the most extensively studied MAO-B inhibitor. At low doses, it is very selective for MAO-B and is not associated with the cheese effect. At higher doses, it is virtually nonselective. L-deprenyl enhances the effect of L-dopa on Parkinson's disease and may retard its natural progression. Although studies have found L-deprenyl to be an effective antidepressant only at nonselective doses, certain subtypes of depression may respond to selective doses. Also, evidence suggests that L-deprenyl has a positive effect on the general function and cognitive abilities of Alzheimer patients. Studies to date, including those showing a significant increase in the life span of rats following L-deprenyl use have led to the speculation that L-deprenyl may not only treat or retard degenerative diseases and acute brain insults, but may prove to be the first antiaging medication. Several other potential applications of MAO-B inhibitors include panic, ADHD, sexual dysfunction, and PTSD. It remains unclear what role MAO-B inhibition plays in the various therapeutic effects of L-deprenyl. Other potential mechanisms are discussed.Copyright © 1990 S. Karger AG, Basel