15. depression and motor retardation

Journal of Affective Disorders 57 (2000) 83–93www.elsevier.com/ locate / jad

Research report

Motor and cognitive aspects of motor retardation in depression

*Michael P. Caligiuri , Joel Ellwanger

Department of Psychiatry (0603), Movement Disorders Laboratory, University of California at San Diego, La Jolla, CA 92093, USA

Received 22 December 1998; accepted 22 March 1999

Abstract

Background: Motor retardation is a common feature of major depressive disorder having potential prognostic andetiopathological significance. According to DSM-IV, depressed patients who meet criteria for psychomotor retardation, mustexhibit motor slowing of sufficient severity to be observed by others. However, overt presentations of motor slowing cannotdistinguish slowness due to cognitive factors from slowness due to neuromotor disturbances. Methods: We examinedcognitive and neuromotor aspects of motor slowing in 36 depressed patients to test the hypothesis that a significantproportion of patients exhibit motor programming disturbances in addition to psychomotor impairment. A novel instrumentaltechnique was used to assess motor programming in terms of the subject’s ability to program movement velocity as afunction of movement distance. A traditional psychomotor battery was combined with an instrumental measure of reactiontime to assess the cognitive aspects of motor retardation. Results: The depressed patients exhibited significant impairment onthe velocity scaling measure and longer reaction times compared with nondepressed controls. Approximately 40% of thepatients demonstrated abnormal psychomotor function as measured by the traditional battery; whereas over 60% exhibitedsome form of motor slowing as measured by the instruments. Approximately 40% of the patients exhibited parkinsonian-likemotor programming deficits. A five-factor model consisting of motor measures predicted diagnosis among bipolar andunipolar depressed patients with 100% accuracy. Limitations: The ability of motor measures to discriminate bipolar fromunipolar patients must be viewed with caution considering the relatively small sample size of bipolar patients. Conclusions:These findings suggest that a subgroup of depressed patients exhibit motor retardation that is behaviorally similar toparkinsonian bradykinesia and may stem from a similar disruption within the basal ganglia. 2000 Elsevier Science B.V.All rights reserved.

Keywords: Depression; Motor retardation; Psychomotor impairment

1. Introduction which, according to DSM-IV, ‘‘ . . . must be severeenough to be observed by others’’ (American Psychi-

Current diagnostic criteria for major depression atric Association, 1994; p. 321). Most features ofinclude the presence of psychomotor retardation motor retardation are easily observed. These consist

of reduced speed, slow speaking rate, delayed motorinitiation, body immobility, loss of facial expression,*Corresponding author. Tel.: 1 1-619-552-8585, ext. 2163.

E-mail address: [email protected] (M.P. Caligiuri) and postural abnormalities (Parker et al., 1993).

0165-0327/00/$ – see front matter 2000 Elsevier Science B.V. All rights reserved.PI I : S0165-0327( 99 )00068-3

84 M.P. Caligiuri, J. Ellwanger / Journal of Affective Disorders 57 (2000) 83 –93

Parker et al. (1993) suggested a ‘trunk and branch’ that neuromotor slowing would manifest as impairedanalogy as a means of modeling motor disturbances velocity scaling stems from extensive research on thein depression. In this model, a truncal psychic mechanism of parkinsonian bradykinesia (Drapercomponent arborises into retarded and agitated bran- and Johns, 1964; Berardelli et al., 1986; Warabi etches. While the model accounts for three potentially al., 1986; Benecke, 1989; Hufschmidt and Lucking,overlapping factors, it ignores the possibility that the 1995). Our findings confirmed the presence of a‘root’, which gives rise to the truncal component, motor programming disorder in all of the Parkinso-may contain elements shared by other neuropsychiat- nian patients studied and in nearly one-third of theric disorders, such as Parkinson’s disease (PD). psychosis patients. In a follow-up study of motorRestricting the criteria for motor disturbances in performance of the depressed and nondepresseddepression to those that are observable, as suggested psychosis patients (Caligiuri et al., 1998b), theby DSM-IV, minimizes the likelihood that the neuro- nondepressed patients exhibited normal psychomotorbiology of depression can be fully understood. performance, but scored in the abnormal range on

It is noteworthy that the motor signs which measures of motor programming. Conversely, de-characterize motor retardation are indistinguishable pressed patients exhibited abnormal psychomotorfrom characteristics of idiopathic PD. This has led performance, but scored within normal limits onsome investigators to hypothesize the presence of a measures of motor programming, even after control-common neurobiological mechanism for motor re- ling for medication and age. These findings suggesttardation in depression and parkinsonism (Sachdev that motor slowing may have a cognitive basis in theand Aniss, 1994), while others have found marked presence of depression and a neuromotor basis in thedifferences in the motor behavior of PD and de- absence of depression.pressed patients (Fleminger, 1992). The evidence for In the present study, we used the velocity scalinga mechanistic overlap between depression and par- measure together with a battery of traditional psy-kinsonism is strong. Depression has been reported as chomotor measures to test the hypothesis that aa feature in PD (Rogers et al., 1987; Tom and significant proportion of depressed patients exhibitCummings, 1988; Tandberg et al., 1997) and psychomotor programming disturbances. Disturbances insis (Prosser et al., 1987), and it is possible that some the programming of movement velocity have beenaspects of motor retardation may actually signal the thought of as contributing to the bradykinesia seenpresence of specific neuromotor pathology or a in patients with Parkinson’s disease (Hallett andmedication side effect (Casey, 1994). Overall, the Khoshbin, 1980; Hallet, 1985). Impaired motorovert signs associated with slowness, such as re- programming in depression would suggest that forduced movement velocities, increased reaction times, these patients, their motor retardation may stem fromand increased movement times are similar in depres- disturbed dopamine neurotransmission within thesion and parkinsonism. basal ganglia. Alternatively, motor slowing in the

In a previous study, (Caligiuri et al., 1998a), we absence of a velocity programming deficit woulddescribed a novel approach for separating motor suggest a more cognitive origin of the slowness inslowing into two components: a basic neuromotor depression.component derived from movement velocity and ahigher level cognitive or attentional componentderived from a measure of reaction time. The 2. Methodspurpose of this dichotomy is to distinguish patientswhose slowness is driven by neuromotor factors, 2.1. Patientssuch as medication side effects, from those whoseslowness is related to cognitive factors. Using wrist Thirty-six depressed outpatients (12 women andmovement velocity, we measured the subject’s abili- 24 men) and 22 nondepressed healthy controls (ninety to program (or scale) movement velocity in women and 13 men) were studied. The patients had aanticipation of changing target distances. The idea mean (S.D.) age of 45.1 (10.7) years and the controls

M.P. Caligiuri, J. Ellwanger / Journal of Affective Disorders 57 (2000) 83 –93 85

had a mean age of 46.7 (16.6) years. Thirty-one of a rotation sensor attached to a handle (electro-the patients met DSM-IV criteria for major depres- goniometer) was used to record wrist rotation. A linesive disorder; whereas five patients met DSM-IV drawing of the instrumental set-up is shown in Fig.criteria for bipolar II disorder. Patients were re- 1. The analog output from the electrogoniometer wascruited from the VA San Diego Healthcare System digitized at 100 samples / s (12-bit) and customClinical Research Center within the Department of software was used to convert the digitized signal to aPsychiatry. Ten patients were currently enrolled in large cursor displayed on the monitor. The positioncognitive behavioral therapy, while the remaining 26 of the cursor along the horizontal plane was cali-patients were enrolled into ongoing clinical trials. brated in degrees of rotation. In addition to theThe control subjects were recruited from psychiatry rotation-based cursor, target boxes were displayed onservice staff and medical center volunteers. For all the monitor, also along the horizontal plane and werepatients, the assessments described herein were made located at 25 or 458 left of midline for right wristduring their initial visit of their respective trials. flexion, and right of midline for left wrist flexion.Because the majority of the patients were enrolling Subjects sat facing a computer monitor while holdinginto pharmaceutical efficacy trials, most patients the electrogoniometer handle with one hand. Sub-were unmedicated at the time of motor assessment. jects were instructed to flex the wrist ‘as quickly andOnly 11 of the 36 patients were on antidepressants at as accurately as possible’ when a target box appearedthe time of assessment. Three patients were receiving on the screen causing the cursor to move horizontallyantipsychotic medication and two patients were on toward one of two target boxes. The target remainedmood stabilizers. Severity of depression was rated displayed for 2 s with an interstimulus interval of 2using the 17-item Hamilton Rating Scale for Depres- s. Two blocks of trials or movements, consisting ofsion (HRSD; Hamilton, 1967) for all patients en- 16 trials for each of two randomly presented targetrolled into pharmaceutical trials and the Beck De- locations were administered for each hand, for a totalpression Inventory (BDI; Beck, 1972) for patients of 64 movements.enrolled in behavioral therapy. On the basis of For velocity scaling, the peak instantaneous ve-established cut-points for these instruments locities and angular distances from each of the 32(Knesevich et al., 1977; Beck et al., 1988), two trials for a given hand were used to compute thepatients exhibited mild, 22 moderate, and 12 severe difference scores for 25 and 408 targets. A velocitydepression. scaling score was derived from the equation: VS 5

(V40 2V25) /(D40 2 D25), where V and D representvelocity and angular distance, respectively, for the 40

2.2. Instrumental assessment of motor and 258 targets. Reaction time was measured byprogramming and slowing obtaining the time from stimulus onset to movement

onset in milliseconds. Peak instantaneous velocityFollowing the clinical assessment, patients who was measured by computing the first derivative of

met DSM-IV criteria for major depressive disorder or rotation (angular velocity). The reliability of thebipolar disorder were provided a description of the procedure was established in a previous studystudy. Those who signed informed consent to partici- (Caligiuri et al., 1998a). In that study, 10 psychosispate in research were referred to the Movement patients were retested within the same session withDisorders Laboratory for motor assessments. Motor the dominant hand. The reliability coefficient for theassessments were conducted within 1 week of the slope was 0.98 suggesting very high repeatability forclinical depression ratings. Reassessments of clinical this measure. This measure may be considered ansymptoms at the time of the motor assessments were example of open loop motor control, insofar as thedeemed unnecessary because of this short interval. rapid wrist movements were ballistic in nature

Three measures were obtained using a single (Schmidt, 1982). Accordingly, analyses were basedinstrument: velocity scaling, reaction time, and peak on the initial peak velocity rather than averageinstantaneous velocity. A platform instrumented with velocity. Feedback-derived corrections would appear


Fig. 1. Line drawing of the subject–apparatus interface showing the wrist electrogoniometer, amplifier and computer monitor. Subject sitsfacing the monitor and responds to target cues presented on the screen. Flexion movements of the wrist cause the subject’s cursor (circle) tomove to target (box). See text for data acquisition and analysis details.

as multiple velocity peaks which were not incorpo- bol substitution test (DSST), Trails A, and Trails B.rated into the measure of velocity scaling. These tests were administered and scored by a

trained staff member.2.3. Assessment of psychomotor function

2.4. Statistical analysesThree psychomotor assessments were administered

for the purpose of comparing performance on tradi- Independent t-tests were used to test differencestional measures of psychomotor retardation with between patients and controls on all instrumentalperformance on the instrumental measures. The motor measures once the group data were found topsychomotor measures are part of the comprehensive satisfy all assumptions for a parametric statistic.Halstead–Reitan battery and included the digit sym- Pearson correlational analyses were used to examine


the relationships between severity of depression and possibility that their motor slowing may have itsperformance on motor measures. Lastly, the effects origin in faulty motor programming. Four of the fiveof medication on motor variables were examined patients (80%) with bipolar disorder exhibited abnor-using t-tests by comparing patients on versus off any mal scores on the velocity scaling measure comparedof three classes of medication: antipsychotics, anti- with 10 of the 31 (32.2%) patients with unipolar

2depressants, and mood stabilizers. depression (x 5 4.13; P 5 0.04). For reaction time,none of the bipolar patients met criteria for abnor-mality; whereas 11 of the 31 patients (35.5%) with

3. Results unipolar depression exhibited abnormally long re-action times.

3.1. Instrumental measures of motor slowing3.2. Psychomotor disturbances

Table 1 shows the descriptive statistics for patientsand controls for the instrumental motor measures. Regarding performance on the psychomotor bat-Results of independent t-tests indicated significant tery, the depressed patients as a group did not exhibitdifferences between depressed patients and nondep- impaired performance relative to standard publishedressed healthy controls on all of the instrumental age and education corrected norms (Heaton et al.,motor measures. Depressed patients exhibited sig- 1986, 1991). Four patients were unable to completenificantly longer reaction times, lower velocities, and the psychomotor battery for various reasons. The rawlower scores on the velocity scaling measure. scores for these measures were converted to t-scores

Additional analyses were performed on the in- for the purpose of correcting for age and education.dividual data to estimate the prevalence of impaired The mean corrected scores (and standard deviations)motor function. Patients were considered to exhibit for the remaining 32 patients for Trails A, Trails B,abnormality if their scores exceeded cut-points of 1.5 and the DSST were 48.0 (11.2), 48.8 (9.7) and 49.9S.D. above the normal control mean for reaction time (10.0), respectively, which did not differ from theand 1.5 S.D. below the normal control mean for peak published normal mean value of 50.0 (10.0). How-velocity, and velocity scaling. Twenty-two of the 36 ever, individually, nine patients (28.1%) met stan-patients (61.1%) exhibited abnormalities on at least dard criteria for impaired performance on Trails A,one instrumental measure based on these cut-points. seven patients (21.8%) met standard criteria forThe proportions of patients meeting this criteria for impaired performance on Trails B, and eight patientsspecific abnormalities of reaction time, velocity (25%) met standard criteria for impaired perform-scaling, and peak velocity were 30.5% (11 patients), ance on the DSST. Overall 14 patients (43.7%)40% (14 patients) and 27.8% (10 patients), respec- exhibited impairment on at least one of the threetively. Nine patients (25.7%) exhibited abnormal psychomotor tests. Interestingly, a similar proportionvelocity scaling in addition to abnormalities on at of bipolar versus unipolar depressed patients ex-least one other instrumental measure, suggesting the hibited abnormal psychomotor performance on at

Table 1Means (and standard deviations) for the instrumental measures of motor slowing for 22 non-depressed healthy controls and 36 depressedpatients

Group Reaction time Velocity at 258 Velocity at 408 Velocity scaling(ms) (deg/s) (deg/s) (deg/s /deg)

Controls 366.07 146.77 198.91 4.27(105.91) (59.10) (71.95) (1.93)

Patients 464.62 110.90 147.02 2.67(88.27) (53.23) (66.36) (1.49)

t-Test 2 3.82 2.38 2.79 3.19P value 0.0003 0.02 0.007 0.002


least one of the three measures with two of the five Table 2 shows the results of analyses of the effectsbipolar patients (40%) and 12 of the 27 unipolar of medication status on selected instrumental andpatients (44%) demonstrating a disturbance. psychomotor variables. Patients on antidepressants

were not less depressed than patients off antidepres-3.3. Relationships between motor slowing and sants. Of the 11 medicated patients, 27% met criteriaclinical factors for severe depression; whereas 36% of the 25

unmedicated patients met criteria for severe depres-2Correlational analyses were performed to examine sion (x 5 0.46; P . 0.10). The findings for the

the relationship between severity of motor impair- effects of antipsychotics and mood stabilizers onment and clinically relevant variables including motor slowing are difficult to interpret because of theseverity of depression, medication status, and age. small sample sizes. However, the results for antide-DSST score and peak velocity to 408 targets were pressants indicate a beneficial effect on the DSSTsignificantly correlated with HRSD with coefficients and average reaction time. Patients on antidepres-of r 5 2 0.61 (P 5 0.002) and r 5 2 0.44 (P 5 sants scored significantly higher on the DSST than0.033), respectively. These findings indicate that as patients off antidepressants (t 5 2 2.33; P 5 0.026).depression severity increased, performance on DSST Similarly, patients on antidepressants exhibited shor-worsened and movement velocities decreased. ter reaction times than patients off antidepressants

Eight patients who were rated at least mild on the (t 5 2.60; P 5 0.013).motor retardation item of the HRSD were compared The question of whether the motor measures offeron the five measures of motor slowing with 18 any diagnostic discriminability was addressed usingpatients who were rated as not exhibiting motor logistic regression. The results of a five-factor modelretardation. While none of the comparisons reached for predicting diagnosis (bipolar disorder versusstatistical significance, patients exhibiting clinically unipolar depression) are shown in Table 3. Therated motor retardation had lower scores for both the five-factor model accurately classified 100% of theTrails A (41.4 vs. 48.7) and DSST (45.7 vs. 50.1), patients into their respective diagnoses (F 5 9.91;slightly longer reaction times (482 vs. 474 ms), P , 0.0001). Removing Trails A and DSST fromlower peak velocities (132 vs. 164 deg/s), and lower the model reduced the overall accuracy to 91.4%,velocity scaling scores (2.06 vs. 3.00 deg/s / s) than classifying 80% of the bipolar disorder patients andpatients rated normal on the motor retardation item 93.3% of the unipolar depressed patients. Positive b

of the HRSD. Seven of the eight patients with values in Table 3 indicate higher scores; whereasobserver-rated motor retardation exhibited abnormal negative b values indicate lower scores for onevelocities, three of the eight exhibited abnormal group versus the other. The results indicate thatreaction times, and four of the eight exhibited patients with bipolar disorder had higher scores onabnormal velocity scaling based on the cut-points Trails A, lower scores on the DSST, higher peakdescribed above. velocities, shorter reaction times, and lower scores

Table 2Means (and S.D.) for the instrumental (reaction time, RT) and non-instrumental (trails A and digit symbol substitution test, DSST) measuresof psychomotor function that were found to be influenced by medication status

Antipsychotics Antidepressants Mood stabilizers

On (n 5 3) Off (n 5 33) On (n 5 11) Off (n 5 25) On (n 5 2) Off (n 5 34)

Trails A 64.0** 47.1 52.9 46.1 53.0 47.8(19.8) (10.2) (12.7) (10.2) (15.5) (11.2)

DSST 55.0 49.5 56.1** 47.6 47.0 50.1(26.8) (9.1) (10.6) (8.9) (11.3) (10.3)

RT 377.7* 474.6 411.2** 488.1 467.6 466.2(68.1) (86.9) (54.7) (90.7) (143.7) (88.1)

*Different from off medication at P , 0.10; **different from off medication at P , 0.05.


Table 3 battery may be explained by a small sample size andResults of the logistic regression for classifying diagnosis as either insufficient statistical power.abipolar disorder or unipolar depression

A novel finding of the present study was thatFactor b t-ratio P value many patients exhibited deficits in the programmingTrails A 2 0.498 2 3.12 0.004 of movement velocity. As many as 40% of theDSST 0.557 3.50 0.002 patients were unable to increase movement velocityPeak velocity (408) 2 0.306 2 2.48 0.020 as target distance increased. For simple ballisticReaction time 0.434 3.54 0.002

movements, the amplitude of the initial agonistVelocity scaling 0.536 4.44 0.0002muscle burst governs movement velocity (Freund

a Positive b values indicate higher scores; whereas negative b and Budingen, 1978). On the basis of disturbances invalues indicate lower scores for unipolar depressives. This five-

the generation and timing of a normal muscle firingfactor model classified patients into their respective diagnosespattern in patients with Parkinson’s disease, inves-with 100% accuracy.tigators have argued that parkinsonian bradykinesiais primarily a deficit in the timing or programming of

on the velocity scaling measure compared with movement velocity (Draper and Johns, 1964; Hallettunipolar depressed patients. and Khoshbin, 1980; Berardelli et al., 1986; Warabi

et al., 1986; Benecke, 1989; Hufschmidt and Luck-ing, 1995). The present findings support the concept

4. Discussion that motor slowing in depressive disorders and thebradykinesia of parkinsonism may stem from a

The results of the present study are consistent with common underlying mechanism, at least for a sub-the notion that motor retardation is an essential group of patients. Such a mechanism could involvefeature of major depressive disorder. As a group, the reduced mesocorticolimbic and prefrontal dopaminepatients in the present study exhibited longer reaction neurotransmission (Price et al., 1978; Javoy-Agidtimes and lower peak velocities compared with and Agid, 1980; Scatton et al., 1982).healthy control subjects. Over 40% of the depressed Support for a dopaminergic role in depressionexhibited mild impairment on traditional measures of comes from several arenas. Lauterbach et al. (1997)psychomotor function. Similar results have been noted that pallidothalamic lesions were associatedpreviously reported for reaction times (see Sobin and with secondary depression in patients with cerebralSackeim, 1997, for review). vascular accidents localized to subcortical areas. On

In Section 1 we emphasized that sensitive in- the basis of an extensive review of the clinical andstrumental measures of motor slowing may allow neuropharmacological literature, Brown and Gershondetection of motor system abnormalities that are not (1993) concluded that dopamine deficiency wasobserved clinically. This is exactly what was ob- responsible for the psychomotor retardation andserved in the present study in which 22% of the diminished motivation observed in depression. Phar-patients were rated as having motor retardation based macological findings indicate that depressed patientson the HRSD compared with 60% based on in- have been reported to exhibit reductions in thestrumental measures. There were no significant rela- dopamine metabolite, homovanillic acid, relative totionships between scores on the retardation item on control subjects (Post et al., 1980) and inhibitedthe HRSD and abnormalities as measured by the prolactin release in response to apomorphine (reflec-present technologies; however, seven of the eight tive of abnormal upregulation of postsynaptic dopa-patients who were impaired on the HRSD motor mine receptors) (Jimerson and Post, 1984). Magneticretardation item also exhibited abnormalities on at resonance imaging studies also support the notionleast one instrumental measure and six patients that the basal ganglia are involved in the patho-exhibited abnormalities on two of the three in- genesis of depression. Husain et al. (1991) foundstrumental measures. The absence of a significant that patients meeting DSM-III criteria for majorstatistical relationship between the HRSD motor depression demonstrated diminished putamenal vol-retardation item and performance on the instrumental umes. Overall, these findings suggest that dopamine


may play a key role in the expression of motor HRSD scores correlated significantly with changes inretardation in depression. The present finding that a reaction time. Similarly, Sabbe et al. (1997) followedsubset of unipolar depressed patients, and nearly all 22 patients through 6 weeks of treatment withof the bipolar depressed patients, exhibited a pattern fluoxetine and found that antidepressants imparted aof motor slowing consistent with a parkinsonian-like significant reduction in the reaction time but notmotor programming deficit provides further support movement time. The findings of the present study arefor a dopaminergic hypothesis in depression. consistent with these previous studies; however, in

The results of the present study may offer insight the absence of longitudinal data, we cannot de-into which aspects of psychomotor slowing are termine whether antidepressants which reduce therelated to state changes and which may be consid- severity of depression impart a parallel reduction inered trait characteristics of depression. It has been the severity of the motor impairment or whether theargued that subtypes of depression may be dis- antidepressants improve motor performance indepen-tinguished on the basis of psychomotor disturbances dent of change in mood symptoms.with melancholic type demonstrating more pervasive The distinction between bipolar and unipolarpsychomotor disturbances (Sobin and Sackeim, depression on the basis of a battery of motor1997). The present study was unable to differentiate measures supports the idea that some aspects ofpatients on the basis of clinical characteristics to motor slowing may be trait characteristics in depres-support or weaken this notion. However, correlation- sion. Despite the very small sample of patients andal analyses between motor signs and clinical symp- the preliminary nature of these findings we foundtoms indicated that some aspects of motor slowing that nearly all of the bipolar depressed patientswere related to severity of depression. In particular, demonstrated abnormalities on the velocity scalingwe found that movement velocity decreased with measure compared with less than one-third of theincreasing severity of depression and performance on unipolar depressed patients. Conversely, none of thethe DSST worsened with increasing severity of bipolar depressed patients demonstrated abnor-depression. These findings are partially consistent malities on the reaction time measure compared withwith the literature on the relationship between mood over one-third of the unipolar depressed patients.symptoms and psychomotor behavior. For example, These findings suggest that motor retardation associ-in a study of 20 melancholic patients, Moffoot et al. ated with bipolar disorder more closely resembles(1994) found that reaction time and movement speed parkinsonian bradykinesia compared with motortracked changes in depression, whereas performance retardation in unipolar depression. This is consistenton the DSST did not track symptoms over a 24-h with previous findings by Sachdev and Aniss (1994)period. The differences between this and the present on similarities between retarded melancholia andstudy could be explained by differences in study Parkinson’s disease and the factor analyses of Parkerdesign. et al. (1993).

A second set of results from the present study also Motor retardation can present with a variety ofsupports the notion that performance on temporal neuropsychiatric conditions including dementiameasures of motor function, such as reaction time, (Nebes et al., 1998), Parkinson’s disease (Sachdevmay be related to state of depression. While we and Aniss, 1994), schizophrenia (Prosser et al.,found that patients on antidepressants scored sig- 1987), and depression (Sobin and Sackeim, 1997).nificantly higher on the DSST and exhibited shorter The observable characteristics of motor slowing arereaction times than patients off antidepressants, the virtually indistinguishable across the spectrum ofcross-sectional design of the present study limits the neuropsychiatric disorders contributing to the hy-interpretation of this finding. Beneficial effects of pothesis that there is a common unified motor

¨ ¨antidepressants on reaction time have been reported retardation syndrome (Widlocher, 1983; Gunther etpreviously (vanHoof et al., 1993; Sabbe et al., 1997). al., 1988; Bermanzohn and Siris, 1992). An alter-vanHoof et al. (1993) studied six patients prior to native hypothesis pursued in this study, is that motorand following 2–3 months of treatment with conven- retardation may have different etiologies andtional tricyclic antidepressants. Their changes in pathophysiologies in at least some of the neuro-


psychiatric conditions in which it is observed. Find- the bipolar depressed patients exhibited a fundamen-ings from this and previous studies (Caligiuri et al., tal disturbance in motor programming and that this1998a,b) suggest that in psychosis or bipolar depres- disturbance may remain hidden from the clinicalsion, motor retardation may stem from a neuro- presentation of motor retardation. The existence of abiological mechanism similar to parkinsonian parkinsonian-like bradykinesia masquerading asbradykinesia; whereas in unipolar depression motor motor retardation in patients with depression hasretardation appears to have both motor and cognitive implications for the potential pharmacological man-bases. Clinical factors which predispose a patient to agement of depression. While there is some evidenceexhibit either the cognitive, motor, or cognitive– to suggest that motor retardation predicts a favorablemotor form of motor retardation remain unclear. On response to pharmacotherapy (Ranelli and Miller,the basis of the present findings, we propose that 1981) and ECT (Buchan et al., 1992), the findingsmotor slowing may have a distinct neurobiological are mixed (see Sobin and Sackeim, 1997). Perhapsbasis (neuromotor retardation) in some forms of the advantage of motor retardation as a prognos-depression, while in others it has a generalized ticator of favorable treatment outcome is carriedcognitive basis (psychomotor retardation). largely by a subgroup of patients who exhibit a

We found marked heterogeneity in motor per- fundamental neuromotor disturbance.formance among unipolar depressed patients. Severalfactors could explain this, including variability inprescribed medication, age, illness severity, and Acknowledgementsillness duration. For example, among unipolar de-pressed patients, illness severity explained 36% of This research was supported in part from USPHSthe variability in DSST performance, 23% of the grants (P30-MH496771, T32-MH19934), the UCSDvariability in peak velocity, and 18% of the vari- Mental Health Clinical Research Center (MH30914),ability in velocity scaling. Despite this heterogeneity, and the Department of Veteran Affairs VISN-22the motor tasks offered meaningful diagnostic or MIRECC. The authors wish to thank the followingdifferential diagnostic information. A five-factor individuals for their assistance on this research: Drmodel consisting of Trails A, DSST, peak velocity, Chris Gillin, Dr John McQuaid, Kathy Resovsky,reaction time, and velocity scaling correctly classi- Lorraine Goyette, and Grace Shiao.fied 100% of the patients as unipolar or bipolardepressed. Thus, in cases of diagnostic uncertaintywhen a patient presents depression and motor slow- Referencesing, the pattern of performance on a motor batterywhich includes psychomotor and neuromotor mea- American Psychiatric Association, 1994. Diagnostic and Statistical

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15. depression and motor retardation

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