Apathy, Depression, and Cognitive Performance in HIV-1 Infection

Steven A. Castellon, Ph.D. Charles H. Hinkin, Ph.D. Stacey Wood, Ph.D. Kathryn T. Yarema, B.A.

The authors examined the relationship between apathy, depression, and cognitive performance in 48 HIV-1seropositive and 21 seronegative (control) subjects, using reaction time (RT) and working memory tasks. Apathy, but not depression, was associated with working memory decits among HIV-seropositive subjects. The cognitiveaffective component of the Beck Depression Inventory (BDI), but not apathy, was associated with slowing and decreased accuracy on a choice RT task. The BDI cognitive-affective component was more closely associated than the BDI somatic component with both RT slowing and apathy. Results suggest that prominent symptoms of apathy, independent of depression, may be an important indicator of CNS involvement in HIV infection. Total BDI scores showed a less consistent relationship with neurocognitive performance, suggesting that somatic symptomatology is diagnostically ambiguous among HIV-infected subjects.
(The Journal of Neuropsychiatry and Clinical Neurosciences 1998; 10:320329)

pathy and depression are frequently observed concomitants of central nervous system disease and are especially prominent in disorders affecting the frontal lobes, limbic regions, and subcortical structures.13 Human immunodeciency virustype 1 (HIV-1) can affect the central nervous system early in the course of illness46 and has been shown to exercise an afnity for subcortical structures.79 It is therefore not surprising that apathy and depression are both observed, concurrently and independently, in a substantial percentage of HIV-infected patients.1012 Research has shown that apathy and depression, although they are overlapping dimensions of behavior, can nonetheless be reliably distinguished from one another.2,13 The two syndromes have been observed both alone and concurrently in a variety of neurologic and psychiatric disorders, including Parkinsons disease (PD), Alzheimers disease, left hemisphere stroke, and negative-syndrome schizophrenia.1417 Because depression and apathy can occur independently, some investigators have hypothesized that they might have different neurophysiological bases.2,17 Starkstein et al.17 suggested that in PD apathy results from dysfunction in catecholaminergic activity, whereas depression is
Received January 7, 1997; revised August 15, 1997; accepted August 26, 1997. From the Departments of Psychology and Psychiatry/ Biobehavioral Sciences, University of CaliforniaLos Angeles, and the Department of Veterans Affairs Medical Center, West Los Angeles, California. Address correspondence to Dr. Castellon, Department of Psychiatry and Biobehavioral Sciences, 760 Westwood Plaza, C8-747, University of CaliforniaLos Angeles, Los Angeles, CA 90024; e-mail: scastell@ucla.edu Copyright 1998 American Psychiatric Press, Inc.

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CASTELLON et al. caused by serotonergic and/or inferior frontal dysfunction. They found that apathetic PD patients (with or without depression) evidenced verbal memory decits and were slower on speed-dependent tasks than were non-apathetic PD patients. In contrast, depression was associated with less accurate, but not slower, performance on Trails B, a speed-dependent task requiring conceptual set-shifting. That apathy and depression were each associated with unique neuropsychological decits strengthened this groups conclusion that the two might have different pathophysiologies. The neuropsychological performance of HIV-infected individuals has been extensively studied, and, clearly, cognitive impairment is consistently observed in this population.1824 Information processing speed and efciency seem to be especially affected by HIV infection; a substantial percentage of HIV-seropositive patients show decits on reaction-time tasks, especially those putting heightened demands on processing capacity.21,25 There are compelling reasons to assume that working memory decits may result from HIV-1 infection. HIV1 infection has been demonstrated to affect frontalsubcortical circuits,79,26 and current research has implicated frontal-subcortical circuits in the mediation of working memory.27 Gabrieli et al.28 recently concluded that the working memory decits exhibited in PD are most likely linked to frontal-subcortical circuits mediated by dopamine, a neurotransmitter that has been found to be decient in HIV-infected patients.29 Additionally, some investigators have suggested that information-processing speed is intimately related to working memory performance,30 and several studies have found decreased processing speed in HIVseropositive patients.20,21,25,31 Although both neuropsychological impairment and depression occur in HIV-infected patients, research to date suggests that the two do not show a consistent relationship to one another.3235 Most of this research has ignored the multifactorial nature of depression and the possibility that the somatic symptoms included so prominently in most depression measures might be indicators of physical illness and, therefore, diagnostically ambiguous. Data from our laboratory36 suggest that somatic items included on the Beck Depression Inventory (BDI) are unrelated to memory measures (both procedural and episodic memory), whereas the cognitiveaffective items of the BDI are signicantly related to procedural memory performance. We have suggested that the cognitive and affective items on the BDI might be more accurate indicators of mood disturbance than the somatic items, especially among medically ill individuals. There has been a paucity of research examining the role of apathy in HIV-1 infection and none examining the relationship of apathy with depression. Similarly, there has yet to be an empirical study of the relationship between apathy and neuropsychological performance in HIV-1 infection, although there are compelling reasons to suspect a potential relationship. In other subcortical diseases or disorders, the connection between cognitive compromise and apathy has been observed,2,17,37 and a recent case study reported an AIDS patient whose increasing cognitive decline mirrored increasing levels of apathy.38 Also, in a recent review article, Brown39 reported that methylphenidate treatment of cognitive compromise in HIV-1 infection was often found to lead to corresponding changes in affective symptoms, including apathy. Investigators in neurology and neuropsychiatry have suggested that apathy may be indicative of frontal-subcortical disruption13 mediated by dopaminergic dysfunction.40 As reported by Gabrieli and colleagues, working memory performance, as measured by neuropsychological tasks such as the Calculation Span, has also been shown to be associated with frontal-subcortical disruption and dopaminergic dysfunction.28 The present study sought to examine the relationship between apathy, depression, information-processing speed, and working memory in a sample of HIVinfected patients and a matched group of seronegative control subjects. In this study, which we believe to be the rst empirical study of apathy in HIV-1 infection, we sought to answer four specic questions: 1. Are apathy and depression related to each other in HIV-1 infection, and if so, are they dissociable behavioral domains? Are apathy and depression more prevalent in HIVinfected patients than in HIV-seronegative control subjects? Do apathy and depression show a differential relationship to neurocognitive performance among HIV-seropositive patients? Is working memory performance, which is theoretically related to frontal-subcortical function, more compromised among apathetic than among nonapathetic HIV-seropositive individuals?

2.

3.

4.

METHODS
Subjects Sixty-nine subjects drawn from three diagnostic groups participated in the current study: 26 HIV-1seropositive patients meeting 1993 Centers for Disease Control and Prevention (CDC) criteria for AIDS (CDC Groups C13, A3, or B3), 22 HIV-infected subjects who had yet to meet

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APATHY, DEPRESSION, AND COGNITION IN HIV diagnostic criteria for AIDS (pre-AIDS: CDC Groups A1, A2, B1, and B2), and 21 HIV-1 seronegative control subjects. A concerted effort was made to recruit ethnic minority subjects; 11 of 21 control subjects (52%) and 28 of 48 HIV-seropositive patients (58%) were from minority groups. No subject was enrolled who had actual or suspected neurological disease, and any subject with a head injury and subsequent loss of consciousness greater than 5 minutes, seizure disorder, current substance use disorder (substance abuse or dependence), or history of psychosis was excluded. HIV serostatus was ascertained for all subjects by using enzyme-linked immunosorbent assay testing with Western blot conrmation. HIVseropositive patients were recruited from an infectious disease clinic at a university-afliated medical center and from a local community organization specializing in serving HIV-infected individuals (AIDS Project Los Angeles). HIV-seronegative control subjects were recruited through newspaper advertisements and through notices posted at both of the above-mentioned sites. The majority of the patients in the current study were gay/ bisexual men (52% of control subjects and 69% of patients), and male-male sexual contact was the most common suspected mode of infection with HIV. However, 11 of the 48 HIV-seropositive subjects denied this risk factor and/or suspected some other mode of infection (such as heterosexual sexual contact or injection drug use). HIV-seropositive participants and HIV-seronegative control subjects did not differ signicantly on any demographic variables, including age (P 0.82), education (P 0.19), and premorbid verbal IQ as estimated by the North American version of the National Adult Reading Test (NAART; P 0.31). The mean age of participants was 38.4 years (range 2063 years), and only 7 of the 69 subjects (10%) did not have at least a high school education (mean 14.5 years, range 820 years). HIVinfected subjects reported signicantly greater past and current drug use (P 0.03 and P 0.02, respectively), whereas rates of current and past alcohol use were roughly equivalent between the two groups (P 0.21 and P 0.86, respectively). Demographic characteristics of the sample are described in Table 1. Measures Depression was measured with the 21-item Beck Depression Inventory, a self-report rating scale that asks about the presence and prominence of cognitive, affective, and somatic symptoms of depression over the past week. Scores on each item can range from 0 (symptom absent) to 3 (presence of symptom is pronounced), yielding a possible range of BDI total scores of 0 to 63. A score of 16 or above is often used to indicate clinically signicant depressive symptomatology.41 Because it has been suggested that positively endorsed somatic items on the BDI might be related to physical illness in a medically ill population and therefore be diagnostically ambiguous, we calculated BDI cognitive-affective and BDI somatic subscores, following the procedure outlined in the BDI manual.41 This method of dividing the BDI into subscales, which considers the rst 14 items to be cognitiveaffective and the nal 7 items to be somatic, has been used by other HIV-1 investigators.42,43 Table 1 includes means and standard deviations of BDI scores for each subject group. Apathy was measured with the Neuropsychiatric Inventory (NPI).44 This is a validated brief interview assessing 10 neuropsychiatric symptom domains over the previous 4-week period and is typically administered to the caregivers of patients with neurologic disorders such as Alzheimers disease or Parkinsons disease. Although the NPI has not been used with HIV-infected patients, it was chosen because it contains an apathy subscale that is easily and briey administered in interview format (with minor changes in the wording of items to allow for the direct, rather than caregiver, assessment of subjects). The apathy subscale contains seven yes/no questions sampling the domain of apathy (e.g., Do you feel like you are less spontaneous or less active than usual? Are you less likely to initiate a conversation with some-

TABLE 1.

Demographic characteristics of the sample (N 69) Mean SD HIV (n 21) 38.14 10.1 15.10 2.3 112.5 10.1 7.38 6.30 5.29 4.74 2.10 2.43 HIV HIV : AIDS (n 26) 39.04 8.6 14.19 2.1 108.5 9.7 16.42 9.64 10.52 7.69 5.89 2.95 HIV HIV : Pre-AIDS (n 22) 38.19 7.7 14.57 2.1 111.8 9.4 15.47 11.52 11.14 8.51 4.33 3.60

Characteristic Age, years Education, years NAART, est. VIQ BDIa Total score Cog-affective Somatic

(combined) 46 42 8 4 43/5 15/33

Ethnicity (%) African American Caucasian Latino/a Other Gender (males/females) Sexual orientation (heterosexual/ homosexual)

43 48 10 10 17/4 10/11

Note: HIV HIV seronegative; HIV HIV seropositive; NAART North American version, National Adult Reading Test; est. VIQ estimated verbal IQ; BDI Beck Depression Inventory; Cog-affective cognitive-affective component. a HIV-seronegative subjects Pre-AIDS AIDS subjects (P 0.05).

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CASTELLON et al. body? and Are you less interested in the activities and plans of other people?), and a subjects apathy score was the total number of positively endorsed items. The item content of this scale is similar to the 18-item Apathy Evaluation Scale designed by Marin, based on the denition of apathy as a simultaneous decrease in the behavioral, cognitive, and emotional concomitants of goaldirected behavior.2 Reaction time (RT) was measured with two computerized tasks. The rst was Simple Cued RT (SRT). The SRT task required subjects to respond by pressing a joystick button with the index nger of the dominant hand as quickly as possible after hearing a 1,000-Hz tone. Stimulus onset was always preceded by a visual cue (a red sign displayed for 1,000 ms at the center of the monitor), and the interstimulus interval (ISI) between stimulus cue offset and stimulus onset was either 250, 500, 1,000, or 2,000 ms in duration. ISI was randomly varied. Following administration of a practice block of 8 trials to ensure that the subject fully understood the task, two experimental blocks of 60 trials were administered (each block consisting of 15 trials at each of the four ISIs). The second task was Choice RT (CRT). The CRT task required subjects to rapidly determine whether two sequential visual stimuli were identical. At 1,000 ms following a warning cue (as described above), a complex design subtending 11 degrees vertically and 10 degrees horizontally was presented to the center of the monitor for a duration of 1,000 ms. A second complex design (either identical to or slightly different from the rst) was then presented 1,000 ms after offset of the rst design. Subjects then vocally responded same or different into a microphone, with the response detected by a voice-activated relay. Twelve different complex designs were used. Subjects were instructed to respond as quickly as possible without sacricing accuracy on the visual discrimination task. Following 8 practice trials, two blocks of 30 trials were administered. For both RT tasks, median reaction times were calculated across trials, with responses at less than 125 ms (anticipatory responses) and greater than 1,800 ms (nonresponses) excluded. Working memory was measured with the Calculation Span (C-SPAN) task. In this task, subjects are orally presented with simple arithmetic problems (e.g., 3 5 . . . ), which they are instructed to solve by immediately afterward selecting the correct answer from among three written choices while also remembering the last digit in each problem (e.g., 5 in the example above). The number of problems presented on each trial is increased successively from one to nine, with three trials presented at each level.45,46 Each level adds one arithmetic problem and thus one additional nal digit to remember. The simple math problems had the following characteristics: 1) they were all addition or subtraction with one-digit numbers from 1 to 9; 2) the answers were all positive numbers; 3) the last digit was never the same for successive problems in a trial; and 4) the answer to a math problem is never the same as the target digit that must be remembered. All subjects were required to proceed through all nine levels of the C-SPAN task. Three variables were scored on the C-SPAN. The Span score consists of the greatest number of nal digits recalled in the correct order for at least two of three trials and can range from 0 to 9. The Trial score is the number of trials in which all nal digits were recalled in the correct order and can range from 0 to 27. The Item score corresponds to the total number of nal digits reported in the correct order across all 9 levels and can range from 0 to 135. The C-SPAN was added to the study protocol after the beginning of subject testing, and for that reason only 53 of the 69 subjects had complete data for this task. Procedures After giving informed consent, all subjects completed the NAART; a detailed demographics questionnaire; the mood, psychotic-spectrum, and substance use disorders modules from the Structured Clinical Interview for DSM-III-R;47 the BDI; and the apathy measure. All diagnostic interviewing was completed by a doctoral-level clinical psychology graduate student (S.A.C.) thoroughly trained in diagnostic interviewing techniques. Subjects then completed all reaction time tasks, including the SRT and CRT tasks detailed above, and nally completed the aforementioned verbal working memory task (the C-SPAN). To minimize any possible effect of fatigue, subjects were instructed to inform the examiner if they felt that they needed breaks in addition to the two mandated 5-minute breaks during the RT tasks. The entire battery (which included several tasks not mentioned above) lasted approximately two hours. Upon completing the study, subjects were paid $25.00 for their participation.

RESULTS
Relationship of Apathy and Depression Among HIV-Seropositive Subjects To evaluate whether apathy and depression were related to one another among HIV-seropositive subjects, Pearson product-moment correlations were calculated for apathy and depression variables. Depression variables included the BDI total score, as well as subscale scores for the cognitive-affective (BDI-Cog) and the somatic (BDI-Som) components. Among HIV-infected

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APATHY, DEPRESSION, AND COGNITION IN HIV subjects apathy showed a moderately strong correlation with BDI total score (r 0.63, P 0.001), suggesting that in this sample of HIV-seropositive individuals these two scales measure related dimensions. Analysis of the relationship between apathy and BDI-Cog and BDI-Som scores showed that apathy was more strongly associated with BDI-Cog (r 0.67, P 0.001) than with BDI-Som (r 0.33, P 0.03). In an attempt to determine whether those individuals with clinically meaningful levels of depression were more likely to be apathetic, we dichotomized HIV-seropositive patients into groups of those with depression (BDI total score 16: n 21) and those without depression (n 27). An independent-samples ttest comparing apathy scores between these two groups showed that those with clinically meaningful selfreported symptoms of depression had signicantly higher apathy scores than did those without (t 5.3, df 47, P 0.001). Prevalence of Apathy and Depression Immediately apparent from examination of descriptive data was the near absence of self-reported apathy among control subjects. In fact, the vast majority of HIVseronegative subjects showed either no or minimal apathy, with only 3 of 21 subjects (14%) endorsing more than 1 item (of the 7 possible items) on the apathy scale. No seronegative subject had a score greater than 3 on the apathy scale, whereas nearly half of all HIVseropositive patients positively endorsed 5 or more items. The distribution of apathy scores across groups is depicted in Figure 1. To ascertain whether apathy scores differed among the three symptom status groups (HIVseronegative, Pre-AIDS and AIDS), a univariate analysis of variance (ANOVA) was conducted, which revealed a signicant main effect for symptom status (F 10.78, df 2,67, P 0.0001). Tukey post hoc comparisons indicated that both Pre-AIDS and AIDS subjects were signicantly more apathetic than the HIV-seronegative control subjects but did not differ from each other (mean SD, AIDS: 3.6 2.7; Pre-AIDS: 2.9 2.8; HIV-seronegative: 0.52 0.87). An ANOVA comparing BDI total scores among the three symptom groups showed that self-reported depression was also more prominent among HIV-infected subjects than among HIVseronegative control subjects (F 6.2, df 2,67, P 0.01), again with both seropositive groups differing from control subjects but not from each other (AIDS: 16.4 9.6; Pre-AIDS: 15.6 11.5; HIV-seronegative: 7.4 6.3). Although as a group HIV-seronegative control subjects had lower BDI total scores than did HIV-seropositive patients, it was not uncommon to nd clinically signicant levels of self-reported depression among HIVseronegative control subjects. Several HIV-seronegative subjects (5/21; 24%) scored in the range typically considered indicative of at least moderate depression (BDI total score 16). Relationship of Apathy and Depression to Neurocognitive Performance To determine whether apathy and depression might be differentially associated with neuropsychological performance in HIV-infected patients, we calculated Pearson correlations for measures of working memory, simple and choice reaction time, apathy, and depression. As can be seen in Table 2, apathy was consistently negatively correlated with working memory performance, but no BDI measure was signicantly associated with

TABLE 2.

Correlations between neuropsychological performance variables, apathy scores, and BDI scores among HIV-seropositive participants Apathy r P r BDI-Cog P BDI-Som r P

Measure FIGURE 1. 14 12 Number of Subjects 10 8 6 4 2 0 0 1 2 3 4 5 6 7 HIV+ HIV Apathy score distribution by HIV serostatus. Working Memory C-SPAN Span Trials Items Simple RT 250 ms 500 ms 1,000 ms 2,000 ms Choice RT Reaction time % correct Apathy

0.46 0.39 0.36 0.19 0.23 0.25 0.20 0.21 0.11

0.01 0.02 0.02 NS NS NS NS NS NS

0.16 0.08 0.06 0.25 0.28 0.26 0.24 0.31 0.27 0.67

NS NS NS NS 0.05 NS NS 0.03 0.06 0.001

0.04 0.03 0.12 0.17 0.19 0.15 0.14 0.06 0.07 0.33

NS NS NS NS NS NS NS NS NS 0.03

Apathy Score

Note: Apathy Apathy subscale of Neuropsychiatric Inventory; BDI Beck Depression Inventory; Cog cognitive-affective component; Som somatic component; C-SPAN Calculation Span task; RT reaction time.

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CASTELLON et al. any of the working memory variables. In contrast, only BDI-Cog was signicantly related to CRT performance, with higher scores on this subscale associated with slower and less accurate CRT performance. Among HIV-seropositive patients, somatic symptoms of depression (on BDI-Som) were not related to any neurocognitive variable. Among HIV-seronegative subjects, neither apathy nor depression was signicantly associated with neuropsychological performance. Relationship of Working Memory Performance to HIV Status and Apathy To examine whether HIV-seronegative, Pre-AIDS, and AIDS subjects differed in working memory performance, three univariate ANOVAs were conducted with symptom status as the grouping variable and C-SPAN variables (Span Score, Trial Score, and Item Score) as dependent variables. A signicant group effect was observed for both Item Score (F 6.26, df 2,51, P 0.004) and Trial Score (F 3.18, df 2,51, P 0.05), with Tukey post hoc comparisons revealing that both HIVseronegative control subjects and Pre-AIDS subjects showed signicantly better performance than did AIDS subjects. These results suggest diminished working memory capacity among patients diagnosed with AIDS, but not in mostly asymptomatic HIV-infected individuals. Because apathy score was signicantly associated with all working memory variables, we sought to examine whether apathy might mediate the relationship between disease stage and working memory performance. Analysis of covariance revealed that signicant group differences in working memory performance were attenuated when apathy score was accounted for statistically. Group differences on Trial Score were no longer statistically signicant (F 1.89, df 3,50, P 0.16), although group differences on Item Score remained signicant (F 4.25, df 3,50, P 0.02). We wished to further explore the association between apathy and working memory performance among HIVseropositive subjects. As can be seen in Figure 1, HIVseropositive patients tended to score at either one or the other extreme of the scale on the apathy measure, with 90% of all subjects at either the low or high end of the scale. Twenty-two subjects (45%) had scores of 0 or 1 (Low Apathy) and 22 subjects (45%) had scores of 5, 6, or 7 (High Apathy). Following Starkstein et al.,17 who found a similar bimodal distribution of apathy scores in Parkinsons disease patients, and using the cutoffs described above, we examined whether High Apathy subjects differed from Low Apathy subjects in terms of working memory performance. Independent samples ttests comparing the High Apathy and Low Apathy groups revealed that the High Apathy subjects were signicantly more impaired on all working memory measures than were Low Apathy patients (Span score: t 3.94, df 35, P 0.005; Trials score: t 3.44, df 35, P 0.01; Items score: t 2.52, df 35, P 0.03). These results are depicted in Figure 2. To examine whether the highest- and lowest-scoring patients on the BDI might also show working memory performance differences, we compared the 16 lowest- and 16 highest-scoring HIVseropositive patients (the top and bottom thirds of our
FIGURE 2. High and Low Apathy groups performance on C-SPAN variables.

3.5

3 Span Score

2.5

P
2

0.005

1.5

Low Apathy Group

High

25

20 Trials Score

15

10

0.01

Low Apathy Group

High

60

50 Item Score

40

P
30

0.03

20

Low Apathy Group

High

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APATHY, DEPRESSION, AND COGNITION IN HIV sample) with one another. No differences were noted between High Depression (BDI 20, mean 28.2) and Low Depression (BDI 9, mean 5.1) subjects on working memory variables. Absolute CD4 count was not correlated with apathy score (P 0.60), nor was it related to apathy group membership (Low Apathy group 318 mm3, High Apathy group 231 mm3). Of the 22 High Apathy subjects, 15 were patients with AIDS, and of the 22 Low Apathy subjects, 11 were patients with AIDS (v2 1.51, P 0.22). then, the overlap between apathy and depression is related to shared phenomenology between the two, which can be seen by the presence of comparable items on measures of each. Lending support to the observation that apathy and depression are dissociable affective and behavioral domains is the observation that they share a differential relationship to neurocognitive performance in HIVseropositive subjects. Apathy, but not depression, was related to working memory impairment; depression, but not apathy, was related to choice reaction time inefciency. (Depressed patients were less accurate and slower.) This double dissociation between apathy and depression and cognitive performance variables is similar to that observed by Starkstein et al.17 in Parkinsons disease patients, where apathy was associated with verbal memory decits and depression with less accurate performance on a task requiring conceptual set-shifting. In other studies of HIV-infected subjects, CRT has been shown to be associated with self-reported depression.25,42 The current study suggests that working memory is impaired in a subset of HIV-infected subjects and that these subjects tend to be in the later stages of the disease (i.e., diagnosed with AIDS). This nding is consistent with other studies of working memory in HIV-1 infection.5052 Consistent with Law and colleagues,50 we did not nd compelling evidence of working memory impairment in asymptomatic HIV-infected patients relative to HIV-seronegative control subjects. However, AIDS patients performed signicantly worse than HIVseronegative and Pre-AIDS subjects on two of the three working memory variables, a nding consistent with those of both Sahakian et al.51 and Stout et al.52 Apathy was strongly associated with compromised working memory performance in HIV-infected subjects; when apathy was treated as a covariate, the signicant group differences on C-SPAN performance between the AIDS group and the other two participant groups were substantially mediated. Additionally, apathy was signicantly correlated with all working memory variables, and High Apathy participants performed signicantly worse than Low Apathy subjects on C-SPAN indices. In our opinion, it is unlikely that increased apathy is the cause of poor neuropsychological performance; rather, both apathy and working memory impairment are best conceptualized as related manifestations of frontalsubcortical disruption, perhaps associated with dopaminergic dysfunction. Gabrieli and colleagues,28 in a study using the same working memory task in patients with Parkinsons disease, suggested that dopaminergic deciency might be contributing to poor working memory performance. HIV infection is in some ways neu-

DISCUSSION
It is perhaps surprising that apathy has not received more empirical scrutiny in HIV-1 research given its prominent role in the clinical presentation of the disease and the disruptive impact it can have on an affected patients quality of life. The results of this study, to our knowledge the rst to empirically examine the relationship between apathy and cognitive performance in HIV-1seropositive subjects, suggest that selfreported symptoms of apathy are quite common among HIV-infected individuals. Although virtually absent in HIV-seronegative control subjects, symptoms of apathy were relatively common in HIV-seropositive patients. This nding suggests that apathy may be specically associated with the neurologic compromise that often accompanies HIV infection and is not commonly observed in individuals without central nervous system involvement. In contrast, elevated levels of depression were present among both HIV-seropositive and control subjects, with nearly one-fourth of our HIV-seronegative subjects reporting clinically signicant levels of depressive symptomatology. This nding underscores the contention that depression is not uncommon among HIVseronegative subjects. Other groups have similarly reported elevated rates of depression among HIVseropositive patients relative to HIV-seronegative control subjects.48,49 Our nding that the cognitive-affective subscale of the BDI was more strongly associated with apathy than was the somatic component of the BDI suggests that the overlap between apathy and self-reported depression may be attributable to symptoms from the cognitive and affective domains. This is not surprising given that three BDI cognitive-affective items are quite similar to items on our apathy measure (BDI item 4: life satisfaction/ enjoyment; BDI item 12: social interest; BDI item 13: ability to make decisions). Marin et al.13 similarly found that the convergence between a different apathy measure and a different depression measure was primarily due to several similar items between the measures. Clearly,

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CASTELLON et al. rochemically similar to PD in that cerebrospinal uid levels of dopamine or its metabolites have been found to be signicantly reduced in some patients with AIDS.29,53 This study suggested that in a sample of HIVseropositive patients, the somatic factor of the BDI is not related to any cognitive performance variable, whereas the cognitive-affective factor is correlated with both SRT and CRT performance. It is interesting to note that the somatic component of the BDI was not highly correlated with the apathy measure in this study (r 0.33), but the cognitive/affective component of the BDI was strongly associated with apathy score (r 0.67). This dissociation between the somatic and cognitive-affective components of the BDI, a consistent nding across multiple research laboratories,36,42 again calls into question the diagnostic utility of somatic symptoms and signs as indicative of depression in HIV-seropositive patients. Limitations of the current study must be noted. The relatively small number of participants indicates the need for caution in generalizing to the entire population of HIV-infected patients. We made a concerted effort to include a diverse group of patients and matched the control subjects accordingly, but we did not have the sample size to perform separate analyses on subgroups of theoretical interest (for example, women versus men; heterosexual versus homosexual; injection drug users versus noniv drug users). It should also be noted that the apathy measure that we used is not as extensive as the Apathy Evaluation Scale developed by Marin.2 It is our belief, however, that the apathy subscale of the NPI, which we used for the current study, contains items that adequately represent the domains mentioned by Marin and covered in his scale. Finally, one must consider the possibility that neuropsychological differences between HIV-infected patients and seronegative control subjects might have been mediated by the patients greater past and current substance use. Upon closer examination of the self-report data relating to substance use, it was clear that the statistically signicant differences between the
References

groups were explained by signicantly greater cannabis consumption among HIV-seropositive patients. Past and present intake of other substances was quite similar. Because there is little evidence suggesting that marijuana use inuences neuropsychological performance, at least in younger subjects,54 it seems unlikely that group differences in neuropsychological performance are an artifact of substance use. There were somewhat equivocal ndings regarding the link between apathy, depression, and disease progression. CD4 count was unrelated to apathy, depression, or cognitive performance, but there was a tendency for High Apathy subjects to be AIDS (rather than PreAIDS) patients. However, the fact that several Pre-AIDS participants were apathetic suggests that apathy is not merely a proxy for disease progression as marked by medical/constitutional status. Finally, these ndings suggest that the presence of apathy is associated with cognitive compromise in HIV-1 infection. Whether apathy contributes to this cognitive compromise or rather merely reects greater CNS involvement cannot be conclusively determined from the current data. That apathy is related to compromised working memory performance in this sample of HIVinfected patients may reect a common frontalsubcortical circuit that becomes increasingly compromised with disease progression. Clearly, more research is needed to continue to explore the relationship between apathy and cognitive performance in HIV-1 infection. The authors thank Nicolette van Sluis, Muriel Veen, and Kim Oostrom for their help with data collection and Dr. Jeffrey L. Cummings for helpful comments on an earlier version of this manuscript. This research was supported in part by grants from the National Institute of Mental Health (1R03 MH54465-01) and the UCLA Academic Senate. Portions of this work were presented at the 25th meeting of the International Neuropsychological Society, Orlando, FL, February 1997.

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