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Psychosomatics 48:217-222, May-June
doi: 10.1176/appi.psy.48.3.217
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Apathy Syndrome After Traumatic Brain Injury Compared With Deficits in Schizophrenia

Vani Rao, M.D., Jennifer R. Spiro, M.S., David J. Schretlen, Ph.D., and Nicola G. Cascella, M.D.

Received September 21, 2005; revised March 21, 2006; accepted March 31, 2006. From the Dept. of Psychiatry and Behavioral Sciences, Johns Hopkins Univ. School of Medicine, Baltimore, MD. Send correspondence and reprint requests to Vani Rao, M.D., Osler 320, Div. of Neuropsychiatry and Geriatric Psychiatry, Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD 21287-7218. e-mail: vrao{at}jhmi.edu


  ABSTRACT

 
TOP
 ABSTRACT
INTRODUCTION
 METHOD
 RESULTS
 DISCUSSION
 REFERENCES
 
The authors compared the severity and clinical profiles of patients with two etiologically different apathy syndromes: apathy after traumatic brain injury (TBI) and deficit schizophrenia (DSS). Patients from both groups were equally apathetic, but those with DSS had more severe anhedonia, blunted affect, and alogia, as measured by the Scale for Assessment of Negative Symptoms. These findings suggest that patients with DSS have a more complex presentation of apathy. Their differences may help to identify anatomical correlates of these apathy syndromes and aid in the design of more effective management strategies for both groups of patients.


  INTRODUCTION

 
TOP
 ABSTRACT
 INTRODUCTION
METHOD
 RESULTS
 DISCUSSION
 REFERENCES
 
Apathy may be defined as a loss of motivation and impairments in behavioral, cognitive, and emotional aspects of goal-directed behavior, in the presence of normal consciousness, cognition, and mood.1 People with apathy are less able to initiate and sustain behavior, formulate plans or goals, and react emotionally to positive or negative events than those without apathy.

Patients who have suffered traumatic brain injury (TBI) often develop apathy. In TBI, the apathy syndrome is characterized by disinterest in day-to-day activities, lack of future goals, poor participation in rehabilitation activities, and limited ability to appreciate recovery made after TBI. Such patients are often referred to doctors by family members, who complain that the patient is "lazy" or has become a "couch potato." Researchers have found increased rates of disinterest and decreased motivation even several years after a brain injury.2,3

Patients with schizophrenia also develop an apathy-like syndrome, commonly referred to as the "deficit syndrome of schizophrenia (DSS)," characterized by restricted affect, diminished emotional range, poverty of speech, curbing of interests, diminished sense of purpose, and diminished social drive.4,5 These symptoms are primary to schizophrenia, pervasive, and enduring, and they are associated with poor premorbid functioning and neurological impairment.6

Apathy as a syndrome has not yet been defined as a diagnostic entity in DSM-IV. However, features of apathy, such as amotivation, anhedonia, social isolation, and poverty of speech occur in several different clinical conditions. Researchers have argued that the "deficit" features of schizophrenia can be found in some patients after closed head injury and that these warrant further investigation.7 Others have defined schizophrenia to include psychosis, apathy, withdrawal, and cognitive impairment associated with social and occupational impairment.8

Apathy after TBI and apathy due to DSS might share a common pathophysiology, involving damage to the frontal-subcortical circuits of the brain.9 Stuss et al.10 have proposed that apathy is a complex construct composed of several "related but separable" subtypes or domains, "depending on the neural substrate and/or the behavioral response involved." They have further postulated that different frontal-subcortical circuits may be involved in different subtypes of apathy. If this is the case, we would expect brain diseases arising from damage in different brain regions to present with different subtypes of apathy. Likewise, different brain diseases may result in more severe impairment in different domains of apathy.

To examine their phenomenological similarities and differences, we administered the Scale for the Assessment of Negative Symptoms (SANS)11 to groups of patients with apathy due to TBI or DSS. Our research question was the following: given comparable levels of apathy, do the two groups show different patterns in their specific manifestations? We hypothesized that TBI and DSS patient groups would be differentially affected on the various SANS domains.


  METHOD

 
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 ABSTRACT
 INTRODUCTION
 METHOD
RESULTS
 DISCUSSION
 REFERENCES
 
Participants
TBI patients (N=12) were recruited from the Brain Injury Clinic at Johns Hopkins Hospital and from local rehabilitation centers. All met DSM-IV criteria for a "personality change secondary to TBI, apathetic subtype." They also met criteria for the "deficit syndrome" on the basis of the Schedule for Deficit Syndrome (SDS),12 even though none was diagnosed with schizophrenia. All had sustained a closed head injury. Details of the injury were obtained from the patient, a collateral informant when available, and by reviewing medical records. The patients with schizophrenia (N=16) met DSM-IV criteria for schizophrenia and also met criteria for the deficit syndrome on the basis of the SDS. Schizophrenia patients were recruited from the outpatient psychiatry clinics at Johns Hopkins. None had neuroleptic-induced akinesia.

We used the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID)13 to diagnose both schizophrenia and personality change secondary to TBI. To ensure that both groups had similar levels of apathy and deficit or negative symptoms, both groups were required to score≥2 on two of the six items of the SDS and≥30 on the clinician version of the Apathy Evaluation Scale (AES).14 Each participant was administered the SDS and AES by one of two board-certified psychiatrists (NC and VR), who were not blinded to diagnosis. Acceptable interrater reliability for the SDS ({kappa}=0.73) was established for both raters after training at the Maryland Psychiatric Research Center. The test–reliability of the AES has been shown to range from 0.76 to 0.94 over 25 days.14

To ensure that depression did not confound the results, any patient with a Hamilton Rating Scale for Depression (Ham-D)15 >12 was excluded from the study. Additional exclusion criteria for both groups were 1) presence of a mood disorder according to DSM-IV criteria; and 2) substance abuse or dependence during the preceding 6 months. The Johns Hopkins Institutional Review Board approved this study, and informed consent was obtained from all participants.

Measures
All patients were administered the SANS,11 a standardized scale for the assessment of negative symptoms, usually in schizophrenia. The SANS assesses five domains: affective flattening, alogia, avolition-apathy, anhedonia-asociality, and attention. We used the SANS to compare the apathy profiles of the two groups, given that the scale clearly taps into the symptoms/behaviors of patients with the apathy syndrome across different clinical conditions. It was administered by a study clinician (NC) not blind to diagnosis. Participants were also administered the National Adult Reading Test (NART),16 to assess premorbid IQ, and the Mini-Mental State Exam (MMSE),17 to assess current cognitive status.

Statistical Analyses
Data were analyzed with SPSS 12.0; t-tests and chi-square tests of independence were conducted to compare the two groups. We performed an ANOVA for each SANS domain, with the adjusted R2 reported.


  RESULTS

 
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 ABSTRACT
 INTRODUCTION
 METHOD
 RESULTS
DISCUSSION
 REFERENCES
 
A total of 17 TBI patients were screened, and 12 met the criteria for the study. Of the 5 subjects excluded, 1 did not have apathy, 1 had open head injury, and 3 had incomplete data and so were excluded from the analysis. For the DSS group, 30 subjects were screened and 16 enrolled; 6 individuals were excluded because of incomplete data, and 8 were excluded because they had non-deficit schizophrenia.

Of the 12 TBI subjects, 6 (50%) had severe, 4 (33.3%) had moderate, and 2 (16.7%) had mild TBI, on the basis of their initial Glasgow Coma Scale18 score (mild: 13–15; moderate: 9–12; severe: ≤8). Mean time-since-injury was 72.5 months (range: 15 months–167 months). Causes of injury included motor vehicle accident (75%), assault (16.7%), or falls (8.3%).

The two groups did not differ in age or gender. However, the TBI group was mostly white; the DSS participants were less educated and had lower premorbid intellectual functioning. The groups had similar scores on the Ham-D and the MMSE (Table 1).


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TABLE 1. Comparison of Demographic Factors in TBI Apathy and DSS Groups



On the SANS, patients with DSS had significantly higher scores (indicating greater severity of impairment) in the domains of alogia, flattened affect, and anhedonia. Group status accounted for 23%–39% of the variance in these domains (Table 2). The two groups did not differ in the AES or the SDS scores, given that they were selected for the study on the basis of these instruments (>2 on the SDS and>30 on the AES). There was no significant difference between the two groups on the negative symptoms of the SDS (Table 3).


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TABLE 2. ANOVA Comparison of TBI Apathy and DSS on the SANS




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TABLE 3. Participants Per Group With Severity Scores >2 Per Domain (N Scoring >2 on Domain, %)




  DISCUSSION

 
TOP
 ABSTRACT
 INTRODUCTION
 METHOD
 RESULTS
 DISCUSSION
REFERENCES
 
The goal of this study was to elucidate, by use of the SANS, the clinical similarities and differences of two "apathy" syndromes of different neuropsychiatric disorders. Patients with DSS differed from the TBI apathy patients by virtue of showing more severe alogia, flattening of affect, and anhedonia. These findings suggest that patients with DSS show differential paucity of speech production, impoverished affective display, and inability to experience pleasurable activities, as assessed by the SANS.

Even though diffuse brain injury is common in both TBI and schizophrenia, significant differences were found between the two groups in the apathy-syndrome profile. The differences may be due to differences in brain regions affected. The limbic-frontal-subcortical circuits that are associated with attention, motivation, executive functioning, and emotional responses to novel stimuli have been implicated in the development of apathy.1,19 It is possible that the frontal-subcortical tracts involved in these two disorders may be different. Three different fronto-subcortical tracts have been implicated in the pathogenesis of apathy.10,20 They include 1) the orbitofrontal cortical–basal ganglia tract, associated with emotional-affective processing such as interest in new learning, reward sensitivity, and appropriate concerns about problems; 2) the dorsolateral prefrontal cortex–basal ganglia pathway, associated with planning, rule-finding, working memory, and set-shifting; and 3) the cingulate–basal ganglia pathway associated with self-initiation of thoughts and self-initiation of action.

It is possible that, in terms of severity, these tracts may be differentially affected in these two disorders. This might have treatment implications: knowing which brain regions are tied most closely to apathy could help identify appropriate pharmacological and nonpharmacological interventions.

Also, identifying the predominant subtype of apathy could inform treatment strategies. For example, greater involvement of the cognitive domain may help us to focus on cognitive-behavior strategies and medications that enhance cognition, whereas greater impairment in the affective domain might respond better to antidepressants and other targeted psychotherapeutic interventions.

In addition to brain injury, there are a host of other factors associated with "apathy" or deficit symptoms. They include medical conditions1 (e.g., hypothyroidism or chronic illness, such as cancer), the person’s premorbid level of motivation,21 psychosocial factors1,8 (e.g., Cluster A personality traits or disorders, poverty, lower socioeconomic status), and personal experiences22 (e.g., multiple failures, resulting in a sense of hopelessness and failure to initiate novel activities). Poorer performance on alogia, anhedonia and affect domains in DSS patients can certainly be confounded by some of these factors.

In our study, a significantly higher percentage of non-Caucasians were found in the DSS group, as compared with the TBI group. Race and culture plays an important role in the "expression and extent of symptoms experienced" in patients with psychiatric illnesses.23 A study comparing symptoms of schizophrenia in Anglo Americans and Mexican Americans revealed that the former reported more psychiatric symptoms (delusions of persecution and anxiety,) whereas the latter reported more physical symptoms.23

Similarly, Fabrega et al.24 described significant differences between black and white patients in symptom presentation in a variety of psychiatric disorders, such as schizophrenia, dementia, and mood disorders. It is possible that some of these factors could have confounded our results. Nonetheless, it is important to note that to make a diagnosis of deficit schizophrenia, the symptoms must be enduring, primary to the illness, and not secondary to social deprivation, depression, hallucinations, delusions, or mental retardation, thereby indicating the minimal role, if any, played by these factors.

Premorbid IQ, as a confounding factor, however, deserves more attention. The premorbid IQ, as assessed by the NART-R, was significantly lower in the deficit-schizophrenia group. Indeed, previous studies25,26 have found similar results. Buchanan et al.25 have argued that differences in intelligence/general abilities between deficit and non-deficit groups may not represent just a "nuisance" to control for, but aspects of a more complex relationship between intelligence and the deficit syndrome that may be difficult to disentangle even on comprehensive neuropsychological tests.

Apathy is associated with several adverse outcomes.19 In subjects with Alzheimer’s disease, apathy is associated with impairment in activities of daily living27 and faster cognitive decline.28 It is also associated with limited response to treatment, such as poor participation in rehabilitation activities.29 Studies have revealed that schizophrenic patients with apathy respond poorly to both pharmacologic30 and nonpharmacologic31 modes of treatment.

A study of clinical correlates and factors associated with functional and cognitive outcome in apathy secondary to various brain diseases is important and necessary, but is not the focus of this study. Ultimately, we would like to explore these questions in future studies, as treatments may be developed to target apathy across disorders.

The lack of difference in negative symptoms on the SDS between the two groups is interesting and unexpected. Most subjects obtained scores of ≥2 in each of the domains. The maximum (most severe score) is 4; so there might be a "ceiling" effect that dilutes the possible differences between the groups. It is also important to note that this scale was designed to diagnose the presence of deficit schizophrenia, not to quantify the severity of negative symptoms.4 There was also no difference between the two groups on the attention domain of the SANS. A possible explanation may be that attention is not a component of the negative-syndrome construct, or that it is not well captured by the SANS Attention domain.32

Major limitations of this study include its small sample size, which precludes us from determining whether the differences found are indeed true or are secondary to other factors. Also, the TBI group was heterogeneous, with varying severities of injury and a wide interval range since time of injury. Information about the injury severity was obtained only from medical records or from subject’s history. The latter is often associated with recall bias. Perhaps the most significant limitation is that the clinician-raters were not blind to diagnosis, because it was impossible to assess apathy without recognizing group differences in positive symptoms. Finally, excluding patients with major depression and matching groups on Ham-D ratings (both groups produced mean scores below 7) might serve to limit the generalizability our findings, because many TBI patients who develop apathy have comorbid major depression.33

Despite these limitations, this is the first time that the symptom profiles of two etiologically different apathy syndromes have been compared. Additional studies that include neuropsychological testing, neuroimaging, and assessment of psychosocial factors will help better understand these syndromes. Future studies should use larger samples and include non-deficit schizophrenia and non-apathetic TBI control groups.


  ACKNOWLEDGMENTS

 
The authors express their gratitude to Dr. Robert Marin, University of Pittsburgh, and Drs. Peter Rabins and Constantine Lyketsos, Johns Hopkins School of Medicine, for their guidance in preparing this manuscript.

This study was supported by the 2000 Young Investigator Award to Nicola G. Cascella from the National Alliance for Research on Schizophrenia and Depression (NARSAD).


  REFERENCES

 
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 ABSTRACT
 INTRODUCTION
 METHOD
 RESULTS
 DISCUSSION
 REFERENCES
 

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