Robert S. Goldman

Dexamethasone suppression test in schizophrenia: Relationship to symptomatology, ventricular enlargement, and outcome

To relieve confusion about the clinical correlates and prognostic implications of the dexamethasone suppression test (DST) in schizophrenia, we conducted a DST in 44 schizophrenic inpatients at drug-free baseline and approximately 4 weeks after neuroleptic treatment. Patients were rated on positive, negative, and depressive symptoms at both times. A head computed tomography (CT) scan was performed and measures of ventricle-brain ratio (VBR) obtained. Clinical improvement was monitored at four weeks, and longer-term outcome assessed at 1 year. Seventeen of the 44 patients were DST nonsuppressors at baseline, and five of these remained nonsuppressors at 4 weeks posttreatment. Postdexamethasone plasma cortisol levels were correlated with negative symptoms at baseline (r = 0.45; p less than 0.01), but not after 4 weeks of neuroleptic treatment. Postdexamethasone plasma cortisols were not related to global severity, positive, or depressive symptoms at either timepoint or to VBR. Persistent nonsuppression was associated with poor outcome, but baseline postdexamethasone cortisol levels were unrelated to outcome at 4 weeks and 1 year. The literature on DST in schizophrenia is reviewed and attempts are made to reconcile discrepant findings and to discuss pathophysiological implications.

VALIDATION OF THE 16-ITEM NEGATIVE SYMPTOM ASSESSMENT

The dimensional structure of the 16-item Negative Symptom Assessment (NSA-16) was validated in a sample of 223 unmedicated schizophrenic inpatients and cross-validated on an independent sample of 276 patients with schizophrenia. Using a confirmatory factor analytic procedure, a five factor model was found to best characterize the structure of this rating instrument. These factors include: Communication, Emotion/Affect, Social Involvement, Motivation, and Retardation. The latent structure of the NSA-16 is similar to the larger instrument from which it was derived. The findings provide support for a multidimensional model of negative symptoms in schizophrenia and offer a useful measure for their assessment.

Neuropsychological Prediction of Treatment Efficacy and One-Year Outcome in Schizophrenia

The present study was conducted to establish the degree of interrelationship between neuropsychological functioning in the acute phase of the schizophrenic illness, clinical measures of treatment response (positive and negative symptoms), and 1-year outcome. Nineteen SADS/RDC schizophrenic inpatients were clinically rated during a 2-week drug washout period and again following 4 weeks of neuroleptic treatment. The findings revealed that reduced attentional ability in the baseline phase significantly predicted the presence of higher residual negative symptoms following 4 weeks of treatment, while neurocognitive status was unrelated to positive symptom response. With respect to prediction of the 1-year outcome, poor functional status of this schizophrenic population was significantly associated with the presence of baseline memory dysfunction.

Interrater reliability in scoring the Wisconsin card sorting test

Neuropsychological instruments continue to proliferate the field, while studies systematically addressing their accuracy and standardization have lagged behind. This paper examines the standard scoring criteria on a widely used neuropsychological test, the Wisconsin Card Sorting Test (WCST). Specifically, the scoring criteria for the perseveration variables are complex and interrater reliability had not yet been established. Study 1 revealed excellent interrater reliability between three individuals experienced with the WCST who had independently learned the scoring procedures. Study 2 demonstrated excellent interrater agreement among six novice raters. Some of the novice scorers used supplemental scoring instructions that were developed in an attempt to improve understanding of the manual. The supplemental scoring instructions reduced training time by 41% without affecting the high reliability between the raters. This paper also illustrates an appropriate use of generalizability theory, a powerful statistical method to examine reliability.

Mutability and relationship between positive and negative symptoms during neuroleptic treatment in schizophrenia

The positive/negative symptom dichotomy is being increasingly utilized to explain the bet- erogeneity of schizophrenia, and poor response to neuroleptic treatment has traditiona!ly been considered to be one of the characteristic fea- tures of the negative syndrome. This issue was emphasized by Crow (1980), who principally based this conclusion on the study by Iohnstone et al. (1978), which found that

Ventricular enlargement, neuropsychological status, and premorbid function in schizophrenia

Ventricular enlargement is one of the most consistently documented neurobiological abnormalities in schizophrenia. The timing of the development of this abnormality in the course of schizophrenic illness and its relationship to neuropsychological dysfunction and premorbid adjustment is, however, unclear. To address these questions, we examined the relationship between ventricle-brain ratio (VBR), premorbid adjustment, and neuropsychological function, in 23 acutely exacerbated chronic schizophrenic inpatients. We observed that larger ventricles were associated with better current neuropsychological test performance, better premorbid cognitive ability, greater cognitive deterioration, better childhood premorbid social function, and greater decline in social function from premorbid levels. These data suggest that at least two developmental processes may operate in the genesis of cognitive and social dysfunction in schizophrenia: (1) childhood onset associated with poor premorbid childhood function, low educational achievement, lower intelligence quotient (IQ) and variably with VBR; and (2) adolescent onset associated with relatively normal childhood social function, higher academic achievement and IQ and increased VBR. Ventricular enlargement may reflect a late developmental or degenerative pathological process in schizophrenia.

POSITIVE AND NEGATIVE SYMPTOMS COVARY DURING CLOZAPINE TREATMENT IN SCHIZOPHRENIA

Summary-Although negative symptoms were traditionally considered to be unresponsive to neuroleptic medication, recent studies have demonstrated that negative symptoms do improve during neuroleptic treatment and that such improvement tends to occur concurrently with improvement in positive symptoms. Clozapine is an atypical neuroleptic that is effective in a significant proportion of otherwise neuroleptic-nonresponsive schizophrenic patients; in contrast to conventional neuroleptics, clozapine is also purported to possess unique efficacy in the amelioration of negative symptoms. How clozapine-associated reduction in negative symptoms relates to change in positive symptoms is not clear. To study the relationship between change in positive and negative symptoms during clozapine treatment, we monitored symptomatology in 40 DSM-III-R schizophrenic patients before and about 8 weeks after a trial of clozapine. Both positive and negative symptoms improved significantly. There was a significant correlation (r = .63, p c.01) between change in positive symptoms and change in negative symptoms; as with conventional neuroleptics, negative symptoms improved concomitantly with positive symptoms during clozapine treatment. Clozapine’s apparent greater efficacy on negative symptoms may be related to its greater efficacy on positive symptoms in otherwise neuroleptic-refractory patients and its lesser propensity to cause extrapyramidal sideeffects.

Covariance of positive and negative symptoms during neuroleptic treatment in schizophrenia: A replication

Although poor response to neuroleptics has traditionally been considered a characteristic feature of negative schizophrenic symptoms (Crow 1980; Andreasen et aJ 1982), several recent studies have documented significant improvement in negative symptoms in schizophrenic patients treated with neuroleptics (Breier et al 1987; vanKammen et al 1987; Kay and Singh 1989; Tendon et al 1990; Meltzer, 1990, Serban et al 1992). The question of whether neuroleptic-induced improvement in negative symptoms is linked to concomitant improvement in positive symptoms (vanKammen et al 1987; Tendon et al 1990; Meltzer 1990) or occurs independently of such improvement (Breier et al 1987; Serban et al 1992) is unresolved. This issue has obvious pathophysiological and therapeutic relevance. in a previous study (Tendon et al 1990), we had observed a significant improvement in negative symptoms with four weeks of neuroleptic treatment in a sample of forty schizophrenic inpatients; a significant correlation between change in positive and negative symptoms was also noted, in an effort to replicate these findings and further evaluate to covariance of positive and neg, ative symptoms in the course of initial neuroleptic treatment, we assessed positive ~nd negative symptoms in another nonoveflapping sample of 80 schizophrenic inpatients at drug-free baseline and four weeks after clinically determined neuroleptic treatment.

Factor structure of the negative symptom assessment

The factor structure of the Negative Symptom Assessment (NSA), a standardized negative symptoms rating scale, was systematically evaluated in a group of 223 inpatients with schizophrenia. Confirmatory factor analyses found that a six-factor model best described the NSA. More specifically, the domains of Communication, Emotion/Affect, Social Involvement, Motivation, Gross Cognition, and Retardation characterized the rating scale. This latent structure of the NSA is consistent with a multidimensional conceptualization of negative symptoms.

Sensitivity of the mini‐mental state examination to frontal lobe dysfunction in normal aging

The present study examined the sensitivity of the Mini-Mental State Examination (MMSE) in detecting the frontal lobe dysfunction that occurs with normal aging. Eighty normal, independently living older adults in four age groupings from 50 to 89 were administered the MMSE along with three neurocognitive measures sensitive to frontal lobe functioning. Results revealed age-related cognitive decline on frontal lobe tasks that also was detected by the MMSE. These findings are noteworthy because the MMSE was intended as a measure of gross cognitive status rather than of frontal lobe functioning.