Effect of treatment with paliperidone palmitate versus oral antipsychotics on frontal lobe intracortical myelin volume in participants with recent-onset schizophrenia: Magnetic resonance imaging results from the DREaM study.

OBJECTIVE: We investigated changes in brain intracortical myelin (ICM) volume in the frontal lobe after 9 months of treatment with paliperidone palmitate (PP) compared with 9 months of treatment with oral antipsychotics (OAP) in participants with recent-onset schizophrenia or schizophreniform disorder from the Disease Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial. METHODS: DREaM included 3 phases: Part I, a 2-month oral run-in; Part II, a 9-month disease progression phase (PP or OAP); and Part III, 9 months of additional treatment (participants receiving PP continued PP [PP/PP] and participants receiving OAP were rerandomized to receive either PP [OAP/PP] or OAP [OAP/OAP]). In Part II, magnetic resonance imaging (MRI) and functional and symptomatic assessment was performed at baseline, day 92, and day 260. ICM volume as a fraction of the entire brain volume was quantified by subtraction of a proton density image from an inversion recovery image. Within-treatment-group changes from baseline were assessed by paired t-tests. Analysis of covariance was used to analyze ICM volume changes between treatment groups, adjusting for country. RESULTS: The MRI analysis sample size included 71 DREaM participants (PP, 23; OAP, 48) and 64 healthy controls. At baseline, mean adjusted ICM fraction values did not differ between groups (PP, 0.057; OAP, 0.058, p = 0.79). By day 92, the adjusted ICM fraction in the OAP group had decreased significantly (change from baseline, -0.002; p = 0.001), whereas the adjusted ICM fraction remained unchanged from baseline in the PP group (0.000; p = 0.80). At day 260, the change from baseline in adjusted ICM fraction was -0.004 (p = 0.004) in the OAP group and -0.001 (p = 0.728) in the PP group. The difference between treatment groups did not reach statistical significance (p = 0.147). CONCLUSIONS: In participants with recent-onset schizophrenia or schizophreniform disorder, frontal ICM volume was preserved at baseline levels in those treated with PP over 9 months. However, a decrease of frontal ICM volume was observed among participants treated with OAPs. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT02431702.

A combined exercise and cognitive training intervention induces fronto-cingulate cortical plasticity in first-episode psychosis patients.

OBJECTIVE: Schizophrenia (SZ) is characterized by neurobiological and associated cognitive and functional deficits, including pronounced cortical thinning, that lead to acute and long-term functional impairment. Research with older adults supports the role of non-pharmacological interventions, such as exercise (E) and cognitive training (CT), for cognitive impairments. This literature influenced the development of combined CT&E treatments for individuals with SZ. However, the impact of longer combined treatment duration (6 months) on neuroanatomy has yet to be explored in patients in the early course of the illness. The impact of adding exercise to cognitive training for key brain regions associated with higher-order cognition was examined here using magnetic resonance imaging (MRI) in first-episode psychosis (FEP) patients. METHODS: UCLA Aftercare Research Program patients with a recent first episode of schizophrenia were randomly assigned to either combined cognitive and exercise training (CT&E) (N = 20) or cognitive training alone (CT) (N = 17) intervention. Cortical thickness was measured longitudinally and analyzed for two regions of interest using FreeSurfer. RESULTS: Compared to patients in the CT group, those in the CT&E group demonstrated an increase in cortical thickness within the left anterior cingulate cortex over the six-month treatment period (ACC: F(1, 35) = 4.666, P < .04). Directional tendencies were similar in the left dorsolateral prefrontal cortex (DLPFC: F(1,35) = 4.132, P < .05). CONCLUSIONS: These findings suggest that exercise and cognitive training may synergistically increase fronto-cingulate cortical thickness to mitigate progressive neural atrophy in the early course of SZ. This combined intervention appears to be a valuable adjunct to standard pharmacologic treatment in FEP patients.

Latent structure of cognition in schizophrenia: a confirmatory factor analysis of the MATRICS Consensus Cognitive Battery (MCCB).

BACKGROUND: The number of separable cognitive dimensions in schizophrenia has been debated. Guided by the extant factor analytic literature, the NIMH Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative selected seven cognitive domains relevant to treatment studies in schizophrenia: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. These domains are assessed in the MATRICS Consensus Cognitive Battery (MCCB). The aim of this study was to conduct a confirmatory factor analysis (CFA) of the beta battery of the MCCB to compare the fit of the MATRICS consensus seven-domain model to other models in the current literature on cognition in schizophrenia. METHOD: Using data from 281 schizophrenia outpatients, we compared the seven correlated factors model with alternative models. Specifically, we compared the 7-factor model to (a) a single-factor model, (b) a three correlated factors model including speed of processing, working memory, and general cognition, and (c) a hierarchical model in which seven first-order factors loaded onto a second-order general cognitive factor. RESULTS: Multiple fit indices indicated the seven correlated factors model was the best fit for the data and provided significant improvement in model fit beyond the comparison models. CONCLUSIONS: These results support the assessment of these seven cognitive dimensions in clinical trials of interventions to improve cognition in schizophrenia. Because these cognitive factors are separable to some degree, it is plausible that specific interventions may have differential effects on the domains.

Theory of mind in the early course of schizophrenia: stability, symptom and neurocognitive correlates, and relationship with functioning.

BACKGROUND: Numerous studies have reported links between theory of mind (ToM) deficits, neurocognition and negative symptoms with functional outcome in chronic schizophrenia patients. Although the ToM deficit has been observed in first-episode patients, fewer studies have addressed ToM as a possible trait marker, neurocognitive and symptom correlations longitudinally, and associations with later functioning. METHOD: Recent-onset schizophrenia patients (n = 77) were assessed at baseline after reaching medication stabilization, and again at 6 months (n = 48). Healthy controls (n = 21) were screened, and demographically comparable with the patients. ToM was assessed with a Social Animations Task (SAT), in which the participants' descriptions of scenes depicting abstract visual stimuli 'interacting' in three conditions (ToM, goal directed and random) were rated for degree of intentionality attributed to the figures and for appropriateness. Neurocognition, symptoms and role functioning were also assessed. RESULTS: On the SAT, patients had lower scores than controls for both intentionality (p < 0.01) and appropriateness (p < 0.01) during the ToM condition, at baseline and 6 months. The ToM deficit was stable and present even in remitted patients. Analyses at baseline and 6 months indicated that for patients, ToM intentionality and appropriateness were significantly correlated with neurocognition, negative symptoms and role functioning. The relationship between ToM and role functioning was mediated by negative symptoms. CONCLUSIONS: The ToM deficit was found in recent-onset schizophrenia patients and appears to be moderately trait-like. ToM is also moderately correlated with neurocognition, negative and positive symptoms, and role functioning. ToM appears to influence negative symptoms which in turn makes an impact on role functioning.

Cognitive functioning in first-episode schizophrenia: MATRICS Consensus Cognitive Battery (MCCB) Profile of Impairment.

BACKGROUND: Although many studies have assessed cognitive functioning in first-episode schizophrenia (FESz), the pattern and severity of impairment across cognitive domains remain unclear. Moreover, few studies have directly compared the pattern of cognitive performance between FESz and chronic schizophrenia (CSz). In this study we examined the cognitive impairment profile in FESz using a standardized neurocognitive battery (MATRICS Consensus Cognitive Battery; MCCB). METHODS: MCCB data were compared from 105 FESz patients, 176 CSz patients and 300 non-psychiatric (NP) participants. Mixed model analysis evaluated group differences in MCCB profiles and relative strengths and weaknesses in the MCCB profiles of patients. Clinical implications of MCCB performance were also examined; we compared the proportion of participants from each group who exhibited clinically-significant global cognitive impairment based on the MCCB Overall Composite score. RESULTS: FESz and CSz showed impaired performance across all MCCB domains relative to NP. With the exception of relative preservation of working memory and social cognition in FESz, the MCCB domain scores were similar in FESz and CSz. The distribution of impairment on the Overall Composite score did not significantly differ between FESz and CSz; compared to NP, both patient groups were overrepresented in moderate and severe impairment categories. CONCLUSION: The pattern, magnitude, and distribution of severity of impairment in FESz were similar to that observed in CSz. However, early in the illness, there may be relative sparing of working memory and social cognition.

Avoidant personality disorder symptoms in first-degree relatives of schizophrenia patients predict performance on neurocognitive measures: the UCLA family study.

Whether avoidant personality disorder symptoms are related to neurocognitive impairments that aggregate in relatives of schizophrenics is unknown. We report the relationship between avoidant personality disorder symptoms and neurocognitive performance in the first-degree relatives of probands with schizophrenia. 367 first-degree relatives of probands with schizophrenia and 245 relatives of community controls were interviewed for the presence of avoidant personality symptoms and symptoms of paranoid and schizotypal personality disorders and administered neurocognitive measures. Relationships between neurocognitive measures and avoidant symptoms were analyzed using linear mixed models. Avoidant dimensional scores predicted performance on the span of apprehension (SPAN), 3-7 Continuous Performance Test (3-7 CPT), and Trail Making Test (TMT-B) in schizophrenia relatives. These relationships remained significant on the SPAN even after adjustment for paranoid or schizotypal dimensional scores and on the TMT-B after adjustment for paranoid dimensional scores. Moreover, in a second set of analyses comparing schizophrenia relatives to controls there were significant or trending differences in the degree of the relationship between avoidant symptoms and each of these neurocognitive measures even after adjustments for paranoid and schizotypal dimensional scores. The substantial correlation between avoidant and schizotypal symptoms suggests that these personality disorders are not independent. Avoidant and in some cases schizotypal dimensional scores are significant predictors of variability in these neurocognitive measures. In all analyses, higher levels of avoidant symptoms were associated with worse performance on the neurocognitive measures in relatives of schizophrenia probands. These results support the hypothesis that avoidant personality disorder may be a schizophrenia spectrum phenotype.

Theory of mind deficits for processing counterfactual information in persons with chronic schizophrenia.

BACKGROUND: Interpersonal communication problems are common among persons with schizophrenia and may be linked, in part, to deficits in theory of mind (ToM), the ability to accurately perceive the attitudes, beliefs and intentions of others. Particular difficulties might be expected in the processing of counterfactual information such as sarcasm or lies. METHOD: The present study included 50 schizophrenia or schizo-affective out-patients and 44 demographically comparable healthy adults who were administered Part III of The Awareness of Social Inference Test (TASIT; a measure assessing comprehension of sarcasm versus lies) as well as measures of positive and negative symptoms and community functioning. RESULTS: TASIT data were analyzed using a 2 (group: patients versus healthy adults) x 2 (condition: sarcasm versus lie) repeated-measures ANOVA. The results show significant effects for group, condition, and the group x condition interaction. Compared to controls, patients performed significantly worse on sarcasm but not lie scenes. Within-group contrasts showed that patients performed significantly worse on sarcasm versus lie scenes; controls performed comparably on both. In patients, performance on TASIT showed a significant correlation with positive, but not negative, symptoms. The group and interaction effects remained significant when rerun with a subset of patients with low-level positive symptoms. The findings for a relationship between TASIT performance and community functioning were essentially negative. CONCLUSIONS: The findings replicate a prior demonstration of difficulty in the comprehension of sarcasm using a different test, but are not consistent with previous studies showing global ToM deficits in schizophrenia.

Avoidant personality disorder is a separable schizophrenia-spectrum personality disorder even when controlling for the presence of paranoid and schizotypal personality disorders The UCLA family study.

It is unresolved whether avoidant personality disorder (APD) is an independent schizophrenia (Sz)-spectrum personality disorder (PD). Some studies find APD and social anxiety symptoms (Sxs) to be separable dimensions of psychopathology in relatives (Rels) of schizophrenics while other studies find avoidant Sxs to be correlated with schizotypal and paranoid Sxs. Rates of APD among first-degree Rels of Sz probands, attention-deficit/hyperactivity disorder (ADHD) probands, and community control (CC) probands were examined. Further analyses examined rates when controlling for the presence of schizotypal (SPD) and paranoid (PPD) personality disorders, differences in APD Sxs between relative groups, and whether APD in Rels of Szs reflects a near miss for another Sz-spectrum PD. Three hundred sixty-two first-degree Rels of Sz probands, 201 relatives of ADHD probands, and 245 Rels of CC probands were interviewed for the presence of DSM-III-R Axis I and II disorders. Diagnoses, integrating family history, interview information, and medical records, were determined. APD occurred more frequently in Rels of Sz probands compared to CC probands (p<0.001) and also when controlling for SPD and PPD (p<0.005). Two Sxs of APD were most characteristic of the Rels of Sz probands: "avoids social or occupational activities..." and "exaggerates the potential difficulties..." 65% of the Rels of Sz probands who had diagnoses of APD were more than one criterion short of a DSM-III-R diagnosis of either SPD or PPD. This indicates that APD is a separate Sz-spectrum disorder, and not merely a sub-clinical form of SPD or PPD.

Clinical outcome following neuroleptic discontinuation in patients with remitted recent-onset schizophrenia.

OBJECTIVE: The goal of this report was to examine the clinical course following neuroleptic discontinuation of patients with recent-onset schizophrenia who had been receiving maintenance antipsychotic treatment for at least 1 year. METHOD: Fifty-three volunteer patients with recent-onset schizophrenia who had been clinically stabilized on a maintenance regimen of fluphenazine decanoate for a mean of 16.7 months had their antipsychotic medications withdrawn under clinical supervision. Participants initially entered a 24-week, double-blind crossover trial in which fluphenazine and placebo were administered for 12 weeks each. For those who did not experience symptom exacerbation or relapse during this period, fluphenazine was openly withdrawn; participants were then followed for up to 18 additional months. RESULTS: When a low threshold for defining symptom reemergence was used, 78% (N=39 of 50) of the patients experienced an exacerbation or relapse within 1 year; 96% (N=48 of 50) did so within 2 years. Mean time to exacerbation or relapse was 235 days. When hospitalization was used as a relapse criterion, only six of 45 of individuals (13%) experiencing an exacerbation or relapse who continued in treatment in the clinic were hospitalized, demonstrating the sensitivity of the psychotic exacerbation criterion. CONCLUSIONS: The vast majority of clinically stable individuals with recent-onset schizophrenia will experience an exacerbation or relapse after antipsychotic discontinuation, even after more than a year of maintenance medication. However, clinical monitoring and a low threshold for reinstating medications can prevent hospitalization for the majority of these patients.

Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study.

BACKGROUND: This study tested the hypothesis that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining if first-degree relatives of COS probands have an increased risk for schizophrenia and schizotypal and paranoid personality disorders. METHODS: Relatives of COS probands (n = 148) were compared with relatives of attention-deficit/hyperactivity disorder (ADHD) (n = 368) and community control (n = 206) probands. Age-appropriate structured diagnostic interviews were used to assign DSM-III-R diagnoses to probands and their relatives. Family psychiatric history was elicited from multiple informants. Diagnoses of relatives were made blind to information about probands' diagnoses. Final consensus diagnoses, which integrated family history, direct interview information, and medical records, are reported in this article. RESULTS: There was an increased lifetime morbid risk for schizophrenia (4.95% +/- 2.16%) and schizotypal personality disorder (4.20% +/- 2.06%) in the parents of COS probands compared with parents of ADHD (0.45% +/- 0.45%, 0.91% +/- 0.63%) and community control (0%) probands. The parents of COS probands diagnosed as having schizophrenia had an early age of first onset of schizophrenia. Risk for avoidant personality disorder (9.41% +/- 3.17%) was increased in the parents of COS probands compared with parents of community controls (1.67% +/- 1.17%). CONCLUSIONS: The psychiatric disorders that do and do not aggregate in the parents of COS probands are remarkably similar to the disorders that do and do not aggregate in the parents of adults with schizophrenia in modern family studies. These findings provide compelling support for the hypothesis of etiological continuity between COS and AOS.

Neurocognitive vulnerability, interpersonal criticism, and the emergence of unusual thinking by schizophrenic patients during family transactions.

BACKGROUND: This study examined whether the combination of patients' neurocognitive deficits and criticism by others would predict the emergence of patients' unusual thinking during stressful family transactions. METHODS: When clinically stable, 41 patients with recent-onset schizophrenia completed 2 versions of a visual vigilance task, the Continuous Performance Test (CPT). One CPT emphasized early perceptual processing, while the other stressed immediate, working memory. On a separate occasion, patients and family members participated in a 20-minute interaction in which the number of relatives' criticisms and patients' unusual thoughts was assessed. RESULTS: In a hierarchical regression model, after entering performance on the CPT demanding immediate, working memory, and the number of criticisms by family members, the interaction of CPT performance and criticism significantly predicted the number of patients' unusual thoughts during the family session (r(2) change = 0.09; P =.03). Post hoc analyses revealed that the number of criticisms and odd thoughts correlated significantly (r = 0.59, P =. 03) for patients who had poor memory-load CPT performance, but were unrelated (r = -0.07) for patients who did well on the memory-load CPT. The CPT emphasizing early visual processing, either alone or in combination with interpersonal criticism, did not predict the number of patients' unusual thoughts during the interaction. CONCLUSION: The results suggest that the combination of patients' working memory deficits and interpersonal criticism jointly predicts psychotic thinking, consistent with a model of schizophrenia that emphasizes the interaction of neurocognitive vulnerability and psychosocial stress factors. Arch Gen Psychiatry. 2000;57:1174-1179.

MMPI discriminators of deficit vs. non-deficit recent-onset schizophrenia patients.

Seventy-four patients with a recent initial onset of schizophrenia were studied during an inpatient hospitalization for a recent onset of schizophrenia as well as during a 12-month period of outpatient treatment as part of a large longitudinal study at UCLA. The Proxy for the Deficit Syndrome (PDS; Kirkpatrick, B., Buchanan, R.W., Carpenter, W.T., 1993. Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Research 47, 47-56.) was calculated based on psychiatric symptoms rated on the Brief Psychiatric Rating Scale every 2 weeks throughout the 12 months. The Minnesota Multiphasic Personality Inventory (MMPI) was administered to the schizophrenia patients at the index hospitalization. The 168-item version of the MMPI (MMPI-168) was administered at the baseline point of the 12-month period of outpatient treatment, and again 1 year later. Normal comparison subjects were tested with the MMPI or MMPI-168 at comparable time intervals. The UCLA Social Attainment Scale, a measure of the adequacy of social functioning and relatedness, was examined at the outpatient baseline and 12-month points. During the outpatient period, the Deficit Schizophrenia group (i.e. schizophrenia patients with high 12-month average PDS scores) had lower T-scores than the Non-deficit Schizophrenia group on several MMPI-168 scales, especially scales related to affective distress and anxiety. The MMPI-168 scores of normal subjects were generally the lowest of the three groups, but not always significantly lower than those of the Deficit Schizophrenia group. Social functioning at the end of the 12-month period was worst for the patient group with high deficit (PDS) scores. The findings are congruent with the concept of a Deficit Syndrome for which the PDS is the proxy.

Life events can trigger depressive exacerbation in the early course of schizophrenia.

Previous studies have linked life events with depression in chronic schizophrenia, but those studies had methodological limitations. Using a prospective research design and examining events that were clearly independent of the patients' illnesses, the authors sought to determine whether stressful life events could trigger depressive symptoms in the early course of schizophrenia. Schizophrenia patients (n = 99) were followed for 1 year from a point of outpatient stabilization. Life event interviews were conducted every 4 weeks and symptom assessments every 2 weeks. Survival analyses showed a significantly increased risk for an exacerbation of significant depressive symptoms following an independent life event. Of interest is that an analysis of competing risk showed that the odds of psychotic exacerbation following a major independent life event were not significantly greater than the odds of depressive exacerbation. The risk of depression and of psychosis after experiencing a stressful life event is significantly increased for the first month, but the risk period can extend to 3 months.

Symptom dimensions in recent-onset schizophrenia and mania: a principal components analysis of the 24-item Brief Psychiatric Rating Scale.

Previous four- and five-factor solutions of the 18-item Brief Psychiatric Rating Scale (BPRS) suggested the possibility of an affective dimension in psychosis. A principal components analysis was used to analyze psychiatric symptom data rated on an expanded 24-item version of the BPRS. BPRS data were collected during a period of acute psychotic and affective illness with 114 young adult, recent-onset schizophrenia and schizoaffective patients and 27 bipolar manic patients. Principal components analyses of the 18-item and 24-item BPRS indicated a four-factor solution was the most interpretable. Principal components analysis of the 24-item BPRS produced a clear mania factor characterized by high loadings from items added to the 18-item BPRS, which included elevated mood, motor hyperactivity, and distractibility. This factor solution suggests that the 24-item BPRS allows for an expanded assessment of affective symptoms relating to a manic dimension. Potentially important symptoms that were added to the traditional 18-item version, namely suicidality, bizarre behavior, and self-neglect, also make clear contributions to other factors.

Trait versus state aspects of the MMPI during the early course of schizophrenia.

Scores on the Minnesota Multiphasic Personality Inventory (MMPI)-168 item version were examined during periods of clinical remission and of psychosis for recent-onset schizophrenia patients (n = 19) and at comparable time intervals for demographically matched normal participants (n = 19). To determine diagnostic specificity, MMPIs for participants with bipolar affective disorder in remission (n = 12) were also examined. Methods for distinguishing between stable vulnerability indicators, mediating vulnerability factors and episode indicators of psychopathology were adapted from Nuechterlein and Dawson (1984). MMPI scales Pa, Sc and validity scale F showed a combination of trait and state qualities, characteristic of mediating vulnerability factors. These scales reflect changes that occur during psychotic episodes but also apparently tap personality characteristics that endure into periods of clinical remission. Unexpectedly, some MMPI scales that are not typically associated with psychotic disorders (i.e. Hs, D, and Hy) were significantly higher in schizophrenia patients across psychotic and clinically remitted states than in normal participants. In clinical remission, higher scores on scales Hs, D and Hy, showed some specificity to schizophrenia relative to bipolar disorder. While MMPI-168 scales Pd and Pt fit the pattern for vulnerability indicators, it was uncertain whether they belonged to the 'stable' versus 'mediating' subtype. MMPI scores that continue to be higher in remission than in a normal sample may reflect either enduring vulnerability factors or the impact of schizophrenia and the individuals' attempts to cope with the disorder. Studies of first-degree relatives will be needed to provide converging evidence that certain personality characteristics reflect genetic predisposition to schizophrenia.

Prediction of the deficit syndrome from initial deficit symptoms in the early course of schizophrenia.

The Proxy for the Deficit Syndrome (PDS) was used with longitudinal symptom assessment data to identify recent-onset schizophrenia patients with the deficit syndrome. We evaluated the stability of deficit symptoms using repeated assessments. Symptom ratings were examined at an initial point of outpatient stabilization on antipsychotic medication as well as prospectively over the subsequent 12 months of outpatient treatment and assessment in 83 recent-onset schizophrenia patients. The vast majority of patients who were classified as non-deficit at the cross-sectional baseline assessment continued to remain non-deficit throughout the first year of treatment. However, patients classified as deficit at baseline did not consistently remain classified as showing deficit syndrome during the follow-through period. Thus, the presence of deficit symptoms detected in a single cross-sectional rating may be an inaccurate way to rate the deficit syndrome, yielding excessive false positives. Our use of longitudinal data allowed the stability criterion of the deficit syndrome to be evaluated using the PDS.

Depressive symptoms in the early course of schizophrenia: relationship to familial psychiatric illness.

OBJECTIVE: This study examined the relation between the presence of depressive symptoms in schizophrenic patients with a recent first psychotic episode and affective disorders among their relatives. METHOD: Data on depressive symptoms in 70 patients with schizophrenia diagnosed according to the DSM-III-R criteria, who had had a recent first psychotic episode, and psychiatric diagnostic information on 293 of their first-degree and 674 of their second-degree relatives were collected. Depressive symptoms in the schizophrenic probands were examined at the index psychotic episode (at study entry) and systematically over a 1-year follow-through period. The majority of first-degree family members were interviewed in person with the use of semistructured diagnostic interviews. RESULTS: The linear regression findings confirmed the hypothesis that depressive symptoms in the early course of schizophrenia are associated with a family history of unipolar affective illness. CONCLUSIONS: Because depression in the patients was associated with a family history of depression, this suggests that depression in schizophrenia is not solely either a reaction to having had a psychotic episode or part of the recovery process. The findings are consistent with a model in which a familial genetic liability to affective disorder, when present, is viewed a s exerting a modifying influence on the patient's schizophrenic illness to increase expression of depressive symptoms.

The role of neurocognitive deficits in understanding adaptive functioning in severe psychiatric illness: commentary on Hawkins and Cooper.

The presentation of Ms. E. by Hawkins and Cooper provides an excellent discussion of the diverse ways in which clinicians and clinical researchers are currently conceptualizing neurocognitive deficits within severe psychiatric disorders. The thorough neuropsychological evaluation of this patient provided a wealth of information that was completely missed by the Mini-Mental State Exam (MMSE; Folstein et al. 1975). As Hawkins and Cooper point out, the tendency of some clinicians to discount the role of neuropsychological deficiency in the face of adequate MMSE scores and evident psychiatric symptoms is not justified by the relevant clinical research literature. Furthermore, recent developments in scientific conceptions of the role of neurocognitive deficits in the more severe psychiatric disorders, such as schizophrenia, schizoaffective disorder, and bipolar mood disorder, deserve more attention in clinical practice.