Gender differences in young adults with first-episode schizophrenia spectrum disorders at baseline in the Danish OPUS study

Gender differences in age at first onset, duration of untreated psychosis, psychopathology, social functioning, and self-esteem were investigated in a group of 578 young adults with a first-episode schizophrenia spectrum disorder. The mean age at first-onset of symptoms, age at first contact, and duration of untreated psychosis were similar for men and women. Men had more severe negative symptoms, poorer premorbid functioning, and poorer social networks, whereas women had more severe hallucinations. More men than women were substance abusers, were unemployed, and lived alone. Women had poorer self-esteem than men, in spite of better scores in functioning. Premorbid social adjustment was significantly related to the level of negative symptoms and number of friends. Conclusion is that men and women with first-episode psychosis showed different psychopathological characteristics and different social functioning, which cannot be explained by older age of onset for women. Women make more suicide attempts and experience lower self-esteem in spite of better social functioning.     

Parenting and adjustment in schizophrenia

OBJECTIVE: Patients with schizophrenia who became parents and those who remained childless were compared on premorbid characteristics and current clinical and social adjustment. METHODS: Subjects were 400 men and women with a DSM-III-R diagnosis of chronic schizophrenia based on the Structured Clinical Interview for DSM-III-R (SCID). Assessments measured concurrent substance abuse and antisocial behavior, positive and negative symptoms using the Positive and Negative Syndrome Scale, functional status using the Global Assessment of Functioning scale, family support, and treatment compliance. A total of 158 patients were parents (47 men and 111 women), and 242 were childless (153 men and 89 women). RESULTS: Compared with childless subjects, parents were more likely to have had better premorbid social adjustment, to have ever been married or involved in a conjugal relationship, and to have become ill at a later age. More than two-thirds of parents entered parenthood before the onset of schizophrenia. More women than men were parents, and parents were more likely to be members of ethnic minority groups. No differences were found in current clinical and social adjustment of parents and childless subjects. CONCLUSIONS: Parenthood was associated with better premorbid social adjustment, but it conferred no advantage in the long-term course of schizophrenia. Patients who experience a later onset of schizophrenia or have better premorbid social skills may be more likely to undertake marriage and parenthood, but they will then also be more likely to need special support for the parenting role once the illness begins and takes its typical course.     

Association of symptoms and executive function in schizophrenia and bipolar disorder

The extent to which cognitive impairment in psychosis is related to the particular disorder or the pattern of symptoms is unclear. We examined executive function in two groups of schizophrenia patients with predominant symptoms of disorganisation (n=15) and psychomotor poverty (n=15), respectively, two groups of bipolar I disorder patients with predominant symptoms of mania (n=15) and depression (n=15), respectively, and 30 healthy controls. We predicted that the pattern of symptoms ('excess' [disorganisation/mania] or 'deficiency' [negative symptoms/depression]) would be more related to executive ability than the underlying disorder. The patient groups showed partially overlapping executive dysfunctions relative to the control group. There were no significant differences between groups with 'excess' symptoms (schizophrenia patients with thought disorder and bipolar patients with mania), or between groups with 'deficiency' symptoms (schizophrenia patients with negative symptoms and bipolar patients with depression). In contrast, differences were noted between groups with the same diagnosis: Schizophrenia patients with disorganisation were less accurate in semantic verbal fluency than those with negative symptoms; and bipolar patients with mania tended to be faster, but less accurate, in sentence completion than those with depression. A statistical comparison of the associations of 'diagnosis' and the 'excess-deficiency' dimension with executive function revealed a trend for a greater association of the latter with two measures of performance accuracy. Executive dysfunction in patients with psychotic disorders may be more related to their symptom profile than their diagnosis.     

Cross-sectional similarities and differences between schizophrenia, schizoaffective disorder and mania or mixed mania with mood-incongruent psychotic features.

BACKGROUND: The cross-sectional clinical differentiation of schizophrenia or schizoaffective disorder from mood-incongruent psychotic mania or mixed mania is difficult, since pathognomonic symptoms are lacking in these conditions. AIMS OF THE STUDY: To compare a series of clinical variables related to mood and cognition in patient groups with DSM-III-R diagnosis of schizophrenia, schizoaffective disorder, mood-incongruent psychotic mania and mood-incongruent psychotic mixed mania. METHODS: One hundred and fifty-one consecutive patients were evaluated in the week prior to discharge by using the structured clinical interview for DSM-III-R-patient edition (SCID-P). Severity of psychopathology was assessed by the 18-item version of the brief psychiatric rating scale (BPRS) and negative symptoms by the scale for assessment of negative symptoms (SANS). Level of insight was assessed with the scale to assess unawareness of mental disorders (SUMD). RESULTS: There were no differences in rates of specific types of delusions and hallucinations between subjects with schizophrenia, schizoaffective disorder, psychotic mania and psychotic mixed mania. SANS factors scores were significantly higher in patients with schizophrenia than in the bipolar groups. Patients with mixed state scored significantly higher on depression and excitement compared to schizophrenia group and, to a lesser extent, to schizoaffective group. Subjects with schizophrenia showed highest scores on the SUMD indicating that they were much more compromised on the insight dimension than subjects with psychotic mania or mixed mania. CONCLUSION: Negative rather than affective symptomatology may be a useful construct to differentiate between schizophrenia or schizoaffective disorders from mood-incongruent psychotic mania or mixed mania.     

The incidence of negative symptoms in early schizophrenia, mania and other psychoses

Despite increasing interest in negative symptoms in schizophrenia there has been little work on their incidence in early schizophrenia or in other psychoses. This study examined 79 nondepressive psychotics within 2 years of onset of illness, diagnosed by Research Diagnostic Criteria and assessed for negative symptoms using the Scale for the Assessment of Negative Symptoms. Marked negative symptoms were observed in nearly half of patients diagnosed as suffering definite schizophrenia and were rarely found in other psychoses. Negative symptoms were not significantly correlated with positive symptoms, depression or exposure to neuroleptics, but were correlated with developing extrapyramidal side effects.     

Differentiating primary from secondary negative symptoms in schizophrenia: a study of neuroleptic-naive patients before and after treatment

OBJECTIVE: The study examined the primary versus secondary character of negative symptoms in a group of first-episode, neuroleptic-naive psychotic patients before and after they started neuroleptic treatment. METHOD: Forty-seven inpatients with a first episode of schizophrenia or related psychotic disorders were examined for the presence of negative symptoms, psychosis, depression, and parkinsonism at admission to an inpatient psychiatric unit, before receiving neuroleptics, and at discharge an average 3.3 weeks later, after starting neuroleptic treatment. RESULTS: Although patients' mean scores on measures of positive, negative, and depressive symptoms decreased significantly over the treatment period, the mean rating of nonakinetic parkinsonism worsened. The mean rating of akinetic parkinsonism did not change significantly over the treatment period. Negative symptoms at admission were not predicted by positive or depressive symptoms at admission. Residual negative symptoms at discharge were mainly predicted by negative symptoms at admission (i.e., primary symptoms) and to a negligible degree by residual positive and depressive symptoms. Change in negative symptoms over the observation period was predicted to a marginal degree by change in depressive symptoms. CONCLUSIONS: Negative symptoms rated during a first psychotic episode before and after starting antipsychotic treatment are mainly primary in character and should be considered as a direct manifestation of the basic dysfunctions of schizophrenia.     

Reversed cerebellar asymmetry in men with first-episode schizophrenia.

BACKGROUND: Abnormalities in cerebellar structure and function have been implicated in the pathophysiology of schizophrenia. In this study, we investigated whether patients experiencing first-episode schizophrenia differed from healthy comparison subjects in regional cerebellar volumes or cerebellar asymmetry. METHODS: Volumes of four cerebellar regions (right, left; anterior, posterior) were measured from contiguous coronal magnetic resonance (MR) images in 69 (37 men, 32 women) patients experiencing first-episode schizophrenia and in 49 (27 men, 22 women) healthy comparison subjects. Patients were rated on the Scale for the Assessment of Negative Symptoms and the Schedule for Affective Disorders and Schizophrenia-Psychosis/Disorganization before the initiation of antipsychotic medication and at the time of the MR imaging exam. RESULTS: Patients and healthy comparison subjects did not differ in regional cerebellar volumes, but male patients demonstrated significantly reversed anterior and posterior asymmetry compared with healthy male subjects. Among male patients, greater reversals in a composite measure of cerebellar asymmetry (i.e., torque) correlated significantly with increased negative symptoms before the initiation of antipsychotic medication. CONCLUSIONS: These findings implicate an aberrant neurodevelopmental process involving the metencephalon in the pathophysiology of schizophrenia and are consistent with prior studies implicating abnormal asymmetry in schizophrenia at the neocortical level.     

Spatial selective attention and inhibition in schizophrenia patients during acute psychosis and at 4-month follow-up.

BACKGROUND: Attentional abnormalities may lie at the core of cognitive symptoms in schizophrenia, but it is unclear how they relate to symptoms. The major aim of our study was to understand the relation between spatial attention and clinical symptoms from acute to chronic state. METHODS: Thirty-six acutely psychotic schizophrenia patients and 42 matched control subjects were assessed on three spatial attention measures: target location detection, interference (concurrent inhibition of distractor), and negative priming (subsequent inhibition of distractor). Symptoms were assessed by the Positive and Negative Syndrome Assessment Scale. Four months later, the same subjects were re-tested, and symptoms were re-assessed. RESULTS: Symptoms were significantly reduced at the follow-up. Schizophrenia patients were slower at detecting target location than control subjects, but they improved significantly over time. Schizophrenia patients and control subjects did not differ on the interference task. Negative priming was abolished during acute psychosis, but 4 months later it was restored. Positive symptoms were correlated with reduced negative priming but not with interference, nor with target detection. Negative priming during acute psychosis was significantly correlated with the clinical symptoms at the follow-up. CONCLUSIONS: These results suggest that reduced negative priming may be associated with increased clinical, symptoms especially the positive symptoms.     

Sex differences in concomitant medication with benzodiazepines or antidepressants in first-break schizophrenic patients treated with antipsychotic medication

During a first episode of psychosis, treatment with antipsychotic drugs can improve both positive and negative symptoms. If sufficient amelioration does not occur, adding psychotropic comedication may result in a favorable outcome. To establish sex differences in psychotropic comedication use, we conducted an exploratory retrospective study among first-break patients diagnosed with schizophrenia or schizophreniform disorder. Concerning patient characteristics, no difference in age or antipsychotic drug use was established. At admission, men significantly more often had comorbid substance abuse. Analysis showed that significantly more women than men received benzodiazepines after the onset of psychosis (OR 1.92, 95% CI 1.13-1.27). No sex difference was found in antidepressant comedication (OR 1.22, 95% CI 0.48-3.11). We established a definite sex difference in concomitant benzodiazepine use in first-break patients with schizophrenia. Since women have a better prognosis, we suggest further research to evaluate the efficacy and safety of early benzodiazepine use in the course of schizophrenia. Furthermore, we recommend investigating the possible correlation between benzodiazepine use and substance abuse as a way of treating premorbid symptoms of schizophrenia.     

Gender,premorbid characteristics and negative symptoms in schizophrenia

The interrelationships among gender, premorbid functioning, and negative symptoms were examined in a first-admission inpatient sample with DSM-III-R schizophrenia. Fifty-two subjects were assessed with the Schedule for the Assessment of Negative Symptoms (SANS) at baseline and 6-month follow-up. Three indicators of premorbid functioning were examined: the Premorbid Adjustment Scale, the Quick Test, and the GAF for the best month in the year prior to the baseline interview. Men and women had relatively similar ratings on each of the 5 SANS global subscales at both times; they were also relatively similar on most of the indicators of premorbid functioning. The men and women were categorized into low vs moderate-high negative symptom groups at baseline, and no differences in premorbid functioning were detected. When the sample was classified into those with and without consistent negative symptoms at baseline and 6-month follow-up, the enduring negative men and women had significantly poorer premorbid functioning in several areas than the consistently non-negative patients. Our findings support the importance of assessing negative symptoms longitudinally and suggest that gender is not strongly associated with negative symptoms and premorbid functioning in patients ascertained at early stages of schizophrenia.     

Cognitive functioning and negative symptoms in first episode schizophrenia: Different patterns of correlates

Negative symptoms of schizophrenia have been related to disturbances of executive functions, memory, attention and motor functioning. The executive functions dimension comprises a variety of cognitive subprocesses, including speed of processing, flexibility and working memory. We independently analysed the relationship between different cognitive tasks and clinical symptoms (negative, positive and disorganized) in a sample of 126 first-episode patients with schizophrenia spectrum disorders. Negative symptoms were significantly associated with performance on executive-functions and motor coordination tasks. Within the executive functions domain only those tests that required speeded performance showed a significant association with the negative dimension. The widely described relationship between negative symptoms and executive impairments in schizophrenia appears to be mediated by likely dysfunctions in the speed of processing instead of by working memory impairment.     

Comparison of older patients with bipolar disorder and schizophrenia/schizoaffective disorder.

OBJECTIVE: The aim of this cross-sectional study was to explore differences in measures of symptoms and cognition, side effects, and functional impairment between older patients with schizophrenia and bipolar disorder. METHODS: Representative samples (N = 132) of older patients (age >54 years) with either bipolar disorder or schizophrenia and schizoaffective disorder were compared on several clinical and psychosocial variables. The measures used included the Brief Psychiatric Rating Scale, The Scale for the Assessment of Negative Symptoms, the Geriatric Depression Scale, the Abnormal Involuntary Movement Scale, the Clinical Global Impression, and the Mini-Mental Status Examination. RESULTS: Despite being similar in age (mean age: 68 years), patients with schizophrenia/schizoaffective disorder had significantly greater negative symptoms (Cohen's d = 1.2), a higher clinical global impression of impairment (Cohen's d = 1.16), were less likely to drive (Cohen's d = 0.79), were less likely to be married (Cohen's d = 0.55), and less likely to live independently (Cohen's d = 0.45). CONCLUSION: Although the absolute ratings suggested both diagnostic samples had significant disability, those with schizophrenia and schizoaffective disorder had a greater degree of impairment.     

Gender differences in the relationship of homelessness to symptom severity, substance abuse, and neuroleptic noncompliance in schizophrenia

This study examined gender differences in the relationship of homelessness in schizophrenia to symptom severity, risk behaviors, and prognostic features. Four hundred subjects with schizophrenia were studied: 100 homeless men, 100 homeless women, 100 never homeless men, and 100 never homeless women. Assessments included derivation of five symptom factors by using the Positive and Negative Syndrome Scale (PANSS). Homelessness for the entire sample was associated with greater severity of positive, activation, and autistic preoccupation symptoms, younger age at first hospitalization, and substance abuse (SA). For men only, homelessness was associated with neuroleptic noncompliance (NN). When NN and SA were statistically controlled, symptom severity was not different between the homeless and never homeless. Women, independent of residential status, had more severe negative, activation, and autistic preoccupation symptoms that were not associated with prognostic features or risk behaviors. For both men and women, SA was associated with homelessness, but independent of residence, SA was less severe in women. Additionally, SA was less severe in homeless women than never homeless men. Thus, symptom severity in homeless individuals with schizophrenia appears as an interaction of symptom profiles and risk behaviors that are gender specific. Although cross-sectional analyses cannot distinguish cause from effect, these findings suggest gender-specific routes to homelessness among indigent urban adults with schizophrenia.     

Nonspecific and attenuated negative symptoms in patients at clinical high-risk for schizophrenia

BACKGROUND: Retrospective studies have shown that nonspecific psychopathology and negative symptoms, including social isolation and academic dysfunction, tend to precede onset of psychosis. The present report describes the baseline psychopathology of subjects in the Hillside Recognition and Prevention (RAP) Program, and presents an operationalized classification algorithm for the prospective study of both positive and negative symptoms of clinical high-risk (CHR) for schizophrenia. METHODS: Eighty-two adolescent and young adult patients were characterized using semi-structured interviews of both a parent informant and the patient. The Scale of Prodromal Symptoms (SOPS) was utilized to derive a three-part classification scheme: CHR- subjects (n=20) were defined as having at least one attenuated negative symptom with no positive symptoms; CHR+ subjects (n=42) were defined as having one or more attenuated positive symptoms without psychosis; schizophrenia-like psychosis (SLP) subjects (n=20) were defined as having a psychotic symptom, but without meeting criterion A, B, or C of DSM-IV schizophrenia. RESULTS: Social isolation was the most common presenting symptom. The three RAP subgroups did not significantly differ in levels of attenuated negative and disorganized symptoms, despite the fact that these were not required for inclusion in the CHR+ and SLP groups. Common co-morbid diagnoses included major depression, attention deficit hyperactivity disorder, avoidant personality disorder, and Cluster A personality disorders. CONCLUSIONS: Negative symptoms and other nonspecific behavioral abnormalities represent clinically important phenomena in prodromal patients, and may provide insight into pathophysiologic mechanisms in schizophrenia and possible preventive interventions.     

Familial liability to schizophrenia: a sibling study of negative symptoms

Negative symptoms are important features in schizophrenia, so in milder form they might also serve as indicators of "unexpressed" liability to schizophrenia among patients' adult relatives without schizophrenia. To address this question, we assessed negative symptoms in 39 stable schizophrenia or schizoaffective outpatients, 39 of their siblings, 38 well control probands, and 38 of their siblings. Negative symptom measures included standard behavior ratings of the core negative symptoms of affective flattening and alogia, as well as a self-report measure of social anhedonia. As expected, even stable outpatients with schizophrenia exhibited significantly more negative symptoms than control probands and control siblings. However, negative behavioral symptoms of affective flattening, alogia, and anhedonia did not significantly differentiate the siblings of the schizophrenia patients from the control probands or their siblings, although there were some trends for anhedonia. The findings suggest that core negative symptoms of observed affective flattening and poverty of speech are not likely to be useful as strong indicators of "unexpressed" liability to schizophrenia.     

A family study of sex differences in the diagnosis of atypical schizophrenia

It has been hypothesized that women are more likely than men to have atypical schizophrenia. Among 984 relatives of patients with typical and atypical schizophrenia, the odds of having atypical schizophrenia did not differ by sex.     

Global-local processing in schizophrenia: hemispheric asymmetry and symptom-specific interference.

The hypothesis of atypical functional hemispheric asymmetry in schizophrenia is tested using the directed global-local paradigm, a lateralizing measure of visual perception. Results indicate low error rates (< 2%) for schizophrenia and normal control groups, but longer response times for the schizophrenia group. In the normal group, detection speed of global and local forms did not differ. In contrast, the schizophrenia group responded significantly faster to local relative to global forms, which supports the asymmetry hypotheses of left hemisphere overactivity-right hemisphere underactivity in schizophrenia. The normal group exhibited a global interference effect (slowed response latency to the local target in the presence of a dissimilar global distractor). When the schizophrenia group was examined according to symptom type and severity, high positive symptom severity was associated with local interference (slowed response latency to the global target in the presence of dissimilar local distractors). Negative symptoms were not associated with interference from the competing local or global forms. Patients with a combination of high positive and low negative symptoms showed significantly greater local interference than patients with high negative and low positive symptoms. Interconnected temporal and frontal systems are postulated to contribute to this pattern of perceptual processing efficiency and distractibility in schizophrenia.     

Planum temporale and Heschl gyrus volume reduction in schizophrenia: a magnetic resonance imaging study of first-episode patients

BACKGROUND: Magnetic resonance imaging studies in schizophrenia have revealed abnormalities in temporal lobe structures, including the superior temporal gyrus. More specifically, abnormalities have been reported in the posterior superior temporal gyrus, which includes the Heschl gyrus and planum temporale, the latter being an important substrate for language. However, the specificity of the Heschl gyrus and planum temporale structural abnormalities to schizophrenia vs affective psychosis, and the possible confounding roles of chronic morbidity and neuroleptic treatment, remain unclear. METHODS: Magnetic resonance images were acquired using a 1.5-T magnet from 20 first-episode (at first hospitalization) patients with schizophrenia (mean age, 27.3 years), 24 first-episode patients with manic psychosis (mean age, 23.6 years), and 22 controls (mean age, 24.5 years). There was no significant difference in age for the 3 groups. All brain images were uniformly aligned and then reformatted and resampled to yield isotropic voxels. RESULTS: Gray matter volume of the left planum temporale differed among the 3 groups. The patients with schizophrenia had significantly smaller left planum temporale volume than controls (20.0%) and patients with mania (20.0%). Heschl gyrus gray matter volume (left and right) was also reduced in patients with schizophrenia compared with controls (13.1%) and patients with bipolar mania (16.8%). CONCLUSIONS: Compared with controls and patients with bipolar manic psychosis, patients with first-episode schizophrenia showed left planum temporale gray matter volume reduction and bilateral Heschl gyrus gray matter volume reduction. These findings are similar to those reported in patients with chronic schizophrenia and suggest that such abnormalities are present at first episode and are specific to schizophrenia.