Non-genomic action of steroids in the nervous system

Past research on the importance of 'soft' neurological signs in schizophrenia has often not examined the relationship between specific groups of neurological signs and different dimensions of schizophrenia psychopathology. Gender differences in the reported relationships have never been explored. In this paper we describe a study of 100 DSM-III-R (65 male and 35 female) schizophrenic patients who were rated for neurological 'soft signs' with the Neurological Evaluation Scale (NES) (1), and for schizophrenic symptomatology with the Scale for Assessment of Negative Symptoms (SANS) and the Scale for Assessment of Positive Symptoms (SAPS). Following a factor analysis of NES items, differential relationships were examined between the five derived NES factors and three well-established dimensions of schizophrenic symptomatology, namely psychomotor poverty, disorganization and reality distortion. Our results failed to show any relationship between NES dimensions and either the reality distortion or disorganization dimensions. There was a modest but differentially significant relationship between psychomotor poverty and an extrapyramidal factor on the NES. This relationship was shown only by male subjects, and was influenced by duration of illness but not by age or neuroleptic medication. On the other hand, female subjects showed a significant relationship between psychomotor poverty and an NES factor reflecting attention and initiative, and between reality distortion and coordination/sequencing of motor activity. These relationships in female subjects were, relative to relationships for male subjects, more independent of the effect of medication and duration of illness.     

Occurrence and clinical correlates of psychiatric comorbidity in patients with psychotic disorders

BACKGROUND: The aim of this study was to explore patterns and clinical correlates of psychiatric comorbidity in patients with schizophrenia spectrum disorders and mood spectrum disorders with psychotic features. METHOD: Ninety-six consecutively hospitalized patients with current psychotic symptoms were recruited and included in this study. Index episode psychotic diagnosis and psychiatric comorbidity were assessed using the Structured Clinical Interview for DSM-III-R-Patient Version (SCID-P). Psychopathology was assessed by the SCID-P, Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, and Hopkins Symptom Checklist. Awareness of illness was assessed with the Scale to Assess Unawareness of Mental Disorders. RESULTS: The total lifetime prevalence of psychiatric comorbidity in the entire cohort was 57.3% (58.1% in schizophrenia spectrum disorders and 56.9% in mood spectrum psychoses). Overall, panic disorder (24%), obsessive-compulsive disorder (24%), social phobia (17.7%), substance abuse (11.5%), alcohol abuse (10.4%), and simple phobia (7.3%) were the most frequent comorbidities. Within the group of mood spectrum disorders, negative symptoms were found to be more frequent among patients with psychiatric comorbidity than among those without comorbidity, while such a difference was not detected within the group of schizophrenia spectrum disorders. Social phobia, substance abuse disorder, and panic disorder comorbidity showed the greatest association with psychotic features. An association between earlier age at first hospitalization and comorbidity was found only in patients with unipolar psychotic depression. Patient self-reported psychopathology was more severe in schizophrenia spectrum patients with comorbidity than in those without, while such a difference was less pronounced in mood spectrum psychoses. CONCLUSION: These findings suggest that psychiatric comorbidity is a relevant phenomenon in psychoses and is likely to negatively affect the phenomenology of psychotic illness. Further studies in larger psychotic populations are needed to gain more insight into the clinical and therapeutic implications of psychiatric comorbidity in psychoses.     

Neurocognitive abnormalities during comprehension of real-world goal-directed behaviors in schizophrenia.

Origins of impaired adaptive functioning in schizophrenia remain poorly understood. Behavioral disorganization may arise from an abnormal reliance on common combinations between concepts stored in semantic memory. Avolition–apathy may be related to deficits in using goal-related requirements to flexibly plan behavior. The authors recorded event-related potentials (ERPs) in 16 patients with medicated schizophrenia and 16 healthy controls in a novel video paradigm presenting congruous or incongruous objects in real-world activities. All incongruous objects were contextually inappropriate, but the incongruous scenes varied in comprehensibility. Psychopathology was assessed with the Scales for the Assessment of Positive and Negative Symptoms (SAPS/SANS) and the Brief Psychiatric Rating Scale. In patients, an N400 ERP, thought to index activity in semantic memory, was abnormally enhanced to less comprehensible incongruous scenes, and larger N400 priming was associated with disorganization severity. A P600 ERP, which may index flexible object–action integration based on goal-related requirements, was abnormally attenuated in patients, and its smaller magnitude was associated with the SANS rating of impersistence at work or school (goal-directed behavior). Thus, distinct neurocognitive abnormalities may underlie disorganization and goal-directed behavior deficits in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identifying subtypes of schizophrenia by cluster analyses

The existence of two subtypes of schizophrenia (positive and negative) is well established. The evidence in favor of other subtypes, particularly a disorganized subtype, is still the subject of some debate. The aim of the study reported in this article is to investigate the possibility of further subtypes of schizophrenia by applying a particular method of cluster analysis to a particular set of data. Ward's method of cluster analysis was applied to the Positive and Negative syndrome Scale (PANSS) scores of 138 patients, defined as having schizophrenia by one of four diagnostic criteria. The validity of the cluster solution was assessed both by examining differences between clusters on a number of clinical characteristics recorded for each patient and by comparing the results obtained from the PANSS with those derived from a cluster analysis using two other instruments (the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms). Results from the cluster analysis suggest the existence of at least four subtypes of schizophrenia: positive, negative, mixed, and disorganized. A fifth subtype includes patients with few symptoms, suggesting the simple schizophrenia named by Bleuler. Evidence for the validity of these subtypes was provided by the differences observed between the clusters on a number of clinical characteristics and by the similarity of the cluster solution obtained from the different instruments. In conclusion, the negative-positive dichotomy in schizophrenia is an oversimplification, and the existence of a more complex structure needs to be taken into account in future research.     

Aspects of dysphoria and symptoms of schizophrenia

BACKGROUND: In the past it has been postulated that dysphoric emotions may be related to positive and/or negative symptoms in schizophrenia. The results of several recent studies have suggested that composite dysphoria indices are more strongly related to positive than negative symptoms. In the current study we use part correlation techniques to examine the possible unique contributions of two aspects of dysphoria--depression and anxiety--to three syndromes of symptoms (reality distortion, disorganization and psychomotor poverty) within schizophrenia. METHODS: Data were obtained from 60 patients with a DSM-III-R diagnosis of schizophrenia. Symptoms of schizophrenia were assessed using the SAPS and SANS and dysphoria was assessed using both self-report (BDI and BAI) and observer ratings (HRSD and HARS). Assessment of schizophrenia symptoms and ratings of depression and anxiety were completed by different observers. In addition, drug induced extrapyramidal side effects were rated. RESULTS: Part correlations showed that unique aspects of anxiety (particularly physiological arousal) were correlated with reality distortion while unique aspects of depression (including psychomotor slowing and loss of social interest) were related to psychomotor poverty. At least part of the latter relationship may be due to extrapyramidal side effects of neuroleptic medication. CONCLUSIONS: Although there is considerable overlap between anxiety and depression, it appears that the unique arousing or activating aspects of anxiety are related to the experience of reality distortion symptoms in schizophrenia and the unique slowing and withdrawal aspects of depression are particularly related to psychomotor poverty. Possible reasons for these relationships are discussed.     

Factor structure and construct validity of the Scale for the Assessment of Negative Symptoms.

Confirmatory factor analysis (CFA) was used to examine the underlying structure of the negative symptoms of schizophrenia as measured by the Scale for the Assessment of Negative Symptoms (SANS). Schizophrenia patients (N?=?457) were assessed with the SANS on at least 1 of 2 occasions: (a) 2–4 weeks after an index hospitalization, and (b) after a clinical stabilization period that lasted 3–6 months. Results of an exploratory factor analysis conducted for the first assessment (n?=?401) were largely supported by the CFAs conducted on the data at the second assessment (n?=?345). The CFA solution included 3 factors: Diminished Expression, Inattention-Alogia, and Social Amotivation. Analysis of patients' clinical characteristics, treatment outcome, chronicity of the illness, premorbid history, and social adjustment supported the validity of the 3 factors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The relationship of catatonia symptoms to symptoms of schizophrenia

OBJECTIVE: To evaluate the relationships of symptoms of catatonic schizophrenia to 77 symptoms relevant for diagnosing schizophrenia and to socioanamnestic variables. METHOD: Data from a sample of 112 Canadian patients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) were evaluated via phi correlation coefficients. RESULTS: Forty-five (40.2%) of our 112 patients had catatonic symptoms, either at the time of this study or in the past. However, only weak correlations (phi < 0.31) to other symptoms relevant for diagnosing schizophrenia were found, and no significant correlations to socioanamnestic variables were found. CONCLUSION: Symptoms of catatonia appear to be independent of the key symptoms of schizophrenia.     

Elevation of CSF somatostatin concentrations in mania

OBJECTIVE: The aim of this study was to compare levels of CSF somatostatin (somatotropin release-inhibiting factor) in drug-free patients with different major psychiatric disorders. METHOD: CSF somatostatin concentrations were measured in 66 drug-free inpatients with Research Diagnostic Criteria diagnoses of schizophrenia, major depressive disorder, manic disorder, or schizoaffective disorder. RESULTS: In comparison with both the patients with schizophrenia and the patients with schizoaffective disorder, the manic patients had markedly elevated CSF somatostatin concentrations. The depressed patients had significantly higher levels than the schizophrenic patients. CONCLUSIONS: Mania is associated with relatively higher CSF somatostatin concentrations.     

Therapeutic implications of microglia activation by lipopolysaccharide and reactive oxygen species generation in septic shock and central nervous system pathologies: a review

OBJECTIVE: Olanzapine, a potent 5-HT2a/2c, dopamine D1D2D4 antagonist with anticholinergic activity, has a profile of known receptor affinity similar to that of clozapine. This pilot study examined the efficacy of olanzapine for treatment-refractory childhood-onset schizophrenia in eight patients who had received 8-week open-label trials. For comparison, data are included from 15 patients who had received 6-week open-label clozapine trials using identical rating instruments (largely by the same raters) in the same treatment setting. METHOD: Twenty-three children and adolescents with an onset of DSM-III-R schizophrenia by age 12 for whom at least two different typical neuroleptics had been ineffective participated in the two separate studies. Some of the patients were intolerant of clozapine, although it had been effective (n = 4). Patients receiving olanzapine were evaluated over 8 weeks with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impressions Scale for Improvement. RESULTS: For the eight patients who received olanzapine trials, at week 8 there was a 17% improvement in the BPRS total score, a 27% improvement in the Scale for the Assessment of Negative Symptoms, and a 1% improvement in the Scale for the Assessment of Positive Symptoms, relative to "ideal" admission status on typical neuroleptics. In contrast, the magnitude of the effect sizes for each of the clinical ratings was larger at week 6 of the previous clozapine trial than for an 8-week olanzapine trial, relative to admission status on typical neuroleptics. For the four children who had received both clozapine and olanzapine, BPRS total scores were significantly lower at week 6 of clozapine treatment compared with week 6 of olanzapine treatment (p = .03). CONCLUSION: These data provide preliminary evidence for the efficacy of olanzapine for some children and adolescents with treatment-refractory schizophrenia, but they also suggest the need for a more rigorous double-blind comparison of these two atypical antipsychotics.     

Follow-up and family study of postpartum psychoses. Part I: Overview

A group of 119 patients suffering from a severe psychiatric postpartum disorder who were admitted for the first time in their life to a psychiatric hospital has been investigated. The onset of illness occurred within 3 months following delivery. The patients represented 92% of the total sample fulfilling the inclusion criteria. A follow-up investigation was performed after a mean of 21 years (range 2-35 years). Of the patients 66% had nonpuerperal psychotic episodes in later life. The diagnosis, taking into account the long-term course, was affective psychosis in 57%, schizoaffective psychosis in 18%, schizophreniform psychosis in 12%, brief reactive psychosis in 4% and schizophrenia in 9%. A bipolar psychosis was found in 31%. The relation of unipolar to bipolar psychoses corresponded to that in a control group of affectively ill women without puerperal onset. The frequency of a manic syndrome in bipolar psychoses at the index episode was the same as in nonpuerperal episodes, which does not suggest a mania-provoking pathoplastic effect of the puerperium. The comparison with female nonpuerperal controls matched for age and diagnosis revealed evidence of a better long-term course in the index patients. The risk of a puerperal relapse for further pregnancies was 35%. The global morbidity risk for functional psychoses in first-degree relatives was 11%, with affective psychoses representing the majority of secondary cases (6.8%). The index patients showed a nonsignificant lower morbidity risk in relatives than a control group of psychotically ill women without puerperal onset. The major aetiological factor found for postpartum psychoses is the relation of these disorders to functional psychoses. There is strong evidence that the postpartum period tends to provoke affective psychoses and other nonschizophrenic psychoses, but not, or only to a lesser degree, narrowly defined schizophrenias. The liability to puerperal decompensations suggests some common pathophysiological mechanism, the nature of which remains unknown.     

Central effects of acamprosate: part 1. Acamprosate blocks the glutamate increase in the nucleus accumbens microdialysate in ethanol withdrawn rats

BACKGROUND: The factor structure of four competing models of positive symptoms and their clinical validity was studied in a sample of 253 schizophrenia inpatients. METHODS: The following models were tested using confirmatory factor analysis: a one-dimension severity model, a two-dimension model comprising a psychosis factor and a disorganization factor, a four-dimension model based on the Scale for the Assessment of Positive Symptoms (SAPS) structure in subscales, and a five-dimension model derived from the previous one by further differentiating Schneiderian delusions from non-Schneiderian ones. RESULTS: More complex multifactorial models fit the data better than simpler models. The five-dimension model was the best adjusted (goodness of fit index = .844, nonnormed fit index = .812, normed fit index = .728). Whereas the one-dimension model did not display significant association with the clinical variables, multidimensional models were related to age at onset and illness severity. The two-dimension model captured well the clinical correlates of the more complex models. CONCLUSION: None of the tested models showed good fit to the data. The one-dimension model displayed both poor factor validity and poor external validity; therefore, research relying on the SAPS total score may reach misleading conclusions.     

The role of high- and low-dose corticotropin tests in the diagnosis of secondary adrenal insufficiency

Mini Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS) and subscales of the BPRS were performed on 73 elderly inpatients (mean age: 67.9 years; standard deviation: 7.2; range: 60-89) diagnosed with DSM-III-R chronic schizophrenia. Forty of the subjects were men and 33 were women. A significant negative correlation was observed between MMSE and the age, factor negative, factor depressive, and total score of BPRS. We believe, however, that it is relatively sufficient to screen for demented illness of schizophrenics using MMSE when considering the age and the psychiatric symptoms (especially negative or depressive symptoms ). Forty-eight (66%) of the 73 patients were categorized as 'demented' by MMSE. These results suggest that the aged inpatients with schizophrenia in a hospital showed certain kinds of cognitive deficits (including senile dementia) more frequently than the general population.     

Stability in schizophrenia symptoms over time: Findings from the Mount Sinai Pilgrim Psychiatric Center Longitudinal Study.

This study examined the stability of symptoms of schizophrenia over time, focusing on the stability of symptom structure. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). The sample consisted of 215 chronic patients followed up for as long as 4 years. Exploratory factor analysis identified 6 factors. Several statistical techniques were used to examine the stability of these symptoms, including longitudinal confirmatory factor analysis. Low-to-moderate rank-order stability and high absolute stability of the factors were found, with the structure of the PANSS-assessed symptoms consistent over time. The results demonstrate that despite changes in the severity of symptoms in individual patients with schizophrenia, the factor structure and interrelatedness of symptoms have considerable stability over time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The onset of schizophrenia

This survey deals with findings and results of systematic clinical-psychiatric and -psychological studies of the true onset of schizophrenia and its significance. Many symptoms precede the psychotic onset of schizophrenia. These have been described by Huber as 'basic symptoms', who developed the concept of basic stages and basic symptoms gradually since the 1950's. The basic symptoms are experiential and not behavioral in kind and only recognizable by the self-reports of the patients. They are rateable using a structural scale (Bonn Schedule for the Assessment of Basic Symptoms: BSABS) described below. They form the two precursor syndromes: (1) prodromes lead on average within 3.3 years to a psychotic episode; and (2) outpost syndromes that are completely remitting on average within 5 months and precede the first psychotic episode on average 10 years. Basic symptoms can be further divided into level 1 (non-specific) and level 2 (characteristic) basic symptoms. Basic symptoms, positive and negative symptoms have to be differentiated; they also develop in this chronological sequence: first non-specific, then characteristic basic symptoms, followed on average many years later by positive symptoms, and, finally by negative symptoms. Structured ratings of the basic symptoms and their recognition in the precursor syndromes enables physicians to detect early symptoms of a schizophrenic illness that, if treated at this stage, can lead to a better long-term outcome.     

Slow-wave sleep and symptomatology in schizophrenia and related psychotic disorders

Deficits in slow-wave sleep (SWS), or delta sleep, are frequently seen in schizophrenia, but their relationship with schizophrenic symptomatology remains unclear. We examined the association between visually scored and automated measures of SWS and positive and negative symptoms in a series of unmedicated patients with schizophrenia and related psychotic disorders. Total and average automated delta wave counts were significantly inversely associated with negative symptoms overall, and the psychomotor poverty syndrome in particular. Total delta counts were also inversely related to the disorganization syndrome. No relation was seen between reality distortion or the Brief Psychiatric Rating Scale (BPRS) positive symptoms and SWS. These findings support the view that SWS deficits may be related to negative symptoms of schizophrenia and may perhaps be mediated by impaired functioning of frontothalamic neural circuits.     

Emotional valence and reference disturbance in schizophrenia.

The authors examined the impact of emotional valence on reference disturbance in patients with schizophrenia and identified factors that moderate individual differences in this relationship. Thirty-nine patients with schizophrenia were given an interview that elicited speech samples in response to 10 neutral and 6 negatively valenced emotional questions. Speech samples were analyzed using the Communication Disturbances Index (N. M. Docherty, M. DeRosa, & N. C. Andreasen, 1996). Participants were also assessed with the Positive and Negative Symptom Scale (S. Kay, 1991) and a single-trial Stroop task (Stroop, 1935). Group analyses indicated that negative questions elicited more unclear references than neutral questions. Both the severity of disorganization symptoms and selective attention deficits predicted increased reference errors in response to emotional questions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Schizophrenic psychoses and the CNTF null mutation

Genetic susceptibility plays an important role in the development of schizophrenic psychoses, and the neural maldevelopment hypothesis is suggested by neuropathological and neuroimaging findings. We investigated the association between a null mutation in the ciliary neurotrophic factor (CNTF) gene and functional psychoses including schizophrenia and schizoaffective disorder. The frequency of mutant allele was significantly increased in patients with schizoaffective disorder, but not in those with schizophrenia in comparison with controls. The CNTF null mutation resulting in CNTF deficiency may confer potential susceptibility to schizoaffective disorder.     

A study of "atypical schizophrenia". Comparison with schizophrenia and affective disorder by sex, age of admission, precipitant, outcome, and family history

Eighty-five cases of atypical schizophrenia were compared with 200 of schizophrenia, 100 of bipolar (mania), and 225 of unipolar (depression) affective disorder. Comparisons were made on the basis of sex, age at admission, precipitating factors, outcome, and a family history of schizophrenia or of affective disorder. The atypical schizophrenia differed remarkably from the schizophrenia and most closely resembled the bipolar affective disorder when allowance was made for a younger age at onset and a higher frequency of precipitants. An analysis of symptoms verified the predominance of schizophrenic features in the atypical schizophrenia, but also showed a high percentage (80%) of patients who had one or more manic symptoms at index admission. It is concluded that great care should be taken in diagnosing schizophrenia in a patient who also has manic symptoms.     

Predictors of relationship functioning for patients with bipolar disorder and their partners.

Previous investigations have examined family functioning, including marital functioning, as an important predictor of the course of bipolar disorder, but limited research exists identifying the factors that influence relationship functioning in patients with bipolar disorder. In the current study, 56 patients with bipolar disorder and their partners were assessed for Axis II pathology, general family functioning, and relationship distress. Patient mood symptoms and Axis II pathology variables were examined as predictors of general relationship functioning (Family Assessment Device, McMaster Clinical Rating Scale, and Dyadic Adjustment Scale) in regression models. Analyses indicated that patients' depressive symptomatology was associated with patient ratings of general family functioning and couple functioning, while patients' manic symptoms were associated with partners' ratings of the romantic relationship. Partners' total Axis II pathology, but not patients' Axis II pathology, was associated with patient and partner perception of the couple's relationship. These findings highlight the importance of mood and personality pathology to relationship functioning, and represent one of the first investigations to verify the impact of personality pathology on patients' and partners' perceptions of relationship functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)