Pseudohypoparathyroidism with osteitis fibrosa cystica: direct demonstration of skeletal responsiveness to parathyroid hormone in cells cultured from bone

The role of aberrant neurodevelopment in the etiology of schizophrenia is reviewed in light of recent neuropathologic, neurochemical, and neuroimaging evidence of cerebral abnormalities in schizophrenic patients. There may exist some genetic defect in the control of brain development. Clinical epidemiologic surveys highlight the importance of obstetric complications, and prenatal exposure to influenza epidemics in contributing to these abnormalities. It is suggested that such environmental hazards and aberrations in the control of early brain development produce the neuronal phenotype that manifests as schizophrenia with early age of onset of symptoms associated with soft neurologic signs and is more common in young males.     

First-contact rate for schizophrenia in community psychiatric care. Consideration of the oestrogen hypothesis

The study deals with the incidence of schizophrenia in Finland. All patients aged 15 years and over who during 1 year for the first time in their life contacted any psychiatric treatment unit in six health care districts (catchment areas), with a total population of 1.1 million people, and suffered from schizophrenia as defined by the DSM-III (schizophrenic and schizophreniform disorders) or ICD-8 classifications were studied and followed for 5 years. A total of 186 DSM-III and 158 ICD-8 schizophrenia patients were registered. The incidence rate of DSM-III schizophrenia was 17 per 100,000 total population and that for ICD-8 schizophrenia 14 per 100,000. The incidence rates for individuals aged 22-34 years, singles and those with low education were higher than average, but there were no gender differences. The comprehensiveness of the psychiatric services may explain why the age distributions were similar for both genders and why the mean age of patients at their first psychiatric contact was lower than in many other studies dealing with hospitalized patients. The patients' age at first psychiatric contact did not support the view that oestrogens specifically delay the onset of schizophrenia in women. There is some evidence, however, that oestrogens as antidopaminergic agents may protect women from psychotic disorders in general and that the reduction in oestrogen production may explain why at menopause and afterwards admissions for psychotic disorders for women increase more than for men.     

Impairment of the semantic network in schizophrenia

It is well established that patients with schizophrenia display a variety of language impairments. Despite considerable research, however, the underlying mechanisms of the language deficits in schizophrenia remain unclear. Representations of semantic networks of 56 patients with schizophrenia and 28 normal comparison (NC) subjects of similar ages and educational levels were generated by multidimensional scaling and Pathfinder analyses of their responses on the Animal Fluency Test. On the basis of traditional scoring techniques (i.e., total number of correct animal names generated in 60 s), all patients performed significantly worse than the NC subjects. More detailed analyses of the underlying semantic networks revealed that performance in the patients varied according to age of onset and subtype of schizophrenia. The semantic network of patients with late-onset schizophrenia (i.e., with onset after age 45) was virtually identical to that of the NC group. In contrast, the semantic network of patients with a younger age of onset was disorganized and differed significantly from that of the NC subjects. Findings demonstrated that patients with nonparanoid subtypes displayed greater disorganization in their semantic networks than patients with a paranoid subtype. Although general fluency impairments (e.g., difficulties in initiation, retrieval, and search mechanisms) may be sensitive to schizophrenia, per se, specific deficits in the structure of semantic knowledge may be associated with certain characteristics of individual patients with schizophrenia, such as an earlier age of onset and nonparanoid subtype.     

Spontaneous abnormal involuntary movements in first-episode schizophrenia and schizophreniform disorder: baseline rate in a group of patients from an Irish catchment area

OBJECTIVE: This study investigated the rate of spontaneous abnormal involuntary movements in a group of patients presenting with a first episode of schizophrenia or schizophreniform psychosis. METHOD: Seventy-nine patients with a first episode of schizophrenia or schizophreniform psychosis who presented to a catchment area psychiatric service over a 3-year period, and who were neuroleptic-naive or had been medicated for less than 1 month, were examined for the presence of involuntary movements with use of the Abnormal Involuntary Movement Scale. RESULTS: Six patients (7.6%) had spontaneous dyskinesia as defined by the criteria of Schooler and Kane, and nine other patients had mild orofacial involuntary movements. The patients with spontaneous dyskinesia had completed significantly fewer years of education than the patients without dyskinesia. Spontaneous involuntary movements were unrelated to age at presentation for treatment. CONCLUSIONS: Spontaneous abnormal involuntary movements were evident among a proportion of patients with first-episode schizophrenia or schizophreniform psychosis at baseline presentation and were associated with reduced educational attainment. This finding supports previous suggestions that abnormal involuntary movements in schizophrenia may be related to the pathophysiology of the illness and therefore cannot be attributed entirely to the adverse effects of neuroleptic medication.     

Month of birth and schizophrenia in Taiwan: effect of gender, family history and age at onset

Schizophrenic patients have been shown to have a moderate excess of winter births in the areas where seasonal variations in weather are large. In this report, we examined the seasonality of schizophrenic births in Taiwan, which has a subtropical climate. Using nationwide hospitalization data (2429 male and 1320 female schizophrenic patients), we applied the life table method to compare the risk of schizophrenia among 12 cohorts of month-of-birth for males and females, respectively. Differences among the risks of the 12 cohorts were tested using the logrank test. The samples were further stratified by family history and age at onset. There was a significant association between the risk of being admitted as a schizophrenic and month of birth for both males and females. The cohorts born in November and January had the highest risks. After stratification, the association was significant only for non-familial, male, and early onset schizophrenic patients. The results indicate that seasonally varying factors might increase the risk of schizophrenia, especially in those without a family history of the disease. Men are more vulnerable to such factors than women, and the schizophrenics resulting from such insults tend to be early onset.     

Negative metabolic effects of cyclic GMP in quiescent cardiomyocytes are not related to L-type calcium channel activity

Evidence of immune system abnormalities in adult schizophrenia has prompted examination of the human leukocyte antigen (HLA) system. Childhood onset schizophrenia offers a unique opportunity to test neurodevelopmental hypotheses of schizophrenia, including those which implicate components of the immune system. In the present study, class I and II HLA antigens were typed using sequence-specific primers and the polymerase chain reaction in 28 childhood onset schizophrenics and 51 ethnically matched healthy subjects. Groups were compared for frequencies of HLA antigens reported to be associated with schizophrenia and/or autoimmune disorders. We hypothesized that antigen frequencies would differ between schizophrenic and healthy children, suggesting that some dimension of the neurodevelopmental disturbance experienced by these children may be mediated by subtle abnormalities of immune function. There were no significant differences between schizophrenic and healthy subjects in the frequency of any antigen tested. These findings do not support HLA-associated pathology in childhood onset schizophrenia.     

Nondementia nonpraecox dementia praecox? Late-onset schizophrenia

Schizophrenia has traditionally been viewed as a psychotic disorder with onset in adolescence or early adulthood and a deteriorating course. Over the past decade, the authors have been studying patients meeting DSM-III-R as well as specified research criteria for late-onset schizophrenia (onset after age 45) and several comparison groups with psychiatric, neurologic, neuropsychologic, brain-imaging, psychophysiological, and psychosocial assessments. Results to date suggest a number of similarities and differences between late-onset schizophrenia and comparison groups of other older patients with psychoses (including earlier-onset schizophrenia). Later-onset schizophrenia is probably a neurobiologically distinct subtype of schizophrenia. Differential involvement of cortico-striato-pallido-thalamic circuitry may explain differences in age at onset. The authors propose a new conceptual model for level of functioning at different stages of life in late-onset schizophrenia.     

Obstetric complications and age at onset in schizophrenia: an international collaborative meta-analysis of individual patient data

OBJECTIVE: An excess of obstetric complications in the histories of schizophrenic patients is a well-replicated finding, but less consistent results have been found concerning the relationships between obstetric complications and family history of schizophrenia, age at onset of schizophrenia, and gender. Small sample size limited the power of previous studies that attempted to assess such relationships. The aim of this study was to use data on individual patients from all available studies to examine the links between a history of obstetric complications and family history of schizophrenia, age at onset, and gender. METHOD: Raw data from 854 schizophrenic patients concerning history of obstetric complications rated according to the Lewis and Murray scale were obtained from 11 different research groups. Weighted average estimates were calculated with the use of regression techniques. RESULTS: A significant association was found between age at onset of schizophrenia and obstetric complications: the earlier the age at onset, the more likely the history of obstetric complications. Subjects with onset of schizophrenia before age 22 were 2.7 times more likely than those with onset at a later age to have had a history of abnormal presentation at birth and 10 times more likely to have had a history of complicated Cesarean birth. No association was found between obstetric complications and family history of schizophrenia or gender. CONCLUSIONS: The association between obstetric complications and early age at onset of schizophrenia indicates that the pathophysiology of early-onset schizophrenia involves neurodevelopmental impairment.     

Age-related practice effects across longitudinal neuropsychological assessments in older people with schizophrenia.

Objective: The relationship between aging and practice effects on longitudinal neuropsychological assessments was investigated in middle-aged and older people with schizophrenia and healthy controls. Method: Older people with schizophrenia (n = 107; M age = 56.1) and age-comparable nonpsychiatric controls (n = 107; M age = 57.7) were scheduled to receive annual assessments on a comprehensive battery of neuropsychological tests for an average of 2.5 years (range 11 months to 4 years). Mixed-model analyses were used to separately examine the effects of practice and age on test performance. Results: Number of prior assessments (practice) was associated with significant performance improvement across assessments, whereas older age was associated with significant decline in performance. The groups did not differ significantly in extent of age-related cognitive decline, but a three-way interaction among group, age, and practice was found, such that greater age-related decline in practice effects were found for older people with schizophrenia relative to nonpsychiatric participants. Conclusions: This study did not find any evidence of neurodegenerative age-related decline in neuropsychological abilities in middle-aged and older people with schizophrenia, but older age was associated with diminished ability to benefit from repeated exposure to cognitive tasks in people with schizophrenia. Cognitive impairment in schizophrenia may combine with cognitive decline associated with normal aging to reduce practice effects in older patients. These findings have important implications for the design of studies examining the longitudinal trajectory of cognitive functioning across the life span of people with schizophrenia, as well as clinical trials that attempt to demonstrate cognitive enhancement in these individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of gender differences in the reduction of etiologic heterogeneity in schizophrenia

Recent research has shown a resurgence of interest in the study of gender differences in schizophrenia. Accumulated evidence suggests that, compared with women, men have a higher incidence of schizophrenia, earlier age of onset, poorer course and medication response, poorer premorbid social and intellectual functioning, fewer affective symptoms, lower family morbid risk of schizophrenia and affective disorders, more evidence of obstetric complications in their mothers, and greater structural brain abnormalities. The roles of estrogen, neurodevelopment, and family history of affective disorder are evaluated as co-contributors to the observed gender differences in schizophrenia. Particular emphasis is given to evaluating the hypothesis that men are more prone to a hypothesized poor-prognosis, neurodevelopmental subtype of schizophrenia, for which early environmental brain insults play an important etiologic role, whereas women may be more prone to a hypothesized good-prognosis, affective subtype that is genetically related to the affective disorders. This hypothesis is evaluated in terms of (a) its ability to account for gender differences in schizophrenia, (b) its ability to link differences in clinical presentation to proposed differences in etiology; and (c) its potential to generate testable predictions for future schizophrenia research.     

Systematic screening of the LDL-PLA2 gene for polymorphic variants and case-control analysis in schizophrenia

Systematic scans of the genome using microsatellite markers have identified chromosome 6p21.1 as a putative locus for schizophrenia in multiply affected families. There is also evidence from a series of studies for a role of abnormal phospholipid metabolism in schizophrenia. In light of these findings, and the role of platelet activating factor in neurotransmission and neurodevelopment, we have examined the LDL-PLA2 (plasma PAF acetylhydrolase, PAF-AH) gene, a serine dependent phospholipase that has been mapped by hybrid mapping to chromosome 6p21.1, as a positional candidate gene for schizophrenia. The gene was systematically screened using SSCP/HD analysis for polymorphisms associated with the disease. Four polymorphic variants were found within the gene and studied in a group of 200 schizophrenic patients and 100 controls. The variant in exon 7 (Iso195Thr) was found to be weakly associated with schizophrenia (p = 0.04) and the variant in exon 11 (Val379Ala) almost reached significance (p = 0.057). After correcting for multiple testing no significant associations were detected. Haplotype analysis combining pairs of polymorphisms also provided no evidence for association of this gene with schizophrenia in our sample of patients.     

Torque and schizophrenic vulnerability.

Counterclockwise spiraling, or left-turning, in structure and behavior is more frequently found in living organisms than is dextro- or right-turning. Children achieving well socially and academically during the developmental years draw circles in a counterclockwise direction with either hand. Left-handed children and children having social and academic difficulties more frequently show mixed left-circling and right-circling behavior. The tendency to circle in a clockwise direction has been called torque. A hypothesis is developed suggesting that children who demonstrate torque during the developmental years are exhibiting an external manifestation of a neural integrative defect in the corpus callosum. The resulting confusion of mixed cerebral dominance interferes with the child's acquiring important cognitive, language, and social skills. It is proposed that children who show torque are more vulnerable to the development of schizophrenia at maturity. At an average age of just under 10 yrs (115.5 mo), 54 children who demonstrated no torque and 52 children who showed torque were evaluated for emotional adjustment a decade later. Based on reports of parents and guardians, with Ss at an average age of 21 yrs, results show that 11 of the Ss who had exhibited torque had in the interim been diagnosed as schizophrenic. One of the no-torque group had received this diagnosis. Limitations of the study and possibilities for furture research are discussed. (71 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lucigenin as a substrate of microsomal NAD(P)H-oxidoreductases

In various genetic disorders it has been observed that the severity of illness increases and the age at onset decreases in successive generations. This phenomenon is termed anticipation. We sampled 15 families, totalling 123 individuals with at least one person affected by a disease of the schizophrenia spectrum in the index generation in each family (IG; n = 33 affected out of a total of 67 individuals) and in the parental generation (PG; n = 16 affected out of a total of 56 individuals). The pedigrees had originally been identified for linkage studies in schizophrenia. We found a significant difference between IG and PG regarding severity of illness as defined by Kendler et al's hierarchical model of categories of the schizophrenia spectrum (p = 0.001). Age at onset was significantly earlier in the IG (21.6 +/- 6.6 years) than in the PG (40.2 +/- 9.2 years) (p = 0.0001). We excluded a potential birth cohort effect by investigating a control sample consisting of two non-overlapping birth cohorts of patients with schizophrenia. Age at onset between the two groups of the control sample did not differ. Anticipation is an important aspect in the investigation of a possible genetic basis, at least for the familial form of schizophrenia. Active research on a molecular level with special emphasis on trinucleotide repeats might be able to shed further light on this phenomenon.     

HIV risk behaviour and HIV testing of psychiatric patients in Melbourne

OBJECTIVES: Patients with chronic mental illnesses constitute an important risk group for HIV infection overseas. This study aimed to determine the prevalence of risk behaviours associated with HIV transmission and factors associated with HIV testing in psychiatric patients in Melbourne. METHODS: Inpatients and outpatients completed an interviewer-administered questionnaire which covered demographics, psychiatric diagnosis, risk behaviour, and HIV education and testing. RESULTS: Of 145 participants, 60% were male and 55.2% had schizophrenia. Injecting drug use (IDU) was reported by 15.9%, a figure approximately 10 times that found in other population surveys. Most patients reported sex in the last decade and over 20% had multiple sexual partners in the last year. Of males, 12.6% reported sex with another male (9.2% anal sex); 19.0% of females reported sex with a bisexual male. Nearly half of the males reported sex with a prostitute, 2.5 times that in a population sample. Only 15.9% reported ever having someone talk to them specifically about HIV and its transmission, although one-third had been tested for HIV. In multivariate analysis, male-male sex, paying for sex, and IDU were associated with HIV testing, but those whose primary language was not English were less likely to be tested. Those who had received HIV education were more likely to have used a condom last time they had sex (OR 4.52, 95%CI 1.49-14.0). CONCLUSIONS: This study provides evidence that those with serious mental illness in Victoria have higher rates of participation in risk behaviour for HIV infection than those in the general community. Attention to HIV education and prevention in this group has been inappropriately scant; strategies to encourage safer behaviour are urgently needed.     

Sex differences in neuropsychological functioning of first-episode and chronically ill schizophrenic patients

OBJECTIVE: The purpose of this study was to determine whether men and women with schizophrenia demonstrate differences in cognitive abilities. METHOD: Two cohorts of patients with schizophrenia, an acute first-episode and a chronically hospitalized group, were evaluated with a neuropsychological battery and compared with a normal group of subjects. RESULTS: After adjustment for age, age at onset, and premorbid IQ, male chronic patients performed worse than female chronic patients on measures of visual memory. These differences were eliminated after control for symptom severity. No other differences were found in cognitive function between men and women in either cohort. CONCLUSIONS: Sex differences in cognitive function in schizophrenic patients are not robust findings.     

Attentional dysfunctions in neuroleptic-naive and neuroleptic-withdrawn schizophrenic patients and their siblings.

This study examined attentional deficits in 44 schizophrenic patients (24 neuroleptic-naive and 20 neuroleptic-withdrawn patients) across changes in medication status and clinical state using a 1–9 continuous performance test (CPT) with distractors. Patients' attentional selectivity scores (A′) were unchanged from the off-medication to on-medication testings (on average, 6 months later), despite significant improvement in both positive and negative symptoms. Both patient groups had significantly lower A′ scores than 44 matched healthy controls at each testing. The nonschizophrenic siblings (n?=?15) of these patients made significantly more errors of omission and commission than healthy controls. The results suggest that attentional deficits, as measured by this CPT, appear to measure stable markers of schizophrenia that may be associated with genetic vulnerability to the illness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mode of presentation and multisystem involvement in Beh?et's disease: the influence of sex and age of disease onset

OBJECTIVE: To evaluate the correlation between the age at onset of Behcet's disease (BD) and sex distribution, mode of disease appearance, and number of organs involved during the disease. METHODS: BD was defined according to the International Study Group criteria. Data from medical files and from patient interviews were collected. Results were analyzed for children and adults, according to age at disease onset. A systemic involvement index was calculated as the sum of visceral organ systems involved. RESULTS: Fifty-nine patients with BD were studied, 26 male and 33 female. The mean age at disease onset was 8.4 +/- 4.5 years in children and 29.8 +/- 7.9 years in adults. The age of onset was significantly lower in male versus female patients. BD presented in children almost entirely as recurrent aphthous stomatitis, while in adults, less than one-third of patients presented first with oral ulcers. The mean age at disease onset of patients who presented first with oral ulcers was significantly lower than the age of patients presenting first with non-oral aphthosis. The mean systemic involvement index was higher in adult onset than in juvenile onset disease. A significant linear correlation was found between age of disease onset and total number of visceral organ systems involved. CONCLUSION: BD was observed to occur earlier in males than in females. The first manifestation of BD in children is almost exclusively in the form of oral ulcers, while older patients have a large proportion of non-oral aphthosis as their first disease manifestation. Disease onset at an older age is positively correlated with increased disease spectrum.     

Remembering the past and imagining the future in schizophrenia.

It has been suggested that patients with schizophrenia experience a distorted sense of continuity of self across time. However, temporal aspects of self-processing have received little empirical attention in schizophrenia. In this study, the authors investigated schizophrenic patients' ability to generate specific mental images of their personal past and future. Results showed that patients recalled fewer specific past events than did healthy controls and were even more impaired in generating specific future events. These deficits were associated with positive symptoms but were not associated with negative symptoms or with performances on verbal fluency tasks. It is suggested that schizophrenic patients' failures to project themselves into specific past and future episodes might be related to difficulties in retrieving contextual details from memory, as well as disturbance of the sense of subjective time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correlated changes in symptoms and neurotransmitter indices during maintenance treatment with clozapine or conventional neuroleptics in adolescents and young adults with schizophrenia

A study of 40 young patients (age 14-22 years) with DSM-III-R schizophrenia (without substance abuse) was conducted following a mean of 3.4 years of neuroleptic treatment. After failing on conventional agents in clinical trials lasting a mean of 2 years, 20 patients were prospectively maintained on open-label clozapine (mean 324 mg daily), and another 20 patients continued on typical neuroleptics (mean 465 mg chlorpromazine-equivalents daily). Patients were then sampled for biochemical measures and assessed for psychopathology (Brief Psychiatric Rating Scale, Scales for the Assessment of Positive/ Negative Symptoms) on six occasions at consecutive 6-week intervals-during maintenance treatment on clozapine or conventional neuroleptics. There were 22-fold interindividual differences in clozapine levels and also high intraindividual differences over time. Maintenance dosage was linearly related to plasma levels of clozapine and its metabolites. Prolactin levels were elevated with typical neuroleptics but not clozapine. Blood levels of serotonin, methoxyhydroxyphenylglycol (MHPG), norepinephrine, and epinephrine (but not dopamine) were significantly higher in clozapine-treated patients than in conventionally treated patients. Higher serotonin levels were associated with significantly fewer negative symptoms, whereas higher MHPG levels were correlated with less depression. These findings suggest involvement of norepinephrine and serotonin in the pathophysiology of schizophrenia (with depression associated with lower MHPG levels and negative symptoms associated with lower serotonin levels) and in the therapeutic actions of clozapine. Speculatively, a treatment strategy of targeting specific neurotransmitter systems might be based on the presence of specific symptoms in adolescents and young adults with schizophrenia.