Psychopathologic precursors and sociodemographic risk factors for the schizophrenia syndrome.

This article presents a prospective analysis of an antecedent psychopathologic features and sociodemographic risk factors in schizophrenia with data from five community sites in the National Institute of Mental Health Epidemiologic Catchment Area Program. Three nonoverlapping psychotic cases were defined using DSM-III definitions as implemented by the Diagnostic Interview Schedule (DIS): (1) DSM-III Schizophrenia Criterion A; (2) Criterion A and Affective Episode; and (3) full Schizophrenia. In a 1-year follow-up period, the cumulative incidence rate of Criterion A was 0.79 per 100, for Criterion A with Affective Episode it was 0.17 per 100, and for Schizophrenia the rate was 0.20 per 100. In multivariable logistic regression modeling, the patterns of associations between sociodemographic factors and DIS/DSM-III Schizophrenia resembled patterns in clinically based registry data. Male subjects had an earlier peak onset than female subjects, and marital status and employment were strongly related to odds of developing DIS/DSM-III Schizophrenia. An interaction between gender and never marrying showed never-married men at 50 times higher odds of developing DIS/DSM-III Schizophrenia, never-married women at 14 times higher odds, and married women at 2.5 times higher odds, relative to married men. Adjusting for sociodemographic factors, DIS/DSM-III Obsessive Compulsive Disorder and Social Phobia were both associated with more than 3.5 times increased odds of developing DIS/DSM-III Schizophrenia. Several other psychopathology items, including panic attacks, were associated with increased odds of developing DIS/DSM-III Schizophrenia. There were both similarities and differences in risk factor structure between DIS/DSM-III Schizophrenia and the other two defined categories of case.     

Gender differences in psychopathology,functional impairment,and familial risk factors among adjudicated delinquents

OBJECTIVE: To test the hypotheses that female juvenile delinquents would have higher rates of psychological symptoms, DSM-IVpsychiatric and substance use disorders, functional impairment, and familial risk factors than male juvenile delinquents. METHOD: A stratified random sample of adjudicated delinquents (n = 513 males, n = 112 females) was drawn from San Diego County administrative databases. Of those sampled youths who could be located, 65.7% completed interviews. Psychological symptoms, DSM-lVdiagnoses, and familial risk factors were assessed between October 1997 and January 1999. RESULTS: Female delinquents scored higher on parent and self-report measures of psychological symptoms and had higher rates of DSM-IVmental disorders than did male delinquents. Girls also experienced greater incidences of physical, emotional, and sexual abuse; physical neglect; and family history of mental illness than their male counterparts. No gender differences were found on parental ratings of youth functional impairment, substance use disorders, comorbidity, or parental history of antisocial behavior. CONCLUSIONS: Findings indicated that female adjudicated delinquents have significantly higher rates of psychopathology, maltreatment history, and familial risk factors than males and suggest that the mental health needs of girls in juvenile justice deserve increased attention.     

Disentangling the pathology of schizophrenia and paraphrenia

With increasing longevity, the number of older schizophrenic patients is growing. Previous criteria used the age of symptom onset to differentiate between the late manifestations of early-onset schizophrenia and late-onset schizophreniform disorders. Current DSM-IV or ICD 10 nomenclatures do not differentiate between early- and late-onset schizophrenia. Many decades of repeated failures to provide for distinguishing neuropathological findings have prompted narrower definition criteria. Since psychotic or schizophreniform symptoms in old age may be a manifestation of Alzheimer's disease, we attempted to base a distinction between both early- and late-onset schizophrenia on the presence of degenerative changes. This study examined the brains of 64 schizophrenic patients and 18 controls immunocytochemically for tau and amyloid staining. We divided patients according to their ages at the onset of symptoms: <40, >40. Using Braak's classification, we assessed the presence of neurofibrillary pathology. Stages III and IV were observed in 11.1% (2/18) of controls, 36.7% (11/30) of early-onset schizophrenics (<40) and 58.8% (20/34) of late-onset (>40) schizophrenics (chi2=11.39, P =0.003). Stages V and VI (definite Alzheimer's disease) did not significantly differ among groups (chi2=3.6, P =0.165). Astrocytes, subependymal and fibroblastic, also exhibited tau-positive tangles. Chi-square analysis of the data revealed a significant association between tau-positive glial tangles and Braak staging ( P =0.002). Amyloid deposits were sparse in comparison to tau-related changes. The restricted limbic tauopathy not only affected a majority of patients with late-onset schizophrenia (19 female: 1 male among positive cases) ( P =0.048) but also appeared in one-third of those elderly schizophrenic patients whose symptom onset occurred before 40 years of age (8 female: 3 male among positive cases) ( P =0.048). The resultant changes define a type of neuronal cytoskeletal disruption that alters the flow of information through the hippocampus and provides a useful clinico-pathological correlate to a group of patients until recently diagnosed as schizophrenic.     

Neuropsychological deficits in children associated with increased familial risk for schizophrenia

By studying neuropsychological performance in children genetically at-risk for schizophrenia, greater understanding may be obtained regarding the developmental processes of schizophrenia and associated cognitive weaknesses. A variety of cognitive deficits in genetically at-risk children have been reported. The present study was designed to examine cognitive tasks that have traditionally differentiated children genetically at-risk for schizophrenia (e.g. working memory) from normal children, while also assessing abilities that have received scant attention in this population. Aspects of emotional perception, verbal abilities, inhibition, visuo-spatial skills, and working memory were assessed in children of schizophrenic parents and normal children. Significant differences in performances were identified in at-risk children on measures of verbal skills, working memory and inhibition. Findings suggest that children genetically at-risk for developing schizophrenia exhibit neurocognitive weaknesses generally consistent with those noted in the literature. However, inhibition also appeared to be a cognitive process that significantly differentiated the groups. The possibility of a developmental expression of neurocognitive deficits is discussed.     

Genetic risk factors in schizophrenia

The high pathogenetic relevance of genetic factors in schizophrenia is beyond doubt based on the findings of epidemiological studies. By means of a complex mode of transmission, it is likely that several genes with weak to moderate effect jointly constitute a genetic basis for a vulnerability to schizophrenia that may well vary for different individuals. Other organic and psychosocial factors also play an individually different -- in some cases significant -- role in terms of pathogenesis, as a result of which an oligogenic/polygenic multifactor model is assumed from the standpoint of aetiopathogenetics. Molecular genetic methods consist in linkage analyses and association analyses. Positive linkage findings accumulate particularly for the chromosomes 1q, 6p, 8p, 13q and 22q. By themselves, individual mutations contribute little to the range of schizophrenic feature characteristics, it was not possible -- irrespective of some subtypes -- to replicate genes of major effect. From the large number of possible candidate genes, although studies on DRD3, DRD2 and HTR2A produced positive results, the magnitudes of effect were low. The findings for alleles of dysbindin, neuregulin 1, DAO, COMT, PRODH, ZDHHC and DISC are less clear. The search for schizophrenia-relevant mutations is hampered by the possibility of a heterogeneous phenotype of schizophrenia in case of a homogeneous genotype as much as by the possibility of inter-individually homogeneous phenotypical characteristics in case of schizophrenia-relevant heterotype in the genome. With the aid of the concept of endo-phenotypes, based on neurobiological phenomena, it might be possible to take a more direct approach that leads from relevant mutations to the risk of schizophrenias. However, replacing schizophrenic alienation with neurobiological aspects leads to difficulties in explaining these complex disorder profiles. Schizophrenic diseases require an explanatory approach that also incorporates personality and developmental psychological aspects from the outset, if the aim is not to restrict type of schizophrenic disease exclusively to loci of molecular genetic changes.     

Main risk factors for schizophrenia: increased familial loading and pre- and peri-natal complications antagonize the protective effect of oestrogen in women

Women fall ill with schizophrenia 3 to 4 years later than men. The neurobiological mechanism, explaining the delay of onset in women until menopause, is presumably due to a sensitivity reducing effect of oestrogen on central d(2) receptors, as we have previously shown in animal experiments and in a controlled clinical study. The gender difference in age at onset seems to disappear in familial cases with schizophrenia, but it increases to highly significant values of 5 years or more in isolated cases according to a recent study by Albus and Maier (Schizophrenia Research 18:51-57, 1995).We tried to replicate these findings and to test the hypothesis of a functional antagonism between genetic predisposition to illness and the protective effect of oestrogen in a population-based sample of 232 first illness episodes of schizophrenia.In women with at least one first-degree relative suffering from schizophrenia, age at onset defined by first psychotic symptom was significantly reduced by several years and the difference with men disappeared. In sporadic female cases (no mental disorder in first-degree relatives) the age at onset was slightly increased compared with the total sample, which was in accordance with our hypothesis. In men with familial schizophrenia, but without a protective agent like oestrogen, the age at onset was only slightly and non-significantly reduced compared with the total group and with sporadic cases. This was in line with Albus and Maier and with our hypothesis that only the protective effect of oestrogen could be antagonized by a strong genetic disposition.The second main risk factor for schizophrenia is pre- and peri-natal complications. We compared men and women from our sample of first illness episodes with a history of pre- and peri-natal complications with those without a history of obstetric complications. In women the age at first psychotic symptom was markedly reduced, but due to small case numbers not significantly, compared with women without the risk factor and with the total group. Again, schizophrenic men with a history of pre- and peri-natal complications showed only a small, non-significant reduction of age at onset compared with the total and the group without the risk factor. Therefore, we concluded that the degree of genetically determined vulnerability and, presumably to a slightly lesser extent, the degree of pre- and peri-natal brain injury antagonizes the onset delaying effect of oestrogen in schizophrenia.     

Socioeconomic and familial factors in the involuntary hospitalization of patients with schizophrenia

In the catchment area of Matsumoto Public Health Center in Japan, 44 schizophrenic patients admitted between April 1992 and March 1997 under the national policy Involuntary Hospitalization Ordered by Prefectural Governor (IHOPG) were compared with 61 schizophrenic patients admitted under another policy, Hospitalization for Medical Care and Protection (HMCP), during the same period. The socioeconomic and familial factors that led patients to IHOPG were evaluated in detail. The results revealed the following characteristics of IHOPG patients as opposed to HMCP patients: (i) their morbidity was of longer duration; (ii) they were more likely to live in a densely populated area; (iii) they were less likely to be financially self-sufficient; (iv) prior to admission they were more likely than HMCP patients to have avoided psychiatric examination and to have refused to take medication, and most had received no treatment before their hospitalization under IHOPG; (v) their relationships with family members were more likely to be poor; and (vi) the family was less likely to have cooperated with treatment or to have solved the patient's problematic behaviors. This investigation and the ensuing discussion revealed that a patient's schizophrenia-based danger to hurt self or others, which is an essential impetus for admission to IHOPG, does not arise suddenly but rather stems from multiple factors developing over time.     

Family structure and risk factors for schizophrenia: case-sibling study

Background  

Several family structure-related factors, such as birth order, family size, parental age, and age differences to siblings, have been suggested as risk factors for schizophrenia. We examined how family-structure-related variables modified the risk of schizophrenia in Finnish families with at least one child with schizophrenia born from 1950 to 1976.     

Individual and familial risk factors for bipolar affective disorders in Denmark

BACKGROUND: Few population-based studies have addressed risk factors for bipolar affective disorder. OBJECTIVE: To study the possible association between bipolar affective disorder and history of mental illness in a parent or sibling; urbanicity of birth place; season of birth; sibship characteristics, including birth order; influenza epidemics during pregnancy; and early parental loss. DESIGN: We used a population-based cohort of 2.1 million individuals based on data from the Danish Civil Registration System linked with the Danish Psychiatric Central Register. SETTING: Nationwide population-based sample of all individuals hospitalized or in outpatient clinic contact for the first time with bipolar affective disorder.Patients Overall, 2299 individuals were first diagnosed with bipolar affective disorder during the 31.8 million person-years of follow-up. RESULTS: Risk of bipolar affective disorder was associated with a history of bipolar affective disorder as well as other psychiatric disorders, including schizophrenia and schizoaffective disorder, in parents or siblings. People with a first-degree relative with bipolar affective disorder had a 13.63-fold (95% confidence interval, 11.81-15.71) increased risk of bipolar affective disorder. No other consistent associations were found with the exception of an association between early parental loss, in particular maternal, and bipolar affective disorder. Children who experienced maternal loss before their fifth birthday had a 4.05 (95% confidence interval, 1.68-9.77) increased risk of bipolar affective disorder. CONCLUSIONS: Early parental loss may represent both environmental and genetic risk factors for bipolar affective disorder. Most of the risk factors included in our study that previously have been associated with schizophrenia were not associated with bipolar affective disorder, supporting that the 2 disorders may be at least partially separate etiological entities.     

P50 suppression in individuals at risk for schizophrenia: the convergence of clinical, familial, and vulnerability marker risk assessment.

BACKGROUND: Identification of individuals at risk for the development of schizophrenia is important because it can lead to a greater understanding of the early stages of the illness. The aim of the present study was to determine whether individuals "at risk" for schizophrenia have deficits in P50 suppression, a preattentive measure of sensory gating. METHODS: Thirty-one at-risk and 21 normal comparison subjects were referred to the CARE (Cognitive Assessment and Risk Evaluation) Program at University of California San Diego. The primary aim of the CARE Program is to identify individuals who are at the greatest risk for conversion to psychosis, with a combination of clinical, familial, and vulnerability markers, including P50 suppression. RESULTS: As a group, the at-risk subjects had modestly lower levels (effect size=.43) of P50 suppression (55.1%, SD=39.8) relative to comparison subjects (71.5%, SD=34.7). At-risk subjects with a first-degree relative with schizophrenia had profoundly deficient P50 suppression (16.4%, SD=33.8) compared with other at-risk (p<.05) and comparison subjects (p<.005). CONCLUSIONS: Ongoing longitudinal follow-up studies will determine whether it is possible to improve the predictive validity of the clinical and familial variables by using P50 suppression alone or in combination with other measures in determining which individuals are at greatest risk for schizophrenia.     

首发精神分裂症复发高危因素的回归分析

目的探讨首发精神分裂症5年内复发的危险因素。方法对406例首发精神分裂症患者痊愈后5年内进行随访，并分析复发患者的临床特点。结果5年复发率为70．3％；回归分析发现DUP（duration of untreated psychosis未治疗的精神病期）、依从性、遗传、年龄、是否按医嘱复诊与复发的关系密切，其中坚持按医嘱复诊、服药是减少复发最重要的条件。结论影响首发精神分裂症复发的因素很多，其中最重要的是遗传、DUP、依从性、年龄以及是否按医嘱复诊。     

Public beliefs about causes and risk factors for depression and schizophrenia

The objective of this study was to carry out a national survey to assess the Australian public's beliefs about causes and risk factors for mental disorders. A national household survey of 2,031 Australian adults was carried out. Half the respondents were presented with a vignette describing a person with major depression and the other half with a vignette describing schizophrenia. Respondents were asked to rate whether various factors are likely causes of problems such as that described in the vignette and to rate whether various groups are at higher or lower risk. For depression, social environmental factors were often seen as likely causes, which is consistent with the epidemiological evidence. However, genetic factors were considered as a likely cause by only half the population. For schizophrenia, social environmental factors were also often seen as causes, which is in contrast to the weak epidemiological evidence for such a role. Genetic factors attracted more support as a cause of schizophrenia than of depression. These finding point to areas where the mental health literacy of the population could be improved, particularly the over-emphasis on social environmental factors in schizophrenia. Of some concern was the belief of half the population that weakness of character is a likely cause of both depression and schizophrenia. This belief implies a negative evaluation of the sufferer as a person.     

Cumulative effect of anatomical risk factors for schizophrenia: an MRI study.

BACKGROUND: Although schizophrenic and control subjects differ on a variety of neuroanatomical measures, the specificity and sensitivity of any one measure for differentiating between groups are low. This study investigated the cumulative effect of deviant brain structure on diagnosis. METHODS: Hemisphere and third ventricle volume and the normalized (Talairach) location of three association cortex sulcal landmarks were measured on high-resolution MRI scans in 37 male patients with schizophrenia and 33 male control subjects matched on age, handedness, and parental socioeconomic status. RESULTS: While there were few group differences on individual anatomical measures, the 10 variables reliably discriminated between the two groups when used in concert in a discriminant function analysis (F[10.59] = 3.6, p < .0009) with 77% of the subjects correctly classified. Five of the measures (left posterior cingulate, left inferior frontal sulcus, right sylvian fissure, and left and right halves of the third ventricle) correlated significantly with the discriminant function (p < .005). CONCLUSIONS: This is the first study to demonstrate that schizophrenics can be distinguished from matched controls on the basis of brain anatomy alone. The risk of schizophrenia may depend on the total amount of neural deviance, rather than on anomalies in a single structure or circuit.     

Longitudinal alterations of executive function in non-psychotic adolescents at familial risk for schizophrenia

Genetic diathesis to schizophrenia may involve alterations of adolescent neurodevelopment manifesting as cognitive deficits. Brain regions mediating executive function (fronto-striatal circuits) develop during adolescence while those supporting elementary aspects of attention (e.g. sustained focused attention) have a more protracted maturation beginning in childhood. We hence predicted that adolescents at risk for schizophrenia would show a failure of normal maturation of executive function. We prospectively assessed 18 offspring and 6 siblings of schizophrenia patients (HR) and 28 healthy controls at baseline, year-1 and year-2 follow-up using the Continuous Performance Test [visual-d′] and Wisconsin Card Sort Test (WCST). Perseverative errors on the WCST in HR remained stable but decreased in controls over the follow-up (study-group by assessment–time interaction, p = 0.01, controlling for IQ). No significant study-group by assessment-time interactions were seen for sustained attentional performance. HR may not improve while healthy subjects progressively improve on executive function during adolescence and early adulthood. Our results suggest an altered maturational trajectory of executive function during adolescence in individuals at familial risk for schizophrenia.