Gender and schizophrenia: implications for understanding the heterogeneity of the illness

This study begins to test the hypothesis that schizophrenic men and women may be at risk for experiencing different subtypes of the illness. Given past research, hypotheses predict that schizophrenic men will have an earlier age of onset, poorer premorbid history, lower family morbid risk, and poorer course. Data consist of 332 schizophrenic patients diagnosed according to DSM-III and 713 of their first-degree relatives from the double-blind Iowa 500 and non-500 family studies. Survival analysis was used to estimate age of onset, and Str?mgren's abridged method for age correction was used to estimate family morbidity risks. Findings support our hypotheses and suggest that men may be at risk for experiencing a more severe form of schizophrenia.     

Gender and the familial risk for schizophrenia. Disentangling confounding factors.

Recent studies of the effect of gender on the familial risk for schizophrenia have shown that relatives of females have a higher risk for schizophrenia than relatives of males. This study attempts to explain the effect by examining factors found to differentiate schizophrenic men and women and found to be related to the familial risk for schizophrenia. Cox proportional hazard regression model was used to examine the simultaneous effects of age at onset, season of birth, and premorbid history, controlled for symptoms that have been found to differ by gender (dysphoria, paranoia, and flat affect). Results showed that the effect of gender on the transmission of schizophrenia could not be explained by gender differences in age at onset, symptom expression, premorbid history, and winter birth. However, premorbid history had an effect on familial risk independent of gender, indicating that probands with a poor premorbid history had a lower familial risk for schizophrenia than those with a good premorbid history. Implications of the findings are discussed.     

Winter birth and biological family history in adopted schizophrenics

To investigate relationships between birth season and biological family history in schizophrenia, this study used a sample of schizophrenics that had the advantages of (a) particularly thorough diagnostic assessments of schizophrenics' relatives, including information from direct interviews as well as chart reviews, and (b) schizophrenic probands who were adopted at early age, mitigating the usual confounding of genetic and postnatal environmental influences of the family. Adopted schizophrenics with no biological family history of schizophrenia-spectrum disorders were significantly more likely to be born in winter months than were either (a) their own biological relatives, including their sibs and half-sibs, (b) schizophrenics with a positive family history for schizophrenia-spectrum disorders, or (c) people in the general population. Family-history-positive schizophrenics and their schizophrenic relatives were, in turn, significantly less likely than their own non-schizophrenic biological relatives to be born in the winter; schizophrenics in these families tended to be born in the milder-weather seasons, particularly the spring and fall. Results suggest that environmental factors associated with winter birth may be etiologically important in schizophrenia, particularly for cases in which familial liability factors are weak. By contrast, a familial, probably genetic, liability factor may be especially important in schizophrenics born in mild weather.     

Familial association of schizotypal traits with psychotic and affective disorders

The criteria for schizotypal personality disorder were developed on the basis of traits observed in biologic relatives of schizophrenic and borderline schizophrenic probands from the Danish adoption studies. In this review, the relationship between schizotypal personality disorder and the schizophrenic spectrum, affective disorders, and psychotic disorders is explored. A dimension of psychosis may overlap with the schizophrenia spectrum to yield chronic schizophrenia, with the affective disorders spectrum to yield psychotic affective disorder, or by itself lead to other psychotic disorders. Schizotypal personality disorder in this model is posited to represent schizophrenia spectrum disorder that does not overlap with psychosis, whereas nonpsychotic affective disorders represent the affective disorders that do not overlap with psychosis. Delusional disorder represents another psychotic disorder that is not specifically related to either schizophrenia or the affective disorders. Evidence suggests that the schizotypal personality disorder criteria, particularly those emphasizing the negative symptoms or deficit-like symptoms of this disorder, specifically identify a unique relationship to the schizophrenia spectrum.     

Gender differences in the course of schizophrenia

This study tested the hypothesis that schizophrenic women experience a less severe course of illness than schizophrenic men. Ninety patients with DSM-III diagnoses of schizophrenia, who were in the early stages of illness, were followed for 10 years with respect to rehospitalizations and length of time in the hospital. Multivariate regression techniques were used to test for gender differences across multiple outcomes. The women experienced fewer rehospitalizations and shorter stays than did the men. These findings were not an artifact of diagnosis. The results suggest that the determinants of gender differences occur during the premorbid period and are manifest early in the development of the disorder.     

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.     

Clinical correlates of the deficit syndrome of schizophrenia

The authors propose using primary and enduring negative or deficit symptoms for dichotomizing schizophrenic patients into two groups, deficit and nondeficit. The validity of this approach was examined by comparing 17 deficit and 17 nondeficit patients for differences in premorbid adjustment and degree of neurological impairment. Deficit patients were characterized by poorer premorbid adjustment and greater neurological impairment. Neurological impairment was not related to premorbid adjustment in either group or in the total patient population. These findings support the utility of deficit symptoms for defining a more homogeneous subgroup of schizophrenia.     

Patterns of sex differences in negative symptoms and social functioning consistent with separate dimensions of schizophrenic psychopathology

In 220 schizophrenic twins, men had greater asociality-withdrawal and poorer premorbid social competence than women but there were no sex differences in symptoms, suggesting that negative symptoms and social functioning reflect different processes in the development and manifestation of schizophrenia and that they should be examined separately.     

The significance of family history in first-episode schizophrenia spectrum disorder

There have been inconsistent findings regarding the significance of family history of schizophrenia spectrum disorders in relation to presentation and course of illness. There has been little research relevant to this issue from first-episode patients. We examined the differences in premorbid adjustment, symptoms, and intellectual functioning between 28 first-episode schizophrenia spectrum patients with a history of such illness in first degree relatives and 28 matched patients without such a family history. The results indicate that whereas the 2 groups did not differ in presenting symptoms, those with a positive family history showed poorer intellectual functioning and less reduction in symptoms at 2 and 3 year follow-up and greater likelihood of abnormal electroencephalogram findings. The findings provide evidence that presence of a positive family history in first-episode patients is associated with a more pernicious form of illness.     

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.     

Relationship of schizotypal personality disorder to schizophrenia: genetics

The adoptive, family, and twin studies show that schizotypal personality features are found among the relatives of schizophrenics. However, it has not been shown that there is a higher risk of schizophrenia among the relatives of schizotypals. An explanation may be that the current DSM-III criteria of schizotypal personality disorder do not adequately define schizotypals genetically related to schizophrenia. While some of the cases that meet DSM-III criteria are within the schizophrenia spectrum, others are unrelated to schizophrenia. There is reason to believe that schizotypals characterized by distant relationship to others, suspiciousness, eccentricity, peculiar communication, and dysfunctional school and work performance are within the schizophrenic sphere, while individuals with psychotic-like symptoms phenomenologically similar to schizophrenia and diagnosed as schizotypal personality disorders in DSM-III represent decompensation of other personality disorders.     

Modern research criteria and the genetics of schizophrenia

The authors assessed the relevance of narrowly defined diagnostic criteria to genetic research in schizophrenia in the nuclear families of 84 chronic schizophrenic probands compared with families of 90 normal control probands. The morbidity risk for narrowly defined schizophrenia in first-degree relatives of patients with the narrow diagnosis was significantly higher than the control rate (3.8% versus 0.3%). The rate of chronic schizophrenia in the relatives of all schizophrenic patients was also significantly higher than the control rate (7.1% versus 0.6%), as was the rate of "spectrum" disorders (33.4% versus 11.3%). The data support the case for familial transmission of narrowly defined schizophrenia.     

Deterioration in premorbid functioning in schizophrenia: a developmental model of negative symptoms in drug-free patients.

OBJECTIVE: The authors examined the relationship between negative symptoms and premorbid variables in drug-free schizophrenic patients. METHOD: The authors studied 63 clinically stable male schizophrenic inpatients who were not receiving any psychoactive medication. The patients were classified as having negative, positive, or mixed symptoms, and their premorbid functioning during childhood, early adolescence, and late adolescence was assessed by using the Premorbid Adjustment Scale. Correlational analyses were applied to the classification and developmental models. RESULTS: Patients with negative symptoms had significantly lower levels of premorbid functioning during late adolescence and significantly greater premorbid deterioration between childhood and early adolescence. Correlational analysis revealed significant positive relationships between premorbid variables and negative symptoms. CONCLUSIONS: The data suggest that a deterioration in social and intellectual functioning between childhood and adolescence is associated with the development of a negative symptom syndrome in schizophrenia. The premorbid deterioration appears to be an early prodrome of the disorder. Whether this residual negative symptom syndrome is in some way related to the deficit syndrome of schizophrenia awaits a prospective study.     

Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits

OBJECTIVE: Patients with schizophrenia spectrum disorders have been shown to have deficits in sensorimotor gating as assessed by prepulse inhibition of the startle response. The authors hypothesized that nonschizophrenic relatives of patients with schizophrenia would also have prepulse inhibition deficits, thereby reflecting a genetically transmitted susceptibility to sensorimotor gating deficits. METHOD: Twenty-five comparison subjects, 23 patients with schizophrenia, 34 relatives of the schizophrenic patients, and 11 subjects with schizotypal personality disorder were assessed in an acoustic startle paradigm. The eye-blink component of the startle response was assessed bilaterally by using electromyographic recordings of orbicularis oculi. RESULTS: The patients with schizophrenia, their relatives, and subjects with schizotypal personality disorder all had reduced prepulse inhibition relative to comparison subjects, and these deficits were more evident in measures of right eye-blink prepulse inhibition. Comparison subjects demonstrated greater right versus left eye-blink prepulse inhibition, whereas the probands, their relatives, and subjects with schizotypal personality disorder showed less asymmetry of prepulse inhibition. CONCLUSIONS: These data suggest a genetically transmitted deficit in prepulse inhibition (sensorimotor gating) in patients with schizophrenia spectrum disorders, including subjects with schizotypal personality disorder and relatives of patients with schizophrenia.     

Mental disorders in first-degree relatives of schizophrenics

A total 215 first-degree relatives of 88 twin probands with schizophrenia, mood disorders and nonaffective psychoses were studied. The twins' parents and siblings were personally interviewed with structured diagnostic instruments and diagnosed in accordance with DSM-III-R criteria. The first-degree relatives were interviewed by interviewers who were blind to the twins' diagnoses. Schizophrenia and schizotypal personality disorder were significantly more frequent in first-degree relatives of schizophrenic twins. Respectively, anxiety and mood disorders were significantly more prevalent among the parents and siblings of probands with mood disorders. Schizophrenic spectrum disorders were significantly more common in the families of schizophrenic probands compared with relatives of mood disorder probands, thus confirming a relationship between schizophrenia and schizophrenic spectrum disorders. However, we cannot, based on our study, specify whether this relationship is caused by genetic or environmental factors.     

Epidemiological and clinical correlates of familial and sporadic schizophrenia

We studied 68 schizophrenic cases with a schizophrenic first-degree relative (familial group) and 62 cases without such a family history (sporadic group). We compared them on: (i) clinical variables, including premorbid adjustment, age of onset and severity of symptoms; (ii) neural abnormalities, including abnormal involuntary movements, neural “soft” and “hard signs”; (iii) neuropsychological tests, including the Wechsler Adult Intelligence Scale and the Continuous Performance Test and (iv) environmental risk factors, including winter birth and obstetrical complications. Sporadic cases were more likely to be born in winter and had more severe psychotic symptoms, but most analyses yielded no difference between the groups. Our results offer some support that sporadic schizophrenia is a more environmental subtype, but they also suggest that the familial vs sporadic distinction of schizophrenia has limited power to identify distinct subgroups.     

The Cantabria first episode schizophrenia study: a summary of general findings

This article describes the general findings of the initial cross-sectional stage of a prospective follow-up study of all first episodes of schizophrenia that occurred in the Autonomous Community of Cantabria over a 2-year period and that established contact with any mental health service. The project comprises: i) a 2-year cross-sectional stage, in which the sample was gathered and studied with structured psychiatric instruments such as the Present State Examination and the Scales for the Assessment of Negative and Positive Symptoms (SANS and SAPS), and; ii) a continuous follow-up. We detected, in the risk age ranged of 15–54 years, an incidence of 1.9 per 10,000 inhabitants per year for schizophrenia and of 1.3 per 10,000 inhabitants per year for the S + CATEGO diagnosis, without any significant gender difference of morbidity. The mean age for the total schizophrenic population was 26 years, being significantly higher in women than in men. In contrast with what happens with marital status, type of household or urban/rural way of life, there was no gender difference in relation to the other sociodemographic variables. The way in which nosological and clinical variables are associated with first episodes of schizophrenia was also examined in this study. We found that 75% of patients reached a maximum CATEGO-ID level, 71% received a S + CATEGO diagnosis, 59% presented first-rank symptoms of schizophrenia and that the percentage of a schizophrenic negative syndrome, as identified by the SANS and SAPS, was very low. Finally, among the clinical variables investigated, only premorbid adjustment, personal history of mental illness and length of admission presented significant gender differences.     

The effects of genetic liability for schizophrenia and maternal smoking during pregnancy on obstetric complications

The purpose of this study was to determine whether a genetic vulnerability for schizophrenia and/or health-risk behaviors among schizophrenic pregnant women were associated with an increased incidence of obstetric complications (OCs). METHOD: A high-risk birth cohort was formed by searching the Finnish Perinatal Register for all births from 1991-2000 with arterial cord pH values below 7.20, an indication of fetal asphyxia. This database was merged with national hospital discharge registries to determine psychiatric morbidity of the mothers and the mothers' first-degree relatives. Mothers were divided into 3 groups: women diagnosed with schizophrenia/schizoaffective disorder (n=53), mothers with a first-degree relative with schizophrenia/schizoaffective disorder (n=590) and healthy controls (n=36,895). RESULT: Schizophrenic women had significantly more OCs than mothers with a first-degree schizophrenic relative and controls. These women had significantly increased rates of eclampsia, premature delivery, prenatal hospitalizations, and marginally significant increases in high blood pressure. Offspring of schizophrenic mothers had significantly decreased APGAR scores and birth weight and increased medical complications after birth. In contrast, women with a schizophrenic first-degree relative had no significant increases in OCs compared to controls. Schizophrenic mothers also smoked more than the other groups and smoking was found to mediate the relationship between maternal schizophrenic status and decreased birth weight among offspring. CONCLUSIONS: Maternal schizophrenia during pregnancy leads to an increased risk of OCs, possibly due to engagement in health-risk behaviors during pregnancy, such as smoking, whereas genetic susceptibility to schizophrenia, by itself, does not appear to be related to incidence of OCs.     

Sex differences in illness presentation, course, and level of functioning in substance-abusing schizophrenia patients

Studies of gender differences in schizophrenia have concluded that women experience a more benign form of the illness than men as evidenced by later age of illness onset, less debilitating psychiatric symptomatology, fewer psychiatric hospitalizations, and better premorbid and overall functioning. Little research, however, has focused on documenting the potential negative impact of substance use on these clinical outcomes. The purpose of this study was to evaluate gender differences in the effects of substance use on the course and presentation of schizophrenia. Two groups of schizophrenia outpatients were evaluated: 34 with substance-use disorders and 33 with no history of substance-use disorders. Sex comparisons were conducted on rates of current psychiatric symptoms, age of onset, number of previous hospitalizations and ratings of general level of functioning. The results suggest that the more benign course and presentation of illness ordinarily seen in women with schizophrenia become muted when they use substances. The data further suggest that women may be especially vulnerable to the adverse effects of substance use. Collectively, these findings highlight the need for additional research and the development of more effective treatment interventions for this population of women.     

Premorbid speech and language impairments in childhood-onset schizophrenia: association with risk factors

OBJECTIVE: As both premorbid neurodevelopmental impairments and familial risk factors for schizophrenia are prominent in childhood-onset cases (with onset of psychosis by age 12), their relationship was examined. METHOD: Premorbid language, motor, and social impairments were assessed in a cohort of 49 patients with childhood-onset schizophrenia. Familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications were assessed without knowledge of premorbid abnormalities and were compared in the patients with and without developmental impairments. RESULTS: Over one-half of the patients in this group had developmental dysfunction in each domain assessed. The patients with premorbid speech and language impairments had higher familial loading scores for schizophrenia spectrum disorders and more obstetrical complications, and their relatives had worse smooth-pursuit eye movements. The boys had more premorbid motor abnormalities, but early language and social impairments did not differ significantly between genders. There were no other significant relationships between premorbid social or motor abnormalities and the risk factors assessed here. CONCLUSIONS: Premorbid developmental impairments are common in childhood-onset schizophrenia. The rates of three risk factors for schizophrenia (familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications) were increased for the probands with premorbid speech and language impairments, suggesting that the pathophysiology of schizophrenia involves the abnormal development of language-related brain regions.