Earlier puberty as a predictor of later onset of schizophrenia in women.

OBJECTIVE: The aim of this study was to determine whether puberty plays a mediating role in onset of schizophrenia. The hypothesis was that there is an inverse relation between age at puberty (menarche) and age at onset in women. METHOD: Competent and consenting individuals with DSM-IV-defined schizophrenia or schizoaffective disorder and their mothers underwent a 45-minute interview to ascertain age at first odd behavior, age at first psychotic symptoms, age at first hospitalization, and ages at various indices of puberty. Information about substance use, head injury, perinatal trauma, and first-degree family history of schizophrenia was also obtained. RESULTS: In the women (N = 35), the earlier the age at menarche, the later the ages at both the first psychotic symptoms and the first hospitalization. There was no significant association between puberty and onset in the men (N = 45). Other than gender, none of the examined variables played a role in the interaction of puberty and onset of illness. CONCLUSIONS: In women, early puberty (whether through hormonal or social influence) was associated with later onset of schizophrenia. This effect was not found in men; in fact, the trend was in the opposite direction.     

Relationship between sex differences in onset of schizophrenia and puberty

Some neurodevelopmental hypotheses of schizophrenia have postulated that sex differences in onset of illness could be explained by sexual dimorphism in onset of puberty, suggesting that early maturation accounts for the later onset of illness in women. The objective of this study was to analyse the relationship between age of menarche and age of onset of schizophrenia in a sample of Chilean patients. The medical records of 105 schizophrenic women diagnosed according to DSM-III-R criteria were studied. In all cases age of onset (first psychotic symptoms) and age of menarche were obtained. Pearson's correlation and student's t-test were used to analyse the data. The mean age of menarche in the sample of female patients (12. 98 years, S.D.=1.49) was significantly different from that of the general population of Santiago, Chile (12.53 years, S.D.=1.32) (t=2. 38; P<0.05). The mean age of onset of schizophrenia in female patients (19.92 years, S.D.=5.13) was significantly earlier in the Chilean sample than that reported in European and North American samples (P<0.05). No differences were observed when comparing the mean age at menarche. The subtypes with the earliest onset presented the earliest age of menarche and the subtypes with the latest onsets showed the latest ages at menarche. However, no correlation was observed between the age at onset of illness and the age at menarche, both in the total sample and in the analysis by subtype. The results of this study do not support a correlation between puberty and age of onset of illness.     

Gender related differences in clinical characteristics and hospital based resource utilization among older adults with schizophrenia

OBJECTIVE: This report is an analysis of gender related differences in clinical characteristics and hospital based health resource utilization among older adults with schizophrenia and schizoaffective disorder in an acute care, state hospital over a one-year period. METHODS: This retrospective record review is an analysis of age of illness onset, psychiatric and medical comorbidity, hospital utilization, and psychotropic medication use. RESULTS: There were a total of 66 individuals with either schizophrenia or schizoaffective disorder. Mean age of this group was 55.2 +/- 4.62 years. Women were significantly over-represented among individuals with late onset schizophrenia and schizoaffective disorder. Men with schizophrenia had more comorbid substance abuse compared to women with schizophrenia (p < 0.05). Women and men did not differ significantly in hospital length of stay, amount or type of antipsychotic medication prescribed, or in utilization of seclusion/restraint in hospital. Both genders had substantial utilization of antipsychotic medication. Use of conventional antipsychotic medication monotherapy was always associated with use of anti-extrapyramidal symptom (anti-EPS) medication, while use of atypical antipsychotic medication monotherapy was more rarely associated with use of anti-EPS medication. CONCLUSIONS: In later life, women and men may have some areas of differing health care needs. Women in particular may benefit from psychoeducational approaches that address the experience of psychiatric illness of relatively recent onset (for example, symptom identification and acceptance of illness). Men may benefit from particular emphasis on treatment of comorbid substance abuse disorders.     

Birth order and the severity of illness in schizophrenia

A proposed risk factor for schizophrenia is materno-foetal incompatibility. We tested the hypothesis that, in multiply affected families, later born children would exhibit a more severe form of schizophrenia than their older siblings. The effect of birth order on (1) severity of the worst ever episode of illness; (2) deterioration from premorbid level of functioning; (3) age of onset; (4) response to medication; and (5) illness course, was assessed in 150 sibling pairs with schizophrenia and schizoaffective disorder. We found that later birth order reduced the likelihood of regaining the premorbid level of functioning after an acute episode and was also associated with an earlier age of presentation. This study lends some support to the hypothesis that later birth order results in a more severe form of the disorder, although there are other possible explanations for our findings. Further work is needed to explore the possibility of maternal-foetal genotype incompatibility as a risk factor for schizophrenia.     

Clinical features of illness in siblings with schizophrenia or schizoaffective disorder

Evidence implicating genetic or prenatal-perinatal environmental causes in the familial aggregation of schizophrenia led us to study 53 sets of siblings, two or more of whom had chronic psychosis, either schizophrenia or schizoaffective disorder. We looked for similarities in clinical features and concordance of diagnosis within sibships to test for shared familial causes. Clinical variables, including diagnosis, specific symptoms, age at onset, and nongenetic perinatal factors, were studied. Auditory hallucinations, paranoid delusions, thought disorder, negative symptoms, and poor premorbid social adjustment did not significantly correlate in siblings. Concordance was found for schizoaffective disorder and history of major depressive episodes, suggesting that schizophrenia with a depressive component and Research Diagnostic Criteria schizoaffective illness may represent a specific etiologic subtype(s) of the illness, whereas the other noted symptoms may represent the variable expression of the disorder. Age at onset and at first hospitalization were significantly correlated, consistent with genetic or other familial factors on time of onset. Birth complications were significantly more frequent among the schizophrenic compared with non-psychotic siblings, had a familial component, and tended to be associated with an earlier age at onset. Thus, nongenetic perinatal factors may increase the risk for schizophrenia in a familial form of the illness and contribute to the correlation of ages at onset in siblings.     

Gender differences in the relationship of childhood trauma and the course of illness in schizophrenia

IntroductionDifferent types of childhood trauma have been repeatedly shown to contribute to psychotic symptoms. Gender differences in schizophrenia are well known. Some studies argue that trauma history means a significantly higher risk of psychosis for women than men. However, there is evidence of early adverse life events to be associated with higher stress-sensitivity in men. Little is known about the connection of specific type of trauma and specific psychotic symptoms as well as the course of illness with explicit regard to gender differences.Methods102 men and women with schizophrenia spectrum disorder were tested using Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Scale for Assessing Positive Symptoms, Early Trauma Inventory-SR.ResultsAlthough, women had a later age at onset without regarding trauma history (d = 0.74), this difference became non-significant when introducing trauma variables. Patients reporting physical abuse had a significantly earlier age at onset, regardless of their sex (V = 0.13, F = 3.11, p = 0.03. Physical abuse predicted an earlier age at onset only in women (R² = 0.23). History of general trauma predicted more frequent hospitalizations only in men (R² = 0.55).ConclusionsAlthough women generally tend to have a more favorable course of illness including a later age at onset men, women with CPA seem to lose this “advantage”. It is necessary to investigate the contribution of gender interacting with adverse life events in contribution to the phenomenology and etiology of schizophrenia.     

A typological model of schizophrenia based on age at onset,sex and familial morbidity

We investigated the age at onset distributions of schizophrenia in men and women and the relationship of age at onset and sex to the familial rates of schizophrenia and manic-depression in data from a Swedish family study of 270 schizophrenic probands. On the logarithmic scale, the age at onset distribution of schizophrenia in both male and female relatives was bimodal, suggesting that broadly defined schizophrenia may be a mixture of 2 (probably related) disorders. The risk of schizophrenia in relatives decreased as a function of the age at onset of the proband, irrespective of the sex of the proband or relative. In contrast, the risk of manic-depression was significantly higher in relatives of female probands with an age at onset in the twenties than in relatives of female probands with earlier or later onset, or in relatives of male probands. This suggests a third disorder related to affective psychosis, with an intermediate age at onset and female preponderance.     

Traumatic life events and PTSD among women with substance use disorders and schizophrenia

OBJECTIVE: The authors assessed the prevalence of traumatic life events and posttraumatic stress disorder (PTSD) among women with schizophrenia or schizoaffective disorder and co-occurring substance abuse or dependence. The association between PTSD and specific traumatic life events was also examined. METHODS: Fifty-four drug-addicted women with schizophrenia or schizoaffective disorder participated in the study. All women were psychiatric outpatients and completed a large battery of structured clinical assessments. RESULTS: High rates of trauma, particularly physical abuse (81 percent), and revictimization--being abused both as a child and as an adult--were reported. The average number of traumatic life events reported was eight, and almost three-quarters of the sample reported revictimization. Rates of current PTSD were considerably higher than those documented in previous study samples of persons with serious mental illness and of drug-addicted women in the general community. PTSD was significantly associated with childhood sexual abuse and revictimization. CONCLUSIONS: The high levels of trauma and revictimization observed in the study highlight the need for the development of evidence-based interventions to treat trauma and its aftermath among women with schizophrenia or schizoaffective disorder. Given the overlap in symptoms between PTSD and schizophrenia, a better understanding is needed of how PTSD is expressed among people with schizophrenia. Recommendations and standards for the assessment of PTSD among this population need to be articulated. Finally, the comparatively high rates of PTSD suggest that the combination of schizophrenia or schizoaffective disorder and substance use disorder makes these women particularly vulnerable to adverse outcomes.     

Cannabis use,gender and age of onset of schizophrenia: Data from the ÆSOP study

An earlier age of onset of schizophrenia has been identified as a poor prognostic indicator. The current study examines the interaction effect of gender and cannabis use on age of onset of schizophrenia and schizoaffective disorder. This research forms part of a two-centre epidemiological study of first-episode psychosis and included individuals with a diagnosis of schizophrenia or schizoaffective disorder and an age of onset between age 16 and 45. Kaplan–Meier curves and Cox proportional hazards regression were used to compare the effects of cannabis use and gender on age of first symptom of schizophrenia. Akaike's information criteria were used to find the model with the best fit to the data. Cannabis users had an earlier age of first symptom than non-users. There was an interaction with gender; the gender difference in age of onset was diminished in cannabis smokers compared with non-cannabis smokers. The model including cannabis use interacting with gender was the most parsimonious model, followed by cannabis use alone. The addition of other illegal drug use did not improve the model. Cannabis use is associated with an earlier age of onset of schizophrenia, and the gender difference in age of onset is reduced among cannabis smokers.     

Course of schizoaffective psychosis: a retrospective study

This study investigated the clinical course and outcome of 72 patients diagnosed as suffering from schizoaffective psychosis according to ICD-9 criteria who also satisfied RDC criteria for schizoaffective disorder. The results show a clear relationship between patients' overall functioning and premorbid personality: a better premorbid social adjustment indicates a better current state. Those who met DSM-III criteria for schizophrenic or schizophreniform disorder had an earlier age of onset and a higher frequency of relapse, followed by schizoaffective and affective patients. Patients who presented interepisodic psychotic symptoms differed from those who did not in that they showed more recurrences, an earlier age of onset and a premorbid personality with poorer social adjustment. The age of onset of the disease was significantly earlier in patients who had hyperthymic episodes. Schizoaffective disorders therefore are a heterogeneous group as regards premorbid personality, DSM-III diagnosis, and the presence or absence of interepisodic psychotic symptoms and hyperthymic episodes.     

Premorbid and social markers of patients with schizoaffective psychoses

The present study reports on findings in international literature regarding premorbid and social factors of schizoaffective patients and also own findings of the Cologne study (72 schizoaffective patients with a mean follow-up period of 25.6 years). Altogether it can be said that more women suffer from schizoaffective disorders than men. The mean age at first manifestation is higher than that of schizophrenic patients and lower than that of affective disorders, although schizoaffective disorders can occur at any age. Premorbid social adjustment and ability to form a stable heterosexual partnership before onset are good in schizoaffective patients. There seems to be no special premorbid personality of schizoaffective patients. Education and level of vocational training are generally good. Only a few schizoaffective patients belong to the lower social classes. Most schizoaffective patients do not come from a "broken home". Although "life events" are frequent in a schizoaffective population, the relevance of this finding has to be limited: If we evaluate "life events" in regard to single episodes, we find that most episodes, especially episodes occurring during the later course, do not have precipitating factors. In conclusion, it can be said that - besides the already known better prognosis of schizoaffective disorders - several differences exist regarding premorbid and social factors, between schizoaffective disorders and schizophrenia.     

Familiality of clinical characteristics in schizophrenia

Few studies have assessed the familiality of clinical characteristics in schizophrenia. Therefore, we set out to investigate the familiality of the following characteristics; age of onset, course of disorder, employment status at onset, impairment during disorder, marital status at onset, mode of onset and premorbid functioning. Clinical characteristics were recorded using the Operational Criteria Checklist for Psychotic Illness for 155 subjects with an RDC diagnosis of schizophrenia, schizoaffective disorder, or psychosis of unknown origin, from 61 families multiply affected by schizophrenia. Age of onset, course of disorder, impairment during disorder, mode of onset, and premorbid functioning were shown to be familial. The familiality of these clinical characteristics supports their use in the delineation of homogeneous subsets for future genetic studies.     

Childhood-onset schizophrenia: premorbid and prodromal diagnostic and treatment histories

OBJECTIVE: There is increasing interest in the possible relationship between the early diagnosis and treatment of schizophrenia during adolescence and improved long-term outcome. This study reviews the premorbid and prodromal diagnostic and treatment histories for childhood-onset schizophrenia, to assess whether early identification and treatment is possible in this school-age group. METHOD: Parents of 17 children with childhood-onset schizophrenia or schizoaffective disorder were questioned retrospectively regarding symptoms, exposure to mental health professionals, diagnoses, and treatments. RESULTS: Initial presenting symptoms clustered around violent aggression and school problems. Age of first recognized psychotic symptoms ranged from 2 to 11 years, followed 2.0+/-2.0 years later by a diagnosis of schizophrenia. Prior to a schizophrenia diagnosis, these children were exposed to stimulants, antidepressants, lower-dose typical neuroleptics, mood stabilizers, alternative treatments, and individual and family therapy. CONCLUSION: Early diagnosis of childhood-onset schizophrenia is met with caution in the psychological and medical community. These children received many diagnoses before schizophrenia or schizoaffective disorder was diagnosed. A diagnosis of schizophrenia or schizoaffective disorder and utilization of effective atypical neuroleptic treatment was delayed until evaluation by a child and adolescent psychiatrist. Obstacles to early identification and treatment are discussed.     

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.     

Panic disorder in schizophrenia.

OBJECTIVE: To determine the frequency of panic attacks and panic disorder in patients with chronic schizophrenia or schizoaffective disorder. METHOD: Fifty-three male outpatients meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for chronic schizophrenia or schizoaffective disorder were administered sections of the Structured Clinical Interview for DSM-IV (SCID). If panic attacks were reported, patients were queried about treatment and about onset relative to psychotic symptoms. RESULTS: Forty-nine patients were sufficiently organized to participate in the evaluation. Twenty-one (43%) experienced panic attacks, and 16 (33%) had current or past panic disorder. Eight (50%) of the 16 with panic disorder had been treated for panic. Substance dependence was not associated with having panic attacks or current or past panic disorder. Patients with paranoid schizophrenia were more likely than patients with schizoaffective or undifferentiated schizophrenia to have experienced panic attacks (57% versus 20%, chi 2 = 6.0, P < 0.02) or panic disorder (47% versus 10%, chi 2 = 6.9, P < 0.01). CONCLUSION: Panic attacks and panic disorder are common in men with schizophrenia or schizoaffective disorder. Panic disorder may be an overlooked comorbid diagnosis in patients with schizophrenia.     

Reproductive factors and clinical features of Parkinson's disease

BackgroundLiterature suggests that sex steroid hormones may modify the risk for Parkinson's disease (PD). We investigated the potential effect of reproductive factors on the clinical features of idiopathic PD (IPD) patients.MethodsAll IPD female patients admitted to and evaluated at our Institute over a 12-month period were included in the present cross-sectional study. We investigated the effect of the following parameters by multivariate linear regression analysis: age at menarche, age at menopause, length of fertile life, duration of exposure to endogenous estrogens and cumulative length of pregnancies, use of contraceptives and hormonal replacement therapy.ResultsIn total, 579 patients were evaluated and 497 reported menopause before PD onset. In this population, age at PD onset was positively associated with age at menarche and at menopause, length of fertile life and duration of estrogen exposure. Moreover, UPDRS motor score was inversely associated with age at menopause, length of fertile life and duration of estrogen exposure. Increasing age at menarche was also associated with predominant resting tremor at PD onset. In models refitted on patients with early PD (disease duration <5 years; N = 226) all the associations found were confirmed. The relationship between surrogates of estrogen exposure and UPDRS motor score actually became more significant.ConclusionsOur observations support the concept that hormonal exposure of the nigro-striatal network during life may influence its susceptibility to degenerative stimuli in later life, but the association does not seem to be unique? unidirectional. In particular, increased severity of PD signs correlates with shorter duration of estrogen exposure. The underlying mechanisms need to be clarified.     

Pubertal trajectory in females with Rett syndrome: A population-based study

Background: Rett syndrome is a severe genetic neurodevelopmental disorder mainly affecting females. The aim of this study was to describe pubertal development in a population-based cohort of females with Rett syndrome. Methods: To assess pubertal trajectory we used six waves of data provided by parents of girls and women, recruited through the Australian population-based Rett Syndrome Database. The age at which adrenarche, thelarche or menarche occurred was used as the parameter for time to event (survival) analysis. The relationships between BMI, mutation type and the trajectories were investigated, using Cox proportional hazards. Results: One quarter of girls reached adrenarche by 9.6 years, half by 11 years and three quarters by 12.6 years. Half reached menarche by 14 years (range 8–23). Being underweight was associated with later age at adrenarche, thelarche and menarche, while higher BMI (overweight) was associated with earlier onset. In general, girls with C-terminal deletions and early truncating mutations reached pubertal stages earlier and those with the p.R168X mutation reached them later. Conclusion: The pubertal course in Rett syndrome may be abnormal, sometimes with early adrenarche but delayed menarche. These features may be genotype dependent and may have varying relationships with growth and bone acquisition.     

Course of adolescent psychotic disorder with schizoaffective episodes

This study examines educational/occupational outcome and social functioning of adolescents treated for psychosis (mean onset age 16.1 yrs±1.3). In a sample of 157 subjects, 26 patients with schizoaffective episodes (defined as any episode meeting ICD-9 criteria for schizoaffective psychosis, occurring at any time during the course of illness) were compared to 101 patients with schizophrenia, and to 30 affective disordered patients, all without schizoaffective episodes. Follow-up information (mean interval 7.3 yrs ±4.3) was obtained on 130 subjects. The three groups did not differ concerning sex, duration of first inpatient treatment, symptoms and social competence at discharge, nor at follow-up. At the time of outcome subjects with schizoaffective episodes showed greater similarities to schizophrenic than to severe affective disorder. Educational and occupational impairment was found in 72% of the schizoaffective group (schizophrenic group 79%, affective group 40%), obvious or more severe social disability in 86% of the schizoaffective group (schizophrenic 79%, affective 40%). Disabilities regarding performance of specific social roles and specific downward educational and occupational drifts were found to be more marked in schizoaffective than in affective disorder. Implications for further research and clinical practice are discussed.     

Pubertal Development in Rett Syndrome Deviates From Typical Females

BackgroundRett syndrome is a unique neurodevelopmental disorder, affecting approximately one in 10,000 live female births, most experiencing reduced growth. We characterized pubertal trajectories in females with Rett syndrome. We hypothesized that pubertal trajectory deviates from the general female population with early pubertal onset and delayed menarche.MethodsParticipants were individuals enrolled in the Rett Syndrome Natural History Study with clinical diagnosis of Rett syndrome or mutations in MECP2. Intervals to thelarche, adrenarche, and menarche were assessed by survival analysis; body mass index, mutation type, clinical severity, and pubertal milestone relationships were assessed by log-likelihood test; pathway synchrony (relationship between thelarche, adrenarche, and menarche) was assessed by chi-squared analysis.ResultsCompared with the general female population, more than 25% initiated puberty early, yet entered menarche later (median age 13.0 years). A total of 19% experienced delayed menarche. Median length of puberty, from thelarche to menarche, was 3.9 years. Higher body mass index correlated with earlier thelarche and adrenarche but not menarche; milder mutations correlated with earlier menarche; and milder clinical presentation correlated with earlier thelarche and menarche. Fifty-two percent entered puberty in synchrony, but different from the general population, 15% led with thelarche and 32% with adrenarche.ConclusionsPubertal trajectories in Rett syndrome differ from general population, entering puberty early and reaching menarche later. Body mass index affects pubertal timing, but the relationship between specific mutations, clinical presentation, and underlying neuroendocrine pathology is less clear.     

Is the psychopathology of acute and transient psychotic disorder different from schizophrenic and schizoaffective disorders?

OBJECTIVE: This study explores psychopathological aspects of acute and transient psychotic disorders (ATPD), a diagnostic category introduced with ICD-10, to elucidate its relationship with schizophrenia and schizoaffective psychoses. METHODS: We recruited all consecutive inpatients fulfilling the ICD-10 criteria of ATPD (F23) during a 5-year period as well as control groups with "positive" schizophrenia (PS) and bipolar schizoaffective disorder (BSAD) matched for gender and age at index episode. For the evaluation of psychopathological parameters during index episode a standardized symptom list was used. Prepsychotic (prodromal) symptoms were also assessed. RESULTS: During the prepsychotic period few differences between the groups were detected. The most important difference between ATPD and the other two other psychotic disorders regarding phenomenology of the full-blown episodes was a higher frequency of "rapidly changing delusional topics", "rapidly changing mood" and anxiety in ATPD. CONCLUSION: ATPD show a characteristic psychopathological picture consistent with earlier concepts such as cycloid psychoses and bouffée délirante. Nevertheless, psychopathology alone is not enough to establish ATPD as an independent nosological entity.