Influence of Sex on Age at Onset of Schizophrenia

Abstract: The age at onset of schizophrenia was investigated in 2,417 inpatients (1,433 males and 984 females) meeting the DSM-III criteria for schizophrenia. About 80% of the patients became schizophrenic before the age of 30. The mean age at onset of the male patients was slightly earlier than that of the female patients. There was a higher cumulative percentage of the male patients who became affected at each age quinquennium. More men than women became schizophrenic before the age of 30.     

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.     

Forty-two-years later: the outcome of childhood-onset schizophrenia

Summary This paper describes the long-term course of 76 patients who had been consecutively admitted to the Department of Child and Adolescent Psychiatry, Philipps University, between 1920 and 1961 with a suspected diagnosis of childhood-onset schizophrenia. By means of a consensus analysis of available data in accordance with ICD-10 criteria, the diagnosis of schizophrenia was confirmed in only 50% of the original sample (n = 38, childhood-onset schizophrenia group); whereas the rest of the sample were allotted other diagnoses (n = 38, non-schizophrenia group). A follow-up investigation was conducted, interviewing all available patients, if possible, or their first-degree relatives or doctors. In the childhood-onset schizophrenia group, age at onset (mean ± S.D.) was 12.7 ± 2.5 (range 5–14) years and age at follow-up was 55.0 ± 4.8 (range 42–62) years. The outcome of this group was poor. According to the Global Assessment Scale (GAS), only 16% had a good (GAS score 71–100) and 24% had a moderate (GAS score 41–70) outcome. In the 16 childhood-onset schizophrenia patients who could be personally investigated at follow-up, 10 (62.5%) displayed severe or moderate depressive symptoms according to the BPRS depressive score. The death rate (including suicide) was significantly higher in the schizophrenia group (n = 15; 39.5%) than in the non-schizophrenia group (n = 7; 18.4%). A comparison of the life-time diagnoses of the total sample (n = 76) at follow-up with the ICD-10 diagnoses made retrospectively revealed a diagnostic stability in 69 (91%) and a change of diagnosis in 7 (9%) cases, among them 4 who were originally diagnosed as having childhood-onset schizophrenia.     

Age of Onset in Schizophrenia Spectrum Disorders: Complex Interactions between Genetic and Environmental Factors

In this study we evaluated the role of a candidate gene for major psychosis, Sialyltransferase (ST8SIA2), in the risk to develop a schizophrenia spectrum disorders, taking into account exposure to stressful life events (SLEs). Eight polymorphisms (SNPs) were tested in 94 Schizophreniainpatients and 176 healthy controls. Schizophrenia patients were also evaluated for SLEs in different life periods. None of the SNPs showed association with schizophrenia. Nevertheless, when crossing genetic variants with childhood SLEs, we could observe trends of interaction with age of onset. Though several limitations, our results support a protective role of ST8SIA2 in individuals exposed to moderate childhood stress.     

Onset of intractability and its course over time: the Dutch study of epilepsy in childhood

Purpose: Intractability in epilepsy is difficult to define, and little is known about its onset, course, and duration. We investigated these aspects (as well as the occurrence of intractability) during long‐term follow‐up in patients with epilepsy, focusing on possible explanations for the variation in time of onset and duration of intractability. Methods: After diagnosis, 453 patients with childhood‐onset epilepsy had a 5‐year follow‐up with regular visits and data collection. Ten years later they received a questionnaire with items concerning epilepsy, which was completed by 413 patients resulting in a mean follow‐up of 15 years. Intractability during the first 5 years was compared with that in the last year of follow‐up. Intractability was defined as having no 3‐month remission during a 1‐year period despite adequate medical treatment. Key Findings: At least 12.1% of the cohort had a period of intractability during the 15‐year follow‐up, and 8.5% were intractable in the final year. Of the patients with idiopathic etiology 4.3% had a period of intractability versus 17.0% for those with cryptogenic, and 22.6% for those with remote symptomatic etiology (p < 0.001). Other risk factors at baseline were younger age at first seizure, generalized cryptogenic/symptomatic or localization‐related symptomatic epilepsy, mental retardation, and febrile convulsions before enrollment. The cumulative risk of a period of intractability was 6.1% (95% confidence interval [CI] 3.7–8.5) at 2 years follow‐up and 8.2% (95% CI 5.4–11.0) at 5 years. The mean time to onset of intractability during the first 5 years of follow‐up was 1.6 (95% CI 1.3–2.0; median 1.0) years and the mean duration of intractability during these 5 years was 3.3 (95% CI 2.8–3.8; median 3.6) years. Fifteen patients were intractable only during the first 5 years of follow‐up (group A), and 19 subjects were intractable both during the first 5 years and the last year of follow‐up (group B). Compared with group A, group B had shorter remission and a longer time to intractability during the first 5 years and more were intractable in the fifth year of follow‐up. Sixteen other patients had a late onset of intractability after 5 years of follow‐up, sometimes after long periods of remission (group C). No significant differences in baseline characteristics were found among groups A, B, and C, but slightly more children in groups B and C became mentally retarded during the follow‐up. In all groups, antiepileptic drugs were of little use in preventing and ending intractability. Significance: There is a large unpredictable variation in time of onset, course, and duration of intractability, with a higher chance of final intractability after a poor course during the first 5 years of follow‐up. The natural course of epilepsy probably best explains the variable course of intractability. The effect of medication seems to be minor.     

Brief Report: Lack of Correlation Between Age of Symptom Onset and Contemporaneous Presentation

The parents/guardians of 50 individuals were surveyed using a semistructured interview to determine the feasibility of this method and to establish ages of symptom onset. Thirty-eight informants were able to recall sufficient detail to allow categorization of the age of symptom onset. Chi-square analysis confirmed a significant association between investigators' categorization and informants' categorization. Contemporaneous presentation was indexed using Childhood Autism Rating Scale, the Autism Behavior Checklist, the Conners Hyperactivity Index, and the Ritvo-Freeman Real Life Rating Scale for Autism. No significant correlations were determined between any of these indices of symptom severity and age of symptom onset.     

Predictors of Treatment-Resistant and Clozapine-Resistant Schizophrenia: A 12-Year Follow-up Study of First-Episode Schizophrenia-Spectrum Disorders

Studies on the long-term development and early predictors of treatment-resistant schizophrenia (TRS) and clozapine-resistant TRS (CR-TRS) in patients with first-episode schizophrenia-spectrum disorders (FES) are limited and have not considered the impact of early intervention services (EIS). This study aimed to explore the development of TRS and CR-TRS among patients with FES over 12 years of follow-up. Of the 1234 patients with FES, 15% developed TRS. A total of 450 patients with schizophrenia or schizoaffective disorder were included in a nested case-control study (157 TRS and 293 non-TRS). Younger age of onset, poorer premorbid social adjustment during adulthood, longer duration of first episode, a greater number of relapses, and a higher antipsychotic dose in the first 24 months were associated with earlier TRS. CR-TRS patients, constituting 25% of TRS patients, had a poorer premorbid social adjustment in late adolescence and longer delay before clozapine initiation compared with non-CR-TRS. CR-TRS had poorer clinical and functional outcomes at 12-year follow-up. However, TRS patients on clozapine had a lower mortality rate compared with non-TRS patients. EIS did not have a significant impact on the development of TRS, but patients in the EIS group had a shorter delay of clozapine initiation. Results suggested that neurodevelopmental factors, early clinical characteristics, and requirement for higher antipsychotic dose may be associated with TRS development, highlighting multiple pathways leading to this form of illness. Specific interventions including relapse prevention and early initiation of clozapine during the early course of illness may reduce the rate of TRS and improve patient outcomes.     

Schizoaffective disorders with and without onset in the puerperium

Summary The premorbid and sociodemographic features, long-term course and long-term outcome (on average 23.8 resp. 26.8 years after onset of illness) were compared in 30 female schizoaffective patients with onset of their illness during the puerperium and 60 female schizoaffective patients with onset at other times. The majority of premorbid and sociodemographic variables as well as course parameters were similar in the two groups. Most of the few differences (in age at first manifestation, marital state at onset, presence of stable heterosexual relationship before onset, acuteness of onset, presence of life events) are closely connected with the inclusion and exclusion criteria applied for the puerperal disorders (exclusion of patients with preexisiting illness or psychiatric symptoms during pregnancy, inclusion only if onset was within 6 weeks of parturition). The puerperal schizoaffective disorders began more frequently with a schizomanic episode and less frequently with a schizodepressive episode than did the non-puerperal schizoaffective disorders, a finding which perhaps reflected the pathoplastic role of the puerperium on psychotic disorders. Several significant differences were found regarding the long-term outcome (frequency of persistent alterations, level of global functioning and disability, non-achievement of the expected social development, loss of autarky), confirming earlier findings that puerperal disorders generally have a better outcome than other psychotic disorders.     

Age at onset of schizophrenia: gender differences and influence of temporal socioeconomic change

This study was undertaken to examine whether males develop schizophrenia at a younger age than females, and whether temporal socioeconomic change affects the age at onset of schizophrenia. The subjects were 848 ICD-9 schizophrenics who were admitted to Nihon University Hospital, Tokyo, Japan, during the period of 1955-64 (n = 468 (214 males and 254 females), group A) or during the period of 1982-91 (n = 380 (220 males and 160 females). group B). Schizophrenic males showed an earlier age at onset than schizophrenic females. However, the mean age at onset of schizophrenia did not differ significantly between group A and group B. These results indicate that the gender difference in age at onset of schizophrenia has not been influenced by temporal socioeconomic change.     

Age at onset and the outcomes of schizophrenia: A systematic review and meta‐analysis

The aim of this study was to analyse the effect of age at onset on the long‐term clinical, social and global outcomes of schizophrenia through a systematic review and a meta‐analysis. Original studies were searched from Web of Science, PsycINFO, Pubmed and Scopus, as well as manually. Naturalistic studies with at least a 2‐year follow‐up were included. Of the 3509 search results, 81 articles fulfilled the inclusion criteria. The meta‐analysis was performed in Stata as a random‐effect analysis with correlation coefficients between age at onset and the outcomes (categorized into remission, relapse, hospitalization, positive symptoms, negative symptoms, total symptoms, general clinical outcome, employment, social/occupational functioning and global outcome). There was a statistically significant (P < .05) correlation between younger age at onset and more hospitalizations (number of studies, n = 9; correlation, r = 0.17; 95% confidence interval, CI 0.09–0.25), more negative symptoms (n = 7; r = 0.14; 95% CI 0.01–0.27), more relapses (n = 3; r = 0.11; 95% CI 0.02–0.20), poorer social/occupational functioning (n = 12; r = 0.15; 95% CI 0.05–0.25) and poorer global outcome (n = 13; r = 0.14; 95% CI 0.07–0.22). Other relationships were not significant. This was the first systematic review of the effects of age at onset on the long‐term outcomes of schizophrenia. The results show that age at onset has a small, but significant impact on some of the outcomes of schizophrenia.     

IQ Trajectory, Cognitive Reserve, and Clinical Outcome Following a First Episode of Psychosis: A 3-Year Longitudinal Study

Comparison of current and estimated premorbid IQ in schizophrenia suggests that there are subgroups with low IQ, deteriorated IQ (DIQ), or preserved IQ and that this is established by psychosis onset. There are no controlled studies examining the trajectory of these IQ subgroups longitudinally or their relationship with clinical and social outcomes. Of 129 individuals with first-episode schizophrenia or schizoaffective disorder, 25% showed stable low IQ, 31% showed stable IQ in the average/high range, and 44% demonstrated intellectual deterioration by 10 points or more. Patients in the low and deteriorated groups were equally impaired on tests of memory and executive function compared with the preserved average/high-IQ group and controls and showed more negative and disorganization symptoms than the preserved average/high-IQ group. Sixty patients and 27 controls were assessed again 1 and 3 years later. There was no evidence that those with IQ deterioration at baseline continued on a declining cognitive trajectory or that those with preserved average/high IQ experienced subsequent IQ decline. The low IQ group showed no change in IQ, whereas both the DIQ and the preserved IQ groups improved. However, the rate of improvement of these 2 subgroups was no greater than that of the healthy controls, suggesting that this reflected practice effects. Both the low and the deteriorated groups had longer index admissions, more core negative symptoms, and worse occupational outcomes at 3 years. These data suggest that following psychosis onset, IQ is stable and that it is IQ at psychosis onset rather than premorbid IQ predicts a more severe illness.     

Course characteristics in the differentiation of dementia of the Alzheimer type and multi-infarct dementia

Clinico-pathological studies have shown that the clinical diagnosis of multi-infarct dementia (MID) is even more difficult than that of dementia of the Alzheimer type (DAT). The study evaluated the significance of course characteristics for the diagnosis of MID and DAT. Course characteristics were rated when 57 demented patients were admitted to our neurogeriatric department. Diagnosis of MID and DAT, respectively, was established after a follow-up study with repeated neurological, psychiatric and neuropsychological investigations. In 21 cases diagnosis was confirmed by postmortem neuropathology. MID lacked the typical course of the disease in about two thirds of patients, while most DAT patients presented with the typical course of primary degenerative dementia. Features of the "typical" clinical course of MID (abrupt onset, stepwise deterioration) helped to exclude DAT, whereas MID could not be excluded on the basis of a history of insidious onset and gradual decline.     

Course and outcome of bipolar II disorder: a retrospective study

To study course and outcome of Bipolar II disorder, 217 major depressive episode (MDE) patients were interviewed with Structured Clinical Interview for DSM-IV. Patients with more than three MDE and patients with fewer MDE were compared. Patients with more than three MDE were 77.8%. Comparisons, controlled for confounding effects of age and illness duration, found that patients with many MDE had significantly lower age at onset and more chronicity. Results support subtyping of Bipolar II in a small good-outcome group, and a large moderate-poor-outcome group.