Lateralized anomalous perceptual experiences in schizophrenia.

Four cases of schizophrenia are described, in which subjects reported anomalous perceptual experiences confined to one visual field, in all cases the left visual field. The pattern, content and laterality of such anomalous perceptions point to the presence of right hemisphere dysfunction in schizophrenia. Further evidence to this effect comes from examining the type of anomalous perceptual experiences reported by subjects with focal lesions in either hemisphere. Those with right hemisphere damage but not those with left hemisphere damage report almost identical experiences to those seen in the 4 schizophrenics described here.     

Age at onset of schizophrenia and neuroleptic dosage

Background: Lower age at onset of schizophrenia has been traditionally associated with poorer response to treatment and less favourable prognosis. The aim of the study was to find out whether age at onset of schizophrenia is related to the dosage of typical neuroleptics in outpatients. Method: Age at onset was defined as age at first seeking of psychiatric help. Demographic, social and disease-related characteristics were studied in a group of 200 stable outpatients with schizophrenia (100 males and 100 females). Psychopathological symptoms were assessed with the Krawiecka Scale. Neuroleptic dosage was converted to milligrams of chlorpromazine equivalents and logarithmically transformed to obtain normal distribution. Results: Onset of schizophrenia occurred earlier in males than in females. The average dosage was 251.7 (SD 303.9) mg chlorpromazine equivalents. In a multivariate linear regression model, lower age at onset and higher sum of symptoms were related to the drug dosage. Conclusion: The results confirm the findings of other authors that patients with lower age at onset are less responsive to typical neuroleptics. Some of the patients with early onset would be more appropriately treated with atypical neuroleptics, which may have better therapeutic efficacy. Accepted: 3 September 1999     

Sex difference in age at onset of schizophrenia

The age at onset of schizophrenia was determined in 100 male and 100 female patients who unequivocally met DSM-III criteria for the illness. Three different indexes of onset were used: first treatment, first hospitalization, and the immediate family's first awareness of psychotic symptoms and signs. The mean age at onset of the male patients was approximately five years earlier than that of the female patients according to all three criteria. About nine of ten male patients, compared with only two of three female patients, became schizophrenic before the age of 30 years. The onset of psychosis after the age of 35 years occurred in 17% of women and in only 2% of men. About 10% of women gave no evidence of psychosis until after the age of 40 years. The reason for the sex difference is not readily apparent, but it could be a valuable clue to some of the causes of schizophrenia.     

Cannabis use and age at onset of schizophrenia

OBJECTIVE: The purpose of the study was to assess the independent influences of gender and cannabis use on milestones of early course in schizophrenia. METHOD: In this population-based, first-contact incidence study conducted in The Hague, the Netherlands, patients (N=133) were interviewed with the Comprehensive Assessment of Symptoms and History, and key informants were interviewed with the Instrument for the Retrospective Assessment of the Onset of Schizophrenia. Milestones of early course were 1) first social and/or occupational dysfunction, 2) first psychotic episode, and 3) first negative symptoms. RESULTS: Male patients were significantly younger than female patients at first social and/or occupational dysfunction, first psychotic episode, and first negative symptoms. Cannabis-using patients were significantly younger at these milestones than were patients who did not use cannabis. Multivariate analyses showed that cannabis use, but not gender, made an independent contribution to the prediction of age at first psychotic episode: male cannabis users were a mean of 6.9 years younger at illness onset than male nonusers. In contrast, age at first social and/or occupational dysfunction and the risk of developing negative symptoms before the first contact with a physician for treatment of possible psychotic disorder were predicted by gender, but not by cannabis use. CONCLUSIONS: The results indicate a strong association between use of cannabis and earlier age at first psychotic episode in male schizophrenia patients. Additional studies examining this possibly causal relationship are needed.     

Admixture analysis of age at onset in schizophrenia

In schizophrenia, clinical, familial and biological characteristics according to age at onset (AAO) suggest that AAO is a valid candidate symptom for genetic studies. However, none of the various thresholds used to define AAO subgroups in schizophrenia has been validated. We aim to define different AAO subtypes by admixture analysis in a sample of prospectively recruited subjects with schizophrenia. Consecutive inpatients and outpatients (N=141) meeting DSM IV criteria for schizophrenia were included. We used admixture analysis to investigate whether the observed AAO distribution consisted of a mixture of gaussian distributions and then compared clinical features and familial risks in the various groups of subjects. The model that best fitted the observed AAO distribution was a mixture of two gaussian distributions (mean+/-S.D.): (19.91+/-3.56 years) and (33.48+/-8.2 years), with a cutoff point at 28 years. The existence of two subgroups according to AAO was further confirmed by the different clinical and familial profiles of these subgroups. The early-onset group consisted predominantly of male patients, with non-paranoid subtypes and with a higher familial risk of schizophrenia spectrum disorders and affective disorders. The late-onset group of patients presented predominantly paranoid subtype, preponderance of females; they were more likely to be married and to have children. We identified two subgroups of schizophrenic subjects with different clinical and familial profiles. This study provides a mathematical validation of the existence of two subgroups defined by an onset of schizophrenia before or after 28 years. These results may have important implications for the search for schizophrenia susceptibility factors. Working with homogeneous subgroups defined on the basis of AAO may facilitate the identification of genetic vulnerability factors in schizophrenia.     

Does family history of schizophrenia influence age at onset of schizophrenia?

The relation between age at onset of schizophrenia diagnosed using DSM-III criteria and the presence or absence of this illness among first-degree relatives was investigated in 2417 patients. The mean age at onset among those with a family history of schizophrenia was slightly and nonsignificantly earlier than that of schizophrenic patients without a positive family history. The former developed their illness before the age of 25 years more frequently than did the latter.     

Asymmetry of the ventricle and age at the onset of schizophrenia

The relationship between lateral ventricular size or its asymmetry and age at the onset of schizophrenia was investigated in 20 schizophrenic patients diagnosed according to DSM-III-R criteria. The ventriclebrain ratio (VBR) was determined using three transaxial slices of magnetic resonance image (MRI) and asymmetry of the lateral ventricle was evaluated from the laterality index of the lateral ventricular area: (left-right/lef+right)×100. Each age at the onset of the prodromal and active phase according to DSM-III-R criteria was determined for each patient. The results showed that asymmetry of the ventricle, but not VBR, was significantly correlated inversely with age at the onset of both the prodromal phase and active phase. Neither asymmetry nor VBR correlated with the duration of illness, age at MRI scanning, or severity of clinical symptoms. It would thus appear that greater asymmetry of the ventricle is associated with earlier onset of schizophrenia.     

The impact of gender and age at onset on the familial aggregation of schizophrenia

Summary Some recent family studies have shown that the familial risk for schizophrenia is higher in female than in male schizophrenics. It is debated whether the risks for the other disorders, such as schizotypal personality disorder or affective disorders in families of schizophrenics are similarly influenced by the proband's gender. Also, the reason for the effect of proband's gender on the recurrence risk for schizophrenia has not been clarified. This family study (159 probands, 589 first degree relatives) confirms that schizophrenia, but also schizophrenia spectrum disorders were more frequent in families of female compared with male schizophrenics. Neither age at onset in probands nor the interaction between gender and age at onset in probands had a relevant impact on the risk figures in relatives. Affective disorders occurred in families independently of the probands' gender. Aetiological heterogeneity or ascertainment bias may account for the modifying effect of proband's gender in schizophrenia.     

Influence of sex on age at onset of schizophrenia

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.     

Ventricle-to-brain ratio and symptoms at the onset of first-break schizophrenia.

Ventricle-to-brain ratio (VBR) was measured from the computed tomographic (CT) scans of 33 very recent-onset psychotic patients. Illness severity and positive and negative symptoms were also assessed in 21 of these patients with schizophreniform disorder. Forty-five neurology patients served as controls. Analyses revealed no significant differences between the VBR of the psychotic group as a whole, the schizophreniform subgroup, the affective psychotic subgroup, and the controls. Control subjects with a neurological diagnosis of vertigo or syncope had significantly higher VBR than the remainder of the control group and the psychotic group. When the psychotic group was compared to the control group minus those controls with syncope or vertigo, the psychotic group had significantly higher VBR. The schizophreniform subgroup also had significantly higher VBR than the control group minus subjects with vertigo or syncope. In the schizophreniform subgroup, positive symptoms and illness severity were associated with smaller VBR. There was no association between negative symptoms and VBR.     

The Maudsley early onset schizophrenia study

OBJECTIVE: To examine the contribution of premorbid function, duration of untreated psychosis (DUP), age of onset, severity of symptoms at presentation, and number of subsequent hospitalisations to the outcome of early onset schizophrenia (EOS; onset before 17th birthday). METHOD: Twenty-three EOS patients (mean age at onset 15.16 +/- 1.39 years) were re-assessed after a mean interval of 4 +/- 1.08 years. At baseline and follow-up clinical diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Axis I Disorders and symptoms were assessed with the Positive and Negative Syndrome Scale. Premorbid function, as measured with the Premorbid Adjustment Scale, age of onset and DUP were assessed at baseline only. Outcome was evaluated using the Social Adaptation Self-Evaluation Scale (SASS) and the Global Assessment of Functioning (GAF) Scale. RESULTS: Mean DUP was 2.95 +/- 3.59 months and mean total PAS score was 6.65 +/- 3.02. They had an average of 2.09 +/- 1.44 hospitalisations and their mean SASS and GAF scores were 37.27 +/- 6.5 and 54.19 +/- 18.99, respectively. Poor childhood premorbid function and the severity of negative symptoms at baseline were correlated with worse SASS and GAF scores. No other significant associations were found. CONCLUSIONS: Poor childhood function is the most significant predictor of outcome in EOS.     

The Maudsley early onset schizophrenia study: cognitive function in adolescents with recent onset schizophrenia

Neuropsychological function has been little studied early in the course of adolescent onset schizophrenia. The present study investigated cognitive function in adolescents with recent onset schizophrenia (n=20) and healthy controls (n=21), employing a comprehensive battery of intelligence, memory and executive function paradigms. Relative to the control group, the patients showed significant or near-significant deficits in more than half of the cognitive variables we examined. A substantial proportion of this broadly based neuropsychological deficit could be accounted for, at least in part, by a mild decrement in general intellectual ability. However, deficits in general and verbal memory remained highly significant after co-varying for IQ.     

Age at onset in schizophrenia. A familial perspective

We examined the impact of familial factors on age at onset in schizophrenia. Results from a literature review and from new analyses of two family studies and one twin study of schizophrenia support the following hypotheses: (1) no strong or consistent relationship exists between age at onset in schizophrenia and recurrence risk for schizophrenia in relatives; (2) age at onset in schizophrenia is not strongly related to the recurrence risk for other psychiatric disorders in relatives; and (3) in systematically ascertained pairs of affected siblings, the age at onset of schizophrenia is modestly correlated, whereas the correlation in age at onset in concordant monozygotic twin pairs is much higher. These results suggest that (1) from a familial perspective, early- and late-onset adult schizophrenia appear to be the same disorder, and (2) given that an individual will develop schizophrenia, familial factors, which may be genetic, influence the age at onset of the condition.     

The nature of overinclusive thinking in schizophrenia

Schizophrenics were compared with neurotic controls on four tests of categorical thinking in an attempt to discover the nature of overinclusive thinking. The tests provided both verbal and nonverbal measures of conceptual loosening, the proportion of out-of-category items, distortion of the internal structure of a category and any tendency towards overcategorization. The results showed that schizophrenics were relatively worse on nonverbal than on verbal categories with, in particular, a greater degree of conceptual loosening and a tendency towards overcategorization. The most striking abnormality emerged during observation of the actual sorting strategy itself. Schizophrenics tackled the task in a way which suggests that they lack the ability to form a Gestalt of the task.     

Evidence of a latitudinal gradient in the age at onset of schizophrenia

Variation in the age at onset of a multifactorial disease often reflects variation in cause. Here we show a linear latitudinal gradient in the mean age at onset of schizophrenia in 13 northern hemisphere cities, ranging from 25 years old in Cali, Columbia (at 4 degrees north) to 35 years old in Moscow, Russia (at 56 degrees north). To our knowledge, this striking association has not been previously reported. We consider several explanations, including the effects of pathogen stress, natural selection, sexual selection, migration, life-history profiles, or some combination of these factors, and we propose a test of competing causal hypotheses.     

Relationship between physical anomalies and age at onset of schizophrenia

Among 50 schizophrenic patients grouped by age at onset, the group with onset at or before age 18 had significantly more subjects with minor physical anomalies. These findings suggest that early-onset schizophrenia is associated with a more compromised CNS.     

The impact of familial loading on gender differences in age at onset of schizophrenia

To evaluate the impact of familial loading and gender on age at onset, 197 schizophrenic patients were investigated. Patients with familial loading had an earlier age at onset without gender differences. In contrast, an earlier age at onset for men was found in sporadic cases. These data support that both gender and familial loading contribute to the heterogeneity of schizophrenia.