Age-at-first-registration for affective psychosis and schizophrenia

We compared the age-at-first-registration for patients with schizophrenia and affective psychosis in a statewide mental health register. After excluding those receiving (1) a diagnosis of both schizophrenia (ICD-9 295.x) and affective psychosis (ICD-9 296.x), or (2) a diagnosis of ICD-9 296.1 (which can cover "major depressive episode"), we adjusted the distributions for the age structure of the background general population. We found that all distributions showed a wide age range of onset, with a similar male modal age group of 20-24 for schizophrenia and 25-29 for affective psychosis. The female modal age group was 50-54 for both diagnoses. Although more individuals were diagnosed with schizophrenia (males = 2,434, females = 1,609) than with affective psychosis (males = 670, females = 913), the shape of the two distributions was similar. This finding suggests that factors influencing age-at-first-registration for schizophrenia and affective psychosis may be similar, especially for females.     

An increased risk of stroke among young schizophrenia patients

OBJECTIVE: This study sets out to estimate the risk of stroke developing among young schizophrenia patients during a five-year follow-up period after hospitalization for episodes of acute exacerbation. METHODS: Hospitalized schizophrenia patients under 45 years of age were identified from the Taiwan National Health Insurance Research Database for the year 1998 (n=5001). Two age-matched cases were randomly selected for each schizophrenia patient from among patients who underwent appendectomies in the same year (n=10,002). Each individual patient was retrospectively followed up from 1998 until the end of 2003 to determine whether any had developed strokes. Cox proportional hazard regressions were carried out to compute the adjusted five-year survival rate. RESULTS: A total of 219 patients (1.46%) developed strokes during the five-year follow-up period, with the attacks occurring among 2.46% of schizophrenia patients and 0.94% of the comparison cohort. Following adjustment for patients' demographic characteristics, select comorbid medical disorders and substance abuse, schizophrenia patients were found to be 2.02 times (p<0.001) more likely to develop strokes during the follow-up period than age-matched appendectomy patients. The adjusted hazard ratios of developing stroke for male and female schizophrenia patients were, respectively, 1.64 (p<0.001) and 2.87 (p<0.001) times greater than their counterparts in the comparison group. CONCLUSIONS: As compared with the comparison group, young schizophrenia patients demonstrated a two-fold increased risk of developing stroke during the five-year period after hospitalization. The risk of developing stroke among schizophrenia patients was found to be much higher for females than males.     

男女儿童青少年精神分裂症患者临床特征的比较

目的:比较儿童青少年精神分裂症男性与女性患者临床特征的差异。方法:对125例男性(男性组)和133例女性(女性组)儿童青少年精神分裂症患者的年龄、发病年龄、病前诱因、阳性家族史、病程特点、住院天数、简明精神病量表(BPRS)、大体评定量表(GAS)及临床疗效总评量表(CGI)评分等临床特征进行比较。结果:男性与女性患者在年龄、发病年龄、病前诱因、阳性家族史、病程特点、住院天数方面比较差异无统计学意义(P均0.05)。BPRS评分中敌对性、动作迟缓、情感淡漠、缺乏活力因子分男性组高于女性组(t=2.164,t=3.317,t=2.096,t=2.230;P0.05或P0.01);幻觉、思维障碍因子分女性组高于男性组(t=3.682,t=2.987;P0.01或P0.001)。入院时GAS、CGI-SI评分及出院时CGI-GI评分两组间差异无统计学意义(P均0.05),出院时CGI-EI评分女性组高于男性组(t=2.466)、自知力评分男性组高于女性组(t=2.403),差异有统计学意义(P均0.05)。结论:男性儿童青少年精神分裂症患者的临床特征以情感淡漠、缺乏活力等阴性症状为主,女性则以幻觉、思维障碍等阳性症状更突出;女性临床疗效优于男性。     

Childhood head injury and expression of schizophrenia in multiply affected families

BACKGROUND: The etiology of schizophrenia is believed to include genetic and nongenetic factors, with the pathogenesis involving abnormal neurodevelopment. We investigated whether mild head injury during brain maturation plays a role in the expression of schizophrenia in multiply affected families. METHODS: We compared the history and severity of head injuries in childhood (age, < or =10 years) and through adolescence (age, < or =17 years) in 67 subjects with narrowly defined schizophrenia and 102 of their unaffected siblings from 23 multiply affected families. In subjects with schizophrenia, only head injuries preceding the onset of psychosis were considered. RESULTS: Subjects in the schizophrenia group (n = 16 [23.9%]) were more likely than the unaffected siblings group (n = 12 [11.8%]) to have a history of childhood head injury (P =.04; odds ratio, 2.35 [95% confidence interval, 1.03-5.36]). Subjects in the schizophrenia group with a history of childhood head injury had a significantly younger median age at onset of psychosis (20 years) compared with those with no such history (25 years; z = -2.98; P =.003). The severity of head injury ranged from minimal to mild, including concussions, but within this narrow range, severity was correlated with younger age at onset (r(s) = -0.66; P =.005). Head injury occurred a median of 12 years before the onset of psychosis. Results were similar if head injuries during adolescence were included, but did not achieve statistical significance. CONCLUSIONS: Mild childhood head injury may play a role in the expression of schizophrenia in families with a strong genetic predisposition. Prospective studies of mild head injury should consider genetic predisposition for possible long-term neurobehavioral sequelae.     

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     

Psychosocial problems and seizure-related factors in children with epilepsy

In this study we describe psychosocial functions and seizure-related factors in a population-based sample of children with epilepsy. Psychosocial problems (Achenbach scales), cognitive function, and socioeconomic status were studied in 117 children with epilepsy aged between 6 and 13 years (mean age 11y [SD 2y 1mo] and 10y 8mo [SD 2y]; 71 males, 46 females) and in randomly selected controls matched with 117 children for sex and age (mean age 11y 2mo [SD 2y 1mo] and 10y 5mo [SD 2y 4mo]; 69 males, 48 females). The children had partial (n=67), generalized (n=43), or undetermined (n=7) epilepsy syndromes, and partial (n=68), generalized (n=47), or other (n=2) main seizure types. Psychosocial problems were more common among children with epilepsy than controls (odds ratio 5-9) and significantly related to epilepsy syndrome, main seizure type, age at onset, and seizure frequency. Mothers and teachers reported males with epilepsy as having more problems than females. Females self-reported psychosocial problems, males did not. Psychosocial problems were common in childhood epilepsy. Females appreciated the problems more realistically than males. Psychosocial problems should be considered an integral part of epilepsy management.     

Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study

OBJECTIVE: Based on clues from epidemiology and animal experiments, low vitamin D during early life has been proposed as a risk factor for schizophrenia. The aim of this study was to explore the association between the use of vitamin D supplements during the first year of life and risk of developing schizophrenia. METHOD: Subjects were drawn from the Northern Finland 1966 Birth Cohort (n=9,114). During the first year of life, data were collected about the frequency and dose of vitamin D supplementation. Our primary outcome measures were schizophrenia, psychotic disorders other than schizophrenia, and nonpsychotic disorders as diagnosed by age 31 years. Males and females were examined separately. RESULTS: In males, the use of either irregular or regular vitamin D supplements was associated with a reduced risk of schizophrenia (Risk ratio (RR)=0.08, 95% CI 0.01-0.95; RR=0.12, 95% CI 0.02-0.90, respectively) compared with no supplementation. In males, the use of at least 2000 IU of vitamin D was associated with a reduced risk of schizophrenia (RR=0.23, 95% CI 0.06-0.95) compared to those on lower doses. There were no significant associations between either the frequency or dose of vitamin D supplements and (a) schizophrenia in females, nor with (b) nonpsychotic disorder or psychotic disorders other than schizophrenia in either males or females. CONCLUSION: Vitamin D supplementation during the first year of life is associated with a reduced risk of schizophrenia in males. Preventing hypovitaminosis D during early life may reduce the incidence of schizophrenia.     

Volume reduction of the left planum temporale gray matter associated with long duration of untreated psychosis in schizophrenia: a preliminary report

A longer duration of untreated psychosis (DUP) in schizophrenia is reported to lead to a poorer clinical outcome, possibly reflecting a neurodegenerative process after the onset of overt psychosis. However, the effect of DUP on brain morphology in schizophrenia is still poorly understood. In this study, we used magnetic resonance imaging to investigate the relation between DUP and volumetric measurements for the superior temporal sub-regions (Heschl's gyrus, planum temporale, and caudal superior temporal gyrus), the medial temporal lobe structures (hippocampus and amygdala), and the frontal lobe regions (prefrontal area and anterior cingulate gyrus) in a sample of 38 schizophrenia patients (20 males and 18 females) whose illness duration was less than five years. We found a significant negative correlation between DUP and the volume of gray matter in the left planum temporale even after controlling for age, age at illness onset, and duration and dosage of neuroleptic medication. There was no such correlation for the other brain regions including each sub-region of the prefrontal cortex (the superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, ventral medial prefrontal cortex, orbitofrontal cortex, and straight gyrus). When subjects were divided into two groups around the median DUP, the long-DUP group had a significantly smaller planum temporale gray matter than the short-DUP group. These findings may reflect a progressive pathological process in the gray matter of the left planum temporale during the initial untreated phase of schizophrenia, whereas abnormalities in the medial temporal regions might be, as has been suggested from previous longitudinal findings, relatively static at least during the early course of the illness.     

Early course of schizophrenia in a representative Dutch incidence cohort

PURPOSE: To describe the early course of psychotic disorders in general and to examine whether certain variables can predict the early course of schizophrenic disorders (DSM-IV: schizophrenia, schizophreniform or schizoaffective disorder). SUBJECTS AND METHOD: Follow-up and re-diagnosis of a highly representative Dutch incidence cohort (N=181), thirty months after first contact with a physician for a psychotic disorder. Poor course was defined as a continuous psychotic illness or a score of less than 39 on the Global Assessment of Functioning scale. RESULTS: The follow-up rate was 92%. 125 Subjects were diagnosed with a schizophrenic disorder. Poor course was present in 70 of these subjects (56%). Univariable analysis showed that male sex, heavy cannabis use during the follow-up period (sometimes or often more than one joint a day) and long duration of dysfunctioning before psychosis onset (>1 month) were predictors of poor course, while age at onset, ethnicity, socioeconomic status and duration of untreated psychosis (trend, p=0.08) were not. The effect of cannabis was confounded by sex. Multivariable analysis showed that male sex was the sole significant and independent predictor of poor course and explained 13% of the variation. The odds ratio for males, adjusted for duration of pre-psychotic dysfunctioning and cannabis use during the follow-up period, was 3.0 (95% CI, 1.0-8.9). STRENGTHS AND LIMITATIONS: This is the first study to examine the influence of cannabis in an epidemiological, highly representative sample. A limitation was the sample size. CONCLUSION: Male sex is an independent risk factor for an unfavorable early course in schizophrenia.     

Age at onset and sex differences in corpus callosum area in schizophrenia

Previous research on neuropsychological function among schizophrenia patients suggests that typical onset males (first psychiatric hospital admission before age 25) and typical onset females (first admission after age 25) may exhibit less lateralization of behavioral function (‘hypolateralization’) than atypical onset males and atypical onset females. To explore whether these differences were reflected in corpus callosum area, brain morphometric data from a large sample of subjects diagnosed with schizophrenia were analyzed. Typical onset females and typical onset males were compared to atypical onset females and atypical onset males on corpus callosum area. While neither sex nor onset effect on total corpus callosum area was statistically significant, analysis of standard subregions of the corpus callosum revealed a significant interaction effect on the posterior 20% area of the corpus callosum, with typical onset women having particularly large corpora callosa. The anterior 50% area did not differ among the groups. The results are discussed in terms of the role of anomalies in the integration and hemispheric transfer of information as underlying mechanisms of schizophrenia.     

Gender differences in cognitive deficits in schizophrenia with and without diabetes

This study investigated gender differences in cognition in schizophrenia with and without diabetes. Cognition was assessed in 263 individuals with schizophrenia with age range (40–68): 67 males and 34 females with schizophrenia with diabetes; and 125 males and 37 females with schizophrenia without diabetes according to the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Fasting glucose, hemoglobin A1c (HbA1c) and lipid levels were measured. Results showed that male individuals performed worse on most cognitive tasks, especially attention, in schizophrenia with than without diabetes. This result was not observed in female individuals. Also, individuals of both genders showed higher fasting glucose and HbA1c in schizophrenia with than without diabetes. In schizophrenia with diabetes, males had significantly worse cognition than females in all cognitive domains. Higher HbA1c, lower high-density lipoprotein, and an earlier age of onset of schizophrenia were found in males compared with female individuals. HbA1c was negatively associated with attention and the RBANS total score for males but not for females. In schizophrenia without diabetes, males showed worse performance in immediate and delayed memory than females. This study support cognition was worse for males with schizophrenia irrespective of whether they have diabetes. However, diabetes exemplified the gender differences, especially in attention.     

Gender and schizophrenia: age at onset and sociodemographic attributes.

A consecutive series of 214 patients (125 males, 89 females) who met the Research Diagnostic Criteria for schizophrenia were studied to determine gender differences in age at onset of the illness and sociodemographic attributes. The immediate family's first awareness of psychotic symptoms or signs and age at first presentation in hospital were used as indices of onset; male patients had a significantly earlier age of onset than females. By the time they were 30 years of age, 83% of male patients had already become ill and only 66% of females had done so. Significantly more females than males were married at the time of first contact with hospital. Married males did not differ from married females in age at onset of illness, suggesting that patients who marry may have late onset.     

A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia

Brain abnormalities have been identified in patients with schizophrenia, but what is unclear is whether these changes are progressive over the course of the disorder. In this longitudinal study, hippocampal and temporal lobe volumes were measured at two time points in 30 patients with first episode psychosis (mean follow-up interval=1.9 years, range 0.54-4.18 years) and 12 with chronic schizophrenia (mean follow-up interval=2.3 years, range 1.03-4.12 years) and compared to 26 comparison subjects (mean follow-up interval 2.2 years, range 0.86-4.18 years). Hippocampal, temporal lobe, whole-brain and intracranial volumes (ICV) were estimated from high-resolution magnetic resonance images. Only whole-brain volume showed significant loss over the follow-up interval in both patient groups. The rate of this volume loss was not different in the first episode group compared to the chronic group. There were no changes in either hippocampal or temporal lobe volumes. The negative findings for the hippocampus and temporal lobes may mean that the abnormalities in these regions are stable features of schizophrenia. Alternatively, the period before the onset of frank psychotic symptoms may be the point of greatest risk for progressive change.     

Somatosensory evoked potentials in patients affected by unilateral cerebrovascular lesions with onset during the perinatal period or adulthood

Unilateral cerebrovascular lesions occurring during adulthood have been reported to be accompanied by high-amplitude somatosensory evoked potentials over the nonaffected hemisphere; however, the mechanisms by which somatosensory evoked potential amplitude increases over the nonaffected hemisphere are still unclear. To investigate the eventual presence of similar amplitude abnormalities in children, we recorded somatosensory evoked potentials in three groups of patients: one with unilateral cerebrovascular lesions that occurred during the perinatal period and another two with unilateral cerebrovascular lesions occurring during late adulthood or old age. Group 1 was comprised of 12 children and young adults (age range 2 3/12-31 years, 6 males and 6 females) who suffered from unilateral cerebrovascular lesion with perinatal onset. Four control groups were arranged with age matched to that of the patients. Adult patients were subdivided into two subgroups (group 2: n = 10, all males; group 3: n = 18, 12 males and 6 females) on the basis of the presence or absence of sensory impairment over the hemiplegic side. In group 1, the four youngest subjects, aged less than 6 years, were found to show somatosensory evoked potentials of abnormally high amplitude over the nonaffected hemisphere, with a "giant" main negative wave at around 45 ms (range 38.7-49.2), strictly localized over the central areas contralateral to the lesion; in normal controls, there was no such wave. All patients in group 2 were found to be affected by large infarctions in the territory of the middle cerebral artery, whereas patients in group 3 presented with subcortical lesions of the internal capsule isolated or in association with an involvement of the frontal and/or temporal cortex. Regarding somatosensory evoked potential parameters measured over the nonaffected hemisphere in adult/elderly subjects, a significant difference was observed for N20 and P22 latency, which was longer in both groups of patients than in controls. There is a significant difference in the neurophysiologic consequences of unilateral cerebrovascular lesion, as well as over the nonaffected hemisphere, if it occurs during early infancy or during adulthood. Our findings show a new type of "giant" somatosensory evoked potentials in some children affected by unilateral cerebrovascular lesion with perinatal onset.     

Is initiation of smoking associated with the prodromal phase of schizophrenia?

OBJECTIVE: Although the association between smoking and schizophrenia is well known, little attention has been paid to the time between initiation of smoking and onset of schizophrenia. Our goal was to study this putative temporal relation among patients with schizophrenia. METHODS: We used data from the Northern Finland 1966 Birth Cohort (n = 11,017) linked with the National Finnish Hospital Discharge Register to study age at initiation of smoking and age at onset of schizophrenia, and we examined associations between family and environmental factors and the retrospectively determined regular smoking among patients with schizophrenia. RESULTS: Our main finding was that the initiation of regular smoking was closely related to the onset of schizophrenia. The mean difference in time between the initiation of regular smoking and the onset of schizophrenia among patients (n = 30) was 2.3 (standard deviation [SD] 6.6) years, which was statistically significantly lower than that for subjects with other psychoses (n = 18) (8.6 [SD 6.3] yr) (p < 0.001). Among patients with schizophrenia, the increased likelihood of smoking was associated only with paternal smoking in the family environment, but not with any other background factors (odds ratio 3.5, 95; confidence interval 1.9-11.3). CONCLUSION: Smoking may be a sign of the prodromal phase of schizophrenia.     

Sex-dependent effects of schizophrenia: an MRI study of gyral folding, and cortical and white matter volume

Alterations, sometimes sex-dependent, in volumes and gyral structure of areas of cerebral cortex have been reported in schizophrenia. Such changes imply an anomaly of connectivity. The gyrification, percentage of tissue volume attributed to white matter, cortical volume and white matter volume were measured from magnetic resonance images in males and females with (n = 61) and without (n = 42) schizophrenia. The frontal, temporal and an amalgam of occipital and parietal lobes were examined in both hemispheres. There was no effect of schizophrenia on the gyrification of the brain. For the volume of occipito-parietal white matter, females with schizophrenia had bilaterally lower volumes, while males with schizophrenia had greater volumes than controls. It is concluded that the changes in connectivity underlying the pathogenesis of schizophrenia are sex-specific and expressed in occipito-parietal white matter.     

Heritability of schizophrenia and major affective disorder as a function of age, in the presence of strong cohort effects

It remains unclear whether age at onset for major psychiatric disorders is a useful marker of etiologic and genetic heterogeneity. The authors examined how heritability of schizophrenia and major affective disorders varied with age at onset. The sample was drawn from a large archival data set collected by Lionel Penrose, comprising 3,109 families with two or more members first hospitalized in Ontario between 1874 and 1944. The authors studied 1,295 sibships with schizophrenia (n = 487), major affective disorder (n = 378), both (n = 234) or neither (n = 196) of these disorders. Proportional hazards models were used to estimate how the hazard of hospitalization for each disorder (schizophrenia or major affective disorder) varied with proband age at onset, adjusted for changes in age at onset distribution between 1874 and 1944. A sibling's risk of hospitalization for the same illness significantly increased for each 10–year decrease in age at onset of the proband both for schizophrenia (hazard ratio = 1.21, 95 % confidence interval: 1.06, 1.39), and for affective disorder (hazard ratio = 1.29,95 % CI: 1.14, 1.45). Gender of proband was unrelated to sibling risk of the same illness, and tests of interaction effects between proband age at onset and gender on sibling risk were nonsignificant.     

Executive functions and seizure-related factors in children with epilepsy in Western Norway

Executive functions (EFs), seizure-related factors, and school performance were studied in a population-based sample of children with epilepsy (n=117; 71 males, 46 females; mean age 10y 5mo [SD 2y]; range 6y-12y 11mo) and a comparison group (n=124; 71 males, 53 females; mean age 10y 1mo [SD 2y 1mo]; range 6y-12y 11mo). EF, cognitive function, depression, socioeconomic status, and school performance were examined. Patients with epilepsy performed significantly lower than the comparison group on all EF measures except incidental memory. Intellectual dysfunction and depression accounted for 43% of EF problems. All epilepsy syndrome groups (except Rolandic epilepsy) were associated with decreased EF in addition to early epilepsy onset, high seizure frequency, and polytherapy. Patients had more school performance problems than comparison children which were attributed partly to EF difficulties. All aspects of EF were affected in children with epilepsy and all epilepsy syndrome groups, except Rolandic epilepsy, influenced EF negatively. EF problems contributed to patients' school difficulties beyond intellectual dysfunction.     

Plasma homocysteine, folate and B12 in chronic schizophrenia

Elevated plasma levels of the amino acid homocysteine have been associated with schizophrenia, particularly in young male patients. Among other factors, low folate and vitamin B12 levels have been implicated in the increase in homocysteine. In order to investigate this association, we determined plasma homocysteine, folate and B12 levels in 97 (67 males and 30 females) inpatients with chronic schizophrenia and 103 (46 males and 57 females) controls. Patients and controls did not differ in folate or B12 levels, after adjusting for age. Patients with schizophrenia had higher plasma homocysteine than controls (mean=15.42 micromol/l in cases versus 11.54 micromol/l in controls: F(1,195)=17.978; p<0.001). This difference persisted after controlling for folate and B12 concentrations. Both male and female patients had increased plasma homocysteine compared to controls [(males: mean=16.61 micromol/l in cases versus mean=13.72 in controls: F(1,110)=5.54; p=0.020) (females: mean=12.78 micromol/l in cases versus mean=9.79 micromol/l in controls: F(1,84)=13.54; p<0.001)]. When dividing our sample into two age groups (age < and > or =50 years), both young and older females and younger males with schizophrenia had increased plasma homocysteine compared to controls. We therefore suggest that homocysteinemia is a general risk factor for schizophrenia. We further suggest that it is not limited to young male patients and is not necessarily associated with low folate or B12 levels.     

Ventricular enlargement in schizophrenia: a primary change in the temporal lobe?

BACKGROUND: The anatomical origin of the enlargement of the cerebral ventricles in schizophrenia is obscure. METHODS: In this study, the volumes of the hemispheres and lateral ventricles were assessed in MRI scans of 43 formalin-fixed brains (23 from patients and 19 comparison subjects) using a spline 'snake' segmentation method. RESULTS: A bilateral ventricular volume increase was found in schizophrenia. Whereas enlargement of the lateral ventricle (mean: 54%) as a whole was related to age of onset and was greater in females than in males, enlargement of the temporal horn (mean: 54%) was not strongly related to age of onset or sex. Lateral ventricle volume was negatively correlated with STG, fusiform and parahippocampal volume in schizophrenia. Hemispheric volumes were unchanged. CONCLUSIONS: The differing correlates of the components of ventricular enlargement suggest a degree of selectivity of the disease process with a focus in the temporal lobe.