Positive Family History Of Schizophrenia Research Articles

IMPACT OF FAMILIAL AND ENVIRONMENTAL RISK FACTORS ON AGE OF ONSET OF SCHIZOPHRENIA

ABSTRACT 
 Objectives: 1.To determines impact of familial risk factor i.e. positive family history of schizophrenia on age of onset of schizophrenia.
 2. To determine impact of environmental risk factor i.e. substance misuse on age of onset of schizophrenia.
 Materials and Methods: In this cross sectional analytical study, 430 patients were enrolled from OPD in Sarhad Hospital for Psychiatric Diseases Peshawar through convenience non probability sampling technique. First Data was dichotomized on the basis of positive and negative family history of schizophrenia. Later on data was again dichotomized on the basis of positive and negative history of substance misuse. Frequency and percentage were calculated for categorical variable while mean and standard deviation for continuous variables. Independent-samples T test was used while comparing categorical variable with continuous variable and Chi-square test was used while comparing two categorical variables in between them.
 Results: The mean age of onset of schizophrenia was 22.28 years with early onset in males than females. In those with familial schizophrenia, the mean ages of onset of schizophrenia in males and females were 22.35 and 22.05 years while in those with sporadic cases, the mean age of onset of schizophrenia in males and females were 21.83 and 25.43 years respectively. Moreover non-tobacco substances and cannabinoids were having statistically significant impact on age of onset of schizophrenia.
 Conclusion: There was significant gender difference in age at onset of schizophrenia and substance misuse. Family history of schizophrenia eliminates the gender difference in age at onset of schizophrenia. Moreover non-tobacco substances and cannabinoids misuse can cause early onset of schizophrenia.

Lower prepulse inhibition in clinical high-risk groups but not in familial risk groups for psychosis compared with healthy controls.

Although the lower level of prepulse inhibition (PPI) of the startle response is well known in schizophrenia, the onset of this difference is not clear. The aim of the present study was to compare PPI in individuals with clinical and familial high risk for psychosis, and healthy controls. We studied PPI in individuals within three groups: ultra-high risk for psychosis (UHR, n = 29), familial high risk for psychosis (FHR, n = 24) and healthy controls (HC, n = 28). The FHR group was chosen among siblings of patients with schizophrenia, whereas UHR was defined based on the Comprehensive Assessment of At-Risk Mental States (CAARMS). We collected clinical data using the BPRS-E, SANS and SAPS when individuals with UHR were antipsychotic-naïve. A cognitive battery that assessed attention, cognitive flexibility, working memory, verbal learning and memory domains was applied to all participants. PPI was lower in the UHR group compared with both the FHR and HC groups. Those with a positive family history for schizophrenia had lower PPI than others in the UHR group. There was no difference in PPI between the FHR and HC groups. We found no relationship between PPI and cognitive performance in the three groups. Startle reactivity was not different among the three groups. Positive and negative symptoms were not related to PPI and startle reactivity in the UHR group. Our findings suggest that clinical and familial high-risk groups for psychosis have different patterns of PPI.

Family history of psychosis and outcome of people with schizophrenia in rural China: 14-year follow-up study.

This study examined the differences in 14-year outcomes of persons with schizophrenia with and without family history of psychosis in a rural community in China. All participants with schizophrenia (n=510) aged 15 years and older were identified in a 1994 epidemiological investigation of 123,572 people and followed up in 2004 and 2008 in Xinjin County, Chengdu, China. Individuals with positive family history of schizophrenia had significantly younger age of first onset than those with negative family history of schizophrenia in 1994 and 2004. Compared with individuals with negative family history of schizophrenia, those with positive family history of schizophrenia had significantly higher rate of homelessness and lower rate of death due to other reasons in 10-year (2004) and 14-year follow-up (2008). There were no significantly differences of mean scores on PANSS, SDSS and GAF in 2008 between positive and negative family history groups. The positive family history of schizophrenia is strongly related to younger age of onset, and may predict a poorer long-term outcome (e.g., higher rate of homelessness) in persons with schizophrenia in the rural community. The findings have implications for further studies on specific family-related mechanisms on clinical treatment and rehabilitation, as well as for planning and delivering of community-based mental health services.

Common familial risk factors for schizophrenia and diabetes mellitus.

The co-occurrence of type 2 diabetes and psychosis is an important form of medical comorbidity within individuals, but no large-scale study has evaluated comorbidity within families. The aim of this study was to determine whether there is evidence for familial comorbidity between type 2 diabetes and psychosis. Data were analysed from an observational study of a nationally representative sample of 1642 people with psychosis who were in contact with psychiatric services at the time of survey (The 2010 Australian National Survey of Psychosis). Participants were aged 18-64 years and met World Health Organization's International Classification of Diseases, 10th Revision diagnostic criteria for a psychotic disorder (857 with schizophrenia, 319 with bipolar disorder with psychotic features, 293 with schizoaffective disorder, 81 with depressive psychosis and 92 with delusional disorder or other non-organic psychoses). Logistic regression was used to estimate the association between a family history of diabetes and a family history of schizophrenia. A positive family history of diabetes was associated with a positive family history of schizophrenia in those with a psychotic disorder (odds ratio = 1.35, p = 0.01, adjusted for age and gender). The association was different in those with an affective versus non-affective psychosis (odds ratio = 0.613, p = 0.019, adjusted for age and gender) and was significant only in those with a non-affective psychosis, specifically schizophrenia (odds ratio = 1.58, p = 0.005, adjusted for age and sex). Adjustment for demographic factors in those with schizophrenia slightly strengthened the association (odds ratio = 1.74, p = 0.001, adjusted for age, gender, diagnosis, ethnicity, education, employment, income and marital status). Elevated risk for type 2 diabetes in people with schizophrenia is not simply a consequence of antipsychotic medication; type 2 diabetes and schizophrenia share familial risk factors.

Genetic liability, prenatal health, stress and family environment: Risk factors in the Harvard Adolescent Family High Risk for Schizophrenia Study

ObjectivesThe familial (“genetic”) high-risk (FHR) paradigm enables assessment of individuals at risk for schizophrenia based on a positive family history of schizophrenia in first-degree, biological relatives. This strategy presumes genetic transmission of abnormal traits given high heritability of the illness. It is plausible, however, that adverse environmental factors are also transmitted in these families. Few studies have evaluated both biological and environmental factors within a FHR study of adolescents. MethodsWe conceptualize four precursors to psychosis pathogenesis: two biological (genetic predisposition, prenatal health issues (PHIs)) and two environmental (family environment, stressful life events (SLEs)). Participants assessed between 1998 and 2007 (ages 13–25) included 40 (20F/20M) adolescents at FHR for schizophrenia (FHRs) and 55 (31F/24M) community controls. ‘Genetic load’ indexed number of affected family members relative to pedigree size. ResultsPHI was significantly greater among FHRs, and family cohesion and expressiveness were less (and family conflict was higher) among FHRs; however, groups did not significantly differ in SLE indices. Among FHRs, genetic liability was significantly associated with PHI and family expressiveness. ConclusionsPrenatal and family environmental disruptions are elevated in families with a first-degree relative with schizophrenia. Findings support our proposed ‘polygenic neurodevelopmental diathesis–stress model’ whereby psychosis susceptibility (and resilience) involves the independent and synergistic confluence of (temporally-sensitive) biological and environmental factors across development. Recognition of biological and social environmental influences across critical developmental periods points to key issues relevant for enhanced identification of psychosis susceptibility, facilitation of more precise models of illness risk, and development of novel prevention strategies.

Elevated homocysteine level in first-episode schizophrenia patients--the relevance of family history of schizophrenia and lifetime diagnosis of cannabis abuse.

Accumulating evidence indicates that elevated homocysteine (Hcy) level occurs in first-episode schizophrenia (FES) patients. We included 56 FES patients and 53 healthy controls (HC). Plasma level of Hcy was significantly higher in FES patients than HC (p = 0.044). In addition, plasma levels of high-density lipoproteins (HDL) and folate were significantly lower in FES than in HC (p < 0.001). Positive family history of schizophrenia was associated with lower plasma HDL (p = 0.041) and vitamin B12 (p = 0.017), as well as higher level of Hcy (p = 0.017). Patients with FES, who abused cannabis, had higher levels of Hcy (p = 0.017), as well as lower levels of vitamin B12 (p = 0.017) and HDL (p = 0.041). Plasma Hcy negatively correlated with duration of untreated psychosis (r = −0.272, p = 0.042). There was a positive correlation between Hcy level and the severity of negative symptoms (r = 0.363, p = 0.006) and general psychopathology (r = 0.349, p = 0.008) assessed using Positive and Negative Syndrome Scale (PANSS). Vitamin B12 level was negatively associated with the severity of negative symptoms (r = −0.406, p = 0.002), while folate level negatively correlated with general psychopathology score (r = −0.365, p = 0.006) in PANSS. These results indicate that the severity of one-carbon metabolism alterations and HDL deficiency might be associated with family history of schizophrenia and cannabis abuse. Lower vitamin B12 and folate along with elevated Hcy may influence the severity of FES psychopathology.

Environmental and familial risk factors for psychotic and non-psychotic severe depression

BackgroundSevere unipolar depression can be classified as either psychotic depression (PD) or non-psychotic depression (non-PD). A number of biological and clinical differences have been detected between PD and non-PD, but it remains unknown whether risk factors for the two subtypes also differ. The aim of the present study was therefore to investigate whether a number of potential risk factors influenced the risk of developing PD and non-PD to different extents. MethodsThis is a register-based historical prospective cohort study following all 2.4 million individuals born in Denmark between 1955 and 1990. During follow-up 2183 and 9101 individuals were registered in the Danish Psychiatric Central Research Register with PD and non-PD respectively. The association between risk factors and the development of PD and non-PD was estimated by survival analysis (Poisson regression) and expressed as incidence rate ratios (IRR). ResultsThe most consistent finding of the study was that of a general overlap in familial and environmental risk factors for PD and non-PD. However, a parental history of bipolar disorder was a risk factor for PD (mother, IRR=1.66, p=0.003. Father, IRR=1.56, p=0.040) and not for non-PD (mother, IRR=0.92, p=0.430. Father, IRR=1.08, p=0.552). Conversely, a positive family history of schizophrenia was associated with neither PD nor non-PD LimitationsDiagnoses were assigned as part of routine clinical practice. ConclusionOur findings justify the distinction between PD and non-PD in the current diagnostic manuals. Furthermore, the fact that parental bipolar disorder and not schizophrenia was a risk factor for PD supports the Kraepelinian dichotomy.

Use of Clozapine for the Treatment of Schizophrenia: Findings of the 2006 Research on the China Psychotropic Prescription Studies

ObjectiveClozapine is one of the most commonly used antipsychotic drugs in China. To date, few studies have investigated the patterns the prescription of clozapine nationwide. The present study examined these patterns in China in 2006 and identified the demographic and clinical characteristics associated with the use of clozapine.MethodsUsing a standardized protocol and data collection procedure, we surveyed 5,898 patients with schizophrenia in 10 provinces with differing levels of economic development.ResultsOverall, clozapine had been prescribed for 31.9% (n=1,883) of the patients; however we found considerable variation among the 10 provinces. The frequency of clozapine use was highest in Sichuan (39.3%) and lowest in Beijing (17.3%). The mean daily dose of clozapine was 210.36±128.72 mg/day, and 25.1% of the patients were treated with clozapine in combination with other antipsychotics. Compared with the group not receiving clozapine, clozapine-user had been treated for longer durations and had experienced a greater number of relapses and hospitalizations. Furthermore, those in the clozapine-user had lower family incomes, were less able to seek psychiatric services, and more likely to be male and have a positive family history of schizophrenia. A multiple logistic regression analysis revealed that age, sex, professional help-seeking behaviors, duration of illness, economic status, educational level, and clinical manifestations were associated with the use of clozapine.ConclusionClozapine use is common in China. However, use of the antipsychotic varies among provinces, and demographic and clinical factors play important roles in the prescription of clozapine.

Executive Functions in Patients with Familial versus Sporadic Schizophrenia and Their Parents

Background: The aim of this study was to investigate the executive functions in patients with sporadic schizophrenia (SS) and familial schizophrenia (FS), and the executive functions in their parents. Methods: The study included 30 patients with FS and their 37 parents with a positive family history of schizophrenia; 30 patients with SS and their 44 parents; 30 controls matched with the patients for gender, age and education, and 40 controls matched with the parents for gender, age and education (211 subjects in total). All the subjects were interviewed with the Structured Clinical Interview for DSM-IV-Axis I (SCID-I). The executive functions were assessed using the Verbal Fluency Test (VFT), the Trail Making Test (TMT), the Wisconsin Card Sorting Test (WCST) and the Stroop Test. Results: Patients with FS and their parents, and patients with SS performed significantly worse than their controls on the VFT, TMT, WCST and the Stroop test. There were no statistically significant differences between parents of patients with SS and their controls on any of the tests except for the Stroop color score. FS parents performed significantly worse than SS parents on all tests. FS patients performed significantly worse than SS patients on the VFT, TMT, Stroop test. Conclusion: Previous studies that investigated the cognitive functions of relatives of patients with schizophrenia brought out inconsistent results. The present study investigated relatives with and without a family history of schizophrenia separately and found that executive functions were impaired only in parents with a positive family history of schizophrenia. These findings suggest that impairment in executive functions may represent a genetic endophenotype for schizophrenia.

Anthropometerical Association of the Craniofacial Dysmorphology with Schizophrenia

Dysmorphology is more concentrated in the craniofacial region of Schizophrenic Patients. So, an early anthropometric assessment of the physical dimensions of the cranium and the face may indicate a potential clue of Schizophrenia. To study the craniofacial dysmorphology in schizophrenic patients and in healthy controls of the Agra region and to find out whether its evaluation could be used as a tool in the early diagnosis of schizophrenia. This was a case-control, cross-sectional study. Schizophrenic Patients well diagnosed by consultant psychiatrists on the basis of the DSM IV criteria of the S.N. Medical College Agra and the Institute of Mental health, Agra and healthy controls of Agra were selected for the study. The total facial height (trichion to gnathion), the upper facial height (trichion to subnasale) and the lower facial height (subnasale to gnathion) were measured among the various groups of patients and the controls. The mean data were statistically correlated by using the t test for the independent variables. The total facial height (trichion to gnathion) was elongated in the Schizophrenic male patients as compared to the controls. When we compared the schizophrenic patients on the basis of the family history of schizophrenia, it was found that there was an elongation of the total facial height in the patients with a positive family history of schizophrenia as compared to the patients without a family history of schizophrenia. There was also a significant elongation of the upper facial height (trichion to subnasale ) in the schizophrenic male and female patients. There was total facial elongation and upper facial region elongation in the schizophrenia patients as compared to the controls.

Âge paternel élevé et risque de schizophrénie

Schizophrenia is an aetiologically heterogeneous syndrome, with a strong genetic component. Despite a reduced fertility in this disorder, its prevalence is maintained and could be explained by de novo genetic mutations. Advanced paternal age (APA) is a major source of new mutations in human beings and could thus be associated with an increased risk of developing schizophrenia in offspring. New mutations related to APA have been implicated as a cause of sporadic cases in several autosomal dominant diseases and also in neurodevelopmental diseases, autism, intellectual disabilities, and social functioning. The aim of the present study was to summarize the results of studies investigating the role of APA, and to discuss some interpretations. All relevant studies were identified through the National Library of Medicine (PubMed(®) database). Keywords used for research were "age" and "schizophrenia" linked to "paternal or father". We have identified and analysed eight cohort studies, five case-control studies, two meta-analyses, and one review concerning different father's mutations potentially transmitted, two studies comparing paternal age at conception between sporadic versus familial cases of schizophrenia. All studies selected have been published between 2000 and 2009. After controlling for several confounding factors including maternal age, the relative risk of schizophrenia increased from 1.84 to 4.62 in offspring of fathers with an older age of fatherhood. Mother's age showed no significant effects after adjusting for paternal age. There was a significant association between paternal age and risk of developing schizophrenia, there was a weaker association with psychosis. The results of these different studies are confirmed by two recent meta-analyses which found an increased risk of schizophrenia in offspring of fathers older than 35 years. Two main hypotheses could explain these results. The first one is based on the presence of new mutations in the spermatogonia, possibly because of accumulating replication errors in spermatogonial cell lines. This hypothesis is confirmed by Malaspina et al. (2002) [19], who found that patients without a family history of schizophrenia had significantly older fathers than probands with a positive family history of schizophrenia. However, this result has not been confirmed by other studies, and paternal age effect could be also explained by a mechanism called imprinting, which is a form of gene regulation. The second hypothesis is based on the fact that fathers with schizophrenia spectrum personality disorder, known to be genetically related to schizophrenia, could have an advanced age at conception. However, regarding this hypothesis, advanced maternal age at conception should be a risk factor for schizophrenia, and this is not the case. Thus, the first hypothesis seems more plausible than the second. APA has been identified as a risk factor for other psychiatric disorders such as autism, bipolar disorder, obsessive-compulsive disorder, and phobia, and thus seems to be a non-specific risk factor. Furthermore, its association with impaired neurocognitive outcomes during infancy and childhood in normal populations raises the question of the phenotype linked to APA. APA at conception appears to be a risk factor for schizophrenia. This risk factor probably interacts with genetic factors in a gene-environment interaction. To date, there is no validated cut-off at which the risk is significantly increased in offspring. In the future, studies could benefit from analyzing the phenotype related to APA.

Depressive symptoms evaluated by the Calgary Depression Scale for Schizophrenia (CDSS): Genetic vulnerability and sex effects

The present study compares the occurrence of depressive symptoms evaluated by the Calgary Depression Scale for Schizophrenia (CDSS) in patients of Multiplex (MS) and Simplex Schizophrenia families (SS). The Positive and Negative Syndrome Scale (PANSS) was used to evaluate psychopathology. A total of 206 paranoid schizophrenia patients were studied according DSM-IV criteria. The Family Interview for Genetic Studies (FIGS) was used to study the families. A result in the FIGS for a positive family history of schizophrenia was referred as MS (patients); its lack as SS (patients). CDSS scores were compared among MS and SS patients and possible sex differences intra- and inter-groups were explored. In the analysis of our sample (30) 19% of the total persons with schizophrenia group was depressed. The depressive symptoms measured by the CDSS were higher in females and the MS males group. Males from MS group showed more depressive symptoms than males from SS group. No differences with females from both groups were found. Findings in this study underscore the importance of gender and family history in understanding the heterogeneity of schizophrenia. This study suggests that sex and familiar history are important to consider in studying depressive symptoms.

A reappraisal of the association between Dysbindin (DTNBP1) and schizophrenia in a large combined case-control and family-based sample of German ancestry

Introduction: Dysbindin (DTNBP1) is a widely-studied candidate gene for schizophrenia (SCZ); however, inconsistent results across studies triggered skepticism towards the validity of the findings. In this HapMap-based study, we reappraised the association between Dysbindin and SCZ in a large sample of German ethnicity. Method: Six hundred thirty-four cases with DSM-IV SCZ, 776 controls, and 180 parent-offspring trios were genotyped for 38 Dysbindin SNPs. We also studied two phenotypically-defined subsamples: 147 patients with a positive family history of SCZ (FH-SCZ+) and SCZ patients characterized for cognitive performance with Trail-Making Tests A and B (TMT-A: n=219; TMT-B: n=247). Given previous evidence of gene-gene interactions in SCZ involving the COMT gene, we also assessed epistatic interactions between Dysbindin markers and 14 SNPs in COMT. Results: No association was detected between Dysbindin markers and SCZ, or in the FH-SCZ+ subgroup. Only one marker (rs1047631, previously reported to be part of a risk haplotype), showed a nominally significant association with performance on TMT-A and TMT-B; these findings did not remain significant after correction for multiple comparisons. Similarly, no pairwise epistatic interactions between Dysbindin and COMT markers remained significant after correction for 504 pairwise comparisons. Conclusions: Our results, based on one of the largest sample of European Caucasians and using narrowly-defined criteria for SCZ, do not support the etiological involvement of Dysbindin markers in SCZ. Larger samples may be needed in order to unravel Dysbindin's possible role in the genetic basis of proposed intermediate phenotypes of SCZ or to detect epistatic interactions.

A reappraisal of the association between Dysbindin (DTNBP1) and schizophrenia in a large combined case–control and family-based sample of German ancestry

BackgroundDysbindin (DTNBP1) is a widely studied candidate gene for schizophrenia (SCZ); however, inconsistent results across studies triggered skepticism towards the validity of the findings. In this HapMap-based study, we reappraised the association between Dysbindin and SCZ in a large sample of German ethnicity. MethodSix hundred thirty-four cases with DSM-IV SCZ, 776 controls, and 180 parent–offspring trios were genotyped for 38 Dysbindin SNPs. We also studied two phenotypically-defined subsamples: 147 patients with a positive family history of SCZ (FH-SCZ+) and SCZ patients characterized for cognitive performance with Trail-Making Tests A and B (TMT-A: n=219; TMT-B: n=247). Given previous evidence of gene–gene interactions in SCZ involving the COMT gene, we also assessed epistatic interactions between Dysbindin markers and 14 SNPs in COMT. ResultsNo association was detected between Dysbindin markers and SCZ, or in the FH-SCZ+ subgroup. Only one marker (rs1047631, previously reported to be part of a risk haplotype), showed a nominally significant association with performance on TMT-A and TMT-B; these findings did not remain significant after correction for multiple comparisons. Similarly, no pair-wise epistatic interactions between Dysbindin and COMT markers remained significant after correction for 504 pair-wise comparisons. ConclusionsOur results, based on one of the largest samples of European Caucasians and using narrowly-defined criteria for SCZ, do not support the etiological involvement of Dysbindin markers in SCZ. Larger samples may be needed in order to unravel Dysbindin's possible role in the genetic basis of proposed intermediate phenotypes of SCZ or to detect epistatic interactions.

Dissection of phenotype reveals possible association between schizophrenia and Glutamate Receptor Delta 1 ( GRID1) gene promoter

Recent linkage and association data have implicated the Glutamate Receptor Delta 1 ( GRID1) locus in the etiology of schizophrenia. In this study, we sought to test whether variants in the promoter region are associated with this disorder. The distribution of CpG islands, which are known to be relevant for transcriptional regulation, was computationally determined at the GRID1 locus, and the putative transcriptional regulatory region at the 5′-terminus was systematically tagged using HapMap data. Genotype analyses were performed with 22 haplotype-tagging single nucleotide polymorphisms (htSNPs) in a German sample of 919 schizophrenia patients and 773 controls. The study also included two SNPs in intron 2 and one in intron 3 which have been found to be significantly associated with schizophrenia in previous studies. For the transcriptional regulatory region, association was obtained with rs3814614 ( p = 0.0193), rs10749535 ( p = 0.0245), and rs11201985 ( p = 0.0222). For all further analyses, the patient samples were divided into more homogeneous subgroups according to sex, age at onset, positive family history of schizophrenia and lifetime history of major depression. The p-value of the schizophrenia association finding for the three markers decreased by approximately one order of magnitude, despite the reduction in the total sample size. Marker rs3814614 (unadjusted p = 0.0005), located ~ 2.0 kb from the transcriptional start point, also withstood a two-step correction for multiple testing ( p = 0.030). No support was obtained for previously reported associations with the intronic markers. Our results suggest that genetic variants in the GRID1 transcriptional regulatory region may play a role in the etiology of schizophrenia, and that future association studies of schizophrenia may require stratification to ensure more homogeneous patient subgroups.

Antisaccade performance is related to genetic loading for schizophrenia

Disturbances of the oculomotor system are promising endophenotypes for schizophrenia. Increased error rates in the antisaccade task and prolonged antisaccade latencies have been found in patients with schizophrenia and their first degree relatives. We investigated oculomotor performance in 41 parents of schizophrenia patients and 22 controls with a prosaccade task and an antisaccade task. Parents were grouped into parents with a positive family history for schizophrenia ( N = 9) and parents with a negative family history for schizophrenia ( N = 32). An overlap-paradigm was applied; eye movements were recorded using infrared oculography. The combined group of parents made more antisaccade direction errors than controls ( p = 0.005) and there was a linear increase in direction errors from controls via negative family history parents to positive family history parents ( p = 0.008). Antisaccade latencies were prolonged in the combined parent group ( p = 0.057) compared to controls and there was a linear increase in latency with genetic loading ( p = 0.018). No group differences were found for prosaccade parameters. These results support the hypothesis that antisaccade impairment is associated with genetic loading for schizophrenia.

White matter alterations in schizophrenic patients with pronounced negative symptomatology and with positive family history for schizophrenia

In recent years, in vivo and post-mortem studies detected structural brain changes in schizophrenia. The aim of our analysis was to investigate potential changes of white matter in schizophrenic patients compared to controls, and the relationship to clinical characteristics. Fifty male, right-handed schizophrenic patients who met DSM-IV criteria for schizophrenia were recruited. Fifty right-handed, age- and sex-matched subjects without a psychiatric disorder were enrolled as controls. Volumes of white matter in several brain regions were measured by 1.5 T MRI using a volumetry and segmentation software (BRAINS). Regions of interest including frontal, temporal, parietal, occipital and subcortical areas were determined using Talairach spaces. No significant differences in white matter volumes of total brain tissue and regions of interest were detected between patients and controls. A significant reduction of white matter in parietal cortex of right hemisphere was found in a subgroup of patients with pronounced negative symptoms. Furthermore, patients with first-grade relatives suffering from schizophrenia showed a reduction of subcortical white matter in the right hemisphere. Our results indicate that subgroups of schizophrenic patients show alterations of white matter in distinct brain regions, including the right parietal lobe.

Positive family history is associated with persistent elevated emotional distress in schizophrenia: Evidence from a 16-month follow-up study

There is some evidence that emotional reactivity to daily life stress is related to a genetic or familial liability to develop schizophrenia. However, it is unclear whether the emotional distress is elevated in schizophrenia patients with positive compared to negative family history. The aim of the study was to test the hypothesis that a persistent higher level of emotional distress in schizophrenia subjects is associated with a positive family history of schizophrenia. This study used the Talbieh Brief Distress Inventory (TBDI), the Positive and Negative Syndrome Scale (PANSS; including dysphoric mood, positive and negative subscales), Montgomery–Åsberg Depression Rating Scale (MADRS), and the Distress Scale for Adverse Symptoms (DSAS) to investigate the difference in the magnitude of emotional distress scores between schizophrenia subjects with and without a positive family history of schizophrenia over time. Data were recorded for 69 multiplex family and 79 singleton patients at admission and about 16 months thereafter. No between-group differences were obtained in PANSS and DSAS scores. With regard to the TBDI: (a) both group of patients had no significant differences in emotional distress scores at admission; (b) patients with negative family history reported improvement in distress severity and depression severity (MADRS) 16 months after admission, while those with positive family history experienced persistent elevated emotional distress, mainly, on obsessiveness, and depression subscales; and (c) both groups of patients are characterized by elevated emotional distress at follow-up examination compared to healthy subjects. Thus, it appears that there is a strong association between positive family history and persistent elevated emotional distress. Because patients with positive and negative family history are likely to differ in genetic risk, our results suggest that long-term elevated levels of emotional distress may be related to a familial (environmental)/genetic vulnerability to schizophrenia.

A comparison of symptoms and family history in schizophrenia with and without prior cannabis use: Implications for the concept of cannabis psychosis

Background There is considerable interest in cannabis use in psychosis. It has been suggested that the chronic psychosis associated with cannabis use, is symptomatically distinct from idiopathic schizophrenia. Several studies have reported differences in psychopathology and family history in people with schizophrenia according to whether or not they were cannabis users. We set out to test the hypotheses arising from these studies that cannabis use is associated with more bizarre behaviour, more thought disorder, fewer negative symptoms including blunted affect, more delusions of reference, more paranoid delusions and a stronger family history of schizophrenia. Method We used a case register that contained 757 cases of first onset schizophrenia, 182 (24%) of whom had used cannabis in the year prior to first presentation, 552 (73%) had not and 3% had missing data. We completed the OPCRIT checklist on all patients and investigated differences in the proportion of people with distractibility, bizarre behaviour, positive formal thought disorder, delusions of reference, well organised delusions, any first rank symptom, persecutory delusions, abusive/accusatory hallucinations, blunted affect, negative thought disorder, any negative symptoms (catatonia, blunted affect, negative thought disorder, or deterioration), lack of insight, suicidal ideation and a positive family history of schizophrenia, using chi square tests. Logistic regression modelling was then used to determine whether prior cannabis use affected the presence of the characteristics after controlling for age, sex and ethnicity. Results There was no statistically significant effect of cannabis use on the presence of any of the above. There remained however a non-significant trend towards more insight (OR 0.65 p = 0.055 for “loss of insight”) and a finding of fewer abusive or accusatory hallucinations (OR 0.65 p = 0.049) of borderline significance amongst the cannabis users. These were in the hypothesised direction. There was no evidence of fewer negative symptoms or greater family history amongst cannabis users. Conclusion We found few appreciable differences in symptomatology between schizophrenic patients who were or were not cannabis users. There were no differences in the proportion of people with a positive family history of schizophrenia between cannabis users and non-users. This argues against a distinct schizophrenia-like psychosis caused by cannabis.

The DTNBP1 (Dysbindin) Gene Contributes to Schizophrenia, Depending on Family History of the Disease

We have investigated the gene for dystrobrevin-binding protein 1 (DTNBP1), or dysbindin, which has been strongly suggested as a positional candidate gene for schizophrenia, in three samples of subjects with schizophrenia and unaffected control subjects of German (418 cases, 285 controls), Polish (294 cases, 113 controls), and Swedish (142 cases, 272 controls) descent. We analyzed five single-nucleotide polymorphisms (P1635, P1325, P1320, P1757, and P1578) and identified significant evidence of association in the Swedish sample but not in those from Germany or Poland. The results in the Swedish sample became even more significant after a separate analysis of those cases with a positive family history of schizophrenia, in whom the five-marker haplotype A-C-A-T-T showed a P value of.00009 (3.1% in controls, 17.8% in cases; OR 6.75; P=.00153 after Bonferroni correction). Our results suggest that genetic variation in the dysbindin gene is particularly involved in the development of schizophrenia in cases with a familial loading of the disease. This would also explain the difficulty of replicating this association in consecutively ascertained case-control samples, which usually comprise only a small proportion of subjects with a family history of disease.