Schizophrenia First-degree Relatives Research Articles

Risk factors of deficit and non-deficit schizophrenia: Results from a cross-sectional study

AimIt has been observed that deficit and non-deficit schizophrenia (SCZ-D and SCZ-ND) might be characterized by different risk factors. Therefore, the present study aimed to assess as to whether previously reported risk factors of schizophrenia are specifically associated with SCZ-D and SCZ-ND. MethodThis study was based on a cohort of 118 stable outpatients with schizophrenia. A diagnosis of SCZ-D was established using the Schedule for the Deficit Syndrome (SDS). Risk factors were recorded using structured interview, the Operational Criteria for Psychotic Illness (OPCRIT) checklist and the Traumatic Experience Checklist (TEC). The following risk factors were explored: male sex, a history of schizophrenia in first-degree relatives, seasonality of birth, birth weight <3000g, delivery by cesarean section, a history of childhood trauma (emotional abuse, emotional neglect, physical abuse and sexual abuse) as well as substance abuse (other than nicotine) and cigarette smoking at psychosis onset. ResultsIndividuals with SCZ-D were more likely to be males as well as reported higher rates of birth weight <3000g and any categories of childhood trauma. In turn, substance abuse (other than nicotine) at psychosis onset was significantly more frequent in patients with SCZ-ND. Binary logistic regression, controlling for multiple comparisons, revealed similar findings, except for the association with any categories of childhood trauma that appeared to be not significant. ConclusionOur findings partially replicate differential patterns of risk factors for SCZ-D (male sex and birth weight <3000g) and SCZ-ND (substance abuse at psychosis onset), likely attributable to the effects of timing of exposure.

Neurocognition and its association with adverse childhood experiences and familial risk of mental illness

Environmental factors such as adverse childhood experiences (ACEs) may affect neurocognition, an endophenotype for several mental illnesses. This study examines the effect of ACEs on neurocognitive performance in first-degree relatives (FDRs) of patients with severe mental illness to determine whether familial risk has a moderating effect on the relationship between ACEs and neurocognition. Unaffected FDRs from multiplex families with severe mental illnesses (schizophrenia, bipolar disorder, obsessive-compulsive disorder, or alcohol use disorder) (n = 324) and healthy controls (with no familial risk) (n = 188) underwent neurocognitive tests for processing speed, new learning, working memory and Theory of Mind. ACEs were measured using the WHO ACE-International Questionnaire (ACE-IQ). Regression models were done to predict each neurocognitive domain by the effect of familial risk, ACE-IQ Score and their interaction (familial risk*ACE-IQ score). The main effect of familial risk predicted poor performance in all domains of neurocognition (p < 0.01), and the interaction had a negative association with global neurocognition (β = −0.093, p = 0.009), processing speed (β = −0.109, p = 0.003) and working memory (β = −0.092, p = 0.01). Among the ACEs sub-domains, only maltreatment (specifically the main effect of physical neglect and the interaction effect of sexual abuse with familial risk) predicted poorer neurocognition. In FDRs of schizophrenia and bipolar disorder, only the main effects of familial risk were significantly associated with poorer neurocognition. We conclude that there is a relationship between ACEs (especially maltreatment) and neurocognitive functioning, which is moderated by the familial risk of mental illnesses. Genetic/familial vulnerability may have a stronger association with neurocognition in schizophrenia and bipolar disorder.

Association of family history of schizophrenia and clinical outcomes in individuals with eating disorders.

Familial co-aggregation studies of eating disorders (EDs) and schizophrenia reveal shared genetic and environment factors, yet their etiological and clinical relationship remains unclear. We evaluate the influence of schizophrenia family history on clinical outcomes of EDs. We conducted a cohort evaluation of the association between family history of schizophrenia and ED clinical features, psychiatric comorbidities, and somatic and mental health burden in individuals born in Sweden 1977-2003 with anorexia nervosa (AN) or other EDs (OED: bulimia nervosa, binge-eating disorder, and ED not otherwise specified). Of 12 424 individuals with AN and 20 716 individuals with OED, 599 (4.8%) and 1118 (5.4%), respectively, had a family history of schizophrenia (in up to third-degree relatives). Among individuals with AN, schizophrenia in first-degree relatives was significantly associated with increased comorbid attention-deficit/hyperactivity disorder (ADHD) [HR(95% CI) 2.26 (1.27-3.99)], substance abuse disorder (SUD) [HR (95% CI) 1.93 (1.25-2.98)], and anxiety disorders [HR (95% CI) 1.47 (1.08-2.01)], but higher lowest illness-associated body mass index (BMI) [1.14 kg/m2, 95% CI (0.19-2.10)]. Schizophrenia in any relative (up to third-degree) in AN was significantly associated with higher somatic and mental health burden, but lower ED psychopathology scores [-0.29, 95% CI (-0.54 to -0.04)]. Schizophrenia in first-degree relatives in individuals with OED was significantly associated with increased comorbid ADHD, obsessive-compulsive disorder, SUD, anxiety disorders, somatic and mental health burden, and suicide attempts. We observed different patterns of ED-related outcomes, psychiatric comorbidity, and illness burden in individuals with EDs with and without family histories of schizophrenia and provide new insights into the diverse manifestations of EDs.

Slow wave oscillations in Schizophrenia First-Degree Relatives: A confirmatory analysis and feasibility study on slow wave traveling

Abnormal sleep oscillations have recently been proposed as endophenotypes of schizophrenia. However, optimization of methodological approaches is still necessary to standardize analyses of their microstructural characteristics. Additionally, some relevant features of these oscillations remain unexplored in pathological conditions. Among others, slow wave traveling is a promising proxy for diurnal processes of brain connectivity and excitability. The study of slow oscillations propagation appears particularly relevant when schizophrenia is conceptualized as a dys-connectivity syndrome. Given the rising knowledge on the neurobiological mechanisms underlying slow wave traveling, this measure might offer substantial advantages over other approaches in investigating brain connectivity.Herein we: 1) confirm the stability of our previous findings on slow waves and sleep spindles in FDRs using different automated algorithms, and 2) report the dynamics of slow wave traveling in FDRs of Schizophrenia patients. A 256-channel, high-density EEG system was employed to record a whole night of sleep of 16 FDRs and 16 age- and gender-matched control subjects. A recently developed, open source toolbox was used for slow wave visualization and detection. Slow waves were confirmed to be significantly smaller in FDRs compared to the control group. Additionally, several traveling parameters were analyzed. Traveled distances were found to be significantly reduced in FDRs, whereas origins showed a different topographical pattern of distribution from control subjects. In contrast, local speed did not differ between groups.Overall, these results suggest that slow wave traveling might be a viable method to study pathological conditions interfering with brain connectivity.

278. ENIGMA-Relatives – Brain Volumes in First-Degree Relatives of Schizophrenia and Bipolar Patients

First-degree relatives of schizophrenia (SZ) and bipolar disorder (BD) patients show brain abnormalities. Through the ENIGMA-SZ and BD Working Groups, we compare different types of SZ or BD first-degree relatives (i.e., co-twins, siblings, offspring, parents) to healthy controls (HC) on global and subcortical brain measures. In this abstract, we limit ourselves to total brain (TB) and hippocampal volume.

M51 - Estimation of Risk of Schizophrenia In First Degree Relatives An Indian Sample

Background Schizophrenia (SZ) is a chronic disabling brain disease that clusters in many families with estimated heritability of 64-88%, based on twin studies. Conventionally, family history of psychosis is the best predictor of risk but environmental and epigenetic factors are equally important. Recurrence risk calculation and stratifying risk may make recurrence more understandable while elucidating environmental risk factors. The present study was conceptualized to stratify the risk of schizophrenia in first degree relatives into above average, moderate and high risk categories so that it is easier for family members to understand their risk for SZ. Methods We recruited prospectively families (n=128) with at least one person affected with SZ and at least one healthy sibling or offspring (18-60 years of age) from OPD of a Government hospital after informed consent process. After ascertaining diagnosis detailed family history on Family Interview for Genetic Studies (FIGS) was obtained and environmental risk elicited. Based on previous studies reported in the literature, we used the beta coefficients for the different risk factors to derive an equation for susceptibility Y=β1x1+β2x2+β3x3+β4x4+β5x5 Where x1 = Type and number of affected members; x2 Age of at risk person;. x3 Gender of at risk individual; x4=Paternal age at conception; x5=Gender of the affected individual Male/Female. We applied this equation to data on each of the siblings and offspring of cases to obtain an “estimate of risk of illness”. Results The mean estimated risk was 5.615±0.337. The distribution of risk of the sample was high (n=19); moderate (n=75) and above average (n=34). The formula was validated against a separate set of sample which was recruited for other studies. The risk of already recruited first degree relative diagnosed with schizophrenia was in high or moderate category according to the formula. Discussion The study stratified the first degree relatives of schizophrenia probands into high, moderate and above average risk categories considering not only their family history but also other factors which affect susceptibility to schizophrenia. This formula is not meant for use in normal populations as the prevalence of schizophrenia is 1% but in families where already at least one person is affected the risk is known to be increased. Risk calculation is important and a fundamental element of genetic counseling.

Theory-of-mind understanding and theory-of-mind use in unaffected first-degree relatives of schizophrenia and bipolar disorder

We assessed theory of mind (ToM) in unaffected first-degree relatives (FDR) of patients with schizophrenia (SC) and bipolar disorder (BD) compared to healthy controls with a revised computerized referential communication task. Results showed that FDR of SC performed worse than FDR of BD and controls on a task requiring ToM-use, but not on a task requiring ToM-understanding. This indicates that deficient ToM-use, rather than ToM-understanding impairments, may represent a potential candidate endophenotype for schizophrenia.

A comparative study of cognitive functions in individuals at ultra high-risk for psychosis

Objective To investigate the differences of cognitive functions among ultra high-risk individuals(UHR), first-episode schizophrenia patients and healthy controls. Methods Twenty four participants meeting clinical inclusion criteria for initial prodromal states (IPS) selected from the first degree relatives of schizophrenia, 23 first onset schizophrenia patients from the same family with UHR as well as 30 healthy controls were assessed with a comprehensive neuropsychological test battery including Trail Making Test (TMT), Stroop color word test and the Continuous Performance Test (CPT) to test the speed of information processing and sustained attention ability. Results ①The time of the Trail Making Test in UHR((45.12±14.87)s) was shorter than first-episode schizophrenia patients((60.43±19.30)s), but longer than healthy controls((27.13±7.74)s). The whole score of the Stroop color word test in UHR(28.46±7.87) was higher than first-episode schizophrenia patients(18.78±6.86), and lower than healthy controls(43.40±9.64). The score of the Continuous Performance Test in UHR(1.86±1.05) was significanly higher than first-episode schizophrenia patients(1.17±0.67), but lower than healthy controls(2.63±0.67), and all these differences were significant(P<0.01). ②Taking age, years of education, occupation status, marital status and the Positive and Negative Syndrome Scale (PANSS) scores as the covariance, the analysis of covariance showed TMT and Stroop color word test were still statistically significant. Conclusion There are cognitive function changes in individuals at ultra high-risk for psychosis, lying between first-episode schizophrenia cases and healthy controls. Key words: Ultra high-risk for psychosis; Cognitive functions; First-episode schizophrenia

Schizophrenia risk variants modulate white matter volume across the psychosis spectrum: evidence from two independent cohorts.

Polygenic risk scores, based on risk variants identified in genome-wide-association-studies (GWAS), explain a considerable portion of the heritability for schizophrenia (SZ) and bipolar disorder (BD). However, little is known about the combined effects of these variants, although polygenic neuroimaging has developed into a powerful tool of translational neuroscience. In this study, we used genome wide significant SZ risk variants to test the predictive capacity of the polygenic model and explored potential associations with white matter volume, a key candidate in imaging phenotype for psychotic disorders.By calculating the combined additive schizophrenia risk of seven SNPs (significant hits from a recent schizophrenia GWAS study), we show that increased additive genetic risk for SZ was associated with reduced white matter volume in a group of participants (n = 94) consisting of healthy individuals, SZ first-degree relatives, SZ patients and BD patients. This effect was also seen in a second independent sample of healthy individuals (n = 89). We suggest that a moderate portion of variance (~4%) of white matter volume can be explained by the seven hits from the recent schizophrenia GWAS.These results provide evidence for associations between cumulative genetic risk for schizophrenia and intermediate neuroimaging phenotypes in models of psychosis. Our work contributes to a growing body of literature suggesting that polygenic risk may help to explain white matter alterations associated with familial risk for psychosis.

Commingling analysis of age-of-onset in bipolar I disorder and the morbid risk for major psychoses in first degree relatives of bipolar I probands

BackgroundAge-of-onset (AO) is increasingly used in molecular genetics of bipolar I disorder (BP-I) as a phenotypic specifier with the goal of reducing genetic heterogeneity. However, questions regarding the cut-off age for defining early onset (EO), as well as the number of onset groups characterizing BP-I have emerged over the last decade with no definite conclusion. The aims of this paper are: 1) to see whether a mixture of three distributions better describes the AO of BP-I than a mixture of two distributions in different independent samples; 2) to compare the morbid risk (MR) for BP-I and for major affective disorders and schizophrenia in first degree relatives of BP-I probands by proband onset group derived from commingling analysis, since the MR to relatives is a trait with strong genetic background. MethodsWe applied commingling (admixture) analysis to the AO of three BP-I samples from Romania (n=621), Germany (n=882), and Poland (n=354). Subsequently, the morbid risk (MR) for BP-I and for major psychoses (BP-I, BP-II, Mdd-UP, schizoaffective disorders, schizophrenia) was estimated in first degree relatives by proband AO-group derived from admixture analysis in the Romanian sample. ResultsIn the three independent samples and in the combined sample two- and three-AO-group distributions fitted the empirical data equally well. The upper EO limit varied between 21 and 25 years from sample to sample. The MR for both BP-I and for all major psychoses was similar in first degree relatives of EO probands (AO≤21) and in relatives of intermediate-onset probands (AO=22–34). Significant MR differences appeared only when comparing the EO group to the late-onset (LO) group (AO>34). Similar to Mdd-UP and schizophrenia, a significant MR decrease in proband first degree relatives was visible after proband AO of 34 years. Under the three-AO-group classification the MR for both BP-I and all major psychoses in first degree relatives did not differ by relative sex in any proband AO-group. Under the two-AO-group classification female relatives of LO probands (AO>24) had a significantly higher MR for all major psychoses than male relatives, while there was no sex difference for the relatives of EO probands. LimitationsMR was not computed in the German and Polish samples because family data were not available and 34% of the relatives of the Romanian probands were not available for direct interview. ConclusionSimilar to other clinical traits, the MR for major psychoses to relatives failed to support a three-AO-group classification in BP-I suggesting that this is not more useful for the molecular analysis than a two-AO-group classification.

Methamphetamine enhances the development of schizophrenia in first-degree relatives of patients with schizophrenia.

Although there is some evidence that methamphetamine (MA) abuse may play a causative role in the development of schizophrenia, studies directly linking these 2 are rare. In our study, the effect of MA abuse on the development of schizophrenia was investigated in 15 MA abusers who are offspring of patients with schizophrenia and 15 siblings of MA abusers without a history of drug abuse. Cognitive deficits and resting-state brain function were evaluated in all participants. Correlations between cognitive deficits and schizophrenia development were investigated. Significantly more cognitive impairments were observed in MA abusers, compared with their siblings without a history of drug use. Significant abnormalities in regional homogeneity (ReHo) signals were observed in resting brain in MA abusers. Decreased ReHo was found to be distributed over the bilateral cingulate gyrus, right Brodmann area 24, and bilateral anterior cingulate cortex. Seven MA abusers were diagnosed with schizophrenia, while 1 control sibling was diagnosed with schizophrenia during the 5-year follow-up. The cognitive scores correlated with the development of schizophrenia in MA abusers. Our study provides direct evidence for the causative role of MA use in the etiology of schizophrenia and highlights the role of MA-induced brain abnormalities in cognitive deficiency and development of schizophrenia.

DNA hypermethylation of serotonin transporter gene promoter in drug naïve patients with schizophrenia

IntroductionDysfunctional serotonin signaling has been linked to the pathogenesis of autism, obsessive compulsive disorder, mood disorders and schizophrenia. While the hypo-activity of serotonin signaling is involved in the pathogenesis of depression, anxiety and obsessive compulsive disorder; LSD, an agonist of serotonin type 2 receptor (5-HTR2A) induces psychosis. Therefore, anxiety and depressive disorders are treated by SSRIs which inhibit serotonin transporter (5-HTT) while psychotic disorders are controlled by drugs that block serotonin and/or dopamine receptors. Since genetic polymorphisms and epigenetic dysregulation of 5-HTT are involved in the pathogenesis of mental diseases, we analyzed DNA methylation of 5-HTT promoter in post-mortem brains and saliva samples of patients with schizophrenia (SCZ) and bipolar disorder (BD) to evaluate its potential application as a diagnostic and/or therapeutic biomarker in SCZ and BD. MethodsWhole genome DNA methylation profiling was performed for a total of 24 samples (including two saliva samples) using the Illumina 27K (for 12 samples) and 450K DNA methylation array platform (for another 12 samples), followed by bisulfite sequencing to identify candidate CpGs for further analysis. Quantitative methylation specific PCR (qMSP) was used to assess the degree of CpG methylation of 5-HTT promoter in 105 post-mortem brains (35 controls, 35 SCZ and 35 BD) and 100 saliva samples (30 controls, 30 SCZ, 20 BD and 20 first degree relatives of SCZ or BD). The U133 2.0 Plus Human Transcriptome array for a total of 30 post-mortem brain samples (each group 10) followed by quantitative real-time PCR was used to study 5-HTT expression in 105 post-mortem brain samples. ResultsThe qMSP analysis for 5-HTT promoter region showed DNA hypermethylation in post-mortem brain samples of SCZ patients (~30%), particularly in drug free patients (~60%, p=0.04). Similarly, there was a trend for DNA hypermethylation in antipsychotic free BD patients (~50%, p=0.066). qMSP analysis of DNA extracted from the saliva samples also exhibited hypermethylation of 5-HTT promoter in patients with SCZ (~30%, p=0.039), which was more significant in drug naïve SCZ patients (>50%, p=0.0025). However, the difference was not significant between the controls and unaffected first degree relatives of patients with SCZ (p=0.37) and versus patients using antipsychotic drugs (p=0.2). The whole genome transcriptome analysis of post-mortem brain samples showed reduced expression of 5-HTT in SCZ compared to the control subjects (~50%, p=0.008), confirmed by quantitative real-time PCR analysis (~40%, p=0.035) which was more significant in drug free SCZ patients (~70%, p=0.022). ConclusionA correlation between reduction in 5-HTT expression and DNA hypermethylation of the 5-HTT promoter in drug naïve SCZ patients suggests that an epigenetically defined hypo-activity of 5-HTT may be linked to SCZ pathogenesis. Furthermore, this epigenetic mark in DNA extracted from saliva can be considered as one of the key determinants in a panel of diagnostic and/or therapeutic biomarkers for SCZ.

Exploring the relationships between tobacco smoking and schizophrenia in first-degree relatives

Up to 90% of individuals with schizophrenia suffer from nicotine dependence. Both schizophrenia and nicotine consumption have strong genetic components, which may overlap. The relationship between schizophrenia and nicotine dependence remains unclear, due in part to confounding factors. Studies of the relationship between nicotine consumption and milder schizophrenia-related phenotypes, such as schizotypy, in first-degree relatives of individuals with schizophrenia could help to better understand the relationship between smoking and schizophrenia while avoiding such confounders. We assessed the proportion of smokers, their level of nicotine dependence and their level of schizotypy in a sample of 98 first-degree relatives of schizophrenic subjects and 110 healthy controls. Partial correlation analysis was used to assess the relationship between schizotypal dimensions and smoking dependence. The prevalence of smoking and nicotine dependence levels were higher in the relatives than in the healthy control group. We found no relationship between nicotine dependence and the magnitude of schizotypal features in either group. Our results support the hypothesis that the relationship between schizophrenia and smoking is largely mediated by common familial factors, which may be genetic.

Poster #86 CLINICAL AND SOCIAL CORRELATES OF LATE ONSET FIRST-EPISODE PSYCHOSIS: FINDINGS FROM THE AESOP STUDY

Les délires chroniques survenant tardivement ont été étudiés essentiellement par des psychiatres européens, et se sont vus classés de façon variable tant dans les nosographies européennes qu’internationales. En Allemagne, Manfred Bleuler a défini la schizophrénie tardive, les psychiatres britanniques parlent de paraphrénie tardive et en France ces tableaux cliniques sont classés dans la catégorie des psychoses hallucinatoires chroniques. Les classifications internationales qui ont à une époque individualisé la schizophrénie tardive l’intègrent actuellement dans le groupe des schizophrénies. Pourtant ces formes à début tardif présentent des particularités que nous avons tenté de définir dans ce travail et qui soulèvent la question de facteurs déclenchants, de l’existence d’une prédictivité, voire même orientent vers des notions de diagnostic précoce.Chronic delusion occurring late in life has essentially been studied by European psychiatrists. « Late-onset schizophrenia » was first described and defined by Manfred Bleuler in 1943, as a form of schizophrenia which occurs after the age of 40. Later, British psychiatrists often used the term « Late-onset paraphrenia » interchangeably with « Late-onset schizophrenia » to designate this disorder. However, late-onset paraphrenia is a British concept which includes all delusional disorders starting after age 60. American psychiatrists had little interest in this patient group, so it is only within the DSM III-R that a separate category was created for patients who developed schizophrenia after age 44. There is now no longer a « late-onset » category for schizophrenia within the DSM IV, nor age criterion for the diagnosis of schizophrenia. In the French nosography, schizophrenia is excluded when a non-affective, non-organic psychosis begins after the age of 40. These chronic delusion syndromes fall into a specific French category : « Psychose Hallucinatoire Chronique» (chronic hallucinatory psychosis).Basing themselves on the analysis of many studies, the authors endeavor to define the characteristics of late-onset schizophrenia. The exact prevalence is not known, but is considered lower than 1 %. There is a preponderance of women over men in this form of disease, that could be explained by the relative excess of dopamine type 2 (D2) receptors in young men (compared with young women), and by a protective role played by estrogens until the menopause, among women predisposed to schizophrenia. Studies of families reveal a lower lifetime risk of schizophrenia in first degree relatives of patients with late-onset schizophrenia, than those with an early onset. Most of these patients have been or are married, and had worked for a long time. Generally at the onset of the illness they are isolated and unemployed. Paranoid and schizoid abnormal premorbid personality traits are frequently noted with the diagnosis of late-onset schizophrenia. An association between late-onset schizophrenia and sensory impairment (visual and auditory) is frequently observed and appear to be in link with auditory and visual hallucinations. The analysis of clinical features reveal that the later the schizophrenia breaks out, the more the patient shows delusion and hallucinatory symptoms, which remain limited to his surroundings, whereas in younger patients, delusion has no limit. Moreover, late-onset schizophrenic patients have a lower prevalence of looseness of associations and negative symptoms than those with an earlier onset. The authors note from the few studies on the treatment, that a number of patients responded well to low dose of antipsychotic agents. The use of « atypical » anti-psychotic drugs is recommended, in order to reduce the adverse effects, notably the extrapyramidal symptoms which are frequent in elderly people.Finally, they conclude that patients with late-onset schizophrenia have symptoms very similar to those of patients with early-onset schizophrenia. But, when taking the different forms of schizophrenia-even the late onset ones-into account, raises the question of the role of trigger factors that could guide research on predictive factors and early diagnosis. This may be one explanation for the survival of the French entity « Psychose Hallucinatoire Chonique ».

Confirmatory Factor Analysis in Neurophysiological and Neuropsychological Dimensions of Schizophrenia

ABSTRACTThis study applied confirmatory factor analysis (CFA) to examine the construct of smooth pursuit eye movements (SPEM) and the Wisconsin Card Sorting Test (WCST) in schizophrenia. Participants were assigned to two groups: Group 1 included 27 probands chosen from families with schizophrenia in first-degree relatives, and Group 2 included 54 schizophrenics who had no families with schizophrenia spectrum disorders. There were no differences in the eye tracking pursuit and the WCST between the sporadic and familial schizophrenics. Gender impacted the catch-up saccades (CUS) and anticipatory saccades (AS) indices of the SPEM, and the conceptual level responses (CLR) index of the WCST. Education impacted the CLR and perseverative errors of the WCST. Although there were no correlation between the SPEM and the WCST, but the two instruments showed good content validity, which might be useful in the subtyping of schizophrenia.

Phase-specific brain change of spatial working memory processing in genetic and ultra-high risk groups of schizophrenia.

Spatial working memory (WM) processing has 3 distinct phases: encoding, maintenance, and retrieval and its dysfunction is a core feature in schizophrenia. We examined phase-specific brain activations associated with spatial WM in first-degree relatives of schizophrenia (genetic high risk, GHR), ultra-high risk (UHR) subjects, patients with schizophrenia, and healthy controls. We used an event-related functional magnetic resonance imaging in 17 GHR subjects, 21 UHR subjects, 15 clinically stable patients with schizophrenia and 16 healthy controls, while subjects were performing a spatial delayed-response task. During the encoding phase, the GHR group showed increased activation in the fronto-parietal regions, whereas the UHR and schizophrenia groups showed significantly less activation in these regions than did the healthy control group. Especially, frontal activation was strongest in GHR subjects, followed by healthy controls, and occurred to a lesser degree in the UHR group, with the least activation occurring in the schizophrenia group. During the maintenance phase, the thalamus showed a differential activation, similar to frontal activation pattern during the encoding phase. During the retrieval phase, no prominent differential activations were found. Increased activations were observed in the superior temporal gyrus during the encoding and maintenance phases in the GHR, UHR, and schizophrenia groups relative to healthy controls. Our findings suggest that functional deficits associated with spatial WM processing emerge in the UHR before the onset of schizophrenia and compensatory neural processes exist in the GHR with genetic liability to schizophrenia.

Morbid risk for schizophrenia in first-degree relatives of people with frontotemporal dementia

Familial co-occurrence of frontotemporal dementia and schizophrenia has never been investigated. To test the hypothesis that frontotemporal dementia and schizophrenia might have a common aetiology in some families in which both syndromes coexist (mixed families). The morbid risk for schizophrenia, calculated in first-degree relatives of 100 frontotemporal dementia probands, was compared with that calculated in first-degree relatives of 100 Alzheimer's disease probands. In mixed families, sequencing analysis of known frontotemporal dementia genes and detailed phenotype characterisation of individuals with frontotemporal dementia and schizophrenia were performed. The morbid risk for schizophrenia was significantly higher in relatives of frontotemporal dementia probands (1.35, s.e. = 0.45) than in relatives of Alzheimer's disease probands (0.32, s.e. = 0.22). Ten mixed families were characterised. In three of them a frontotemporal dementia causal mutation was identified that was present in individuals with schizophrenia. Several specific clinical features were noted in people with schizophrenia and frontotemporal dementia in mixed families. Co-occurrence of schizophrenia and frontotemporal dementia could indicate, in some families, a common aetiology for both conditions.

Effects of sdf-concealment on mental health levd and life quanty of the first degree relatives of the sdhizophrenia pattents

Objective To explore the effects of self-concealment on mental health state and life quality of the first degree relatives of the schizophrenia patients.Methods The physiological children and siblings of the schizophrenia patients who meet the DSM-Ⅳ criteria had been tested using Self-concealment Scale(SCS)and divided to one higher group and another lower group according to their scales.Then the results of the two groups had been compared with the scales from the testing with Symptom Checklist 90(SCL-90)and General Quality of Life Inventory(GQLI)respectively.Results The scales of 186 first degree relatives of schizophrenia were 36.24±11.02,significantly higher than 29.20±8.73 of normal model(t=5.21,P＜0.01).36 were in higher group with average scales of40.57±11.64 and 27 were in lower group with average scales of 32.81±9.04(t=2.81.P＜0.01).In higher self-concealment group most factor-scales of SCL-90 except of psychotic factor were significantly higher than those of lower group(P＜0.05)while the scales of GQLI in higher group were significantly lower than those in lower group(P＜0.05P or＜0.01).The scales of SCS in the first degree relatives of schizophrenia had a positive correlation with the scales of SCL-90(correlation index 0.384,P＜0.01)and a negative correlation with the scales of GQLI(correlation index-0.336,P＜0.01).Conclusion Self-concealment level in the first degree relatives has significant effect on their mental health and life quality.Higher group leads a bad mental health and life quality than lower group. Key words: Schizophrenia; First-degree relatives; Self-concealment; Mental health; Life quality

Twins with KBG Syndrome and Autism

Twins with KBG Syndrome and Autism

Meta-analytic Evidence for Familial Coaggregation of Schizophrenia and Bipolar Disorder

Several data sources suggest a link between schizophrenia and bipolar disorder (BD); however, family studies have not revealed coaggregation of these disorders. To systematically review family studies of probands with schizophrenia and BD and to determine whether these disorders coaggregate in families. MEDLINE and PsycINFO databases. All family studies published from January 1, 1980, to December 31, 2006, reporting morbid risk or raw counts of schizophrenia or BD in first-degree relatives (FDRs) of a proband group with DSM-III or later; International Classification of Diseases, Ninth or Tenth Revision; or research diagnostic criteria schizophrenia or BD were included. Of the original 2326 studies identified through the database search, 38 studies were used to investigate rates of BD in FDRs of probands with schizophrenia, while 39 studies were used to examine rates of schizophrenia in FDRs of BD probands. Data were analyzed with a novel random-effects bootstrapping technique that allows for the inclusion of studies lacking a patient or control group, which made up a substantial portion of the available data. Data were also blindly weighted for methodological quality. The FDRs of probands with schizophrenia showed significantly (P = .01) increased rates of BD relative to control FDRs (odds ratio [OR] = 2.08). The FDRs of probands with BD showed marginally (P = .06) increased rates of schizophrenia relative to control FDRs (OR = 2.10); this analysis was significant (P = .02) when studies that did not report morbid risk estimates were excluded (in this case, OR = 3.49). This meta-analysis provides direct evidence for familial coaggregation of schizophrenia and BD, a finding that argues against the view that these disorders are entirely discrete diagnostic entities. Rather, a continuum model is supported.