Familial Schizophrenia Research Articles

Language, Motor Ability and Related Deficits in Children at Familial Risk of Schizophrenia or Bipolar Disorder.

It is known that impairments in linguistic ability and motor function tend to co-occur in children, and that children from families with parental mental illness such as schizophrenia tend to perform poorly in both domains, but the exact nature of these links has not yet been fully elucidated. In this study, we leveraged the first wave of the Danish High Risk and Resilience Study (VIA 7), which includes both genetic data and measures covering multiple developmental domains. The VIA 7 cohort comprises 522 7-year-old children born to parents with schizophrenia (N = 202), bipolar disorder (N = 120) or neither (N = 200). We investigated the relationships between linguistic ability and motor function using correlation and regression analyses, focusing on developmental coordination disorder (DCD) and specific language impairment (SLI) and their potential associations with the three risk groups. We found significant correlations between most measures of language and motor function and significant associations of DCD and SLI with language and movement measures, respectively, the largest effect being that of DCD on receptive language, with a significant interaction effect: DCD was associated with poorer performance in children from schizophrenia families compared to bipolar disorder and control families. Both disorders showed higher prevalence among children with familial high risk of mental illness. We did not find significant evidence of genetic overlap between DCD and SLI. Our results suggest strong links between the domains of motor function and linguistic ability. Children of parents with schizophrenia are at high risk of comorbid language and movement disorders.

Hierarchical Genomic Analysis of Susceptibility to Schizophrenia in Sudanese multi-case families

Background Schizophrenia, with its diverse and complex presentation, is a prime candidate for genetic investigation. Its heritability in both familial and sporadic cases, clinical overlap with other psychiatric conditions, and individual variations in response to treatment contribute to its complexity. Numerous genes and associated biochemical pathways show significant differences at the population, familial, and individual levels. Additionally, schizophrenia may represent an evolutionary trade-off for human brain development, creativity, and intellectual performance. Material and Methods This case pseudo-control study analyzed the whole genomes/exomes of seven Sudanese families with multiple siblings affected by schizophrenia. We examined shared variants among family members, including both cases and controls, and unique variants shared between patients but not controls. These variants were filtered based on their impact on protein function, expression levels, allele frequencies, ACMG classification for rare variants, and disease associations. Networks were created to identify central genes and common biological pathways. Results and Discussion The examination of this complex disorder in Sudanese families revealed numerous variants, both common and rare, showing differences between families and between our population and those reported in the literature. This highlights the challenge of accounting for the known heritability of the disease. Our hierarchical approach demonstrates that schizophrenia’s etiology involves the cumulative effect of various interacting variants in an ascending order of influence. Common variants are shared among all samples, while rare variants are shared among two or three families, most of which are associated with schizophrenia. In conclusion The significance lies not merely in the number of detected variants but in understanding their interactive roles, step by step, to reveal the complete picture of the disease’s phenotype.

Family journey in the process of recovery of schizophrenia: A qualitative study

ABSTRACT Objective: The aim of this research is to explore the life experiences of schizophrenic families in accompanying the recovery process. Methods: This study uses a qualitative method with descriptive phenomenology to explain phenomena from family experiences. The number of the participants was eight families who had family members with schizophrenia. Sampling was determined by purposive sampling. Data were collected through in-depth interviews and analyzed using the Colaizzi method. Results: The results of this study show four themes that emerged including (1) psychological burden on the family, (2) families needing support in the recovery process, (3) obstacles due to social stigma, and (4) family gratitude for being able to pass the test patiently. Conclusion: The schizophrenia family’s journey in the recovery process is very long. They are required to endure in assisting the recovery process. Experiences felt by the family include feelings, obstacles, and hopes that arise in carrying out their role to assist the recovery process which aims to improve the health of schizophrenia patients. The findings from this study provide insight for nurses to be able to pay attention to family psychological problems by strengthening families through home visits and health promotion related to the recovery process of survivor schizophrenia.

Differential predictors of expressed emotion toward individuals with schizophrenia between families and halfway houses.

This study investigated patient- and caregiver-related predictors of expressed emotion (EE) toward individuals with schizophrenia in families and halfway houses and yet understudied differential effects across settings. We included 40 individuals with schizophrenia living with their families ("outpatients") and 40 "inpatients" in halfway houses and recorded the EE of 56 parents or 22 psychiatric nurses, respectively, through Five Minutes Speech Sample. Each outpatient was rated by one to two parents; each inpatient was rated by two to five nurses. As EE ratings had a multilevel structure, EE predictors were investigated in backward stepwise generalized linear mixed models using the "buildmer" R package. We first fitted models including either caregiver- or patient-related predictors in each setting and finally included both types of predictors. Setting-specific patient-related effects were investigated in interaction analyses. Adjustment for multiple tests identified the most robust associations. In multivariate models including either caregiver- or patient-related predictors, nurses' higher age, shorter work experience and lower inpatients' negative symptoms robustly predicted higher emotional overinvolvement (EOI). In the final models including both types of predictors, nurses robustly displayed lower EOI (i.e., reduced concern and disengagement) toward inpatients with higher negative symptoms. Several other features were nominally associated with criticism and EOI in each setting. However, no feature robustly predicted criticism in inpatients and criticism/EOI in outpatients after adjustment for multiple tests. In interaction analyses, higher negative symptoms differentially predicted lower EOI in nurses only. Our findings suggest setting-specific pathogenetic pathways of EOI and might help customize psychoeducational interventions to staff in halfway houses.

Differential correlates of criticism versus emotional overinvolvement towards patients with schizophrenia living in halfway houses or with their families

PurposeThis study systematically searched for differential correlates of criticism vs. emotional overinvolvement (EOI) towards patients with schizophrenia in families and halfway houses, which have only incidentally been reported in previous research. Identified patterns were compared across settings.MethodsWe included 40 inpatients with schizophrenia living in halfway houses and 40 outpatients living with their families and recorded the expressed emotion (EE) of 22 psychiatric nurses or 56 parents, respectively, through Five Minutes Speech Samples. Each nurse rated 1–12 inpatients and each inpatient was rated by 2–5 nurses. Each outpatient was rated by one or both parents. As EE ratings had a multilevel structure, weighted Spearman correlations of criticism and EOI with various patient- and caregiver-related characteristics were calculated and compared with Meng’s z-test.ResultsCriticism was weakly negatively correlated with EOI in nurses but negligibly in parents. Distinct patterns of significant differential correlates arose across settings. Outpatients’ aggressive behavior and parents’ related burden were mainly associated with higher criticism. Inpatients’ symptoms (agitation/aggression, negative and other psychotic symptoms) and nurses’ burnout (Depersonalization) were mainly associated with lower EOI. Inpatients’ perceived criticism and outpatients’ previous suicide attempts were equally associated with higher criticism and lower EOI (mirror correlations). Finally, various inpatient attributes (older age, chronicity, unemployment and smoking) triggered higher EOI only. Inpatients’ age, psychopathology (esp. agitation/aggression and negative symptoms) and perceived criticism survived adjustment for multiple comparisons.ConclusionOur findings suggest setting-specific pathogenetic pathways of criticism and EOI and might help customize psychoeducational interventions to staff and families.

TULP4, a novel E3 ligase gene, participates in neuronal migration as a candidate in schizophrenia.

TUB-like protein 4 (TULP4) is one of the distant members of tubby family proteins, whose function remains largely unknown. In the present study, we intend to identify the role of TULP4 in schizophrenia from human samples and animal models. Whole-exome sequencing was used to detect the four schizophrenia families collected. In different cell lines, the effects of identified variants in TULP4 gene on its expression and localization were analyzed. Knockdown models in utero and adult mice were employed to investigate the role of Tulp4 on neuronal migration and schizophrenia-related behavior. Subsequently, co-IP assays were used to search for proteins that interact with TULP4 and the effects of mutants on the molecular function of TULP4. For the first time, we identified five rare variants in TULP4 from schizophrenia families, of which three significantly reduced TULP4 protein expression. Knockdown the expression of Tulp4 delayed neuronal migration during embryological development and consequently triggered abnormal behaviors in adult mice, including impaired sensorimotor gating and cognitive dysfunction. Furthermore, we confirmed that TULP4 is involved in the formation of a novel E3 ligase through interaction with CUL5-ELOB/C-RNF7 and the three deleterious variants affected the binding amount of TULP4 and CUL5 to a certain extent. Together, we believe TULP4 plays an important role in neurodevelopment and subsequent schizophrenic-related phenotypes through its E3 ubiquitin ligase function.

The psychosis risk factor RBM12 encodes a novel repressor of GPCR/cAMP signal transduction

RBM12 is a high-penetrance risk factor for familial schizophrenia and psychosis, yet its precise cellular functions and the pathways to which it belongs are not known. We utilize two complementary models, HEK293cells and human iPSC-derived neurons, and delineate RBM12 as a novel repressor of the G protein-coupled receptor/cAMP/PKA (GPCR/cAMP/PKA) signaling axis. We establish that loss of RBM12 leads to hyperactive cAMP production and increased PKA activity as well as altered neuronal transcriptional responses to GPCR stimulation. Notably, the cAMP and transcriptional signaling steps are subject to discrete RBM12-dependent regulation. We further demonstrate that the two RBM12 truncating variants linked to familial psychosis impact this interplay, as the mutants fail to rescue GPCR/cAMP signaling hyperactivity in cells depleted of RBM12. Lastly, we present a mechanism underlying the impaired signaling phenotypes. In agreement with its activity as an RNA-binding protein, loss of RBM12 leads to altered gene expression, including that of multiple effectors of established significance within the receptor pathway. Specifically, the abundance of adenylyl cyclases, phosphodiesterase isoforms, and PKA regulatory and catalytic subunits is impacted by RBM12 depletion. We note that these expression changes are fully consistent with the entire gamut of hyperactive signaling outputs. In summary, the current study identifies a previously unappreciated role for RBM12 in the context of the GPCR-cAMP pathway that could be explored further as a tentative molecular mechanism underlying the functions of this factor in neuronal physiology and pathophysiology.

Identifying novel risk conferring genes involved in glycosylation processes with familial schizophrenia in an Indian cohort: Prediction of ADAMTS9 gene variant for structural stability

Schizophrenia is a complex neuropsychiatric disorder and heritability is as high as 80 % making it the most heritable mental disorder. Although GWAS has identified numerous variants, the pathophysiology is still elusive. Here, an attempt was made to identify genetic risk factors in familial cases of schizophrenia that are associated with a common causative pathway. To achieve this objective, exome sequencing was done in 4 familial cases and identified six unique coding variants in five genes. Among these genes, PIGQ gene has two pathogenic variants, one nonsense and in-frame deletion. One missense variant in GALNT16 and one in GALNT5 have variable damaging score, however, the other variants, in ADAMTS9 and in LTBP4 have the highest damaging score. Further analysis showed that the variant of LTBP4 was not present in the functional domain. The other missense variant in the ADAMTS9 gene was found to be significant and was present in the thrombospondin repeat motif, one of the important motifs. Detailed molecular dynamics simulation study on this variant showed a damaging effect on structural stability. Since, all these genes culminated into the glycosylation process, it was evident that an aberrant glycosylation process may be one of the risk factors. Although, extracellular matrix formation through glycosylation have been shown to be associated, the involvement of ADAMTS9 and PIGQ gene mediated glycosylation has not been reported. In this paper, a novel link between ADAMTS9 and PIGQ gene with schizophrenia have been reported. Therefore, this novel observation has contributed immensely to the existing knowledge on risk factor of Schizophrenia.

A case-control study of aggressiveness in adolescents with schizophrenia family history

IntroductionViolence is a common behavioral and health concern among adolescents, aged 12 to 18 years old. In fact, aggressiveness may result in severe outcome in a critical age characterised by biological, psychological, and social changes. Schizophrenia is a severe and chronic condition, with elevated level of aggressiveness. Since unaffected biological relatives of schizophrenia patients share similar though less severe neurocognitive and behavioral abnormalities seen in their affected relatives, they are at increased risk of violence mainly during adolescence. However, studies including adolescents with schizophrenia first degree history are scarce.ObjectivesThe aim of this survey was to evaluate the aggressiveness among unaffected adolescents with fist degree family history of schizophrenia and in a control group of adolescents with no family psychiatric history.MethodsIn this purpose wo conducted a case-control cross sectional study in Razi hospital during three months: from July to September 2022. Unaffected adolescents aged 12 to 18 whom first-degree relatives were diagnosed with schizophrenia according to DSM-5 criteria were included. Adolescents with psychiatric conditions or medical affections associated with psychiatric presentation were not included. Control group was selected amongst the population. Sociodemographic data were collected on a preestablished questionnaire and the following scales were used: The Life History of Aggression LHA, an 11 items self-reported tool, in the Arabic version, The Aggression Questionnaire AQ which is a 29 items self-reported scale in Arabic version. Written informed consent was obtained from the legal tutor of each adolescent.ResultsResults of this survey are ongoing.ConclusionsResults of this survey are ongoing.Disclosure of InterestNone Declared

Relationship between polygenic risk scores and symptom dimensions of schizophrenia and schizotypy in multiplex families with schizophrenia.

Psychotic disorders and schizotypal traits aggregate in the relatives of probands with schizophrenia. It is currently unclear how variability in symptom dimensions in schizophrenia probands and their relatives is associated with polygenic liability to psychiatric disorders. To investigate whether polygenic risk scores (PRSs) can predict symptom dimensions in members of multiplex families with schizophrenia. The largest genome-wide data-sets for schizophrenia, bipolar disorder and major depressive disorder were used to construct PRSs in 861 participants from the Irish Study of High-Density Multiplex Schizophrenia Families. Symptom dimensions were derived using the Operational Criteria Checklist for Psychotic Disorders in participants with a history of a psychotic episode, and the Structured Interview for Schizotypy in participants without a history of a psychotic episode. Mixed-effects linear regression models were used to assess the relationship between PRS and symptom dimensions across the psychosis spectrum. Schizophrenia PRS is significantly associated with the negative/disorganised symptom dimension in participants with a history of a psychotic episode (P = 2.31 × 10-4) and negative dimension in participants without a history of a psychotic episode (P = 1.42 × 10-3). Bipolar disorder PRS is significantly associated with the manic symptom dimension in participants with a history of a psychotic episode (P = 3.70 × 10-4). No association with major depressive disorder PRS was observed. Polygenic liability to schizophrenia is associated with higher negative/disorganised symptoms in participants with a history of a psychotic episode and negative symptoms in participants without a history of a psychotic episode in multiplex families with schizophrenia. These results provide genetic evidence in support of the spectrum model of schizophrenia, and support the view that negative and disorganised symptoms may have greater genetic basis than positive symptoms, making them better indices of familial liability to schizophrenia.

Examining the source of increased bipolar disorder and major depressive disorder common risk variation burden in multiplex schizophrenia families

Psychotic and affective disorders often aggregate in the relatives of probands with schizophrenia, and genetic studies show substantial genetic correlation among schizophrenia, bipolar disorder, and major depressive disorder. In this study, we examined the polygenic risk burden of bipolar disorder and major depressive disorder in 257 multiplex schizophrenia families (N = 1005) from the Irish Study of High-Density Multiplex Schizophrenia Families versus 2205 ancestry-matched controls. Our results indicate that members of multiplex schizophrenia families have an increased polygenic risk for bipolar disorder and major depressive disorder compared to population controls. However, this observation is largely attributable to the part of the genetic risk that bipolar disorder or major depressive disorder share with schizophrenia due to genetic correlation, rather than the affective portion of the genetic risk unique to them. These findings suggest that a complete interpretation of cross-disorder polygenic risks in multiplex families requires an assessment of the relative contribution of shared versus unique genetic factors to account for genetic correlations across psychiatric disorders.

What outcomes in community mental health research are important to caregivers of people with schizophrenia? An exploratory qualitative analysis of an online survey.

This study investigated outcomes in community mental health research that were important to caregivers of people with schizophrenia. Using an online survey conducted from August 1 to 31, 2020, data were collected from caregivers belonging to the LINE Schizophrenia Family Association. Caregivers identified outcomes important in community mental health research. Two researchers categorized caregivers' statements into research outcomes. A total of 132 caregivers completed the online selfreported questionnaire, and 296 caregiver statements were identified. Qualitative analysis identified 17 outcome categories. The caregivers tended to value having more free time, maintaining an appropriate relationship with people with schizophrenia, and being able to cope with their symptoms. This exploratory study newly demonstrates the outcomes that caregivers of people with schizophrenia consider important in community mental health research. The findings may be useful in selecting outcomes for future studies of caregivers.

Evaluating the role of common risk variation in the recurrence risk of schizophrenia in multiplex schizophrenia families

Multiplex families have higher recurrence risk of schizophrenia compared to the families of sporadic cases, but the source of this increased recurrence risk is unknown. We used schizophrenia genome-wide association study data (N = 156,509) to construct polygenic risk scores (PRS) in 1005 individuals from 257 multiplex schizophrenia families, 2114 ancestry-matched sporadic cases, and 2205 population controls, to evaluate whether increased PRS can explain the higher recurrence risk of schizophrenia in multiplex families compared to ancestry-matched sporadic cases. Using mixed-effects logistic regression with family structure modeled as a random effect, we show that SCZ PRS in familial cases does not differ significantly from sporadic cases either with, or without family history (FH) of psychotic disorders (All sporadic cases p = 0.90, FH+ cases p = 0.88, FH− cases p = 0.82). These results indicate that increased burden of common schizophrenia risk variation as indexed by current SCZ PRS, is unlikely to account for the higher recurrence risk of schizophrenia in multiplex families. In the absence of elevated PRS, segregation of rare risk variation or environmental influences unique to the families may explain the increased familial recurrence risk. These findings also further validate a genetically influenced psychosis spectrum, as shown by a continuous increase of common SCZ risk variation burden from unaffected relatives to schizophrenia cases in multiplex families. Finally, these results suggest that common risk variation loading are unlikely to be predictive of schizophrenia recurrence risk in the families of index probands, and additional components of genetic risk must be identified and included in order to improve recurrence risk prediction.

Caregiving burden and positive aspects of caregiving among family caregivers of people living with schizophrenia: Two sides of the same coin

BackgroundCaring for a family member with schizophrenia is associated with a significant burden, but may also bring about positive transformation among caregivers, which were rarely studied simultaneously. AimsThe current study aims to investigate the association between caregiver burden and positive aspects of caregiving (PAC), as well as explore and compare the correlates of each. MethodsA cross-sectional study was conducted on a representative urban sample of schizophrenia family caregivers in China (N = 406). Participants were interviewed individually to complete questionnaires regarding socio-demographics, caregiver burden, PAC, and psychosocial factors that included social support, coping, and family functioning. ResultsThe caregivers reported moderate levels of both caregiver burden (mean:43.05 ± 18.26, range: 0–88) and PAC (mean: 25.88 ± 9.59, range: 0–36), which were not significantly associated with each other (r = −0.06, p = 0.25) and had different correlates. Parent caregivers, middle and high school education, additional dependents, lower level of social support, and frequent endorsement of active and passive coping were all associated with more caregiver burden. Higher levels of social support, active coping, and family functioning were associated with higher PAC. ConclusionsCaring for a family member with schizophrenia can be both burdensome and rewarding. Caregiver burden and PAC coexist yet are unrelated with different correlates. Future research and intervention programs should not only focus on mitigating caregiver burden but also enhancing PAC, which may be realized through the improvement of social support, active coping, and family functioning while paying special attention to various socio-demographics.

The 14-3-3 Protein Family and Schizophrenia.

Schizophrenia is a debilitating mental disorder that affects approximately 1% of the world population, yet the disorder is not very well understood. The genetics of schizophrenia is very heterogenous, making it hard to pinpoint specific alterations that may cause the disorder. However, there is growing evidence from human studies suggesting a link between alterations in the 14-3-3 family and schizophrenia. The 14-3-3 proteins are abundantly expressed in the brain and are involved in many important cellular processes. Knockout of 14-3-3 proteins in mice has been shown to cause molecular, structural, and behavioral alterations associated with schizophrenia. Thus, 14-3-3 animal models allow for further exploration of the relationship between 14-3-3 and schizophrenia as well as the study of schizophrenia pathology. This review considers evidence from both human and animal model studies that implicate the 14-3-3 family in schizophrenia. In addition, possible mechanisms by which alterations in 14-3-3 proteins may contribute to schizophrenia-like phenotypes such as dopaminergic, glutamatergic, and cytoskeletal dysregulations are discussed.

Experience Caring for People with Schizophrenia in Families in West Sumatera

BACKGROUND: Schizophrenia is a severe neurobiological brain disorder that continues and has poor insight so that it affects the functioning of the lives of individuals, families, and communities. Caregivers of people with schizophrenia had more stressed because of the nature, symptoms, and prolonged duration of illness of people with schizophrenia. AIM: This study aimed to determine the family’s experience in the practice of caring for people with schizophrenia in the family in West Sumatra. METHODS: The research population was families who cared for people with schizophrenia in Sumatera Barat and have been caring for people with schizophrenia for more than a year. It had determined with the purposive-sampling method with an in-depth interview technique. The researchers, the main instrument, explore the caregiver’s experience through five family development tasks. RESULTS: The results of this study obtained five major themes, namely, recognizing problems, making treatment decisions, how families treat people with schizophrenia, difficulties faced by families, and utilization of health services. CONCLUSION: In caring for people with schizophrenia, the family has carried out care tasks in the family, namely, recognizing problems, making decisions about treatment, families caring for sick family members, and families can take advantage of health services optimally.

Recreational Marijuana Use, Adolescent Cognitive Development, and Schizophrenia Susceptibility

BackgroundWe investigated how low marijuana (MJ) use levels, the typical use pattern in most adolescent users, affect cognitive maturation and schizophrenia risk. MethodsIn two complementary adolescent samples where the majority reported minimal MJ use, we compared cognitive performances before and after MJ use initiation. The Iowa sample (40 first-degree relatives and 54 second-degree relatives of patients with schizophrenia and 117 control subjects with no schizophrenia family history) underwent a battery of standardized neuropsychological tests at 0, 18, and 36 months. Based on self-administered Timeline Followback interviews, 26.5% of adolescents had emergent MJ use (eMJ) during follow-up. The second sample (n = 3463), derived from a birth cohort, received substance use and sustained attention assessments between ages 10 and 15 years. Mixed linear models and regression analyses tested the effects of eMJ on longitudinal changes in cognitive performance. ResultsIn the Iowa sample, longitudinal changes in 5 of 8 cognitive domains were significantly associated with eMJ. On sustained attention, visuospatial working memory, and executive sequencing, adolescents with eMJ showed less age-expected improved performance. In addition, first-degree relatives with eMJ were less improved on processing speed and executive reasoning than first-degree relatives without eMJ. In the birth cohort, greater intraindividual variability in reaction times (indicative of poorer sustained attention) was significantly associated with more frequent MJ use and with recreational use levels. ConclusionsNonheavy MJ use disrupts normal adolescent maturation and compounds aberrant adolescent maturation associated with familial schizophrenia risk. These findings underscore the importance of reducing adolescent MJ access in the context of increased availability to high-potency MJ.

Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study.

Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case-control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD). Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons. In case-control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case-case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54-0.92] and PRS-D (OR = 1.31, 95% CI 1.06-1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23-3.74). Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.

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.

Familial Co-Aggregation of Dementia with Schizophrenia: A Cross Sectional Pedigree Analysis.

Background:Cognitive impairment is the core outcome defining feature in schizophrenia. Schizophrenia, in the context of a broader neurodegenerative conceptualization, may have shared etiology with major neurocognitive disorders (MNCD). To elucidate this association there is definite need to explore the familial loading of dementia, in families of patients with schizophrenia.Methods:The authors compared relatives including parental generation and siblings of 100 cases (schizophrenia probands) and 100 controls (anxiety disorder) in order to assess the familial co-aggregation of MNCD. All cases and control were screened with Mini International Neuropsychiatric Interview screen for psychiatric morbidity. The pedigree analysis was conducted by family history method and Family Interview for Genetic Studies. Cognitive impairment in pedigree was screened by community screening instrument for dementia.Results:There was nonreporting of MNCD in the total 2538 relatives (proband siblings +parental generation) of both cases and controls. Diabetes mellitus was the most common somatic morbidity, found significantly more among the parental generation of cases than healthy controls (χ2 (1, 1713) = 6.452, P < 0.05). The odds of having various psychiatric and medical morbidities in the schizophrenia families compared to control are less than 1.Conclusion:There is no familial co-aggregation of MNCD in schizophrenia probands and common etiology between the two is less likely. Either schizophrenia could be counter-intuitively protective for MNCD or a reversible risk factor that can be prevented by effective treatments