Schizophrenia In Offspring Research Articles

Malnutrition Role to the Risk of Developing Schizophrenia A Literature Review

Some evidence suggests that nutritional factors in-utero may contribute to the development of schizophrenia in offspring. To better understand the relationship between in-utero exposure to nutritional deficiency as a determinant of schizophrenia, a narrative review was conducted. Natural studies involving prenatal exposure to famines were identified and described. The relationship between malnutrition, low birth weight, and obstetric complications was evaluated as implicated in schizophrenia development. In addition to malnutrition, various micronutrients and the complementary biological mechanisms were reviewed including, iron, Vitamin D, and folate. Given the inherent link between poverty and malnutrition, associations between income and risk of schizophrenia were examined. The review concluded that prenatal malnutrition may be associated with an increased risk of schizophrenia. Given the relatively high prevalence of nutritional deficiencies during pregnancy, this work has the potential to offer substantial benefits for the intervention and prevention of schizophrenia in the population. More work and research are needed to directly observe malnutrition’s impact on schizophrenia, but such opportunities are limited due to ethical considerations. To address these limitations, future research could explore innovative methodologies to bridge the gap in understanding and provide insights into the complex interplay between prenatal malnutrition and schizophrenia.

Maternal vitamin D levels during pregnancy and offspring schizophrenia

BackgroundFindings from previous studies on maternal 25(OH)D levels during pregnancy and offspring schizophrenia are limited and inconsistent. MethodsWe used nationwide population-based register data with a nested case-control design to examine the association between maternal 25(OH)D levels during pregnancy and offspring schizophrenia. The cases of schizophrenia (n = 1145) were born from 1987 to 1997, and received a diagnosis of schizophrenia by 2017, and were matched with equal number of controls. A quantitative immunoassay was used to measure maternal 25(OH)D in archived maternal serum in the national biobank of the Finnish Maternity Cohort, collected during the first and early second trimesters. Conditional logistic regression models examined the association between maternal 25(OH)D levels and offspring schizophrenia. ResultsNo significant association was found between log-transformed maternal 25(OH)D levels and schizophrenia in unadjusted (OR 0.96, 95 % CI 0.78–1.17, p = 0.69) or adjusted analyses (aOR 0.98, 95 % CI 0.79–1.22, p = 0.89). Analyses by quintiles also revealed no association between the lowest quintile of maternal 25(OH)D levels and schizophrenia (OR 1.09, 95 % CI 0.81–1.45, p = 0.55; aOR 1.06, 95 % CI 0.78–1.45, p = 0.71). Maternal 25(OH)D levels, measured in categories, either in deficient category (OR 1.07 (0.85–1.35), p = 0.52; aOR 1.05 (0.81–1.34), p = 0.88) or insufficient category (OR 1.13, 95 % CI 0.92–1.40, p = 0.23; aOR 1.13, 95 % CI 0.90–1.41, p = 0.27) were also not associated with offspring schizophrenia. ConclusionsMaternal vitamin D levels in early pregnancy were not associated with offspring schizophrenia. Future studies measuring vitamin D during different stages of gestation are needed to draw firm conclusions.

Mutual effects of gestational diabetes and schizophrenia: how can one promote the other?: A review.

Although the physical complications of gestational diabetes mellitus (GDM) are well known, emerging evidence suggests a significant link with psychiatric conditions such as schizophrenia (SCZ). This review aimed to explore the extent, nature, and implications of the association between GDM and SCZ, exploring how the 2 conditions may reciprocally influence each other. We conducted a comprehensive literature review and, analyzed clinical and mechanistic evidence supporting the mutual effects of GDM and SCZ. This review examined factors such as neurodevelopment and the impact of antipsychotics. The study found that Maternal GDM increases the risk of SCZ in offspring. Conversely, women with SCZ were more prone to hyperglycemic pregnancies. The research highlights significant regional variations in GDM prevalence, with the highest rate in the Middle East, North Africa, and South-East Asia regions. These regional variations may have an impact on the epidemiology of SCZ. Furthermore, this review identifies the potential biological and environmental mechanisms underlying these associations. There is a bidirectional relationship between GDM and SCZ, with each disorder potentially exacerbating the others. This relationship has significant implications for maternal and offspring health, particularly in regions with high GDM prevalence. These findings underline the need for integrated care approaches for women with SCZ during pregnancy and the importance of monitoring and managing GDM to mitigate the risk of SCZ in the offspring. Notably, this study recognizes the need for further research to fully understand these complex interactions and their implications for healthcare.

Brain developmental trajectories in offspring of parents with schizophrenia or bipolar disorder

AbstractEarly diagnosis and intervention are essential for managing and improving long-term outcomes of severe mental illness, highlighting the need for reliable early biomarkers. This longitudinal study explores whether the development of the brain during childhood and adolescence differs between offspring of parents with and without schizophrenia or bipolar disorder. Moreover, we will assess if the age-dependent change over time in brain volume, cortical thickness and surface, structural network indices, and cortical gyrification are related to the presence and severity of psychiatric symptoms and level of IQ. We obtained 286 T1-weighted MRI scans of 184 offspring (aged 8–18 years at baseline) of at least one parent diagnosed with bipolar disorder (n=78) or schizophrenia (n=52) and offspring of parents without severe mental illness (n=54); 102 offspring underwent a follow-up scan (on average 3.9 years between scans).Group comparisons and the associations with clinical and cognitive measures were analysed with linear mixed-effects models. To correct for multiple comparisons, we applied a Benjamini-Hochberg false discovery rate (FDR) correction (q=0.05). A significant effect of age was found on most of the included brain features, with suggestive evidence for subtle deviations in trajectories in the cortical thickness, structural network indices but not in gyrification index, sulcal depth, length and width or surface area in offspring of parents with schizophrenia. Interestingly, these deviations in brain development in schizophrenia offspring remained significant after taking the presence of a diagnosis or level of IQ into account. These findings suggest the aberrant brain development in familial high-risk youngsters is associated with being at familial risk and not with (also) being at clinical high-risk.Disclosure of InterestNone Declared

The psychopathology among the offspring of schizophrenia and bipolar I disorder patients in an Egyptian sample: A comparative study.

A variety of psychiatric illnesses can develop in children of parents who suffer from bipolar affective disorder. The purpose of the research was to investigate, among the offsprings of patients diagnosed with schizophrenia and bipolar disorder type I, the prevalence of a variety of psychiatric diseases as well as a range of behavioral abnormalities. This was a cross-sectional observational comparative study. The outpatient psychiatric clinics at Shebin Elkom Mental Health Hospital, Menofia Governorate, Egypt 500 offspring (there were 250 offspring of parents both diagnosed with schizophrenia and 250 offsprings born to parents with bipolar affective disorder). Statistically significant association of male gender with somatic complaints, social problems, and attention problems in the bipolar offspring group. In addition, there was a statistically significant association between female gender and anxiety or depression in the bipolar offspring group. Moreover, there was a statistically significant association between male gender and thought problems and aggressive behavior in the schizophrenia group. Assessment of psychiatric symptoms using K-SADS in relation to gender revealed a statistically significant association of male gender with affective disorder, behavioral disorder, and substance use disorder in the bipolar offspring group. Moreover, there was a statistically significant association between female gender and psychotic disorder in the schizophrenia group. We concluded that offspring with bipolar illness had a significant association with somatic symptoms, anxiety/depressive disorder, social issues, attention problems, and aggressive behavior. Schizophrenia offspring were strongly related to thought issues.

Exploring the complex relationship between caffeine consumption and schizophrenia: A review of epidemiological and clinical studies.

This review delves into the intricate interplay between caffeine consumption and schizophrenia, examining evidence from epidemiological and clinical studies. While epidemiological research offers conflicting findings regarding the association between coffee intake and schizophrenia risk, clinical studies reveal diverse impacts of caffeine on symptomatology and cognition in individuals with schizophrenia. Some epidemiological studies suggest a potential protective effect of coffee consumption against schizophrenia, whereas others fail to establish a significant correlation. Clinical investigations highlight the complexity of caffeine's influence, with varied effects on symptom severity and cognitive function observed among schizophrenia patients. Notably, caffeine may exacerbate positive symptoms while alleviating negative symptoms and cognitive deficits in this population. However, limitations such as small sample sizes and reliance on self-reported data hinder the generalizability of these findings. Furthermore, genetic factors, prenatal exposure, and substance abuse contribute to the complexity of the relationship between caffeine and schizophrenia. Studies indicate that individuals with a genetic predisposition to schizophrenia may be more vulnerable to the effects of caffeine, while prenatal exposure to caffeine may elevate the risk of schizophrenia in offspring. Additionally, substance abuse, including high caffeine and nicotine consumption, is prevalent among individuals with schizophrenia, exacerbating symptom severity. Future research directions include addressing methodological limitations, such as small sample sizes and reliance on self-reported data, and exploring the effects of caffeine on schizophrenia using larger, more diverse cohorts and controlled methodologies. A deeper understanding of caffeine's impact on schizophrenia is crucial for informing clinical practice and developing personalized interventions for patients. Ultimately, this review underscores the need for further investigation into the complex relationship between caffeine consumption and schizophrenia to improve patient outcomes and inform evidence-based interventions.

Emerging psychopathology and clinical staging in adolescent offspring of parents with bipolar disorder or schizophrenia-A longitudinal study.

Offspring of parents with bipolar disorder (BDo) and schizophrenia (SZo) are at increased risk for these disorders and general psychopathology. Little is known about their (dis)similarities in risk and developmental trajectories during adolescence. A clinical staging approach may help define the developmental course of illness. The Dutch Bipolar and Schizophrenia Offspring Study is a unique cross-disorder and prospective cohort study, established in 2010. In total, 208 offspring (58 SZo, 94 BDo, and 56 control offspring [Co]) and their parents participated. Offspring were 13.2 years (SD = 2.5; range: 8-18 years) at baseline and 17.1 years (SD = 2.7) at follow-up (88.5% retention rate). Psychopathology was assessed using the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Lifetime Version, and Achenbach System of Empirically Based Assessment parent-, self- and teacher-reports. Groups were compared on (1) the presence of categorical psychopathology, (2) timing and development of psychopathology using a clinical staging perspective, and (3) dimensional psychopathology using a multi-informant approach. SZo and BDo showed more categorical psychopathology and (sub)clinical symptoms, as compared to Co. SZo have, compared to BDo, an increased risk for developmental disorders, a younger age of onset, and more (sub)clinical symptoms of the mood and behavioral spectrum as reported by multiple informants. Our study shows that the phenotypical risk profile overlaps between SZo and BDo, although an earlier onset of developmental psychopathology was found specifically in SZo, suggesting of a potentially different ethiopathophysiology. Longer follow-up and future studies are needed.

Prenatal organochlorine pollutant exposure and risk of schizophrenia in a national birth cohort

Non-genetic prenatal exposures have been associated with schizophrenia risk. However, the role of prenatal exposure to environmental neurotoxicants in offspring schizophrenia risk has been studied in only limited instances. Polychlorinated biphenyls (PCBs) and the pesticide metabolite p,p′-dichlorodiphenyl dichloroethylene (DDE) have been linked to neurodevelopmental outcomes, including impairments implicated in schizophrenia. To determine whether prenatal maternal levels of organochlorine pollutants including PCBs or DDE are associated with schizophrenia in the offspring, an investigation was conducted in the Finnish Prenatal Study of Schizophrenia (FIPS-S), a case-control study nested in a national birth cohort. Cases were born in 1987–1991 and had at least two diagnoses of schizophrenia (ICD-10 F20; ICD-9 295) or schizoaffective disorder (ICD-10 F25; ICD-9 295.7) recorded in the national Care Register for Health Care. Each case was individually matched to a control on sex, date of birth, and residence in Finland on the date of case diagnosis. In 500 case-control pairs, PCB congeners 74, 99, 118, 138, 153, 156, 170, 180, 183, 187, and some widespread organochlorine pesticides or their metabolites including DDE were measured in archived prenatal maternal sera using gas chromatography - high triple quadrupole mass spectrometry. Maternal total PCBs were quantified as the sum of concentrations of the measured congeners. Associations with schizophrenia were examined using conditional logistic regression. Maternal PCB or DDE levels greater than the 75th percentiles of the control distributions showed no evidence of association with offspring schizophrenia (PCBs: adjusted odds ratio (aOR) = 1.13, 95 % CI = 0.85–1.50), p = 0.41; DDE: aOR = 1.08, 95 % CI = 0.80–1.45; p = 0.63). Maternal levels of either pollutant dichotomized at the 90th percentile or considered as a continuous variable also did not show evidence for association with offspring schizophrenia. This study found a lack of evidence that prenatal maternal levels of the organochlorine pollutants DDE and PCBs are associated with offspring risk of schizophrenia.

Schizophrenia and obesity: May the gut microbiota serve as a link for the pathogenesis?

Schizophrenia (SZ) places a tremendous burden on public health as one of the leading causes of disability and death. SZ patients are more prone to developing obesity than the general population from the clinical practice. The development of obesity frequently causes poor psychiatric outcomes in SZ patients. In turn, maternal obesity during pregnancy has been associated with an increased risk of SZ in offspring, suggesting that these two disorders may have shared neuropathological mechanisms. The gut microbiota is well known to serve as a major regulator of bidirectional interactions between the central nervous systemand the gastrointestinal tract. It also plays a critical role in maintaining physical and mental health in humans. Recent studies have shown that the dysbiosis of gut microbiota is intimately associated with the onset of SZ and obesity through shared pathophysiological mechanisms, particularly the stimulation of immune inflammation. Therefore, gut microbiota may serve as a common biological basis for the etiology in both SZ and obesity, and the perturbed gut-brain axis may therefore account for the high prevalence of obesity in patients with SZ. On the basis of these findings, this review provides updated perspectives and intervention approaches on the etiology, prevention, and management of obesity in SZ patients by summarizing the recent findings on the role of gut microbiota in the pathogenesis of SZ and obesity, highlighting the role of gut-derived inflammation.

Is paternal immune activation just as important as maternal immune activation? Time to rethink the bi-parental immune priming of neurodevelopmental model of schizophrenia

The neurodevelopmental origin of schizophrenia is a paradigmatic etiological construct. Parental exposure to environmental adversities and altered parental immune and stress-regulatory pathways affect the neurodevelopment of the fetus and may enhance the risk of schizophrenia in offspring. With respect to the parental contribution to these neurodevelopmental aberrations, most research has been on the maternal contribution. Maternal Immune activation, induced by maternal infections has been identified as a key pathway in the neurodevelopmental model of schizophrenia. Recent understanding points towards the fact that both the maternal and paternal priming offers survival advantages of the offspring to pathogen exposure. However, notwithstanding common epigenetic mechanisms applicable to both sexes, there is a lack of empirical data on the effect of paternal immune activation on neurodevelopmental aberrations and the consequent risk of schizophrenia in offspring.Large birth-cohort studies suggest a comparable impact of maternal and paternal infections on the risk of schizophrenia in offspring. The link between maternal infection and the risk of schizophrenia is mediated by the elements of the immune system through induction of maternal immune activation and subsequent neural and immune developmental aberrations. The contribution of paternal immune activation to schizophrenia risk has not yet been adequately explored. It is rational to assume that paternal infections might also enhance the risk of schizophrenia in offspring through paternal immune activation leading to neuroimmunodevelopmental aberrations. However, the underlying mechanisms whereby paternal infections as well as paternal immune activation might confer the risk of schizophrenia in the offspring seem to be distinct from maternal infection as the modes of transfer of the maternal and paternal factors are different. Maternal immune priming during gestation seems primarily through the direct effect of soluble immune factors, while the paternal immune priming might be mediated predominantly by epigenetic processes or through the effect of modifying factors in sperm. An account of plausible underlying mechanisms linking paternal immune activation and risk of schizophrenia are highlighted in this article. Furthermore, we propose the possibility of bi-parental immune priming in driving the neuroimmunodevelopmental abnormality as a risk mechanism of schizophrenia. It is envisaged that the neuroimmunodevelopmental aberration-associated risk of schizophrenia could be the result of cumulative effects of maternal as well as paternal immune stimulation. Delineation of the underlying maternal and paternal immune priming mechanism(s) will have important implications in resolving dilemmas of schizophrenia etiology as well as prevention.

Proxy gene-by-environment Mendelian randomization study of the association between cigarette smoking during pregnancy and offspring mental health.

Smoking prevalence is higher among individuals with schizophrenia or depression, and previous work has suggested this relationship is causal. However, this may be due to dynastic effects, for example reflecting maternal smoking during pregnancy rather than a direct effect of smoking. We used a proxy gene-by-environment Mendelian randomization approach to investigate whether there is a causal effect of maternal heaviness of smoking during pregnancy on offspring mental health. Analyses were performed in the UK Biobank cohort. Individuals with data on smoking status, maternal smoking during pregnancy, a diagnosis of schizophrenia or depression, and genetic data were included. We used participants' genotype (rs16969968 in the CHRNA5 gene) as a proxy for their mothers' genotype. Analyses were stratified on participants' own smoking status in order to estimate the effect of maternal smoking heaviness during pregnancy independently of offspring smoking. The effect of maternal smoking on offspring schizophrenia was in opposing directions when stratifying on offspring smoking status. Among offspring of never smokers, each additional risk allele for maternal smoking heaviness appeared to have a protective effect [odds ratio (OR) = 0.77, 95% confidence interval (CI) 0.62 to 0.95, P = 0.015], whereas among ever smokers the effect of maternal smoking was in the reverse direction (OR = 1.23, 95% CI 1.05 to 1.45, P = 0.011, Pinteraction <0.001). There was no clear evidence of an association between maternal smoking heaviness and offspring depression. These findings do not provide clear evidence of an effect of maternal smoking during pregnancy on offspring schizophrenia or depression, which implies that any causal effect of smoking on schizophrenia or depression is direct.

Bounce of caregivers expressed emotions on schizophrenia

Schizophrenia is a severe type of mental illness that is both persistent and burdensome. Because they are under a lot of stress coping with caring for schizophrenia patients, family members of these patients often have a negative attitude and a wide spectrum of expressed emotion towards them. The quality of interaction patterns and the type of family ties among family caregivers and individuals with schizophrenia and other psychiatric conditions are classified as an unfavorable family environment. [1] Large volumes of emotion directed directly at a person or within a family environment are referred to as “high expressed emotion.”One or more parents’ critical or emotionally over-involved attitudes and behaviors toward their schizophrenia offspring are referred to as expressed emotion. [2]. Any aberrant processes inside a family, such as conflict, communication problems, cold parenting, criticism, control, and excessive amounts of expressed emotions, are referred to as family dysfunction.. These could be risk factors for schizophrenia onset and maintenance. Schizophrenics who returned home to such a family were more prone to relapse than those who returned home to a family that expressed little or no emotion. While not on medication, returning to a high expressed emotion family resulted in a large rate of recurrence. [20] Family members of schizophrenia patients require psychosocial nursing care to assist them cope with their stress. [21]

A sister's search for the seeds of psychosis

Dr. Dolores Malaspina sought a better way to understand the origins of psychosis than a schizophrenogenic mother, as her family had been informed upon her sisters illness. She moved her attention from environmental biology and zoology, to medical science and assembled knowledge on the multilevel components purported to underpin severe mental illness. Her studies cross levels to consider connections among exposures and genetic etiologies, intrinsic homeostatic mechanisms, stimuli perception and clinical illness features. Original contributions include associating later paternal age with increasing risk for schizophrenia in offspring and proposing that de novo mutations with shorter cell cycles explained the association, showing increased resting hippocampal blood flow in psychosis and that it was associated with inflammation, and that autonomic nervous system dysfunction was related to hippocampal inflammation, plausibly reflecting vascular abnormalities. She has been a professor of psychiatry in medical schools at Columbia University, New York University and at Mount Sinai in New York, USA.

Reprint of: Advanced paternal age and risk of schizophrenia in offspring – Review of epidemiological findings and potential mechanisms

A large number of studies have examined the association between advanced paternal age (APA) and risk of schizophrenia in offspring. Here we present an overview of epidemiological studies on this subject published since 2000, and systematically summarize their methodologies and results. Next, we discuss evidence to elucidate the potential mechanisms contributing to the association between APA and offspring schizophrenia, considering paternal psychiatric morbidity and genetic liability, maternal factors, and findings from family design studies. We propose that multiple mechanisms, including causal and non-causal pathways, contribute to the observed relationship between APA and schizophrenia in offspring, and conclude by highlighting the need for multi-disciplinary studies in disentangling these complex, non-mutually exclusive mechanisms.

Paternal age and 13 psychiatric disorders in the offspring: a population-based cohort study of 7 million children in Taiwan.

Although paternal age has been linked to certain psychiatric disorders, the nature of any causal relationship remains elusive. Here, we aimed to comprehensively assess the magnitude of a wide range of offspring's psychiatric risk conferred by paternal age, leveraging a pedigree inferred from covered-insurance relationship (accuracy >98%) in Taiwan's single-payer compulsory insurance program. We also examined whether there is an independent role of paternal age and explored the potential effect of parental age difference. A total cohort of 7,264,788 individuals born between 1980 and 2018 were included; 5,572,232 with sibling(s) were selected for sibling-comparison analyses and 1,368,942 and 1,044,420 children with information of paternal-grandparents and maternal-grandparents, respectively, were selected for multi-generation analyses. Using inpatient/outpatient claims data (1997-2018), we identified schizophrenia, autism, bipolar disorder (BPD), attention deficit-hyperactivity disorder (ADHD), major depressive disorder (MDD), eating disorder (ED), substance use disorder (SUD), mental retardation (MR), tic disorder, obsessive-compulsive disorder (OCD), anxiety, and somatoform disorder. We identified suicides using death certificates. Logistic regression analysis was used to estimate the paternal/maternal/grand-paternal age association with psychiatric risk in the offspring. The total cohort and sibling-comparison cohort resulted in similar estimates. Paternal age had a U-shaped relationship with offspring's MDD, ED, SUD, and anxiety. A very young maternal age (<20 years) was associated with markedly higher risk in offspring's SUD, MR, and suicide. Older paternal age (>25 years) was linearly associated with offspring's schizophrenia, autism, BPD, ADHD, MDD, ED, SUD, MR, OCD, anxiety, and suicide. Older grand-paternal age was linearly associated with offspring's schizophrenia, autism, ADHD, and MR. Dissimilar parental age was positively associated with offspring's ADHD, MDD, SUD, MR, anxiety, and suicide, and negatively associated with offspring's OCD. This comprehensive assessment provides solid evidence for the independent role of paternal age in psychiatric risk in the offspring and clarifies the significance of both early parenthood and delayed paternity.

Prenatal Exposure to SARS-Cov-2 and Schizophrenia Development: What to Expect?

IntroductionSchizophrenia is a complex and multifactorial psychiatric condition characterized by thought, speech, perception and behaviour disorders, and social and occupational impairment. It has been related that viral prenatal infection may contribute to schizophrenia development. As such, there are some hypotheses regarding SARS-Cov-2 prenatal infection and its potential relation with “future” offspring schizophrenia.ObjectivesLiterature review of schizophrenia development and relation with viral infections, and data research of COVID-19 neurotropic effects.MethodsNon-systematic review through literature using databases as Pubmed and UpToDate. Keywords used: schizophrenia, prenatal, viral infection, COVID-19, SARS-Cov-2.ResultsSeveral studies had shown a relationship between prenatal viral infections, such as Influenza, and development of schizophrenia in the offspring. It relates with viral neurotropism mechanisms and inflammatory processes in the fetal neurology system. Regarding SARS-Cov-2, it is early to assume a relation between prenatal COVID-19 and offspring schizophrenia development. However, literature describes psychiatric manifestations post COVID, such as psychotic and manic episodes. As such, a SARS-Cov-2 neurotropic effect is demonstrated.ConclusionsSchizophrenia has a multifactorial etiology. Since prenatal viral infections may interfere and contribute to schizophrenia development, it is logical to assume prenatal SARS-Cov-2 infection may also contribute. It may be relevant to investigate whether these offspring will manifest schizophrenia symptoms.DisclosureNo significant relationships.

Developmental vitamin D-deficiency increases the expression of microRNAs involved in dopamine neuron development

Schizophrenia is a neurodevelopmental disorder associated with abnormal dopamine (DA) signalling and disruptions in early brain development. We have shown that developmental vitamin D-deficiency (DVD-deficiency) increases the risk of schizophrenia in offspring and impairs various aspects of brain development in rodents, particularly that of DA neurons, however the molecular basis of these impairments remains unclear. Here, we explore whether small non-coding microRNAs (miRNAs) are involved. miRNAs regulate gene expression post-transcriptionally via translational repression and destabilisation of mRNA. While dysregulation of multiple miRNAs has been reported in post-mortem brain of patients with schizophrenia, the biological pathways affected by these small RNAs are not clear. Here we identified differential expression of 18 miRNAs in DA neurons isolated from DVD-deficient embryos. Three miRNAs were selected for further functional studies of dopaminergic neuron differentiation based on their interactions with transcripts involved in neuronal maturation. In particular, we show upregulation of miR-181c-5p suppresses neurite outgrowth of dopaminergic neurons. These findings provide further evidence that an environmental risk factor for schizophrenia – DVD-deficiency – disrupts the development of DA neurons and suggests increased miRNA expression may be one possible mechanism. This disruption potentially underlies the long-term alterations in DA mediated brain function in DVD-deficient offspring, and by inference in schizophrenia.

Bioinformatics-based screening of key genes between maternal preeclampsia and offspring schizophrenia

Converging lines of evidence suggest an association between schizophrenia and prenatal neurodevelopmental disorders. Preeclampsia is a multisystem disease based on the coexistence of pregnancy and elevated blood pressure, which increases the risk for offspring abnormal neurodevelopment. Previous studies have showed maternal preeclampsia is associated with an increased risk of offspring schizophrenia, but the molecular mechanism remains unclear. In this study, we sought to identify key protein-coding genes between maternal preeclampsia and offspring schizophrenia. GSE53987 and GSE166846 datasets from Gene Expression Omnibus (GEO) database were analysed to obtain common differentially expressed genes (DEGs) between preeclampsia and schizophrenia. GSE62105 dataset was analysed to identify the DEGs' expressions in neural cells from one control and one schizophrenic patient. GSE92845 dataset was analysed to describe the changes of the DEGs in human neural stem cells. In total, we obtained ten common DEGs. All of them expressed differently in neural cells of the control and schizophrenic patient. We chose the six DEGs that had similar trend in both neural cells and UCB from preeclampsia patients and analysed their expressions in human neural stem cells over time. We found the expressions of CKAP5 and SAT1 in day 30 had significant difference comparing with those in day 0. The KEGG pathway analysis of their interaction proteins showed they were involved with metabolism. Our results may provide a new insight for genetic basis of relationship between maternal preeclampsia and offspring schizophrenia.

Increased genetic risk and epigenetic age deacceleration in bipolar disorder and schizophrenia offspring

Increased genetic risk and epigenetic age deacceleration in bipolar disorder and schizophrenia offspring

Parental consanguinity among patients with schizophrenia in a rural community of South India: A clinical and genetic investigation.

Studies from certain regions of the world indicate that consanguineous marriages are a risk factor for the development of schizophrenia in offspring. However the evidence is inconsistent partly due to methodological limitation of which hospital based recruitment contributing to significant bias. The studies from the Indian subcontinent, is scarce, where rates of consanguinity is high. The schizophrenia patients living in a geographically defined rural south Indian community and randomly selected controls dwelling in the same community sharing sociocultural, economic and lifestyle factors were recruited. They were assessed for parental consanguinity using the clinical interviews as well as DNA-based estimates. The latter was conducted by calculating the coefficient of inbreeding 'f'. A participant was considered to have consanguineous parentage if his/her parents shared a common ancestor no more remote than a great-great-grandparent, corresponding to DNA-based estimates of 'f' ≥ 0.0156. The rates of parental consanguinity assessed by clinical interview were comparable in both groups (Cases: 10.71 %, Controls: 7.25 %; χ2 = 0.493, p = 0.4825). However, DNA-based rates of parental consanguinity showed that 'f' was significantly higher among cases than controls (Mann-Whitney U = 11315.5; p = 0.022). Seventy-five cases (62.5 %) and 108 control participants (48.6 %) had 'f' ≥ 0.0156 (χ2 = 6.008; p = 0.014). The results were consistent across different quality control measures. Schizophrenia is associated with higher parental consanguinity, suggesting a role for multiple recessive risk alleles in its etiology. Replication in future studies in diverse settings would add further strength to this.