Schizophrenia In Offspring Research Articles

Systematic Literature Review and Quantitative Analysis of Health Problems Associated with Sexually Transmitted Neisseria gonorrhoeae Infection.

ObjectiveNeisseria gonorrhoeae (Ng) is the second most common sexually transmitted bacterial infection (STI), leading to serious health problems in men, women and newborns. While early antibiotic treatment is effective, infections are increasingly antibiotic-resistant. No systematic reviews present health problems associated with Ng infections or their likelihood of occurrence. The objective, therefore, was to conduct a systematic literature review to address these gaps.MethodsA systematic literature review was conducted of all studies with an English abstract published since 1950 (Pubmed)/1966 (Embase). The search included patients with a history of/current sexually transmitted Ng infection. Expected outcomes were defined from published reviews of gonorrhoea health problems. Observational studies with a control group were included. A decision tree determined the best quality studies for each outcome, prioritising generalisable populations, laboratory-confirmed diagnosis, clearly defined outcomes, no STI co-infections, adjusted analyses and risk estimates. Where feasible, a meta-analysis was performed; otherwise, the best quality study estimates were identified.FindingsIn total, 46 studies were included, and 22 health problems were identified. Of these problems, Ng infection was statistically significantly associated with preterm premature ruptures of membranes, preterm birth, low birth weight, stillbirth, infant death, neonatal ophthalmia, schizophrenia in offspring, pelvic inflammatory disease and subsequent tubal infertility, human immunodeficiency virus and prostate cancer/problems. High-quality evidence was generally lacking, with high heterogeneity across studies, and limited or inconclusive data on other health problems.ConclusionNg infection is associated with severe health problems in women, men and newborns. More high-quality comparative studies are needed to address the limitations in current knowledge.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00481-z.

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.

Prenatal infection and schizophrenia: A decade of further progress

Epidemiologic studies have provided evidence that prenatal exposure to maternal infection is associated with an increased risk of developing schizophrenia in the offspring. Research over the past decade has added further to our understanding of the role of prenatal infection in schizophrenia risk. These investigations include several well-powered designs, and like some earlier studies, measured maternal antibodies to specific infectious agents in stored serum samples and large registers to identify clinically diagnosed infections during pregnancy. Convergent findings from antibody studies suggest that prenatal maternal infection with Toxoplasma gondii is associated with increased schizophrenia risk in the offspring, while associations with HSV-2 infection are likely attributable to confounding. Maternal influenza infection remains a viable candidate for schizophrenia, based on an early serological study, though there has been only one attempt to replicate this finding, with a differing methodology. A prior association between maternal serologically confirmed cytomegalovirus infections require further study. Clinically diagnosed maternal infection, particularly bacterial infection, also appears to be associated with increased risk of offspring schizophrenia, and heterogeneity in these findings is likely due to methodological differences between studies. Further clarification may be provided by future studies that address the timing, type, and clinical features of infections. Important insight may be gained by examining the long-term offspring outcomes in emerging epidemics such as Zika virus and COVID-19, and by investigating the interaction between exposure to prenatal infection and other risk or protective factors.

Maternal allergic inflammation in rats impacts the offspring perinatal neuroimmune milieu and the development of social play, locomotor behavior, and cognitive flexibility

Maternal systemic inflammation increases risk for neurodevelopmental disorders like autism, ADHD, and schizophrenia in offspring. Notably, these disorders are male-biased. Studies have implicated immune system dysfunction in the etiology of these disorders, and rodent models of maternal immune activation provide useful tools to examine mechanisms of sex-dependent effects on brain development, immunity, and behavior. Here, we employed an allergen-induced model of maternal inflammation in rats to characterize levels of mast cells and microglia in the perinatal period in male and female offspring, as well as social, emotional, and cognitive behaviors throughout the lifespan. Adult female rats were sensitized to ovalbumin (OVA), bred, and challenged intranasally on gestational day 15 of pregnancy with OVA or saline. Allergic inflammation upregulated microglia in the fetal brain, increased mast cell number in the hippocampus on the day of birth, and conferred region-, time- and sex- specific changes in microglia measures. Additionally, offspring of OVA-exposed mothers subsequently exhibited abnormal social behavior, hyperlocomotion, and reduced cognitive flexibility. These data demonstrate the long-term effects of maternal allergic challenge on offspring development and provide a basis for understanding neurodevelopmental disorders linked to maternal systemic inflammation in humans.

P.829Clinical characteristics of schizophrenia offspring, children diagnosed with attention deficit hiperactivity disorder and healthy controls

The relevance of human papillomavirus (HPV)-related features in cutaneous, non-anogenital SCC is not known and not incorporated into current diagnostic categories and treatment algorithms. Here, we describe the case of a 78-year-old male with bilateral inguinal warty-basaloid carcinoma, which is an HPV-related SCC that, in men, has been described only in a penile location. The patient underwent surgical excision without lymphadenectomy and declined radiation therapy due to concerns of poor wound healing. Adjuvant chemotherapy was not offered given the patient's Stage IV chronic kidney disease and undefined degree of benefit in the absence of concurrent radiotherapy. We therefore opted for close follow up and surveillance with PET/CT imaging and full body skin exams. The patient also received HPV vaccination. No clinical evidence of recurrence or metastasis was apparent at 6 months following initial excision. The identification of HPV-associated cutaneous SCC and correlation with patient outcomes is necessary to evaluate the prognostic significance of these features and to clarify the role of different treatment strategies in this setting.

Association between paternal age and risk of schizophrenia: a nationwide population-based study.

To study the association between paternal age and schizophrenia in offspring. This report describes a nationwide population-based cohort study from 1997 to 2013. Data from Taiwan's National Health Insurance Research Database were utilized to answer the research question. A total of 17,649 offspring with schizophrenia were selected from 11 million offspring in the general population. Additionally, we established the offspring without schizophrenia as the comparison group by matching the study cohort by age, gender in a 1:4 ratio (n = 70,596). The median age at first presentation with schizophrenia was 20years (interquartile range (IQR), 17 to 24). Comparison of the schizophrenia and non-schizophrenia groups indicated that father's age at birth (30.0 (IQR), 27 to 33 vs. 29.0 (IQR), 26 to 32years), mother's age at birth (26.0 (IQR), 24 to 29 vs. 26.0 (IQR), 23 to 29years), paternal schizophrenia (2.6% vs. 0.6%), and maternal schizophrenia (4.4% vs. 0.7%) were all significantly greater in the schizophrenia group. In addition, each 5-year increase in father's age increased the odds of being diagnosed with schizophrenia (model 1: aOR = 1.22; 95% CI 1.20, 1.24; model 2: aOR = 1.20; 95% CI 1.18, 1.23). Subgroup analysis showed that each 5-year increase in father's age increased the odds of being diagnosed with schizophrenia in male and female offspring, as well as in offspring of mothers and fathers with or without schizophrenia (aOR = 1.20 to 2.20, all p values < 0.01). This study indicated that advanced paternal age increased the risk of schizophrenia in offspring. Offspring born to fathers older by 5-year increments were at heightened risk of schizophrenia.

T33. NEUROIMMUNE MECHANISMS OF PSYCHIATRIC DISORDERS: LONGITUDINAL EVALUATION OF DIFFUSION MEASURES OF EXTRACELLULAR FREE WATER IN A NON-HUMAN PRIMATE MODEL OF MATERNAL IMMUNE ACTIVATION

BackgroundA key finding in developmental neurobiology is a widespread role for immune molecules in normal brain development and synaptic function and evidence has been accumulating for an immune-based developmental pathophysiology in psychiatric disorders, particularly in schizophrenia. Epidemiological studies have revealed an increased incidence of schizophrenia in offspring of mothers who had an infection during pregnancy while GWAS studies have identified genetic links to the major histocompatibility complex and peripheral changes in immune markers are widely reported in the illness. The murine maternal immune activation model system is widely used to investigate the effects of immune activation during pregnancy on brain development in behavior in offspring. Here we report findings from an ongoing study of a unique cohort on non-human primates (NHP) who underwent MIA (compared to controls) on a promising biomarker of neuroimmune perturbation in vivo--extracellular free water--a diffusion magnetic resonance imaging measure obtained with a multi-shell acquisition, which we have shown in multiple studies to be increased in young people with early psychosis.MethodsFourteen pregnant rhesus monkeys (Macaca mulatta) received polyICLC and 14 control animals have been scanned prospectively from both to their current age of 3.5 years. The offspring from both groups underwent a diffusion MRI scan on a 3 Tesla Siemens Skyra scanner in which multiple b-value shells were acquired to improve estimation of extracellular free water. Data were collected when the offspring were 1, 6, 12, 24 and 36 months to date. Diffusion images were nonlinearly aligned to individual subject MPRAGE scans, which were segmented and parcellated into regions of interest using multi-atlas techniques. For this preliminary analysis, frontal, cingulate, and temporo-limbic regions were selected as a priori ROIs in addition to whole-brain gray and white matter masks. Group differences were assessed using repeated measures ANOVA and independent samples t-tests.ResultsResults from birth to age 2 years showed a significant main effect of group in both white (p<.05) and gray (p<.001) cingulate cortex free water, with MIA-exposed offspring showing higher free water. Similar trends were also identified in prefrontal white matter free water (p=.07) and whole-brain white (p=.11) and gray matter free water (p=.07). No significant group by time interactions were identified. Data analysis is currently underway including the 3-year time point.DiscussionDespite the lack of gross behavioral abnormalities at age 2, extracellular free water values are increased in MIA-exposed offspring, particularly in the cingulate cortex. More global whole-brain free water group differences, however, did not reach statistical significance, which may indicate some regional specificity to these changes early in development. These NHP MIA model complement the human schizophrenia literature in which extracellular free water increases have been repeatedly identified. And show that changes in the brain occur early in life, well before the emergence of atypical behaviors in the NHP model.

M115. COGNITIVE FUNCTION IN BIPOLAR AND SCHIZOPHRENIA OFFSPRING: FINDINGS ACROSS THE NEURODEVELOPMENTAL CONTINUUM

BackgroundNeurocognitive impairment is considered to lie on a continuum of severity across schizophrenia (SZ) and bipolar disorder (BP), possibly reflecting a continuum of neurodevelopmental load. Due to the known heterogeneity, performance patterns across both disorders have been examined using clustering approaches, which previously identified subgroups with different levels of impairment, from none to widespread and severe. We, for the first time, used this approach to examine cognitive function in children and youth at familial risk of developing SZ and BP, in order to investigate cognitive profiles earlier on in the neurodevelopmental pathway.Methods220 participants, 49 offspring of individuals with schizophrenia (SZO), 90 offspring of individuals with bipolar disorder (BPO) and 81 healthy controls (HC), underwent a comprehensive cognitive assessment. Measures of attention, verbal memory, visual memory, executive function, working memory, and processing speed were used to group high-risk offspring. The k-means clustering with elbow method was used to determine the optimal number of clusters. High-risk offspring were then each assigned to a specific cluster. Cognitive performance within each of the clusters was compared to that of HC in order to describe the distribution of impairments across different cognitive domains and their severity. Between–cluster comparisons were then performed in terms of clinical and functioning variables.ResultsThree cognitive subgroups were identified for high-risk offspring: a global impairment group (19.5%) with severe impairments across most cognitive domains, a selective impairment group (46%) with moderate deficits across specific domains, and a cognitively intact group (34.5%) with performance comparable to that of healthy controls. Both SZO and BPO were represented in each of the three clusters. However a larger proportion of the SZO (30.6%) than of the BPO (13.3%) were characterised by widespread cognitive dysfunction, whereas BPO (41.1%) were more frequently cognitively spared relative to SZO (22.4%). Individuals in the global cognitive impairment group displayed significantly poorer clinical and functioning measures relative to the other two clusters.DiscussionThree cognitive subgroups were identified in BP and SZ offspring, a global impairment group, a selective impairment group and a cognitively intact group. The clustering pattern identified overlaps with that previously observed after illness onset.Findings are in line with the known heterogeneity in cognitive impairment across SZ and BP and can contribute to elucidate the timeframe of its emergence.Using cognitive function as a proxy measure of neurodevelopmental load, the findings point to a gradient in individuals at genetic risk of SZ and BP. They have therefore important implications for the understanding of potentially different neurodevelopmental trajectories within SZ and BP, hence for patient stratification in research and clinical practice.

S20. LIFETIME PSYCHOPATHOLOGY IN CHILD AND ADOLESCENT OFFSPRING OF PARENTS DIAGNOSED WITH SCHIZOPHRENIA OR BIPOLAR DISORDER

BackgroundHaving one parent diagnosed with a severe mental disorder is considered one of the main risk factors for developing that disorder in adulthood and it also increases the risk of a wide range of mental disorders in the offspring from early childhood and adolescence. The aim of this study is to analyze the prevalence of several psychopathological diagnoses, the presence of prodromal symptoms and global functioning in schizophrenia offspring (SZoff) or bipolar offspring (BDoff) compared to community control offspring (CCoff) at baseline and 2-year follow-up.Methods41 SZoff, 97 BDoff and 107 CCoff between 7 and 17 years were included. Clinical assessment consisted of a clinical evaluation using the following instruments: structured interview KSADS-PL or SCID-I, semi-structured Interview for Prodromal Syndromes (SIPS) and the Children’s Global Assessment Scale (CGAS). To test between-group differences in DSM-IV diagnoses multilevel mixed-effect logistic regression models (categorical variables) or linear (continuous variables) regression models were conducted with group (SZoff, BDoff and CCoff), time (baseline or 2-year follow-up), interaction time x group, age, gender and socio-economic status as fixed variables.ResultsSignificant differences between groups were found in any lifetime axis I disorder (F=8.720; p<0.001), mood disorders (F=4.774; p=0.009), anxiety disorders (F=4.368; p=0.013), ADHD (F=21.593; p<0.001), disruptive behavioral disorders (F=10.788; p<0.001) and comorbidity (F=5.588; P=0.004). Significant differences between groups were also found in the positive (F=6.088; p=0.003), negative (F=4.423; p=0.015), disorganized (F=3.866; p=0.024) and total (F=6.394; p= 0.002) sub-scales of the SOPS and CGAS (F=11.613;p<0.001). Interestingly, mood disorders were more prevalent in BDoff and disruptive disorders were more prevalent in SZoff. Prodromal symptoms were higher in SZoff compared to CCoff, while the BPoff group showed an intermediate pattern. Finally, global functioning was lower in the SZoff group compared to BDoff and CCoff.DiscussionScreening patients’ children is clinically relevant since, as a group, they have an elevated risk of developing a psychiatric disorder and of experiencing their first symptoms during childhood and adolescence.

Prenatal zinc supplementation attenuates lipopolysaccharide-induced behavioral impairments in maternal immune activation model

Maternal infection during pregnancy is considered a key risk factor for developing schizophrenia in offspring. There is evidence that maternal exposure to infectious agents is associated with fetal zinc deficiency. Due to the essential role of zinc in brain function and development, in the present study, we activated maternal immune system using lipopolysaccharide (LPS) as a model of schizophrenia to examine whether zinc supplementation throughout pregnancy can reverse LPS-induced deleterious effects.To test the hypothesis, pregnant rats were treated with intraperitoneal injection of either saline or LPS (0.5 mg/kg) at gestational day 15 and 16, and zinc supplementation (30 mg/kg) was administered throughout pregnancy by gavage. At postnatal day 60, Y-maze was used to evaluate working memory of offspring. Moreover, the expression levels of catechol O-methyltransferase (COMT) and glutamate decarboxylase 67 (GAD67) were measured in the frontal cortex of the brain samples.Only male offspring prenatally exposed to LPS showed a significant impairment in working memory. In addition, prenatal LPS exposure causes a moderate decrease in GAD67 expression level in the male pups, while COMT expression was found unchanged. Interestingly, zinc supplementation restored the alterations in working memory as well as GAD67 mRNA level in the male rats. No alteration was detected for neither working memory nor COMT/GAD67 genes expression in female offspring.This study demonstrates that zinc supplementation during pregnancy can attenuate LPS-induced impairments in male pups. These results support the idea to consume zinc supplementation during pregnancy to limit neurodevelopmental deficits induced by infections in offspring.

Maternal cortisol during pregnancy and offspring schizophrenia: Influence of fetal sex and timing of exposure

IntroductionMaternal stress during pregnancy has been repeatedly linked to increased risk for schizophrenia; however, no study has examined maternal cortisol during pregnancy and risk for the disorder. Study aims were to determine whether prenatal cortisol was associated with risk for schizophrenia and risk for an intermediate phenotype—decreased fetal growth—previously linked to prenatal cortisol and schizophrenia. Timing of exposure and fetal sex also were examined given previous findings. MethodsParticipants were 64 cases diagnosed with schizophrenia spectrum disorders (SSD) and 117 controls from a prospective birth cohort study. Maternal cortisol was determined from stored sera from each trimester and psychiatric diagnoses were assessed from offspring using semi-structured interviews and medical records review. ResultsMaternal cortisol during pregnancy was not associated with risk for offspring schizophrenia. There was a significant interaction between 3rd trimester cortisol and case status on fetal growth. Specifically, cases exposed to higher 3rd trimester maternal cortisol had significantly decreased fetal growth compared to controls. In addition, these findings were restricted to male offspring. ConclusionsOur results indicate that higher prenatal cortisol is associated with an intermediate phenotype linked to schizophrenia, fetal growth, but only among male offspring who developed schizophrenia. Findings were consistent with evidence that schizophrenia genes may disrupt placental functioning specifically for male fetuses, as well as findings that males are more vulnerable to maternal cortisol during pregnancy. Finally, results suggest that examining fetal sex and intermediate phenotypes may be important in understanding the mechanisms involved in prenatal contributors to schizophrenia.

Public interest through web search trends of neuromodulation treatments in the United States

Maternal antenatal depression may alter offspring neurodevelopment, but long follow-up studies are lacking. We studied the risks for mood disorders and schizophrenia in adult offspring of antenatally depressed mothers, taking account parental severe mental disorders.In the general population-based Northern Finland 1966 Birth Cohort with 12,058 children, 13.9% of the mothers reported themselves depressed at mid-gestation. The offspring were followed 43 years. Severe mood disorders and schizophrenia in the offspring and severe mental disorders in the parents were detected using the Care Register for Healthcare. Maternal smoking during pregnancy, perinatal complications, fathers´ social class, family type at birth, and grand multiparity were considered as confounding variables.The offspring of antenatally depressed mothers had an elevated risk for depression (adjusted OR 1.5; 95% CI 1.03–2.2), compared to cohort members without maternal antenatal depressed mood. The offspring with maternal antenatal depressed mood and parental severe mental disorder had markedly elevated risks for depression (3.3; 1.8–6.2), and schizophrenia (3.9; 2.0–7.5), compared to the offspring without one or both of these risk factors.Maternal antenatal depressed mood was determined by one question and did not necessarily signify a clinical condition. Data on maternal postnatal mood was not available.The offspring with maternal antenatal depressed mood and parental severe mental disorder had high risk for depression and schizophrenia. Early interventions in parental severe mental disorder might present an opportunity for decreasing the risk for mood disorders and schizophrenia in the offspring.

Transgenerational Interaction of Alzheimer's Disease with Schizophrenia through Amyloid Evolvability.

Alzheimer’s disease (AD), the most common neurodegenerative dementia, leads to memory dysfunction due to widespread neuronal loss associated with aggregation of amyloidogenic proteins (APs), while schizophrenia (SCZ) represents a major psychiatric disorder characterized by delusions, hallucinations, and other cognitive abnormalities, the underlying mechanisms of which remain obscure. Although AD and SCZ partially overlap in terms of psychiatric symptoms and some aspects of cognitive impairment, the causal relationship between AD and SCZ is unclear. Based on the similarity of APs with yeast prion in terms of stress-induced protein aggregation, we recently proposed that evolvability of APs might be an epigenetic phenomenon to transmit stress information of parental brain to cope with the stressors in offspring. Although amyloid evolvability may be beneficial in evolution, AD might be manifested during parental aging as the mechanism of antagonistic pleiotropy phenomenon. Provided that accumulating evidence implicates stress as an important factor in SCZ, the main objective of this paper is to better understand the possible connection of AD and SCZ through amyloid evolvability. Hypothetically, the delivery of information of stress by APs may be less efficient under the decreased evolvability conditions such as disease-modifying treatment, leading to SCZ in offspring. Conversely, the increased evolvability conditions including gene mutations of APs are supposed to be beneficial for offspring, but might lead to AD in parents. Collectively, AD and SCZ might transgenerationally interfere with each other through amyloid evolvability, and this could explain why both AD and SCZ have not been selected out through evolution.

Advanced Paternal Age and Early Onset of Schizophrenia in Sporadic Cases: Not Confounded by Parental Polygenic Risk for Schizophrenia

BackgroundWhether paternal age effect on schizophrenia is a causation or just an association due to confounding by selection into late parenthood is still debated. We investigated the association between paternal age and early onset of schizophrenia in offspring, controlling for both paternal and maternal predisposition to schizophrenia as empirically estimated using polygenic risk score (PRS) derived from the Psychiatric Genomics Consortium. MethodsAmong 2923 sporadic schizophrenia cases selected from the Schizophrenia Trio Genomic Research in Taiwan project, 1649 had parents’ genotyping data. The relationships of paternal schizophrenia PRS to paternal age at first birth (AFB) and of maternal schizophrenia PRS to maternal AFB were examined. A logistic regression model of patients’ early onset of schizophrenia (≤18 years old) on paternal age was conducted. ResultsAdvanced paternal age over 20 years exhibited a trend of an increasing proportion of early onset of schizophrenia (odds ratio per 10-year increase in paternal age = 1.28, p = .007) after adjusting for maternal age, sex, and age. Older paternal AFB also exhibited an increasing trend of paternal schizophrenia PRS. Additionally, a U-shaped relationship between maternal AFB and maternal schizophrenia PRS was observed. After adjusting for both paternal and maternal schizophrenia PRS, the association of paternal age with patients’ early onset of schizophrenia remained (odds ratio = 1.29, p = .04). ConclusionsThe association between paternal age and early onset of schizophrenia was not confounded by parental PRS for schizophrenia, which partially captures parental genetic vulnerability to schizophrenia. Our findings support an independent role of paternal age per se in increased risk of early onset of schizophrenia in offspring.

Severe mood disorders and schizophrenia in the adult offspring of antenatally depressed mothers in the Northern Finland 1966 Birth Cohort: Relationship to parental severe mental disorder

BackgroundMaternal antenatal depression may alter offspring neurodevelopment, but long follow-up studies are lacking. We studied the risks for mood disorders and schizophrenia in adult offspring of antenatally depressed mothers, taking account parental severe mental disorders. MethodsIn the general population-based Northern Finland 1966 Birth Cohort with 12,058 children, 13.9% of the mothers reported themselves depressed at mid-gestation. The offspring were followed 43 years. Severe mood disorders and schizophrenia in the offspring and severe mental disorders in the parents were detected using the Care Register for Healthcare. Maternal smoking during pregnancy, perinatal complications, fathers´ social class, family type at birth, and grand multiparity were considered as confounding variables. ResultsThe offspring of antenatally depressed mothers had an elevated risk for depression (adjusted OR 1.5; 95% CI 1.03–2.2), compared to cohort members without maternal antenatal depressed mood. The offspring with maternal antenatal depressed mood and parental severe mental disorder had markedly elevated risks for depression (3.3; 1.8–6.2), and schizophrenia (3.9; 2.0–7.5), compared to the offspring without one or both of these risk factors. LimitationsMaternal antenatal depressed mood was determined by one question and did not necessarily signify a clinical condition. Data on maternal postnatal mood was not available. ConclusionThe offspring with maternal antenatal depressed mood and parental severe mental disorder had high risk for depression and schizophrenia. Early interventions in parental severe mental disorder might present an opportunity for decreasing the risk for mood disorders and schizophrenia in the offspring.

Relationship of Advanced Paternal Age and Onset of Schizophrenia

Background: Increased paternal age has been associated with an increased risk of spontaneous abortion, premature birth, infant mortality, congenital malformations, childhood cancer, epilepsy, autism, bipolar and schizophrenia in offspring. The biological mechanisms behind this relationship are not known but may be associated with de novo mutations and epigenetic changes in male cells with short and long term health consequences for their offspring. Males are responsible for most of the new mutations in the gene group, to the permanent distribution of reproductive cells and the number of mutations increases significantly with age.&#x0D; Objective: The aim of the study to determine the correlation between paternal age and onset of schizophrenia. Method: This study was correlation analysis with cross sectional approach with The subject is 92 schizophrenia patient. Analysis of the data using statistical test that is chi-square.&#x0D; Result: the study findings showed there was significant correlation between paternal age with schizophrenic aged onset of 0.001 (p &lt;0.05).

Prenatal exposure and fetal programming of schizophrenia

Schizophrenia (SCZ) is a neurodevelopmental disorder, which results to cognitive dysfunction and memory decline. Maternal undernutrition during fetal development alters epigenomic programming, and this might result to SCZ in offspring later in life because of the disruption of fetal brain development and synaptogenesis. Maternal stress, exposure to teratogens and neurotoxic agent, hypoxia, and viral infection alters fetal neurodevelopmental mechanisms because of an increase in inflammatory proteins. Interleukin 8 and tumor necrosis factor released due to stress and infection increase the risk of offspring developing SCZ later in life. Having infections linked to Toxoplasma gondii, Chlamydia, and some pathogens seropositivity during pregnancy or the period preceding childbirth are high-risk factors for offspring to develop SCZ later in life. This review was conducted by extracting papers using key terms indicating Schizophrenia, fetal programming of neurodevelopmental disorders, maternal undernutrition, maternal immune activation, and genome-wide studies through PubMed, Science Direct, PsychINFO, Medline, Web of Science, and Google Scholar. Maternal Stress was found to induce hypermethylation resulting to poor expression of reelin, which causes a reduction in GABAergic neurons in animal models. In vivo animal experimentation indicated that poor maternal care, unfavorable environmental factors, and conditions produce aberrant deoxyribonucleic acid methylation patterns at various gene loci in the medial prefrontal cortex of the brain, thus altering and modifying the network of genes involved in mental activities. However, the epigenomic mechanisms behind the fetal programming of SCZ have not been fully understood; more facts could be unraveled in the future.

Maternal diabetes in early pregnancy, and psychotic experiences and depressive symptoms in 10-year-old offspring: A population-based birth cohort study

Epidemiological studies have suggested that maternal diabetes in pregnancy increases the risk of schizophrenia in offspring. A recent cohort study observed that maternal diabetes in early pregnancy is also associated with psychotic experiences in the general adolescent population. However, it remains unclear whether maternal diabetes in early pregnancy is specifically associated with psychotic experiences, or is generally associated with broader mental health problems, including depressive symptoms in adolescence. The present study investigated the longitudinal associations between maternal diabetes in early pregnancy, and psychotic experiences and depressive symptoms in 10-year-old offspring. Our data were derived from the Tokyo Early Adolescence Survey, a population-based survey of early adolescents (N = 4478) and their primary caregivers. Diabetes in early pregnancy was determined by records in the mother's Maternal and Child Health Handbook, documented during the pregnancy. Psychotic experiences and depressive symptoms were established through self-report by the offspring at 10 years of age. Diabetes in early pregnancy was associated with an increased risk of hallucination in the offspring (auditory hallucination [odds ratio {OR} 4.33, 95% confidence interval {CI} 1.12–16.75]; visual hallucination [OR 6.58, 95% CI 1.69–25.66]), even after adjusting for depressive symptoms and other covariates. However, the association between maternal diabetes and delusional thoughts was not significant and diabetes in early pregnancy was not associated with adolescent depressive symptoms. Our investigation suggests that maternal diabetes in early pregnancy may specifically affect the risk of hallucinatory experiences in adolescent offspring.

Association of maternal exposure to terror attacks during pregnancy and the risk of schizophrenia in the offspring: A population-based study

This study tested the hypothesis that maternal exposure to terror attacks during pregnancy is associated with the risk of schizophrenia in the offspring. A population-based study was conducted of Israeli children born between 1975 and 1995 and that were registered in the Ministry of Interior and followed up in the Ministry of Health from birth to 2015 for the risk of schizophrenia (N = 201,048). The association between maternal exposure to terror attacks during pregnancy and the risk of schizophrenia in the offspring was quantified with relative risks (RR) and their 95% confidence intervals (CI) fitting Cox regression models unadjusted and adjusted for confounders. Sensitivity analyses were performed to test the robustness of the results. The RR of schizophrenia in offspring of mothers exposed to terror attacks during pregnancy compared to offspring of mothers not exposed during pregnancy were estimated unadjusted (RR = 2.51, 95% CI, 1.33, 4.74) and adjusted (RR = 2.53, 95% CI, 1.63, 3.91). In the sensitivity analyses adjusted RRs were estimated using a sibling-based study design (2.85, 95% CI: 1.31–6.21) and propensity matching (2.45, 95% CI: 1.58–3.81). Maternal exposure to terror attacks during pregnancy was associated with an increased risk of schizophrenia in the offspring, possibly indicating a critical period of neurodevelopment that is sensitive to the stress of terror attacks and affected by epigenetic modifications.

S197. OBSTETRIC COMPLICATIONS, NEUROCOGNITION, AND SCHIZOPHRENIA

BackgroundSchizophrenia is a disorder with a heterogeneous genetic and neurobiological background that influences early brain development. The symptoms is the behavioural outcome of deviations in early neurodevelopment, including prenatal insults such as obstetric complications (OC). OC have been linked to an increased risk for schizophrenia in offspring, especially in early-onset schizophrenia (EOS). Extensive cognitive deficits occur in EOS, whereof executive function is one of the best documented. Cognitive dysfunction reflects underlying abnormalities in the brain neurodevelopment, and is considered to be an intermediate variable between OC and schizophrenia. Our research group (Teigset et al, 2016) is the only study that has investigated the relationship between OC and cognition in EOS. This study aimed to examine the frequency of OC in EOS compared to controls, and also investigate the relationship between OC and neurocognitive dysfunction. In the present presentation we will focus upon executive function and report the findings when comparing the same sample of patients and controls as in the Teigset et al study.MethodsNineteen EOS patients and 53 healthy controls were tested with the MATRICS Consensus Cognitive Battery(MCCB), and two tests for assessment of executive functioning. The selected subtests for measuring executive function were the D-KEFS Color Word Interference Test (Stroop) and the Wisconsin Card Sorting Test. WCST assesses perseverative responses and failure to maintain set, and the Stroop assesses time in seconds for completing the Inhibition and Switching conditions. The cognitive measures were combined with data from the Norwegian Birth Registry (NMBR). Information on OC was collected from the NMBR containing information about all births in Norway, including information about maternal health before and during pregnancy, and any complications arising during pregnancy or birth. The registry includes information about medication during pregnancy, labor interventions, birth complications, maternal complications after birth, whether this was a live birth, any diagnoses in the child or evidence of congenital abnormalities.ResultsGroup differences in OC were studied with Student’s t-tests and Chi-square tests. The association between OC and cognitive function were studied using linear regression analyses. The results indicated no group differences in OC in EOS and healthy controls. However, a shorter gestational length in the EOS group led to significant decreases in the overall neurocognitive composite score (MCCB), in processing speed and in the two executive function tasks.DiscussionOur findings indicate that a shorter gestational length did not increase the risk for developing EOS, but was significantly associated with the cognitive difficulties in this group. In particular, executive functioning were affected, a finding in line with those of Brown et al (2009), showing that prenatal infections were associated with impaired executive function. Interestingly, reductions in neurocognitive performance among those exposed to OC was less extensive in the healthy control group with the same labor-conditions, which may indicate a greater effect of OC on neuropsychological development in schizophrenia. In conclusion, gestational length does not increase the risk for developing EOS, but significantly affects the cognitive difficulties - particularly executive function - seen among cases.