Sex effects on DNA methylation affect discovery in epigenome-wide association study of schizophrenia.

Sex differences in the epidemiology and clinical characteristics of schizophrenia are well-known; however, the molecular mechanisms underlying these differences remain unclear. Further, the potential advantages of sex-stratified meta-analyses of epigenome-wide association studies (EWAS) of schizophrenia have not been investigated. Here, we performed sex-stratified EWAS meta-analyses to investigate whether sex stratification improves discovery, and to identify differentially methylated regions (DMRs) in schizophrenia.

Differences in white blood cell proportions between schizophrenia cases and controls are influenced by medication and variations in time of day.

Cases with schizophrenia (SCZ) and healthy controls show differences in white blood cell (WBC) counts and blood inflammation markers. Here, we investigate whether time of blood draw and treatment with psychiatric medications are related to differences in estimated WBC proportions between SCZ cases and controls. DNA methylation data from whole blood was used to estimate proportions of six subtypes of WBCs in SCZ patients (n = 333) and healthy controls (n = 396).

Aging biological markers in a cohort of antipsychotic-naïve first-episode psychosis patients.

Schizophrenia is a severe and multifactorial disorder with an unknown causative pathophysiology. Abnormalities in neurodevelopmental and aging processes have been reported. Relative telomere length (RTL) and DNA methylation age (DMA), well-known biomarkers for estimating biological age, are both commonly altered in patients with schizophrenia compared to healthy controls.

LINE-1 hypomethylation is associated with poor risperidone response in a first episode of psychosis cohort.

We investigated the DNA methylation profile over LINE-1 in antipsychotic-naive, first-episode psychosis-patients (n = 69) before and after 2 months of risperidone treatment and in healthy controls (n = 62). Patients were evaluated using standardized scales and classified as responders and nonresponders. DNA from blood was bisulfite converted and LINE-1 fragments were amplified and pyrosequencing was performed.

Gene expression changes associated with trajectories of psychopathology in a longitudinal cohort of children and adolescents.

We aimed to identify blood gene expression patterns associated to psychopathological trajectories retrieved from a large community, focusing on the emergence and remission of general psychiatric symptoms. Hundred and three individuals from the Brazilian High-Risk Cohort Study (BHRCS) for mental disorders were classified in four groups according to Child Behavior Checklist (CBCL) total score at the baseline (w0) and after 3 years (w1): low-high (L-H) (N = 27), high-low (H-L) (N = 12), high-high (H-H) (N = 34) and low-low (L-L) groups (N = 30). Blood gene expression profile was measured using Illumina HT-12 Beadchips, and paired analyses comparing w0 and w1 were performed for each group.

Are serum brain-derived neurotrophic factor concentrations related to brain structure and psychopathology in late childhood and early adolescence?

Objective: Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents.

Association between spontaneous activity of the default mode network hubs and leukocyte telomere length in late childhood and early adolescence.

The impact of early life stress on mental health and telomere length shortening have been reported. Changes in brain default mode network (DMN) were found to be related to a myriad of psychiatric conditions in which stress may play a role. In this context, family environment and adverse childhood experiences (ACEs) are potential causes of stress.

Detecting multiple differentially methylated CpG sites and regions related to dimensional psychopathology in youths.

Background: Psychiatric symptomatology during late childhood and early adolescence tends to persist later in life. In the present longitudinal study, we aimed to identify changes in genome-wide DNA methylation patterns that were associated with the emergence of psychopathology in youths from the Brazilian High-Risk Cohort (HRC) for psychiatric disorders. Moreover, for the differentially methylated genes, we verified whether differences in DNA methylation corresponded to differences in mRNA transcript levels by analyzing the gene expression levels in the blood and by correlating the variation of DNA methylation values with the variation of mRNA levels of the same individuals.

Gene expression over the course of schizophrenia: from clinical high-risk for psychosis to chronic stages.

The study of patients with schizophrenia (SZ) at different clinical stages may help clarify what effects could be due to the disease itself, to the pharmacological treatment, or to the disease progression. We compared expression levels of targeted genes in blood from individuals in different stages of SZ: clinical high risk for psychosis (CHR), first episode of psychosis (FEP), and chronic SZ (CSZ). Then, we further verified whether single-nucleotide polymorphisms (SNPs) could be related to gene expression differences.

Effects of the interaction between genetic factors and maltreatment on child and adolescent psychiatric disorders.

We evaluated the effects of the interaction between child maltreatment (CM) and single nucleotide polymorphisms (SNPs) on development of mental disorders (MD) and psychopathology. We genotyped 720 individuals from a Brazilian community school-based prospective study, focusing on SNPs in 21 genes known to be associated with mental disorders. CM was assessed via a multi-informant-measure, which was previously validated.

Effect of male-specific childhood trauma on telomere length.

Child maltreatment (CM) is a global issue with serious lifelong consequences. In fact, maltreatment during childhood might be an important risk factor for the development of psychiatric disorders. Furthermore, previous studies showed a strong relationship between telomere length (TL) and early life stress.

Polygenic risk score analyses of symptoms and treatment response in an antipsychotic-naive first episode of psychosis cohort.

In this study, we aimed to test if the schizophrenia (SCZ) polygenic risk score (PRS) was associated with clinical symptoms in (a) the first episode of psychosis pre-treatment (FEP), (b) at nine weeks after initiation of risperidone treatment (FEP-9W) and (c) with the response to risperidone. We performed a detailed clinical assessment of 60 FEP patients who were antipsychotic-naive and, again, after nine weeks of standardized treatment with risperidone. After blood collection and DNA isolation, the samples were genotyped using the Illumina PsychArrayChip and then imputed.

Accessing Gene Expression in Treatment-Resistant Schizophrenia.

Schizophrenia (SCZ) is a mental disorder arising from a complex interaction of genetic and environmental factors. It has been suggested that treatment-resistant schizophrenia (TRS) is a distinct, more severe, and homogenous subgroup of schizophrenia that could present specific biological markers. Our aim was to characterize expression of target genes in blood of TRS patients compared with non-TRS (NTRS) patients and healthy controls (HC).

Effects of the brain-derived neurotropic factor variant Val66Met on cortical structure in late childhood and early adolescence.

Background: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been associated with several neuropsychiatric disorders and regional structural brain changes in adults, but little is known about Val66Met's effect on brain morphology during typical or atypical neurodevelopment. Windows of vulnerability to psychopathology may be associated with the different alleles of the Val66Met polymorphism during childhood and adolescence.

Methodology: We investigated the effect of Val66Met on cortical thickness in MRI scans of 718 children and adolescents (6-12 years old) with typical development, and in those meeting DSM criteria for a psychiatric disorder.

Leukocyte telomere length variation in different stages of schizophrenia.

Recent research has demonstrated that telomere maintenance might be a key integrating point for the cumulative effect of genetic and environmental factors in patients with first-episode psychosis (FEP) and schizophrenia (SCZ). Eighty-one participants with antipsychotic-naïve FEP, 173 with SCZ and 438 HC were enrolled in this study. Psychiatric diagnosis was assessed using the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I).

Gene expression in blood of children and adolescents: Mediation between childhood maltreatment and major depressive disorder.

Investigating major depressive disorder (MDD) in childhood and adolescence can help reveal the relative contributions of genetic and environmental factors to MDD, since early stages of disease have less influence of illness exposure. Thus, we investigated the mRNA expression of 12 genes related to the hypothalamic-pituitary-adrenal (HPA) axis, inflammation, neurodevelopment and neurotransmission in the blood of children and adolescents with MDD and tested whether a history of childhood maltreatment (CM) affects MDD through gene expression. Whole-blood mRNA levels of 12 genes were compared among 20 children and adolescents with MDD diagnosis (MDD group), 49 participants without MDD diagnosis but with high levels of depressive symptoms (DS group), and 61 healthy controls (HC group).

Catechol-O-methyltransferase (COMT) polymorphisms modulate working memory in individuals with schizophrenia and healthy controls.

Objective: Cognitive impairment is a core feature of schizophrenia, related to dopaminergic dysfunction in the prefrontal cortex (PFC). It is hypothesized that functional single nucleotide polymorphism (SNP) rs4680 of the catechol-O-methyltransferase (COMT) gene could mediate the relationship between cognition and dopamine activity in the PFC. Other COMT SNPs could also play a role.

Summaries of plenary and selected symposia sessions at the XXIV World Congress of Psychiatric Genetics; Jerusalem, Israel; 30 October 2016-3 November 2016.

The XXII World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics, took place in Jerusalem, Israel, from 30 October 2016 to 3 November 2016. A total of 372 participants gathered to discuss the latest findings in the field. The following report was written by early career investigator travel awardees, and student and postdoctoral attendees.

Depression, Cytokine, and Cytokine by Treatment Interactions Modulate Gene Expression in Antipsychotic Naïve First Episode Psychosis.

In schizophrenia, genetic and environmental factors affect neurodevelopment and neuroprogressive trajectory. Altered expression of neuro-immune genes and increased levels of cytokines are observed, especially in patients with comorbid depression. However, it remains unclear whether circulating levels of cytokines and expression of these genes are associated, and how antipsychotic treatments impact this association.

Increased expression of NDEL1 and MBP genes in the peripheral blood of antipsychotic-naïve patients with first-episode psychosis.

Schizophrenia is a multifactorial neurodevelopmental disorder with high heritability. First-episode psychosis (FEP) is a critical period for determining the disease prognosis and is especially helpful for identifying potential biomarkers associated with the onset and progression of the disorder. We investigated the mRNA expression of 12 schizophrenia-related genes in the blood of antipsychotic-naïve FEP patients (N=73) and healthy controls (N=73).

Gene expression analysis in blood of ultra-high risk subjects compared to first-episode of psychosis patients and controls.

Objectives: This study aimed to investigate peripheral blood gene expression in ultra-high-risk subjects (UHR) compared to first-episode psychosis individuals (FEP) and healthy controls (HC).

Methods: We enrolled 22 UHR, 66 FEP and 67 HC and investigated the expression of 12 genes using Taqman assays. We used the Univariate General Linear Model, as well as Bonferroni correction for multiple comparisons.

Effects of risperidone on cytokine profile in drug-naïve first-episode psychosis.

Background: There is robust evidence that schizophrenia is characterized by immune-inflammatory abnormalities, including variations on cytokine levels. The results of previous studies, however, are heterogeneous due to several confounding factors, such as the effects of antipsychotic drugs. Therefore, research on drug-naïve first-episode psychosis (FEP) patients is essential to elucidate the role of immune processes in that disorder.