Gene expression changes related to immune processes associate with cognitive endophenotypes of schizophrenia

Schizophrenia is a heterogeneous disorder characterized by a spectrum of symptoms and many different underlying causes. Thus, instead of using the broad diagnosis, intermediate phenotypes can be used to possibly decrease the underlying complexity of the disorder. Alongside the classical symptoms of delusions and hallucinations, cognitive deficits are a core feature of schizophrenia. To increase our understanding of the biological processes related to these cognitive deficits, we performed a genome-wide gene expression analysis. A battery of 14 neuropsychological tests was administered to 844 individuals from a Finnish familial schizophrenia cohort. We grouped the applied neuropsychological tests into five factors for further analysis. Cognitive endophenotypes, whole blood mRNA, genotype, and medication use data were studied from 47 individuals. Expression level of several RNA probes were significantly associated with cognitive performance. The factor representing Verbal Working Memory was associated with altered expression levels of 11 probes, of which one probe was also associated with a specific sub-measure of this factor (WMS-R Digit span backward). While, the factor Processing speed was related to one probe, which additionally associated among 55 probes with a specific sub-measure of this factor (WAIS-R Digit symbol). Two probes were associated with the measure recognition memory performance. Enrichment analysis of these differentially expressed probes highlighted immunological processes. Our findings are in line with genome-wide genetic discoveries made in schizophrenia, suggesting that immunological processes may be of biological interest for future drug design towards schizophrenia and the cognitive dysfunctions that underlie it.Peer reviewe

Night Awakening in Infancy : Developmental Stability and Longitudinal Associations With Psychomotor Development

Fragmented sleep is common in infancy. Although night awakening is known to decrease with age, in some infants night awakening is more persistent and continues into older ages. However, the influence of fragmented sleep on development is poorly known. In the present study, the longitudinal relationship between fragmented sleep and psychomotor development (Bayley Scales of Infant and Toddler Development [Bayley-III]; Bayley, 2009) was investigated in infants with (>= 3 night awakenings, n = 81) and without fragmented sleep (Peer reviewe

Anxiety symptoms in a major mood and schizophrenia spectrum disorders

Background: Comorbid anxiety symptoms and disorders are present in many psychiatric disorders, but methodological variations render comparisons of their frequency and intensity difficult. Furthermore, whether risk factors for comorbid anxiety symptoms are similar in patients with mood disorders and schizophrenia spectrum disorders remains unclear. Methods: The Overall Anxiety Severity and Impairment Scale (OASIS) was used to measure anxiety symptoms in psychiatric care patients with schizophrenia or schizoaffective disorder (SSA, n = 113), bipolar disorder (BD, n = 99), or depressive disorder (DD, n = 188) in the Helsinki University Psychiatric Consortium Study. Bivariate correlations and multivariate linear regression models were used to examine associations of depressive symptoms, neuroticism, early psychological trauma and distress, self-efficacy, symptoms of borderline personality disorder, and attachment style with anxiety symptoms in the three diagnostic groups. Results: Frequent or constant anxiety was reported by 40.2% of SSA, 51.5% of BD, and 55.6% of DD patients; it was described as severe or extreme by 43.8%, 41.4%, and 41.2% of these patients, respectively. SSA patients were significantly less anxious (P = 0.010) and less often avoided anxiety-provoking situations (P = 0.009) than the other patients. In regression analyses, OASIS was associated with high neuroticism, symptoms of depression and borderline personality disorder and low self-efficacy in all patients, and with early trauma in patients with mood disorders. Conclusions: Comorbid anxiety symptoms are ubiquitous among psychiatric patients with mood or schizophrenia spectrum disorders, and in almost half of them, reportedly severe. Anxiety symptoms appear to be strongly related to both concurrent depressive symptoms and personality characteristics, regardless of principal diagnosis. (C) 2016 Elsevier Masson SAS. All rights reserved.Peer reviewe

Signaled night awakening and its association with social information processing and socio-emotional development across the first two years

Study objectives: Night awakening is common in infancy, and some infants continue to have signaled night awakenings throughout early childhood. However, the influence of signaled night awakening on children's social development is less explored. In the present study, longitudinal associations between signaled night awakening, social information processing, and socio-emotional development were measured within the CHILD-SLEEP birth cohort in two groups formed based on parent-reported night awakenings. Methods: At 8 months, there were 77 infants in the waking group (≥3 awakenings) and 69 infants in the nonwaking group (≤1 awakening). At 8 and 24 months, social information processing was measured as children's attention to neutral and emotional faces, and at 24 months, parent-reported socio-emotional behavior was measured with the Brief Infant Toddler Social Emotional Assessment (BITSEA) questionnaire. Results: The two groups showed different patterns of attention to emotional faces. The waking group had a more pronounced attentional bias to fearful vs. happy faces, whereas in the nonwaking group, attention to fearful and happy faces did not differ. In addition, at 24 months, the waking group had more dysregulation problems and lower social competence than the nonwaking group, but no clear differences in internalizing or externalizing problems were found. Conclusions: Our results contribute to the literature by showing that during the first two years of life, signaled night awakening is associated with social information processing and socio-emotional behavior.Study objectives: Night awakening is common in infancy, and some infants continue to have signaled night awakenings throughout early childhood. However, the influence of signaled night awakening on children's social development is less explored. In the present study, longitudinal associations between signaled night awakening, social information processing, and socio-emotional development were measured within the CHILD-SLEEP birth cohort in two groups formed based on parent-reported night awakenings. Methods: At 8 months, there were 77 infants in the waking group (≥3 awakenings) and 69 infants in the nonwaking group (≤1 awakening). At 8 and 24 months, social information processing was measured as children's attention to neutral and emotional faces, and at 24 months, parent-reported socio-emotional behavior was measured with the Brief Infant Toddler Social Emotional Assessment (BITSEA) questionnaire. Results: The two groups showed different patterns of attention to emotional faces. The waking group had a more pronounced attentional bias to fearful vs. happy faces, whereas in the nonwaking group, attention to fearful and happy faces did not differ. In addition, at 24 months, the waking group had more dysregulation problems and lower social competence than the nonwaking group, but no clear differences in internalizing or externalizing problems were found. Conclusions: Our results contribute to the literature by showing that during the first two years of life, signaled night awakening is associated with social information processing and socio-emotional behavior.Peer reviewe

Self-reported psychosis-like experiences in patients with mood disorders

Background: Self-reported psychosis-like experiences (PEs) may be common in patients with mood disorders, but their clinical correlates are not well known. We investigated their prevalence and relationships with self-reported symptoms of depression, mania, anxiety, borderline (BPD) and schizotypal (SPD) personality disorders among psychiatric patients with mood disorders. Methods: The Community Assessment of Psychic Experiences (CAPE-42), Mood Disorder Questionnaire (MDQ), McLean Screening Instrument (MSI), The Beck Depressive Inventory (BDI), Overall Anxiety Severity and Impairment Scale (OASIS) and Schizotypal Personality Questionnaire-Brief form (SPQ-B) were filled in by patients with mood disorders (n = 282) from specialized care. Correlation coefficients between total scores and individual items of CAPE-42 and BDI, SPQ-B, MSI and MDQ were estimated. Hierarchical multivariate regression analysis was conducted to examine factors influencing the frequency of self-reported PE. Results: PEs are common in patients with mood disorders. The "frequency of positive symptoms" score of CAPE-42 correlated strongly with total score of SPQ-B (rho = 0.63; P <0.001) and moderately with total scores of BDI, MDQ OASIS and MSI (rho varied from 0.37 to 0.56; P <0.001). Individual items of CAPE-42 correlated moderately with specific items of BDI, MDQ SPQ-B and MSI (r(phi) varied from 0.2 to 0.5; P <0.001). Symptoms of anxiety, mania or hypomania and BPD were significant predictors of the "frequency of positive symptoms" score of CAPE-42. Conclusions: Several, state- and trait-related factors may underlie self-reported PEs among mood disorder patients. These include cognitive-perceptual distortions of SPD; distrustfulness, identity disturbance, dissociative and affective symptoms of BPD; and cognitive biases related to depressive or manic symptoms. (C) 2016 Elsevier Masson SAS. All rights reserved.Peer reviewe

Alu element in the RNA binding motif protein, X-linked 2 (RBMX2) gene found to be linked to bipolar disorder

Objective We have used long-read single molecule, real-time (SMRT) sequencing to fully characterize a similar to 12Mb genomic region on chromosome Xq24-q27, significantly linked to bipolar disorder (BD) in an extended family from a genetic sub-isolate. This family segregates BD in at least four generations with 24 affected individuals. Methods We selected 16 family members for targeted sequencing. The selected individuals either carried the disease haplotype, were non-carriers of the disease haplotype, or served as married-in controls. We designed hybrid capture probes enriching for 5-9Kb fragments spanning the entire 12Mb region that were then sequenced to screen for candidate structural variants (SVs) that could explain the increased risk for BD in this extended family. Results Altogether, 201 variants were detected in the critically linked region. Although most of these represented common variants, three variants emerged that showed near-perfect segregation among all BD type I affected individuals. Two of the SVs were identified in or near genes belonging to the RNA Binding Motif Protein, X-Linked (RBMX) gene family-a 330bp Alu (subfamily AluYa5) deletion in intron 3 of the RBMX2 gene and an intergenic 27bp tandem repeat deletion between the RBMX and G protein-coupled receptor 101 (GPR101) genes. The third SV was a 50bp tandem repeat insertion in intron 1 of the Coagulation Factor IX (F9) gene. Conclusions Among the three genetically linked SVs, additional evidence supported the Alu element deletion in RBMX2 as the leading candidate for contributing directly to the disease development of BD type I in this extended family.Peer reviewe

Self-reported symptoms of schizotypal and borderline personality disorder in patients with mood disorders

Background: Distinguishing between symptoms of schizotypal (SPD) and borderline personality disorders (BPD) is often difficult due to their partial overlap and frequent co-occurrence. We investigated correlations in self-reported symptoms of SPD and BPD in questionnaires at the levels of both total scores and individual items, examining overlapping dimensions. Methods: Two questionnaires, the McLean Screening Instrument (MSI) for BPD and the Schizotypal Personality Questionnaire Brief (SPQ-B) for SPD, were filled in by patients with mood disorders (n = 282) from specialized psychiatric care in a study of the Helsinki University Psychiatric Consortium. Correlation coefficients between total scores and individual items of the MSI and SPQ-B were estimated. Multivariate regression analysis (MRA) was conducted to examine the relationships between SPQ-B and MSI. Results: The Spearman's correlation between total scores of the MSI and SPQ-B was strong (rho = 0.616, P <0.005). Items of MSI reflecting disrupted relatedness and affective dysregulation correlated moderately (r(phi) varied between 0.2 and 0.4, P <0.005) with items of SPQ. Items of MSI reflecting behavioural dysregulation correlated only weakly with items of SPQ. In MRA, depressive symptoms, sex and MSI were significant predictors of SPQ-B score, whereas symptoms of anxiety, age and SPQ-B were significant predictors of MSI score. Conclusions: Items reflecting cognitive-perceptual distortions and affective symptoms of BPD appear to overlap with disorganized and cognitive-perceptual symptoms of SPD. Symptoms of depression may aggravate self-reported features of SPQ-B, and symptoms of anxiety features of MSI. Symptoms of behavioural dysregulation of BPD and interpersonal deficits of SPQ appear to be non-overlapping. (C) 2016 Elsevier Masson SAS. All rights reserved.Peer reviewe

Genetic polymorphisms in COMT and BDNF influence synchronization dynamics of human neuronal oscillations

Neuronal oscillations, their inter-areal synchronization, and scale-free dynamics constitute fundamental mechanisms for cognition by regulating communication in neuronal networks. These oscillatory dynamics have large inter-individual variability that is partly heritable. We hypothesized that this variability could be partially explained by genetic polymorphisms in neuromodulatory genes. We recorded resting-state magnetoencephalography (MEG) from 82 healthy participants and investigated whether oscillation dynamics were influenced by genetic polymorphisms in catechol- -methyltransferase ( ) Val Met and brain-derived neurotrophic factor ( ) Val Met. Both and polymorphisms influenced local oscillation amplitudes and their long-range temporal correlations (LRTCs), while only polymorphism affected the strength of large-scale synchronization. Our findings demonstrate that and genetic polymorphisms contribute to inter-individual variability in neuronal oscillation dynamics. Comparison of these results to computational modeling of near-critical synchronization dynamics further suggested that and polymorphisms influenced local oscillations by modulating the excitation-inhibition balance according to the brain criticality framework