Additional layers of gene regulatory complexity from recently discovered microRNA mechanisms

In recent years microRNAs have become recognized as pervasive, versatile agents of gene regulation. Some widely embraced rules involving Watson-Crick hybridization of microRNAs with mRNAs have generated great interest as scientists envision potential RNA cargoes for gene therapy and other experimental systems. However, while researchers ardently seek simplifying principles, nature seems very uncooperative. This article reviews some small RNA mechanisms that potentially regulate genes and which are not covered by previous microRNAs characterizations. In addition, we report here results of fluorescence microscopy experiments to directly demonstrate nuclear importation of small RNAs equal in length to typical mature microRNAs, implying that gene regulation at the locus of transcription might be possible

Assessment of social judgments and complex mental states in the early phases of psychosis

Social cognition plays an important role in the functioning of individuals with psychosis. In this study, we explored two areas of social cognition not previously investigated early in the course of psychosis

Social skill and social cognition in adolescents at genetic risk for psychosis

Adolescents at genetic high risk (GHR) for schizophrenia have shown social skill impairments and there is some evidence to suggest they have Theory of Mind (ToM) deficits; however no research has used a standardized, performance-based behavioral measure to assess social functioning in this population nor evaluated ToM with a well-validated measure. We evaluated the psychometric properties of a new, theoretically-derived assessment of social functioning in GHR adolescents: the "High-Risk Social Challenge" task (HiSoC). The second aim was to explore whether GHR adolescents would show social skill and ToM deficits as compared to a nonpsychiatric control (NPC) group. The present study evaluated social functioning with the HiSoC and ToM with the Eyes Test in 23 GHR adolescents and 31 NPCs. The HiSoC demonstrated high levels of reliability and validity. The GHR adolescents showed social skill impairments, but not ToM deficits. The results suggest that the HiSoC is a potentially useful new measure of social functioning in GHR adolescents. Furthermore, the findings add to the current body of literature that indicates that social skill impairments are related to schizophrenia vulnerability

microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder

BACKGROUND: microRNAs (miRNAs) are small, noncoding RNA molecules that are now thought to regulate the expression of many mRNAs. They have been implicated in the etiology of a variety of complex diseases, including Tourette's syndrome, Fragile × syndrome, and several types of cancer. RESULTS: We hypothesized that schizophrenia might be associated with altered miRNA profiles. To investigate this possibility we compared the expression of 264 human miRNAs from postmortem prefrontal cortex tissue of individuals with schizophrenia (n = 13) or schizoaffective disorder (n = 2) to tissue of 21 psychiatrically unaffected individuals using a custom miRNA microarray. Allowing a 5% false discovery rate, we found that 16 miRNAs were differentially expressed in prefrontal cortex of patient subjects, with 15 expressed at lower levels (fold change 0.63 to 0.89) and 1 at a higher level (fold change 1.77) than in the psychiatrically unaffected comparison subjects. The expression levels of 12 selected miRNAs were also determined by quantitative RT-PCR in our lab. For the eight miRNAs distinguished by being expressed at lower microarray levels in schizophrenia samples versus comparison samples, seven were also expressed at lower levels with quantitative RT-PCR. CONCLUSION: This study is the first to find altered miRNA profiles in postmortem prefrontal cortex from schizophrenia patients

User experiences of an American-adapted moderated online social media platform for first-episode psychosis: Qualitative analysis

Objectives The current study sought to qualitatively characterize the experiences of American users in a recent open trial of the Horyzons digital platform. Methods In total, 20 users on Horyzons USA completed semistructured interviews 12 weeks after their orientation to the platform and addressed questions related to (1) the platform, (2) their online therapist, and (3) the peer workers and community space. A hybrid inductive-deductive coding strategy was used to conduct a thematic analysis of the data (NCT04673851). Results The authors identified seven prominent themes that mapped onto the three components of self-determination theory. Features of the platform itself as well as inter- and intra-personal factors supported the autonomous use of Horyzons. Users also reflected that their perceived competence in social settings and in managing mental health was increased by the familiarity, privacy, and perceived safety of the platform and an emphasis on personalized therapeutic content. The behaviors or traits of online therapists as perceived by users and regular contact with peers and peer support specialists satisfied users’ need for relatedness and promoted confidence in social settings. Users also described aspects of Horyzons USA that challenged their satisfaction of autonomy, competence, and relatedness, highlighting potential areas for future iterations of the platform's content and interface. Conclusions Horyzons USA is a promising digital tool that provides young adults with psychosis with the means to access tailored therapy material on demand and a supportive digital community to aid in the recovery process

User experiences of an American-adapted moderated online social media platform for first-episode psychosis : Qualitative analysis

Objectives The current study sought to qualitatively characterize the experiences of American users in a recent open trial of the Horyzons digital platform. Methods In total, 20 users on Horyzons USA completed semistructured interviews 12 weeks after their orientation to the platform and addressed questions related to (1) the platform, (2) their online therapist, and (3) the peer workers and community space. A hybrid inductive-deductive coding strategy was used to conduct a thematic analysis of the data (NCT04673851). Results The authors identified seven prominent themes that mapped onto the three components of self-determination theory. Features of the platform itself as well as inter- and intra-personal factors supported the autonomous use of Horyzons. Users also reflected that their perceived competence in social settings and in managing mental health was increased by the familiarity, privacy, and perceived safety of the platform and an emphasis on personalized therapeutic content. The behaviors or traits of online therapists as perceived by users and regular contact with peers and peer support specialists satisfied users’ need for relatedness and promoted confidence in social settings. Users also described aspects of Horyzons USA that challenged their satisfaction of autonomy, competence, and relatedness, highlighting potential areas for future iterations of the platform's content and interface. Conclusions Horyzons USA is a promising digital tool that provides young adults with psychosis with the means to access tailored therapy material on demand and a supportive digital community to aid in the recovery process

Altered fronto–limbic activity in children and adolescents with familial high risk for schizophrenia

Early symptoms of schizophrenia tend to emerge during adolescence, which is a critical period for development of executive and emotional processing. While individuals with familial high risk (FHR) for schizophrenia may show cognitive and emotional changes, the neural mechanisms underlying the development of these changes remain unclear. The goal of this study was to identify functional differences in fronto-striato-limbic regions in children with FHR. Functional MRI data was collected from 21 children with a first-degree family member with schizophrenia and 21 controls without FHR. Participants performed an emotional oddball task requiring both selective attention and suppression of task-irrelevant emotional information. During selective attention, the group with FHR showed enhanced activation in inferior frontal gyrus and caudate, with decreases in middle frontal gyrus and insular activation. The FHR group also showed greater age-related recruitment of anterior cingulate, temporal and occipital cortical areas during selective attention. During emotional processing, the FHR group showed decreased anterior cingulate activation, with decreased age-related recruitment of inferior frontal, parietal and occipital areas. The results suggest that FHR for schizophrenia may be associated with abnormal hyperactivation and hypoactivation of the neural circuitry engaged during executive and emotional processing and with age-related changes in neural recruitment during adolescence

Imaging Frontostriatal Function in Ultra-High-Risk, Early, and Chronic Schizophrenia During Executive Processing

Individuals experiencing prodromal symptoms of schizophrenia (ultra-high-risk group) demonstrate impaired performance on tasks of executive function, attention, and working memory. The neurobiological underpinnings of such executive deficits in ultra-high-risk individuals remains unclear

Differences in subcortical structures in young adolescents at familial risk for schizophrenia: A preliminary study

Schizophrenia has been associated with reduced volumes of subcortical structures on MRI, but the relation of these reductions to familial risk for the disorder is unclear. We investigated the effect of familial risk for schizophrenia on regional subcortical volumes during adolescence, a period marked by steep maturational changes in brain structure and the emergence of psychotic symptoms. A group of 26 non-help-seeking, first-degree relatives of patients with schizophrenia and 43 matched healthy comparisons, between 9 and 18 years of age, underwent MRI scanning and were rated for the presence of prodromal symptoms. Five subcortical regions-of-interest were tested for group differences and group by age interactions, as well as correlations with low-level prodromal symptoms in the familial risk group. Relative to comparisons, familial risk subjects demonstrated greater positive volume-age relationships in hippocampus, putamen, and globus pallidus. These results suggest that relatives of individuals with schizophrenia exhibit structural abnormalities in the subcortex as early as pre-adolescence, which may reflect altered neurodevelopment of these regions