Transcriptomic changes in the frontal cortex associated with paternal age

Advanced paternal age is robustly associated with several human neuropsychiatric disorders, particularly autism. The precise mechanism(s) mediating the paternal age effect are not known, but they are thought to involve the accumulation of de novo (epi)genomic alterations. In this study we investigate differences in the frontal cortex transcriptome in a mouse model of advanced paternal age

The 20-year longitudinal trajectories of social functioning in individuals with psychotic disorders

Objective: Social impairment is a long-recognized core feature of schizophrenia and is common in other psychotic disorders. Still, to date the long-term trajectories of social impairment in psychotic disorders have rarely been studied systematically. Methods: Data came from the Suffolk County Mental Health Project, a 20-year prospective study of first-admission patients with psychotic disorders. A never-psychotic comparison group was also assessed. Latent class growth analysis was applied to longitudinal data on social functioning from 485 respondents with schizophrenia spectrum disorders and psychotic mood disorders, and associations of the empirically derived trajectories with premorbid social adjustment, diagnosis, and 20-year outcomes were examined. Results: Four mostly stable trajectories of preserved (N=82; 59th percentile of comparison group sample distribution), moderately impaired (N=148; 17th percentile), severely impaired (N=181; 3rd percentile), and profoundly impaired (N=74; 1st percentile) functioning best described the 20-year course of social functioning across diagnoses. The outcome in the group with preserved functioning did not differ from that of never-psychotic individuals at 20 years, but the other groups functioned significantly worse. Differences among trajectories were already evident in childhood. The two most impaired trajectories started to diverge in early adolescence. Poorer social functioning trajectories were strongly associated with other real-world outcomes at 20 years. Multiple trajectories were represented within each disorder. However, more participants with schizophrenia spectrum disorders had impaired trajectories, and more with mood disorders had better functioning trajectories. Conclusions: The results highlight substantial variability of social outcomes within diagnoses—albeit overall worse social outcomes in schizophrenia spectrum disorders—and show remarkably stable long-term impairments in social functioning after illness onset across all diagnoses

Lifespan evolution of neurocognitive impairment in schizophrenia - A narrative review

Cognitive impairment is a well-recognized key feature of schizophrenia. Here we review the evidence on (1) the onset and sensitive periods of change in cognitive impairment before and after the first psychotic episode, and (2) heterogeneity in neurocognitive presentations across cognitive domains between and within individuals. Overall, studies suggest that mild cognitive impairment in individuals who develop schizophrenia or related disorders is already present during early childhood. Cross-sectional studies further suggest increasing cognitive impairments from pre- to post-psychosis onset, with the greatest declines between adolescence, the prodrome, and the first psychotic episode and with some variability between domains. Longitudinal studies with more than 10 years of observation time are scarce but support mild cognitive declines after psychosis onset until late adulthood. Whether and how much this cognitive decline exceeds normal aging, proceeds further in older patients, and is specific to certain cognitive domains and subpopulations of patients remains to be investigated. Finally, studies show substantial heterogeneity in cognitive performance in schizophrenia and suggest a variety of impairment profiles. This review highlights a clear need for long-term studies that include a control group and individuals from adolescence to old age to better understand critical windows of cognitive change and its predictors. The available evidence stresses the importance of interventions that aim to counter cognitive decline during the prodromal years, as well as careful assessment of cognition in order to determine who will profit most from which cognitive training

Psychotic experiences, working memory, and the developing brain: a multimodal neuroimaging study

Psychotic experiences (PEs) occur in the general population, especially in children and adolescents, and are associated with poor psychosocial outcomes, impaired cognition, and increased risk of transition to psychosis. It is unknown how the presence and persistence of PEs during early adulthood affects cognition and brain function. The current study assessed working memory as well as brain function and structure in 149 individuals, with and without PEs, drawn from a population cohort. Observer-rated PEs were classified as persistent or transient on the basis of longitudinal assessments. Working memory was assessed using the n-back task during fMRI. Dynamic causal modeling (DCM) was used to characterize frontoparietal network configuration and voxel-based morphometry was utilized to examine gray matter. Those with persistent, but not transient, PEs performed worse on the n-back task, compared with controls, yet showed no significant differences in regional brain activation or brain structure. DCM analyses revealed greater emphasis on frontal connectivity within a frontoparietal network in those with PEs compared with controls. We propose that these findings portray an altered configuration of working memory function in the brain, potentially indicative of an adaptive response to atypical development associated with the manifestation of PEs

Advantageous developmental outcomes of advancing paternal age

AbstractAdvanced paternal age (APA) at conception has been associated with negative outcomes in offspring, raising concerns about increasing age at fatherhood. Evidence from evolutionary and psychological research, however, suggests possible link between APA and a phenotypic advantage. We defined such advantage as educational success, which is positively associated with future socioeconomic status. We hypothesised that high IQ, strong focus on the subject of interest and little concern about ‘fitting in’ will be associated with such success. Although these traits are continuously distributed in the population, they cluster together in so-called ‘geeks’. We used these measures to compute a ‘geek index’ (GI), and showed it to be strongly predictive of future academic attainment, beyond the independent contribution of the individual traits. GI was associated with paternal age in male offspring only, and mediated the positive effects of APA on education outcomes, in a similar sexually dimorphic manner. The association between paternal age and GI was partly mediated by genetic factors not correlated with age at fatherhood, suggesting contribution of de novo factors to the ‘geeky’ phenotype. Our study sheds new light on the multifaceted nature of the APA effects and explores the intricate links between APA, autism and talent.</jats:p

Teacher Residency as a Path to Teacher Diversity: Negotiating Tensions in Role and Identity

This phenomenological qualitative study examined the experiences of graduate-level teacher candidates enrolled in teacher residency programs and serving as teacher aides or assistants (TAs). Some participants were graduate-level teacher candidates already employed as TAs in a large urban district and enrolled in an Urban Pipeline Residency Program, a state-funded diversity initiative designed to increase the number of teachers from underrepresented groups by supporting TAs to pursue teacher certification. Additional participants were enrolled in the Traditional Residency Program and completed residencies in other local districts. Survey and interview data from TA/teacher candidates, mentors, and instructors showed that TA/teacher candidates in both groups experienced conflicting roles and identities, balanced demands of different classroom settings, lacked access to knowledge and materials, and balanced demands on their time. Informed by role theory, identity work, and culturally responsive pedagogy, this study suggests that programs for TA/teacher candidates may benefit from negotiating these tensions through: 1) support for TA/teacher candidates to develop their identities as teachers to address role conflict, 2) strong communication protocols to address role clarity, and 3) increased access to tools and knowledge to address role enactment

Volumetric, relaxometric and diffusometric correlates of psychotic experiences in a non-clinical sample of young adults

BACKGROUND: Grey matter (GM) abnormalities are robust features of schizophrenia and of people at ultra high-risk for psychosis. However the extent to which neuroanatomical alterations are evident in non-clinical subjects with isolated psychotic experiences is less clear. METHODS: Individuals (mean age 20 years) with (n = 123) or without (n = 125) psychotic experiences (PEs) were identified from a population-based cohort. All underwent T1-weighted structural, diffusion and quantitative T1 relaxometry MRI, to characterise GM macrostructure, microstructure and myelination respectively. Differences in quantitative GM structure were assessed using voxel-based morphometry (VBM). Binary and ordinal models of PEs were tested. Correlations between socioeconomic and other risk factors for psychosis with cortical GM measures were also computed. RESULTS: GM volume in the left supra-marginal gyrus was reduced in individuals with PEs relative to those with no PEs. The greater the severity of PEs, the greater the reduction in T1 relaxation rate (R1) across left temporoparietal and right pre-frontal cortices. In these regions, R1 was positively correlated with maternal education and inversely correlated with general psychopathology. CONCLUSIONS: PEs in non-clinical subjects were associated with regional reductions in grey-matter volume reduction and T1 relaxation rate. The alterations in T1 relaxation rate were also linked to the level of general psychopathology. Follow up of these subjects should clarify whether these alterations predict the later development of an ultra high-risk state or a psychotic disorder

The association between premorbid cognitive ability and social functioning and suicide among young men: A historical-prospective cohort study

Previous studies have found associations between low cognitive ability and later completed suicide. The aim of this study was to examine the association between cognitive ability and social functioning in adolescence, and later completed suicide in a large population-based longitudinal study. Data from the Israeli Draft Board Register for 634,655 Israeli male adolescents aged 16 and 17 was linked to a causes-of-death data registry, with a mean follow-up of 10.6 years for completed suicide. Our results show that in males without a psychiatric diagnosis, both low (adjusted HR=1.51, 95% CI: 1.19–1.92) and high (adjusted HR=1.36, 95% CI: 1.04–1.77) cognitive ability, and very poor (adjusted HR=2.30, 95% CI: 1.34–3.95) and poor (adjusted HR=1.64, 95% CI: 1.34–2.07) social functioning were associated with increased risk for later completed suicide; however positive predictive values were low (PPVs=0.09% and 0.10%, for low cognitive ability and very poor or poor social functioning, respectively). No association between cognitive ability or social functioning and risk for suicide was found in males with a psychiatric diagnosis. These data do not support the clinical utility of screening for such potential predictors