Search

We investigated the potential of machine learning for diagnostic classification in late-life major depression based on an advanced whole brain white matter segmentation framework. Twenty-six late-life depression and 12 never depressed individuals aged > 55 years, matched for age, MMSE, and education underwent brain diffusion tensor imaging and a multi-contrast, multi-atlas segmentation in MRIcloud. Fractional anisotropy volume, mean fractional anisotropy, trace, axial and radial diffusivity (RD) extracted from 146 white matter parcels for each subject were used to train and test the AdaBoost classifier using stratified 12-fold cross validation. Performance was evaluated using various measures. The statistical power of the classifier was assessed using label permutation test. Statistical analysis did not yield significant differences in DTI measures between the groups. The classifier achieved a balanced accuracy of 71% and an Area Under the Receiver Operator Characteristic Curve (ROC-AUC) of 0.81 by trace, and a balanced accuracy of 70% and a ROC-AUC of 0.80 by RD, in limbic, cortico-basal ganglia-thalamo-cortical loop, brainstem, external and internal capsules, callosal and cerebellar structures. Both indices shared important structures for classification, while fornix was the most important structure for classification by both indices. The classifier proved statistically significant, as trace and RD ROC-AUC scores after permutation were lower than those obtained with the actual data (P = 0.022 and P = 0.024, respectively). Similar results were obtained with the Gradient Boosting classifier, whereas the RBF-kernel Support Vector Machine with k-best feature selection did not exceed the chance level. Finally, AdaBoost significantly predicted the class using all features together. Limitations are discussed. The results encourage further investigation of the implemented methods for computer aided diagnostics and anatomically informed therapeutics. [ABSTRACT FROM AUTHOR]

Objective: Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely provision of pharmacological interventions for apathy is greatly needed. Design: A systematical literature review of existing studies was conducted up to 30 May 2023 in several databases (PubMed, PsychInfo, Cochrane, Google Scholar, etc.) that included randomized controlled trials (RCTs) and meta-analyses assessing pharmacological treatments for apathy in aging neurocognitive disorders. The quality of the studies was appraised. Results: In patients with Alzheimer's Disease (AD), donepezil, galantamine, rivastigmine, methylphenidate, and gingko biloba were proven efficacious for apathy, while rivastigmine, cognitive enhancer IRL752 and piribedil were found to be beneficial in patients with Parkinson's Disease (PD) and agomelatine in patients with Frontotemporal Dementia (FD). The extensive proportion of RCTs in which apathy was used as a secondary outcome measure, along with the considerable methodological heterogeneity, did not allow the evaluation of group effects. Conclusions: Pharmacological interventions for apathy in aging neurocognitive disorders are complex and under-investigated. The continuation of systematic research efforts and the provision of individualized treatment for patients suffering from these disorders is vital. [ABSTRACT FROM AUTHOR]

Findings of genetic overlap between Schizophrenia, Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) contributed to a renewed conceptualization of these disorders as laying on a continuum based on aetiological, pathophysiological and neurodevelopmental features. Given that cognitive impairments are core to their pathophysiology, we compared patients with schizophrenia, ADHD, ASD, and controls on ocular-motor and manual-motor tasks, challenging crucial cognitive processes. Group comparisons revealed inhibition deficits common to all disorders, increased intra-subject variability in schizophrenia and, to a lesser extent, ADHD as well as slowed processing in schizophrenia. Patterns of deviancies from controls exhibited strong correlations, along with differences that posited schizophrenia as the most impaired group, followed by ASD and ADHD. While vector correlations point towards a common neurodevelopmental continuum of impairment, vector levels suggest differences in the severity of such impairment. These findings argue towards a dimensional approach to Neurodevelopmental Disorders' pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Wearable technologies and digital phenotyping foster unique opportunities for designing novel intelligent electronic services that can address various well-being issues in patients with mental disorders (i.e., schizophrenia and bipolar disorder), thus having the potential to revolutionize psychiatry and its clinical practice. In this paper, we present e-Prevention, an innovative integrated system for medical support that facilitates effective monitoring and relapse prevention in patients with mental disorders. The technologies offered through e-Prevention include: (i) long-term continuous recording of biometric and behavioral indices through a smartwatch; (ii) video recordings of patients while being interviewed by a clinician, using a tablet; (iii) automatic and systematic storage of these data in a dedicated Cloud server and; (iv) the ability of relapse detection and prediction. This paper focuses on the description of the e-Prevention system and the methodologies developed for the identification of feature representations that correlate with and can predict psychopathology and relapses in patients with mental disorders. Specifically, we tackle the problem of relapse detection and prediction using Machine and Deep Learning techniques on all collected data. The results are promising, indicating that such predictions could be made and leading eventually to the prediction of psychopathology and the prevention of relapses. [ABSTRACT FROM AUTHOR]

Disorders with neurodevelopmental aetiology such as Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD) and Schizophrenia share commonalities at many levels of investigation despite phenotypic differences. Evidence of genetic overlap has led to the concept of a continuum of neurodevelopmental impairment along which these disorders can be positioned in aetiological, pathophysiological and developmental features. This concept requires their simultaneous comparison at different levels, which has not been accomplished so far. Given that cognitive impairments are core to the pathophysiology of these disorders, we provide for the first time differentiated head-to-head comparisons in a complex cognitive function, visual search, decomposing the task with eye movement-based process analyses. N = 103 late-adolescents with schizophrenia, ADHD, ASD and healthy controls took a serial visual search task, while their eye movements were recorded. Patients with schizophrenia presented the greatest level of impairment across different phases of search, followed by patients with ADHD, who shared with patients with schizophrenia elevated intra-subject variability in the pre-search stage. ASD was the least impaired group, but similar to schizophrenia in post-search processes and to schizophrenia and ADHD in pre-search processes and fixation duration while scanning the items. Importantly, the profiles of deviancy from controls were highly correlated between all three clinical groups, in line with the continuum idea. Findings suggest the existence of one common neurodevelopmental continuum of performance for the three disorders, while quantitative differences appear in the level of impairment. Given the relevance of cognitive impairments in these three disorders, we argue in favour of overlapping pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

The gut-microbiota-brain axis is a complex bidirectional communication system linking the gastrointestinal tract to the brain. Changes in the balance, composition and diversity of the gut-microbiota (gut dysbiosis) have been found to be associated with the development of psychosis. Early-life stress, along with various stressors encountered in different developmental phases, have been shown to be associated with the abnormal composition of the gut microbiota, leading to irregular immunological and neuroendocrine functions, which are potentially responsible for the occurrence of first-episode psychosis (FEP). The aim of the present narrative review was to summarize the significant differences of the altered microbiome composition in patients suffering from FEP vs. healthy controls, and to discuss its effects on the occurrence and intensity of symptoms in FEP. [ABSTRACT FROM AUTHOR]

Abstract: There is growing interest in the connection between neurological soft signs (NSS) and schizophrenia spectrum disorders such as schizotypal personality disorder. The association between NSS and schizotypy was investigated in a subgroup of 169 young healthy male military conscripts included in the Athens Study of Psychosis Proneness and Incidence of Schizophrenia. During their first 2weeks in the National Basic Air Force Training Centre (T1—first assessment), subjects completed the Schizotypal Personality Questionnaire (SPQ), the Symptom Checklist-90—Revised (SCL-90-R), and the Raven''s Progressive Matrices (RPM). Then, 2years later (T2—second assessment), at the time of military discharge, they were tested for NSS with the Neurological Evaluation Scale (NES) and reevaluated with the SPQ, the SCL-90-R and additionally the Structured Clinical Interview for Personality Disorders (SCID-II) for the Diagnostic and Statistical Manual of Mental Disorders Third Edition, Revised (DSM-III-R). NSS were more prominent in conscripts with high schizotypy; scores on Sequencing of Complex Motor Acts (SCMA) and the “Other Soft Signs” (OSS) subscales were correlated with high schizotypy at both T1 and T2. Increased levels of SCMA as well as the total NSS score were correlated at both T1 and T2 with the interpersonal SPQ factor (reflecting negative schizotypy). The findings support the proposal that negative schizotypy might be associated with subtle neurodevelopmental abnormalities. [Copyright &y& Elsevier]

• Multisensory Integration (MSI) speeds up reaction time (gain) in healthy controls. • Using a novel method, we confirmed MSI gain in 78 % of healthy controls. • 26 % of patients with Autism and 48 % of patients with schizophrenia. • MSI resulted in increased peak amplitudes for sensory and cognitive ERP components. • These ERP effects could not explain MSI differences among groups. The process of integrating information from different sensory channels, known as multisensory integration (MSI) was assessed in two disorders, Autism Spectrum Disorder (ASD) and Schizophrenia (SCZ). 32 healthy controls (HC), 35 SCZ patients, and 23 ASD patients performed an audiovisual (AV) synchronous target detection task while reaction time (RT) and scalp recorded electrophysiological (EEG) activity were measured. MSI in the AV condition resulted in faster and less variable RTs compared to the unimodal conditions. Using our novel bootstrap method, MSI gain was observed in 78 % of HC, 26 % of ASD, and 48 % of SCZ patients. At the neural level, MSI in the AV condition resulted in larger amplitude of sensory evoked responses and cognitive P3 response compared to the corresponding unimodal conditions. These neural effects of MSI were not related to the behavioural MSI gain identified at the individual level and could not explain the deficits in behavioural MSI of patient groups. In conclusion, a robust MSI gain deficit in RT was observed in both patient groups that was not reflected in early perceptual and cognitive electro-cortical responses, suggesting that behavioural MSI deficits in ASD and SCZ may arise at late processing stages such as response selection. [ABSTRACT FROM AUTHOR]

Highlights • Processing speed measured by Reaction Time (RT) is slower in schizophrenia patients. • Patients, healthy patient siblings and controls performed two-choice RT tasks. • Ex-Gaussian RT model and Drift Diffusion Model (DDM) was applied on RT distributions. • Ex-Gaussian RT parameters dissociated patients and siblings from controls. • The rising decision signal in DDM dissociated patients and siblings from controls. • RT distribution modeling reveals novel candidate endophenotypes of schizophrenia. Abstract Increased reaction time (RT) and variability of RT in fast decision tasks is observed in patients with schizophrenia and their first degree relatives. This study used modelling of the RT distribution with the aim of identifying novel candidate endophenotypes for schizophrenia. 20 patients with schizophrenia, 15 siblings of patients and 25 healthy controls performed an oddball task of varying working memory load. Increases in mean and standard deviation (SD) of RT were observed for both patients and siblings compared to controls and they were again independent of working memory load. Ex-Gaussian modelling of the RT distribution confirmed that parameters μ, σ and τ increased significantly in patients and siblings compared to controls. The Drift Diffusion Model was applied on RT distributions. A decrease in the diffusion drift rate (v) modeling the accumulation of evidence for reaching the decision to choose one stimulus over the other, was observed in patients and siblings compared to controls. The mean time of the non-decisional sensorimotor processes (t0) and it's variance (st0) was also increased in patients and siblings compared to controls. In conclusion modeling of the RT distribution revealed novel potential cognitive endophenotypes in the quest of heritable risk factors for schizophrenia. [ABSTRACT FROM AUTHOR]

Highlights • Academic Premorbid malAdjustment (APA) predicts cognitive dysfunction in schizophrenia. • Deteriorating APA predicts post-onset IQ decline, poorer executive function and verbal learning. • A premorbid cognitive dysmaturational process (CDP) in schizophrenia is suggested. • CDP differentially impedes the developmental progression of various cognitive functions. • Premorbid CDP leads to a pronounced cognitive decline post-diagnosis. Abstract Premorbid adjustment (PA) in academic and social domain is a key-predictor of cognitive performance in schizophrenia. Prior studies provided inconsistent findings regarding the differential relationships of PA domains with post-illness cognition. Multivariate associations of academic and social PA in each developmental stage (childhood, early and late adolescence) with post-onset cognitive variables were explored. Furthermore, possible differential relationships of PA domain deterioration courses with post-onset cognitive dysfunction were investigated. Seventy-five schizophrenia patients were evaluated with Premorbid Adjustment Scale (PAS). General cognitive ability, verbal IQ, verbal memory and learning, processing speed, working memory, executive function and premorbid IQ were assessed. Canonical Correlation Analyses revealed that poorer academic PA across childhood and early adolescence was related to worse post-onset verbal IQ, working memory, verbal learning and executive function, while academic PA deterioration between early and late adolescence was associated with poorer verbal learning and executive function and, as further analysis indicated, predicts IQ decline. Academic PA was exclusively associated with post-onset cognitive impairment. New evidence emerged for the specificity of each developmental period in constructing academic PA in its relation to post-illness cognition. Early premorbid academic maladjustment possibly constitutes the onset of a cognitive dysmaturational process which results to post-diagnosis impaired cognition. [ABSTRACT FROM AUTHOR]

While predominant (PP) and onset polarity (OP) have considerable clinical and treatment implications in bipolar disorder (BD), the neurobiological underpinnings of PP and OP from a radiological perspective remain largely unknown. The main objective of this study is to investigate the neuroanatomical profile of polarity subphenotypes (PP and OP) in euthymic BD patients, using a standardized multimodal neuroimaging protocol to evaluate regional gray matter (GM) volumes, cortical thickness, as well as white matter (WM) integrity of major projection, commissural and association tracts. Forty-two euthymic BD patients stratified for PP and OP and 42 healthy controls (HC) were included in this computational neuroimaging study to comprehensively characterize gray and white matter alterations. Univariate analyses of covariance (ANCOVAs) were conducted with Bonferroni corrections for each MRI modality and Cohen's d effect sizes were calculated for group comparisons. Phenotype-associated cortical thickness abnormalities and volumetric alterations were identified, but no WM changes ascertained. Specifically, we found a main effect of OP on GM volume of left middle frontal gyrus and of OP and PP (either or both) on cortical thickness of various regions previously implicated in BD, i.e. inferior frontal gyrus-pars opercularis (left) and pars orbitalis (bilateral), left lateral orbitofrontal gyrus, bilateral medial segment of the superior frontal gyrus, left planum polare, right anterior cingulate gyrus, left anterior and posterior insula, bilateral frontal operculum (both OP and PP); left anterior and posterior orbitofrontal gyrus, left transverse temporal gyrus, right posterior insula (only OP); and right medial frontal cortex (only PP). Based on the magnitude of differences on pairwise comparisons, we found a large effect of OP on cortical thickness in a single region (left anterior orbitofrontal gyrus) (OP-M > OP-D), while PP subgroups showed large or medium effect size differences in cortical thickness (PP-M > PP-D) in a wider array of regions (right medial frontal cortex, left frontal operculum, left inferior frontal gyrus-pars opercularis, bilateral medial segment of the superior frontal gyrus). For most regions, PP-D patients showed the greatest decreases in cortical thickness compared to HC while PP-M showed the smallest, with PP-U showing an "unspecified" pattern mostly lying in-between PP-D and PP-M. Our multimodal imaging findings suggest specific polarity BD subgroups with compromised cortical thickness; we recorded a greater impact of PP on brain structure compared to OP, which provides additional evidence that PP can be considered as a neurobiological specifier in BD. • Neuroimaging of onset (OP) and predominant polarity (PP) in BD is understudied. • We performed a multimodal neuroimaging study of OP and PP in euthymic BD patients. • We mainly found widespread cortical thickness changes across polarity subgroups. • PP had a greater impact on cortical thickness compared to OP. • Cortical thickness was affected most by depressive PP and least by manic PP. [ABSTRACT FROM AUTHOR]

The antisaccade task is a prominent tool to investigate the response inhibition component of cognitive control. Recent theoretical accounts explain performance in terms of parallel programming of exogenous and endogenous saccades, linked to the horse race metaphor. Previous studies have tested the hypothesis of competing saccade signals at the behavioral level by selectively slowing the programming of endogenous or exogenous processes e.g. by manipulating the probability of antisaccades in an experimental block. To gain a better understanding of inhibitory control processes in parallel saccade programming, we analyzed task-related eye movements and blood oxygenation level dependent (BOLD) responses obtained using functional magnetic resonance imaging (fMRI) at 3T from 16 healthy participants in a mixed antisaccade and prosaccade task. The frequency of antisaccade trials was manipulated across blocks of high (75%) and low (25%) antisaccade frequency. In blocks with high antisaccade frequency, antisaccade latencies were shorter and error rates lower whilst prosaccade latencies were longer and error rates were higher. At the level of BOLD, activations in the task-related saccade network (left inferior parietal lobe, right inferior parietal sulcus, left precentral gyrus reaching into left middle frontal gyrus and inferior frontal junction) and deactivations in components of the default mode network (bilateral temporal cortex, ventromedial prefrontal cortex) compensated increased cognitive control demands. These findings illustrate context dependent mechanisms underlying the coordination of competing decision signals in volitional gaze control. [ABSTRACT FROM AUTHOR]

In this study predictions of the dual-route cascaded (DRC) model of word reading were tested using fMRI. Specifically, patterns of co-localization were investigated: (a) between pseudoword length effects and a pseudowords vs. fixation contrast, to reveal the sublexical grapho-phonemic conversion (GPC) system; and (b) between word frequency effects and a words vs. pseudowords contrast, to reveal the orthographic and phonological lexicon. Forty four native speakers of Greek were scanned at 3 T in an event-related lexical decision task with three event types: (a) 150 words in which frequency, length, bigram and syllable frequency, neighborhood, and orthographic consistency were decorrelated; (b) 150 matched pseudowords; and (c) fixation. Whole-brain analysis failed to reveal the predicted co-localizations. Further analysis with participant-specific regions of interest defined within masks from the group contrasts revealed length effects in left inferior parietal cortex and frequency effects in the left middle temporal gyrus. These findings could be interpreted as partially consistent with the existence of the GPC system and phonological lexicon of the model, respectively. However, there was no evidence in support of an orthographic lexicon, weakening overall support for the model. The results are discussed with respect to the prospect of using neuroimaging in cognitive model evaluation. [ABSTRACT FROM AUTHOR]

The ongoing coronavirus disease 2019 (COVID-19) pandemic has had a widespread impact on individuals' mental health through indirect psychological and social mechanisms, related to factors such as fear of infection or death, social isolation, lack of social support and financial instability. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has also been associated with the development or recurrence of neuropsychiatric symptoms, both during the acute phase, as well as during the post-acute 'long-COVID' phase. In addition to the COVID-19 survivors with a mental health history that are at a high risk of experiencing a range of neuropsychiatric symptoms following resolution of acute COVID-19, there is accumulating evidence that a diagnosis of COVID-19 may also be associated with new-onset neuropsychiatric morbidity among survivors without pre-existing mental health disorders. In particular, studies investigating the incidence of post-acute neuropsychiatric sequelae, based mostly on retrospective cohort study designs and data from national health registries, have reported the development of new-onset manifestations, including depression, anxiety, psychotic symptoms, sleep disturbances and fatigue. Nevertheless, when COVID-19 survivors were compared with SARS-CoV-2-negative controls and especially survivors of other disorders (such as influenza), the findings regarding the risk of incident neuropsychiatric manifestations varied among studies. While there is evidence of an association between SARS-CoV-2 infection and the subsequent occurrence of new-onset neuropsychiatric symptoms, especially among patients with increased disease severity, further research using methodological approaches less susceptible to confounding bias is required to establish causal relationships. [ABSTRACT FROM AUTHOR]

The representation of visual orientation is more accurate for cardinal orientations compared to oblique, and this anisotropy has been hypothesized to reflect a low-level visual process (visual, 'class 1' oblique effect). The reproduction of directional and orientation information also leads to a mean error away from cardinal orientations or directions. This anisotropy has been hypothesized to reflect a high-level cognitive process of space categorization (cognitive, 'class 2,' oblique effect). This space categorization process would be more prominent when the visual representation of orientation degrades such as in the case of working memory with increasing cognitive load, leading to increasing magnitude of the 'class 2' oblique effect, while the 'class 1' oblique effect would remain unchanged. Two experiments were performed in which an array of orientation stimuli (1-4 items) was presented and then subjects had to realign a probe stimulus within the previously presented array. In the first experiment, the delay between stimulus presentation and probe varied, while in the second experiment, the stimulus presentation time varied. The variable error was larger for oblique compared to cardinal orientations in both experiments reproducing the visual 'class 1' oblique effect. The mean error also reproduced the tendency away from cardinal and toward the oblique orientations in both experiments (cognitive 'class 2' oblique effect). The accuracy or the reproduced orientation degraded (increasing variable error) and the cognitive 'class 2' oblique effect increased with increasing memory load (number of items) in both experiments and presentation time in the second experiment. In contrast, the visual 'class 1' oblique effect was not significantly modulated by any one of these experimental factors. These results confirmed the theoretical predictions for the two anisotropies in visual orientation reproduction and provided support for models proposing the categorization of orientation in visual working memory. [ABSTRACT FROM AUTHOR]

In this paper, a methodological scheme for identifying distinct patterns of oculomotor behavior such as saccades, microsaccades, blinks and fixations from time series of eye's angular displacement is presented. The first step of the proposed methodology involves signal detrending for artifacts removal and estimation of eye's angular velocity. Then, feature vectors from fourteen first-order statistical features are formed from each angular displacement and velocity signal using sliding, fixed-length time windows. The obtained feature vectors are used for training and testing three artificial neural network classifiers, connected in cascade. The three classifiers discriminate between blinks and non-blinks, fixations and non-fixations and saccades and microsaccades, respectively. The proposed methodology was tested on a dataset from 1392 subjects, each performing three oculomotor fixation conditions. The average overall accuracy of the three classifiers, with respect to the manual identification of eye movements by experts, was 95.9%. The proposed methodological scheme provided better results than the well-known Velocity Threshold algorithm, which was used for comparison. The findings of the present study indicate that the utilization of pattern recognition techniques in the task of identifying the various eye movements may provide accurate and robust results. [ABSTRACT FROM AUTHOR]

Abstract: Increased Reaction Time (RT) studies intra-subject variability is an emerging and consistent finding in RT studies of schizophrenia. A group of 23 patients suffering from DSM-IV schizophrenia and a group of 23 age-matched control subjects performed two RT tasks requiring basic sensorimotor processing and engaging two different motor systems: the Finger Lift Reaction Time task and the Voluntary Saccade Reaction Time task. The Ex-Gaussian model was applied to the RT distributions measuring the mean (mu), and standard deviation (sigma) of a Gaussian component thought to reflect sensorimotor processing and an exponential component (tau), thought to reflect an intermediate decision process. In both tasks, a significantly larger RT intra-subject variability effectively dissociated patients from controls. RT intra-subject variability in the two tasks was highly correlated only for patients. Both sigma and tau were significantly higher in the patient group with tau being the best predictor of schizophrenia. Furthermore, only in the patient group were sigma and tau highly correlated between the two tasks. The results reflect a deficit in information processing that may not be confined to decision processes related to the frontal cortex; rather, they may indicate dysfunction in distributed neural networks modulating adaptive regulation of performance. [Copyright &y& Elsevier]

Increased catechol-O-methyltransferase activity associated with variation in catechol-O-methyltransferase valine158 methionine genotypesmay result in reduced dopamine neurotransmission in the prefrontal cortex and thus contribute to the poor performance of frontally mediated cognitive tasks and the occurrence of associated negative symptoms observed in patients with schizophrenia; however, reported associations between catechol-O-methyltransferase valine158 methionine genotypes and measures of cognition have not been consistent.Catechol-O-methyltransferase genotyping, measures of schizotypy, cognitive measures of memory and attention, as well as the antisaccade eye movement task, a measure sensitive to prefrontal cortical function, were obtained in a sample of 543 young men representative for that age group (mean age 21 years).None of the cognitive measures was associated with catechol-O-methyltransferase valine158 methionine genotypes; however, there was an effect of high-activity allele loading on schizotypy, in particular the negative and disorganization dimensions.Previously reported inconsistencies in the relationship between catechol-O-methyltransferase valine158 methionine genotypes and cognition were not resolved; however, catechol-O-methyltransferase genotype may affect expression of negative schizotypy by direct or indirect effects on central dopamine neurotransmitter signaling. [Copyright &y& Elsevier]

This longitudinal study aimed to investigate the predictive factors of suicidal ideation during the second lockdown in Greece. The respondents presented a 4.32% suicidal ideation in the second lockdown, which did not differ significantly to the initial 4.81%. Anxiety, depression, suicidal ideation during the first lockdown and living with a person with frail health and vulnerable for COVID-19 severe infection emerged as significant risk factors for suicidal ideation during the second lockdown, after controlling for gender, age, and mental health history. Depression was found as the only significant prognostic factor for suicidal ideation incidence of the second lockdown. [ABSTRACT FROM AUTHOR]

Background: Deficits in Multisensory Integration (MSI) in ASD have been reported repeatedly and have been suggested to be caused by altered long-range connectivity. Here we investigate behavioral and ERP correlates of MSI in ASD using ecologically valid videos of emotional expressions., Methods: In the present study, we set out to investigate the electrophysiological correlates of audiovisual MSI in young autistic and neurotypical adolescents. We employed dynamic stimuli of high ecological validity (500 ms clips produced by actors) that depicted fear or disgust in unimodal (visual and auditory), and bimodal (audiovisual) conditions., Results: We report robust MSI effects at both the behavioral and electrophysiological levels and pronounced differences between autistic and neurotypical participants. Specifically, neurotypical controls showed robust behavioral MSI for both emotions as seen through a significant speed-up of bimodal response time (RT), confirmed by Miller's Race Model Inequality (RMI), with greater MSI effects for fear than disgust. Adolescents with ASD, by contrast, showed behavioral MSI only for fear. At the electrophysiological level, the bimodal condition as compared to the unimodal conditions reduced the amplitudes of the visual P100 and auditory P200 and increased the amplitude of the visual N170 regardless of group. Furthermore, a cluster-based analysis across all electrodes revealed that adolescents with ASD showed an overall delayed and spatially constrained MSI effect compared to controls., Conclusion: Given that the variables we measured reflect attention, our findings suggest that MSI can be modulated by the differential effects on attention that fear and disgust produce. We also argue that the MSI deficits seen in autistic individuals can be compensated for at later processing stages by (a) the attention-orienting effects of fear, at the behavioral level, and (b) at the electrophysiological level via increased attentional effort ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Stefanou, Dundon, Bestelmeyer, Biscaldi, Smyrnis and Klein.)

A guideline is proposed that comprises the minimum items to be reported in research studies involving an eye tracker and human or non-human primate participant(s). This guideline was developed over a 3-year period using a consensus-based process via an open invitation to the international eye tracking community. This guideline will be reviewed at maximum intervals of 4 years., (© 2023. The Author(s).)

Background: This study investigated patient- and caregiver-related predictors of expressed emotion (EE) toward individuals with schizophrenia in families and halfway houses and yet understudied differential effects across settings., Methods: We included 40 individuals with schizophrenia living with their families ("outpatients") and 40 "inpatients" in halfway houses and recorded the EE of 56 parents or 22 psychiatric nurses, respectively, through Five Minutes Speech Sample. Each outpatient was rated by one to two parents; each inpatient was rated by two to five nurses. As EE ratings had a multilevel structure, EE predictors were investigated in backward stepwise generalized linear mixed models using the "buildmer" R package. We first fitted models including either caregiver- or patient-related predictors in each setting and finally included both types of predictors. Setting-specific patient-related effects were investigated in interaction analyses. Adjustment for multiple tests identified the most robust associations., Results: In multivariate models including either caregiver- or patient-related predictors, nurses' higher age, shorter work experience and lower inpatients' negative symptoms robustly predicted higher emotional overinvolvement (EOI). In the final models including both types of predictors, nurses robustly displayed lower EOI (i.e., reduced concern and disengagement) toward inpatients with higher negative symptoms. Several other features were nominally associated with criticism and EOI in each setting. However, no feature robustly predicted criticism in inpatients and criticism/EOI in outpatients after adjustment for multiple tests. In interaction analyses, higher negative symptoms differentially predicted lower EOI in nurses only., Conclusion: Our findings suggest setting-specific pathogenetic pathways of EOI and might help customize psychoeducational interventions to staff in halfway houses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ferentinos, Douki, Kourkouni, Dragoumi, Smyrnis and Douzenis.)

Expressed emotion (EE) toward patients with schizophrenia is typically reported to be lower in psychiatric halfway houses than in families. This is the first study directly comparing EE between these settings and investigating the pathways mediating EE differences. We included 40 inpatients in halfway houses and 40 outpatients living with their families and recorded 22 psychiatric nurses' and 56 parents' EE, respectively, through Five Minutes Speech Samples. Each inpatient was rated by 2-5 nurses and each outpatient by 1-2 parents. As EE ratings had a multilevel structure, generalized linear mixed models were fitted, adjusting for patient-related confounders and caregiver demographics. Mediatory effects were investigated in multilevel structural equation models. Outpatients were younger, less chronic, and better educated, with higher negative symptoms and perceived criticism than inpatients. Nurses were younger and better educated than parents. Before adjustment, EE rates were equally high across settings. After adjusting for patient-related confounders, emotional overinvolvement was significantly higher in parents. However, after also adjusting for caregiver demographics, only criticism was significantly higher in nurses. Patients' age, negative symptoms, and perceived criticism and caregivers' age and sex significantly mediated EE group differences. Our findings highlight pathways underlying EE differences between halfway houses and families and underscore the importance of staff and family psychoeducation.

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder with various medical and psychological adverse effects. Well-being in patients with T2DM is often compromised. The aim of the present study was to investigate clinicodemographic predictors of well-being in patients with T2DM with no known psychiatric history and explore the mediatory role of undiagnosed anxiety and depression. We recruited 175 outpatients with T2DM (54.3% males, aged 34-79 (mean 59.9) years) followed-up at the Diabetes Center of the General Hospital of Nikaia-Peiraeus in Athens. Patients included had no severe diabetes-related complications or known psychiatric history. Well-being was measured with the Mental Health Continuum Short-Form (MHC-SF), a novel 14-item tool measuring the emotional (EWB), social (SWB) and psychological (PWB) dimensions of well-being, as well as a total score of well-being (WBT). Hospital Anxiety and Depression Scale (HADS) was used for screening for undiagnosed anxiety (HADS-A) and depression (HADS-D). Patients' demographics, Body Mass Index (BMI), glycemic control (HbA1c), T2DM duration, comorbid hypertension or dyslipidemia and type of antidiabetic medication were investigated as predictors of well-being or its dimensions in stepwise linear regression models, also including or excluding HADS-A and HADS-D. Mediational effects of HADS-A and HADS-D were explored in structural equation models through path analyses. Results showed that 21.1% of participants had comorbid depression (HADS-D≥11) and 5.1% comorbid anxiety disorder (HADS-A≥11). In the models without HADS, higher WBT as well as EWB and PWB were significantly predicted by lower HbA1c (all p=0.001) and lower BMI (p=0.015, 0.019 and 0.030, respectively). After being included in the model, HADS-A and HADS-D significantly predicted WBT and every dimension of well-being, but the effects of HbA1c and BMI were no longer statistically significant. In path analyses, the indirect effects of HbA1c and BMI on well-being via HADS-D were statistically significant, while the direct and indirect effects via HADS-A were not. Therefore, the effects of HbA1c and BMI on EWB, PWB and WBT were completely mediated by HADS-D. Concludingly, this is the first study using MHC-SF to measure well-being in patients with T2DM. High levels of undiagnosed depression were recorded, in agreement with other studies. Depression was predicted by HbA1c and BMI and finally predicted well-being. Undiagnosed depression fully explained the effects of HbA1c and BMI on well-being. The interplay of glycemic control and positive mental health should be further investigated.

Introduction: Monitoring biometric data using smartwatches (digital phenotypes) provides a novel approach for quantifying behavior in patients with psychiatric disorders. We tested whether such digital phenotypes predict changes in psychopathology of patients with psychotic disorders., Methods: We continuously monitored digital phenotypes from 35 patients (20 with schizophrenia and 15 with bipolar spectrum disorders) using a commercial smartwatch for a period of up to 14 months. These included 5-min measures of total motor activity from an accelerometer (TMA), average Heart Rate (HRA) and heart rate variability (HRV) from a plethysmography-based sensor, walking activity (WA) measured as number of total steps per day and sleep/wake ratio (SWR). A self-reporting questionnaire (IPAQ) assessed weekly physical activity. After pooling phenotype data, their monthly mean and variance was correlated within each patient with psychopathology scores (PANSS) assessed monthly., Results: Our results indicate that increased HRA during wakefulness and sleep correlated with increases in positive psychopathology. Besides, decreased HRV and increase in its monthly variance correlated with increases in negative psychopathology. Self-reported physical activity did not correlate with changes in psychopathology. These effects were independent from demographic and clinical variables as well as changes in antipsychotic medication dose., Discussion: Our findings suggest that distinct digital phenotypes derived passively from a smartwatch can predict variations in positive and negative dimensions of psychopathology of patients with psychotic disorders, over time, providing ground evidence for their potential clinical use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kalisperakis, Karantinos, Lazaridi, Garyfalli, Filntisis, Zlatintsi, Efthymiou, Mantas, Mantonakis, Mougiakos, Maglogiannis, Tsanakas, Maragos and Smyrnis.)

Working memory (WM) impairments are well recognized in schizophrenia patients (PSZ) and contribute to poor psycho-social outcomes in this population. Distinct neural networks underlay the ability to encode and recall visual and spatial information raising the possibility that profile of visual working memory performance may help pinpoint dysfunctional neural correlates in schizophrenia. This study assessed the resolution and associative aspects of visual working memory deficits in schizophrenia and whether these deficits arise during encoding or maintenance processes. A total of 60 participants (30 PSZ and 30 healthy controls) matched in age, gender and education assessed on a modified object in place (OiPT), a delayed non-match-to-sample (DNMST) and a delayed spatial estimation (DSET) task. Patients demonstrated lower accuracy than controls in binding visual features of the same object and recognizing novel objects as well as lower precision recalling the location of a memorized target. Moreover, response choice set size affected recognition accuracy more in PSZ than controls. However, delay duration affected spatial recall precisions, binding, and recognition accuracy equally in the two groups. Our results suggest that visual working memory (vWM) impairments in schizophrenia predominantly reflect spatial and non-spatial binding deficits, with largely preserved discrete feature information. Moreover, these impairments likely arise more during encoding than during maintenance. These binding deficits may reflect impaired effective neural functional connectivity observed in schizophrenia., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Background: The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia., Methods: Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects., Results: There was a 3-year later age at onset for females ( P  < .001) and lower rates of negative symptoms ( P  < .01) and higher depression/anxiety measures ( P  < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages ( P  = .001). No significant effects were found concerning duration of illness., Discussion: Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

Background: This study examined the connection between two prominent deficits in schizophrenia: the deficit in parasympathetic regulation and the deficit in cognitive inhibitory control, within the framework of the Neurovisceral Integration Model (NIM)., Study Design: Thirty healthy controls and 30 patients with schizophrenia performed the internationally standardized antisaccade protocol while their electrocardiographic data were recorded. The interaction between the group, the cognitive inhibitory control as measured with error rate (ER) in the antisaccade task and parasympathetic activity as measured with the High Frequency power component of Heart Rate Variability (HF-HRV) was tested., Study Results: Findings confirmed that decreased HF-HRV was specifically related to increased ER in patients with schizophrenia. In contrast, patient deficits in other oculomotor function measures such as reaction time and reaction time variability related to volitional movement control and cognitive stability respectively were not linked to the deficit in parasympathetic regulation., Conclusions: Our study validates the theory behind NIM proposing that cognitive inhibition has common physiological substrate with parasympathetic regulation. Future research could test this brain-heart link in other mental disorders especially those with a prominent deficit in inhibitory cognitive function., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

While Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD) and Schizophrenia (SCZ) differ in many clinically relevant features such as symptomatology and course, they may also share genetic underpinnings, affective problems, deviancies in social interactions, and are all characterized by some kind of cognitive impairment. This situation calls for a joint investigation of the specifics of cognitive (dys-)functions of the three disorders. Such endeavor should focus, among other domains, on the inter-section of processing cognitive, affective and social information that is crucial in effective real-life interactions and can be accomplished when attentional preferences for human facial expressions of emotions is studied. To that end, attention to facial expressions of basic emotions was examined in young adults with ASD, ADHD, or SCZ in the present study. The three clinical groups were compared with an age-matched group of typically-developing participants (TD) during the free contemplation of five different facial emotions presented simultaneously, by varying identities, through the registration of eye movements. We showed, that dwell times and fixation counts differed for the different emotions in TD and in a highly similar way in ADHD. Patients with ASD differed from TD by showing a stronger differentiation between emotions and partially different attentional preferences. In contrast, the SCZ group showed an overall more restricted scanning behavior and a lack of differentiation between emotions. The ADHD group, showed an emotion-specific gazing pattern that was highly similar to that of controls. Thus, by analyzing eye movements, we were able to differentiate three different viewing patterns that allowed us to distinguish between the three clinical groups. This outcome suggests that attention for emotion may not tap into common pathophysiological processes and argues for a multi-dimensional approach to the grouping of disorders with neurodevelopmental etiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bretthauer, Canu, Thiemann, Fleischhaker, Brauner, Müller, Smyrnis, Biscaldi, Bender and Klein.)

There is a growing body of evidence highlighting the role of gut microbiota as a biological basis of psychiatric disorders. The existing literature suggest that cognitive and emotional activities can be influenced by microbes through the microbiota-gut-brain axis and implies an association between alterations in the gut microbiome and several psychiatric conditions, such as autism, depression, bipolar disorder and psychosis. The aim of this review is to summarise recent findings and provide concise updates on the latest progress of the role of gut microbiota in the development and maintenance of psychiatric symptoms in schizophrenia and the first episode of psychosis. Despite the lack of consistent findings in regard to specific microbiome changes related to psychosis, the emerging literature reports significant differences in the gut microbiome of schizophrenic subjects compared to healthy controls and increasingly outlines the significance of an altered microbiome composition in the pathogenesis, development, symptom severity and prognosis of psychosis. Further human studies are, however, required, which should focus on identifying the drivers of microbiota changes in psychosis and establish the direction of causality between psychosis and microbiome alterations.

Paradoxes are a special form of reasoning leading to absurd inferences in contrast to logical reasoning that is used to reach valid conclusions. A functional MRI (fMRI) study was conducted to investigate the neural substrates of paradoxical and deductive reasoning. Twenty-four healthy participants were scanned using fMRI, while they engaged in reasoning tasks based on arguments, which were either Zeno's like paradoxes (paradoxical reasoning) or Aristotelian arguments (deductive reasoning). Clusters of significant activation for paradoxical reasoning were located in bilateral inferior frontal and middle temporal gyrus. Clusters of significant activation for deductive reasoning were located in bilateral superior and inferior parietal lobe, precuneus, and inferior frontal gyrus. These results confirmed that different brain activation patterns are engaged for paradoxical vs. deductive reasoning providing a basis for future studies on human physiological as well as pathological reasoning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Belekou, Papageorgiou, Karavasilis, Tsaltas, Kelekis, Klein and Smyrnis.)

Interleukin-1 beta (IL1β) is primarily produced by monocytes in the periphery and the brain. Yet, IL1β protein levels have to date been investigated in major depressive disorder (MDD) and antidepressant response using either plasma or serum assays although with contradictory results, while mononuclear cell assays are lacking despite their extensive use in other contexts. In this pilot study, we comparatively assessed IL1β in mononuclear lysates and plasma in depressed MDD patients over treatment and healthy controls (HC). We recruited 31 consecutive adult MDD inpatients and 25 HC matched on age, sex, and BMI. Twenty-six patients completed an 8-week follow-up under treatment. IL1β was measured in both lysates and plasma in patients at baseline (T0) and at study end (T1) as well as in HC. We calculated ΔIL1β(%) for both lysates and plasma as IL1β percent changes from T0 to T1. Seventeen patients (65.4% of completers) were responders at T1 and had lower baseline BMI than non-responders ( p = 0.029). Baseline IL1β from either plasma or lysates could not efficiently discriminate between depressed patients and HC, or between responders and non-responders. However, the two response groups displayed contrasting IL1β trajectories in lysates but not in plasma assays (response group by time interactions, p = 0.005 and 0.96, respectively). ΔIL1β(%) in lysates predicted response ( p = 0.025, AUC = 0.81; accuracy = 84.6%) outperforming ΔIL1β(%) in plasma ( p = 0.77, AUC=0.52) and was robust to adjusting for BMI. In conclusion, ΔIL1β(%) in mononuclear lysates may be a longitudinal biomarker of antidepressant response, potentially helpful in avoiding untimely switching of antidepressants, thereby warranting further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ferentinos, Maratou, Antoniou, Serretti, Smyrnis and Moutsatsou.)

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing., (© 2021. The Author(s).)

Chronic cannabis use and schizophrenia are both thought to affect reward processing. While behavioural and neural effects on reward processing have been investigated in both conditions, their interaction has not been studied, although chronic cannabis use is common among these patients. In the present study eighty-nine participants divided into four groups (control chronic cannabis users and non-users; schizophrenia patient cannabis users and non-users) performed a two-choice decision task, preceded by monetary cues (high/low reward/punishment or neutral), while being scanned using functional magnetic resonance imaging. Reward and punishment anticipation resulted in activation of regions of interest including the thalamus, striatum, amygdala and insula. Chronic cannabis use and schizophrenia had opposing effects on reward anticipation sensitivity. More specifically control users and patient non-users showed faster behavioural responses and increased activity in anterior/posterior insula for high magnitude cues compared to control non-users and patient users. The same interaction pattern was observed in the activation of the right thalamus for reward versus punishment cues. This study provided evidence for interaction of chronic cannabis use and schizophrenia on reward processing and highlights the need for future research addressing the significance of this interaction for the pathophysiology of these conditions and its clinical consequences.

Sensory processing deficits and altered long-range connectivity putatively underlie Multisensory Integration (MSI) deficits in Autism Spectrum Disorder (ASD). The present study set out to investigate non-social MSI stimuli and their electrophysiological correlates in young neurotypical adolescents and adolescents with ASD. We report robust MSI effects at behavioural and electrophysiological levels. Both groups demonstrated normal behavioural MSI. However, at the neurophysiological level, the ASD group showed less MSI-related reduction of the visual P100 latency, greater MSI-related slowing of the auditory P200 and an overall temporally delayed and spatially constrained onset of MSI. Given the task design and patient sample, and the age of our participants, we argue that electro-cortical indices of MSI deficits in ASD: (a) can be detected in early-adolescent ASD, (b) occur at early stages of perceptual processing, (c) can possibly be compensated by later attentional processes, (d) thus leading to normal MSI at the behavioural level.

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected ("concordant") direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive ("discordant") relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10 -8 . Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms-early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways-that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness., (Copyright © 2019. Published by Elsevier Inc.)

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol. 21, 2017, 2597-2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229-237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from 'inflation in the FDR [false discovery rate]', as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88), and are not 'more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence'.

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7 , but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10 -8 ) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Schizotypal personality traits may increase proneness to psychosis and likely index familial vulnerability to schizophrenia (SZ), implying shared genetic determinants with SZ. Here, we sought to investigate the contribution of common genetic risk variation for SZ on self-reported schizotypy in 2 ethnically homogeneous cohorts of healthy young males during compulsory military service, enrolled in the Athens Study of Proneness and Incidence of Schizophrenia (ASPIS, N = 875) and the Learning on Genetics of Schizophrenia Spectrum study (LOGOS, N = 690). A follow-up psychometric assessment was performed in a sub-sample of the ASPIS (N = 121), 18 months later at military service completion. Polygenic risk scores (PRS) for SZ were derived based on genome-wide association meta-analysis results from the Psychiatric Genomics Consortium. In the ASPIS, higher PRSSZ significantly associated with lower levels of positive (ie, perceptual distortions), disorganization and paranoid facets of schizotypy, whereas no association with negative (ie, interpersonal) facets was noted. Importantly, longitudinal data analysis in the ASPIS subsample revealed that PRSSZ was inversely associated with positive schizotypy at military induction (stressed condition) but not at follow-up (nonstressed condition), providing evidence for environmental rather than SZ-implicated genetic influences. Moreover, consistent with prior reports, PRSSZ was positively correlated with trait anxiety in the LOGOS and additionally the recruits with higher PRSSZ and trait anxiety exhibited attenuated paranoid ideation. Together, these findings do not support an etiological link between increased polygenic liability for SZ and schizotypy, suggesting that psychosocial stress or trait anxiety may impact schizotypal phenotypic expressions among healthy young adults not genetically predisposed to SZ.

Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)