Classification of Major Depressive Disorder via Multi-Site Weighted LASSO Model

Large-scale collaborative analysis of brain imaging data, in psychiatry and neurology, offers a new source of statistical power to discover features that boost accuracy in disease classification, differential diagnosis, and outcome prediction. However, due to data privacy regulations or limited accessibility to large datasets across the world, it is challenging to efficiently integrate distributed information. Here we propose a novel classification framework through multi-site weighted LASSO: each site performs an iterative weighted LASSO for feature selection separately. Within each iteration, the classification result and the selected features are collected to update the weighting parameters for each feature. This new weight is used to guide the LASSO process at the next iteration. Only the features that help to improve the classification accuracy are preserved. In tests on data from five sites (299 patients with major depressive disorder (MDD) and 258 normal controls), our method boosted classification accuracy for MDD by 4.9% on average. This result shows the potential of the proposed new strategy as an effective and practical collaborative platform for machine learning on large scale distributed imaging and biobank data

Acceptability and feasibility of a multidomain harmonized data collection protocol in youth mental health

Objective To develop targeted treatment for young people experiencing mental illness, a better understanding of the biological, psychological, and social changes is required, particularly during the early stages of illness. To do this, large datasets need to be collected using standardized methods. A harmonized data collection protocol was tested in a youth mental health research setting to determine its acceptability and feasibility. Method Eighteen participants completed the harmonization protocol, including a clinical interview, self-report measures, neurocognitive measures, and mock assessments of magnetic resonance imaging (MRI) and blood. The feasibility of the protocol was assessed by recording recruitment rates, study withdrawals, missing data, and protocol deviations. Subjective responses from participant surveys and focus groups were used to examine the acceptability of the protocol. Results Twenty-eight young people were approached, 18 consented, and four did not complete the study. Most participants reported positive subjective impressions of the protocol as a whole and showed interest in participating in the study again, if given the opportunity. Participants generally perceived the MRI and neurocognitive tasks as interesting and suggested that the assessment of clinical presentation could be shortened. Conclusion Overall, the harmonized data collection protocol appeared to be feasible and generally well-accepted by participants. With a majority of participants finding the assessment of clinical presentation too long and repetitive, the authors have made suggestions to shorten the self-reports. The broader implementation of this protocol could allow researchers to create large datasets and better understand how psychopathological and neurobiological changes occur in young people with mental ill-health

Transdiagnostic structural neuroimaging features in depression and psychosis:A systematic review

Background: Previous research suggests that there may be similarities in structural brain changes seen in patients with depression and psychosis compared to healthy controls. However, there is yet no systematic review collating studies comparing structural brain changes in depression and psychosis. Establishing shared and specific neuroanatomical features could aid the investigation of underlying biological processes. Aims: To identify structural neuroimaging similarities and differences between patients with depression and psychosis. Method: We searched PubMed, PsychInfo, Embase, NICE Evidence, Medline and the Cochrane Library were searched from inception to 30/06/2021 using relevant subject headings (controlled vocabularies) and search syntax. Papers were assessed for quality using the Newcastle-Ottawa Scale. Results: Five-hundred and twenty papers were retrieved, seven met inclusion criteria. In narrative collation of results, grey matter volume (GMV) reductions were found in the medial frontal gyrus (MFG), hippocampus and left-sided posterior subgenual prefrontal cortex in both psychosis and depression. GMV reductions affected more brain regions in psychosis, including in the insula and thalamus. White matter volume (WMV) decline was found in both depression and psychosis. Reduced fractional anisotropy (FA) was more commonly seen in depression. Conclusions: Our results suggest potential transdiagnostic patterns of GMV and WMV reductions in areas including the MFG, hippocampus, and left-sided posterior subgenual prefrontal cortex. These could be investigated as a future biomarker of transdiagnostic signature across mental illnesses. However, due to the limited number and poor quality of studies future research in large samples and harmonised imaging data is first needed

Structural and Functional Brain Abnormalities Associated With Exposure to Different Childhood Trauma Subtypes: A Systematic Review of Neuroimaging Findings

Background: Childhood trauma subtypes sexual abuse, physical abuse, emotional maltreatment, and neglect may have differential effects on the brain that persist into adulthood. A systematic review of neuroimaging findings supporting these differential effects is as yet lacking.Objectives: The present systematic review aims to summarize the findings of controlled neuroimaging trials regarding long-term differential effects of trauma subtypes on the human brain.Methods: A systematic literature search was performed using the PubMed and PsycINFO databases from January 2017 up to and including January 2018. Additional papers were identified by a manual search in the reference lists of selected papers and of relevant review articles retrieved by the initial database search. Studies were then assessed for eligibility by the first author. Only original human studies directly comparing neuroimaging findings of exposed and unexposed individuals to well-defined emotional, physical or sexual childhood maltreatment while controlling for the effects of other subtypes were included. A visual summary of extracted data was made for neuroimaging modalities for which comparison between trauma subtypes was feasible, taking the studies' numbers and sample sizes into account.Results: The systematic literature search yielded 25 publications. Sexual abuse was associated with structural deficits in the reward circuit and genitosensory cortex and amygdalar hyperreactivity during sad autobiographic memory recall. Emotional maltreatment correlated with abnormalities in fronto-limbic socioemotional networks. In neglected individuals, white matter integrity and connectivity were disturbed in several brain networks involved in a variety of functions. Other abnormalities, such as reduced frontal cortical volume, were common to all maltreatment types.Conclusions: There is some evidence for long-term differential effects of trauma subtypes on the human brain. The observed alterations may result from both protective adaptation of and damage to the brain following exposure to threatening life events. Though promising, the current evidence is incomplete, with few brain regions and neuroimaging modalities having been investigated in all subtypes. The comparability of the available evidence is further limited by the heterogeneity of study populations regarding gender, age and comorbid psychopathology. Future neuroimaging studies should take this potentially differential role of childhood trauma subtypes into account

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

SmartSense-D:A safety, feasibility, and acceptability pilot study of digital phenotyping in young people with major depressive disorder

Background: Digital assessment of behaviours, including physical activity, sleep, and social interactions could be associated with changes in mood and other mental health symptoms. This study assessed the safety, feasibility, acceptability, and potential predictive value of passive and active sensing in young people with major depressive disorder (MDD). Methods: Over eight weeks, passive (smartphone sensing, actigraphy) and active (ecological momentary assessment; EMA) data were collected from 40 young participants with MDD (aged 16–25 years). We assessed the safety, feasibility, and acceptability of daily active and passive sensing in this population. Additionally, linear mixed models and correlation analysis explored associations between passive and active sensing measures. Results: Of the 48 young participants, 83% (n = 40) completed the full protocol. No adverse events were reported. Over eight weeks, participants averaged 35.9 days (65.3%) with EMAs and 37.9 days (69%) with actigraphy data. Smartphone sensors recorded communication for 21.1 days (38.4%), location for 43.1 days (78.4%), maximum unlock duration for 43.4 days (79%), social media use for 34.8 days (63.3%), and inter-key delay for 32.8 days (59.6%). Regarding acceptability, 83.1% found the application usable and comfortable. Secondary measures showed significant correlations between sleep and physical activity, and between location and phone use sensors. There was a significant negative association between daily positive mood ratings and QIDS total scores (Beta coefficient [95% CI]: 2.66 [−3.98, −1.34]; p = 0.002). Conclusion: Passive and active sensing methods were safe, and acceptable among young people with MDD.</p

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness