A review of diffusion MRI in mood disorders: mechanisms and predictors of treatment response.

By measuring the molecular diffusion of water molecules in brain tissue, diffusion MRI (dMRI) provides unique insight into the microstructure and structural connections of the brain in living subjects. Since its inception, the application of dMRI in clinical research has expanded our understanding of the possible biological bases of psychiatric disorders and successful responses to different therapeutic interventions. Here, we review the past decade of diffusion imaging-based investigations with a specific focus on studies examining the mechanisms and predictors of therapeutic response in people with mood disorders.

Modulation of habenular and nucleus accumbens functional connectivity by ketamine in major depression.

Introduction: Major depressive disorder (MDD) is associated with dysfunctional reward processing, which involves functional circuitry of the habenula (Hb) and nucleus accumbens (NAc). Since ketamine elicits rapid antidepressant and antianhedonic effects in MDD, this study sought to investigate how serial ketamine infusion (SKI) treatment modulates static and dynamic functional connectivity (FC) in Hb and NAc functional networks.

Methods: MDD participants (n = 58, mean age = 40.

Ketamine treatment modulates habenular and nucleus accumbens static and dynamic functional connectivity in major depression.

Dysfunctional reward processing in major depressive disorder (MDD) involves functional circuitry of the habenula (Hb) and nucleus accumbens (NAc). Ketamine elicits rapid antidepressant and alleviates anhedonia in MDD. To clarify how ketamine perturbs reward circuitry in MDD, we examined how serial ketamine infusions (SKI) modulate static and dynamic functional connectivity (FC) in Hb and NAc networks.

Hippocampal subfield volumes in treatment resistant depression and serial ketamine treatment.

Introduction: Subanesthetic ketamine is a rapidly acting antidepressant that has also been found to improve neurocognitive performance in adult patients with treatment resistant depression (TRD). Provisional evidence suggests that ketamine may induce change in hippocampal volume and that larger pre-treatment volumes might be related to positive clinical outcomes. Here, we examine the effects of serial ketamine treatment on hippocampal subfield volumes and relationships between pre-treatment subfield volumes and changes in depressive symptoms and neurocognitive performance.

White matter microstructural perturbations after total sleep deprivation in depression.

Background: Total sleep deprivation (TSD) transiently reverses depressive symptoms in a majority of patients with depression. How TSD modulates diffusion tensor imaging (DTI) measures of white matter (WM) microstructure, which may be linked with TSD's rapid antidepressant effects, remains uncharacterized.

Methods: Patients with depression ( = 48, mean age = 33, 26 women) completed diffusion-weighted imaging and Hamilton Depression Rating (HDRS) and rumination scales before and after >24 h of TSD.

Neurocognitive effects of subanesthetic serial ketamine infusions in treatment resistant depression.

Introduction: Ketamine treatment prompts a rapid antidepressant response in treatment-resistant depression (TRD). We performed an exploratory investigation of how ketamine treatment in TRD affects different cognitive domains and relates to antidepressant response.

Methods: Patients with TRD (N = 66; 30 M/35F; age = 39.

Changes in white matter microstructure following serial ketamine infusions in treatment resistant depression.

Ketamine produces fast-acting antidepressant effects in treatment resistant depression (TRD). Though prior studies report ketamine-related changes in brain activity in TRD, understanding of ketamine's effect on white matter (WM) microstructure remains limited. We thus sought to examine WM neuroplasticity and associated clinical improvements following serial ketamine infusion (SKI) in TRD.

A critical role of brain network architecture in a continuum model of autism spectrum disorders spanning from healthy individuals with genetic liability to individuals with ASD.

Studies have shown cortical alterations in individuals with autism spectrum disorders (ASD) as well as in individuals with high polygenic risk for ASD. An important addition to the study of altered cortical anatomy is the investigation of the underlying brain network architecture that may reveal brain-wide mechanisms in ASD and in polygenic risk for ASD. Such an approach has been proven useful in other psychiatric disorders by revealing that brain network architecture shapes (to an extent) the disorder-related cortical alterations.

Schizophrenia Polygenic Risk During Typical Development Reflects Multiscale Cortical Organization.

Background: Schizophrenia is widely recognized as a neurodevelopmental disorder. Abnormal cortical development in otherwise typically developing children and adolescents may be revealed using polygenic risk scores for schizophrenia (PRS-SCZ).

Methods: We assessed PRS-SCZ and cortical morphometry in typically developing children and adolescents (3-21 years, 46.

Tractostorm 2: Optimizing tractography dissection reproducibility with segmentation protocol dissemination.

The segmentation of brain structures is a key component of many neuroimaging studies. Consistent anatomical definitions are crucial to ensure consensus on the position and shape of brain structures, but segmentations are prone to variation in their interpretation and execution. White-matter (WM) pathways are global structures of the brain defined by local landmarks, which leads to anatomical definitions being difficult to convey, learn, or teach.

Cortical Surfaces Integration with Tractography for Structural Connectivity Analysis.

Mapping diffusion MRI tractography streamlines to the cortical surface facilitates the integration of white matter features onto gray matter, especially for connectivity analysis. In this work, we present methods that combine cortical surface meshes with tractography reconstruction to improve endpoint precision and coverage. This cortical mapping also enables the study of structural measures from tractography along the cortex and subcortical structures.

Distinct influence of parental occupation on cortical thickness and surface area in children and adolescents: Relation to self-esteem.

Studies of socioeconomic disparities have largely focused on correlating brain measures with either composite measure of socioeconomic status (SES), or its components-family income or parental education, giving little attention to the component of parental occupation. Emerging evidence suggests that parental occupation may be an important and neglected indicator of childhood and adolescent SES compared to absolute measures of material resources or academic attainment because, while related, it may more precisely capture position in social hierarchy and related health outcomes. On the other hand, although cortical thickness and surface area are brain measures with distinct genetic and developmental origins, large-scale neuroimaging studies investigating regional differences in interaction of the composite measure of SES or its components with cortical thickness and surface area are missing.

Neural correlates of polygenic risk score for autism spectrum disorders in general population.

Autism spectrum disorder is a highly prevalent and highly heritable neurodevelopmental condition, but studies have mostly taken traditional categorical diagnosis approach (yes/no for autism spectrum disorder). In contrast, an emerging notion suggests a continuum model of autism spectrum disorder with a normal distribution of autistic tendencies in the general population, where a full diagnosis is at the severe tail of the distribution. We set out to investigate such a viewpoint by investigating the interaction of polygenic risk scores for autism spectrum disorder and Age on neuroimaging measures (cortical thickness and white matter connectivity) in a general population (=391, with age ranging from 3 to 21 years from the Pediatric Imaging, Neurocognition and Genetics study).

Genome-wide mapping of brain phenotypes in extended pedigrees with strong genetic loading for bipolar disorder.

Bipolar disorder is a highly heritable illness, associated with alterations of brain structure. As such, identification of genes influencing inter-individual differences in brain morphology may help elucidate the underlying pathophysiology of bipolar disorder (BP). To identify quantitative trait loci (QTL) that contribute to phenotypic variance of brain structure, structural neuroimages were acquired from family members (n = 527) of extended pedigrees heavily loaded for bipolar disorder ascertained from genetically isolated populations in Latin America.

Brain status modeling with non-negative projective dictionary learning.

Accurate prediction of individuals' brain age is critical to establish a baseline for normal brain development. This study proposes to model brain development with a novel non-negative projective dictionary learning (NPDL) approach, which learns a discriminative representation of multi-modal neuroimaging data for predicting brain age. Our approach encodes the variability of subjects in different age groups using separate dictionaries, projecting features into a low-dimensional manifold such that information is preserved only for the corresponding age group.

Neurodegenerative disease biomarkers Aβ, Aβ, tau, and p-tau in the vervet monkey cerebrospinal fluid: Relation to normal aging, genetic influences, and cerebral amyloid angiopathy.

Background: The Caribbean vervet monkey () is a potentially valuable animal model of neurodegenerative disease. However, the trajectory of aging in vervets and its relationship to human disease is incompletely understood.

Methods: To characterize biomarkers associated with neurodegeneration, we measured cerebrospinal fluid (CSF) concentrations of Aβ, Aβ, total tau, and p-tau in 329 members of a multigenerational pedigree.

JAKMIP1, a Novel Regulator of Neuronal Translation, Modulates Synaptic Function and Autistic-like Behaviors in Mouse.

Autism spectrum disorder (ASD) is a heritable, common neurodevelopmental disorder with diverse genetic causes. Several studies have implicated protein synthesis as one among several of its potential convergent mechanisms. We originally identified Janus kinase and microtubule-interacting protein 1 (JAKMIP1) as differentially expressed in patients with distinct syndromic forms of ASD, fragile X syndrome, and 15q duplication syndrome.

Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span.

Multisystem component phenotypes of bipolar disorder for genetic investigations of extended pedigrees.

Importance: Genetic factors contribute to risk for bipolar disorder (BP), but its pathogenesis remains poorly understood. A focus on measuring multisystem quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that affect BP as well as its component phenotypes.

Objective: To identify quantitative neurocognitive, temperament-related, and neuroanatomical phenotypes that appear heritable and associated with severe BP (bipolar I disorder [BP-I]) and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk.