Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium.

Developmental emergence of cortical neurogliaform cell diversity.

GABAergic interneurons are key regulators of cortical circuit function. Among the dozens of reported transcriptionally distinct subtypes of cortical interneurons, neurogliaform cells (NGCs) are unique: they are recruited by long-range excitatory inputs, are a source of slow cortical inhibition and are able to modulate the activity of large neuronal populations. Despite their functional relevance, the developmental emergence and diversity of NGCs remains unclear.

Bimodal modulation of L1 interneuron activity in anterior cingulate cortex during fear conditioning.

The anterior cingulate cortex (ACC) plays a crucial role in encoding, consolidating and retrieving memories related to emotionally salient experiences, such as aversive and rewarding events. Various studies have highlighted its importance for fear memory processing, but its circuit mechanisms are still poorly understood. Cortical layer 1 (L1) of the ACC might be a particularly important site of signal integration, since it is a major entry point for long-range inputs, which is tightly controlled by local inhibition.

Dysfunctional temporal stages of eye-gaze perception in adults with ADHD: A high-density EEG study.

ADHD has been associated with social cognitive impairments across the lifespan, but no studies have specifically addressed the presence of abnormalities in eye-gaze processing in the adult brain. This study investigated the neural basis of eye-gaze perception in adults with ADHD using event-related potentials (ERP). Twenty-three ADHD and 23 controls performed a delayed face-matching task with neutral faces that had either direct or averted gaze.

Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach.

Background: Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.

Aims: To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.

Downregulation of the schizophrenia risk-gene Dgcr2 alters early microcircuit development in the mouse medial prefrontal cortex.

Alterations in the generation, migration and integration of different subtypes of neurons in the medial prefrontal cortex (mPFC) microcircuit could play an important role in vulnerability to schizophrenia. Using in vivo cell-type specific manipulation of pyramidal neurons (PNs) progenitors, we aim to investigate the role of the schizophrenia risk-gene DiGeorge Critical Region 2 (Dgcr2) on cortical circuit formation in the mPFC of developing mice. This report describes how Dgcr2 knock down in upper-layer PNs impacts the functional maturation of PNs and interneurons (INs) in the mPFC.

Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients.

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium's therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes.

Temporal controls over inter-areal cortical projection neuron fate diversity.

Interconnectivity between neocortical areas is critical for sensory integration and sensorimotor transformations. These functions are mediated by heterogeneous inter-areal cortical projection neurons (ICPN), which send axon branches across cortical areas as well as to subcortical targets. Although ICPN are anatomically diverse, they are molecularly homogeneous, and how the diversity of their anatomical and functional features emerge during development remains largely unknown.

HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders.

Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region.

PlexinA4-Semaphorin3A-mediated crosstalk between main cortical interneuron classes is required for superficial interneuron lamination.

In the mammalian cerebral cortex, the developmental events governing allocation of different classes of inhibitory interneurons (INs) to distinct cortical layers are poorly understood. Here we report that the guidance receptor PlexinA4 (PLXNA4) is upregulated in serotonin receptor 3a-expressing (HTR3A) cortical INs (hINs) as they invade the cortical plate, and that it regulates their laminar allocation to superficial cortical layers. We find that the PLXNA4 ligand Semaphorin3A (SEMA3A) acts as a chemorepulsive factor on hINs migrating into the nascent cortex and demonstrate that SEMA3A specifically controls their laminar positioning through PLXNA4.

Prediction of lithium response using genomic data.

Predicting lithium response prior to treatment could both expedite therapy and avoid exposure to side effects. Since lithium responsiveness may be heritable, its predictability based on genomic data is of interest. We thus evaluate the degree to which lithium response can be predicted with a machine learning (ML) approach using genomic data.

Maladaptive emotion regulation traits predict altered corticolimbic recovery from psychosocial stress.

Background: Adaptive recovery from stress promotes healthy cognitive affective functioning, whereas maladaptive recovery is linked to poor psychological outcomes. Neural regions, like the anterior cingulate and hippocampus, play critical roles in psychosocial stress responding and serve as hubs in the corticolimbic neural system. To date, however, it is unknown how cognitive emotion regulation traits (cER), adaptive and maladaptive, influence corticolimbic stress recovery.

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder.

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLiGen) study.

Linking alpha oscillations, attention and inhibitory control in adult ADHD with EEG neurofeedback.

Abnormal patterns of electrical oscillatory activity have been repeatedly described in adult ADHD. In particular, the alpha rhythm (8-12 Hz), known to be modulated during attention, has previously been considered as candidate biomarker for ADHD. In the present study, we asked adult ADHD patients to self-regulate their own alpha rhythm using neurofeedback (NFB), in order to examine the modulation of alpha oscillations on attentional performance and brain plasticity.

MCF2 is linked to a complex perisylvian syndrome and affects cortical lamination.

The combination of congenital bilateral perisylvian syndrome (CBPS) with lower motor neuron dysfunction remains unusual and suggests a potential common genetic insult affecting basic neurodevelopmental processes. Here we identify a putatively pathogenic missense mutation in the MCF2 gene in a boy with CBPS. Using in utero electroporation to genetically manipulate cortical neurons during corticogenesis, we demonstrate that the mouse Mcf2 gene controls the embryonic migration of cortical projection neurons.

Altered Electroencephalographic Resting-State Large-Scale Brain Network Dynamics in Euthymic Bipolar Disorder Patients.

Neuroimaging studies provided evidence for disrupted resting-state functional brain network activity in bipolar disorder (BD). Electroencephalographic (EEG) studies found altered temporal characteristics of functional EEG microstates during depressive episode within different affective disorders. Here we investigated whether euthymic patients with BD show deviant resting-state large-scale brain network dynamics as reflected by altered temporal characteristics of EEG microstates.

Eye-gaze processing in the broader bipolar phenotype revealed by electrical neuroimaging.

Previous studies have documented atypical brain responses to faces in individuals with bipolar disorder (BD) and in their relatives. In view of previous findings of atypical face processing in youths at risk for BD, the aim of this study was to examine whether BD patients and offspring would show differential activation in networks of the social brain when processing eye-gaze. Data from 18 euthymic BD patients and 18 offspring, as well as 36 age-matched healthy controls, were collected using a delayed face-matching paradigm, event related potentials and electrical neuroimaging methods.

Psychiatric disorders among offspring of patients with Bipolar and Borderline Personality Disorder.

Objective: As part of a larger study investigating biological risk factors for bipolar disorder (BD) and borderline personality disorder (BPD), we investigated the prevalence of psychiatric diagnoses presented by young BD or BPD offspring. With respect to the scarcity of studies interested in psychiatric disorders among BPD offspring, we have chosen to report these results despite the small sample size for a prevalence study.

Method: We recruited 21 BD and 22 BPD offspring and 23 control subjects.

Increased Reactivity of the Mesolimbic Reward System after Ketamine Injection in Patients with Treatment-resistant Major Depressive Disorder.

What We Already Know About This Topic: The antidepressant effect of ketamine is associated with increased activity in the reward circuitry of the brain and a suppression of circuitry that mediates perceptual processing of negative emotions. The duration of ketamine effect on these brain structures remains to be defined.

What This Article Tells Us That Is New: As expected, ketamine administration led to an improvement in mood and global vigilance.

Rumination related activity in brain networks mediating attentional switching in euthymic bipolar patients.

Introduction: Mood disorder patients have a tendency to be more internally oriented, with difficulties in switching attentional focus, which might result in the generation of negative thoughts, such as rumination. The present study explored self-referential neural activity correlating with rumination tendency and attentional switching capacity in bipolar disorder.

Methods: Twenty euthymic bipolar patients and twenty matched healthy controls underwent a novel introspection task of switching between internally and externally focused attention during a word processing task, while their brain activity was assessed using functional MRI.