Resting state EEG in young children with Tuberous Sclerosis Complex.

Background: Tuberous Sclerosis Complex (TSC) manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations. Such a biomarker could be useful in clinical trials as an endpoint or predictor of treatment response.

Alterations in the Serum Proteome Following Electroconvulsive Therapy for a Major Depressive Episode: A Longitudinal Multicenter Study.

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but the biological changes induced by ECT remain poorly understood.

Methods: This study investigated alterations in blood serum proteins in 309 patients receiving ECT for a major depressive episode. We analyzed 201 proteins in samples collected at 3 time points (T): just before the first ECT treatment session (T0), within 30 minutes after the first ECT session (T1), and just before the sixth ECT session (T2).

Polygenic risk scores of lithium response and treatment resistance in major depressive disorder.

Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate the genetic overlap between treatment response and resistance in MDD.

In Context: A Developmental Model of Reward Processing, With Implications for Autism and Sensitive Periods.

Objective: Differences in reward processing have been associated with numerous psychiatric disorders, including autism and attention-deficit/hyperactivity disorder (ADHD). Many attempts to understand reward processing characterize differences in clinical populations after disorder onset; however, divergence may begin much earlier. In fact, the typical developmental progression of reward processing in infancy and early childhood is poorly understood.

Association Between Polygenic Risk Scores and Outcome of ECT.

Objective: Identifying biomarkers associated with response to electroconvulsive therapy (ECT) may aid clinical decisions. The authors examined whether greater polygenic liabilities for major depressive disorder, bipolar disorder, and schizophrenia are associated with improvement following ECT for a major depressive episode.

Methods: Between 2013 and 2017, patients who had at least one treatment series recorded in the Swedish National Quality Register for ECT were invited to provide a blood sample for genotyping.

Genome-wide association study of patients with a severe major depressive episode treated with electroconvulsive therapy.

Although large genome-wide association studies (GWAS) of major depressive disorder (MDD) have identified many significant loci, the SNP-based heritability remains notably low, which might be due to etiological heterogeneity in existing samples. Here, we test the utility of targeting the severe end of the MDD spectrum through genome-wide SNP genotyping of 2725 cases who received electroconvulsive therapy (ECT) for a major depressive episode (MDE) and 4035 controls. A subset of cases (n = 1796) met a narrow case definition (MDE occurring in the context of MDD).

A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants.

Objective: Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships.

Methods: This international study included 547 individuals (mean age, 12.

Does the Factor Structure of IQ Differ Between the Differential Ability Scales (DAS-II) Normative Sample and Autistic Children?

The Differential Abilities Scales, 2nd edition (DAS-II) is frequently used to assess intelligence in autism spectrum disorder (ASD). However, it remains unknown whether the DAS-II measurement model (e.g.

International Consortium on the Genetics of Electroconvulsive Therapy and Severe Depressive Disorders (Gen-ECT-ic).

Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines.

Evaluation of the Social Motivation Hypothesis of Autism: A Systematic Review and Meta-analysis.

Importance: The social motivation hypothesis posits that individuals with autism spectrum disorder (ASD) find social stimuli less rewarding than do people with neurotypical activity. However, functional magnetic resonance imaging (fMRI) studies of reward processing have yielded mixed results.

Objectives: To examine whether individuals with ASD process rewarding stimuli differently than typically developing individuals (controls), whether differences are limited to social rewards, and whether contradictory findings in the literature might be due to sample characteristics.

Critical region within 22q11.2 linked to higher rate of autism spectrum disorder.

Background: Previous studies have reported no clear critical region for medical comorbidities in children with deletions or duplications of 22q11.2. The purpose of this study was to evaluate whether individuals with small nested deletions or duplications of the LCR-A to B region of 22q11.

22q11.2 duplication syndrome: elevated rate of autism spectrum disorder and need for medical screening.

Background: Widespread use of microarray technology has led to increasing identification of 22q11.2 duplication syndrome (22q11.2DupS), the reciprocal syndrome of the well-characterized 22q11.

Attention Bias to Emotional Faces Varies by IQ and Anxiety in Williams Syndrome.

Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N = 46).

An electronic health records study of long-term weight gain following antidepressant use.

Importance: Short-term studies suggest antidepressants are associated with modest weight gain but little is known about longer-term effects and differences between individual medications in general clinical populations.

Objective: To estimate weight gain associated with specific antidepressants over the 12 months following initial prescription in a large and diverse clinical population.

Design, Setting, And Participants: We identified 22,610 adult patients who began receiving a medication of interest with available weight data in a large New England health care system, including 2 academic medical centers and affiliated outpatient primary and specialty care clinics.

Bipolar polygenic loading and bipolar spectrum features in major depressive disorder.

Objectives: Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of the present study was to determine whether this shared genetic liability influences clinical presentation.

Methods: A polygenic risk score for bipolar disorder, derived from a large genome-wide association meta-analysis, was generated for each subject of European-American ancestry (n = 1,274) in the Sequential Treatment Alternatives to Relieve Depression study (STAR*D) outpatient major depressive disorder cohort.

Rare copy number variation in treatment-resistant major depressive disorder.

Background: While antidepressant treatment response appears to be partially heritable, no consistent genetic associations have been identified. Large, rare copy number variants (CNVs) play a role in other neuropsychiatric diseases, so we assessed their association with treatment-resistant depression (TRD).

Methods: We analyzed data from two genome-wide association studies comprising 1263 Caucasian patients with major depressive disorder.

QT interval and antidepressant use: a cross sectional study of electronic health records.

Objective: To quantify the impact of citalopram and other selective serotonin reuptake inhibitors on corrected QT interval (QTc), a marker of risk for ventricular arrhythmia, in a large and diverse clinical population.

Design: A cross sectional study using electrocardiographic, prescribing, and clinical data from electronic health records to explore the relation between antidepressant dose and QTc. Methadone, an opioid known to prolong QT, was included to demonstrate assay sensitivity.

Incident user cohort study of risk for gastrointestinal bleed and stroke in individuals with major depressive disorder treated with antidepressants.

Objective: To examine the association between exposure to newer antidepressants and risk of gastrointestinal (GI) and other bleeding complications among individuals with major depressive disorder (MDD).

Design: This study uses an incident user cohort design to compare associations between incidence of vascular/bleeding events and the relative affinity (low, moderate or high) of the antidepressant for the serotonin transporter during an exposure risk period for each patient.

Setting: New England healthcare system electronic medical record database.