Proteomic profiles of cytokines and chemokines in moderate to severe depression: Implications for comorbidities and biomarker discovery.

Objective: This study assessed the proteomic profiles of cytokines and chemokines in individuals with moderate to severe depression, with or without comorbid medical disorders, compared to healthy controls. Two proteomic multiplex platforms were employed for this purpose.

Metods: An immunofluorescent multiplex platform and an aptamer-based method were used to evaluate 32 protein analytes from 153 individuals with moderate to severe major depressive disorder (MDD) and healthy controls (HCs).

Toward a Precision Treatment Approach for Metabolic Depression: Integrating Epidemiology, Neuroscience, and Psychiatry.

Background: Individuals with comorbid major depressive disorder and type 2 diabetes represent an important subgroup of patients for whom conventional treatment may be insufficient. A precision treatment approach that addresses insulin resistance with an outcome of a positive response to antidepressants may prove beneficial.

Methods: This study utilized an emulated target trial on a large dataset from the Optum Clinformatics Data Mart Database.

Longitudinal Digital Mood Charting in Bipolar Disorder: Experiences with ChronoRecord Over 20 Years.

Introduction: Longitudinal study is an essential methodology for understanding disease trajectories, treatment effects, symptom changes, and long-term outcomes of affective disorders. Daily self-charting of mood and other illness-related variables is a commonly recommended intervention. With the widespread acceptance of home computers in the early 2000s, automated tools were developed for patient mood charting, such as ChronoRecord, a software validated by patients with bipolar disorder.

Prevalence and outcomes of rapid cycling bipolar disorder: Mixed method systematic meta-review.

Rapid-cycling in bipolar disorder (RC-BD) is associated with greater illness morbidity and inferior treatment response but many aspects remain unclear, prompting this systematic review of its definitions, prevalence, and clinical characteristics. We searched multiple literature databases through April 2022 for systematic reviews or meta-analyses on RC-BD and extracted associated definitions, prevalence, risk-factors, and clinical outcomes. We assessed study quality (NIH Quality Assessment Tool) and levels of evidence (Oxford criteria).

Carnitine octanoyltransferase is important for the assimilation of exogenous acetyl-L-carnitine into acetyl-CoA in mammalian cells.

In eukaryotes, carnitine is best known for its ability to shuttle esterified fatty acids across mitochondrial membranes for β-oxidation. It also returns to the cytoplasm, in the form of acetyl-L-carnitine (LAC), some of the resulting acetyl groups for posttranslational protein modification and lipid biosynthesis. While dietary LAC supplementation has been clinically investigated, its effects on cellular metabolism are not well understood.

Endophenotypic correlates of cognitive function in reproductive-age individuals with polycystic ovary syndrome.

Objective: To characterize cognitive performance in relation to hormonal and metabolic factors in women with polycystic ovary syndrome (PCOS).

Design: Cross-sectional study.

Setting: Tertiary university center.

Insulin resistance and accelerated cognitive aging.

Insulin resistance may be an early sign of metabolic dysfunction with the potential to lead to neuropsychiatric sequelae in the long term. In order to identify whether insulin resistance in otherwise healthy young and middle-aged adults is associated with preclinical signs of neuropsychiatric impairment, we recruited 126 overweight but nondiabetic, nondepressed individuals who completed an insulin suppression test for direct measurement of insulin resistance as well as a battery of cognitive and neuropsychiatric measures. Insulin resistance was associated with weaker performance on a fine motor task (Purdue Pegboard) as well as increases in subclinical symptoms of depression.

Association between polarity of first episode and solar insolation in bipolar I disorder.

Objective: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I.

Family history of diabetes moderates metabolic depression endophenotypes in overweight/obese adults.

Objective: Insulin resistance (IR) is linked to depressive disorders, and there is growing evidence that targeting IR may be beneficial in treating them. We examine the association between depressive symptoms and a direct measure of IR, and whether family history of type 2 diabetes (FHx-T2DM) or major depressive disorder (FHx-MDD) moderate this relationship.

Methods: Cross-sectional data were collected from 96 primarily overweight/obese adults ages 25-50 without diabetes or clinical depression.

Maternal attachment insecurity, maltreatment history, and depressive symptoms are associated with broad DNA methylation signatures in infants.

The early environment, including maternal characteristics, provides many cues to young organisms that shape their long-term physical and mental health. Identifying the earliest molecular events that precede observable developmental outcomes could help identify children in need of support prior to the onset of physical and mental health difficulties. In this study, we examined whether mothers' attachment insecurity, maltreatment history, and depressive symptoms were associated with alterations in DNA methylation patterns in their infants, and whether these correlates in the infant epigenome were associated with socioemotional and behavioral functioning in toddlerhood.

Lower functional hippocampal connectivity in healthy adults is jointly associated with higher levels of leptin and insulin resistance.

Background: Metabolic dysregulation is currently considered a major risk factor for hippocampal pathology. The aim of the present study was to characterize the influence of key metabolic drivers on functional connectivity of the hippocampus in healthy adults.

Methods: Insulin resistance was directly quantified by measuring steady-state plasma glucose (SSPG) concentration during the insulin suppression test and fasting levels of insulin, glucose, leptin, and cortisol, and measurements of body mass index and waist circumference were obtained in a sample of healthy cognitively intact adults (n = 104).

A novel peripheral biomarker for depression and antidepressant response.

In contrast to healthy controls, the heterotrimeric G protein, Gsalpha (Gsα) is ensconced predominantly in lipid rafts in subjects with major depressive disorder (MDD) resulting in impaired stimulation of adenylyl cyclase. In this small proof-of-concept study, we examined the hypothesis that translocation of Gsα from lipid rafts toward a more facile activation of adenylyl cyclase is a biomarker for clinical response to antidepressants. There were 49 subjects with MDD (HamD score ≥15) and 59 healthy controls at the screen visit.

Shared genetic influences on depression and menopause symptoms.

Background: Women experience major depression and post-traumatic stress disorder (PTSD) approximately twice as often as men. Estrogen is thought to contribute to sex differences in these disorders, and reduced estrogen is also known to be a key driver of menopause symptoms such as hot flashes. Moreover, estrogen is used to treat menopause symptoms.

Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes.

Major depressive disorder (MDD) is a primary psychiatric illness worldwide; there is a dearth of new mechanistic models for the development of better therapeutic strategies. Although we continue to discover individual biological factors, a major challenge is the identification of integrated, multidimensional traits underlying the complex heterogeneity of depression and treatment outcomes. Here, we set out to ascertain the emergence of the novel mitochondrial mediator of epigenetic function acetyl-L-carnitine (LAC) in relation to previously described individual predictors of antidepressant responses to the insulin-sensitizing agent pioglitazone.

Incident Major Depressive Disorder Predicted by Three Measures of Insulin Resistance: A Dutch Cohort Study.

Objective: Major depressive disorder is the leading cause of disability worldwide. Yet, there remain significant challenges in predicting new cases of major depression and devising strategies to prevent the disorder. An important first step in this process is identifying risk factors for the incidence of major depression.

Hippocampal volume reduction is associated with direct measure of insulin resistance in adults.

Hippocampal integrity is highly susceptible to metabolic dysfunction, yet its mechanisms are not well defined. We studied 126 healthy individuals aged 23-61 years. Insulin resistance (IR) was quantified by measuring steady-state plasma glucose (SSPG) concentration during the insulin suppression test.

Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin.

Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression.

Association of Insulin Resistance With Depression Severity and Remission Status: Defining a Metabolic Endophenotype of Depression.

This study investigates whether insulin resistance was positively associated with the presence, severity, or chronicity of major depression.

Association between Adherence with an Atypical Antipsychotic and with Other Psychiatric Drugs in Patients with Bipolar Disorder.

Background: Using U.S. pharmacy and medical claims, medication adherence patterns of patients with serious mental illness suggest that adherence to atypical antipsychotics may be related to adherence to other prescription drugs.