Metformin for the Prevention of Antipsychotic-Induced Weight Gain: Guideline Development and Consensus Validation.

Background: Overweight and obesity are highly prevalent in people with severe mental illness (SMI). Antipsychotic-induced weight gain (AIWG) is one of the most commonly reported and distressing side effects of treatment and people living with SMI place a high value on the avoidance of this side effect. Metformin is the most effective pharmacological intervention studied for the prevention of AIWG yet clear guidelines are lacking and evidence has not translated into practice.

Regulation of energy balance by leptin as an adiposity signal and modulator of the reward system.

Background: Leptin is an adipose tissue-derived hormone that plays a crucial role in body weight, appetite, and behaviour regulation. Leptin controls energy balance as an indicator of adiposity levels and as a modulator of the reward system, which is associated with liking palatable foods. Obesity is characterized by expanded adipose tissue mass and consequently, elevated concentrations of leptin in blood.

The Dysregulation of the Glymphatic System in Patients with Psychosis Spectrum Disorders Minimally Exposed to Antipsychotics: La dérégulation du système glymphatique en présence de troubles psychotiques chez des patients peu exposés à des antipsychotiques.

Objective: The pathophysiological mechanisms influencing psychosis spectrum disorders are largely unknown. The glymphatic system, which is a brain waste clearance pathway, has recently been implicated in its pathophysiology and has also been shown to be disrupted in various neurodegenerative and vascular diseases. Initial studies examining the glymphatic system in psychosis spectrum disorders have reported disruptions, but the findings have been confounded by medication effects as they included antipsychotic-treated patients.

The impact of weight gain on antipsychotic nonadherence or discontinuation: A systematic review and meta-analysis.

Background: Nonadherence/discontinuation of antipsychotic (AP) medications represents an important clinical issue in patients across psychiatric disorders, including schizophrenia spectrum disorders (SSDs). While antipsychotic-induced weight gain (AIWG) is a reported contributor to nonadherence, a systematic review of the association between AIWG and medication nonadherence/discontinuation has not been explored previously.

Method: A systematic search was conducted in MEDLINE, EMBASE, PsychINFO, CINAHL, and CENTRAL databases, among others, to help identify all studies which explored adherence, study dropouts, AP switching and/or discontinuations attributable to AIWG among individuals with severe mental illness.

Glycocalyx shedding patterns identifies antipsychotic-naïve patients with first-episode psychosis.

Psychotic disorders have been linked to immune-system abnormalities, increased inflammatory markers, and subtle neuroinflammation. Studies further suggest a dysfunctional blood brain barrier (BBB). The endothelial Glycocalyx (GLX) functions as a protective layer in the BBB, and GLX shedding leads to BBB dysfunction.

Protocol for the hyperinsulinemic euglycemic clamp to measure glucose kinetics in rats.

In rats, cannulation of the jugular vein and the carotid artery precedes the use of the hyperinsulinemic euglycemic clamp to determine insulin sensitivity in vivo. Here, we present a vascular surgery protocol to allow the infusion of substances via the vein and the collection of blood samples from the artery on the day of the hyperinsulinemic euglycemic clamp. We describe steps for preparing for and performing catheterization surgery.

Development of Novel Tools for Dissection of Central Versus Peripheral Dopamine D2-Like Receptor Signaling in Dysglycemia.

Dopamine (DA) D2-like receptors in both the central nervous system (CNS) and the periphery are key modulators of metabolism. Moreover, disruption of D2-like receptor signaling is implicated in dysglycemia. Yet, the respective metabolic contributions of CNS versus peripheral D2-like receptors, including D2 (D2R) and D3 (D3R) receptors, remain poorly understood.

Development of novel tools for dissection of central versus peripheral dopamine D-like receptor signaling in dysglycemia.

Dopamine (DA) D-like receptors in both the central nervous system (CNS) and the periphery are key modulators of metabolism. Moreover, disruption of D-like receptor signaling is implicated in dysglycemia. Yet, the respective metabolic contributions of CNS versus peripheral D-like receptors including D (D2R) and D (D3R) receptors remain poorly understood.

Neurocognitive correlates of metabolic dysregulation in individuals with mood disorders: a systematic review and meta-analysis.

Individuals with mood disorders are predisposed to metabolic dysfunction, while those with metabolic dysregulation such as diabetes and obesity experience more severe depressive symptoms. Both metabolic dysfunction and mood disorders are independently associated with cognitive deficits. Therefore, given their close association, this study aimed to explore the association between metabolic dysfunction in individuals with mood disorders in relation to cognitive outcomes.

Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures.

Antipsychotic (AP)-naive first-episode psychosis (FEP) patients display early dysglycemia, including insulin resistance and prediabetes. Metabolic dysregulation may therefore be intrinsic to psychosis spectrum disorders (PSDs), independent of the metabolic effects of APs. However, the potential biological pathways that overlap between PSDs and dysglycemic states remain to be identified.

In vivo techniques for assessment of insulin sensitivity and glucose metabolism.

Metabolic tests are vital to determine in vivo insulin sensitivity and glucose metabolism in preclinical models, usually rodents. Such tests include glucose tolerance tests, insulin tolerance tests, and glucose clamps. Although these tests are not standardized, there are general guidelines for their completion and analysis that are constantly being refined.

Central insulin dysregulation in antipsychotic-naïve first-episode psychosis: In silico exploration of gene expression signatures.

Antipsychotic drug (AP)-naïve first-episode psychosis (FEP) patients display premorbid cognitive dysfunctions and dysglycemia. Brain insulin resistance may link metabolic and cognitive disorders in humans. This suggests that central insulin dysregulation represents a component of the pathophysiology of psychosis spectrum disorders (PSDs).

Management of dyslipidaemia in individuals with severe mental illness: a population-based study in the Greater Copenhagen Area.

Background: Severe mental illness (SMI) is associated with increased cardiovascular risk. Dyslipidaemia is a potentially modifiable risk factor, which may be inadequately managed in patients with SMI.

Objectives: To assess management of dyslipidaemia in patients with SMI healthy controls (HCs) in 2005 and 2015.

White matter microstructural integrity is associated with retinal vascular caliber in adolescents with bipolar disorder.

Objective: Reduced white matter integrity is observed in bipolar disorder (BD), and is associated with cardiovascular risk in adults. This topic is underexplored in youth, and in BD, where novel microvascular measures may help to inform understanding of the vascular-brain connection. We therefore examined the association of retinal vascular caliber with white matter integrity in a cross-sectional sample of adolescents with and without BD.

Salsalate and/or metformin therapy confer beneficial metabolic effects in olanzapine treated female mice.

Antipsychotic medications are used in the management of schizophrenia and a growing number of off-label conditions. While effective at reducing psychoses, these drugs possess noted metabolic side effects including weight gain, liver lipid accumulation and disturbances in glucose and lipid metabolism. To counter the side effects of antipsychotics standard of care has typically included metformin.

Promising translatable pharmacological interventions for body weight management in individuals with severe mental illness - a narrative review.

Introduction: Psychotropic medications, especially antipsychotics, have been consistently shown to cause weight gain in individuals with severe mental illness (SMI), a population inherently challenged by poor physical health. Consequently, compared to the general population, this contributes to an increased cardiometabolic burden, including the risk of type 2 diabetes, dyslipidemia, and hypertension. Furthermore, comorbid obesity leads to treatment nonadherence, decreased quality of life, and increased risk of relapse, posing a challenge in the management of mental health.

Depression in caregivers of patients with schizophrenia: a scoping review.

Purpose: Caregivers play a vitally important role in the lives of people with schizophrenia. However, their mental health can often be overlooked. In recent years, with increasing attention to mental health and wellness, common mental illness such as depression in caregivers of people with schizophrenia has received renewed attention.

Metabolomic signatures associated with weight gain and psychosis spectrum diagnoses: A pilot study.

Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain.

Semaglutide for the treatment of antipsychotic-associated weight gain in patients not responding to metformin - a case series.

Metformin is the currently accepted first-line treatment for antipsychotic-associated weight gain (AAWG). However, not all patients benefit from metformin. Glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown promise in the management of obesity in the general population, with preliminary evidence supporting efficacy in AAWG.

Enhancing endogenous levels of GLP1 dampens acute olanzapine induced perturbations in lipid and glucose metabolism.

Olanzapine is a second-generation antipsychotic (SGA) used in the treatment of schizophrenia and several on- and off-label conditions. While effective in reducing psychoses, acute olanzapine treatment causes rapid hyperglycemia, insulin resistance, and dyslipidemia and these perturbations are linked to an increased risk of developing cardiometabolic disease. Pharmacological agonists of the glucagon-like peptide-1 (GLP1) receptor have been shown to offset weight-gain associated with chronic SGA administration and mitigate the acute metabolic side effects of SGAs.