Extant literature implicates the role of glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists (GLP-1RAs) on modulating alcohol-associated behaviors, with a particular emphasis of these agents on neural circuits subserving reward and appetite control. Herein, we explore the potential effects of GLP-1RAs on alcohol-associated behaviors in brain regions implicated in reward processing facilitating the repurposing of these agents for the treatment and prevention of problematic drinking. Understanding how GLP-1's analogs interact with alcohol-related behaviors may underscore the development of therapeutic strategies for alcohol use disorder (AUD) and those with comorbid metabolic disorders.

A systematic review was conducted, wherein relevant literature was identified through Web of Science, PubMed, and OVID (MedLINE, Embase, AMED, PsycInfo, JBI EBP) from database inception to October 27th, 2024. Preclinical and clinical studies examining the association between GLP-1RAs and alcohol-related behaviors were assessed.

Preclinical studies (n = 19) indicate that GLP-1RAs attenuate alcohol-related behaviors, with exenatide demonstrating significant dose-dependent effects in high alcohol-consuming phenotypes. Semaglutide and liraglutide are associated with reduced alcohol intake, though their effects were often transient. In human studies (n = 2) with AUD, semaglutide significantly reduced alcohol consumption, while exenatide showed mixed results, with reductions in alcohol drinking within high BMI subpopulations.

Extant preclinical and clinical literature provides preliminary support for the potential therapeutic role of GLP-1RAs in attenuating alcohol consumption and preference. There is a need for large well controlled studies evaluating the effect of GLP-1RAs as a treatment strategy for behavioral modifications in individuals living with alcohol use disorder.

Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) administration has been associated with neuroproliferative effects and modulatory effects in neuronal pathways. Herein, we conducted a comprehensive synthesis of the effects of GLP-1 and GLP-1 RAs on neurogenesis.

We examined studies that investigate changes in neurogenesis mediated by GLP-1 and GLP-1 RA administration in both human and animal populations. Relevant articles were retrieved through OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), PubMed, and Web of Science from database inception to July 2nd. Primary studies investigating the role of GLP-1 and GLP-1 RAs on neurogenesis were included for analysis.

GLP-1 and GLP-1 RAs (i.e. exenatide, geniposide, liraglutide, lixisenatide, and semaglutide), increased neurogenesis within the dentate gyrus, hippocampus, olfactory bulb, and the medial striatum in animal models. Additionally, GLP-1 and GLP-1 RAs were associated with modulating changes in multiple apoptotic pathways and upregulating survival pathways.

GLP-1 and GLP-1 RAs are positively associated with neurogenesis. This effect may have translational implications insofar as disparate mental disorders that are characterized by neurogenesis defects (e.g. depressive disorders and neurocognitive disorders) may be benefitted by these agents.

Previous studies on the etiology of attention deficit/hyperactivity disorder (ADHD) highlight high heritability, structural/functional brain abnormalities, and dopamine/noradrenaline imbalances, emphasizing gene-environment interactions. While maternal smoking during pregnancy and low-grade peripheral inflammation have been implicated, its neurobiological basis remains incompletely understood. Our aim was to elucidate neuroinflammatory signaling contributing to ADHD and investigate behavioural and molecular changes in a mouse model.

We examined neuroinflammatory signaling using prenatal nicotine exposed (PNE) mice via immunohistochemistry combined with cortical thickness (CT) measurement in the subregions of the prefrontal cortex (PFC). Mice were exposed to nicotine via drinking water containing 300 μg/ml nicotine and 2% sucrose until weaning 2 weeks prior to mating to induce ADHD-like symptoms, as opposed to controls receiving drinking water containing 2% sucrose alone. Behavioral tests were conducted to assess ADHD-like behaviors and accompanying anxiety on postnatal week 5. Inflammatory pathways in the anterior cingulate cortex (ACC), prelimbic cortex (PL) and infralimbic cortex (IL) were examined using Iba-1 and NF-κB immunolabeling, and microglial morphology was analyzed.

Findings showed increased CT, microglial cell number, activity, and NF-κB activation in the ACC, which correlated with attention-related impairment in PNE mice. Increased Iba-1 levels in the PL and IL, along with elevated NF-κB activation in the IL, were observed in PNE mice, which corresponded with a significant increase in anxiety-like behaviors compared to controls. PNE mice also morphologically exhibited microglia activation in all three subregions.

Perinatal nicotine exposure contributes to ADHD development through neuroinflammatory signaling, a common end pathway.

Folate and cobalamin deficiency or impaired function due to genetic variants in key enzymes, have been associated with neuropsychiatric symptoms. The aim of this study was to compare folate and cobalamin status in patients admitted to an acute psychiatric unit to patients from primary health care, in order to reveal factors which may be important in the follow-up of patents with mental disorders.

Anonymous blood samples tested for folate, cobalamin, the metabolic marker total homocysteine (tHcy), creatinine and glomerular filtration rate, as well as age and gender in patients admitted to a psychiatric acute unit (n=981) and patients from primary health care (controls) (n=32201) were reviewed retrospectively.

Median serum folate was 18% lower and median serum cobalamin was 11% higher in patients with mental disorders compared to controls. Folate deficiency was associated with 54% higher median tHcy levels among patients with mental disorders compared to controls. The prevalence of folate deficiency was 31% and of cobalamin deficiency 6% in patients admitted to a psychiatric acute unit in a Norwegian hospital in 2024.

Folate, but not cobalamin deficiency, was prevalent in Norwegian patients with mental disorders. The higher tHcy levels in folate deficient patients with mental disorders indicate an impaired folate metabolism, which might be related to genetic factors, such as polymorphisms in the MTHFR gene. Ensuring a serum folate concentration above 15 nmol/L and a serum cobalamin above 250 pmol/L might improve symptoms in patients with mental disorders.