incretins and Mental-Disorders

Obesity and diabetes are both risk factors and consequences of psychiatric disorders. Glucagon like peptide 1 (GLP-1) receptor agonists such as liraglutide are widely used in the treatment of diabetes and obesity. There are considerable amounts of preclinical studies showing the effects of liraglutide on promotion of neurogenesis, while preventing apoptosis and oxidation. Preliminary clinical evidence has suggested that liraglutide could decrease weight gain, improve cognition and prevent cognitive decline. Accordingly, liraglutide has been regarded as a potential candidate for the management of psychiatric disorders. Herein, we will discuss the association between obesity/diabetes and psychiatric disorders, and the emerging use of liraglutide in psychiatry.

Topics: Alzheimer Disease; Animals; Brain; Feeding and Eating Disorders; Humans; Incretins; Liraglutide; Mental Disorders

Type 2 diabetes mellitus (T2DM) is a fast progressing disease reaching pandemic proportions. T2DM is specifically harmful because of its severe secondary complications. In the course of the disease, most patients require treatment with oral antidiabetic drugs (OADs), for which a relatively large number of different options are available. The growing number of individuals affected by T2DM as well as marked interindividual differences in the response to treatment call for individualized therapeutic regimens that can maximize treatment efficacy and thus reduce side effects and costs. A large number of genetic polymorphisms have been described affecting the response to treatment with OADs; in this review, we summarize the most recent advances in this area of research. Extensive evidence exists for polymorphisms affecting pharmacokinetics and pharmacodynamics of biguanides and sulfonylureas. Data on incretin-based medications as well as the new class of sodium/glucose cotransporter 2 (SGLT2) inhibitors are just starting to emerge. With diabetes being a known comorbidity of several psychiatric disorders, we also review genetic polymorphisms possibly responsible for a common treatment response in both conditions. For all drug classes reviewed here, large prospective trials are necessary in order to consolidate the existing evidence and derive treatment schemes based on individual genetic traits.

Topics: Administration, Oral; Comorbidity; Diabetes Mellitus, Type 2; Genotype; Humans; Hypoglycemic Agents; Incretins; Mental Disorders; Pharmacogenetics; Pharmacogenomic Variants; Phenotype; Polymorphism, Genetic; Treatment Outcome

Mood disorders may be conceptualized as progressive neurodegenerative disorders associated with cognitive decline. Novel treatments capable of preserving and/or enhancing cognitive function represent an area of priority for research in the future. Insulin, insulin-like growth factor (IGF)-1 and incretins may play a critical role in both physiological and pathophysiological processes of the CNS. An emerging paradigm regarding the pathophysiology of mood disorders posits that alterations in biological networks that mediate stress compromise optimal neuronal and glial function. A growing body of evidence indicates that central administration of insulin may enhance cognitive function in both healthy and cognitively impaired individuals. The neuroactive peptides, insulin, IGF-1 and incretins, or agents that facilitate their central effects (e.g. insulin-sensitizing agents), may constitute novel and possibly disease-modifying neurocognitive treatments.

Topics: Animals; Central Nervous System; Cognition Disorders; Homeostasis; Humans; Incretins; Insulin; Insulin-Like Growth Factor I; Mental Disorders