Treating cognitive impairment in schizophrenia with GLP-1RAs: an overview of their therapeutic potential.

INTRODUCTION: Schizophrenia is a neuropsychiatric disorder that affects approximately 1% of individuals worldwide. There are no available medications to treat cognitive impairment in this patient population currently. Preclinical evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve cognitive function. There is a need to evaluate how GLP-1 RAs alter specific domains of cognition and whether they will be of therapeutic benefit in individuals with schizophrenia. AREAS COVERED: This paper summarizes the effects of GLP-1 RAs on metabolic processes in the brain and how these mechanisms relate to improved cognitive function. We provide an overview of preclinical studies that demonstrate GLP-1 RAs improve cognition and comment on their potential therapeutic benefit in individuals with schizophrenia. EXPERT OPINION: To understand the benefits of GLP-1 RAs in individuals with schizophrenia, further preclinical research with rodent models relevant to schizophrenia symptomology are needed. Moreover, preclinical studies must focus on using a wider range of behavioral assays to understand whether important aspects of cognition such as executive function, attention, and goal-directed behavior are improved using GLP-1 RAs. Further research into the specific mechanisms of how GLP-1 RAs affect cognitive function and their interactions with antipsychotic medication commonly prescribed is necessary.

Neural changes induced by antipsychotic administration in adolescence: A review of studies in laboratory rodents.

Adolescence is characterized by major remodelling processes in the brain. Use of antipsychotic drugs (APDs) in adolescents has increased dramatically in the last 20 years; however, our understanding of the neurobiological consequences of APD treatment on the adolescent brain has not kept the same pace and significant concerns have been raised. In this review, we examined currently available preclinical studies of the effects of APDs on the adolescent brain. In animal models of neuropsychiatric disorders, adolescent APD treatment appears to be protective against selected structural, behavioural and neurochemical phenotypes. In "neurodevelopmentally normal" adolescent animals, a range of short- and long-term alterations in behaviour and neurochemistry have been reported. In particular, the adolescent brain appears to be sensitive to long-term locomotor/reward effects of chronic atypical APDs in contrast with the outcomes in adults. Long-lasting changes in dopaminergic, glutamatergic and gamma-amino butyric acid-ergic systems induced by adolescent APD administration have been observed in the nucleus accumbens. A detailed examination of other potential target regions such as striatum, prefrontal cortex and ventral tegmental area is still required. Through identification of specific neural pathways targeted by adolescent APD treatment, future studies will expand the current knowledge on long-term neural outcomes which are of translational value.