Antipsychotics, Metabolic Adverse Effects, and Cognitive Function in Schizophrenia

Abstract

Cognitive impairment is a core symptom domain of schizophrenia. The effect of antipsychotics, the cornerstone of treatment in schizophrenia, on this domain is not fully clear. There is some evidence suggesting that antipsychotics may partially improve cognitive function, and that this improvement may vary depending on the specific cognitive domain. However, this research is confounded by various factors, such as age, duration/stage of illness, medication adherence, and extrapyramidal side effects that complicate the relationship between antipsychotics and cognitive improvement. Furthermore, antipsychotics—particularly the second generation, or “atypical” antipsychotics—can induce serious metabolic side effects, such as obesity, dyslipidemia and type 2 diabetes, illnesses which themselves have been linked to impairments in cognition. Thus, the inter-relationships between cognition and metabolic side effects are complex, and this review aims to examine them in the context of schizophrenia and antipsychotic treatment. The review also speculates on potential mechanisms underlying cognitive functioning and metabolic risk in schizophrenia. We conclude that the available literature examining the inter-section of antipsychotics, cognition, and metabolic effects in schizophrenia is sparse, but suggests a relationship between metabolic comorbidity and worse cognitive function in patients with schizophrenia. Further research is required to determine if there is a causal connection between the well-recognized metabolic adverse effects of antipsychotics and cognitive deficits over the course of the illness of schizophrenia, as well as, to determine underlying mechanisms. In addition, findings from this review highlight the importance of monitoring metabolic disturbances in parallel with cognition, as well as, the importance of interventions to minimize metabolic abnormalities for both physical and cognitive health.

N-(2-Hydroxyphenyl)-1-[3-(2-oxo-2,3-dihydro-1H- benzimidazol-1-yl)propyl]piperidine-4-Carboxamide (D2AAK4), a Multi-Target Ligand of Aminergic GPCRs, as a Potential Antipsychotic

“…In addition, risperidone impaired PA performance, but only at doses that were 10-fold greater than those active in the test of inhibition of hyperlocomotion induced by MK-801 predictive of antipsychotic-like activity, while aripiprazole did not impair PA performance but was poorly active in the MK-801 test [54]. On the other hand, multiple studies have shown that the second-generation antipsychotics (SGAs) improved set-shifting ability (cognitive flexibility) (as reviewed in [55]). For instance, clozapine and olanzapine presented positive effects in attention and verbal fluency with improvements in executive functioning and delayed recall, while olanzapine also showed improvement in selective attention, vigilance, verbal learning and memory (as reviewed in [55]).…”

“…On the other hand, multiple studies have shown that the second-generation antipsychotics (SGAs) improved set-shifting ability (cognitive flexibility) (as reviewed in [55]). For instance, clozapine and olanzapine presented positive effects in attention and verbal fluency with improvements in executive functioning and delayed recall, while olanzapine also showed improvement in selective attention, vigilance, verbal learning and memory (as reviewed in [55]).…”

5-HT3 Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface

“…Unlike the first generation antypsychotic, owing to the lack of interaction with DA D 2 R, setrons do not promote and, as stated above, may even act to counteract tardive dyskinesia (Naidu and Kulkarni, 2001). Moreover, unlike atypical antipsychotics that cause insulin intolerance and obesity (MacKenzie et al, 2018), setrons lack metabolic effects and rather exert a positive effect on glucose metabolism (Fig. 3).…”

The influence of typical and atypical antipsychotics on neurocognitive functions in patients with psychotic disorders

“…Efekti tipičnih i atipičnih antipsihotika na kognitivne funkcije kod pacijenata sa psihotičnim poremećajima A Jovan M. Javorac 1 , Gorana G. Janjić 2 , Dejan B. Živanović 3 , Tijana M. Javorac 4 , Ana R. Marković 5,6 A 1 Medicinski fakultet, Univerzitet u Novom Sadu, Novi Sad, Srbija 2 Student -apsolvent Medicinskog fakulteta, Univerzitet u Novom Sadu, Novi Sad, Srbija 3 Visoka škola strukovnih studija za obrazovanje vaspitača i trenera, Katedra za medicinske nauke, biotehnologiju i hemiju, Subotica, Srbija 4 Apoteka ZEGIN, Novi Sad, Srbija 5 Katedra za psihijatriju i medicinsku psihologiju, Medicinski fakultet, Univerzitet u Novom Sadu, Novi Sad, Srbija 6 Klinika za psihijatriju, Klinički centar Vojvodine, Novi Sad, Srbija…”

“…In patients with psychotic disorders, the generalized cognitive defi cit is dominant, with the possibility of diff erentiating certain specifi c cognitive functions (attention, working memory, short-term and long-term memory, information processing speed, execute functions) that are more dominantly damaged than other cognitive functions (language, non-expressive memory) which have been preserved, but still remain defi cient in comparison to the healthy population [4,5].…”