Current Neuropharmacology - Volume 23, Issue 4, 2025

Co-occurrence of substance use disorders is frequent in patients with mental health disorders is a condition known as “dual diagnosis”. The use of substances worsens the prognosis and lowers the quality of life of psychiatric patients. It also increases the risk of hospitalization and suicide rate.

To assess the effects of aripiprazole therapy on substance use and other psychiatric outcomes in dually diagnosed patients.

We performed a systematic review conducted on 3 databases PUBMED, SCOPUS, and Web of Science, selecting original studies and analyzing the impact of aripiprazole therapy on dually diagnosed patients. Six hundred and fifty-five articles were founded and, after removing duplicates (n = 274) and applying the exclusion criteria, 12 articles were included in our systematic review.

12 studies were included, among which 6 were Randomized Controlled Trials. The Most frequent psychiatric diagnosis were schizoaffective disorders, schizophrenia, and bipolar disorders. Alcohol and cocaine use disorders were the most used substances. Eleven studies showed a clinical improvement after aripiprazole treatment. 8 studies evaluated craving and found a significant reduction after treatment with aripiprazole. No definitive conclusions can be drawn on substance usage and maintenance of abstinence.

The present findings suggest aripiprazole may be associated with reducing substance craving and improving depression, psychosis, and schizoaffective disorders in dually diagnosed patients.

Administration of olanzapine (OLA) is closely associated with obesity and glycolipid abnormalities in patients with schizophrenia (SCZ), although the exact molecular mechanisms remain elusive.

We conducted comprehensive animal and molecular experiments to elucidate the mechanisms underlying OLA-induced weight gain.

We investigated the mechanisms of OLA-induced adipogenesis and lipid storage by employing a real-time ATP production rate assay, glucose uptake test, and reactive oxygen species (ROS) detection in 3T3-L1 cells and AMSCs. Rodent models were treated with OLA using various intervention durations, dietary patterns (normal diets/western diets), and drug doses. We assessed body weight, epididymal and liver fat levels, and metabolic markers in both male and female mice.

OLA accelerates adipogenesis by directly activating glycolysis and its downstream PI3K signaling pathway in differentiated adipocytes. OLA promotes glucose uptake in differentiated 3T3-L1 preadipocytes. In mouse models with normal glycolipid metabolism, OLA administration failed to increase food intake and weight gain despite elevated GAPDH expression, a marker related to glycolysis and PI3K-AKT. This supports the notion that glycolysis plays a significant role in OLA-induced metabolic dysfunction.

OLA induces glycolysis and activates the downstream PI3K-AKT signaling pathway, thereby promoting adipogenesis.

Diabetes, a widespread chronic metabolic disease, is projected to affect 783 million people globally by 2045. Recent studies emphasize the neuroprotective potential of dipeptidyl peptidase 4 (DPP4i) inhibitors, pointing toward a promising avenue for intervention in addressing cognitive challenges associated with diabetes. Due to limited data on the effect of DPP4i on brain pathways involvedin diabetes-related neurocognitive disorders, the decision was made to conduct this study to fill existing knowledge gaps on this topic.

The primary aim of our study was to evaluate the potential of DPP4 inhibitors (DPP4i) in preventing cognitive decline in mice with type 2 diabetes (T2D), placing special emphasis on gaining insight into the complex molecular mechanisms underlying this action.

We examined drug efficacy in modulating neurotrophic factors, calcium levels, and the expression of key genes (HIF1α, APP, Arc) crucial for neural plasticity. Conducting cognitive assessments with the hole board and passive avoidance tests, we discerned a remarkable influence of short-term gliptin usage on the limiting progress of cognitive dysfunction in diabetic mice. The administration of DPP4 inhibitors ledto heightened neurotrophin levels, increased HIF1α in the prefrontal cortex, and a significant elevation in Arc mRNA levels.

Our findings reveal that DPP4 inhibitors effectively limit the progression of diabetes-related cognitive disorders. This breakthrough discovery not only opens new research avenues but also constitutes a potential starting point for creating innovative strategies for the treatment of central nervous system disorders focused on improving cognitive abilities.

With the frequent use of antipsychotics, the metabolic disorder (MetD) caused by drugs has received increasing attention. However, the mechanism of drug-induced MetD is still unclear and is being explored. Keeping abreast of the progress and trending knowledge in this area is conducive to further work.

The aim of this study is to analyze the latest status and trends of research on antipsychotic-induced metabolic disorder (AIMetD) by bibliometric and visual analysis.

3478 publications of AIMetD from 2006 to 2021 were retrieved from the Web of Science Core Collection database. R-biblioshiny was used for descriptive analysis, CiteSpace for cooperative network, co-citation analysis and burst detection, and VOSviewer for co-occurrence keywords was used.

Since 2006, the publications have been growing fluctuantly. These studies have extensive cooperation among countries/regions. The most influential country/region, institution and author are the USA, King's College London and Christoph U Correll. Analysis of references shows the largest cluster of “antipsychotic-induced metabolic dysfunction”, which is an important basis for MetD. The recent contents of the burst citation are related to “glucose homeostasis” and “cardiovascular metabolism”. Several bursting keywords were discerned at the forefront, including “LC-MS/MS”, “major depressive disorder”, “expression”, and “homeostasis”.

The AIMetD study is in a state of sustained development. Close cooperation between countries/regions has promoted progress. For grasping the foundation, development, and latest trends of AIMetD, it is recommended to focus on active institutions and authors. Based on AIMetD, subdivision areas such as “LC-MS/MS”, “expression”, and “homeostasis” are forefronts that deserve constant attention.

Alterations of dopamine (DA) transmission in the brain reward system can be associated with an addictive-like state defined as food addiction (FA), common in obese individuals. Subjects affected by FA experience negative feelings when abstinent from their preferred diet and may develop mood disorders, including depression, sustained by alterations in brain DA pathways.

This study aims to investigate the impact of long-term abstinence from a palatable diet on depressive-like behavior in rats, exploring neurochemical alterations in monoamine and endocannabinoid signaling in DA-enriched brain regions, including ventral tegmental area, dorsolateral striatum, substantia nigra and medial prefrontal cortex.

Rats underwent exposure and subsequent abstinence from a palatable cafeteria diet. During abstinence, animals were treated with fatty acid amide hydrolase (FAAH) inhibitor PF-3845 (10 mg/kg, intraperitoneal administration every other day). Lastly, animals were subjected to a forced swimming test, and their brains were dissected and processed for high-performance liquid chromatography measurement of monoamines and western blot analyses of markers of the endocannabinoid machinery.

After the withdrawal from the palatable diet, animals showed depressive-like behavior, coupled with significant variations in the concentration of brain monoamines and in the expression of endocannabinoid signalling machinery proteins in cited brain areas. Treatment with PF-3845 exerted an antidepressant-like effect and restored part of the alterations in monoaminergic and endocannabinoid systems.

Overall, our results suggest that abstinence from a cafeteria diet provokes emotional disturbances linked to neuroadaptive changes in monoamines and endocannabinoid signalling in brain areas partaking to DA transmission that could partially be restored by the enhancement of endocannabinoid signalling through FAAH inhibition.

Naringin and MCC950 as an inflammasome inhibitor have exhibited numerous pharmacological activities, including antioxidant and anti-inflammatory effects. The present study has examined the combined impacts of naringin and MCC950 on the levels of oxidative stress, demyelination, and inflammation in the cuprizone (CPZ)-induced demyelination model.

In order to induce demyelination, CPZ (0.2% w/w) was added to the normal diet of mice for 42 days. Subsequently, the male C57BL/6 mice received naringin (oral administration), MCC950 (intraperitoneal injection), or their combination for 14 days. Working memory was tested by the Y maze. FluoroMyelin staining, MOG, and GFAP immunostaining assessed the demyelination extent, myelin intensity, and astrocyte activation, respectively. Oxidant/antioxidant biomarkers were measured using colorimetric techniques. The expression levels of MBP, PDGFRα, Olig2, Nrf2, HO-1, NQO-1, GSK3β, IL1β, and IL18 were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Our results indicated that the co-administration of naringin and MCC950 improved working memory and antioxidant capacity. A significant reduction was found in the extent of demyelination and inflammatory mediatorsin naringin and MCC950-treated mice. In addition, co-administration of naringin and MCC950 elevated the expression levels of pro-myelinating and antioxidant markers.

These findings indicated improvement of the working memory through co-administration of naringin and MCC950, which might be partly mediated by enhancing antioxidant capacity, promoting remyelination, and mitigating inflammation in the CPZ-induced demyelination model.