Discussion
cognitive impairment, weight gain, metabolic dysfunction, cognitive impairments, schizophrenia
HYPERGLYCEMIA, INSULIN RESISTANCE, CORTEX, DYSLIPIDEMIA
To our knowledge, this is the first clinical proof that metformin could significantly improve cognitive impairments in patients with schizophrenia, especially in speed of processing, working memory, verbal learning, and visual learning. Few studies investigating pharmacological treatments for cognitive impairment in schizophrenia report positive findings [Nevertheless, not all metformin studies have yielded significant improvements. Despite the previously reported correlations between metabolic dysfunction and cognition [Another important finding of our study was that metformin enhanced the FC between the DLPFC subregion and the anterior and middle cingulate cortex (ACC/MCC) as well as enhancing the FC between the DLPFC subregions. Furthermore, the correlation analyses and mediation analyses indicated that the efficacy of metformin for cognitive impairment in patients with schizophrenia might be achieved by enhancing the FC between DLPFC and ACC/MCC. The DLPFC is a key node of the frontoparietal network [This study has some limitations. First, it was not a double-blind study, which may have caused bias and overestimated the effect of metformin on improving cognitive function. Our preliminary evidence of efficacy requires confirmation in a multicenter, double-blind, placebo-controlled trial. Second, we confined the analysis to the DLPFC and did not examine other brain areas known to be recruited into a network for cognitive performance. Third, although the effects of metformin on cognition and on metabolism are correlated, subsequent studies are needed to demonstrate a possible causal relationship. At last, we did not administer daily functioning or quality-of-life scales, which may have led to a conceptually narrow evaluation of cognition.The present study found that metformin effectively improves cognition in patients with schizophrenia. The fMRI activity index in the DLPFC increases with metformin treatment and correlates with cognitive performance. More than 50% patients with schizophrenia had metabolic dysfunction, including weight gain, hyperglycemia, dyslipidemia, and insulin resistance [