Changes of Serum Insulin-like Growth Factor-2 Response to Negative Symptom Improvements in Schizophrenia Patients Treated with Atypical Antipsychotics

Abstract

SummaryAccumulating evidence suggests that a disruption of early brain development, in which insulin-like growth factor-2 (IGF-2) has a crucial role, may underlie the pathophysiology of schizophrenia. Our previous study has shown that decreased serum IGF-2 was correlated with the severity of psychopathology in patients with schizophrenia. Here we conducted a prospective observation trial to investigate the effects of atypical antipsychotics on serum IGF-2 level and its relationship with clinical improvements in schizophrenia patients. Thirty-one schizophrenia patients with acute exacerbation and 30 healthy individuals were recruited in this study. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and serum IGF-2 levels were determined using ELISA. We found that schizophrenia patients with acute exacerbation had lower serum IGF-2 levels than control individuals at baseline (P<0.05). After 2 months of atypical antipsychotic treatment, a significant improvement in each PANSS subscore and total score was observed in patients (all P<0.01), and the serum IGF-2 levels of patients were significantly increased compared with those at baseline (203.13±64.62 vs. 426.99±124.26 ng/mL; t =−5.044, P<0.001). Correlation analysis revealed that the changes of serum IGF-2 levels in patients were significantly correlated with the improvements of negative symptoms (r=−0.522, P=0.006). Collectively, our findings demonstrated changes of serum IGF-2 response to improvements of negative symptoms in schizophrenia patients treated with atypical antipsychotics, suggesting that serum IGF-2 might be a treatment biomarker for schizophrenia.

Insulin-like Growth Factor 2 (IGF-2) and Insulin-like Growth Factor Binding Protein 7 (IGFBP-7) Are Upregulated after Atypical Antipsychotics in Spanish Schizophrenia Patients

“…However, the levels of both IGF-2 and IGFBP-7 significantly increased in the FE drug-naïve group of patients after a short period with atypical antipsychotics (aripiprazole, olanzapine, or risperidone), suggesting that the increase could be mediated by the treatment itself regardless of long-term conditioning and even be drug-type independent, as was recently observed for IGF-2 in Chao et al’s (2020) study [ 37 ].…”

“…These results contrast with the negative correlation that was found in Yang et al (2020) [ 36 ]. Nevertheless, that correlation has not been observed in other studies, but they have noticed a significant correlation between the increase in IGF-2 levels and the reduction of PANSS-N scores in patients that had been through therapy with atypical antipsychotics [ 37 ]. IGFBP-7 has been less studied in this context, and to our knowledge, no correlation has been found with any PANSS subscale, and the same was observed for IGFBP-3 [ 36 ].…”

“…As has been previously mentioned, IGF-2 has been found to be either upregulated [ 30 ] or downregulated [ 36 , 37 ]. In our case, we have found that the levels of both IGF-2 and IGFBP-7 are upregulated in chronic patients when compared to healthy controls, and so far, it constitutes the first data on a Spanish (Caucasian) SZ cohort.…”

“…Then, Yang et al (2020) observed that IGF-2 was actually downregulated in a Chinese population of SZ patients that had been without treatment 3 months before protein measurement took place [ 36 ]. Shortly after, Chao et al (2020) proved that IGF-2 was also downregulated in Chinese SZ patients, and interestingly, IGF-2 levels increased after 8 weeks of treatment regardless of the atypical antipsychotic administered (aripiprazole, clozapine, olanzapine, or risperidone) [ 37 ]. It is notable that the only study that has addressed IGF-2 gene expression found that the IGF-2 gene was the top downregulated gene in the prefrontal cortex of chronic SZ patients [ 38 ], which might represent the state of IGF-2 in circulation.…”

Protein Plasma Levels of the IGF Signalling System Are Altered in Major Depressive Disorder

“…In the context of psychiatric disorders, IGF-2 peripheral levels have been previously studied in schizophrenia [29][30][31][32] and in neurodegenerative disorders that impair memory or cognitive status, such as Alzheimer's disease [33][34][35], Huntington's disease [36] and Parkinson's disease [37]. However, to the best of our knowledge, there is no literature available on IGF-2 peripheral levels in major depressive disorders involving human samples.…”