Altered insulin-like growth factor-2 signaling is associated with psychopathology and cognitive deficits in patients with schizophrenia

Abstract

BackgroundSchizophrenia is linked with abnormal brain neurodevelopment, on which IGF-2 (insulin-like growth factor-2) has a great impact. The purpose of this study was to assess the levels of serum IGF-2 and its binding proteins IGFBP-3 and IGFBP-7 in schizophrenia patients and the associations of these proteins with schizophrenia psychopathology and cognitive deficits. -Q, et al. (2020) Altered insulin-like growth factor-2 signaling is associated with psychopathology and cognitive deficits in patients with schizophrenia. PLoS ONE 15(3): e0226688. ConclusionsOur study demonstrates that serum IGF-2 was significantly correlated with negative and cognitive symptoms in patients with schizophrenia, suggesting that altered IGF-2 signaling may be implicated in the psychopathology and cognitive deficits in schizophrenia. BackgroundAccording to a hypothesis about schizophrenia, if an adult suffers from severe mental illness, the central nervous system must have developed in a disrupted manner [1,2]. This has been widely indicated by studies in areas of epidemiology, genetics and neuroimaging [3]. For example, structural brain abnormalities are apparent in the beginning stages of schizophrenia [4,5]; there were cases in which young people frequently suffered abnormal cognition and emotion abilities just before the appearance of the mental illness [6]; and primates suffering neonatal lesions had a disabled motion capability [7].As a type of insulin-like protein, insulin-like growth factor (IGF) is an integral component of the cell system in human bodies that serves as a communication channel regarding the physiological circumstances [8]. Accumulated evidence has convincingly demonstrated that IGF has an indispensable and crucial role to play in nerve growth [9]. During the development of brains, IGF signaling regulates the growth survival, maturations, and proliferation of many types of nerve cells, such as astrocytes, oligodendrocytes, NPC (nerve precursor cell) and NSC (nerve stem cell) [9]. In addition, IGF sends basic signals to NSC cells directing them to grow into particular lineages in early development and influences their specific biological roles in late development, with the help of other nerve signals [9]. Individuals suffering from IGF gene mutations are vulnerable to physically disabled growth, nanocephaly or intellectual disability [10,11,12].Two different IGF ligands, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2), have drawn much attention in recent studies. Researchers have shown that IGF-1 signaling plays a role in schizophrenia pathogenesis [13,14,15]. Specifically, plasma IGF-1 levels were decreased in antipsychotic-naive schizophrenia patients and were inversely correlated with positive symptom scores and hallucination subscores [13]. Antipsychotic treatment can increase serum IGF-1 levels in schizophrenia patients, and those patients with a greater increase showed a reduction in positive symptom scores to a higher extent [14]. Palomino et al. studied and showed that the...

Sex differences in association between cognitive impairment and clinical correlates in Chinese patients with first-episode drug-naïve schizophrenia

“…Language ability, executive function, attention, and the ability to lter irrelevant stimuli are all impaired. Working memory and executive function of patients with schizophrenia are also impaired [27][28][29]. Consistent with this nding, several cognitive de cits have been reported in adolescent schizophrenia.…”

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

“…As one of the IGFs, IGF-2 is expressed in brains not only during the development period but also during adulthood [14] . Recent studies have demonstrated that alterations of IGF-2 signaling are implicated in the pathogenesis of schizophrenia [15][16][17][18] . Specifically, a large CommonMind consortium RNA-sequencing study revealed that IGF-2 was the top downregulated gene in the prefrontal cortex of patients with schizophrenia [15] .…”

Insulin-Like Growth Factor 2 As a Possible Neuroprotective Agent and Memory Enhancer—Its Comparative Expression, Processing and Signaling in Mammalian CNS

“…Altered IGF-2 expression was reported in various diseases. For example, it was shown that schizophrenia patients who are not taking any antipsychotic medication have a decreased serum IGF-2 concentration compared with healthy controls [ 17 ]. On the contrary, patients who had been receiving a stable dose of oral antipsychotic medications had increased serum IGF-2 level [ 18 ].…”