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

Abstract

Insulin-like growth factor 2 (IGF-2) and IGF binding protein 7 (IGFBP-7) have been related to schizophrenia (SZ) due to their implication in neurodevelopment. The purpose of this study was to assess whether the alterations in IGF-2 and IGFBP-7 in SZ patients are intrinsically related to the psychiatric disorder itself or are a secondary phenomenon due to antipsychotic treatment. In order to test this hypothesis, we measured plasma IGF-2 and IGFBP-7 in drug-naïve first episode (FE) and multiple episodes or chronic (ME) SZ Caucasian patients who have been following treatment for years. A total of 55 SZ patients (FE = 15, ME = 40) and 45 healthy controls were recruited. The Positive and Negative Syndrome Scale (PANSS) and the Self-Assessment Anhedonia Scale (SAAS) were employed to check schizophrenic symptomatology and anhedonia, respectively. Plasma IGF-2 and IGFBP-7 levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA). The FE SZ patients had much lower IGF-2, but not IGFBP-7, than controls. Moreover, both IGF-2 and IGFBP-7 significantly increased after atypical antipsychotic treatment (aripiprazole, olanzapine, or risperidone) in these patients. On the other hand, chronic patients showed higher levels of both proteins when compared to controls. Our study suggests that circulatory IGF-2 and IGFBP-7 increase after antipsychotic treatment, regardless of long-term conditions and being lower in drug-naïve FE patients.

Plasma IGFBP-3 and IGFBP-5 levels are decreased during acute manic episodes in bipolar disorder patients

“…One study conducted in Spain found that there was no significant difference in IGF-1 levels between first-psychotic episode BD patients and controls neither at baseline nor after 1, 6, and 12 months of treatment ( Palomino et al, 2013 ). Although we could not study first-episode BD patients, we had previously showed that both IGF-2 and IGFBP-7 were significantly increased in first-episode SZ Spanish patients ( Fernández-Pereira et al, 2022 ). Curiously, during the first psychotic episode, the levels of IGF-1 in SZ patients were significantly higher than those in BD patients but not in controls ( Palomino et al, 2013 ).…”

“…Nonetheless, to the best of our knowledge, no study has yet evaluated peripheral IGF-2 levels in BD patients. Our group previously reported that the plasma levels of IGF-2 were significantly increased in chronic patients of related psychiatric disorders such as schizophrenia (SZ) ( Fernández-Pereira et al, 2022 ) and major depressive disorder (MDD) ( Fernández-Pereira et al, 2023 ) during either a psychotic or a depressive episode, and those levels were normalized after a period of treatment with antipsychotics or antidepressants, respectively. From our perspective, exploring the peripheral relation of inflammatory markers and IGF proteins could be of interest in BD patients.…”

MiRNA Differences Related to Treatment-Resistant Schizophrenia

“…2023, 24, 1891 2 of 20 response to at least two sequential non-clozapine antipsychotic trials of sufficient dose, duration, and adherence [6]. Patients with TRS have higher rates of substance abuse, early cognitive decline, and higher rates of suicide ideation [7][8][9][10]. As pharmacological and therapeutic approaches differ between SZ and TRS [11][12][13][14], early identification of the resistance condition is essential for a rapid and effective pharmacological intervention, limiting damage to the patient and their environment and improving the adherence to treatment [15].…”

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.…”

“…In contrast, peripheral IGF-1 has received far more attention in the last few decades, not just in depression [38][39][40][41][42][43][44][45][46][47][48][49], but also in other mental conditions such as schizophrenia [29,[49][50][51][52][53][54][55][56] and bipolar disorder [57][58][59][60][61][62]. On the other hand, circulating IGFBPs have been less widely studied than their ligand counterparts in the field of psychiatry, and always in a context of their IGF-dependent actions [29][30][31][32]38,55,[63][64][65]. Some IGFBPs have received more attention than others.…”