Insulin-like growth factor-dynamics during electroconvulsive therapy: a neuropsychopharmacological signature?

Introduction: Mood disorders, schizophrenia and schizoaffective disorders rank among the most common and disabling psychiatric conditions worldwide, with an overall increasing incidence of mental disorders in recent years. Electroconvulsive therapy (ECT) is one of the most effective biological treatments for severe mood and psychotic disorders, yet its molecular mechanisms remain incompletely understood. Some studies suggest that cytokines and growth factors may be modulated by ECT. The insulin‑like growth factor (IGF)-system is implicated in neurogenesis, synaptic plasticity and neuroprotection and is altered across psychiatric diagnoses. Yet, longitudinal data on the IGF-system during ECT are lacking. We therefore aimed to investigate the trajectories of the peripheral IGF-system over the course of an acute ECT series and their link with clinical outcome.

Aims: Our primary objective was to investigate longitudinal alterations in the circulating IGF-system components across the course of an ECT series and to determine whether these trajectories differ between clinical responders and non-responders. In a secondary analysis, we quantified associations between clinical improvement and levels of the IGF-system components.

Methods: Thirty‑two adults with mood disorders, schizophrenia or schizoaffective disorders undergoing an ECT series were included. The insulin‑like growth factor (IGF)-system, consisting of IGF-1, IGF-2, IGF-binding protein 3 (IGFBP‑3) and the IGF‑1/IGFBP‑3 ratio (proxy of bioavailable IGF‑1) in serum was measured at baseline (pre‑ECT, t0), after the sixth ECT (t1), and at the end of the ECT series (t2). Clinical improvement was evaluated with the Clinical Global Impression - Improvement Scale (CGI‑I). Response was defined as CGI‑I ≤ 2 at end of the ECT series (t2). Linear mixed models adjusted for age, sex, body mass index, main diagnosis and response (response vs. non-response) examined temporal changes of the IGF-system and its association with clinical improvement. As a secondary analysis, linear mixed models were calculated assessing the link of clinical improvement as continuous variable (CGI-I score) with the IGF-system, adjusted for age, sex, body mass index and main diagnosis.

Results: The patients assessed had an average age of 51 ± 18 years. Our data showed that IGF‑1 concentrations and the IGF‑1/IGFBP‑3 ratio increased significantly from baseline to the sixth ECT (β = 0.42, p = 0.009; β = 0.34, p = 0.031), independent of treatment response after adjustment for confounders. Less favourable clinical improvement was related to higher overall IGF‑1 levels (β = 0.33, p = 0.021) but not IGF‑1/IGFBP‑3 levels (β = 0.21, p = 0.070) or other levels of the IGF-system.

Conclusions: To our knowledge, this study is the first to investigate the IGF-system components during an ECT series across multiple diagnoses. The findings suggest an unspecific IGF-1 and IGF-1/IGFBP-3 elevation during ECT and higher overall IGF-1 levels upon lower clinical improvement, possibly reflecting compensatory neuroprotective mechanisms, warranting replication and mechanistic investigation in future studies.

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