Elevated Copper Level in Schizophrenia Results in Neurotransmitter and Cognitive Alteration.

Elevated copper (Cu) levels, altered neurotransmitter and BDNF (Brain-Derived Neurotrophic Factor) signaling have been implicated in the pathophysiology of several neurodegenerative and neuropsychiatric conditions. However, the relationship between Cu and these factors in Schizophrenia (SZ) remains unclear. Our previous study reported a high Cu level associated with disease severity in SZ patients. Therefore, this study aimed to investigate whether elevated Cu levels are associated with neurotransmitters, BDNF, and cognitive function in individuals with SZ, thereby providing insights into potential mechanistic links to the neurobiological processes. To achieve this aim, a total of thirty-six SZ patients and thirty-six healthy controls (HCs) were enrolled. Blood samples were collected from AIIMS, Jodhpur, India and analyzed using inductively coupled plasma optical emission spectroscopy (ICP-OES) for Cu, RT-qPCR for BDNF expression, and ELISA for neurotransmitter analysis. Compared to healthy controls, SZ patients showed higher levels of Cu, dopamine (DA), serotonin (SE), and GABA. Cu showed a positive association with GABA level and a negative association with Stroop total scores. Additionally, DA and GABA demonstrated negative correlations with Stroop color word (ρ = -0.43 and − 0.39), and DA was negatively linked with Stroop color (ρ = -0.40), Stroop total scores (ρ = -0.40). In conclusion, elevated Cu levels in individuals with SZ may disrupt neurotransmitter homeostasis, contributing to cognitive impairments. These findings highlight a potential mechanistic link between Cu dysregulation and the neurobiological processes, suggesting that copper homeostasis could play a crucial role in the SZ pathophysiology.