Perturbations of Zinc Homeostasis and Onset of Neuropsychiatric Disorders

Zinc (Zn²⁺) is a trace element essential for its catalytic, antioxidant, and immunomodulatory roles extending to synaptic signalling in the central nervous system. In this narrative review, we aim to offer the reader evidence linking perturbations of the Zn²⁺ homeostasis, including deficiency, excess, or transportation anomalies, to neuropsychiatric conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD). A targeted, unsystematic PubMed search followed by an extensive pearl-growing strategy was applied to further augment study selection based on the extensive expertise of study authors. Overall, most of the evidence currently available suggests a modest benefit for a Zn²⁺ supplement of around 25-30 mg/day as an augmentation to MDD treatment, with potential benefits of smaller magnitude in paediatric ADHD. Evidence for perturbations of Zn²⁺ as a biomarker of risk for these neuropsychiatric disorders remains unconvincing. The role of Zn²⁺ supplements in the treatment of the selected conditions remains largely unknown due to the lack of specific, randomised controlled trials conducted to explore their efficacy. The long-term safety, optimal doses for specific applications, and the exploration of possible biomarkers to stratify patient selection to identify the optimal candidate for Zn²⁺ supplements remain unanswered questions.