Common Neural Mechanisms Underlying Emotional and Cognitive Disorders: Circuits, Neurotransmitters, and Network Interactions

Abstract

Emotional disorders such as major depressive disorder (MDD) and bipolar disorder (BD), and cognitive disorders such as Alzheimer’s disease (AD) and schizophrenia, have imposed an increasingly heavy burden on the global community and often occur simultaneously, which indicates that there are overlapping biological mechanisms. Current diagnostic frameworks remain categorical, and symptom based. This study examines shared neural mechanisms involving prefrontal–limbic circuits, large-scale networks, neurotransmitters, and neuro-immune–endocrine systems across these disorders. Evidence highlights convergent disruptions of the prefrontal–limbic circuit, including weakened top-down prefrontal control, hippocampal degeneration, and abnormal amygdala reactivity, which leads to executive, memory, and affective deficits. Wholebrain neuroimaging analyses implicate dysregulation of the default mode network (DMN), central executive network (CEN), and salience network (SN) as a unifying network signature underlying attentional dysfunction and impaired cognitive flexibility. At the neurochemical level, monoaminergic imbalance, dopaminergic dysregulation, and glutamate GABA imbalance collectively link mood instability with cognitive decline. Systemically, neuroinflammation and HPA axis hyperactivity disrupt neurotransmission, synaptic plasticity, and network function, which couples affective symptoms with cognitive impairment. These findings support a transdiagnostic model in which interacting circuit, network, and systemic abnormalities produce shared mechanisms across disorders. Recognising these common mechanisms may pave the way for improved therapeutics across emotional and cognitive disorders. For example, network-based biomarkers could enable earlier detection and precision diagnosis, while mechanism targeted interventions may reduce treatment resistance and enhance personalised outcomes.