Fig. 1: Model of how corticolimbic brain circuit dysfunction may contribute to positive, negative and cognitive symptoms in schizophrenia spectrum disorders (SSD) as adapted from previous models by Grace and colleagues.

A Abnormalities have been identified in corticolimbic structure, functional activation and connectivity in SSD. B Diagram displaying a model for interactions between corticolimbic brain circuits and mechanisms leading to symptom domains. Hippocampal hyperactivity and alterations of rhythmicity cause downstream effects within the nucleus accumbens, ventral pallidum and ventral tegmental area, resulting in increased striatal dopamine signalling and positive symptoms. It may also cause negative symptoms by affecting emotional processing and reward outcomes via the amygdala, and impacting decision-making through the medial prefrontal, anterior cingulate and orbitofrontal cortices. Increased excitatory output from the hippocampus to the dorsolateral prefrontal cortex may lead to reduced synaptic density and disruption to the oscillatory activity necessary for cognitive functions.