Increased Functional Coupling between VTA and Hippocampus during Rest in First-Episode Psychosis

Abstract

Animal models suggest that interactions between the hippocampus and ventral tegmental area (VTA) underlie the onset and etiology of psychosis. While a large body of research has separately characterized alterations in hippocampal and VTA function in psychosis, alterations across the VTA and hippocampus have not been characterized in first-episode psychosis (FEP). As the phase of psychosis most proximal to conversion, studies specifically focused on FEP are valuable to psychosis research. Here, we characterize alterations in VTA-hippocampal interactions across male and female human participants experiencing their first episode of psychosis using resting state functional magnetic resonance imaging (rsfMRI). In comparison to age and sex matched healthy controls (HCs), FEP individuals had significantly greater VTA-hippocampal functional coupling but significantly less VTA-striatal functional coupling. Further, increased VTA-hippocampal functional coupling in FEP correlated with individual differences in psychosis-related symptoms. Together, these findings demonstrate alterations in mesolimbic-hippocampal circuits in FEP and extend prominent animal models of psychosis.

Circuit-Based Approaches to Understanding Corticostriatothalamic Dysfunction Across the Psychosis Continuum

“…A second trend in Figure 2 is that lower FC between the hippocampus, when either seeding the whole structure or just the anterior hippocampus, and striatum has also been reported across all stages, with the ventral striatum being involved consistently when symptom severity triggers help-seeking behavior (i.e., from ARMS individuals to chronic patients) (130,(147)(148)(149)(150)(151)(152). A third trend in Figure 2 is that dysconnectivity of the midbrain has been reported only in at-risk and clinical cohorts, with little involvement in subclinical psychosis (140,148,(151)(152)(153)(154)(155)(156). This trend suggests that midbrain dysfunction may be a trait marker of genetic risk and/or clinically significant symptoms.…”

The locus coeruleus‐dorsal hippocampal CA1 pathway is involved in depression‐induced perioperative neurocognitive disorders in adult mice

“…Especially the role of dopamine in the dorsal hippocampus in mediating different models of learning and memory has been increasingly discovered 44 . The ventral tegmental area (VTA) is the main source of dopamine in the brain, which has a highly reciprocal connection with the hippocampus 45 . Therefore, for decades, the VTA has been deemed the main source of hippocampal dopamine that mediates learning and memory 39 .…”

Macro- and Micro-Structural Alterations in the Midbrain in Early Psychosis

“…The midbrain is one of the critical brain systems affected in EP; 24 however, few studies have focused on the midbrain and EP. The ventral tegmental area (VTA), a critical brain region for reward learning and memory located in midbrain, is impaired in the early stages of psychosis: VTA-hippocampal functional connectivity is increased in EP, while VTA-striatal connectivity is reduced 25,26 , suggesting differential effects of dopaminergic circuits mediating seemingly contradictory effects in behavior (i.e., hypodopaminergic like anhedonia vs hyperdopaminergic like delusion or paranoia). VTA-hippocampal functional connectivity correlates with individual differences in the overall symptom severity as determined by the Brief Psychiatric Rating Scale 25 .…”