Hippocampal Resting State Functional Connectivity in Patients With Schizophrenia and Unaffected Family Members

Abstract

The hippocampus is an important candidate region in the study of functional connectivity alterations in schizophrenia (SZ) given its role as a functional hub for multiple brain networks. Although studies have implicated the hippocampus in SZ, no studies have compared hippocampal functional connectivity in healthy participants, patients with SZ, and unaffected family members (UAFMs). Patients and UAFM likely share biomarkers associated with susceptibility to SZ; the study of UAFM may also reveal compensatory markers. Patients with SZ, UAFM, and healthy control (HC) participants underwent resting state magnetic resonance imagingty and completed the Wisconsin Card Sort Task (WCST) as a measure of general cognitive function. We compared functional coupling with a hippocampus seed across the three groups. SZ and UAFM groups shared reductions in connectivity between the hippocampus and the striatum relative to HC. We also identified a significant positive correlation between WCST errors and hippocampal-striatal connectivity in the UAFM group. Hippocampal-striatal rsFC may be associated with familial susceptibility to SZ and with subtle cognitive deficits in the UAFM of individuals with SZ.

Dysmaturation Observed as Altered Hippocampal Functional Connectivity at Rest Is Associated With the Emergence of Positive Psychotic Symptoms in Patients With 22q11 Deletion Syndrome

“…In line with our findings, abnormal ACC resting state connectivity in patients with 22q11DS has been previously implicated as one of the J o u r n a l P r e -p r o o f main discriminative patterns in the presence of psychotic symptoms (35,52). Moreover, previous research has already suggested aberrant HIP connectivity with PFC in schizophrenia and similarly in non-syndromic individuals at a higher risk for psychosis (21,(53)(54)(55)(56)(57). Particularly, our longitudinal approach demonstrated that deficits in HIP-PFC connectivity in PPS(+) patients emerge from a developmental drop during adolescence, which, in turn, is known as a critical period for the emergence of sub-threshold psychotic symptoms both in 22q11DS and in the general population (58).…”

“…Correspondingly, disrupted structural connectivity between hippocampus and cortical regions has been frequently proposed as a relevant marker in schizophrenia (16,17). Moreover, deficits in functional coordination between hippocampus and various brain regions such as para-hippocampal gyri, medial prefrontal cortex J o u r n a l P r e -p r o o f (mPFC) and, more largely, the default mode network (DMN) have been documented (18)(19)(20)(21). Similar but less severe alterations in functional connectivity have been reported in patients in the prodromal phase of the disease, specifically in regards to the prefrontal cortex and anterior cingulate (21)(22)(23).…”

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models

“…For a long while, it has been well-known that structural aberrations of the hippocampus are a common hallmark of schizophrenia ( Figure 1 ). Over decades, the evidence of severe hippocampal abnormalities in schizophrenia patients is mounting and includes a remarkable reduction of the hippocampal volume [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ], a dysregulation of synaptic protein levels [ 26 , 27 , 28 ] and a dysconnectivity of the hippocampus from further parts of the CNS [ 29 , 30 , 31 , 32 ]. The general reduction of the hippocampal volume can already be observed in patients with a high risk for psychosis [ 33 ].…”

“…In addition to the hyperactivity of the hippocampus in patients at high risk for psychosis and schizophrenia patients, a functional dysconnectivity has been described for the hippocampo-striatal and the hippocampo-prefrontal pathway [ 29 , 31 , 82 ]. In a recently published study, the connectivity of the anterior hippocampus in patients with a first-episode psychosis is therefore discussed as a useful predictor for the response of an antipsychotic treatment [ 83 ].…”

Shared and distinct functional connectivity of hippocampal subregions in schizophrenia, bipolar disorder, and major depressive disorder

“…The different subregions have different structural foundations and perform different functions in memory and cognition ( 24 ). Recent research has revealed that the different hippocampal subregions are differentially affected in SZ, BD, and MDD ( 25 – 28 ). Therefore, we postulate that the hippocampal subregions may reflect some intrinsic features among these three psychiatric disorders.…”