Resting Hyperperfusion of the Hippocampus, Midbrain, and Basal Ganglia in People at High Risk for Psychosis

Abstract

A high risk for psychosis was associated with increased resting activity in the hippocampus, midbrain, and basal ganglia. Subsequent resolution of the high-risk state was linked to a normalization of activity in these regions. These findings are consistent with animal models that propose that psychotic symptoms may be generated when hippocampal hyperactivity drives hyperactivity in regions involved in subcortical dopamine signaling.

Increased resting perfusion of the hippocampus in high positive schizotypy: A pseudocontinuous arterial spin labeling study

“…Contrary to our second hypothesis derived from CHR studies (Allen et al, 2017, 2016; Kindler et al, 2018), we did not find any group differences in resting perfusion of the basal ganglia or midbrain. Mechanistically, animal models strongly implicate hippocampal hyperactivity as a primary factor leading to downstream subcortical hyperdopaminergia and psychotic‐like behaviors (Lisman et al, 2008; Lodge & Grace, 2011).…”

“…The two previous ASL studies in CHR subjects did also not observe significant correlations between levels of prodromal symptoms and hippocampal CBF (Allen et al, 2017, 2016). We cannot exclude the possibility that, by selecting subjects scoring above a certain threshold to determine high positive schizotypy, the range of O‐LIFE symptom scores was limited in both groups.…”

“…To our knowledge, this is the first application of the ASL method to investigate differences in resting perfusion in a schizotypy group. Given that the study groups only differed on the presence of schizotypal traits, and that hippocampal hyperperfusion has been reported in patients with psychosis (Friston et al, 1992; Liddle et al, 1992; Malaspina et al, 2004; Pinkham et al, 2011; Schobel et al, 2013, 2009; Talati et al, 2014, 2015; although see Andreasen et al, 1997; Catafau et al, 1994; Early et al, 1987; Parellada et al, 1994), and in people at CHR of sychosis (Allen et al, 2017, 2016; Schobel et al, 2013), our study findings suggest that increased hippocampal activity (reflected in an elevation of regional perfusion) is also involved in the expression of subclinical psychotic‐like experiences.…”

“…In terms of the clinical or functional correlates of CBF abnormalities along the psychosis spectrum, previous longitudinal studies in CHR individuals reported that (a) elevated hippocampal cerebral blood volume as measured with the contrast agent gandolinium was linked to the risk of later transition to psychosis (Schobel et al, 2013, 2009), (b) increased hippocampal CBF as measured with ASL was subsequently normalized in CHR subjects who remitted from their CHR state (Allen et al, 2016), and (c) hippocampal CBF and medial prefrontal GABA+ concentrations were associated in CHR individuals who subsequently developed a psychotic disorder (Modinos et al, 2018). Although the observation of an increase in resting hippocampal perfusion in HS is consistent with the majority of previous studies in CHR and schizophrenia with a specific focus on the hippocampus, as discussed above, the cross‐sectional nature of the present study prevents investigating whether this finding is prospectively linked to a subsequent emergence of mental health disorders in schizotypy (Cannon et al, 2015).…”

“…An independent samples t test was used to test for significant differences between the HS and LS groups using a voxel‐wise region of interest (ROI) approach. ROIs were specified a priori using the coordinates from a previous CBF study comparing CHR subjects with healthy controls (Allen et al, 2016): MNI coordinates in right x , y , z  = 20, −28, −8 and left hippocampus x , y , z  = −22, −28, −8; basal ganglia: right x , y , z  = 22, −12, −4 and left x , y , z  = −18, −8, −4 pallidum/putamen; and in the left midbrain x , y , z  = −10, −32, −18. These coordinates were used for small volume correction (SVC) with a 6‐mm sphere.…”