Enhanced brainstem cerebral blood flow accompanies symptoms of anhedonia in young adults

Abstract

Study: Midbrain serotonergic projections are of crucial theoretical significance for mood disorders. Furthermore, learned helplessness (LH) is associated with enhanced metabolic activity in rodent serotonergic midbrain models. However, little evidence supports serotonergic projections in predicting illness severity. We employed arterial spin labeling (ASL) to measure whole brain cerebral blood flow (CBF) in distressed and healthy individuals varying in anxiety and anhedonia. Methods: 36 distressed (27 females; mean age=22.2, SD=2.1) and 34 healthy (19 females; mean age=21.5, SD=1.8) individuals underwent a resting acquisition. Blood flow was measured using a multiband pseudo continuous ASL sequence. Regional cerebral perfusion data was collected with 25 slices, multiband factor=5, 4mm slick thickness, FA=90, 64x64 resolution, FOV=192x912, TR/TE=3.5s/19ms, labeling time=1.5s and postlabeling delay=1.7s. Anhedonia was measured using the Mood and Anxiety Symptom Questionnaire Anhedonic Depression Scale (MASQ-ADS), with the Snaith–Hamilton Pleasure Scale (SHAPS) as a secondary measure. Anxiety was measured using the MASQ General Distress Anxious Symptoms Scale. Anhedonia, anxiety and group were included in the regression model. Results: Anhedonia (MASQ-ADS) was associated with increased CBF in the midbrain (T=5.24, p_FWE=0.033), proximal to putative locations of the dorsal/median raphe nuclei (-12, -34, -26). Similar, although weaker, findings were observed with the SHAPS. Conclusion: Anhedonia is associated with altered CBF in the midbrain in a young adult population showing heterogeneous symptoms of distress. Significance: ASL may provide a particularly promising tool to examine enhanced local perfusion, potentially reflecting underlying midbrain serotonergic activity, which is predicted on the basis of LH studies in rodents but has thus far been difficult to investigate in humans.