The association of post-stroke anhedonia with salivary cortisol levels and stroke lesion in hippocampal/parahippocampal region

Luisa Terroni,1 Edson Amaro Jr,2 Dan V Iosifescu,3 Patricia Mattos,4 Fabio I Yamamoto,5 Gisela Tinone,5 Adriana B Conforto,5 Matildes FM Sobreiro,1 Valeri D Guajardo,1 Mara Cristina S De Lucia,7 Ayrton C Moreira,6 Milberto Scaff,5 Claudia C Leite,2 Renerio Fraguas1 1Consultation-Liaison Psychiatry Group, Department and Institute of Psychiatry, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil; 2Department of Radiology, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil; 3Mood and Anxiety Disorders Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil; 5Department of Neurology, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil; 6Department of Medicine, University of São Paulo, School of Medicine, Ribeirão Preto, Brazil; 7Division of Psychology, Central Institute, Clinical Hospital, University of São Paulo School of Medicine, São Paulo, Brazil Background: Anhedonia constitutes a coherent construct, with neural correlates and negative clinical impact, independent of depression. However, little is known about the neural correlates of anhedonia in stroke patients. In this study, we investigated the association of post-stroke anhedonia with salivary cortisol levels and stroke location and volume.Patients and methods: A psychiatrist administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition to identify anhedonia in 36 inpatients, without previous depression, consecutively admitted in a neurology clinic in the first month after a first-ever ischemic stroke. Salivary cortisol levels were assessed in the morning, evening, and after a dexamethasone suppression test. We used magnetic resonance imaging and a semi-automated brain morphometry method to assess stroke location, and the MRIcro program according to the Brodmann Map to calculate the lesion volume.Results: Patients with anhedonia had significantly larger diurnal variation (P-value =0.017) and higher morning levels of salivary cortisol (1,671.9±604.0 ng/dL versus 1,103.9±821.9 ng/dL; P-value =0.022), and greater stroke lesions in the parahippocampal gyrus (Brodmann area 36) compared to those without anhedonia (10.14 voxels; standard deviation ±17.72 versus 0.86 voxels; standard deviation ±4.64; P-value =0.027). The volume of lesion in the parahippocampal gyrus (Brodmann area 36) was associated with diurnal variation of salivary cortisol levels (rho=0.845; P-value =0.034) only in anhedonic patients.Conclusion: Our findings suggest that anhedonia in stroke patients is associated with the volume of stroke lesion in the parahippocampal gyrus and with dysfunction of the hypothalamic–pituitary–adrenal axis. Keywords: anhedonia, stroke, glucocorticoids, depression, hippocampus, parahippocampa