Negative symptoms, repetitive transcranial magnetic stimulation and heart rate variability in schizophrenia and depression

Sammanfattning: Negative symptoms comprise anhedonia, avolition, and blunted affect. Although first described in schizophrenia, these symptoms share phenomenology with the depressive state. Pharmacological treatment has not been successful in reducing negative symptoms. Repetitive transcranial magnetic stimulation (rTMS) is a non-pharmacological treatment option for moderate to severe depression. There have also been attempts to treat negative symptoms in both schizophrenia and depression with rTMS.Cardiovascular disease is common in schizophrenia and depression. Heart rate variability (HRV) is an established proxy for cardiac autonomic functioning and numerous studies have found lower HRV in patients with schizophrenia and depression. The impact of psychopharmacological treatment on HRV has been extensively studied and anticholinergic compounds have been found to decrease HRV.Lastly, since the most commonly used rTMS depression targets are also the brain regions involved in central autonomic regulation, there is reason to consider a potential effect of rTMS on HRV.The overall aim of this thesis was to investigate negative symptoms, rTMS, and HRV in schizophrenia and depression.Study I was a validation study of a Swedish translation of the Clinical Assessment Interview for Negative Symptoms (CAINS). Thirty-four patients with schizophrenia were interviewed and it was concluded that the Swedish version of the CAINS exhibited acceptable psychometric properties.Study II was a double-blind randomized controlled trial of rTMS for negative symptoms in schizophrenia and depression. There was a significant decrease of negative symptoms in the depression group, but not in the schizophrenia group. There were no effects on overall depressive symptoms in either group.Study III assessed determinants of HRV in schizophrenia, depression, and healthy controls. The results indicated lower HRV in both patient groups, even after controlling for several factors, and also that anticholinergic burden impacted HRV.In Study IV, the relationship between HRV and the functional and structural connectivity of the anterior cingulate cortex was investigated in patients with schizophrenia and compared with that in healthy controls. It was found that connectivity with the cerebellum might play a role in the autonomic modulation network in patients with schizophrenia.Lastly, in Study V, the effect of a treatment course with rTMS on HRV was investigated in patients with depression, as well as HRV’s relationship to symptom change. No effects on HRV were detected, nor any correlations between HRV and symptom change. Further, baseline HRV could not predict treatment response.

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