The present study explored anxious apprehension in panic disorder patients and controls in two threat conditions, darkness and threat of shock. Autonomic arousal and startle eyeblink reflexes were recorded in 26 panic disorder patients and 22 controls during adaptation, a safe condition, threat of shock, and darkness. Exposure to darkness resulted in a clear potentiation of the startle reflex. Panic patients but not controls responded with an increase in heart rate that was positively related to severity of agoraphobic avoidance. Threat of shock resulted in a startle potentiation that tended to be stronger in panic patients without comorbid depression than controls and attenuated in those patients who suffered from severe depression. These data suggest that only panic patients without depression belong to the fear disorders spectrum whereas panic patients with comorbid depression might rather belong to the distress disorders profile.
Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA methylation. Hdac1 overexpression in neurons of the medial prefrontal cortex, but not in the dorsal or ventral hippocampus, mimics schizophrenia-like phenotypes induced by ELS. Systemic administration of an HDAC inhibitor rescues the detrimental effects of ELS when applied after the manifestation of disease phenotypes. In addition to the hippocampus and prefrontal cortex, mice subjected to ELS exhibit increased Hdac1 expression in blood. Moreover, Hdac1 levels are increased in blood samples from patients with schizophrenia who had encountered ELS, compared with patients without ELS experience. Our data suggest that HDAC1 inhibition should be considered as a therapeutic approach to treat schizophrenia.
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