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Affected autonomic heart regulation is implicated in the pathophysiology of cardiovascular diseases and is associated with posttraumatic stress disorder (PTSD). However, although sympathetic hyperactivation has been repeatedly shown in PTSD, research has neglected parasympathetic function. The objective of this study is the long-term assessment of heart rate (HR) dynamics and its diurnal changes as an index of autonomic imbalance in PTSD. Since tonic parasympathetic activity underlies long-range correlation of heartbeat interval fluctuations in the healthy state, we included nonlinear (unifractal) analysis as an important and sensitive readout to assess functional alterations. We conducted electrocardiogram recordings over a 24-h period in 15 deployed male subjects with moderate to high levels of combat exposure (PTSD: n = 7; combat controls: n = 8) in the supine position. HR dynamics were assessed in two 5-h sub-epochs in the time and frequency domains, and by nonlinear analysis based on detrended fluctuation analysis. Psychiatric symptoms were assessed using structured interviews, including the Clinician Administered PTSD Scale. Subjects with PTSD showed significantly higher baseline HR, higher LF/HF ratio in the frequency domain, blunted differences between day and night-time measures, as well as a higher scaling coefficient αfast during the day, indicating diminished tonic parasympathetic activity. Diminished diurnal differences and blunted tonic parasympathetic activity altering HR dynamics suggest central neuroautonomic dysregulation that could represent a possible link to increased cardiovascular disease in PTSD.

Factors determining individuality are still poorly understood. Rodents are excellent model organisms to study individuality, due to a rich behavioral repertoire and the availability of well-characterized isogenic populations. However, most current behavioral assays for rodents have short test duration in novel test environments and require human interference, which introduce coercion, thereby limiting the assessment of naturally occurring individuality. Thus, we developed an automated behavior system to longitudinally monitor conditioned fear for assessing PTSD-like behavior in individual mice. The system consists of a safe home compartment connected to a risk-prone test compartment (TC). Entry and exploration of the TC is solely based on deliberate choice determined by individual fear responsiveness and fear extinction. In this novel ethological assay, C57BL/6J mice show homogeneous responses after shock exposure (innate fear), but striking variation in long-lasting fear responses based on avoidance and risk assessment (learned fear), including automated stretch-attend posture quantification. TC entry (retention) latencies after foot shock differed >24 h and the re-explored TC area differed >50% among inbred mice. Next, we compared two closely related C57BL/6 substrains. Despite substantial individual differences, previously observed higher fear of C57BL/6N vs. C57BL/6J mice was reconfirmed, whereas fear extinction was fast and did not differ. The observed variation in fear expression in isogenic mice suggests individual differences in coping style with PTSD-like avoidance. Investigating the assumed epigenetic mechanisms, with reduced interpretational ambiguity and enhanced translational value in this assay, may help improve understanding of personality type-dependent susceptibility and resilience to neuropsychiatric disorders such as PTSD.