Abstract Initially explored in military settings, post-traumatic stress disorder (PTSD) has shown increasing prevalence in the general population. The high comorbidity rates between bipolar disorder (BD) and PTSD have raised the issue of whether some characteristics of BD could represent risk factors for PTSD. In combat-related PTSD, the 18 kDa mitochondrial translocator protein (TSPO), essential for steroid synthesis, was found to be decreased. Aims of the present study were: 1) the assessment of the TSPO mitochondrial density in lymphomonocytes from civilian patients with non-combat-related PTSD, without current or lifetime Axis I mood comorbidity, versus controls; 2) the exploration of the correlations between TSPO density and the presence of comorbid manic/hypomanic lifetime spectrum symptoms. Assessments included the Structured Clinical Interview for DSM-IV (SCID), the Impact of Event Scale (IES), and the lifetime Mood Spectrum Self-Report (MOODS-SR). Blood samples were processed to assess TSPO binding parameters in lymphomonocyte mitochondrial membranes. PTSD patients showed a significant decrease in TSPO density, without changes in mitochondrial citrate synthase activity. Further, TSPO density correlated with the number of lifetime manic/hypomanic spectrum symptoms. For the first time, TSPO density was found to be decreased in non-war-related PTSD and such decreases correlated with comorbid manic/hypomanic spectrum symptoms, indicating a possible role of sub-threshold bipolar comorbidity in PTSD-related neurobiological dysregulation.