Mitochondrial dysfunction might have a central role in the pathophysiology of depression. Phenotypically, depression is characterized by lack of energy, concentration problems and fatigue. These symptoms might be partially explained by reduced availability of adenosine triphosphate (ATP) as a consequence of impaired mitochondrial functioning. This study investigated mitochondrial respiration in peripheral blood mononuclear cells (PBMCs), an established model to investigate the pathophysiology of depression. Mitochondrial respiration was assessed in intact PBMCs in 22 individuals with a diagnosis of major depression (MD) compared with 22 healthy age-matched controls using high-resolution respirometry. Individuals with MD showed significantly impaired mitochondrial functioning: routine and uncoupled respiration as well as spare respiratory capacity, coupling efficiency and ATP turnover-related respiration were significantly lower in the MD compared with the control group. Furthermore, mitochondrial respiration was significantly negatively correlated with the severity of depressive symptoms, in particular, with loss of energy, difficulties concentrating and fatigue. The results suggest that mitochondrial dysfunction contributes to the biomolecular pathophysiology of depressive symptoms. The decreased immune capability observed in MD leading to a higher risk of comorbidities could be attributable to impaired energy supply due to mitochondrial dysfunction. Thus mitochondrial respiration in PBMCs and its functional consequences might be an interesting target for new therapeutical approaches in the treatment of MD and immune-related comorbidities.

Cognitive functions and spontaneous neural activity show significant changes over the life-span, but the interrelations between age, cognition and resting-state brain oscillations are not well understood. Here, we assessed performance on the Trail Making Test and resting-state magnetoencephalographic (MEG) recordings from 53 healthy adults (18-89 years old) to investigate associations between age-dependent changes in spontaneous oscillatory activity and cognitive performance. Results show that healthy aging is accompanied by a marked and linear decrease of resting-state activity in the slow frequency range (0.5-6.5[emsp14]Hz). The effects of slow wave power on cognitive performance were expressed as interactions with age: For older (>54 years), but not younger participants, enhanced delta and theta power in temporal and central regions was positively associated with perceptual speed and executive functioning. Consistent with previous work, these findings substantiate further the important role of slow wave oscillations in neurocognitive function during healthy aging.

Posttraumatic stress disorder (PTSD) is associated with an enhanced risk for cardiovascular and other inflammatory diseases. Chronic low-level inflammation has been suggested as a potential mechanism linking these conditions. We investigated plasma cytokine levels as well as spontaneous and lipopolysaccharide (LPS)-stimulated cytokine production by peripheral blood mononuclear cells (PBMCs) in a group of 35 severely traumatized PTSD patients compared to 25 healthy controls. Spontaneous production of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α by isolated PBMCs was significantly higher in the PTSD compared to the control group and even correlated with PTSD symptom severity within the PTSD group. In contrast, circulating plasma levels of pro- and anti-inflammatory cytokines such as IL-6, IL-8, IL-10, TNF-α, or monocyte chemotactic protein (MCP)-1 were not significantly altered in PTSD patients compared to healthy controls. Our findings indicate that PBMCs of PTSD patients are already pre-activated in vivo, providing further evidence for low-grade inflammation in PTSD. This might possibly represent one psychobiological pathway from PTSD to poor physical health.

Social phobia has been associated with abnormal processing of angry faces, which directly signal disapproval--a situation that social phobics fear. This study investigated the electrophysiological correlates of emotional face processing in socially phobic and non-phobic individuals. Subjects identified either the gender (modified emotional Stroop task) or the expression of angry, happy, or neutral faces. Social phobics showed no deviations from controls in reaction times, heart rates, P1, or P2 amplitudes in response to angry faces, although elevated FSS scores were associated with higher P1 amplitudes in social phobic persons. In addition, social phobic persons showed enhanced right temporo-parietal N170 amplitudes in response to angry faces in the emotion identification task. Furthermore, higher scores on the Social Phobia and Anxiety Inventory (SPAI) were associated as a trend with larger N170 amplitudes in response to angry faces in the emotion identification task. Thus, the present results suggest that social phobics show abnormalities in the early visual processing of angry faces, as reflected by the enhanced right-hemispheric N170 when the emotion of the angry face was the focus of attention, while behavioral responses and heart rates showed no evidence for preferred processing of angry facial expressions.

From The Journal of Clinical Psychiatry: