Pseudohypoalgesia on the skin: a novel view on the paradox of pain perception in depression.

Previous studies reported increased heat pain thresholds and decreased ischemic pain thresholds in patients experiencing depression. The increased sensitivity to ischemic muscle pain was assumed to represent a model for the investigation of physical symptoms in the disease. Here, we explored how the serotonin and noradrenaline reuptake inhibitor duloxetine influences experimental pain thresholds and tolerances in depressed patients during treatment. Twenty-two patients experiencing unipolar depression were included. Pain assessments were conducted unmedicated at baseline, after 1 week, and after 6 weeks of duloxetine treatment. We observed the expected clinical response of patients indicated by a significant reduction in the Montgomery Depression Rating Scale after 6 weeks. At baseline, we found increased heat pain thresholds in patients in comparison to controls while patients simultaneously rated augmented pain perception on the visual analog scale. In contrast, patients were significantly more perceptive to ischemic muscle pain at baseline. During treatment, the examined pain thresholds showed differential changes: Increased heat pain thresholds of patients normalized during treatment, whereas no significant change was observed for ischemic pain thresholds. Thus, our results might change the view on the paradox of pain perception in major depression because increased heat pain thresholds are associated with augmented pain perception in the disease.

Autonomy of autonomic dysfunction in major depression.

OBJECTIVE: To investigate cardiac autonomic dysfunction in patients with major depressive disorder (MDD). Research in this area has faced several limitations because of the heterogeneity of the disease, the influence of medication, and methodological shortcomings. METHODS: Participants were 75 patients suffering from an acute recurrent episode of MDD and 75 matched controls. All participants were assessed at baseline for linear and nonlinear parameters of heart rate variability, QT variability and baroreflex sensitivity. Participants with MDD were reassessed after 7 to 9 days of treatment with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin and noradrenaline selective reuptake inhibitor (SNRI) antidepressant. RESULTS: In the initial examination, patients showed an overall shift of autonomic balance toward sympathetic predominance as compared with matched controls, with a decrease in parasympathetic parameters and baroreflex sensitivity, and an increase in sympathetically influenced QT variability. Overall, antidepressant treatment exacerbated this imbalance, with differential effects observed for SSRI and SNRI treatment. In contrast to autonomic dysfunction in other disorders, such as schizophrenia, autonomic dysfunction in MDD appeared to be independent of disease severity. CONCLUSIONS: Patients suffering from MDD show profound autonomic dysfunction, which is exacerbated by SNRI and to a lesser degree by SSRI treatment. This information could prove important when selecting antidepressant medication for patients at risk for cardiac arrhythmias.

Heartbeat evoked potentials mirror altered body perception in depressed patients.

OBJECTIVE: Awareness of stimuli originating inside of the body (interoceptive awareness) is thought to have an impact on psychopathology. The aim of the present study was to analyze whether heartbeat perception accuracy is reduced in depressed patients. Furthermore, we investigated whether putative differences are reflected in heartbeat-evoked potentials. METHOD: We assessed the heartbeat perception score in 16 depressed patients and in matched healthy controls. A 63-channel EEG was recorded while participants counted pseudo-randomly presented target tones or heartbeats during a fixed number of cardiac cycles. ECG R-waves served as the trigger for EEG averaging. The cardiac-field artifact was minimized using independent component analysis and current-source density. RESULTS: Behaviorally, the depressed sample showed less accurate heartbeat perception in comparison to the control group (p=.011). The two groups also demonstrated psychophysiological differences, showing that heartbeat-evoked potentials were significantly reduced in depressed patients. CONCLUSIONS: Our results suggest that heartbeat evoked potentials are objective markers of altered bodily awareness. Reduced interoception during depression may be linked to alexithymia, as well as to both decreased capacity for decision-making and for cognitive processing. SIGNIFICANCE: It may be helpful to practice interoceptive awareness to improve depressive symptoms, for example by practicing meditation.

Differential processing of laser stimuli by Aδ and C fibres in major depression.

Clinical studies have revealed that up to 92% of major depressed patients report pain complaints such as back or abdominal pain. Furthermore, patients suffering from depression exhibit increased superficial pain thresholds and decreased ischemic (deep) pain thresholds during experimental pain testing in comparison to healthy controls. Here, we aimed to investigate a putative role of Aδ- and C-fibre activation in altered pain perception in the disease. Laser-evoked potentials (LEPs) of 27 unmedicated depressed patients and 27 matched controls were recorded. Aδ and C fibres were activated separately. Amplitudes and latencies of N2 and P2 peaks of Aδ- (Aδ-LEP) and C-fibre- (C-LEP) related LEPs were evaluated. Depressed patients showed significantly decreased Aδ-LEP amplitudes (N2 peak: P=0.019; P2 peak: P=0.024) and delayed C-LEP latencies (P2 peak: P=0.0495; N2 peak: P=0.0556). In contrast, C-LEP amplitudes and Aδ-LEP latencies were unaffected. Our results might be suggestive of the differential impact of physiological changes on pain processing in depression. Thus, Aδ-LEP might reflect the physiological correlate of the augmented superficial pain thresholds during depression. On the contrary, the C-fibre component mediates the facets of pain processing, outlasting the stimulation period, and has been shown to be exaggerated in chronic pain states. Therefore, the functional over-representation of the C-fibre component found in our study might be a possible link between depression and associated pain complaints.

Increased sensitivity to heat pain after sad mood induction in female patients with major depression.

Patients suffering from major depressive disorder (MDD) have been shown to exhibit increased thresholds towards experimentally induced thermal pain applied to the skin. In contrast, the induction of sad mood can increase pain perception in healthy controls. Here, we aimed to test the hypothesis that heat pain thresholds are further increased after sad mood induction in depressed patients. Thermal pain thresholds were obtained from 25 female depressed patients and 25 controls before and after sad mood induction applying a modified Velten Mood Induction procedure (MIP). Valence and arousal ratings were obtained using the self-assessment manikin. The Montgomery Depression Rating Scale and the Beck Depression Inventory (BDI) were obtained at baseline from all participants. Pain thresholds at baseline did not significantly differ between groups. Pain thresholds and valence of mood significantly decreased both in patients and controls, while arousal showed an inverse time course between groups. Therefore, our hypothesis could not be confirmed. From these data, we propose that the depressed mood as seen in MDD patients influences pain experience differently as compared to the shorter-lasting mood change after MIP. A differential interaction of both affective states with brain areas of the pain matrix might be assumed. Eventually, the induction of sad mood might mirror the increased number of pain complaints in depressed patients and thus adds to the current concept of adjuvant antidepressant treatment both in depressed patients with pain complaints and in chronic pain patients.

Autonomic dysfunction in unaffected first-degree relatives of patients suffering from schizophrenia.

Recent studies revealed cardiac autonomic dysfunction in patients with acute schizophrenia, which appears to be mainly related to reduced vagal and increased sympathetic modulation. To understand the significance of cardiac autonomic function in patients with schizophrenia, we extended these studies to relatives of patients. In this study, we assessed cardiac autonomic modulation in healthy first-degree relatives of patients with schizophrenia (n = 36) to investigate a putative genetic influence. Data were compared with control subjects matched for age, gender, and physical activity as well as to patients suffering from schizophrenia. First-degree relatives showed an attenuated, yet identical pattern in autonomic dysfunction as patients with decreased vagal modulation of heart rate, decreased baroreflex sensitivity, but no difference in blood pressure variability could be detected. The patients' relatives also showed a similar pattern in regards to QT variability. In addition, the subgroup comparison of offspring vs. siblings showed a significant difference in heart rate variability suggesting a higher degree of heritability in offspring. In conclusion, the pattern of autonomic dysfunction seen in patients and relatives might indicate underlying disease-inherent genetic vulnerability, especially because autonomic parameters are heritable. In addition, these findings may be of value to identify the high-risk group of patients' relatives in regards to serious cardiovascular events so that early preventive measures can be taken.