Silke Boettger

Pain perception in major depression depends on pain modality.

&NA; One frequently described feature of depression is an increased vulnerability to pain complaints, and chronic pain is frequently accompanied by symptoms of depression. In contrast to this, a decreased sensitivity to experimental pain has been described in major depression. The physiological basis of this phenomenon is yet elusive. We investigated 30 patients suffering from a major depressive disorder and matched controls. Pain testing (threshold and tolerance) was performed on both sides of the body and included assessment of thermal, electrical and ischemic pain. While confirming hypoalgesia to heat and electrical pain in comparison to controls, we found hyperalgesia to ischemic muscle pain. Furthermore, thermal pain tolerance and electrical pain tolerance were significantly increased on the right hand side confirming previous results of a lateralized perception of pain in depression. Our main finding suggests that painful stimuli are processed differentially depending on the localization of pain induction in depression. This knowledge may enable us to understand and ultimately treat pain complaints more appropriately in depressed patients.

Increased Prefrontal Activation During Pain Perception in Major Depression

BACKGROUND To further elucidate the close interrelation of pain and depression, we investigated cerebral responses to parametrically varied thermal pain intensities in female patients suffering from major depressive disorder (MDD) (n = 13) and matched control subjects (n = 13) by means of functional magnetic resonance imaging (fMRI). METHODS After the assessment of the individual thermal pain threshold, an fMRI-compatible thermode was used to deliver thermal painful stimuli to the right arm. All stimuli were initiated for 10 sec from a baseline resting temperature (32 degrees C) in three different conditions (37 degrees C, 42 degrees C, 45 degrees C). Statistical Parametric Mapping 2 (SPM2) software was used for image processing and statistical analyses. RESULTS Patients displayed significantly increased thermal pain thresholds. A comparable increase in blood oxygenation level-dependent (BOLD) signal was observed in key structures of the pain matrix in patients and control subjects. Patients displayed hyperactivation in comparison with control subjects for the painful 45 degrees C condition in the left ventrolateral thalamus, in the right ventrolateral prefrontal cortex (VLPFC) and dorsolateral prefrontal cortex (DLPFC), as well as a stronger parametric BOLD signal increase in the right VLPFC, DLPFC, and in the contralateral insula. Symptom severity correlated positively with the BOLD signal in the left ventrolateral nucleus of the thalamus. CONCLUSIONS We present evidence that cortical structures of the pain matrix are similarly activated in depressed patients and healthy subjects. We report increased prefrontal and lateral thalamic activation during the presentation of painful stimuli, which might explain reduced thermal pain perception on the skin in depressed patients.

Altered diurnal autonomic variation and reduced vagal information flow in acute schizophrenia

OBJECTIVE This study aimed to further investigate autonomic function in schizophrenic patients using long-term electrocardiographic (ECG) recordings. METHODS Twenty unmedicated patients suffering from an acute episode of paranoid schizophrenia and 20 matched control subjects were recruited and 24-h ambulatory electrocardiograms were recorded. In order to investigate complexity of heart rate fluctuations related to different physiological time scales, linear heart rate variability (HRV) as well as autonomic information flow (AIF) parameters were calculated from day and night time intervals. RESULTS While heart rates were increased, root mean successive square difference (RMSSD), a measure for vagal function as well as standard deviation of 5-min mean NN-intervals (SDANN), reflecting parasympathetic and sympathetic tone, were decreased in schizophrenia. Furthermore, a decrease of vagal information flow was apparent during night time (decreased mean high frequency peak decay (PD(mHF))). In addition, increased INT(NN) (area under the AIF curve) as well as decreased beat decay (BD(NN)) and mean very low frequency PD (PD(mVLF)) indicated reduced complexity in patients during day and night time. CONCLUSIONS HRV and AIF parameters indicate altered diurnal autonomic variation in schizophrenia. SIGNIFICANCE Reduced vagal modulation and loss of complexity might both contribute to the increased risk for sudden cardiac death in schizophrenia.

Relationship between cardiovagal modulation and psychotic state in patients with paranoid schizophrenia.

Disturbed autonomic nervous system (ANS) function in schizophrenia might contribute to increased cardiovascular mortality. We obtained heart rate variability indices from 40 unmedicated schizophrenic patients and 58 matched controls. Mainly we found that patients displaying stronger psychotic symptoms as assessed by the Brief Psychiatric Rating Scale exhibit more severe cardiac ANS disturbances compared with controls.

Decreased sensitivity to experimental pain in adjustment disorder

An altered perception of pain has been described for several psychiatric disorders. To date the influence of adjustment disorders (AD) on pain perception has not been described.

Nonlinear broad band dynamics are less complex in major depression.

OBJECTIVES Cardiac mortality is known to be increased in depressive patients. However, the underlying mechanisms remain elusive to date. Decreased heart rate variability (HRV) has been discussed as contributing to increased cardiac mortality, but studies examining patients suffering from major depressive disorder (MDD) have revealed inconsistent results. This study aimed to investigate long-term and broad band parameters of heart rate regulation in MDD, which have been shown to be more sensitive for the assessment of autonomic dysfunction. METHODS A total of 18 non-medicated patients suffering from MDD and 18 matched control subjects without cardiac disease were recruited and 24-h ambulatory electrocardiograms were recorded. Data were recorded during three distinct time intervals linear and nonlinear parameters as well as autonomic information flow (AIF) were calculated. RESULTS The power law slope was significantly reduced in the patient group for all intervals investigated and correlated with symptom severity, whereas standard deviation of the 5-min NN intervals (SDANN) and area under the AIF curve (INT(NN)) showed significant differences between groups in the morning hours only. Analysis of standard HRV parameters in the time and frequency domain revealed no significant differences between groups. CONCLUSIONS The evidence for decreased complexity of cardiac regulation in depressed patients presented here might be useful as an indicator of the increased cardiac mortality known in depression, especially since these parameters are capable of predicting cardiac mortality in other diseases. The importance of these parameters for patients at risk should be evaluated in future prospective studies.

Physical fitness and heart rate recovery are decreased in major depressive disorder.

Objective: To investigate whether physical fitness is decreased in patients with major depressive disorder (MDD) in comparison to matched healthy controls because low physical fitness has been shown to be associated with metabolic syndrome or autonomic dysfunction. Cardiovascular morbidity and mortality are known to be increased in patients with MDD. Furthermore, the effect of a single exhaustive exercise task on heart rate recovery (HRR) and mood was examined. Methods: Peak oxygen consumption (VO2peak), maximum workload (Ppeak), and individual anaerobic threshold (IAT) were assessed in 22 patients suffering from MDD and 22 controls in a stepwise exhaustion protocol, using spirometry and lactate diagnostics. HRR was detected within the first minute after recovery. The Self-Assessment Manikin (SAM) was used to assess mood before and after exercise. Results: VO2peak, Ppeak, and IAT were decreased significantly in patients, indicating reduced physical fitness in MDD as compared with control subjects. A single exercise exhaustion significantly improved mood in patients, but not in controls. Mood improvement in patients correlated with maximum lactate levels. Significantly reduced HRR values in patients further point to an elevated cardiovascular risk profile and autonomic dysfunction. Conclusions: Our results indicate reduced physical fitness in patients with MDD. Thus, special training programs should be developed to improve their cardiovascular risk profile. In addition, the intriguing finding of a correlation between lactate levels and mood changes should be followed up in future studies to unravel putative mechanisms. BDI = Beck Depression Inventory; BMI = body mass index; CO2 = carbon dioxide; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; ECG = electrocardiogram; HAMD-21 = Hamilton Depression Rating Scale; HRR = heart rate recovery; IAT = individual anaerobic threshold; IPAQ = international physical activity questionnaire; MDD = major depressive disorder; MET = metabolic equivalent; Ppeak = maximal work load; RQ = respiratory quotient; rpm = revolutions per minute; SAM = Self-Assessment Manikin; SCID = Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders; VO2 = oxygen consumption; VO2peak = peak oxygen consumption; W = Watt.

Heart Rate Variability, QT Variability, and Electrodermal Activity during Exercise

PURPOSE Various measures of autonomic function have been developed, and their applicability and significance during exercise are controversial. METHODS Physiological data were therefore obtained from 23 sport students before, during, and after exercise. Measures of R-R interval variability, QT variability index (QTvi), and electrodermal activity (EDA) were calculated. We applied an incremental protocol applying 70%, 85%, 100%, and 110% of the individual anaerobic threshold for standardized comparison. RESULTS Although HR increased stepwise, parasympathetic parameters such as the root mean square of successive differences were not different during exercise and do not mirror autonomic function satisfactorily. Similar results were observed with the approximate entropy of R-R intervals (ApEnRR). In contrast, the increase in sympathetic activity was well reflected in the EDA, QTvi, and ApEn of the QT interval (ApEnQT)/ApEnRR ratio. CONCLUSION We suggest that linear and nonlinear parameters of R-R variability do not adequately reflect vagal modulation. Sympathetic function can be assessed by EDA, QTvi, or ApEnQT/ApEnRR ratio.

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.

Inflammatory changes upon a single maximal exercise test in depressed patients and healthy controls

Patients with major depressive disorder (MDD) have repeatedly been described to exhibit both a humoral as well as a cellular pro-inflammatory state. Acute exercise, representing physical stress, can further aggravate such an immune dysbalance. In the light of recommended exercise programmes for depressed patients, we aimed to investigate the inflammatory response to exercise in patients with MDD. Blood cells counts and concentrations of the pro-inflammatory cytokines IL-1ss and IL-6 as well as the anti-inflammatory cytokine IL-10 were obtained before and after a single maximum exercise test in 15 patients suffering from MDD and 15 controls applying a stepwise exhaustion protocol. Patients showed increased white cell counts before and after exercise. While starting from different baseline levels, however, the relative increase in both humoral and cellular inflammatory parameters did not differ between groups. The results from this study suggest that physical training programmes for MDD patients do not bear a dramatically increased risk for acute pro-inflammatory exacerbations. Thus, continuous training programmes that have been shown to reduce the pro-inflammatory state in these patients can be recommended.