Frank Euteneuer

Dissociation of decision-making under ambiguity and decision-making under risk in patients with Parkinson's disease: A neuropsychological and psychophysiological study

Decision-making impairments in Parkinsons disease (PD) are most likely associated with dysfunctions in fronto-striatal loops. Recent studies examined decision-making in PD either in ambiguous situations with implicit rules, using the Iowa Gambling Task (IGT), or in risky situations with explicit rules, using the Game of Dice Task (GDT). Both tasks have been associated with the limbic-orbitofrontal-striatal loop, involved in emotional processing. However, the GDT has additionally been highly associated with the dorsolateral prefrontal-striatal loop, being involved in executive functions. The present study is the first one which examined decision-making in PD patients with both, IGT and GDT. We studied 21 non-demented PD patients on dopaminergic medication and 23 healthy controls with both tasks and a neuropsychological test battery with focus on executive functions. To analyse possible abnormalities in emotional processing, electrodermal responses (EDRs) were assessed while performing the tasks. We found that PD patients were significantly impaired in the GDT, but not in the IGT. Executive dysfunctions correlated with GDT but not with IGT performance. In both tasks, PD patients showed significantly reduced feedback EDRs after losses, but not after gains, indicating a primary decline of sensitivity to negative feedback. Our behavioural data suggest that dysfunctions in the dorsolateral prefrontal loop might be stronger than in the limbic loop, resulting in deficits in executive functions and GDT performance but unimpaired IGT performance. Reduced sensitivity to negative feedback is discussed with regard to dysfunctions in the limbic loop, which may result from pathology of limbic structures or dopaminergic medication.

Subjective social status and health.

Purpose of review Subjective social status (SSS) predicts health outcomes above and beyond traditional objective measures of social status, such as education, income and occupation. This review summarizes and integrates recent findings on SSS and health. Recent findings Current studies corroborate associations between low SSS and poor health indicators by extending previous findings to further populations and biological risk factors, providing meta-analytic evidence for adolescents and by demonstrating that negative affect may not confound associations between SSS and self-rated health. Recent findings also highlight the relevance of SSS changes (e.g. SSS loss in immigrants) and the need to consider cultural/ethnical differences in psychological mediators and associations between SSS and health. Summary SSS is a comprehensive measure of ones social position that is related to several poor health outcomes and risk factors for disease. Future investigation, particularly prospective studies, should extend research on SSS and health to further countries/ethnic groups, also considering additional psychological and biological mediators and dynamic aspects of SSS. Recently developed experimental approaches to manipulate SSS may also be promising.

Psychobiological differences between depression and somatization.

BACKGROUND Comorbidity studies have shown that depression and somatization (multiple somatoform symptoms) often overlap. Therefore it has been suggested to classify at least some patients with somatization syndromes under the category of depressive disorders. We wanted to investigate whether psychobiological investigations confirm the lumping of somatization and depression, or whether psychobiological pathways favor distinguishing these disorders. METHOD An overview is presented summarizing psychobiological studies including patients with depression and/or somatization-associated syndromes. We focus on the following topics: heritability, polymorphisms in special candidate genes, immune activation, hypothalamic-pituitary-adrenal (HPA) axis reactivity, serotonergic pathways, monoamino acids, and fatty acid concentrations. RESULTS Immunological activation seems to be associated with specific features of somatoform disorders, namely, sickness behavior and pain thresholds. Genetic factors can also contribute to somatic complaints, e.g., via serotonergic pathways, HPA-axis response, immune activation, and other biological systems that contribute to the self-description of not being healthy. Some results indicate that psychobiological aspects of depression and somatization overlap in part (e.g., the relevance of serotonergic pathways), but there is clearly more evidence for discrepancies of psychobiological pathways in depression and somatization (e.g., the relevance of proinflammatory immune processes; HPA-axis activity; monoamino acid availability; omega-3-concentration; the role of triallelic subtypes of 5-HTTLPR). CONCLUSION Many psychobiological pathways act differently in depression and somatization. These differences in psychobiology favor the distinction of these syndromes in classification approaches.

Depression, cytokines and experimental pain: Evidence for sex-related association patterns

BACKGROUND There is robust evidence that altered neural-immune interactions including increased levels of proinflammatory cytokines are involved in both the pathogenesis of depression and altered pain processing. Proinflammatory cytokines induce sickness behavior, a constellation of symptoms that bears a strong similarity to those of depression. A feature of sickness behavior is enhanced pain sensitivity and it has been suggested that proinflammatory cytokines interact with pain processing directly and via several neurobiological pathways. Previous research indicates that depression and pain are closely related. We investigated the association between proinflammatory cytokines and experimental pain in major depression. METHODS Psychopathological variables, pressure pain thresholds (PPT) and concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured in 37 outpatients with major depression and 48 healthy controls. RESULTS Compared with controls, depressed patients exhibited significantly higher levels of TNF-α and significantly decreased PPT indicating enhanced pain sensitivity. The group differences were robust when adjusting for sex and body mass index, although sex was significantly related to PPT. No group difference was observed in IL-6. PPT correlated significantly with TNF-α in women but not in men. LIMITATIONS Because of the cross-sectional design, causality of the relation between TNF-α and pain cannot be determined. Results should be considered preliminary given the small sample size. CONCLUSION The present findings suggest that increased pain sensitivity in depression may be linked to increased TNF-α concentration. The absence of this association in men is discussed in terms of pain-related psychobiological sex differences.

The predictive value of somatic and cognitive depressive symptoms for cytokine changes in patients with major depression

Context Elevated concentrations of proinflammatory cytokines have been hypothesized as an important factor in the pathophysiology of depression. Depression itself is considered to be a heterogeneous disorder. Current findings suggest that “cognitive” and “somatic” symptom dimensions are related to immune function in different ways. So far, little research has been done on the longitudinal aspects of inflammation in patients with major depression, especially with respect to different symptom dimensions of depression. Therefore, we investigated which aspects of depression may predict changes in tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 over 4 weeks. Methods Forty-one patients with major depression diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and 45 healthy controls were enrolled. Serum measurements of TNF-alpha and IL-6 were conducted at baseline and 4 weeks later. Psychometric measures included the assessment of cognitive-affective depressive symptoms and somatic symptoms during the last 7 days as well as somatic symptoms during the last 2 years. Results Patients with depression showed increased levels of TNF-alpha (P<0.05) compared to healthy controls. Hierarchical regression analyses indicated that neither depressive nor somatic symptoms predict changes in proinflammatory cytokines in the whole sample of depressed patients. Moderation analyses and subsequent sex-stratified regression analyses indicated that higher somatoform symptoms during the last 2 years significantly predict an increase in TNF-alpha in women with major depression (P<0.05) but not in men. Exploratory analyses indicated that the stability of TNF-alpha and IL-6 (as indicated by intraclass correlation coefficients) over 4 weeks was high for TNF-alpha but lower for IL-6. Conclusion The present study demonstrated that a history of somatoform symptoms may be important for predicting future changes in TNF-alpha in women with major depression.

Childhood adversities and laboratory pain perception

Childhood adversity has frequently been related to a wide range of psychosomatic complaints in adulthood. The present study examined the relationship between different forms of childhood adversity and laboratory measures of pain. Heat pain tolerance and perceived heat pain intensity were measured in a community-based sample of 62 women (aged 20-64 years). Participants completed the Childhood Trauma Questionnaire (CTQ), which assesses five forms of childhood adversity: physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional neglect. Somatic symptoms, depressive symptoms, and pain catastrophizing were assessed as potential mediators. Bivariate analyses indicated that emotional abuse but no other forms of childhood adversity were significantly related to decreased heat pain tolerance (r=-0.27; P<0.05). Accordingly, multiple regression analyses revealed that only emotional abuse was a significant predictor of heat pain tolerance (β=-0.62; P=0.034) when entering all CTQ subscales simultaneously. Although emotional abuse was also related to somatic symptoms, depressive symptoms, and pain catastrophizing, none of these variables mediated the relationship between childhood adversity and laboratory pain (P>0.1). No significant associations were found between any forms of childhood adversity and heat pain intensity. Our findings indicate that the severity of emotional childhood abuse is associated with decreased pain tolerance, an affective component of pain, but not with heat pain intensity, which has been described as a sensory component of pain.

Subjective social status predicts in vivo responsiveness of β-adrenergic receptors.

OBJECTIVE Several poor health outcomes, including cardiovascular risk, have been associated with both subjective social status (SSS) and sympathetic overactivity. Because prolonged sympathetic overactivation down regulates beta adrenergic receptor (β-AR) function, reduced β-AR responsiveness is considered an indicator of sympathetic overactivity and a cardiovascular risk factor. Though prior research has focused on objective social status and β-AR function, no studies have examined the association between SSS and β-AR function. We aimed to learn whether SSS predicts the in vivo responsiveness of β-ARs. METHODS We assessed the chronotropic 25 dose (CD25), an in vivo marker of β-AR responsiveness, in 94 healthy participants. The MacArthur scales of subjective social status were used to assess SSS in the U.S.A. (SSS-USA) and in the local community (SSS-C). Objective social status was analyzed by calculating the Hollingshead two-factor index. RESULTS β-AR responsiveness was reduced (as indicated by higher CD25 values) in participants with lower SSS-USA (p = .007) and lower SSS-C (p < .001). The relationship between CD25 and SSS was particularly robust with respect to SSS-C. Hierarchical regression analyses revealed that SSS-C remained a significant predictor of CD25 (p < .001) and accounted for 14% of the total variance (32%) in CD25 after adjusting for sociodemographic variables (age, ethnicity, gender), health factors (exercise, smoking status, body mass index) and objective social status. CONCLUSION Our results indicate that β-AR function may be an important component of the link between SSS and health.

Psychobiological aspects of somatization syndromes: Contributions of inflammatory cytokines and neopterin

Previous research suggests a dysregulation of immune-to-brain communication in the pathophysiology of somatization syndromes (multiple somatoform symptoms). We compared blood levels of the inflammatory markers tumor necrosis factor-alpha (TNF-α), interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6) and neopterin between 23 patients with somatization syndromes (Somatoform Symptom Index-8, SSI-8), 23 age- and sex-matched healthy controls and 23 patients with major depression. No group differences were found for IL-1ra and IL-6. While TNF-α was increased in both clinical groups, neopterin was only increased in somatization syndromes. Correlational analyses revealed that neopterin tended to be related to somatoform pain complaints in patients with somatization syndromes. This study is the first to demonstrate increased levels of TNF-α and neopterin in patients with somatization syndromes without a diagnosis of depression, which may support a role of immune alterations in somatization syndromes. Neopterin is a reliable indicator for interferon-γ (IFN-γ) which was identified as the only cytokine that induces significant production of neopterin. Considering recent research indicating that IFN-γ can lead to increased neuronal responsiveness and body perceptions by reducing inhibitory tone in the dorsal horn, the observed association between somatization syndromes and neopterin might support the idea of central sensitization in the pathogenesis of somatoform symptoms.

Increased soluble interleukin-2 receptor levels are related to somatic but not to cognitive-affective features in major depression.

Cell-mediated immune activation may play a role in the pathogenesis of depression as indicated by findings of increased soluble tumor necrosis factor receptor (sTNF-R) levels and meta-analytic evidence for elevated soluble interleukin-2 receptor (sIL-2R) concentrations. However, little research has been done on how these soluble cytokine receptors are differently related to specific features in patients with depression. We measured levels of the soluble cytokine receptors sIL-2R, sTNF-R1 and sTNF-R2 in 25 non-medicated patients with major depression (DSM-IV) and 22 healthy controls. Psychometric measures included cognitive-affective depressive symptoms, somatoform symptoms, somatic and cognitive dimensions of anxiety and current mood states. While patients with depression showed increased levels of sIL-2R (p<0.01), differences in sTNF-R1 (p=0.09) and sTNF-R2 (p=0.08) marginally failed to reach significance. Increased concentrations of sIL-2R were related to somatic measures such as the severity of somatoform symptoms and somatic anxiety symptoms but not to cognitive-affective measures or current mood states. Our findings may suggest some specificity in the relationship between sIL-2R and symptom dimensions and highlight potential pathways by which T cell mediated immune activation may underpin somatic symptoms in depression.

Social exclusion and shame in obesity

Weight bias often results in the social exclusion of individuals with obesity. The direct, short-term psychological effects of social exclusion in obesity have not been investigated yet. This study experimentally tests whether social exclusion elicits stronger negative emotions in individuals with obesity compared to normal-weight controls. Specifically, we test whether social exclusion has a specific impact on shame. In total, N=299 individuals (n=130 with body mass index [BMI]≤30 and n=169 with BMI>30) were randomly assigned to a social exclusion condition or a control condition that was implemented with an online Cyberball paradigm. Before and after, they filled out questionnaires assessing state emotionality. Social exclusion increased negative emotionality in both groups compared to the control condition (p<0.001) according to a multivariate ANOVA. However, the interaction of group and social exclusion was also significant (p=0.035) and arose from a significant, specific increase of shame in the group with obesity during social exclusion (p<0.001, Cohens d=0.7). When faced with social exclusion, individuals with obesity do not respond with more intensive negative emotions in general compared to controls, but with a specific increase in shame. As social exclusion is frequent in individuals with obesity, psychological interventions focussing shame-related emotional distress could be crucial.