Neural reward processing in individuals remitted from major depression.

BACKGROUND: Dysfunctional behavioural and neural processing of reward has been found in currently depressed individuals. However, little is known about altered reward processing in remitted depressed individuals. METHOD: A total of 23 medication-free individuals with remitted major depressive disorder (rMDD) and 23 matched healthy controls (HCs) performed a reward task during functional magnetic resonance imaging. We also investigated reward dependence, novelty seeking and harm avoidance using the Tridimensional Personality Questionnaire and their association with neural responses of reward processing. RESULTS: Compared to HCs, individuals with rMDD exhibited enhanced responses to reward-predicting cues in the hippocampus, amygdala and superior frontal gyrus. When reward was delivered, rMDD subjects did not significantly differ from HCs. In both groups neural activity during reward anticipation was negatively correlated with harm avoidance. CONCLUSIONS: Our results show that rMDD is characterized by hyperactivation in fronto-limbic regions during reward anticipation. Alterations in neural activation during reward processing might reflect an increased effort in remitted depressed individuals to allocate neural activity for executive and evaluative processes during anticipatory reward processing.

Subjective quality of life aspects predict depressive symptoms over time: results from a three-wave longitudinal study.

OBJECTIVE: Little is known about predictive effects of quality of life aspects on the course of depressive symptoms in clinical and non-clinical settings. This study examines longitudinal associations between depressive symptoms and subjective quality of life (QOL) dimensions using a parallel sample of depressed patients and community controls. METHOD: Eighty-two depressed patients were investigated 1, 6, and 42 months after hospital discharge together with 76 community controls regarding depressive symptoms measured by Montgomery Asberg Depression Rating Scale (MADRS) and QOL (WHOQOL-BREF). Data analysis included time-lagged linear models. RESULTS: Physical, psychological, environmental and overall QOL, controlled for depressive symptoms, predicted future depression levels. Group status did not moderate these associations. Depressive symptoms predicted future QOL levels only regarding social relations. CONCLUSION: Our study suggests that subjective QOL domains have prognostic value for the course of depressive symptoms over time, both in patient and community samples. Respective self-perceptions should therefore be directly addressed by therapeutic and preventive interventions.

Repetitive negative thinking in daily life and functional connectivity among default mode, fronto-parietal, and salience networks.

Repetitive negative thinking (RNT) is a maladaptive response to sadness and a transdiagnostic risk-factor. A critical challenge hampering attempts to promote more adaptive responses to sadness is that the between-person characteristics associated with the tendency for RNT remain uncharacterized. From the perspective of the impaired disengagement hypothesis, we examine between-person differences in blood-oxygen-level-dependent (BOLD) functional networks underlying cognitive conflict signaling, self-referential thought, and cognitive flexibility, and the association between sadness and RNT in daily life. We pair functional magnetic resonance imaging with ambulatory assessments deployed 10 times per day over 4 consecutive days measuring momentary sadness and RNT from 58 participants (40 female, mean age = 36.69 years; 29 remitted from a lifetime episode of Major Depression) in a multilevel model. We show that RNT increases following sadness for participants with higher than average between-network connectivity of the default mode network and the fronto-parietal network. We also show that RNT increases following increases in sadness for participants with lower than average between-network connectivity of the fronto-parietal network and the salience network. We also find that flexibility of the salience network's pattern of connections with brain regions is protective against increases in RNT following sadness. Our findings highlight the importance of functional brain networks implicated in cognitive conflict signaling, self-referential thought, and cognitive flexibility for understanding maladaptive responses to sadness in daily life and provide support for the impaired disengagement hypothesis of RNT.

[Stalking--what does the family doctor need to know?]. / Wann wird's bedrohlich und wie kann man sich wehren?

Stalking is a widespread phenomenon, which for the stalked person is associated with a not inconsiderable risk of becoming the victim of an act of violence. Furthermore, stalked persons may develop significant psychological problems, and therefore often seek out a doctor as their first contact. Another reason for this is the still unsatisfactory legal situation and widespread ignorance of the stalking problem on the part of the police and the courts. In the light of the above, it is of great importance that the physician should thoroughly familiarize himself with the problems associated with stalking.

Gender differences in the short-term course of unipolar depression in a follow-up sample of depressed inpatients.

OBJECTIVE: This paper examined sex differences in the short-term course of depression and assessed the impact of possibly outcome-affecting factors, including sex-specific recall artefacts and demographic and clinical characteristics. METHODS: A cohort of 179 unipolar depressed inpatients was followed up 1 (T1) and 7 months (T2) after discharge. RESULTS: Residual depression at T1 was comparable in both sexes as was the rate of follow-up nonremissions in patients who had failed to remit from the index episode at T1. In contrast, female gender was a significant predictor of relapse. This sex difference was partly attributable to women who relapsed after T1 and were again in remission at T2. Potential sex-related recall artefacts were tested by contrasting the patients' retrospective assessment of their T1-depression status reported at T2 with their interviewer-rated depression status assessed at T1. Results suggest that the observed sex difference in relapses could neither be explained by memory artefacts nor by differences in demographic and clinical sample compositions. CONCLUSIONS: It is concluded that due to their higher risk for early relapses, particular efforts with regard to continuation treatment are required for women during the critical period of remission.

PCLO rs2522833 impacts HPA system activity in healthy young adults.

Recent genetic studies showed evidence for a role of the single-nucleotide polymorphism rs2522833 within the PCLO gene in the etiology of major depression, and rs2522833 has been shown to modulate hypothalamic pituitary adrenal (HPA) axis activity during antidepressant treatment. Monoaminergic modulation of the HPA system may be one possible pathomechanism by which PCLO exerts its effect on depression. In the present study, we investigated the effect of rs2522833 on the cortisol awakening response (CAR) in healthy young adults. A total of 66 healthy volunteers from the community (36 men and 30 women) aged 18-25 years without individual or family history of affective disorders and schizophrenia collected saliva cortisol samples at 0, 30, 45 and 60 min after awakening on two consecutive working days. We identified a blunted CAR (AUCinc) in rs2522833 risk-allele (C) carriers, possibly indicating exhausted regulatory mechanisms underlying the HPA system. We also identified higher neuroticism scores in rs2522833 risk-allele carriers but no phenotypic correlation between the CAR (AUCinc) and neuroticism. These findings suggest that the rs2522833 risk variant might increase vulnerability to depression both by physiological and behavioral pathways, which appear, however, not to be substantially overlapped. Replication with larger samples is warranted.

Rumination, distraction and mindful self-focus: effects on mood, dysfunctional attitudes and cortisol stress response.

BACKGROUND: Although aggravating effects of rumination on dysfunctional cognitions and endocrine stress responses have been proposed, experimental studies testing these assumptions are lacking. In parallel, mindfulness theory suggests beneficial effects of mindfulness on dysfunctional cognitions. This study aimed to investigate the effects of induced rumination, distraction and mindful self-focus on mood and dysfunctional attitudes and to assess the possible impact of induced rumination on participants' cortisol responses. METHOD: Sixty university students were subjected to negative mood induction and subsequently randomly assigned to a rumination, distraction or mindful self-focus condition. The latter included statements focusing on self-acceptance and awareness of the breath. Four saliva cortisol samples were selected during the session. RESULTS: Compared to induced rumination, distraction showed a clear beneficial effect on the course of dysphoric mood, whereas a mindful self-focus did not. In contrast to distraction and mindful self-focus, participants induced to ruminate showed significant increases in dysfunctional attitudes from baseline to post-induction. Although rumination was not itself linked to higher cortisol responses, participants scoring high on the Beck Depression Inventory (BDI)-II who were induced to ruminate showed a smaller decrease in cortisol levels than those scoring low on the BDI-II. CONCLUSIONS: This study indicates that rumination as a dysfunctional mode of cognitive processing is able to maintain depression-linked dysfunctional thought content. Furthermore, our study revealed preliminary indications for a link between induced rumination and the cortisol stress response in vulnerable individuals.

Effects of stressor controllability on psychophysiological, cognitive and behavioural responses in patients with major depression and dysthymia.

BACKGROUND: The experience of uncontrollability and helplessness in the face of stressful life events is regarded as an important determinant in the development and maintenance of depression. The inability to successfully deal with stressors might be linked to dysfunctional prefrontal functioning. We assessed cognitive, behavioural and physiological effects of stressor uncontrollability in depressed and healthy individuals. In addition, relationships between altered cortical processing and cognitive vulnerability traits of depression were analysed. METHOD: A total of 26 unmedicated depressed patients and 24 matched healthy controls were tested in an expanded forewarned reaction (S1-S2) paradigm. In a factorial design, stressor controllability varied across three consecutive conditions: (a) control, (b) loss of control and (c) restitution of control. Throughout the experiment, error rates, ratings of controllability, arousal, emotional valence and helplessness were assessed together with the post-imperative negative variation (PINV) of the electroencephalogram. RESULTS: Depressed participants showed an enhanced frontal PINV as an electrophysiological index of altered information processing during both loss of control and restitution of control. They also felt more helpless than controls. Furthermore, frontal PINV magnitudes were associated with habitual rumination in the depressed subsample. CONCLUSIONS: These findings indicate that depressed patients are more susceptible to stressor uncontrollability than healthy subjects. Moreover, the experience of uncontrollability seems to bias subsequent information processing in a situation where control is objectively re-established. Alterations in prefrontal functioning appear to contribute to this vulnerability and are also linked to trait markers of depression.

Gender differences in unipolar depression: an update of epidemiological findings and possible explanations.

OBJECTIVE: To give an update on epidemiological findings on sex differences in the prevalence of unipolar depression and putative risk factors. MATERIAL AND METHODS: Systematic review of the literature. RESULTS: Recent epidemiological research yields additional evidence for a female preponderance in unipolar depression, holding true across different cultural settings. Current explanations include artefacts, genetic, hormonal, psychological and psychosocial risk factors. Rather consistently, intrapsychic and psychosocial gender role related risk factors have been identified which may contribute to the higher depression risk in women. Gender role aspects are also reflected in endocrine stress reactions and possibly influence associated neuropsychological processes. CONCLUSION: There is a need for more integrative models taking into account psychological, psychosocial, and macrosocial risk factors as well as their interactions, which also connect these factors with physiological and endocrine responses. Furthermore, it is conceivable that across the life span, as well as across cultural settings, individual risk factors will add with varying emphasis to the higher prevalence of depression in women.

Responses to depression in unipolar depressed patients: an investigation of Nolen-Hoeksema's response styles theory.

BACKGROUND: The response styles theory suggests that rumination in response to depressed mood exacerbates and prolongs depression, while distraction ameliorates and shortens it. Gender differences in response styles are said to contribute to the observed gender differences in the prevalence of unipolar depression. While empirical support for the theory has been found from a variety of non-clinical studies, its generalizability to clinically depressed patient populations remains unclear. METHODS: A cohort of 52 unipolar depressed in-patients was assessed with the Response Styles Questionnaire during in-patient stay (T1) and 4 weeks after discharge (T2). The patients were followed up 4 months after discharge (T3). Clinical assessment included the SCAN-PSE-10. RESULTS: Moderate and statistically significant retest-stabilities for rumination and distraction were found, comparable for patients with stable and changing depression status from T1 to T2. A cross-sectional diagnosis of a major depressive episode was associated with rumination, while gender was not. Post-discharge baseline rumination (T2), adjusted for concurrent depression, predicted follow-up levels of depression (T3), and, in patients who were non-remitted at post-discharge baseline, it predicted presence of a major depressive episode at follow-up (T3). Results on distraction were more ambiguous. CONCLUSIONS: Our results suggest that rumination is likely to have a deteriorating impact on the course of clinical episodes of depression in unipolar depressed patients. Larger longitudinal patient studies are needed to validate these findings.

Potential impact of colonic irrigation on the indigenous intestinal microflora.

Under normal physiological conditions, the indigenous intestinal microflora is stable. The stability protects the host from colonization of nonindigenous microorganisms, including pathogens. Indigenous microorganisms capable of producing toxins are held in check by competing microflora, but any accidentally absorbed toxins are efficiently detoxified by the liver in the absence of hepatic pathology. Antibiotics are known to disrupt the normal flora leading to increased susceptibility to infection with other members of the normal flora or to toxins produced by them. It is possible that mechanical disruption of the flora by colonic irrigation could have a similar effect. Inadequately disinfected colonic irrigation machines have been the source of documented iatrogenic infection with Entamoeba histolytica. The potential for iatrogenic transmission of AIDS in a similar fashion must be considered.