Christine Kuehner

A meta-analysis of neurofunctional imaging studies of emotion and cognition in major depression

Major depressive disorder (MDD) is characterized by altered emotional and cognitive functioning. We performed a voxel-based whole-brain meta-analysis of functional neuroimaging data on altered emotion and cognition in MDD. Forty peer-reviewed studies in English-language published between 1998 and 2010 were included, which used functional neuroimaging during cognitive-emotional challenge in adult individuals with MDD and healthy controls. All studies reported between-groups differences for whole-brain analyses in standardized neuroanatomical space and were subjected to Activation Likelihood Estimation (ALE) of brain cluster showing altered responsivity in MDD. ALE resulted in thresholded and false discovery rate corrected hypo- and hyperactive brain regions. Against the background of a complex neural activation pattern, studies converged in predominantly hypoactive cluster in the anterior insular and rostral anterior cingulate cortex linked to affectively biased information processing and poor cognitive control. Frontal areas showed not only similar under- but also over-activation during cognitive-emotional challenge. On the subcortical level, we identified activation alterations in the thalamus and striatum which were involved in biased valence processing of emotional stimuli in MDD. These results for active conditions extend findings from ALE meta-analyses of resting state and antidepressant treatment studies and emphasize the key role of the anterior insular and rostral anterior cingulate cortex for altered emotion and cognition in MDD.

Rumination, distraction, and mindful self-focus in depressed patients.

Rumination has been proposed as a cognitive risk factor for the onset and maintenance of depression. In parallel, mindfulness interventions have shown to reduce the risk for recurrence of depressive episodes. This study aimed to investigate effects of short periods of induced rumination, distraction, and mindful self-focus on sad mood in depressed patients and to assess possible moderator effects of habitual variables on respective mood changes. Seventy-six depressed patients 3.5 years after discharge from inpatient treatment were subjected to negative mood induction and subsequently randomly assigned to a rumination, distraction, or mindful self-focus induction. Habitual aspects of rumination, distraction, and mindfulness were assessed by questionnaires. Compared to rumination, the induction of a mindful self-focus and of distraction showed clear beneficial effects on the course of negative mood. While habitual distraction predicted better mood outcomes across all conditions, patients high in habitual mindfulness tended to show stronger negative mood reduction specifically after the induction of a mindful self-focus. This study indicates that - similar to distraction - an experimentally induced mindful self-focus is able to reduce negative mood in depressed patients. Implications regarding possible subgroups of patients who might particularly benefit from mindfulness-based interventions are discussed.

Decreased cortisol response to awakening is associated with cognitive vulnerability to depression in a nonclinical sample of young adults.

Due to its high intraindividual stability, the cortisol awakening response (CAR) may be regarded as a trait measure of the dynamics of the HPA-axis activity. The present study aimed at investigating associations of the CAR with rumination as a cognitive vulnerability marker for depression assessed by both a trait measure and by experimental manipulation. After induction of sad mood by viewing a sad sequence of a movie, 42 healthy university students were randomly induced to either ruminatively self-focus on their feelings or to distract themselves from their mood by concentrating on respective text cards for 8min. Trait rumination and distraction were measured by the Response Styles Questionnaire (RSQ) at baseline (T0), while current mood was recorded before (T1) and after (T2) the mood induction as well as after the rumination/distraction induction (T3) using the Positive and Negative Affect Schedule (PANAS). Basal saliva cortisol levels were measured independently on a different day. After mood induction, levels of mood were lowered significantly. Participants subsequently induced to ruminate kept their negative mood whereas participants induced to distract themselves showed a reduction in negative mood. Self-focused trait rumination amplified low mood in both induction conditions. A decreased CAR was associated with self-focused rumination and with less improvement of sad mood after induced distraction. We conclude that the two variables apparently share specific vulnerability qualities towards depression by hampering the adaptive shift of attention to external cues during dysphoric moods, probably involving lowered disinhibition of task-irrelevant negative emotional processing. The present study provided first indications of a possible relationship between a cognitive vulnerability marker for depression and characteristics of basal neuroendocrine activity regarding their association with the course of experimentally induced dysphoric mood.

A longitudinal study of rumination and distraction in formerly depressed inpatients and community controls.

The response styles theory (S. Nolen-Hoeksema, B. E. Wisco, & S. Lyubomirsky, 2008) supposes that ruminative coping is a cognitive risk factor for the course of depression, whereas distractive coping has protective effects. The authors present a longitudinal study on reciprocal relations between coping styles and depressive symptoms. They investigated 82 formerly depressed inpatients 4 weeks, 6 months, and 3.5 years after hospital discharge together with 76 age- and gender-matched community controls. Depressive symptoms predicted future symptom-focused rumination over the initial short-term interval in both samples. In former inpatients, this predictive effect was also significant over the subsequent long-term interval. Symptom-focused rumination and distraction were significant predictors of future depressive symptoms across both intervals, with sample-specific effects. In the community sample, symptom-focused rumination predicted more depressive symptoms, whereas in former inpatients, distractive coping predicted fewer depressive symptoms over time. The authors conclude that interventions aimed at reducing rumination should preferably be applied in preventive and early intervention settings, although in individuals with a history of more severe and long-standing depression rumination might gradually lose its capacity to predict the further illness course. In these persons, interventions should particularly strengthen distractive coping.

Why is depression more common among women than among men

Women are about twice as likely as are men to develop depression during their lifetime. This Series paper summarises evidence regarding the epidemiology on gender differences in prevalence, incidence, and course of depression, and factors possibly explaining the gender gap. Gender-related subtypes of depression are suggested to exist, of which the developmental subtype has the strongest potential to contribute to the gender gap. Limited evidence exists for risk factors to be specifically linked to depression. Future research could profit from a transdiagnostic perspective, permitting the differentiation of specific susceptibilities from those predicting general psychopathologies within and across the internalising and externalising spectra. An integration of the Research Domain Criteria framework will allow examination of gender differences in core psychological functions, within the context of developmental transitions and environmental settings. Monitoring of changing socioeconomic and cultural trends in factors contributing to the gender gap will be important, as well as the influence of these trends on changes in symptom expression across psychopathologies in men and women.

Altered neural reward and loss processing and prediction error signalling in depression

Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression.

Measuring depression with a well-being index: further evidence for the validity of the WHO Well-Being Index (WHO-5) as a measure of the severity of depression.

BACKGROUND In recent years, the WHO Wellbeing Index (WHO-5) has been used as a screening measure for depression. Nevertheless, research on the validity of this measure in the context of clinical depression is sparse. QUESTIONS The aim of the present study was to investigate the measurement invariance of the WHO-5 across depressed and non-depressed individuals, as well as the shape and specificity of its relationship to measures of depression severity. METHOD Of the 414 subjects who completed the WHO-5 and the Beck Depression Inventory-II (BDI-II), 207 had a diagnosis of a major depressive episode (MDE). A subsample also completed the Beck Anxiety Inventory (BAI) and was assessed by clinicians using the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). RESULTS The WHO-5 demonstrated strong measurement invariance regarding the presence or absence of a current MDE. The WHO-5 showed a very high negative association with self- and observer-rated measures of depressive symptoms, especially in the range of mild to moderate symptoms. These associations were still substantial after controlling for measures of anxiety symptoms. LIMITATIONS In addition to a diagnostic interview, only one measure for self- and observer-rated symptoms of depression was used. Furthermore, the observer-rated measure was only assessed in one subsample that exhibited a somewhat restricted range of depression severity. CONCLUSION Although this index was originally designed as a measure of well-being, the results support the use of the WHO-5 in the context of depression research.

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.

The epidemiology and characteristics of stalking.

Purpose of review This article summarizes major results in the field of epidemiology and characteristics of stalking, as published in literature between 2003 and October 2005. Recent findings Although stalking had been only recently conceptualized, it soon became evident that it represents a significant social and medical problem. Community-based studies on the prevalence of stalking are scarce and predominantly from English-speaking countries. All epidemiological studies, however, revealed that stalking is a widespread phenomenon with lifetime prevalence rates of stalking victimization ranging 12–16% among women and 4–7% among men. With regard to the impact of stalking, studies suggest that stalking can cause serious economic, social, medical and psychiatric consequences. Growing evidence suggests that serious violence and even homicide may occur in the context of stalking, and research on risk assessment has yielded an improved understanding of risk factors. Research on therapy of stalkers and stalking victims is still at its beginning; however, there are some preliminary reports with encouraging results. Summary Although there are research activities in the main fields, many basic questions still remain to be adequately addressed. Increased social and political awareness and expanded research funding are obligatory prerequisites to realize sound and well designed studies.

GENDER AS PREDICTOR AND MODERATOR OF OUTCOME IN COGNITIVE BEHAVIOR THERAPY AND PHARMACOTHERAPY FOR ADULT DEPRESSION: AN “INDIVIDUAL PATIENT DATA” META-ANALYSIS

It has yet to be established whether gender moderates or predicts outcome of psychological and pharmacological treatments for adult depression because: (1) individual randomized trials typically lack sufficient statistical power to detect moderators and predictors and (2) meta‐analyses cannot examine such associations directly.