Andrea Reinecke

Effect of Acute Antidepressant Administration on Negative Affective Bias in Depressed Patients

OBJECTIVEnAcute administration of an antidepressant increases positive affective processing in healthy volunteers, an effect that may be relevant to the therapeutic actions of these medications. The authors investigated whether this effect is apparent in depressed patients early in treatment, prior to changes in mood and symptoms.nnnMETHODnIn a double-blind, placebo-controlled, between-groups randomized design, the authors examined the effect of a single 4-mg dose of the norepinephrine reuptake inhibitor reboxetine on emotional processing. Thirty-three depressed patients were recruited through primary care clinics and the community and matched to 31 healthy comparison subjects. Three hours after dosing, participants were given a battery of emotional processing tasks comprising facial expression recognition, emotional categorization, and memory. Ratings of mood, anxiety, and side effects were also obtained before and after treatment.nnnRESULTSnDepressed patients who received placebo showed reduced recognition of positive facial expressions, decreased speed in responding to positive self-relevant personality adjectives, and reduced memory for this positive information compared to healthy volunteers receiving placebo. However, this effect was reversed in patients who received a single dose of reboxetine, despite the absence of changes in subjective ratings of mood or anxiety.nnnCONCLUSIONSnAntidepressant drug administration modulates emotional processing in depressed patients very early in treatment, before changes occur in mood and symptoms. This effect may ameliorate the negative biases in information processing that characterize mood and anxiety disorders. It also suggests a mechanism of action compatible with cognitive theories of depression.

Changes in Automatic Threat Processing Precede and Predict Clinical Changes with Exposure-Based Cognitive-Behavior Therapy for Panic Disorder

BACKGROUNDnCognitive behavioral therapy (CBT) is an effective treatment for emotional disorders such as anxiety or depression, but the mechanisms underlying successful intervention are far from understood. Although it has been a long-held view that psychopharmacological approaches work by directly targeting automatic emotional information processing in the brain, it is usually postulated that psychological treatments affect these processes only over time, through changes in more conscious thought cycles. This study explored the role of early changes in emotional information processing in CBT action.nnnMETHODSnTwenty-eight untreated patients with panic disorder were randomized to a single session of exposure-based CBT or waiting group. Emotional information processing was measured on the day after intervention with an attentional visual probe task, and clinical symptoms were assessed on the day after intervention and at 4-week follow-up.nnnRESULTSnVigilance for threat information was decreased in the treated group, compared with the waiting group, the day after intervention, before reductions in clinical symptoms. The magnitude of this early effect on threat vigilance predicted therapeutic response after 4 weeks.nnnCONCLUSIONSnCognitive behavioral therapy rapidly affects automatic processing, and these early effects are predictive of later therapeutic change. Such results suggest very fast action on automatic processes mediating threat sensitivity, and they provide an early marker of treatment response. Furthermore, these findings challenge the notion that psychological treatments work directly on conscious thought processes before automatic information processing and imply a greater similarity between early effects of pharmacological and psychological treatments for anxiety than previously thought.

Predicting rapid response to cognitive-behavioural treatment for panic disorder: the role of hippocampus, insula, and dorsolateral prefrontal cortex.

Although cognitive-behavioural therapy (CBT) is an effective first-line intervention for anxiety disorders, treatments remain long and cost-intensive, difficult to access, and a subgroup of patients fails to show any benefits at all. This study aimed to identify functional and structural brain markers that predict a rapid response to CBT. Such knowledge will be important to establish the mechanisms underlying successful treatment and to develop more effective, shorter interventions. Fourteen unmedicated patients with panic disorder underwent 3 T functional and structural magnetic resonance imaging (MRI) before receiving four sessions of exposure-based CBT. Symptom severity was measured before and after treatment. During functional MRI, patients performed an emotion regulation task, either viewing negative images naturally, or intentionally down-regulating negative affect by using previously taught strategies of cognitive reappraisal. Structural MRI images were analysed including left and right segmentation and volume estimation. Improved response to brief CBT was predicted by increased pre-treatment activation in bilateral insula and left dorsolateral prefrontal cortex (dlPFC) during threat processing, as well as increased right hippocampal gray matter volume. Previous work links these regions to improved threat processing and fear memory activation, suggesting that the activation of such mechanisms is crucial for exposure-based CBT to be effective.

Attentional bias in untreated panic disorder.

The role of attentional biases in panic disorder has been well characterised. However, recent studies suggest an important effect of antidepressant and anxiolytic drugs on cognitive bias and most studies have included medicated patients in their sample. This study therefore examined cognitive bias in an untreated sample of participants with panic disorder (PD). A sample of 23 untreated participants with panic disorder with or without agoraphobia (PPD) and 22 healthy controls (HC) were tested with a Facial Expression Recognition task featuring different emotional intensities, a Faces Dot Probe task, a Self Beliefs task and an Emotional Stroop task. PPD showed exaggerated attentional biases to negative face and word stimuli in two different paradigms and endorsed more panic-related and negative self-attributions. They also showed enhanced perception of facial expressions of sadness. These tasks are sensitive to cognitive bias in a community-based sample of untreated PD participants. Attentional biases in panic disorder cannot be explained by the use of medication in this group and may therefore play a critical role in the underlying pathogenesis of the disorder.

Paradoxical effects of short-term antidepressant treatment in fMRI emotional processing models in volunteers with high neuroticism.

BACKGROUNDnShort-term antidepressant administration has been reported to decrease amygdala response to threat in healthy volunteers and depressed patients. Neuroticism (N) is a risk factor for depression but has also been associated with slow or incomplete remission with antidepressant drug treatment. Our aim was to investigate early selective serotonin reuptake inhibitor (SSRI) administration neural effects on implicit processing of fearful facial expressions in volunteers with high levels of N.nnnMETHODnHighly neurotic subjects received 20 mg/day citalopram versus placebo for 7 days in a double-blind, between-groups design. On the last day haemoperfusion and functional magnetic resonance imaging (fMRI) data during a gender discrimination task with fearful and happy faces were acquired. A control group of non-neurotic volunteers was also tested.nnnRESULTSnHigh-N volunteers had reduced responses to threatening facial expressions across key neural circuits compared to low-N volunteers. SSRI treatment was found to elevate resting perfusion in the right amygdala, increase bilateral amygdalae activation to positive and negative facial expressions and increase activation to fearful versus happy facial expressions in occipital, parietal, temporal and prefrontal cortical areas.nnnCONCLUSIONSnThese results suggest that 7 days of SSRI administration can increase neural markers of fear reactivity in subjects at the high end of the N dimension and may be related to early increases in anxiety and agitation seen early in treatment. Such processes may be involved in the later therapeutic effects through decreased avoidance and increased learning about social threat cues.

Different neural and cognitive response to emotional faces in healthy monozygotic twins at risk of depression

BACKGROUNDnNegative cognitive bias and aberrant neural processing of emotional faces are trait-marks of depression. Yet it is unclear whether these changes constitute an endophenotype for depression and are also present in healthy individuals with hereditary risk for depression.nnnMETHODnThirty healthy, never-depressed monozygotic (MZ) twins with a co-twin history of depression (high risk group: nxa0=xa013) or without co-twin history of depression (low-risk group: nxa0=xa017) were enrolled in a functional magnetic resonance imaging (fMRI) study. During fMRI, participants viewed fearful and happy faces while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping strategies.nnnRESULTSnHigh-risk twins showed increased neural response to happy and fearful faces in dorsal anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), pre-supplementary motor area and occipito-parietal regions compared to low-risk twins. They also displayed stronger negative coupling between amygdala and pregenual ACC, dmPFC and temporo-parietal regions during emotional face processing. These task-related changes in neural responses in high-risk twins were accompanied by impaired gender discrimination performance during face processing. They also displayed increased attention vigilance for fearful faces and were slower at recognizing facial expressions relative to low-risk controls. These effects occurred in the absence of differences between groups in mood, subjective state or coping.nnnCONCLUSIONSnDifferent neural response and functional connectivity within fronto-limbic and occipito-parietal regions during emotional face processing and enhanced fear vigilance may be key endophenotypes for depression.

Generalized implicit fear associations in Generalized Anxiety Disorder

Background: Cognitive schema theories of anxiety postulate that higher‐level cognitive processes such as attention and memory are guided by underlying distorted fear associations. While numerous studies investigated these disorder‐specific, biased processes, hardly any research addressed the underlying schemata themselves. In particular, no study has ever addressed implicit fear associations in Generalized Anxiety Disorder (GAD). In addition, no study has ever experimentally investigated the clinical observation that in GAD, patients worry processes seem to be triggered by a broad range of materials, even by neutral or positive stimuli. Methods: We used a Single Target Implicit Association Task (STIAT) to investigate implicit associations and stimulus generalization with clearly negative worry‐related words (e.g., cancer, bankruptcy) and neutral words that are only indirectly related to worry topics (e.g., doctor, bank). Participants were 39 GAD patients and 23 healthy controls. Results: In line with our expectations, both groups showed negative implicit associations with negative target words, and only GAD patients also associated neutral words with negative attributes. Conclusions: These results support the hypothesis that GAD patients fear associations generalize to stimuli that are only peripherally related to the core of their worries. Depression and Anxiety, 2010.

Optimizing the ingredients for imagery-based interpretation bias modification for depressed mood: Is self-generation more effective than imagination alone?

Negative interpretation is thought to be crucial in the development and maintenance of depression. Recently developed cognitive bias modification paradigms, intending to change these biases towards a more optimistic interpretation tendency (CBM-I), seem to offer new promising implications for cognitive therapy innovation. This study aimed to increase our knowledge of the underlying mechanisms of action of imagery-based CBM-I in the context of depressed mood. We therefore compared the efficacy of CBM-I requiring participants to imagine standardized positive resolutions to a novel, more active training version that required participants to generate the positive interpretations themselves. Fifty-four participants were randomly allocated to (1) standardized CBM-I, (2) self-generation CBM-I or (3) a control group. Outcome measures included self-report mood measures and a depression-related interpretation bias measure. Both positive training variants significantly increased the tendency to interpret fresh ambiguous material in an optimistic manner. However, only the standardized imagery CBM-I paradigm positively influenced mood.

Treatment sensitivity of implicit threat evaluation, avoidance tendency and visual working memory bias in specific phobia.

Cognitive theories of anxiety postulate that negative processing biases play a causal role in the pathogenesis of a disorder, while a normalisation of bias drives recovery. To test these assumptions it is essential to investigate whether biases seen in anxiety are treatment-sensitive, or whether they instead represent enduring vulnerability factors. Twenty-nine spider fearfuls were tested before and after brief cognitive-behaviour therapy (CBT), with half of them additionally being tested before a waiting period to control for retest effects. Using three cognitive bias tasks, we measured implicit threat evaluation (Extrinsic Affective Simon Task), avoidance tendency (Approach-Avoidance Task), and working memory for threat. CBT significantly enhanced negative implicit evaluation and avoidance. This indicates that these cognitive biases are no stable risk factors and provides further evidence for their potential key role in the development and remission of anxiety.

Sexuelle Dysfunktionen bei Patienten einer verhaltenstherapeutischen Hochschulambulanz: Häufigkeit, Erkennen, Behandlung

Prevalence data on sexual dysfunctions indicate a high need for therapy and health care for sexual problems. One of the study’s aims was to investigate the extent of that need in patients of a psychotherapeutic university outpatient clinic. Besides, we examined to what extent sexual problems are recognised and treated by behaviour therapists in training. Patients and Methods: In a patient study, we tested 173 outpatients (aged 16-64 years, 71.7% female) who were seeking psychotherapy. By completing the German version of the Massachusetts General Hospital Sexual Functioning Questionnaire, participants rated their sexual interest, their ability to sexual arousal, to experience orgasm, to attain erection/lubrication and their general sexual satisfaction in the past month. In a therapist study, we examined whether 16 therapists in training were able to differentiate between patients with and without sexual dysfunction, whether they brought up the topic during therapy and whether they treated the sexual dysfunction. Results: Depending on the type of problem, one out of two to three women and one out of three to five men report sexual problems. Therapists recognise sexual problems in half of the patients, and bring up the issue of sexuality in every second patient. In fact, every third case of sexual dysfunction is treated. Conclusion: Behaviour therapy training should put a stronger emphasis on the topic of ‘sexual dysfunctions’.