Training emotion regulation through real-time fMRI neurofeedback of amygdala activity.

Being in control of one's emotions is not only desirable in many everyday situations but is also a great challenge in a variety of mental disorders. Successful intentional emotion regulation is related to down-regulation of amygdala activity. Training mental interventions supported by neurofeedback of one's own amygdala activity using real-time (rt-)fMRI might be beneficial for mental health and well-being. Rt-fMRI guided amygdala-downregulation using cognitive interventions such as a "reality check", however, have not been well-investigated. Fifteen healthy subjects underwent four rt-fMRI sessions with neurofeedback of their own amygdala activity while applying a reality check as an emotion regulation strategy in order to down-regulate their amygdala signal during a stimulation with emotional pictures. The Control group comprised of eleven subjects also trained emotion regulation but without obtaining feedback. We hypothesized more prominent down-regulation of amygdala activity at the end of the training in the Feedback group. We investigated effects over time and between groups and further task specific connectivity of the amygdala by using psychophysiological interaction analyses. Four weekly amygdala-based feedback sessions resulted in significantly decreased amygdala activity (p = 0.003, d = 0.93), also compared to the Control group (p = 0.014, d = 1.12). Task specific connectivity of the amygdala with the anterior cingulate cortex, hippocampus and distinct prefrontal areas was increased in the Feedback group. Training of emotion regulation supported by rt-fMRI neurofeedback resulted in a prominent amygdala down-regulation compared to training without feedback. The finding implicates successful emotion regulation, compliant with emotion control models, through an easily applicable reality check strategy. Rt-fMRI neurofeedback may support emotion regulation learning and bears clinical potential for psychotherapy.

Increased fronto-striatal reward prediction errors moderate decision making in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been linked to functional abnormalities in fronto-striatal networks as well as impairments in decision making and learning. Little is known about the neurocognitive mechanisms causing these decision-making and learning deficits in OCD, and how they relate to dysfunction in fronto-striatal networks. METHOD: We investigated neural mechanisms of decision making in OCD patients, including early and late onset of disorder, in terms of reward prediction errors (RPEs) using functional magnetic resonance imaging. RPEs index a mismatch between expected and received outcomes, encoded by the dopaminergic system, and are known to drive learning and decision making in humans and animals. We used reinforcement learning models and RPE signals to infer the learning mechanisms and to compare behavioural parameters and neural RPE responses of the OCD patients with those of healthy matched controls. RESULTS: Patients with OCD showed significantly increased RPE responses in the anterior cingulate cortex (ACC) and the putamen compared with controls. OCD patients also had a significantly lower perseveration parameter than controls. CONCLUSIONS: Enhanced RPE signals in the ACC and putamen extend previous findings of fronto-striatal deficits in OCD. These abnormally strong RPEs suggest a hyper-responsive learning network in patients with OCD, which might explain their indecisiveness and intolerance of uncertainty.

Pattern of structural brain changes in social anxiety disorder after cognitive behavioral group therapy: a longitudinal multimodal MRI study.

Social anxiety disorder (SAD) is characterized by fears of social and performance situations. Cognitive behavioral group therapy (CBGT) has in general positive effects on symptoms, distress and avoidance in SAD. Prior studies found increased cortical volumes and decreased fractional anisotropy (FA) in SAD compared with healthy controls (HCs). Thirty-three participants diagnosed with SAD attended in a 10-week CBGT and were scanned before and after therapy. We applied three neuroimaging methods-surface-based morphometry, diffusion tensor imaging and network-based statistics-each with specific longitudinal processing protocols, to investigate CBGT-induced structural brain alterations of the gray and white matter (WM). Surface-based morphometry revealed a significant cortical volume reduction (pre- to post-treatment) in the left inferior parietal cortex, as well as a positive partial correlation between treatment success (indexed by reductions in Liebowitz Social Anxiety Scale) and reductions in cortical volume in bilateral dorsomedial prefrontal cortex. Diffusion tensor imaging analysis revealed a significant increase in FA in bilateral uncinate fasciculus and right inferior longitudinal fasciculus. Network-based statistics revealed a significant increase of structural connectivity in a frontolimbic network. No partial correlations with treatment success have been found in WM analyses. For, we believe, the first time, we present a distinctive pattern of longitudinal structural brain changes after CBGT measured with three established magnetic resonance imaging analyzing techniques. Our findings are in line with previous cross-sectional, unimodal SAD studies and extent them by highlighting anatomical brain alterations that point toward the level of HCs in parallel with a reduction in SAD symptomatology.

Common and differential alterations of general emotion processing in obsessive-compulsive and social anxiety disorder.

BACKGROUND: Obsessive compulsive disorder (OCD) and social anxiety disorder (SAD) are characterized by biased perception and processing of potentially threatening stimuli. A hyper-reactivity of the fear-circuit [e.g. amygdala, anterior cingulate (ACC)] has been consistently reported using functional magnetic resonance imaging (fMRI) in SAD in comparison with healthy controls (HCs). Studies investigating the processing of specific emotional stimuli in OCD reported mainly orbitofrontal-striatal abnormalities. The goal of this study was to examine similar/common and differential neurobiological responses in OCD and SAD using unspecific emotional stimuli. METHOD: Fifty-four subjects participated: two groups (each n = 18) of outpatients with a current diagnosis of OCD or SAD, and 18 HCs. All subjects underwent fMRI while anticipating and perceiving unspecific visual stimuli with prior announced emotional valence (e.g. positive). RESULTS: Compared to HCs, the combined patient group showed increased activation in amygdala, caudate and prefrontal/orbitofrontal cortex while anticipating unspecific emotional stimuli. Caudate was more active in the combined patient group during perception. A comparison between the OCD and the SAD samples revealed increased amygdala and decreased rostral ACC activation in OCD patients during perception, but no differences in the anticipation phase. CONCLUSIONS: Overall, we could identify common fronto-subcortical hyper-reactivity in OCD and SAD while anticipating and perceiving unspecific emotional stimuli. While differential neurobiological responses between OCD and SAD when processing specific stimuli are evident from the literature, differences were less pronounced using unspecific stimuli. This could indicate a disturbance of emotion regulation common to both OCD and SAD.

[Psychotherapy for everyone? On the indications for psychotherapeutic treatment]. / Psychotherapie für alle? : Zur Indikation für psychotherapeutische Behandlungen.

BACKGROUND: The effectiveness of psychotherapy for the treatment of most mental disorders is empirically very convincingly documented; however, there are not enough therapists by far available globally to enable all people suffering from mental disorders to be adequately provided with psychotherapy. AIMS AND METHODS: Considerations are made regarding which illnesses, disorders and problems in general should be treated by means of psychotherapy, who should best conduct the treatment and in which way the dissemination of evidence-based psychotherapeutic approaches could be improved in spite of scarce resources. RESULTS: The more severely pronounced a health problem is, the greater is normally the therapeutic benefit of a given intervention. This applies to psychotherapy as well; however, to date severely ill people in particular are often not treated with effective psychotherapeutic interventions. One of the reasons is that there are only few validated treatment protocols for multimorbid patients with both mental and physical illnesses. Another reason is that treatment of such patients requires specific medical knowledge as well as other special skills and experiences that not all psychotherapists have at their command. CONCLUSION: The indications for psychotherapy should always be made with a sense of proportion, taking into consideration the currently available scientific evidence and clinical experience. In the future, the training of psychotherapists, scientific investigations of psychotherapies and clinical service provision should increasingly concentrate on patients with severe mental disorders and/or with psychological and physical comorbidities.

Neural circuits associated with positive and negative self-appraisal.

Self-worth is particularly influenced by self-appraisal, which is negatively biased in many psychiatric disorders. Positive and negative self-appraisals also shape current emotional states or even evoke defensive reactions, when they are incongruent with a subject's current state. Prior studies have mainly used externally given evaluative appraisals. In this study, 30 subjects used individual negative and positive self-appraisals during functional magnetic resonance imaging. We additionally investigated the effects of such self-appraisals onto the subsequent perception of photos of the individual subjects. Both self-appraisal conditions activated dorsomedial and dorsolateral prefrontal cortex compared to the neutral condition. Positive self-appraisal evoked stronger activity than negative self-appraisal in the amygdala, ventral striatum and anterior cingulate cortex, whereas negative self-appraisal was associated with increased activity in the occipital regions. Positive self-appraisal had no effect on the perception of a photo of oneself, whereas negative appraisal increased activity in the anterior insula and parietal regions. Overall, positive self-appraisal activated more emotion-related brain regions, whereas negative self-appraisal had a relatively stronger influence on perception-related brain activity. These findings could on the one hand explain the effect of negative self-appraisal on the behavior in the real world and on the other hand support a stronger focus of psychotherapy on enhancing positive self-appraisals.

[Postgraduate training for specialists in psychiatry and psychotherapy. Problem-based learning - evaluation of a pilot project]. / Facharztweiterbildung Psychiatrie und Psychotherapie. Problemorientiertes Lernen - Evaluation eines Modellprojekts.

Problem-based learning (PBL) emphasizes the student's individual needs, their ability to solve complex clinical problems, and a professional attitude that facilitates communication among colleagues. Thus, PBL appears to provide a perfectly suitable didactic format for postgraduate training of medical specialties. To date, it is only rarely used in this area though. In a pilot project, we implemented PBL into the curriculum of postgraduate training in psychiatry and psychotherapy, and evaluated the program over a period of 12 months, using structured questionnaires. A total of 41 PBL courses were held, with 447 residents participating. Participants as well as tutors assessed 19 of 21 aspects as good or very good (5-point Likert scale, mean value >4). Overall, PBL was rated as highly suitable for advanced training (participants: 4.5±0.8; tutors: 5.0±0.2). The results of this pilot project suggest that PBL might be a useful element of multifaceted advanced training programs, strengthening their practical component and the applicability of knowledge in the daily clinical routine.

Impact of emotion on cognition in trauma survivors: what is the role of posttraumatic stress disorder?

BACKGROUND: Cognitive theories of anxiety disorders postulate an increased attentional bias to environmental cues associated with threat that underlies the exaggerated fear response. The role of trauma, which may represent strong competitive advantage for attention, remains unclear. We investigated the influence of trauma exposure and the presence of anxiety/stress disorders on the impact of emotional distractors on cognitive performance. METHODS: Fourteen trauma-exposed subjects with PTSD, 12 trauma-exposed subjects with anxiety disorders other than PTSD, 12 trauma-exposed healthy subjects and 19 non-trauma-exposed healthy controls participated in this study. The impact of emotion on cognition was determined by the Affective Stroop task that measures the effect of irrelevant emotional distractors on the speed of operant responding. RESULTS: The speed of cognitive performance was significantly reduced in the presence of negative distractors versus neutral or positive distractors in subjects with PTSD, while there was no significant influence of the distractor type on performance in the other diagnostic groups (diagnosis-by-distractor type interaction, p<0.001). While negative distractors induced the same levels of anxiety and depersonalization in subjects with PTSD and subjects with other anxiety disorders, distractor-induced depersonalization was associated with slowing of cognitive performance in PTSD (p=0.02) but not in other groups. LIMITATIONS: Different types of anxiety disorders in the non-PTSD group might reduce the selectivity of the results; some subjects received medication possibly impacting on their cognitive functioning. CONCLUSIONS: The cognitive impairments in the presence of negative distractors specifically found in PTSD call for research into novel psychotherapeutic approaches, e.g. attentional training, for PTSD.

[Quality of life and alexithymia in somatoform pain disorder]. / Lebensqualität und alexithyme Merkmale bei Patienten mit somatoformer Schmerzstörung.

BACKGROUND: Patients with somatoform pain disorders (SPD) frequently display reduced quality of life (QoL) and increased levels of alexithymia. This study investigated the association of QoL and alexithymia in a sample of SPD. PATIENTS AND METHODS: Fifty-one patients with SPD (average time since onset: 11.6 years) were assessed in terms of alexithymia (TAS-20), QoL (WHOQOL-BREF), psychological distress and somatisation (SCL-90-R), and depression (MADRS). RESULTS: In SPD patients a significant negative correlation was observed between QoL and alexithymia, particularly the psychological domain of QoL and the TAS-20 total score (r=-.63, p<.001). The TAS-20 subscale "Difficulty Describing Feelings" was revealed to be a significant predictor of the psychological domain of QoL (beta=-.34, p<.01), even after controlling for depression, somatisation and gender. CONCLUSION: Patients with SPD show a remarkably reduced QoL and alexithymia appears to play a significant role for low QoL. Clinicians need to pay careful attention to alexithymia with regard to diagnosis and treatment planning in SPD patients.

Changes in quality of life following cognitive-behavioral group therapy for panic disorder.

BACKGROUND: Data about quality of life (QoL) are important to estimate the impact of diseases on functioning and well-being. The present study was designed to assess the association of different aspects of panic disorder (PD) with QoL and to examine the relationship between QoL and symptomatic outcome following brief cognitive-behavioral group therapy (CBGT). METHOD: The sample consisted of 55 consecutively recruited outpatients suffering from PD who underwent CBGT. QoL was assessed by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) at baseline, post-treatment and six months follow-up. SF-36 baseline scores were compared with normative data obtained from a large German population sample. RESULTS: Agoraphobia, disability, and worries about health were significantly associated with decreased QoL, whereas frequency, severity and duration of panic attacks were not. Treatment responders showed significantly better QoL than non-responders. PD symptom reduction following CBGT was associated with considerable improvement in emotional and physical aspects of QoL. However, the vitality subscale of the SF-36 remained largely unchanged over time. CONCLUSIONS: Our results are encouraging for cognitive-behavior therapists who treat patients suffering from PD in groups, since decrease of PD symptoms appears to be associated with considerable improvements in QoL. Nevertheless, additional interventions designed to target specific aspects of QoL, in particular vitality, may be useful to enhance patients' well-being.

Brain imaging in psychiatry - a study of 435 psychiatric in-patients at a university clinic.

OBJECTIVE: The use of brain imaging in psychiatry still lacks clear guidelines. We investigated the referral practice, outcome and predictive factors of neuroimaging in a Swiss psychiatric university clinic. METHOD: Medical files were reviewed retrospectively for 435 consecutively hospitalized patients who were subjected to neuroimaging. The association between the sociodemographic and clinical characteristics and the scan results was analyzed using bivariate and multivariate analyses. RESULTS: Of overall examinations, 69.4% were normal, 16.3% equivocal and 14.3% abnormal; 2.9% of scans ordered for screening only showed pathology. Neurologic signs and advanced age of patients predicted abnormal scan findings, whereas other variables such as EEG results showed no significant association. CONCLUSION: Our results support the need for clear indications for using brain imaging in psychiatric in-patients. Focal neurologic signs and advanced patient age seems to predict abnormal scan results. However, these criteria are not sufficiently sensitive to predict significant scan findings in all patients.

Symptom dimensions in obsessive-compulsive disorder: prediction of cognitive-behavior therapy outcome.

OBJECTIVE: A significant number of patients with obsessive-compulsive disorder (OCD) fail to benefit sufficiently from treatments. This study aimed to evaluate whether certain OCD symptom dimensions were associated with cognitive-behavioral therapy (CBT) outcome. METHOD: Symptoms of 104 CBT-treated in-patients with OCD were assessed with the clinician-rated Yale-Brown Obsessive-Compulsive Scale symptom checklist. Logistic regression analyses examined outcome predictors. RESULTS: The most frequent OCD symptoms were aggressive and contamination obsessions, and compulsive checking and cleaning. Patients with hoarding symptoms at baseline (n = 19) were significantly less likely to become treatment responders as compared to patients without these symptoms. Patients with sexual and religious obsessions tended to respond less frequently, although this failed to reach statistical significance (P = 0.07). Regression analyses revealed that higher scores on the hoarding dimension were predictive of non-response, even after controlling for possible confounding variables. CONCLUSION: Our results strongly indicate that in-patients with obsessive-compulsive hoarding respond poorly to CBT.

[Trichotillomania: clinical presentation, causes, treatment options]. / Trichotillomanie--eine Störung zwischen Zwang und Impuls. Wenn Haare ausreissen Beruhigung verschafft.

Trichotillomania (compulsive pulling out of hair) is a disorder belonging in the group of obsessive-compulsive disorders, the frequency of which is underestimated. It is a complex clinical condition comprising both compulsive and impulsive elements, which makes it anything but easy to treat. Currently, the best documented treatment options are behavioral therapy and pharmacotherapy with selective serotonin reuptake inhibitors.

[Specific behaviour therapy day clinic]. / Die spezifische Verhaltenstherapie-Tagesklinik.

Psychiatric day care has a long tradition. However, psychotherapeutic day care institutions specialising in particular disorders or certain therapeutic approaches are still the exception. A day care unit for behaviour therapy was established at the Clinic for Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf in 1998 as part of a complex inpatient, day care, and outpatient behaviour therapy unit. The immediate and high acceptance by patients and their doctors indicates a strong need of such a treatment setting. We present how this day care unit works and how it differs from the traditional psychiatric day care.

[Bile acid stimulation test with ceruletide]. / Der Gallensäuren-Stimulationstest mit Ceruletid.

The bile acid stimulation test is a sensitive and liver specific test to check liver function. In contrast to the postprandial estimation of serum bile acids which has been used up to now, it offers the advantage of a better standardization. Furthermore there are hardly any side effects. The test requires three blood samples at 0, 20, and 40 minutes after an i.m. injection of 0.3 micrograms/kg KM Ceruletid (Takus). The normal values in the fasting state are under 5.0 mumol/l, 20 and 40 minutes after stimulation under 15.0 mumol/l serum bile acids.

Regulation of connexin-43, GFAP, and FGF-2 is not accompanied by changes in astroglial coupling in MPTP-lesioned, FGF-2-treated parkinsonian mice.

Basic fibroblast growth factor (bFGF; FGF-2) has potent trophic effects on developing and toxically impaired midbrain dopaminergic (DAergic) neurons which are crucially affected in Parkinson's disease. The trophic effects of FGF-2 are largely indirect, both in vitro and in vivo, and possibly involve intermediate actions of astrocytes and other glial cells. To further investigate the cellular and molecular mechanisms underlying the restorative actions of FGF-2, and to analyse in more detail the changes within astroglial cells in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-lesioned striatum, we have studied striatal expression and regulation of connexin-43 (cx43), the principal gap junction protein of astroglial cells, along with the expression of glial fibrillary acidic protein (GFAP), FGF-2, and functional coupling. Our results show an immediate, yet transient increase in cx43 mRNA, and a sustained increase in FGF-2 mRNA, GFAP-positive cells, and cx43-immunoreactive punctata following the MPTP lesion, without any induction of functional coupling between astrocytes and other glial cells as revealed by dye coupling of patched cells. Unilateral administration of FGF-2 in a piece of gelfoam caused a further increase in cx43-positive punctata immediately adjacent to the implant, which was more pronounced than after application of a gelfoam containing the nontrophic control protein cytochrome C. These changes were parallelled by a small increase in cx43 protein determined by Western blot, but not by alterations in the coupling state of cells in the vicinity of the gelfoam implant. Although our data indicate that MPTP and exogenous FGF-2 may alter expression and protein levels of cx43, they do not support the notion that increases in cellular coupling may underly the trophic and widespread actions of FGF-2 in the MPTP-model of Parkinson's disease.

Early effects of FGF-2 on glial cells in the MPTP-lesioned striatum.

Fibroblast growth factor-2 (FGF-2), locally administered in gelfoam to the striatum of mice treated with the neurotoxic drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has restorative and neuroprotective effects on dopaminergic neurons and associated striatal transmitter systems. Most of the beneficial alterations are apparently indirect. FGF-2 must therefore act through a series of cellular and molecular intermediate steps, which have not been explored. We have previously shown that FGF-2 does not significantly affect the astroglial reaction at the time, when the neuroprotective effect of FGF-2 reaches a peak (Day 11). In this study we have investigated the effect of FGF-2 at earlier time points after MPTP treatment. We report now that as early as 6 h after administration of the gelfoam containing either FGF-2 or control protein, FGF-2 immunoreactivity disappears from astroglial nuclei, while appearing in small ramified GFAP- and S-100-negative cells, most likely microglia. At 18 h, numbers and staining intensities of GFAP-ir astroglial cells are greater in FGF-2- than in cytochrome C-treated animals. At this time FGF-2-ir reappears in astroglia nuclei of cytochrome C-treated animals, but remains undetectable in the striatum carrying the FGF-2-containing gelfoam. Ramified GFAP/S-100-negative presumed microglial cells are now intensely ir for FGF-2. Signs of an FGF-2-mediated astrogliotic reaction are very pronounced at 18 h and 2 days, but no longer at 11 days, when the astrogliosis reaction has become equally strong in FGF-2- and cytochrome C-treated striata. Our results suggest that administration of FGF-2 to the MPTP-lesioned striatum has early effects on astro- and presumed microglia cells, notably on the nuclear FGF-2-ir of astrocytes. These changes may be involved in mediating the neuroprotective effects of FGF-2 in the MPTP-model of Parkinsonism.

Presence and regulation of transforming growth factor beta mRNA and protein in the normal and lesioned rat sciatic nerve.

The transforming growth factors beta (TGF-beta), a family of regulatory polypeptides, are involved in numerous vital processes including inflammation and wound healing. Since repair of a peripheral nerve lesion includes a series of well-defined steps of cellular actions possibly controlled by TGF-beta s, and since TGF-beta mRNA and immunoreactivity have been found in the normal peripheral nerve, we have examined in the lesioned peripheral nerve. Sciatic nerves of adult rats were either crushed (allowing axonal regeneration) or transfected (to prevent axonal regeneration and to induce Wallerian degeneration in the distal stump). After intervals of 6 hours, 2 and 6 days post-lesion, the rats were sacrificed and each nerve was cut into four segments, two proximal and two distal to the lesion site. TGF-beta 1-3 mRNA were determined for each segment. We demonstrate that TGF-beta 1 mRNA levels are higher than those of TGF-beta 3; the amplitude of mRNA regulation depends on time, type of lesion and localization relative to the lesion site. TGF-beta 2 mRNA could not be detected. For TGF-beta 1-3 immunocytochemistry, animals were sacrificed 12, 24, 48, 72 hours and 7 and 14 days after surgery. TGF-beta immunoreactivity (IR) was observed for all isoforms in lesioned and unlesioned nerves. In the segment directly adjacent to the lesion at its proximal side, an increase of TGF-beta-IR became apparent as soon as 12 hours after surgery; it remained elevated during the whole period observed in both models. In the segment adjoining the distal side of the lesion, an increase of TGF-beta-IR was observed after 48 hours, which was still present after 14 days. At day 7 after crush or transection, an increase of TGF-beta-IR was detected in the most distal segments, which reached its highest levels at the end of our observation period. Our results suggest that the presence of axonal contact might induce an enhancement of TGF-beta expression by Schwann cells in the distal stump of a lesioned and regenerating peripheral nerve. Since we demonstrate an increase of TGF-beta mRNA and protein expression also in the distal stump of transected nerves where Schwann cells are not able to contact sprouting axons from the proximal part, other regulatory pathways must exist. The acquisition of a "reactive" Schwann cell phenotype after peripheral nerve lesion might involve an upregulation of TGF-beta expression.