Gereon Heuft

Decreased gray matter volumes in the cingulo-frontal cortex and the amygdala in patients with fibromyalgia.

Objective: Studies in fibromyalgia syndrome with functional neuroimaging support the hypothesis of central pain augmentation. To determine whether structural changes in areas of the pain system are additional preconditions for the central sensitization in fibromyalgia we performed voxel based morphometry in patients with fibromyalgia and healthy controls. Methods: We performed 3 Tesla magnetic resonance imaging of the brain in 14 patients with fibromyalgia and 14 healthy controls. Regional differences of the segmented and normalized gray matter volumes in brain areas of the pain system between both groups were determined. In those areas in which patients structurally differed from healthy controls, the correlation of disease-related factors with gray matter volumes was analyzed. Results: Patients presented a decrease in gray matter volume in the prefrontal cortex, the amygdala, and the anterior cingulate cortex (ACC). The duration of pain or functional pain disability did not correlate with gray matter volumes. A trend of inverse correlation of gray matter volume reduction in the ACC with the duration of pain medication intake has been detected. Conclusions: Our results suggest that structural changes in the pain system are associated with fibromyalgia. As disease factors do not correlate with reduced gray matter volume in areas of the cingulo-frontal cortex and the amygdala in patients, one possible interpretation is that volume reductions might be a precondition for central sensitization in fibromyalgia. ACC = anterior cingulate cortex; fMRI = functional magnetic resonance imaging; FMS = fibromyalgia syndrome; HADS = Hospital Anxiety and Depression Scale; PAG = periaqueductal grey; PDI = Pain Disability Index; PTSD = posttraumatic stress disorder; ROI = region of interest; SPM = statistical parametric mapping; SSRIs = selective serotonin reuptake inhibitors; TCAs = tricyclic antidepressants; VBM = voxel-based morphometry; 3T = 3 Tesla.

Treatment of chronic pruritus with the selective serotonin re-uptake inhibitors paroxetine and fluvoxamine: results of an open-labelled, two-arm proof-of-concept study.

Chronic pruritus is difficult to treat and requires the evaluation of new therapeutic modalities. We initiated an open-labelled, two-arm prospective, proof-of-concept study applying two selective serotonin re-uptake inhibitors on a long-term basis. Paroxetine and fluvoxamine were tested in a total of 72 pruritic patients (27 men, 45 women, age range 28-88 years, mean age 59.2 years). The reduction in pruritus was evaluated by analysis of visual analogue scores and determination of the maximal antipruritic effect (maximal percentual reduction in pruritus). Forty-nine of 72 patients (68.0%) experienced a weak (n=9), good (n=16) or very good (n=24) antipruritic effect. Statistical analysis proved the efficacy of paroxetine and fluvoxamine with no significant difference. The best response was observed in patients with pruritus due to atopic dermatitis, systemic lymphoma and solid carcinoma. Chronic scratch lesions healed completely in 14/31 patients and partially in 17/31 patients. Adverse drug effects were observed in 70.8% of patients, resulting in discontinuation of treatment in 18 patients. These results support previous reports of high antipruritic potency of selective serotonin re-uptake inhibitors, which are a good alternative treatment modality in chronic pruritus. This should be confirmed in future double-blind studies.

Abnormal brain activation during movement observation in patients with conversion paralysis.

Dissociative paralysis in conversion disorders has variably been attributed to a lack of movement initiation or an inhibition of movement. While psychodynamic theory suggests altered movement conceptualization, brain activation associated with observation and replication of movements has so far not been assessed neurobiologically. Here, we measured brain activation by functional magnetic resonance imaging during observation and subsequent imitative execution of movements in four patients with dissociative hand paralysis. Compared to healthy controls conversion disorder patients showed decreased activation of cortical hand areas during movement observation. This effect was specific to the side of their dissociative paralysis. No brain activation compatible with movement inhibition was observed. These findings indicate that in dissociative paralysis, there is not only derangement of movement initiation but already of movement conceptualization. This raises the possibility that strategies targeted at reestablishing appropriate movement conceptualization may contribute to the therapy of dissociative paralysis.

The Prevalence and Differential Diagnosis of Subclinical Depressive Syndromes in Inpatients 60 Years and Older

Background: Depressive syndromes that do not comply with the diagnostic criteria for specific depressive disorders are designated as ‘subclinical’ or ‘subsyndromal’ depressive syndromes. Using our own data from a clinical study, this paper outlines the significance of subclinical depressive syndromes and demonstrates the problems of differentiating between depressive and subclinical depression (SD) syndromes and organic mood disorders especially in an elderly population with medical comorbidity. Methods: Two hundred and sixty-two patients aged 60 years and older in a general hospital were investigated, using a clinical psychiatric interview, expert ratings and self-report scales after extensive internal medical diagnostic evaluation. Results: When, without further differentiation as to their origin, all symptoms required by symptom checklists according to ICD-10 were considered for the diagnosis of major depression (MD), 35.5% of the study participants fulfilled the diagnostic criteria. After differentiating for etiology of symptoms, MD was found in only 14.1%, SD was diagnosed in 17.6% and organic mood disorder in 12.2% of the study participants. In another 41 patients (15.6%), symptoms of depression not fulfilling ICD-10 criteria were classified as being of organic or drug-induced origin. SD patients were in a mean position between nondepressive and depressive patients with regard to social isolation and physical impairment; women were overrepresented in the depressive and subdepressive groups. Conclusions: SD and organic mood disorder are common and helpful diagnostic categories in the elderly. The results show that in old age there is substantial danger of confounding MD, SD and organic mood disorder, thus leading to erroneously high prevalence rates of MD and underestimations of organic mood disorder if depressive symptoms are recorded only by self-report scales or a symptom checklist. Both internal and psychosomatic-psychotherapeutic competence as well as a liaison service in general hospitals are necessary for the differential diagnosis of MD, SD and organic mood disorder in the elderly with medical comorbidity.

Is there a benefit from intensified medical and psychological interventions in patients with functional dyspepsia not responding to conventional therapy

Aim In a prospective randomized, controlled trial, to compare the long‐term outcome of intensive medical therapy (with or without cognitive‐behavioural or muscle relaxation therapy) vs. standard medical therapy in patients with refractory functional dyspepsia (FD), referred to a tertiary referral medical center.

Psychological factors in prurigo nodularis in comparison with psoriasis vulgaris : results of a case-control study

Background  It has been suggested that psychological factors such as repressing anger and altruistic interpersonal behaviour may play a role in the aetiology of chronic itching in prurigo nodularis (PN). Whether these issues are specific for PN or are also common in other chronic skin diseases, e.g. psoriasis, has not been investigated until now.

Clinical presentation and personality factors are predictors of the response to treatment in patients with functional dyspepsia ; a randomized, double-blind placebo-controlled crossover study

The role of psychological factors or symptom pattern for the response to treatment in patients with unexplained (functional) dyspepsia is unknown. We hypothesized that patients with reflux- and ulcer-like symptoms would be more likely to respond to acid-lowering therapy, while psychological disturbances would be associated with a less favorable response to treatment. Seventy-eight patients with a diagnosis of functional dyspepsia were recruited and 75 completed the trial. Patients were treated for 4 weeks in a double-blind, placebo-controlled crossover trial starting in random order with either active drug (ranitidine, 150 mg b.d.) or placebo. Every 7 days, medication was switched from active drug to placebo, or vice versa. At entry, patient characteristics were assessed utilizing a semistructured standardized interview and standardized questionnaires, and weekly intensity of symptoms was assessed utilizing a visual analogue scale. Patients with a greater reduction of the symptom score during active treatment and an overall reduction of the global symptom score by more than 50% at the end of the study period were categorized as responders. Logistic regression analysis was utilized to assess the influence of symptom type and presence of psychological disturbances on the treatment response. During treatment the symptom score decreased significantly, from 32.1 ± 1.44 (SD) to 21.3 ± 1.9 at the end of the trial (P < 0.001). Twenty of 75 were responders. High scores for somatization (OR, 3.6; 95% Cl, 1.2–11.4), anxiety (OR, 3.3; 95% Cl, 0.9–11.8), and reflux-like symptoms (OR, 5.3; 95% Cl, 1.7–16.7) were associated with response to treatment, while dysmotility-like symptoms were associated with an unfavorable response (OR, 0.3; 95% Cl, 0.1–0.9). Symptom pattern and psychological disturbances are independent predictors of treatment response. Patients with reflux-like symptoms and greater psychological disturbances are more likely to respond to an acid-lowering compound.

Brain correlates of hypnotic paralysis—a resting-state fMRI study

Hypnotic paralysis has been used since the times of Charcot to study altered states of consciousness; however, the underlying neurobiological correlates are poorly understood. We investigated human brain function during hypnotic paralysis using resting-state functional magnetic resonance imaging (fMRI), focussing on two core regions of the default mode network and the representation of the paralysed hand in the primary motor cortex. Hypnotic suggestion induced an observable left-hand paralysis in 19 participants. Resting-state fMRI at 3T was performed in pseudo-randomised order awake and in the hypnotic condition. Functional connectivity analyses revealed increased connectivity of the precuneus with the right dorsolateral prefrontal cortex, angular gyrus, and a dorsal part of the precuneus. Functional connectivity of the medial frontal cortex and the primary motor cortex remained unchanged. Our results reveal that the precuneus plays a pivotal role during maintenance of an altered state of consciousness. The increased coupling of selective cortical areas with the precuneus supports the concept that hypnotic paralysis may be mediated by a modified representation of the self which impacts motor abilities.

Impairment of health-related quality of life in functional dyspepsia and chronic liver disease : the influence of depression and anxiety

Background  Health‐related quality of life (HRQOL) is a marker of disease severity. Data on the relative impairment of HRQOL in chronic liver disease (CLD) and functional gastrointestinal disorders are lacking and no studies have assessed the link between impairment of HRQOL and psychosocial factors yet.

Cerebral mechanisms of experimental hyperalgesia in fibromyalgia

The present study examined the hyperresponsiveness of the central nervous system in patients with fibromyalgia syndrome (FMS) related to mechanical hyperalgesia. The goals were to differentiate between increased pain ratings and hyperalgesia related either to peripheral or to central sensitization and to correlate with cerebral activation pattern. Seventeen patients and 17 healthy controls were examined, placing an experimental incision in the right volar forearm and causing tonic pain. Experimental pain, primary and secondary hyperalgesia were assessed during the time course of the experimental pain, and the changes in hyperalgesia were correlated to brain activation (functional magnetic resonance imaging). Patients with FMS experienced the experimental pain during the time course as more painful than healthy controls (Fscore = 3.93, pscore = 0.008). While they did not present a different course of primary hyperalgesia (Fscore = 1.01, pscore = 0.40), they did show greater secondary hyperalgesia (Fscore = 5.45, pscore = 0.004). In patients with FMS, the cerebral pattern corresponding to secondary hyperalgesia was altered. The activity in the dorsolateral prefrontal cortex was inversely correlated with secondary hyperalgesia in healthy controls (R = −0.34 p = 0.005); in patients, this correlation was disrupted (R = 0.19 p = 0.12). These findings point to an alteration of pain transmission at the central level in FMS (e.g., loss of inhibition) and might be related to changes in cerebral‐midbrain‐spinal mechanisms of pain inhibition.