Altered interoceptive activation before, during, and after aversive breathing load in women remitted from anorexia nervosa.

BACKGROUND: The neural mechanisms of anorexia nervosa (AN), a severe and chronic psychiatric illness, are still poorly understood. Altered body state processing, or interoception, has been documented in AN, and disturbances in aversive interoception may contribute to distorted body perception, extreme dietary restriction, and anxiety. As prior data implicate a potential mismatch between interoceptive expectation and experience in AN, we examined whether AN is associated with altered brain activation before, during, and after an unpleasant interoceptive state change. METHODS: Adult women remitted from AN (RAN; n = 17) and healthy control women (CW; n = 25) underwent functional magnetic resonance imaging during an inspiratory breathing load paradigm. RESULTS: During stimulus anticipation, the RAN group, relative to CW, showed reduced activation in right mid-insula. In contrast, during the aversive breathing load, the RAN group showed increased activation compared with CW in striatum and cingulate and prefrontal cortices (PFC). The RAN group also showed increased activation in PFC, bilateral insula, striatum, and amygdala after stimulus offset. Time course analyses indicated that RAN responses in interoceptive processing regions during breathing load increased more steeply than those of CW. Exploratory analyses revealed that hyperactivation after breathing load was associated with markers of past AN severity. CONCLUSIONS: Anticipatory deactivation with a subsequent exaggerated brain response during and after an aversive body state may contribute to difficulty predicting and adapting to internal state fluctuation. Because eating changes our interoceptive state, restriction may be one method of avoiding aversive, unpredictable internal change in AN.

No association of clock gene T3111C polymorphism and affective disorders.

CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation. Using PCR and RFLP, we investigated in patients with unipolar depression and bipolar disorder (BP) whether the CLOCK T3111C SNP is associated with affective disorders (n=102) compared to healthy controls (n=103). No differences were found either in genotype or allele frequency distributions of T3111C polymorphism between patients compared to healthy controls (p>0.2). No deviations from Hardy-Weinberg Equilibrium (HWE) were detected either in patients, or healthy controls. Results suggest that there is no association between the T3111C SNP and affective disorders in general. Data of our sample replicate prior findings of Desan et al. [Am. J. Med. Genet. 12 (2000) 418]. Subsamples of patients with high numbers of affective episodes did show some deviations in genotypes (p=0.0585).

[Depressive pseudodementia]. / Depressive Pseudodemenzen.

Elderly depressive patients complaining about cognitive symptoms are at particular risk of being labelled as demented. It is well documented that depressive disorders frequently cause mild cognitive deficits which manifest in psychometric procedures. A wide spectrum of potentially reversible cognitive deficits related to a depressive syndrome are summarized under the term of "Depressive Pseudodementia (DPD)". Most depressive patients who are referred to "DPD" suffer from cognitive dysfunctions outside the range of dementia. The clinical interface between depression and dementia is complex. There is some evidence that depression may be a risk factor for the expression of Alzheimer's disease in later life and that depression may occur as a prodrome for Alzheimer dementia. Moreover, depression often complicates the course of dementing disorders. However, there is no evidence that depressive disorders cause dementia without coexisting depressive symptoms. It is essential to search for depressive symptoms even after cognitive symptoms have been found.

[123I] beta-CIT and single photon emission computed tomography reveal reduced brain serotonin transporter availability in bulimia nervosa.

BACKGROUND: Impaired serotonin transmission has been implicated in the pathophysiology of eating disorders. We investigated the in vivo availability of brain serotonin transporters and dopamine transporters in bulimia nervosa patients. METHODS: Approximately 24 hours after injection of [123I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I] beta-CIT), single photon emission computed tomography scans were performed in 10 medication-free, female bulimic patients and 10 age-matched, healthy females. For quantification of brain serotonin transporter and dopamine transporter availability, a ratio of specific to nonspecific [123I] beta-CIT brain binding was used (V(3)" = target region - cerebellum/cerebellum). RESULTS: Drug-free bulimia nervosa patients showed a 17% reduced brain serotonin transporter availability in the hypothalamus and thalamus, as compared with healthy control subjects (2.4 +/- 0.4 vs. 2.9 +/- 0.4, p =.026), and a similar reduction in striatal dopamine transporter availability. There was a negative correlation of illness duration and serotonin transporter availability (r = -.65; p =.042) and a strong positive correlation between hypothalamic/thalamic and striatal V(3)" (r =.80, p <.001). CONCLUSIONS: This first report of reduced [123I] beta-CIT binding in a relatively small group of patients with bulimia nervosa suggests a reduced hypothalamic and thalamic serotonin transporter availability in bulimia, which is more pronounced with longer duration of illness.

Reboxetine in the treatment of bulimia nervosa: a report of seven cases.

Controlled trials in patients with bulimia nervosa have demonstrated efficacy of antidepressant medications with serotonergic function (e.g. fluoxetine) as well as noradrenergic function (e.g. desipramine). Seven outpatients with bulimia nervosa according to DSM-IV criteria were treated openly with 8 mg of reboxetine, a selective noradrenaline reuptake inhibitor (NRI) over a 12-week period. The patients were assessed with the Structured Clinical Interview for DSM, Clinical Global Impression, 17-item Hamilton Depression Rating scale (HAM-D), Eating Disorder Inventory, Eating Disorders Questionnaire, daily self-ratings of eating behaviour, and the UKU side-effect rating scale. Three patients dropped out prematurely, one after 6 weeks and two after 4 weeks of reboxetine treatment. The reasons for premature attrition were rapid remission in one patient after 2 weeks and constipation, which led to an increase in episodes of laxative intake in two patients. In the total group, the monthly binge eating frequency showed a reduction of 73% and the frequency of vomiting episodes per month decreased by 67%. Furthermore, there was a concomitant decrease of depression ratings (HAM-D: from 12.2-6.1). Reboxetine seems to be an option for the treatment of bulimia nervosa.

Genome scan for susceptibility loci for schizophrenia.

OBJECTIVE: Schizophrenia is a relatively common, often chronic and debilitating mental illness. Evidence from various studies has clearly demonstrated that genetic factors contribute substantially to the etiology. The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. METHODS: A genome-wide map of 388 microsatellite DNA markers was genotyped in 5 schizophrenia families. Nonparametric linkage analysis (Genehunter) was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease. RESULTS: Nonparametric linkage scores did not reach a genome-wide level of statistical significance (p < 0.00002) or a p value suggestive of linkage (p < 0.007) for any marker; however, one p value suggested replicated linkage (p < 0.01) at chromosome 6p24 in region D6S309 (p = 0.0047). Furthermore, 11 markers resulted in p < 0.05 at chromosomes 6p, 6q, 10q, 12q and 14q. CONCLUSIONS: Despite the differences in diagnostic schemes, in markers used and methods of analyses between studies published so far, we think that our result supports the notion that there is possibly some consistent evidence for replicated linkage of a schizophrenia susceptibility locus around the region of D6S309 at chromosome 6p24.

Occurrence of mirtazapine-induced delirium in organic brain disorder.

Mirtazapine is the first of a new class of antidepressants, the noradrenergic and specific serotonergic antidepressants. Its antidepressant effect appears to be related to its dual enhancement of both noradrenergic neurotransmission and serotonin 5-HT1 receptor-mediated serotonergic neurotransmission. Mirtazapine has demonstrated superior tolerability to the tricyclic antidepressants, primarily on account of its relative absence of anticholinergic, adrenergic and serotonin-related adverse effects. We observed mirtazapine-induced delirium in one organically depressed and two major depressed patients with subclinical brain disease. The appearance of hallucinations, psychomotoric agitation and cognitive changes after initiation of mirtazapine, and their prompt improvement after drug discontinuation, led to the impression that these were drug-induced phenomena. One possible hypothesis for the observed deliria is a central increase of norepinephrine after acute administration of mirtazapine. Subclinical brain disease might have favoured the occurrence of delirium in the three cases.

[Diagnosis and therapy of eating disorders]. / Diagnose und Therapie von Essstörungen.

Even though there is no convincing evidence that eating disorders in general are on the rise, there has been an enormous increase in "treated" cases of patients with eating disorders. This review will cover important aspects of diagnosis and treatment of eating disorders. Psychotherapeutical and pharmacological treatment strategies in anorexia and bulimia nervosa will be discussed. For both eating disorders, psychotherapy is the treatment of choice. Drugs with a serotonergic function, e.g. serotonin-reuptake-inhibitors (SSRI), have demonstrated significant results in the treatment of bulimia nervosa and eating disorders with comorbid depression. In clinical practice "treatment packages" are offered because of the complexity of the disorders. The paper also deals with medical complications of eating disorders, motivational interviewing in anorexia nervosa and treatment with self-help manuals in bulimia nervosa.

[Osteoporosis in anorexia nervosa. New aspects of pathogenesis and therapy]. / Osteoporose bei Anorexia nervosa. Neue Aspekte der Pathogenese und Therapie.

Osteoporosis has been shown to be a relatively common complication of anorexia nervosa (AN). So far the exact mechanisms which are implicated are not fully clarified. Several factors such as malnutrition, reduced body weight, amenorrhea, and hypercortisolaemia seem to be involved. There is a strong relationship with the duration of amenorrhea and--in some studies--with the age of onset. Osteoporosis is for a long time a "silent" disease and the first symptoms such as back pain, loss of height, kyphosis, and fractures are late complications. Therefore, routine screening methods for bone density measurements should be established. The most accurate is the dual energy X-ray absorptiometry (DEXA). Therapeutically the primary aim should be to reach restoration of both normal body weight and regular menses. As AN is a chronic disease clinicians should be aware of the dangers of osteoporosis and start with the treatment and/or prevention of osteoporosis early. However, at this stage it is difficult to provide an evidence-based management plan for osteoporosis in AN. Hormone replacement therapy (HRT) as well as calcium and vitamin D-supplementation are under discussion, however, further controlled investigations are warranted.

Osteopenia in anorexia nervosa: specific mechanisms of bone loss.

Osteopenia is a well recognized medical complication of anorexia nervosa (AN). The mechanism of bone loss is not fully understood and there is uncertainty about its management. New markers of bone turnover have been developed. C-terminal type 1 propeptide (PICP) is a measure of bone formation and urinary pyridinolines such as deoxypyridinoline (DPYRX) and serum carboxyterminal crosslinked telopeptide (ICTP) are markers of bone resorption. The aim of this study was to examine these bone markers in patients with AN. Twenty female patients with AN and 12 healthy controls were included in the study. Bone mineral density (BMD) of AN patients was measured by dual energy X-ray absorptiometry (DEXA). Lumbar bone density was significantly reduced in the AN group compared to standardised values of thirty year old adults (t-score 83.2%, S.D. 12.1). Femoral neck bone density showed an even greater reduction (t-score 79.4%, S.D. 13.5). We found a significant negative correlation between femoral BMD and the duration of the illness. Femoral BMD correlated significantly with minimal body weight (r(16) = 0.504, p = 0.033). The markers of bone resorption were significantly higher in the patients with AN compared to the values of the control group (ICTP t(30) = -2.15, p = 0.04, DPYRX t(25) = -2.26, p = 0.033), whereas the markers of bone formation did not differ significantly between the groups. AN appears to be a low turn over state associated with increased bone resorption without concomitant bone formation. This pattern differs from osteopenia in menopausal women and should, therefore, lead to the development of specific therapeutic strategies in AN associated osteopenia. Hormone replacement therapy as well as calcium and vitamine D-supplementation are so far discussed controversially. Long-term treatment studies are warranted.

Atypical eating disorder in a male patient.

In the literature there is evidence that a substantial proportion of patients with bulimia nervosa can be helped by cognitive behavioural self-help manuals. As there are no specific recommendations or strategies for the treatment of males with eating disorders we were therefore especially interested in the way a man might deal with such a self-help manual. In this case the book Getting better bit(e) by bit(e) by Treasure and Schmidt (also available in German translation) was given to a young man with an atypical eating disorder (atypical anorexia nervosa according to ICD-10). The patient was offered a maximum of 16 short visits and was seen by a first-year psychiatry resident. Treatment with this self-help manual was effective and the patient succeeded in changing his former eating behaviour. The case report provides preliminary evidence that a self-help manual may be a useful addition to the range of possible interventions in the treatment of eating disorders in men. Self-help manuals are less intensive and less costly than other forms of treatment and might be the lowest-step intervention in a stepped-care approach to treatment.

[Mirtazapine in inpatient treatment of depressed patients]. / Mirtazapin bei stationär behandelten depressiven Patienten.

Mirtazapine is a new antidepressant with a specific pharmacological profile which is different from all other currently available antidepressants. It is a so-called noradrenergic and specific serotonergic antidepressant (NaSSA). 46 in-patients were treated with mirtazapine. The mean dose was 56 mg mirtazapine per day (SD: 23; range: 15 to 90). The duration of treatment was 3.6 weeks (SD +/- 3.4). Patients presented with following diagnosis: 29 (= 63%) were diagnosed as having a unipolar depression, 26% (n = 12) suffered from a depression in the course of a bipolar disorder. 37% (n = 17) were moderately depressed, 52% (n = 24) were severely depressed. 2 patients (= 4%) met ICD-10 (international Classification of Diseases) criteria for a schizoaffective disorder, 2 patients (= 4%) suffered from dysthymia. 1 patient suffered from an organic depressive disorder. The efficacy of the treatment was evaluated with CGI (Clinical Global Impression), when patients were discharged from hospital. 68% of the patients were in partial or full remission (CGI 2, 3 and 4), 17% were unimproved (CGI 5 and 6), in 15% of the patients the treatment was stopped before. Our observations are indicative that mirtazapine is effective in the treatment of moderately and severely depressed patients and therefore confirm the data obtained in phase III-trials. Furthermore we found mirtazapine in either mono- or combination-therapy with various other antidepressants to be tolerated well. Side effects did not cause in a single patient a discontinuation in treatment.

Comorbidity of obsessive compulsive disorder in patients with eating disorders.

OBJECTIVE: We investigated the prevalence of obsessive compulsive disorder (OCD) among patients with eating disorders (ED). METHOD: 66 female inpatients who met the DSM-IV criteria for anorexia nervosa (AN) or bulimia nervosa (BN) participated in the study. The Structured Clinical Interview for DSM III-R diagnoses (SCID), the Eating Disorder Inventory (EDI), the revised 90-item Symptom-Checklist (SCL-90-R), the Beck Depression Inventory (BDI), and the Toronto Alexithymia Scale (TAS-20) were carried out. RESULTS: Twelve patients (18.2%) met the DSM-III-R criteria for lifetime OCD: 7 had a current OCD and 5 had a past history of OCD. These patients had significantly higher (more pathological) mean scores on the EDI and the SCL-90-R total scales. Analyses of the EDI subscales revealed significantly higher scores for ineffectiveness, perfectionism, interoceptive awareness, and maturity fears. As expected, analyses of the SCL-90-R subscales revealed significantly higher scores for OCD. In addition, there was a trend towards higher somatization scores in patients with comorbid OCD. We could not find any significant differences in the BDI and the TAS total scores. In addition, patients with comorbid OCD showed a significantly higher lifetime prevalence of bipolar disorder, simple phobia, and somatoform disorders. DISCUSSION: Our results confirm previous reports of a strong association between ED and OCD and suggest that the prevalence of OCD may be correlated with a higher severity of the eating disorder and general psychopathological parameters.