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Biomedical subjects

E Hilger

Publications and source records attributed to E Hilger.

At least 19 recordsLinked to original sources

Affective state of women following a prenatal diagnosis: predictors of a negative psychological outcome.

OBJECTIVE: The benefits of prenatal diagnostic procedures are well documented. However, the investigation of psychological consequences related to these procedures has remained a surprisingly neglected area of research. The main aim of the present study was to investigate the potential relationship between psychological outcome and associated (socio-demographic, psychological and obstetric) variables in women attending a tertiary referral center for prenatal diagnosis and therapy for ultrasound scanning (due to the suspicion of a fetal malformation raised by the gynecologist in private practice), amniocentesis or chorionic villus sampling. METHODS: Affective state was assessed by means of standardized measures of anxiety and depression (State-Trait Anxiety Inventory; Mood Scale) in 77 consecutive, unselected women. A follow-up investigation, including an additional assessment of coping mechanisms, took place 6 months after the first contact. Given the considerable number of intervening and correlating factors, a path analysis was undertaken. RESULTS: We found that all women in our sample experienced acute distress, not only those with proven fetal malformations, genetic disorders or intrauterine fetal death, but also those with the diagnosis of a sonographic sign. At baseline (i.e. immediately after the diagnostic procedure), mood and anxiety scores in our sample were found to be comparable to those of patients with a major depressive episode. A high trait anxiety level, implementation of negative coping strategies and loss of the child during pregnancy were found to be predictive of a negative psychological outcome at follow-up. Socio-demographic variables did not have a significant predictive function for the psychological outcome. CONCLUSIONS: We assume that a considerable number of women undergoing prenatal diagnostic procedures experience psychological distress, which may be underestimated by workers in prenatal care. Establishment of interdisciplinary treatment settings, in which access to psychological support is facilitated, may be extremely beneficial for women following a prenatal diagnosis.

Adaptation, Psychological↗

Context-Oriented Model Development in Psychotherapy Planning ('COMEPP'): a useful adjunct to diagnosis and therapy of severe personality disorders.

OBJECTIVE: Pathogenous interpersonal (e.g. interfamilial) relationships and reference styles can compromise treatment efforts in severely disturbed (i.e. psychotic or borderline) patients. The integration of family- and individual-centred starting points may be useful in establishing interdisciplinary treatment concepts in these patients. Context-Oriented Model Development in Psychotherapy Planning (COMEPP) represents a diagnostic and therapy planning process, integrating both systemic and psychoanalytic conceptualizations. METHOD: COMEPP is exemplified by the case of a young man with psychotic personality disorder who had previously been unresponsive to pharmacological and psychological treatment. RESULTS: After psycho-dynamical conflicts (i.e. primitive projective processes from the patient's mother to her son) had been elucidated during the COMEPP process, a sufficient treatment setting could be established. CONCLUSION: COMEPP provides a psychotherapeutical approach to treatment planning on case-specific premises and may serve as an adjunct to concomitant pharmacological and psychological treatment strategies in so-called 'therapy refractory' patients.

Adult↗

A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder.

Serotonergic mechanisms are thought to play an important role in the pathogenesis of seasonal affective disorder (SAD). The expression of the serotonin transporter (5-HTT) is regulated in part by an insertion/deletion polymorphism in the serotonin transporter gene promoter region (5-HTTLPR). The 5-HTTLPR short allele (s) has been associated with anxiety-related personality traits and depression, and one study observed an association between the 5-HTTLPR s-allele and SAD and the trait of seasonality. We genotyped 138 SAD patients and 146 healthy volunteers with low seasonality for 5-HTTLPR. No difference between patients and controls was found for genotype distribution and s-allele frequency. However, genotype distribution and allele frequencies were strongly associated with DSM-IV depression subtypes. Melancholic depression was associated with the 5-HTTLPR long (l) allele and atypical depression with the 5-HTTLPR s-allele (two-sided Fisher's exact test: genotype distribution: P=0.0038; allele frequencies: P=0.007). Our data are compatible with the hypothesis of a disease process that is not causally related to 5-HTTLPR, but involves 5-HT neurotransmission and 5-HTTLPR somewhere on its way to phenotypic disease expression.

Bipolar Disorder↗

[Seasonal affective depression in 2 German speaking university centers: Bonn, Vienna. Clinical and demographic characteristics].

Six hundred ten patients with seasonal affective disorder (SAD) were diagnosed and treated at the university hospitals for psychiatry in Bonn, Germany (1989-1992) and Vienna, Austria (1993-2001). The aim of this study was to compare our sample with other SAD populations in the literature and to investigate differences between the two study locations. We found female:male sex ratios of 5.0:1.0 in unipolar depressives and 1.5:1.0 in patients with bipolar affective disorder. Of our patients, 21.7% suffered from bipolar II disorder, and 1.3% were diagnosed as having bipolar I. Our patients obtained a mean global seasonality score (GSS) of 15.4. Women had a higher GSS than men (t = 2.127, P = 0.035), and Viennese patients had higher scores than patients in Bonn (t = 3.104, P = 0.002). Totals of 66.3% of all patients suffered from atypical depression and 17.8% from melancholic depression. Patients with atypical depression were more frequent in Vienna, whereas patients with melancholic depression predominated in Bonn (chi 2 = 54.952, df = 2, P < 0.001). The demographic and clinical characteristics of the patients described in this article confirm the findings of other epidemiological investigations obtained in non-German-speaking samples.

Adult↗

Changes of clinical pattern in seasonal affective disorder (SAD) over time in a German-speaking sample.

OBJECTIVE: The goals of this study are to provide estimates of clinical and demographic variables of patients with seasonal affective disorder (SAD) in Germany and Austria, to compare our results with those of previously published SAD studies, and to find out whether the clinical pattern of SAD remained stable over several years. METHOD: We investigated 610 SAD patients from the outpatient clinics in Bonn (n = 190) and Vienna (n = 420). Patients in Bonn were recruited in the fall-winter season of the years 1989-1992, those in Vienna in the years 1993-2001. RESULTS: We observed a change in the clinical pattern in our patients: patients from Bonn, who were diagnosed and treated about 5 years earlier, were more likely to suffer from melancholic depression, whereas Viennese patients rather suffered from atypical depression (chi(2) = 54.952, df = 2, p < 0.001). The symptoms of hypersomnia, daytime fatigue, increased eating and carbohydrate-craving were more frequent in the Viennese sample, anxiety and deterioration of patients' capacity to perform at work predominated in Bonn. In addition, patients from Vienna obtained a higher GSS (global seasonality score, measured by the SPAQ - Seasonal Pattern Assessment Questionnaire) than those from Bonn (15.7 +/- 3.3 and 14.6 +/- 4.1 respectively; t = 3.104, p = 0.002). Taken together, our results were in good accordance to other published SAD materials, but we were able to demonstrate that our patients reported "feeling worst" (measured by item 13H of the SPAQ) in November and December, whereas SAD patients in the USA clearly had their worst months in January and February. CONCLUSIONS: We suggest that an increase in awareness of fall-winter depression in the last decade by both doctors, who referred patients, as well as patients or the entire population must have caused patients to sign up for light therapy at the Viennese SAD clinic because of having heard about the atypical symptom profile. This increased awareness of SAD can also be measured by a statistically significant reduction in the diagnostic latency (from the age of onset to the diagnosis of SAD) when comparing the two study locations.

Adult↗

[Pharmacotherapy of seasonal depression].

Seasonal affective disorder (SAD), first described in 1984, is a condition characterized by recurring depressive episodes in fall and winter alternating with nondepressive episodes in spring and summer. Various neurotransmitters have been implicated in the etiology of SAD, with the strongest evidence for an involvement of serotonin. Moreover, researchers have focused on the development of treatment modalities for SAD. Despite the proven efficacy of light therapy in SAD, some patients do not experience sufficient relief of depressive symptoms with light, and a number of them feel unable to comply because of logistical difficulties in administering bright light therapy. Comparatively few studies have examined the role of pharmacotherapy in the treatment of SAD. So far, selective serotonin reuptake inhibitors and possibly compounds with a distinct noradrenergic mechanism of action seem to be the treatment of choice for seasonal depression. There is, however, a clear need for further placebo-controlled studies to evaluate pharmacological treatment options for SAD.

Antidepressive Agents↗

Intravenous mirtazapine in the treatment of depressed inpatients.

Mirtazapine is a novel antidepressant with a noradrenergic and specific serotonergic mode of action. So far, mirtazapine has been administered orally. This naturalistic study evaluates the antidepressant efficacy, safety, and tolerability of mirtazapine 15 mg/day administered intravenously to 27 inpatients with moderate to severe major depression. Compared with baseline, we found a significant decrease of the Hamilton Depressive Rating Scale (HDRS) total score (P<0.001). Side effects were mild and transient. Altogether, the results of this preliminary study show that intravenous mirtazapine is an effective, safe and well tolerated treatment for depressed inpatients.

Adrenergic alpha-Antagonists↗

[Depressive pseudodementia].

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.

Aged↗

[Atypical antipsychotics in the treatment of bipolar affective disorders].

Antipsychotics are commonly used in the treatment of bipolar affective disorder. The use of conventional antipsychotic agents, though effective as antimanic agents, is associated with a number of limitations such as their acute side effect profile and their unsufficient mood stabilizing activity. In addition, exposure to conventional neuroleptics poses a risk for the development of tardive dyskinesia, especially in mood disorder patients. Growing evidence suggests that the novel, so-called atypical neuroleptics may offer a number of advantages in the treatment of bipolar disorder, including their thymoleptic activity and minimal risk for acute and long-term extraypyramidal symptoms. Clinical experience with clozapine and olanzapine as mood stabilizers suggests greater antimanic than antidepressant properties, while risperidone may have greater antidepressant properties with some liability for triggering or exacerbating mania. The mood stabilizing properties of further atypical drugs are currently under investigation. This review focuses on the use of atypical antipsychotics in the treatment of bipolar disorder. We also present an overview concerning potential pharmakokinetic interactions based on the cytochrome P450 enzyme system when antipsychotics are combined with other mood stabilizing compounds. In conclusion, atypical antipsychotics should come to play an increasingly important role in the acute and long-term management of bipolar disorder, but there is a clear need for further controlled trials in this indication.

Anticonvulsants↗

The effect of orlistat on plasma levels of psychotropic drugs in patients with long-term psychopharmacotherapy.

Weight gain induced by long-term psychopharmacotherapy has emerged as a relevant clinical issue because it is a major problem affecting compliance and long-term outcome. The novel antiobesity drug orlistat inhibits gastrointestinal lipases, thus lowering the absorption of dietary fat and raising the possibility of decreased absorption of fat-soluble vitamins and certain concomitantly administered drugs in some individuals. We monitored plasma levels of several psychotropic agents in eight psychiatric patients receiving orlistat to determine the potential influence of orlistat on the bioavailability of these drugs. We found no clinically relevant changes in plasma concentrations of haloperidol, clozapine, clomipramine, desipramine, or carbamazepine over an 8-week period in orlistat recipients. We therefore consider orlistat to be compatible with use during long-term pharmacotherapy. Our preliminary findings suggest that orlistat may offer a pharmacological treatment option to support dietary efforts in obese and overweight psychiatric patients. However, so far no data about the potential influence of orlistat on pharmacokinetics of psychotropics have been published; therefore, plasma level monitoring is recommended.

Adult↗

In vivo (123)I IBZM SPECT imaging of striatal dopamine 2 receptor occupancy in schizophrenic patients.

RATIONALE: Single photon emission computed tomography (SPECT) using (123)I iodobenzamide (IBZM) as tracer substance has been shown to be a useful tool to visualize dopamine 2 (D2) receptor occupancy. OBJECTIVES: We investigated the striatal D2 receptor occupancy of zotepine which is referred to the class of atypical antipsychotic drugs. METHODS: (123)I IBZM and SPECT were used to visualize striatal dopamine 2 (D2) receptor occupancy in zotepine-treated schizophrenic patients. Two groups of schizophrenic patients receiving either 150 mg/day zotepine (n=6) or 300 mg/day (n=6) underwent examination. For the quantification of striatal D2 receptor occupancy, striatal IBZM binding in patients treated with antipsychotics was compared to untreated healthy controls (n=8) reported earlier. RESULTS: Zotepine led to a mean overall striatal D2 receptor occupancy of 73%. Patients with 150 mg daily showed a significantly lower occupancy (65.8%, SD=6.2) than patients with 300 mg/day (77.8%, SD=10.7; P<0.05). No clinically relevant extrapyramidal side effects occurred during treatment with zotepine. CONCLUSIONS: There was no correlation between the degree of striatal D2 receptor occupancy and clinical improvement.

Adult↗

Prevalence of premenstrual dysphoric disorder in female patients with seasonal affective disorder.

BACKGROUND: Both seasonal affective disorder/winter type (SAD) and premenstrual dysphoric disorder (PMDD) are cyclical disorders characterized by so-called atypical depressive symptoms. In the present study we compared the point prevalence rates of PMDD between a sample of premenopausal female patients suffering from SAD and healthy female controls. METHODS: Forty-six female patients with SAD and 46 healthy controls were included in our study. All subjects underwent a semistructured clinical interview according to DSM IV criteria and completed the Seasonal Pattern Assessment Questionnaire. PMDD was diagnosed in a self-rating interview for PMDD according to DSM IV criteria. To verify the diagnosis of PMDD, all patients were followed up in stable summer remission using daily self-rating scales for two full menstrual cycles. RESULTS: Patients with SAD fulfilled significantly more often the diagnostic criteria for PMDD than female healthy controls (46% vs. 2%, respectively; chi-square: P<0.001). CONCLUSIONS: These results provide preliminary evidence for a high point prevalence rate of PMDD in premenopausal females with SAD. CLINICAL IMPLICATIONS: It would be worthwhile to investigate whether an additional diagnosis of PMDD has an impact on the clinical outcome and the response to bright light therapy in female patients with SAD.

Adult↗

Reboxetine in seasonal affective disorder: an open trial.

Seasonal affective disorder (SAD), winter type, is a condition characterized by the annual recurrence of depressive episodes during fall/winter, alternating with spring/summer euthymia or hypomania. Various neurotransmitters have been implicated in the etiology of SAD, the strongest evidence involving serotonin. Recently, increasing attention has been paid to the potential role of catecholaminergic pathways in the pathophysiology of SAD. We investigated the efficacy and tolerability of reboxetine, a selective noradrenaline inhibitor, in patients with SAD. Eleven out of sixteen patients who were included in a 6-week drug surveillance during winter season experienced full remission of depressive symptoms. Nine patients reported a rapid relief of preexistent severe atypical depressive symptoms within the first treatment week. Reboxetine might therefore be an effective and well-tolerated treatment option for SAD patients. In conclusion, our preliminary results are in line with evidence from recent studies suggesting that catecholaminergic systems might also be involved in the pathophysiology of SAD.

Adult↗

Dopamine transporter availability in symptomatic depressed patients with seasonal affective disorder and healthy controls.

BACKGROUND: During recent years hypotheses about the pathophysiology of seasonal affective disorder/winter type (SAD) have focused monoaminergic mechanisms. There is substantial evidence that serotonergic systems play an important role. The potential role of catecholaminergic pathways has not been fully explored. METHODS: Eleven drug-free, symptomatic depressed patients with SAD and 11 healthy age- and gender-matched healthy controls were invited to participate in a 123Ibeta-CIT single photon emission computed tomography (SPECT) study to assess striatal density of dopamine transporters (DATs). The cerebellum was used as reference region. Ratios were calculated between mean counts in left and right striatum and cerebellum. These ratios minus I represent specific/non-displaceable binding and are assumed to be directly related to DAT availability at the time of binding equilibrium. RESULTS: Displaceable 153Ibeta-CIT binding in the area corresponding to the left striatum was significantly reduced in SAD patients compared to healthy controls (10.49+/-0.91 v. 1195+/-1.54, respectively; 2-tailed P = 0.017, Mann-Whitney U test). CONCLUSIONS: These data suggest reductions in the availability of striatal DAT binding sites in untreated symptomatic depressed SAD patients. It remains unclear whether these reductions represent a primary defect or an attempt to overcome a state of possible lowered dopamine availability in the synaptic cleft during a depressive episode of SAD. However, these findings provide evidence that brain dopaminergic systems may be involved in the pathophysiology of SAD.

Adult↗

Monoaminergic function in the pathogenesis of seasonal affective disorder.

Seasonal affective disorder/winter type (SAD) is characterized by recurrent depressive episodes during autumn and winter alternating with non-depressive episodes during spring and summer. Light therapy with full-spectrum, bright white light has been shown to be effective for this condition. Several hypotheses have been discussed in the literature about the pathogenesis of SAD. The most prominent includes disturbances in central monoaminergic transmission. Evidence can be inferred from studies showing a seasonal rhythm of central and peripheral serotonergic functioning which may be a predisposing factor for SAD. Some of the symptoms of SAD are believed to represent an attempt to overcome a putative deficit in brain serotonergic transmission. Moreover, 5-HT receptor challenge studies suggest altered activity at or downstream to central 5-HT receptors. Monoamine depletion studies support hypotheses about serotonergic and catecholaminergic dysfunctions in SAD and suggest that light therapy may well compensate for this underlying deficit. Further, albeit indirect, support for the importance of monoaminergic mechanisms in SAD and its involvement in the mechanism of the action of light therapy comes from studies showing antidepressant efficacy of serotonergic and noradrenergic antidepressants in the treatment of SAD. Altogether, disturbances in brain monoaminergic transmission seem to play a key role in the pathogenesis of SAD; monoaminergic systems may also play an important role in the mechanisms of the action of light therapy.

Biogenic Monoamines↗

[Atypical neuroleptics: new approaches to drug therapy of schizophrenic disorders].

The introduction of conventional antipsychotics revolutionized the management of psychotic disorders in the 1950s. The use of these agents has been marked by several shortcomings, including their association with severe motor disturbances and their limited efficacy in treating the negative and cognitive symptoms of schizophrenia. Patients noncompliance has largely been the result of subjectively distressing extrapyramidal motor side-effects (EPMS). It was therefore necessary to develop antipsychotic drugs with selective pharmacological profiles, e.g. limbic selectivity. A defining characteristic of atypical neuroleptics is a higher ratio of serotonin receptor blockade to D2 receptor blockade. Their primary advantage is their superior side-effect profile. The implications of EPMS reduction touch several domains of pathology in schizophrenia such as short- and long-term movement disorders, noncompliance, relapse rate, negative symptoms and cognitive dysfunction. Novel antipsychotics may represent the second pharmacological revolution in the treatment of psychotic disorders. There is, however, still a need for a critical evaluation of the risk-benefit-ratio of differing atypical agents.

Aged↗

[123I]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder.

BACKGROUND: Numerous findings indicate alterations in brain serotonin systems in seasonal affective disorder (SAD). [(123)I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([(123)I]-beta-CIT) labels serotonin transporters (5-HTTs) in the midbrain. We performed a [(123)I]-beta-CIT single photon emission computer tomography (SPECT) study under the hypothesis of lower [(123)I]-beta-CIT binding reflecting reduced central 5-HTT availability in depressed SAD patients. METHODS: Depressed SAD patients and healthy control subjects were investigated using [(123)I]-beta-CIT SPECT 4 hours and again 24 hours after tracer injection. Subjects had either never used psychotropic medication or had been drug-free for at least 6 months prior to the investigation. Specific-to-nondisplaceable partition coefficient (V(3)") was calculated for the thalamus-hypothalamus and the midbrain-pons; the cerebellum served as a reference region. RESULTS: Patients showed a reduction in V(3)" in thalamus-hypothalamus (2.41+/-0.3 vs. 2.84+/-0.4; p = .026) 24 hours post tracer injection (p.i.). No difference between patients and control subjects was found in midbrain-pons (1.31+/-0.2 vs. 1.42+/-0.2; p = .39). No differences were detected in the SPECT acquisitions 4 hours p.i. CONCLUSIONS: Depressed SAD patients showed lower specific-to-nondisplaceable [(123)I]-beta-CIT binding in the region of interest (ROI) thalamus-hypothalamus. The small size of the midbrain-pons ROI may have contributed to the failure to show a difference in this ROI as well. Similar to reduced midbrain 5-HTT availability in nonseasonal depression, depression in SAD seems to be associated with reduced 5-HTT availability to the thalamus-hypothalamus.

Adult↗

Reboxetine: the first selective noradrenaline re-uptake inhibitor.

Several treatment approaches are available for treatment of depression. However, reboxetine is the first selective noradrenaline re-uptake inhibitor. Whereas formerly only noradrenaline re-uptake inhibitors with a mixed mechanism of action were available. These included action not only at noradrenergic, but also at serotonergic and other neurotransmitter-sites. Thus, reboxetine represents the first of a new class of antidepressant agents with specificity for the noradrenergic system. Reboxetine has been shown to be an effective first-line treatment for patients with all grades of depression, to be effective in the prevention of relapse and recurrence and to offer significant benefits in terms of relieving the impaired social functioning associated with depressive disorders. Reboxetine was significantly superior to the serotonergic compound fluoxetine in improvement of social functioning in both the general depressed population and in those patients who achieved symptomatic remission, indicating a superior quality of remission. Altogether reboxetine was well tolerated during the acute and long-term treatment phase; side-effects such as increased sweating, constipation and dry mouth were the most prominent to be reported. The availability of reboxetine represents a significant addition to the currently available pharmacologic armamentarium for the treatment of depression.

Adrenergic Uptake Inhibitors↗