Neuroactive steroids as modulators of depression and anxiety.

Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3alpha-reduced pregnane steroids are potent positive allosteric modulators of the GABA type A-receptor. During major depression there is a dysequilibrium of 3alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment.

Soft x-ray therapy for cutaneous basal cell and squamous cell carcinomas.

Background: We have used a schedule for soft x-ray therapy of epithelial malignancies that takes into account the clinically diagnosed tumor involution under treatment.

Objective: We sought to evaluate the effectiveness of this schedule in terms of cure rate and late ulcerations.

Methods: Patients with 1267 consecutively irradiated (1988-1992) basal cell and squamous cell carcinomas were followed up (average 77 months).

Antidepressants and antipsychotic drugs colocalize with 5-HT3 receptors in raft-like domains.

Despite different chemical structure and pharmacodynamic signaling pathways, a variety of antidepressants and antipsychotics inhibit ion fluxes through 5-HT3 receptors in a noncompetitive manner with the exception of the known competitive antagonists mirtazapine and clozapine. To further investigate the mechanisms underlying the noncompetitive inhibition of the serotonin-evoked cation current, we quantified the concentrations of different types of antidepressants and antipsychotics in fractions of sucrose flotation gradients isolated from HEK293 (human embryonic kidney 293) cells stably transfected with the 5-HT3A receptor and of N1E-115 neuroblastoma cells in relation to the localization of the 5-HT3 receptor protein within the cell membrane. Western blots revealed a localization of the 5-HT3 receptor protein exclusively in the low buoyant density (LBD) fractions compatible with a localization within raft-like domains.

Striatal dopamine release after prefrontal repetitive transcranial magnetic stimulation in major depression: preliminary results of a dynamic [123I] IBZM SPECT study.

Though there is considerable evidence that prefrontal repetitive transcranial magnetic stimulation (rTMS) exerts antidepressant effects, the neurobiological action of rTMS in patients with depression is poorly understood. Preclinical studies in animals and humans have demonstrated that prefrontal rTMS can induce dopamine release in mesostriatal and mesolimbic regions. We therefore investigated whether rTMS also modulates striatal dopaminergic neurotransmission in depressed patients using a dynamic [123I] iodobenzamide (IBZM) single photon emission computed tomography (SPECT) approach.

Neuropsychopharmacological properties of neuroactive steroids in depression and anxiety disorders.

Neuroactive steroids modulate neurotransmission through modulation of specific neurotransmitter receptors such as gamma-aminobutyric acid type A (GABAA) receptors. Preclinical studies suggested that neuroactive steroids may modulate anxiety- and depression-related behaviour and may contribute to the therapeutical effects of antidepressant drugs. Attenuations of 3alpha-reduced neuroactive steroids have been observed during major depression.

Saccadic eye velocity after selective GABAergic treatment with tiagabine in healthy volunteers.

Background: Saccadic eye velocity (SEV) has been shown to be a reliable neurophysiological tool for the assessment of gamma-aminobutyric acid GABA(A) receptor sensitivity. Administration of benzodiazepines targeting the GABA(A) receptor decreases SEV in healthy volunteers. Tiagabine is a new antiepileptic drug which acts via selective blockade of GABA reuptake.

Genetic variants in the angiotensin I-converting-enzyme (ACE) and angiotensin II receptor (AT1) gene and clinical outcome in depression.

The insertion/(I)/deletion (D) polymorphism of the angiotensin-converting enzyme gene (ACE) is of increasing interest in etiology and treatment of various neuropsychiatric disorders. The present study aimed to replicate own earlier findings that depressive patients with the ACE D-allele are responding better to treatment with antidepressants than those with the II genotype. We further investigated a common polymorphism (A1166C) in the angiotensin II receptor gene (AT1) to examine a possibly combined influence.

Selective GABAergic treatment for panic? Investigations in experimental panic induction and panic disorder.

gamma-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the central nervous system (CNS). It exerts its rapid inhibitory action mostly through GABA(A) receptors, which are targets for benzodiazepines, barbiturates, neuroactive steroids and distinct anticonvulsive agents. There is considerable evidence that dysfunction of GABA(A) receptors or dysregulation of GABA concentrations in the CNS (or both) plays an important role in the pathophysiology of panic disorder.

The influence of 4-week treatment with sertraline on the combined T3/TRH test in depressed patients.

In the present study, the influence of a 4-week treatment with sertraline on the regulation of hypothalamic-pituitary-thyroid (HPT) axis activity in depression was investigated, in particular the impact of sertraline on the thyroid receptor (TR)-mediated negative feedback control as measured by the combined T3/TRH test. In 20 drug-free patients (8 men, 12 women) suffering from a major depressive episode according to DSM-IV criteria the single TRH-stimulation test (administration of 200 microg TRH at 09:00h) was carried out followed by a combined T3/TRH test (pre-treatment with 40 microg 3,5,3'-triiodothyronine [T3] the night before; administration of 200 microg TRH at 09:00h the next day). After 4 weeks of treatment with sertraline at a standard dosage of 50 mg/day, both the single TRH test and the combined T3/TRH test were repeated in the depressed patients.

Plasma concentrations of neuroactive steroids before and after electroconvulsive therapy in major depression.

There is evidence that both cerebrospinal fluid (CSF) and plasma concentrations of 3alpha-reduced neuroactive steroids are decreased in major depressive disorder. Successful antidepressant pharmacotherapy, for example, with selective serotonin reuptake inhibitors (SSRIs), over several weeks is accompanied by an increase in CSF and plasma concentrations of these neuroactive steroids. However, no such increase has been observed during nonpharmacological treatments such as partial sleep deprivation or repetitive transcranial magnetic stimulation.

The combined T3/TRH test in depressed patients and healthy controls.

It is well established that depressed patients show a blunted TSH response in the TRH-stimulation test. However, it has not been investigated so far whether pre-treatment with 3,5,3'-triiodothyronine (T3) is able to further suppress the TRH-induced TSH response in depressed patients or whether it may cause an escape-phenomenon with paradoxically enhanced TSH stimulation in a subsequent TRH test. In 20 drug-free depressed patients (eight men, 12 women) suffering from a major depressive episode according to DSM-IV criteria and in 20 age- and sex-matched healthy controls, the single TRH-stimulation test (administration of 200 microg TRH at 09:00 h) was carried out followed by a combined T3/TRH test (pre-treatment with 40 microg T3 at 23:00 h the night before; administration of 200 microg TRH at 09:00 h the next day).

Neuroactive steroids in responders and nonresponders to sleep deprivation.

Evidence from preclinical and clinical studies indicates that concentrations of neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy. However, data on the impact of sleep deprivation on concentrations of neuroactive steroids are not available. Therefore, 29 drug-free patients (12 men, 17 women) with major depression according to DSM-IV criteria were treated with partial sleep deprivation (PSD).

Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment.

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples.

[Diagnosis and treatment of panic disorder].

Panic disorder is defined as, recurrent, unexpected panic attacks. Panic attack means a period of intensive fear or discomfort, accompanied by a range of physical or psychological symptoms. Subsequently, anticipatory anxiety and avoidance behavior often develop.

Panic induction with cholecystokinin-tetrapeptide (CCK-4) Increases plasma concentrations of the neuroactive steroid 3alpha, 5alpha tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) in healthy volunteers.

3alpha-reduced neuroactive steroids such as 3alpha, 5alpha-tetrahydroprogesterone (3alpha, 5alpha-THP) and 3alpha, 5alpha-tetrahydrodeoxycorticosterone (3alpha, 5alpha-THDOC) are potent positive allosteric modulators of gamma-aminobutyric acid type A (GABAA) receptors and display pronounced anxiolytic activity in animal models. Experimental panic induction with cholecystokinin-tetrapeptide (CCK-4) and sodium lactate is accompanied by a decrease in 3alpha, 5alpha-THP concentrations in patients with panic disorder, but not in healthy controls. However, no data are available on 3alpha, 5alpha-THDOC concentrations during experimental panic induction.

Speckled lentiginous nevus syndrome: report of a further case.

A 42-year-old man had a large speckled lentiginous nevus on the left side of his trunk. The involved area was painful when touched and paresthetic. Moreover, the ipsilateral half of his body showed a pronounced hyperhidrosis.

[Electroconvulsive therapy at the Department of Psychiatry and Psychotherapy, University of Munich. Development during the years 1995-2002].

Background: So far, electroconvulsive therapy (ECT) has been proven to be a reliable and the most effective somatic treatment of depression or schizophrenia. This holds especially true for disturbances, which are refractory to pharmacological treatments.

Patients And Methods: We evaluated 4803 treatments in 445 patients.

Osmotic stress of salmon stimulates upregulation of a cold inducible RNA binding protein (CIRP) similar to that of mammals and amphibians.

Salmon are subjected to hyperosmotic stress during transition from freshwater to the marine environment. A variety of mechanisms have evolved to allow movement of the animal from a hydrating to a dehydrating environment. Using differential assay of mRNA expression, a 1.

The dysbindin gene in major depression: an association study.

The pathophysiological mechanisms, as well as the molecular loci of antidepressant drug action have not yet been established, but recent models proposed that several adaptive mechanisms in signal transduction cascades beyond the receptor and reuptake systems are involved in antidepressant action and play an important role in the etiology of affective disorders. In this context, the dysbindin gene (dystrobrevin-binding-protein 1, DTNBP1), which was recently reported to be associated with schizophrenia seems to be an interesting candidate gene for affective disorders. Dysbindin is widely expressed in the human brain and binds to the dystrophin-associated protein complex (DPC) which appears to be involved in signal transduction pathways, which have been repeatedly investigated and described as altered or disturbed in affective disorders [McLeod et al.

The angiotensin I converting enzyme insertion/deletion polymorphism influences therapeutic outcome in major depressed women, but not in men.

Angiotensin converting enzyme (ACE) is expressed in the central nervous system (CNS), where its primary function comprises degradation of neuropeptides including substance P (SP). Because of the possible antidepressant effects of SP antagonists, the influence of SP on both pathophysiology and mitigation of depression has been hypothesized. It was shown that ACE plasma concentration is determined by an insertion/deletion (I/D) polymorphism represented by the presence or absence of a 287 bp DNA fragment within the ACE gene.

SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression.

Tryptophan hydroxylase (TPH), being the rate-limiting enzyme in the biosynthesis of serotonin plays a major role as candidate gene in several psychiatric disorders. Recently, a second TPH isoform (TPH2) was identified in mice, which was exclusively present in the brain. In a previous post-mortem study of our own group, we could demonstrate that TPH2 is also expressed in the human brain, but not in peripheral tissues.

Results of a surveillance programme for patients at high risk of malignant melanoma using digital and conventional dermoscopy.

Patients with a high number of atypical naevi and a personal and/or family history of melanoma are at high risk of malignant melanoma. The objective of this study was to design a special documentation and surveillance programme using epiluminescence microscopy (ELM) and digital epiluminescence microscopy (DELM) to improve the surveillance of these patients. High-risk patients (n=212) were categorized by the number and phenotype of their naevi and their personal and family history of melanoma.

The gamma amino butyric acid (GABA) receptor alpha-3 subunit gene polymorphism in unipolar depressive disorder: a genetic association study.

There is evidence that genes coding for the gamma aminobutyric acid (GABA) receptor may be involved in the etiology of affective disorders. Recently, an association between a CA-repeat in the GABRA 3 gene and bipolar disorder had been reported. The present study aimed at investigating the association between this polymorphism and unipolar major depressive disorder.