Kirsten Engel

Oral Miltefosine for Leishmaniasis in Immunocompromised Patients: Compassionate Use in 39 Patients with HIV Infection

Oral miltefosine was administered to 39 human immunodeficiency virus (HIV)-infected patients with leishmaniasis for whom standard leishmaniasis treatment had failed. Initial response was achieved in 25 patients (64%), including 16 patients (43%) with initial parasitological cure. Repeated responses after relapse and tolerability of long courses of treatment indicate the potential for development of optimized dosage schemes.

Neuroimaging in anxiety disorders

Neuroimaging studies have gained increasing importance in validating neurobiological network hypotheses for anxiety disorders. Functional imaging procedures and radioligand binding studies in healthy subjects and in patients with anxiety disorders provide growing evidence of the existence of a complex anxiety network, including limbic, brainstem, temporal, and prefrontal cortical regions. Obviously, “normal anxiety” does not equal “pathological anxiety” although many phenomena are evident in healthy subjects, however to a lower extent. Differential effects of distinct brain regions and lateralization phenomena in different anxiety disorders are mentioned. An overview of neuroimaging investigations in anxiety disorders is given after a brief summary of results from healthy volunteers. Concluding implications for future research are made by the authors.

Attachment style, anxiety coping, and personality-styles in withdrawn alcohol addicted inpatients.

BackgroundInsecure early attachment experiences have been reported to play an important role in the manifestation in alcoholism. The purpose of this study was to investigate the relationship of attachment styles with anxiety, anxiety coping and dysfunctional personality styles, as well as with the prevalence of personality disorders, and adverse life-events in adolescence.Methods59 inpatient alcohol addicted male (n=43) and female (n=16) patients were characterized by an attachment style scale (Relationships-style-questionnaire-RSQ) and completed a questionnaire battery comprising the State-Trait-Anxiety-Inventory (STAI), the Anxiety-Coping-Inventory (ABI), Temperament-and-character-inventory (TCI), Personality-system-interaction-inventory (PSI), and gave information on sociodemography, alcohol history, and adolescent adverse events. A structured interview (SKID-II) was performed to diagnose personality disorders.ResultsOnly 33% of subjects had a secure attachment style. Insecure attachment was associated with significantly higher trait-anxiety, higher cognitive avoidance to control anxiety, and higher values on most personality style dimensions directed to the pathological pole.ConclusionsDespite the limitation due to a small sample size, the results of this study show that the consideration of attachment styles is of significance in the diagnosis and therapy of alcohol addiction. Attachment may characterize different styles to control emotional aspects, anxiety cues and interpersonal relationships in individuals suffering from alcohol addiction.

A randomized, controlled trial of aerobic exercise in combination with paroxetine in the treatment of panic disorder

Abstract Objectives. Regular aerobic exercise (running) has been shown to be superior to a pill placebo in the treatment of panic disorder. Combined drug and exercise treatment has not been investigated in randomized controlled studies to date. Methods. This is a randomized, 10-week, controlled, parallel group, pilot study. A total of 75 outpatients with panic disorder with or without agoraphobia (DSM-IV and ICD-10) received either (1) exercise plus paroxetine 40 mg/day (n=21), (2) relaxation plus paroxetine (n=17), (3) exercise plus pill placebo (n=20), or (4) relaxation plus pill placebo (n=17). Changes in the Panic and Agoraphobia Scale (P&A), and the Clinical Global Impression Scale (CGI) underwent repeated measure analysis. Results. Effects sizes were large for all groups (d=1.53–3.87), however not significantly different. Paroxetine-treated patients were significantly more improved than placebo-treated patients. On the CGI, patients in the exercise groups (plus paroxetine or placebo) had a trend toward better improvement compared to relaxation (P=0.06). Response and remission rates were higher in the paroxetine compared to pill placebo groups. Conclusions. While paroxetine was superior to placebo, aerobic exercise did not differ from relaxation training in most efficacy measures.

Nocturnal Urinary Cortisol Excretion Over a Randomized Controlled Trial with Paroxetine vs. Placebo Combined with Relaxation Training or Aerobic Exercise in Panic Disorder

INTRODUCTION Data on basal hypothalamo-pituitary-adrenomedullary (HPA) function over controlled treatment trials with serotonergic drugs in anxiety disorders are still rare. METHODS 29 patients with panic disorder participating in a 10 week randomized, controlled trial (paroxetine vs. placebo with exercise or relaxation; N=60) collected urine for cortisol excretion over 3 consecutive nights before start and before termination of the treatment episode. Urinary cortisol was measured by radioimmunoassay. Efficacy measures were the Clinical Global Impression Scale (CGI) and the Panic and Agoraphobia Scale (P&A). 83% were female (p<.05 vs. males). 55% received additional aerobic exercise, and 45% relaxation. 55% received paroxetine treatment, and 45% placebo. Significantly fewer males received placebo treatment (p<.05). RESULTS All subjects improved significantly. Cortisol excretion did not differ between treatment groups or at pre-/post measurements. Females showed a significantly higher variability of cortisol excretion compared to males, at pre-(p<.005) and post (p=.015) assessments. Males displayed a trend to lower basal HPA function at end of treatment (p=.08). HPA variability after treatment showed a trend to be higher in the paroxetine (p=.052) -who clinically improved significantly better- compared to the placebo group. No relationship between HPA activity and treatment response or with exercise was detected. DISCUSSION HPA function shows significant gender differences, with females having a higher HPA function variability. Future studies on HPA function in treatment trials should address gender and medication effects.

Serotonergic function, substance craving, and psychopathology in detoxified alcohol-addicted males undergoing tryptophan depletion

Alcohol addiction is associated with alterations of central nervous dopaminergic and serotonergic functions. Acute tryptophan depletion has not yet been applied in detoxified alcohol-addicted patients in order to investigate its impact on psychopathology, psychoneuroendocrinology, and substance craving behaviour. 25 alcohol-addicted males randomly either received a tryptophan-free or tryptophan-containing amino acid drink and 7 days later the respective other drink. Anxiety, depression, and craving were assessed before and 5 h after the drink. Tryptophan, 5-HIAA, dopamine, norepinephrine, epinephrine, and HVA in serum were measured before and after both treatments. Nocturnal urinary cortisol measurements and genotyping for the HTTLPR polymorphism of the SLC6A4 gene were performed. Tryptophan depletion resulted in a significant reduction of total and free serum tryptophan while the tryptophan-rich drink increased serum levels. Both treatments caused a significant increase of serum serotonin levels, however, serum 5-HIAA was decreased after depletion but increased after sham depletion. Dopamine and norepinephrine were elevated after tryptophan depletion and sham. Depletion increased depression scores (MADRS), while the full amino acid drink improved state and trait anxiety ratings (STAI) and substance craving. Urinary cortisol excretion was not affected by both treatments. Patients with the ll genotype of the serotonin transporter gene displayed lower baseline tryptophan levels compared to patients with the heterozygous genotype. Results suggest an impaired serotonergic function in alcohol-addicted males.

Functional MRI activation in response to panic-specific, non-panic aversive, and neutral pictures in patients with panic disorder and healthy controls.

There is evidence that besides limbic brain structures, prefrontal and insular cortical activations and deactivations are involved in the pathophysiology of panic disorder. This study investigated activation response patterns to stimulation with individually selected panic-specific pictures in patients with panic disorder with agoraphobia (PDA) and healthy control subjects using functional magnetic resonance imaging (fMRI). Structures of interest were the prefrontal, cingulate, and insular cortex, and the amygdalo-hippocampal complex. Nineteen PDA subjects (10 females, 9 males) and 21 healthy matched controls were investigated using a Siemens 3-Tesla scanner. First, PDA subjects gave Self-Assessment Manikin (SAM) ratings on 120 pictures showing characteristic panic/agoraphobia situations, of which 20 pictures with the individually highest SAM ratings were selected. Twenty matched pictures showing aversive but not panic-specific stimuli and 80 neutral pictures from the International Affective Picture System were chosen for each subject as controls. Each picture was shown twice in each of four subsequent blocks. Anxiety and depression ratings were recorded before and after the experiment. Group comparisons revealed a significantly greater activation in PDA patients than control subjects in the insular cortices, left inferior frontal gyrus, dorsomedial prefrontal cortex, the left hippocampal formation, and left caudatum, when PA and N responses were compared. Comparisons for stimulation with unspecific aversive pictures showed activation of similar brain regions in both groups. Results indicate region-specific activations to panic-specific picture stimulation in PDA patients. They also imply dysfunctionality in the processing of interoceptive cues in PDA and the regulation of negative emotionality. Therefore, differences in the functional networks between PDA patients and control subjects should be further investigated.

Steckt eine Angststörung dahinter

Anxiety disorders represent a widespread illness. Those affected with initial symptoms usually seek the help of their family doctor. In many cases, considerable time passes before the diagnosis has been established and specialised treatment applied, with the result that chronification is furthered. Physical symptoms of an anxiety disorder, and fears of contracting somatic disease are almost always the first to be described. In patients abusing alcohol and/or hypnotics consideration must always be given to an anxiety disorder. Previously existing symptoms almost always include depressive moods or avoidance behavior. Stressful life events and other psychosocial stressful factors may also point the way to the early diagnosis of an anxiety disorder.ZusammenfassungWährend manche Dinge oder Situationen dem Gesunden völlig alltäglich erscheinen, versetzen diese den Angstpatienten in einen Ausnahmezustand. Nicht wenige von ihnen suchen Entspannung in Alkohol oder Hypnotika und bereiten damit den Weg in die Abhängigkeit. Wenn Sie Auslöser, Vorboten und Begleitsymptome von Angst- und Panikstörungen kennen, können Sie gerade als Hausarzt lenkend eingreifen, noch bevor sich die Störung manifestiert.

Grey matter structural differences in alcohol-dependent individuals with and without comorbid depression/anxiety—an MRI study

Although depression and anxiety disorders are common comorbid conditions in alcohol dependence, few structural brain imaging studies have compared alcohol-dependent subjects with and without such comorbidity. In the current study, brain scans of 35 alcohol-dependent with and 40 individuals without diagnosis of a comorbid ICD-10 depressive or anxiety disorder receiving detoxification inpatient treatment were evaluated. Thickness and volumes of automatically segmented neuroanatomical structures were measured in FreeSurfer. Furthermore, associations of brain structure with biological markers and clinical severity markers of alcohol dependence were assessed. Despite comparable addiction severity, the non-comorbid group had evidence of higher cytotoxic effects of alcohol use on hepatic and haematological markers, and showed significantly smaller volumes of total cerebral, and cerebellar grey matter. Similarly, they showed unexpected smaller hippocampal and nucleus accumbens volumes, and thinner frontal, temporal and occipital cortices. Smaller brain volumes correlated with increased markers of hepatic and haematological dysfunction, and with longer duration of alcohol dependence in the non-comorbid group. Evidence of higher biomarkers of alcohol use may be indicative of more severe alcohol dependence or higher vulnerability to ethanol toxicity in this group. Furthermore, psychopathology-related drug treatment, which occurred in 53% of the comorbid group over the recent years, or tissue inflammation may have a moderate effect on the grade of cerebral atrophy in alcohol-dependent patients. Longitudinal studies are needed to investigate this issue more fully.

Die soziale Angststörung : Diagnostik und Behandlungsmöglichkeiten

Im folgenden Text wird die Stellung der sozialen Angststörung bzw. Sozialphobie in das Gefüge der Angststörungen eingeordnet sowie die besonderen Probleme, die zu einer deutlichen Unterdiagnostizierung führen, herausgearbeitet. Wesentliche Diagnoseaspekte und Charakteristika der Störung werden erläutert, insbesondere unter differenzialdiagnostischen Aspekten. Besonderheiten von Störungsbeginn und Verlauf sowie Theorien zur Entstehung werden im Überblick besprochen. Psychotherapeutische und psychopharmakologische Behandlungsmöglichkeiten, die evidenzbasiert angewendet werden können, werden dargestellt und es wird ein Ausblick auf diesbezügliche, zukünftig zu erwartende Entwicklungen gegeben.