Effect of serotonin transporter genotype on carbon dioxide-induced fear-related behavior in mice.

Background: Inhaling 35% carbon dioxide induces an emotional and symptomatic state in humans closely resembling naturally occurring panic attacks, the core symptom of panic disorder. Previous research has suggested a role of the serotonin system in the individual sensitivity to carbon dioxide. In line with this, we previously showed that a variant in the gene, encoding the serotonin transporter, moderates the fear response to carbon dioxide in humans.

Inverse autonomic stress reactivity in depressed patients with and without prior history of depression.

Background: There is a considerable association between major depressive disorder (MDD) and cardiovascular disease, most possibly relying on abnormalities in the autonomic nervous system (ANS)-related cardiac reactivity, although the exact underlying pathophysiological pathway is unclear. This study tends to shed some additional light on this background by investigating ANS reactivity in MDD with respect to previous depression history through an objective stress challenge paradigm.

Methods: The study assessed the effects of an overnight hypothalamus-pituitary-adrenal (HPA) axis stimulation with metyrapone (MET) on baseline ANS activity through linear and non-linear heart rate variability (HRV) measures in the morning of two continuous days in a group of 14 physically healthy, antidepressant-free patients with clinical, non-psychotic MDD, to investigate differences in autonomic reactivity with respect to prior MDD history.

Vagal effects of endocrine HPA axis challenges on resting autonomic activity assessed by heart rate variability measures in healthy humans.

Background: The hypothalamic-pituitary-adrenal axis (HPA axis) and the autonomic nervous system (ANS) are considered to play the most crucial role in the pathophysiology of stress responsiveness and are increasingly studied together. However, only few studies have simultaneously assessed HPA axis and ANS activity to investigate their direct interaction in pathophysiology, while no study so far has assessed the dynamic interplay between the two systems in healthy subjects through endocrine challenges.

Methods: The present study assessed the direct effects of overnight pharmacoendocrine HPA axis challenges with dexamethasone (suppression) and metyrapone (stimulation) on ANS activity at rest as determined by linear and nonlinear measures of heart rate variability (HRV) in 39 young healthy individuals.

Assessing Panic: Bridging the Gap Between Fundamental Mechanisms and Daily Life Experience.

Panic disorder (PD) is one of the most common psychiatric disorders. Recurrent, unexpected panic attacks (PAs) are the primary symptom and strongly impact patients' quality of life. Clinical manifestations are very heterogeneous between patients, emphasizing the need for a dimensional classification integrating various aspects of neurobiological and psychological circuits in line with the Research Domain Criteria (RDoC) proposed by the US National Institute of Mental Health.

Transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder: current perspectives.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neurostimulation technique receiving increasing attention in the treatment of different psychiatric disorders. Evidence for rTMS use in obsessive-compulsive disorder (OCD) is accumulating and informing further developments in the neurostimulation field, the latest being deep transcranial magnetic stimulation (dTMS). dTMS allows direct stimulation of deeper subcortical structures and larger brain volume than conventional rTMS.

Validation of the Mnemonic Similarity Task - Context Version.

Objective: Pattern separation (PS) is the ability to represent similar experiences as separate, non-overlapping representations. It is usually assessed via the Mnemonic Similarity Task - Object Version (MST-O) which, however, assesses PS performance without taking behavioral context discrimination into account, since it is based on pictures of everyday simple objects on a white background. We here present a validation study for a new task, the Mnemonic Similarity Task - Context Version (MST-C), which is designed to measure PS while taking behavioral context discrimination into account by using real-life context photographs.

Amiloride-sensitive cation channel 2 genotype affects the response to a carbon dioxide panic challenge.

Until recently, genetic research into panic disorder (PD) has had only limited success. Inspired by rodent research, demonstrating that the acid-sensing ion channel 1a (ASIC1a) is critically involved in the behavioral fear response to carbon dioxide (CO) exposure, variants in the human homologue gene amiloride-sensitive cation channel 2 (ACCN2) were shown to be associated with PD. However, the relationship between changes in brain pH and ACCN2, as done in rodents by CO exposure, has not been investigated yet in humans.

Pharmacokinetic Drug-Drug Interactions of Mood Stabilizers and Risperidone in Patients Under Combined Treatment.

Background: The combination of anticonvulsant mood stabilizers with antipsychotic drugs may lead to clinically relevant drug-drug interactions. The objective of the study was to identify pharmacokinetic interactions of different mood stabilizers on the metabolism of risperidone (RIS) under natural conditions.

Methods: A large therapeutic drug monitoring database containing plasma concentrations of RIS and its metabolite 9-hydroxy-RIS (9-OH-RIS) of 1,584 adult patients was analyzed.

Pharmacokinetic patterns of risperidone-associated adverse drug reactions.

Purpose: The aim of the study was to investigate a correlation between plasma concentrations of risperidone (RIS), its active metabolite 9-hydroxyrisperidone (9-OH-RIS) and the active moiety (AM) (RIS + 9-OH-RIS), and adverse drug reactions (ADRs) in a naturalistic sample.

Methods: Plasma concentrations of RIS, 9-OH-RIS, and AM in patients out of a therapeutic drug monitoring (TDM) database complaining ADRs were categorized according to the Udvalg for Kliniske Undersogelser side effect rating scales (UKU) (n = 97) and compared to patients without ADRs (n = 398).

Results: Patients in the ADR group received a significantly lower daily dosage of risperidone (trimmed mean 3.

The relation between depressive and obsessive-compulsive symptoms in obsessive-compulsive disorder: Results from a large, naturalistic follow-up study.

Objective: Despite the frequent occurrence of depressive symptoms in obsessive-compulsive disorder (OCD), little is known about the reciprocal influence between depressive and obsessive-compulsive symptoms during the course of the disease. The aim of the present study is to investigate the longitudinal relationship between obsessive-compulsive and depressive symptoms in OCD patients.

Method: We used the baseline and 1-year follow-up data of the Netherlands Obsessive Compulsive Disorder Association (NOCDA) study.

Pharmacokinetic considerations in the treatment of hypertension in risperidone-medicated patients - thinking of clinically relevant CYP2D6 interactions.

Background: Treatment of arterial hypertension in patients with severe mental illnesses often results in polypharmacy, potentially leading to drug-drug interactions. The objective of the study was to analyse the in vivo inhibitory potential of two antihypertensive drugs, amlodipine and metoprolol on CYP2D6 catalysed 9-hydroxylation of risperidone (RIS).

Methods: A therapeutic drug monitoring database with plasma concentrations of RIS and 9-hydroxyrisperidone (9-OH-RIS) of 1584 patients was analysed.

Risperidone-induced extrapyramidal side effects: is the need for anticholinergics the consequence of high plasma concentrations?

Antipsychotic drugs can induce various undesirable adverse motor reactions, such as extrapyramidal side effects (EPS). A widely accepted pharmacodynamic mechanism underlying EPS includes an increase in striatal D2-receptor occupancy. However, less is known about the pharmacokinetic background of EPS.

Is there cardiac risk in panic disorder? An updated systematic review.

Background: The recognized relationship between panic disorder (PD) and cardiac disorders (CDs) is not unequivocal. We reviewed the association between PD and coronary artery disease (CAD), arrhythmias, cardiomyopathies, and sudden cardiac death.

Methods: We undertook an updated systematic review, according to PRISMA guidelines.

Experience sampling-based personalized feedback and positive affect: a randomized controlled trial in depressed patients.

Objectives: Positive affect (PA) plays a crucial role in the development, course, and recovery of depression. Recently, we showed that a therapeutic application of the experience sampling method (ESM), consisting of feedback focusing on PA in daily life, was associated with a decrease in depressive symptoms. The present study investigated whether the experience of PA increased during the course of this intervention.

Intensive behavioral therapy for agoraphobia.

Background: We investigated the efficacy of an intensive 1-week behavioral therapy program focusing on agoraphobia for panic disorder patients with agoraphobia (PDA).

Design And Methods: The study design was a case-control study. Main outcome measure was the agoraphobia score of the Fear Questionnaire (FQ-AGO).

The weight of cognitions in panic: the link between misinterpretations and panic attacks.

In cognitive theory it is hypothesized that panic attacks are provoked by catastrophic misinterpretations of bodily sensations. The aim of the present study was to investigate the ability of associated word pairs referring to catastrophic thinking (e.g.

Carbon dioxide inhalation as a human experimental model of panic: the relationship between emotions and cardiovascular physiology.

Inhaling carbon dioxide (CO2)-enriched air induces fear and panic symptoms resembling real-life panic attacks, the hallmark of panic disorder. The present study aimed to describe the emotional and cardiovascular effects evoked by inhaling CO2, taking shortcomings of previous studies into account. Healthy volunteers underwent a double inhalation of 0, 9, 17.

The Netherlands Obsessive Compulsive Disorder Association (NOCDA) study: design and rationale of a longitudinal naturalistic study of the course of OCD and clinical characteristics of the sample at baseline.

In half of Obsessive Compulsive Disorder (OCD) patients the disorder runs a chronic course despite treatment. The factors determining this unfavourable outcome remain unknown. The Netherlands Obsessive Compulsive Disorder Association (NOCDA) study is a multicentre naturalistic cohort study of the biological, psychological and social determinants of chronicity in a clinical sample.

Endogenous opioid release in the human brain reward system induced by acute amphetamine administration.

Background: We aimed to demonstrate a pharmacologically stimulated endogenous opioid release in the living human brain by evaluating the effects of amphetamine administration on [(11)C]carfentanil binding with positron emission tomography (PET).

Methods: Twelve healthy male volunteers underwent [(11)C]carfentanil PET before and 3 hours after a single oral dose of d-amphetamine (either a "high" dose, .5 mg/kg, or a sub-pharmacological "ultra-low" dose, 1.

35% CO2 sensitivity in social anxiety disorder.

The 35% carbon dioxide (CO(2)) challenge is a well-established model of panic. This study aimed to investigate 35% CO(2) sensitivity in patients with social anxiety disorder (SAD) compared with patients with panic disorder (PD) and normal controls. First, a 35% CO(2) challenge was conducted including 16 patients with generalized SAD, 16 with PD and 16 normal subjects.

Paroxetine augmentation in patients with generalised social anxiety disorder, non-responsive to mirtazapine or placebo.

Objectives: The aim of the study was to investigate if combination of mirtazapine with paroxetine causes a greater therapeutic effect and less sexual side effects than paroxetine monotherapy in social anxiety disorder (SAD).

Methods: Twenty one patients with generalised SAD, non-responsive to a 12 week trial with mirtazapine and 22 patients, non-responsive to placebo received paroxetine (20-40 mg) in addition to their double-blind treatment with mirtazapine or placebo for another 12 weeks. The Liebowitz Social Anxiety Scale (LSAS) and the Clinical Global Impression-Improvement (CGI-I) scale were used to measure efficacy.

Cigarette smoking and panic: a critical review of the literature.

Objective: Cigarette smoking increases the risk of panic disorder with or without agoraphobia's emerging. Although the cause of this comorbidity remains controversial, the main explanations are that (1) cigarette smoking promotes panic by inducing respiratory abnormalities/lung disease or by increasing potentially fear-producing bodily sensations, (2) nicotine produces physiologic effects characteristic of panic by releasing norepinephrine, (3) panic disorder promotes cigarette smoking as self-medication, and (4) a shared vulnerability promotes both conditions. The aim of this review was to survey the literature in order to determine the validity of these explanatory models.

Cigarette smoking and 35% CO(2) induced panic in panic disorder patients.

Background: A disproportionately large number of persons with panic disorder (PD) smoke cigarettes compared to people in the general population and individuals with other anxiety disorders. Clinical and epidemiological data suggest that cigarette smoking increases the risk for the development and maintenance of PD. The carbon dioxide (CO(2)) challenge is well established as experimental model for panic.

Negative affectivity in smokers applying to smoking cessation clinics: a case-control study.

Objective: The objective of this study was to assess whether subjects applying to smoking cessation clinics display a higher level of affective symptoms than smokers recruited from the general population.

Methods: The study was conducted according to a cross-sectional, case-control design. Cases were smokers applying to public smoking cessation clinics for the first time and controls were smokers recruited from the general population.