Anhedonia revisited: is there a role for dopamine-targeting drugs for depression?

It is 16 years since we reviewed anhedonia in depression. Since then, there have been important developments in the study of anhedonia, mainly using the new techniques that neuroimaging made available, which provide very interesting new insights. It is becoming increasingly apparent that anhedonia, with psychomotor retardation, defines a dimension in depressive disorder that seems to be distinct from a dimension encompassing mood plus somatic symptoms.

Sleep in schizophrenia: time for closer attention.

Recent sleep research has highlighted two specific anomalies in schizophrenia that have a proven impact on cognition. One is an abnormality of circadian rhythm, reported in this journal in two separate studies over the past year, and the other is the finding in electroencephalograms of reduced sleep spindles.

Effects of acute tryptophan depletion in serotonin reuptake inhibitor-remitted patients with generalized anxiety disorder.

Background: Serotonergic antidepressants [selective serotonin reuptake inhibitor (SSRI)] are first-line treatments for generalised anxiety disorder (GAD); however, it is not known if synaptic serotonin (5-HT) availability is important for SSRI efficacy. The present study tested the hypothesis that temporary reduction in central 5-HT transmission, through acute tryptophan depletion (ATD), would reverse the therapeutic effect of the SSRIs in GAD patients.

Methods: Twelve patients (six males) with GAD, who showed sustained clinical improvement with SSRI treatment, underwent ATD in a double-blind, placebo-controlled, within-subjects design over 2 days, 1 week apart.

Rapid tryptophan depletion following cognitive behavioural therapy for panic disorder.

Objective: The aim of this study was to examine the effect of rapid tryptophan depletion (RTD) combined with a panicogenic challenge in patients with panic disorder who had responded to treatment with cognitive behavioural therapy (CBT). We hypothesised that RTD (compared with the control drink) would result in an increase in anxiety symptoms when provoked by a panicogenic challenge with the benzodiazepine antagonist, flumazenil.

Methods: Nine patients with panic disorder who had responded to CBT received a tryptophan-free amino acid drink on one occasion and a control drink on the other in a double-blind crossover design.

Redistribution of slow wave activity of sleep during pharmacological treatment of depression with paroxetine but not with nefazodone.

It has been suggested that increase in delta sleep ratio (DSR), a marker for the relative distribution of slow wave activity (SWA) over night time, is associated with clinical response to antidepressant treatment. We examined this index and its relationship to rapid eye movement (REM) suppression before and during long-term treatment with nefazodone, which does not suppress REM sleep, and paroxetine which does. The effect of serotonin (5-HT(2A)) receptor blockade on the evolution of SWA during treatment was also investigated.

Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study.

Background: The importance of the neurotransmitter serotonin (5-HT) in the pathophysiology of anxiety is well known. A key role for postsynaptic 5-HT(1A) receptors has recently been suggested in studies of genetic knockout mice.

Aims: To measure 5-HT(1A) receptor binding in patients with panic disorder in the untreated state and after recovery on treatment with selective serotonin reuptake inhibitors (SSRIs).

Development and validation of the Generalized Anxiety Disorder Inventory (GADI).

The psychometric tools used for the assessment of generalized anxiety disorder (GAD) either do not conform to the current concept of the condition or have important limitations. We aimed to develop and validate a new questionnaire for the assessment of symptom profile and severity of GAD. An original pool of potential scale items was subjected to a series of studies in non-clinical and clinical populations, in order to determine the final composition of the scale.

Depleting serotonin enhances both cardiovascular and psychological stress reactivity in recovered patients with anxiety disorders.

Serotonin-promoting drugs show cardioprotective properties in patients with anxiety or depression, but it is not known if this is a direct effect of increasing serotonin. We aimed to characterize the effect of serotonin manipulation through acute tryptophan depletion on cardiovascular and psychological responses to stress challenge in recovered patients with anxiety disorders. In 27 recovered patients with anxiety disorders (panic disorder treated by selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy, social anxiety disorder treated by SSRIs), we performed a double-blind randomized crossover study.

Sleep disturbances in depression and the effects of antidepressants.

Depressed patients often report sleep problems, which usually include difficulties with initiation and maintenance of sleep, as well as poor subjective quality of sleep. Such reports are confirmed by objective analysis of depressed patients' sleep through polysomnography, although there is no exact correspondence between subjective and objective measurements. In the present paper, we discuss some methodological problems related to the subjective estimates of sleep.

Antidepressants and sleep: a qualitative review of the literature.

Most antidepressants change sleep; in particular, they alter the physiological patterns of sleep stages recorded overnight with EEG and other physiological measures. These effects are greatest and most consistent on rapid eye movement (REM) sleep, and tend to be in the opposite direction to the sleep abnormalities found in major depression, but are usually of greater degree. Reductions in the amount of REM sleep and increases in REM sleep onset latency are seen after taking antidepressants, both in healthy volunteers and in depressed patients.

Dopaminergic mechanism of antidepressant action in depressed patients.

Clinical studies have not yet determined a common mechanism of action for antidepressant drugs, which have primary sites of action on a variety of different neurotransmitter systems. However, a large body of evidence from animal studies demonstrates that sensitisation of D2-like dopamine receptors in the mesolimbic dopamine system may represent a 'final common pathway' in antidepressant action. The present study aimed to determine whether, consistent with data from animal studies, the clinical antidepressant action of selective serotonin reuptake inhibitors (SSRIs) is reversed by acute administration of a receptor antagonist selective for D2-like receptors in the mesolimbic dopamine system.

Behavioral and cardiovascular effects of 7.5% CO2 in human volunteers.

The study of carbon dioxide (CO2) inhalation in psychiatry has a long and varied history, with recent interest in using inhaled CO2 as an experimental tool to explore the neurobiology and treatment of panic disorder. As a consequence, many studies have examined the panic-like response to the gas either using the single or double breath 35% CO2 inhalation or 5-7% CO2 inhaled for 15-20 min, or rebreathing 5% CO2 for a shorter time. However, this lower dose regime produces little physiological or psychological effects in normal volunteers.

Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorder.

Background: Tryptophan depletion studies have suggested that central serotonin (5-hydroxytryptamine, 5-HT) function mediates the therapeutic effect of selective serotonin reuptake inhibitors (SSRIs) in depression and panic disorder. The present study tested the hypothesis that temporary reduction in central 5-HT transmission, through acute tryptophan depletion, could reverse the therapeutic effect of the SSRIs in social anxiety disorder (SAD) patients.

Methods: Fourteen patients with SAD who showed sustained clinical improvement with SSRI treatment underwent tryptophan depletion in a double-blind, placebo-controlled, crossover design, over 2 days 1 week apart.

Correlation of subjective and objective sleep measurements at different stages of the treatment of depression.

Studies of the correlation of subjective and objective sleep measures in depressed patients have produced mixed results so far. Further, they were carried out in sleep laboratories and tended to obtain one-off assessments, thus not taking into account the effect of treatment. We investigated forty (40) patients over the course of 8-week treatment of depression with either paroxetine or nefazodone.

Venlafaxine: a new class of antidepressant.

Venlafaxine represents a new class of antidepressant, the serotonin and noradrenaline re-uptake inhibitor (or SNRI). This article discusses its evolution, pharmacological properties and role in the treatment of depression and related disorders, beginning with an outline of the biology of depression.

Inhalation of 35% CO(2) results in activation of the HPA axis in healthy volunteers.

Background: The hypothalamo-pituitary-adrenal (HPA) axis is a major stress responsive system in humans. Although there are numerous ways of testing responsiveness of the HPA in experimental animals, this is much more difficult in man. Hypercapnea is a very stressful stimulus for humans and has been used as an anxiogenic probe in psychiatric patients.

Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients recovered on paroxetine.

The neurobiological basis of panic disorder has not been clearly established, although a role for serotonin (5-HT) has been postulated. It is clear that drugs which increase 5-HT neurotransmission are effective in treating the condition but how they do so remains a point of debate. The aim of this study was to determine if lowering brain serotonin activity using the technique of tryptophan depletion provoked a short-term relapse of panic symptoms in patients with panic disorder who had responded to drug treatment.