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. The psychometric properties of the new scale, the Generalized Anxiety Disorder Inventory (GADI), were evaluated using a factor analytic model suitable for ordinal data and the Graded Response Model. The precision of measurement of the GADI was quantified through the item information functions.A total of 197 outpatients and 522 non-clinical subjects participated in four studies and completed the GADI. The final 18-item scale was derived from an original pool of 30 potential items. The GADI showed good reliability, convergent and divergent validity. The scale comprises three factors, relating to cognitive, somatic and sleep symptoms. It accurately distinguished GAD patients from non-patient controls. The cognitive factor also distinguished GAD from other anxiety disorders and depression. The GADI is a useful tool in the assessment of the breadth of symptoms and the severity of generalized anxiety disorder in clinical settings.

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. At the peak time of depletion, the participants also underwent three behavioral challenges: autobiographical script, verbal task, and neutral script. Psychological outcome was assessed with the Spielberger State Anxiety Inventory (STAI) Form Y-1 and visual analog scales (VAS) measuring anxiety, depression, and somatic symptoms. RESULTS: Anxiety was significantly increased on the depletion day compared with the control day, both on the STAI Form Y-1 and composite VAS score. Furthermore, there was a significant depletion x time interaction, explained mainly by the anxiogenic effect of the autobiographical script. In contrast, the verbal and the neutral tasks failed to differentiate between depletion and placebo. CONCLUSIONS: Tryptophan depletion induced significant increase of anxiety in treated SAD patients, which was more prominent during the recital of an autobiographical script. This finding supports the notion that SSRIs improve social anxiety by increasing 5-HT availability. The autobiographical script seems to be a more robust challenge test for SAD than the stressful verbal task.

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. We have now investigated whether the simple challenge of a single 35% inhalation of CO(2) activates the neuroendocrine system as evidenced by changes in HPA activity, as well as cardiovascular and subjective responses, in healthy volunteers. METHODS: Fourteen healthy male volunteers were recruited. They underwent single vital capacity inhalation of room air and 35% CO(2), in a single blind fashion. Neuroendocrine, cardiovascular and subjective fear measures were taken at regular intervals. RESULTS: CO(2) inhalation produced significant activation of the HPA axis in all subjects, as measured with plasma cortisol. Heart rate was decreased and systolic blood pressure was significantly increased shortly after the inhalation of CO(2). The subjects reported short-lived symptoms of fear with the experimental gas. CONCLUSIONS: Single vital capacity inhalation of 35% CO(2) activated the HPA axis in healthy volunteers. It also had a significant cardiovascular and psychological (anxiogenic) effect, as expected from previous published studies. The test is potentially useful in studying the responsivity of the HPA axis in health and disease.

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. We used home polysomnography at baseline, nights 3 and 10, and week 8 of treatment, with extensive assessments of subjective sleep, the morning after each sleep recording. The patients were able to judge accurately their total sleep time and sleep onset latency, both before and during treatment. However, they were inaccurate in estimating the number of times they woke up during the night. Sleep satisfaction correlated negatively with Stage 1 sleep at baseline. Sleep quality was represented by a combination of subjective parameters measuring the ease of initiation and maintenance of sleep, and it appeared to derive from slow wave sleep and sleep continuity as seen in polysomnography. The partial discrepancy between subjective and objective measures suggests that a cognitive element is combined with the biological element to produce the sleep problems reported by depressed patients.

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). METHOD: Nine symptomatic untreated patients with panic disorder, seven patients recovered on SSRI medication and nineteen healthy volunteers underwent a single positron emission tomography (PET) scan using the 5-HT(1A) tracer [(11)C]WAY-100635. RESULTS: In comparison with controls, both presynaptic and postsynaptic 5-HT(1A) receptor binding was reduced in untreated patients, with the most significant reductions being in the raphe, orbitofrontal cortex, temporal cortex and amygdala. In recovered patients presynaptic binding was reduced, but there was no significant reduction in postsynaptic binding. CONCLUSIONS: Panic disorder is associated with reduced 5-HT(1A) receptor availability, which is also known to have a key role in depression.