Thea Overbeek

Effects of tryptophan depletion on carbon dioxide provoked panic in panic disorder patients

Results of an earlier study in healthy volunteers suggest that the serotonergic system is involved in anxiety-related mechanisms. We studied the influence of tryptophan depletion on the response to a 35% carbon dioxide challenge. Twenty-four panic disorder patients received a mixture of amino acids, either with or without tryptophan, under double-blind conditions. There was a significant increase in anxiety as well as in neurovegetative symptoms in the depletion group, compared to the placebo condition. Furthermore, when we compare the results of the placebo group with earlier panic provocation studies, it also seems that a balanced amino acid mixture might have a protective effect against a panic provocation. We conclude that the panic-enhancing effect of tryptophan depletion as well as the potential protective effect of tryptophan administration in panic disorder patients can be explained by the Deakin-Graeff theory of anxiety.

Acute l-5-hydroxytryptophan administration inhibits carbon dioxide-induced panic in panic disorder patients

Previous research showed that lowering the availability of serotonin to the brain by tryptophan depletion increases the vulnerability of panic disorder patients for an experimental 35% CO(2) panic challenge. The results also suggested that increased availability of serotonin inhibits the response to such a challenge. In the present study, this latter possibility is examined. The reaction of 24 panic disorder patients and 24 healthy volunteers to a 35% CO(2) panic challenge was assessed following administration of 200-mg L-5-hydroxytryptophan (the immediate precursor of serotonin) or placebo. L-5-Hydroxytryptophan significantly reduced the reaction to the panic challenge in panic disorder patients, regarding subjective anxiety, panic symptom score and number of panic attacks, as opposed to placebo. No such effect was observed in the healthy volunteers. L-5-Hydroxytryptophan acts to inhibit panic, which supports a modulatory role of serotonin in panic disorder.

Sleep Complaints in Panic Disorder Patients

Patients with anxiety disorders often report difficulty sleeping. The present study assesses the prevalence of sleep complaints in panic disorder (PD) patients, compares them with sleep complaints in a normal population, and investigates the role of comorbid depression and nocturnal panic attacks in sleep complaints in the PD patients. Seventy PD patients and 70 healthy controls were asked about their subjective sleep characteristics by means of the Sleep-Wake Experience List, which assesses sleep/arousal complaints over a 24-hour period. Sixty-seven percent of the PD patients reported sleep complaints, compared with 20% of the controls. Eighty-six percent of the depressed PD patients and 59% of the nondepressed had sleep difficulties; 77% of the PD patients with nocturnal panic attacks reported sleep complaints, versus 53% of the PD patients without nocturnal panic. It is concluded that PD patients demonstrate a higher prevalence of sleep complaints than normal controls; this can only partly be explained by comorbid depression, and cannot be explained by the presence of nocturnal panic attacks.

10μG CCK-4 premedication and 35% CO2 challenge in healthy volunteers

Abstract 1. 1. The purpose of the study was to confirm whether a subtreshold dose of CCK-4 would enhance the vulnerability of healthy subjects to a 35% carbon dioxide challenge. 2. 2. 40 subjects, with no prior or present psychiatric disorder and in good physical health were challenged with a vital capacity breath of a 35% carbon dioxide 65% oxygen mixture, immediatly after an intravenous injection of 10 μg CCK-4 or placebo, according to a random order, double blind, separate group design 3. 3. Subjects reported significantly less anxiety and panic symptoms upon carbon dioxide after premedication with CCK-4 than after placebo. 4. 4. CCK-4 and carbon dioxide seem to inhibit rather than enhance each others effects, possibly through an effect on different neurobiological systems.

Therapygenetics: 5-HTTLPR genotype predicts the response to exposure therapy for agoraphobia

This study was intended to assess the extent to which the low-expression allele of the serotonin transporter gene promoter predicts better response to exposure-based behavior therapy in patients with panic disorder with agoraphobia (PDA). Ninety-nine patients with PDA underwent a 1-week in vivo exposure-based behavior therapy program and provided saliva samples to extract genomic DNA and classify individuals according to four allelic forms (SA, SG, LA, LG) of the 5-HTT-linked polymorphic region (5-HTTLPR). We determined whether the 5-HTTLPR genotype predicted change in avoidance behavior in PDA following treatment. After controlling for pre-treatment avoidance behavior, the 5-HTTLPR low-expression genotypes showed a more favorable response to exposure therapy two weeks following treatment, compared to the other patients. This study suggests a genetic contribution to treatment outcome following behavior therapy and implicates the serotonergic system in response to exposure-based treatments in PDA.

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. In 276 patients with a lifetime diagnosis of obsessive-compulsive disorder, depressive and obsessive-compulsive symptoms were assessed at baseline and at one-year follow-up with the Beck Depression Inventory (BDI) and the Yale-Brown Obsessive Compulsive Symptom (Y-BOCS) scale. Relations were investigated using a cross-lagged panel design. RESULTS The association between the severity of depressive symptoms at baseline and obsessive-compulsive symptoms at follow-up was significant (β=0.244, p<0.001), while the association between the severity of obsessive-compulsive symptoms at baseline and depressive symptoms at follow-up was not (β=0.097, p=0.060). Replication of the analyses in subgroups with and without current comorbid major depressive disorder (MDD) and subgroups with different sequence of onset (primary versus secondary MDD) revealed the same results. LIMITATIONS There may be other factors, which affect both depressive and obsessive-compulsive symptoms that were not assessed in the present study. CONCLUSION The present study demonstrates a relation between depressive symptoms and the course of obsessive-compulsive symptoms in OCD patients, irrespective of a current diagnosis of MDD and the sequence of onset of OCD and MDD.

Cigarette smoking and 35% CO2 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. The present study seeks to examine whether cigarette smoking has an influence on laboratory elicited panic in PD patients. METHODS In total 92 subjects (46 smokers and 46 non-smokers) with PD, according to the DSM-IV criteria, were compared. All subjects received a baseline clinical assessment and underwent a 35% CO(2) challenge. Response to the challenge was evaluated via the Panic Symptom List and the Visual Analogue Fear Scale. RESULTS The two samples did not differ on baseline anxiety level. Smokers had a significantly higher increase in panic symptoms in response to the challenge compared to non-smokers (p=0.04). LIMITATIONS This type of study does not provide information concerning the underlying mechanisms of the link between smoking and panic. Study limitations include lack of formal assessment of personality and of inter-rater reliability. CONCLUSIONS The present findings are consistent with the idea that smoking facilitates panic in PD subjects. This may have clinical implications, as quitting smoking could become one of the relevant steps in the treatment of PD patients.

Blood-injury related phobic avoidance as predictor of nonresponse to pharmacotherapy in panic disorder with agoraphobia.

BACKGROUND Several factors have been investigated as possible predictors of nonresponse to pharmacotherapy in Panic Disorder (PD) patients. In 1995 a study was published by Slaap et al. in this journal that found high Blood-Injury phobia scores on the Marks and Matthews Fear Questionnaire were predictive for a worse treatment-outcome for drug treatment in PD. METHODS The present paper describes a replication study with 61 PD patients, by means of a retrospective chart analysis, who were assessed at baseline and after 12 weeks of SSRI-treatment. Nonresponse was defined as still having panic attacks. Response was defined as absence of panic attacks and/or a reduction of at least 50% on the FQ Agoraphobia subscale. RESULTS Twenty (32%) patients were nonresponders. Nonresponders had a higher score on the FQ Blood-Injury subscale more often (55%) than responders (19.5%), significant at P=0.008. These results fully support the findings of Slaap et al. Implications of these findings are further discussed. LIMITATIONS Limitations of this study are the retrospective design, and the absence of other psycho-physiological parameters of the specific blood-injury phobic complex. CONCLUSIONS However, it is tentatively concluded that the presence of comorbid blood-injury related phobic symptoms negatively affects treatment for panic disorder and agoraphobia.

Effects of low-dose cholecystokinin on respiratory function in healthy volunteers

Injection of high doses of cholecystokinin tetrapeptide (CCK-4), a recent experimental model for panic, causes panic attacks and respiratory stimulation, a key feature of panic, in healthy volunteers. However, it has not yet been established whether respiratory stimulation is specifically linked to panic or merely an effect of arousal in general. Results of the present study show that respiratory stimulation is not merely linked to higher arousal and suggest a link between CCK-provoked panic and respiratory stimulation.

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 outcomes on the FQ-AGO of a 1-week intensive therapy (96 patients) and a twice-weekly therapy (98 patients) were compared. RESULTS Agoraphobia improved significantly in both groups, 1 week and 3 months after therapy. Effect size for changes in the 1-week intensive therapy on the FQ-AGO was 0.75. LIMITATIONS Limitations are use of antidepressants, no placebo group, and no long term follow-up. CONCLUSION Behavioral therapy for agoraphobia can be shortened significantly if intensified without affecting therapy outcome, thus allowing patients a more rapid return to work and resumption of daily activities.