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 (ß=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 (ß=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.

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.

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.

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. 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.

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.

Experimental affective symptoms in panic disorder patients.

OBJECTIVE: To date, carbon dioxide (CO2) challenge tests in panic disorder (PD) patients have focused on anxiety as the sole outcome measure. This study assesses a broader range of symptoms in patients with PD. METHOD: We administered a gas mixture of 35% CO2 and 65% oxygen (O2) to 25 patients with PD. Nine patients met the criteria for a comorbid major depressive disorder (MDD), and 16 did not. We assessed not only subjects' symptoms of anxiety but also their symptoms of depression and aggression. RESULTS: Baseline ratings did not differ across the 2 subgroups. Postchallenge ratings were higher for PD and MDD patients on all the assessed affective symptoms, except for specific panic symptoms. CONCLUSION: These findings suggest that, in addition to anxiety, CO2 challenge induces depressive and aggressive symptoms, specifically in PD patients with comorbid depression.

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.

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.

Comorbidity of obsessive-compulsive disorder and depression: prevalence, symptom severity, and treatment effect.

BACKGROUND: The goal of this study was to investigate the co-occurrence of depressive disorders in obsessive-compulsive disorder (OCD) and the effect of these disorders on combined pharmacologic and behavioral treatment for OCD. METHOD: A retrospective chart analysis was performed on baseline ratings of 120 OCD patients and posttreatment ratings of 72 of these patients. For depressive symptoms, the Montgomery-Asberg Depression Rating Scale and the Self-Rating Depression Scale were applied; for obsessive-compulsive symptoms, the Yale-Brown Obsessive Compulsive Scale and the Maudsley Obsessive Compulsive Inventory were used; and for general anxiety symptoms, the Self-Rating Anxiety Scale, the Clinical Anxiety Scale, and the State-Trait Anxiety Inventory were given. RESULTS: One third of the OCD patients in our sample were found to be depressed. Symptom severity on OCD symptoms at baseline did not differ between depressed and nondepressed OCD patients; on general anxiety symptoms, the comorbid group was more severely affected. Both depressed and nondepressed OCD patients responded well to treatment, as reflected in assessments for depressive, obsessive-compulsive, and general anxiety symptoms. However, comorbid depression had a negative effect on treatment: depressed OCD patients showed less improvement than nondepressed OCD patients on most scales. CONCLUSION: Depression frequently accompanies OCD and appears to affect treatment outcome negatively. While both groups of patients improved with combination treatment, the OCD-alone group had more improvement than the group that had comorbid depression.