Platelet serotonin transporter function and heart rate variability in patients with panic disorder.

Many studies showed abnormal serotonin transporter (5-HTT) function and heart rate variability (HRV) in panic disorder patients. The present study investigated the relationship between HRV power spectral analysis findings and platelet serotonin uptake in panic disorder patients. Short-term HRV over 5 min and platelet serotonin transporter uptake parameters (V(max) and K(m)) were measured both in 45 patients with panic disorder and in 30 age-matched normal healthy control subjects. Low frequency power (LF) normalized unit (nu) and LF/high frequency power (HF) were significantly higher, whereas HF and HF nu were lower in the patient group than in the control group. V(max) and K(m) were all significantly lower (i.e., reflects decreased 5-HTT function) in patients with panic disorder than in normal controls. In the patient group, K(m) was negatively correlated with LF/HF and LF nu whereas no such correlations between them were found in the control group. By multivariate analysis based on multiple hierarchical linear regression, a low K(m) independently predicted an increased LF nu even after controlling for age, sex, and body mass index in the patient group. These results suggest that impaired 5-HTT function is closely related to dysregulation of autonomic nervous system in panic disorder.

Platelet serotonin transporter function after short-term paroxetine treatment in patients with panic disorder.

Dysfunctions in serotonin neurotransmission have been implicated in some psychiatric disorders, and in particular, altered serotonin transporter function has been noted in panic disorder. In this study, the authors compared platelet [(3)H]serotonin uptake parameters, including maximum velocities (V(max)) and affinity constants (K(m)), in patients with panic disorder not undergoing treatment (n=21) and in healthy subjects (n=20). V(max) and K(m) values were re-examined after 12 weeks of paroxetine treatment. Values of V(max) and K(m) were lower in panic disorder patients at baseline than in healthy subjects. After treatment, K(m) normalized in panic patients, whereas V(max) did not change. A significant inverse correlation was found between increased K(m) and changes in anxiety levels. These results support a hypothesis of serotonergic transporter abnormalities in panic disorder, and suggest that increased K(m) values of platelet serotonin transporters parallel clinical improvement after short-term pharmacotherapy in panic disorder.

Sympathetic nervous function and the effect of the catechol-O-methyltransferase Val(158)Met polymorphism in patients with panic disorder.

BACKGROUND: Sympathetic nervous function abnormalities have long been suggested to be a possible etiology of panic disorder (PD). Catechol-O-methyltransferase (COMT) affects sympathetic activities, and the COMT Val(158)Met polymorphism has been suggested to be related to PD. The authors examined the relationship between sympathetic nervous function and the COMT Val(158)Met polymorphism in PD patients. METHODS: Fifty-eight patients [Val/Val (51.7%) and Met allele carriers (48.3%)] and 58 age-matched normal control subjects [Val/Val (56.9%) and Met allele carriers (43.1%)] were compared in terms of finger skin temperature, which is known to be a useful marker of sympathetic nervous function. RESULTS: A significant COMT Val(158)Met polymorphismxdiagnosis interaction was found. Specifically, the met allele was found to be associated with a lower skin temperature in PD patients. CONCLUSION: These results suggest that the COMT Met allele is related to the higher sympathetic nervous function observed in PD.

beta-adrenoceptor affinity as a biological predictor of treatment response to paroxetine in patients with acute panic disorder.

BACKGROUND: Few studies have reported on the functional differences of the beta-adrenoceptor between treatment responders and non-responders in panic disorder (PD). The aim of this study was to compare the nature of the beta-adrenoceptor function and clinical variables between treatment responders and non-responders to paroxetine treatment in acute PD patients. METHOD: Paroxetine was administered to all of the panic patients for 12 weeks. The lymphocyte beta-adrenoceptor density (Bmax), affinity (1/Kd), and sensitivity (cAMP ratio) were measured in 22 untreated outpatients with acute PD and 22 age, sex and BMI matched control subjects. Psychological assessments were conducted using the HAM-A, and HAM-D, STAI-S and STAI-T, Anxiety sensitivity index (ASI), and Acute panic inventory (API). RESULTS: A significantly higher Kd was observed in the panic patients before treatment as compared with the control subjects, but there was no significant difference in Kd between the panic patients and control subjects after the treatment. Among the 22 patients, the 11 treatment responders (50%) showed a significantly higher Kd and lower mean scores of HAM-D, STAI-S, STAI-T, and ASI at baseline, compared with the non-responders. Logistic regression revealed that the pretreatment Kd and HAM-D were significantly reliable predictors for treatment response (p<0.05). CONCLUSION: The beta-adrenoceptor affinity (1/Kd) was decreased and adaptively normalized after treatment with paroxetine in the acute panic patients. In addition, a low pretreatment beta-adrenoceptor affinity (1/Kd) was found to predict the treatment response and can be suggested as a biological predictor of treatment response in acute PD.