Peripheral‐type benzodiazepine receptors in anxiety disorders

Abstract

Peripheral benzodiazepine receptors (pBDZr) were analyzed in lymphocyte membranes from patients with anxiety disorders (generalized anxiety disorder (GAD), n = 15; panic disorder (PD), n = 10; obsessive-compulsive disorder (OCD), n = 18), other mental disorders (n = 40) and 50 healthy controls, by the specific binding of 3H-PK11195. The number of binding sites (Bmax) was significantly decreased in groups with both GAD and OCD as compared with age-matched controls, by 45% and 25% respectively, whereas the binding affinity (Kd) was the same in all disorder and control groups. Conversely, no changes in binding capacity was observed in the other disorder groups and particularly in the one with PD. The abnormality in pBDZr observed in patients with GAD was restored to a normal value after long-term treatment with 2'-chloro-N-desmethyldiazepam, which also coincided with their recovery from anxiety. Our data suggest that the clinical heterogeneity in anxiety disorders might be related to different biological mechanisms and that lymphocyte pBDZr might be useful in demonstrating these differences.

Changes in Peripheral Benzodiazepine Receptors in Patients with Panic Disorder and Obsessive-Compulsive Disorder

“…Previous ly, a decreased density of ?H-PK-11195 binding sites has been observed in the episodic type of OCD [27], All our patients presented a chronic course, so that our results must be considered in line with this report. It is however noteworthy to underline the lack of effectiveness of BDZs in OCD.…”

“…Although no seasonal change in the binding has been observed up to now, at least in healthy controls, we performed all the blood sample analyses within a limited period of time (from March to June). Our results in patients with PD confirm and extend a previous report of our group [34], but are at variance with the observation of no change in peripheral BDZ receptors in lymphocytes of patients with PD [27], However, most of the patients included in that study were also suffering from a mild to a moderate depression, so that it is possible that the concomitance of this disorder with PD might have masked eventual changes in peripheral BDZ recep tors due to PD alone.…”

“…Stressing situations, such as that of sitting for an exam [23] or a parachute-training course [24] influence the density of the receptors, in the sense that an acute stress seems to provoke an up-regulation, while a repeated stress provokes a down-regulation. There exists also a growing literature on the study of these receptors in some neuropsychiatric conditions, such as generalized anxiety disorder, obsessive-compulsive disorder and Alz heimer's disease [25][26][27],…”

No association of two missense variations of the benzodiazepine receptor (peripheral) gene and mood disorders in a Japanese sample

“…The neurosteroids generated through the activation of the receptor elicit potent short-term allosteric modulatory effects on the action of GABA at the GABA A receptor [Majewska, 1992], producing an anxiolytic effect [Auta et al, 1993]. Decreased platelet BZRP density was observed in patients with anxiety disorders [Rocca, 1991] with post-traumatic stress disorder and in adolescent inpatients with repeated suicide attempts [Soreni et al, 1999]. Thus, the possibility cannot be excluded that the BZRP gene plays a role in the genetic predisposition of anxiety disorders and/or stressrelated disorders.…”

Short-term rebound anxiolytic effects and long-term changes in platelet benzodiazepine binding after pentylenetetrazole-kindling in two strains of rat

“…However, there is also growing evidence that a decrease in the number of peripheral benzodiazepine receptors is associated with anxiety disorders (Beoni et al, 1995;Rocca et al, 1991;Weizman et al, 1987). These binding changes have been observed in both platelets and lymphocytes and we therefore investigated changes in platelet benzodiazepine binding in the rats exposed to the kindling procedure and to an acute dose of pentylenetetrazole, in order to determine whether any changes in binding would parallel changes in anxiety.…”