Decreased platelet peripheral-type benzodiazepine receptors in adolescent inpatients with repeated suicide attempts

Abstract

Background: Peripheral-type benzodiazepine receptors (PBR) are responsible for mitochondrial cholesterol uptake, the rate limiting step of steroidiogenesis. They have been shown to be increased after acute stress, and decreased during exposure to chronic stressful conditions, and in patients with generalized anxiety disorder and post-traumatic stress disorder. In view of the proven connection between adolescent suicidal behavior and stress, we hypothesized that PBR may be decreased in the suicidal adolescent population.

Methods: We measured [³H] PK 11195 binding to platelet membrane in nine adolescent (age 13–20 years) inpatients with a history of at least three suicidal attempts and ten age-matched psychiatric inpatients with no history of suicide attempts. Suicidality was assessed with the Suicide Risk Scale (SRS), and symptom severity with the Beck Depression Inventory, State-Trait Anxiety Inventory (STAI), Overt Aggression Scale (OAS), and Impulsivity Scale (IS).

Results: Suicide Risk Scale scores were significantly higher in the suicidal group. The suicidal group showed a significant decrease in platelet PBR density (−35%) compared to the controls (p < 0.005).

Conclusions: Our results of PBR depletion in adolescent suicide are in accordance with the findings in patients with generalized anxiety disorder and posttraumatic stress disorder and lend further support to the role of PBR in human response to chronic stress in adolescent suicide.

Introduction

Peripheral-type benzodiazepine receptors (PBR) play a role in cholesterol translocation from the outer to the inner mitochondrial membrane (Krueger and Papadopoulos 1990), which is the rate limiting step of steroidogenesis. Studies have shown that PBR are sensitive to hormonal changes and stress Drugan et al 1986, Ferrarese et al 1990, Burgin et al 1996, Drugan 1996; upregulation was demonstrated after exposure to acute stress, while downregulation is a consistent finding during chronic stressful conditions Drugan et al 1986, Drugan et al 1987, Drugan et al 1988, Novas et al 1987, Okun et al 1988, Karp et al 1989, Rago et al 1989a, Rago et al 1989b, Dar et al 1991, Rocca et al 1991, Weizman et al 1994, Johnson et al 1998. This bidirectional effect of stress on PBR expression may be important in the regulation of adrenal steroid biosynthesis Weizman and Gavish 1993, Weizman et al 1994, Burgin et al 1996. A decrease in PBR have also been demonstrated in several psychiatric disorders, such as generalized anxiety disorder (GAD) Weizman et al 1987, Ferrarese et al 1990, Rocca et al 1998, generalized social phobia (GSP) (Johnson et al, 1998), panic disorder (PD) (Marazziti et al 1994), and post-traumatic stress disorder (PTSD) (Gavish et al 1996), but not in obsessive-compulsive disorder (OCD) Weizman et al 1993, Weizman and Gavish 1993, Weizman et al 1996, Marazziti et al 1994, major depression (Weizman et al 1995), or attention-deficit hyperactivity disorder (ADHD) Weizman et al 1993, Weizman and Gavish 1993, Weizman et al 1993.

Adolescent suicide is a major public health problem (Spirito et al 1989) that is often associated with both acute and chronic stress (Rudd 1990). Research indicates that adolescents who have attempted suicide have high levels of life stress (Lewinsohn et al 1994), and that adolescents who have committed suicide were significantly more likely to have experienced stressful interpersonal conflicts, legal problems, and disruption of romantic attachments than community control subjects (Brent et al 1993). In view of these findings, we hypothesized that adolescents who have made repeated suicidal attempts may have decreased PBR density.