Postmortem Findings in Suicide Victims. Implications for in Vivo Imaging Studies^a

Abstract

Alterations in serotonergic and noradrenergic receptor binding in membrane homogenates from the brain of suicide victims suggest a biological substrate for the vulnerability to commit suicide. We and others have employed high-resolution quantitative autoradiography of full coronal sections of the prefrontal cortex to map the locus of maximal change in receptor binding. We found alterations in binding to the serotonin transporter, the 5-HT1A, and the 5-HT2A receptors primarily in the ventral and ventrolateral prefrontal cortex of suicide victims. Importantly, these changes are often modest in magnitude and anatomically restricted to one or two Brodmann areas. Furthermore, we have found that care in case selection is essential, because sex, age, drugs, and comorbid diagnoses contribute to receptor binding. The implications for in vivo imaging are considerable, directing the focus of such studies toward the ventrolateral prefrontal cortex. However, because ligands are limited, as is the resolution of current methods, including PET, automated analyses that produce statistical images, rather than manual selection of individual slices, will likely lack the ability to detect the discrete receptor changes found postmortem. Alternatively, the advantages of examining large numbers of subjects, imaging the entire brain, obtaining detailed clinical information in the living patient, and magnifying the changes with neuropharmacological challenges present a promising outlook for making major advances into the identification of brain abnormalities associated with suicide risk.

Altered 5-HT2A Receptor Binding after Recovery from Bulimia-Type Anorexia Nervosa: Relationships to Harm Avoidance and Drive for Thinness

“…In particular, we found relationships with the Harm Avoidance subscale 2, which particularly assesses fear of uncertainty (Cloninger et al, 1994), in temporal and other regions. Our data are consistent with the literature that implicates that 5-HT activity is related to anxiety and impulsivity in ill BN subjects (Steiger et al, 2001a, b, c) and to impulsive, aggressive behaviors in men (Arango et al, 1997;Coccaro et al, 1997;New et al, 1997;Siever and Trestman, 1993).…”

Elevated cytokine expression in the orbitofrontal cortex of victims of suicide

“…The orbitofrontal cortex including Brodman area 11 has been strongly implicated as a structure associated with inhibition of aggression, impulsivity and suicidal behavior (16,31,32). In addition, postmortem studies have demonstrated neurotransmitter abnormalities in this area of the brain of suicides such as decreased serotonin transporter binding sites and increased 5-HT1A and 5-HT2A receptor binding (32,33).…”

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

“…Since the demonstration of decreased levels of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin (5-HT), in the cerebrospinal fluid of a subgroup of depressed suicide attempters 30 years ago, 7 substantial additional evidence has accumulated that implicates the serotonergic system in both depression and suicide. 3,4,[8][9][10][11] Despite some inconsistencies across these studies and their inability to distinguish between neurobiological factors associated with suicide from those associated with the comorbid mental illness, these findings have raised the possibility of specific suicide-associated differences in various aspects of serotonergic function (for example, receptors, transporters, metabolic enzymes and their functional regulation). Recent studies have suggested abnormalities in mRNA editing of one of the serotonin receptors-2C (5-HT 2C R)-in depressed suicide victims.…”