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Identifying Neurobiological Correlates of Suicide Risk in Depression

Identifying Neurobiological Correlates of Suicide Risk in Depression

Patients suffering from depressive disorders, particularly those with a history of suicide attempt, are at increased risk for future suicidal acts. Neurobiological studies of suicidal behavior have investigated anomalies that distinguish suicide attempters and completers from individuals who are depressed but do not engage in any suicidal behavior. To aid in the development of a predictive model in which both biological measures and clinical instruments are used to identify those at risk for future suicidal acts, studies have focused on biological correlates of behavioral and other factors identified by clinical studies as indicative of higher risk for suicidal behavior, such as aggression/impulsivity.

Neuroendocrine challenge and cerebrospinal fluid (CSF) studies suggest that suicide attempters have decreased function in the serotonin system (Malone et al., 1996; Siever et al., 1984; Virkkunen et al., 1989). Among individuals with depression, high-lethality suicide attempts are associated with even lower serotonergic function (Malone et al., 1996; Mann and Malone, 1997). Neuroendocrine challenges and CSF measures are, however, unable to provide specific information about the anatomical location of abnormality. So far, it is known from studies mapping postmortem serotonin receptor binding that cortical serotonergic abnormalities associated with suicide are localized to the ventral prefrontal cortex (PFC) region of the brain (Arango et al., 1997). Positron emission tomography (PET) studies offer a distinct advantage over previous methodologies, allowing for more precise in vivo identification and study of the activity of brain regions that differ in those who have survived a suicide attempt of high lethality, compared to those surviving a low-lethality attempt. Given the findings of CSF and neuroendocrine studies with respect to differences in serotonin levels between high- and low-lethality attempters, PET studies of high-lethality attempters would be expected to reveal pronounced differences.

In a recent study, my colleagues and I examined regional brain glucose metabolism with placebo and after administration of fenfluramine (Pondimin), a serotonin-releasing drug, in order to discern regional differences in glucose metabolism associated with serotonergic activity between high- and low-lethality depressed suicide attempters (Oquendo et al., 2003). Changes in metabolism, which include both increases and decreases, reflect changes in neuronal activity, owing to the surge of serotonergic activity caused by fenfluramine. The changes can occur in both directions because serotonin has both inhibitory and indirect excitatory effects in different brain regions. These differences in response by different brain regions due to serotonergic activity can be visualized with PET.

Our PET study of the regional serotonergic function in patients who are depressed and have a history of high-lethality suicide attempts compared to patients who are depressed and have a history of low-lethality suicide attempts revealed differences in brain activity between the two groups (Oquendo et al., 2003). High-lethality suicide attempters showed less activity in the ventral, medial and lateral PFC, compared to low-lethality suicide attempters, indicating a relative hypofunction in the PFC in high-lethality attempters. There were two specific regions of interest (ROIs) where differences were identified between low- and high-lethality attempters. One was in the anterior cingulate and the medial frontal gyri (ROI #1) and the second in the anterior cingulate and right superior frontal gyri (ROI #2). The first ROI was located bilaterally in the anterior cingulate and medial frontal gyrus (BA 32 and 8). The second ROI was located in the right midcingulate and superior frontal gyri (BA 24 and 6).


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