In the Journals

PET imaging may measure risk for suicidal ideation, attempts, death

Greater raphe nuclei serotonin1A binding potential, as indicated in positron emission tomography imaging, predicted higher suicidal ideation and greater risk for death by suicide, according to recent findings.

“Suicidal behavior occurs in the context of a diathesis characterized by impairments in mood and emotion regulation, decision making, problem solving, and social appraisal. Suicidal behavior is also associated with specific biomarkers, mostly involving the serotonergic system and hypothalamic pituitary adrenal axis,” APA president Maria A. Oquendo, MD, of New York State Psychiatric Institute, and colleagues wrote. “We found individuals with major depressive disorder (MDD) who attempt suicide have lower in vivo midbrain serotonin transporter binding compared with those who do not attempt suicide, suggesting that the differences in the proportions of suicide attempters studied may contribute to discrepant positron emission tomography (PET) findings in MDD.”

Maria A. Oquendo

To determine if serotonin transporter binding in the lower midbrain predicted suicide attempts and if higher raphe nuclei (RN) serotonin1A binding predicted suicidal ideation and lethality of future suicide attempts, researchers conducted a prospective 2-year observational study among 100 individuals presenting for treatment for a major depressive episode. Study participants underwent PET using a serotonin1A antagonist, carbon 11–labeled N-(2-(1-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl))-N-(2-pyridyl)-cyclohexanecarboxamide ([11C]WAY-100635). A subset of 50 participants also underwent imaging with a serotonin transporter radioligand, carbon 11–labeled 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]DASB). Imaging was conducted from May 1999 to March 2008 and follow-up was completed in May 2010.

Overall, 15 participants attempted suicide, including two who died by suicide.

Higher RN serotonin1A binding potential predicted suicidal ideation at 3 months (P = .001) and 12 months (P = .001) and greater lethality of subsequent suicidal behavior (P = .01).

Exploratory analysis indicated serotonin1A binding of the insula (P = .04), anterior cingulate (P = .04) and dorsolateral prefrontal cortex (P = .03) also predicted lethality.

Serotonin1A binding in any brain region did not predict suicidal intent and midbrain serotonin transporter binding potential did not predict future attempts.

“We found that greater RN serotonin1A BPF, measured with [11C]WAY-100635 PET, predicted more lethal suicidal behavior during a 2-year period. Our results suggest that this association is at least partly mediated through more severe suicidal ideation. Identifying neurobiological characteristics of high-lethality suicide attempters has intrinsic scientific importance, and discovery of molecular-level markers of high-lethality behavior may eventually improve clinical screening to detect those at risk for suicide,” the researchers concluded. – by Amanda Oldt

Disclosure: Oquendo reports receiving royalties from the Research Foundation for Mental Hygiene for commercial use of the Columbia Suicide Severity Rating Scale and family ownership of stock in Bristol-Myers Squibb. Please see the full study for a list of all authors’ relevant financial disclosures.

Greater raphe nuclei serotonin1A binding potential, as indicated in positron emission tomography imaging, predicted higher suicidal ideation and greater risk for death by suicide, according to recent findings.

“Suicidal behavior occurs in the context of a diathesis characterized by impairments in mood and emotion regulation, decision making, problem solving, and social appraisal. Suicidal behavior is also associated with specific biomarkers, mostly involving the serotonergic system and hypothalamic pituitary adrenal axis,” APA president Maria A. Oquendo, MD, of New York State Psychiatric Institute, and colleagues wrote. “We found individuals with major depressive disorder (MDD) who attempt suicide have lower in vivo midbrain serotonin transporter binding compared with those who do not attempt suicide, suggesting that the differences in the proportions of suicide attempters studied may contribute to discrepant positron emission tomography (PET) findings in MDD.”

Maria A. Oquendo

To determine if serotonin transporter binding in the lower midbrain predicted suicide attempts and if higher raphe nuclei (RN) serotonin1A binding predicted suicidal ideation and lethality of future suicide attempts, researchers conducted a prospective 2-year observational study among 100 individuals presenting for treatment for a major depressive episode. Study participants underwent PET using a serotonin1A antagonist, carbon 11–labeled N-(2-(1-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl))-N-(2-pyridyl)-cyclohexanecarboxamide ([11C]WAY-100635). A subset of 50 participants also underwent imaging with a serotonin transporter radioligand, carbon 11–labeled 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]DASB). Imaging was conducted from May 1999 to March 2008 and follow-up was completed in May 2010.

Overall, 15 participants attempted suicide, including two who died by suicide.

Higher RN serotonin1A binding potential predicted suicidal ideation at 3 months (P = .001) and 12 months (P = .001) and greater lethality of subsequent suicidal behavior (P = .01).

Exploratory analysis indicated serotonin1A binding of the insula (P = .04), anterior cingulate (P = .04) and dorsolateral prefrontal cortex (P = .03) also predicted lethality.

Serotonin1A binding in any brain region did not predict suicidal intent and midbrain serotonin transporter binding potential did not predict future attempts.

“We found that greater RN serotonin1A BPF, measured with [11C]WAY-100635 PET, predicted more lethal suicidal behavior during a 2-year period. Our results suggest that this association is at least partly mediated through more severe suicidal ideation. Identifying neurobiological characteristics of high-lethality suicide attempters has intrinsic scientific importance, and discovery of molecular-level markers of high-lethality behavior may eventually improve clinical screening to detect those at risk for suicide,” the researchers concluded. – by Amanda Oldt

Disclosure: Oquendo reports receiving royalties from the Research Foundation for Mental Hygiene for commercial use of the Columbia Suicide Severity Rating Scale and family ownership of stock in Bristol-Myers Squibb. Please see the full study for a list of all authors’ relevant financial disclosures.