Incongruent Reduction of Serotonin Transporter Associated with Suicide Attempts in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM

Abstract

Background:Much evidence supports the role of the serotonin transporter (SERT) in the pathophysiology and pharmacotherapy of major depressive disorder (MDD) and suicidal behaviors.Methods:In this study, we recruited 17 antidepressant-naïve patients with MDD and 17 age- and gender-matched healthy controls. SERT availability was measured in vivo with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) positron emission tomography (PET) imaging. The 21-item Hamilton Depression Rating Scale (HDRS) and Beck Scale for Suicide Ideation were used to assess the severity of depression and the intent of suicide ideation prior to PET imaging. All subjects with MDD were in a current state of depression with HDRS scores ≧18. Subjects who attempted suicide within two weeks of the study onset were recruited in the depressed suicidal group (n = 8). Subjects with MDD who denied any prior suicide attempt were recruited into the depressed non-suicidal group (n = 9).Results:A significant reduction of SERT availability in the midbrain, thalamus, and striatum was noted in the MDD group relative to the control group (Bonferroni-adjusted p-value < 0.05). Moreover, this effect was more pronounced in the depressed suicidal group compared to the control group (Bonferroni-adjusted p-value < 0.01). Relative to both the depressed non-suicidal and control groups, the depressed suicidal group showed an increased prefrontal cortex (PFC)/midbrain SERT binding ratio (Bonferroni-adjusted p-value < 0.01).Conclusions:This study suggests an incongruent reduction of PFC SERT binding relative to the midbrain might discriminate between depressed suicide attempters and non-attempters in patients with MDD and may be involved in the pathophysiology of suicide behaviors.

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

“…The SERT is responsible for 5-HT reuptake from the synaptic cleft and thus determines the magnitude and duration of the 5-HT synaptic signal. A reduction of SERT sites in the brain (particularly in midbrain and amygdala) of depressed patients has been demonstrated both by functional imaging (Gryglewski et al 2014;Yeh et al 2014) and post-mortem brain studies (Mann et al 2000). As the binding to the SERT and the 5-HT uptake capacity remain low after recovery, low SERT activity has been suggested as a trait marker for mood disorders (Lesch 2001).…”

Ketamine and suicidal ideation in depression: Jumping the gun?

“…Further, lower ventromedial prefrontal cortex activity was associated with higher suicidal intent and higher lethality suicide attempts [179]. Whereas the 5-HT1A binding in prefrontal cortex or raphe regions did not differ among major depression patient groups of suicide attempters and non-attempters [180], prefrontal cortex/midbrain SERT binding ratio was increased in depressed suicidal patients [181]. Further, fMRI studies in recurrent major depression and bipolar II depression implicate the striatalcortical midline circuit in suicidal ideation and that the functional connectivity in the posterior cingulate cortex is associated with suicidal ideation in unipolar but not in the bipolar II depression [182][183][184].…”

Molecular, Functional, and Structural Imaging of Major Depressive Disorder

“…Altered SERT has been reported in MDD patients [116][117][118], and has been considered to be involved in the pathophysiology of depression [119] and suicide [115]. Recently, a study by Yeh et al [120] …”

“…It manifested an inverse correlation between HDRS and midbrain SERT BP ND . SERT, serotonin transporter; BP ND , binding potential of non-displaceable region [120]. (reprint permission was obtained from both the publisher and the corresponding author) midbrain SERT availability is an endophenotype for MDD, however, remains to be further elucidated.…”

“…Bars represent mean values. SERT, serotonin transporter; BP ND , binding potential of non-displaceable region; PFC, prefrontal cortex [120]. (reprint permission was obtained from both the publisher and the corresponding author)…”