Low brain serotonin transporter binding in major depressive disorder

Myrna Brind Center of Integrative Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Psychiatry Research (Impact Factor: 2.68). 06/2012; 202(2):161-7. DOI: 10.1016/j.pscychresns.2011.12.015
Source: PubMed

ABSTRACT We examined midbrain, medial temporal lobe, and basal ganglia serotonin transporter (SERT) distribution volume ratio (DVR) values in subjects with major depressive disorder versus healthy volunteers using a selective SERT radioligand and single photon emission computed tomography (SPECT). We hypothesized that the DVR value for SERT binding would be lower in depressed versus non-depressed subjects. [(123)I]-ADAM SPECT scans were acquired from 20 drug free, depressed subjects and 20 drug-free depressed subjects and 10 drug-free healthy volunteers. The primary outcome measure was the DVR value for [(123)I]-ADAM uptake in the midbrain, medial temporal lobe, and basal ganglia regions. Depressed subjects demonstrated significantly lower DVR values in the midbrain, right and left medial temporal lobe, and right and left basal ganglia. There was significant probability that lower DVR values could distinguish between depressed and non-depressed subjects in the midbrain, medial temporal lobe, and the right and left basal ganglia. These findings confirm prior observations of lower SERT binding in depression, and suggest that low SERT binding may represent a putative biomarker of depression. Future studies are needed to confirm these observations.

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    ABSTRACT: Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). The study aimed to examine whether the pretreatment SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcome to SERT-targeted antidepressants. We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more. Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Non-responders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders. The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcome in patients with MDD. © The Author 2015. Published by Oxford University Press on behalf of CINP.
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    ABSTRACT: Much evidence supports the role of the serotonin transporter (SERT) in the pathophysiology and pharmacotherapy of major depressive disorder (MDD) and suicidal behaviors. 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-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-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). 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 depressed suicidal group compared to the control group (Bonferroni-adjusted p-value < 0.01). Relative to both 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). This study suggests an incongruent reduction of PFC SERT binding relative to midbrain might discriminate depressed suicide attempters from non-attempters in patients with MDD and may be involved in the pathophysiology of suicide behaviors. © The Author 2014. Published by Oxford University Press on behalf of CINP.

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