Prediction of SSRI treatment response in major depression based on serotonin transporter interplay between median raphe nucleus and projection areas

Lanzenberger, Rupert; Kranz, Georg S.; Haeusler, Daniela; Akimova, Elena; Savli, Markus; Hahn, Andreas; Mitterhauser, Markus; Spindelegger, Christoph; Philippe, Cécile; Fink, Martin; Wadsak, Wolfgang; Karanikas, Georgios; Kasper, Siegfried

doi:10.1016/j.neuroimage.2012.07.023

Cited by 120 publications

(106 citation statements)

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“…49 Remarkably, in our recent PET study, high baseline 5-HTT ratios between amygdala and median raphe nucleus was associated with better treatment response to selective serotonin reuptake inhibitors. 50 …”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Molecular Imaging of Serotonin Transporters in Major Depression

Gryglewski

Lanzenberger

Kranz

et al. 2014

J Cereb Blood Flow Metab

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205

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The success of serotonin-selective reuptake inhibitors has lent support to the monoamine theory of major depressive disorder (MDD). This issue has been addressed in a number of molecular imaging studies by positron emission tomography or single-photon emission computed tomography of serotonin reuptake sites (5-HTT) in the brain of patients with MDD, with strikingly disparate conclusions. Our meta-analysis of the 18 such studies, totaling 364 MDD patients free from significant comorbidities or medication and 372 control subjects, revealed reductions in midbrain 5-HTT (Hedges' g=−0.49; 95% CI: (−0.84, −0.14)) and amygdala (Hedges' g=−0.50; 95% CI: (−0.78, −0.22)), which no individual study possessed sufficient power to detect. Only small effect sizes were found in other regions with high binding (thalamus: g=−0.24, striatum: g=−0.32, and brainstem g=−0.22), and no difference in the frontal or cingulate cortex. Age emerged as an important moderator of 5-HTT availability in MDD, with more severe reductions in striatal 5-HTT evident with greater age of the study populations (P<0.01). There was a strong relationship between severity of depression and 5-HTT reductions in the amygdala (P=0.01). Thus, molecular imaging findings indeed reveal widespread reductions of ∼10% in 5-HTT availability in MDD, which may predict altered spatial–temporal dynamics of serotonergic neurotransmission.

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Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Molecular Imaging of Serotonin Transporters in Major Depression

Gryglewski

Lanzenberger

Kranz

et al. 2014

J Cereb Blood Flow Metab

Self Cite

205

View full text Add to dashboard Cite

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“…That is, the greater the SERT binding potential in terminal projection regions of serotonergic neurons in median raphe in relation to SERT binding in the median raphe itself, the better was the treatment outcome. This finding suggests that the antidepressant effects of SSRIs resulted from down-regulation of SERT activity in terminal regions receiving serotonergic projection [148].…”

Section: Depressionmentioning

confidence: 91%

The role of lateral habenula–dorsal raphe nucleus circuits in higher brain functions and psychiatric illness

Zhao

Zhang

Yang

et al. 2015

Behavioural Brain Research

111

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Serotonergic neurons in the dorsal raphe nucleus (DRN) play an important role in regulation of many physiological functions. The lateral nucleus of the habenular complex (LHb) is closely connected to the DRN both morphologically and functionally. The LHb is a key regulator of the activity of DRN serotonergic neurons, and it also receives reciprocal input from the DRN. The LHb is also a major way-station that receives limbic system input via the stria medullaris and provides output to the DRN and thereby indirectly connects a number of other brain regions to the DRN. The complex interactions of the LHb and DRN contribute to the regulation of numerous important behavioral and physiological mechanisms, including those regulating cognition, reward, pain sensitivity and patterns of sleep and waking. Disruption of these functions is characteristic of major psychiatric illnesses, so there has been a great deal of interest in how disturbed LHb-DRN interactions may contribute to the symptoms of these illnesses. This review summarizes recent research related to the roles of the LHb-DRN system in regulation of higher brain functions and the possible role of disturbed LHb-DRN function in the pathogenesis of psychiatric disorders, especially depression.

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“…The CT analysis may be affected by several factors, such as sample sizes, medication status (Lanzenberger et al, 2012, Foland-Ross et al, 2011), or heterogeneity in the patient samples. Most studies published to date have included patients who were taking medications.…”

Section: Introductionmentioning

confidence: 99%

Common and Specific Abnormalities in Cortical Thickness in Patients with Major Depressive and Bipolar Disorders

et al. 2017

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Major depressive disorder (MDD) and bipolar disorder (BD) are severe psychiatric diseases with overlapping symptomatology. Although previous studies reported abnormal brain structures in MDD or BD patients, the disorder-specific underlying neural mechanisms remain poorly understood. The purpose of this study was to investigate the whole-brain gray matter morphological patterns in unmedicated patients with MDD or BD and to identify the shared and disease-specific brain morphological alterations in these two disorders.We acquired high-resolution brain structural MRI data from a sample of 36 MDD patients, 32 BD patients, and 30 healthy controls. Using FreeSurfer, we estimated their brain cortical thickness (CT) and compared between-group difference in multiple locations across the continuous cortical surface.Compared to the healthy controls, both the MDD and BD patient groups showed significantly reduced CT in the left inferior temporal cortex (ITC). However, compared to the MDD patients, the BD patients showed a significantly thinner CT in the left rostral middle frontal region. In addition, compared to the healthy controls, the BD patients displayed thinner CT in the left ITC, left frontal pole (FPO), left superior frontal, right lateral occipital, right pars triangularis (PTRI) and right lateral orbitofrontal regions. Further analysis revealed a significantly positive correlation between the mean CT in the left FPO and the onset age, but a negative correlation between the mean CT in the right PTRI and the number of episodes, in the BD patients.Our findings revealed that the BD and MDD patients had variations in CT that were in common, but many more that were distinct, suggesting potential differences in their neural mechanisms.

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Prediction of SSRI treatment response in major depression based on serotonin transporter interplay between median raphe nucleus and projection areas

Cited by 120 publications

References 50 publications

Meta-Analysis of Molecular Imaging of Serotonin Transporters in Major Depression

Meta-Analysis of Molecular Imaging of Serotonin Transporters in Major Depression

The role of lateral habenula–dorsal raphe nucleus circuits in higher brain functions and psychiatric illness

Common and Specific Abnormalities in Cortical Thickness in Patients with Major Depressive and Bipolar Disorders

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