Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity?

Pillai, Rajapillai L I; Zhang, Mengru; Yang, Jie; Boldrini, Maura; Mann, J. John; Oquendo, María A.; Parsey, Ramin V.; DeLorenzo, Christine

doi:10.1002/da.22721

Cited by 13 publications

(10 citation statements)

References 59 publications

(114 reference statements)

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“…In contrast, patients with bipolar disorders were found to have higher 5-HT 1A receptor binding using [ 18 F]FCWAY BP p , a measure of binding relative to plasma concentrations of PET tracer ( Nugent et al, 2013a , 2013b ). That finding in bipolar disorder is comparable with our prior work reporting higher 5-HT 1A receptor BP F using [ 11 C]WAY-100635 in patients with current depression or bipolar disorder ( Sullivan et al, 2009 ; Pillai et al, 2018 ; Zanderigo et al, 2018 ), healthy high-risk offspring of parents with mood disorders ( Milak et al, 2018 ), as well as in remitted MDD patients ( Miller et al, 2009 ), suggestive of a biological trait that could confer vulnerability to depression. Some of these discrepancies in terms of the abnormality in depression being high or low binding could be due to discrepancies in PET binding outcome measures (BP ND , BP P , BP F, or BP P /BP F ) and modeling approach for outcome measure estimation, the radioligand used, or the choice of a reference region ( Parsey et al, 2010 ).…”

Section: Discussionsupporting

confidence: 90%

“…In a meta-analysis of 10 positron emission tomography (PET) imaging studies, lower 5-HT 1A receptor binding in the mesiotemporal cortex was reported in depressed patients compared with healthy controls ( Wang et al, 2016 ). However, other studies, which were not included in this meta-analysis, found elevated binding in depression during an acute episode and between episodes in remitted patients ( Miller et al, 2009 ; Sullivan et al, 2015 ; Milak et al, 2018 ; Pillai et al, 2018 ). Higher binding was also observed in offspring of parents with major depression and was highest among those who went on to develop depression, indicating that this could be a familial trait ( Milak et al, 2018 ).…”

Section: Introductionmentioning

confidence: 69%

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Brain 5-HT1A Receptor PET Binding, Cortisol Responses to Stress, and the Familial Transmission of Suicidal Behavior

Melhem

Zhong

Miller

et al. 2021

International Journal of Neuropsychopharmacology

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Background The serotonin 1A (5-HT1A) receptor has been implicated in depression and suicidal behavior. Lower resting cortisol levels are associated with higher 5-HT1A receptor binding, and both differentiate suicide attempters with depression. However, it is not clear whether 5-HT1A receptor binding and cortisol responses to stress are related to familial risk and resilience for suicidal behavior. Methods [ 11C]CUMI-101 PET imaging to quantify regional brain 5-HT1A receptor binding was conducted in individuals considered to be at high-risk for mood disorder or suicidal behavior on the basis of having a first or second degree relative(s) with an early onset mood disorder and history of suicidal behavior. These high-risk subjects were subdivided into: high-risk resilient having no mood disorder or suicidal behavior (HR-R, n=29); high-risk with mood disorder and no suicidal behavior history (HR-MOOD n=31); and high-risk with mood disorder and suicidal behavior (HR-SA/MOOD, n=25). Groups were compared to healthy volunteers without a family history of mood disorder or suicidal behavior (HV, n=34). Participants underwent the Trier Social Stress Task (TSST). All subjects were free from psychotropic medications at the time of the TSST and PET scanning. Results We observed no group differences in 5-HT1A receptor binding considering all regions simultaneously, nor did we observe heterogeneity of the effect of group across regions. These results were similar across outcome measures (BPND for all subjects and BPp in a subset of the sample), and definitions of regions of interest (ROIs; standard or serotonin system-specific ROIs). We also found no group differences on TSST outcomes. Within HR-SA/MOOD, lower BPp binding [β=-0.084, Standard Error or SE=0.038, p=0.048] and higher cortisol reactivity to stress [β=9.25, 95% CI (3.27,15.23), p=0.004] were associated with higher lethality attempts. There were no significant relationships between 5-HT1A binding and cortisol outcomes. Conclusions 5-HT1A receptor binding in ROIs was not linked to familial risk or resilience protecting against suicidal behavior or mood disorder although it may be related to lethality of suicide attempt. Future studies are needed to better understand the biological mechanisms implicated in familial risk for suicidal behavior and how HPA axis function influences such risk.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 69%

Brain 5-HT1A Receptor PET Binding, Cortisol Responses to Stress, and the Familial Transmission of Suicidal Behavior

Melhem

Zhong

Miller

et al. 2021

International Journal of Neuropsychopharmacology

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“…Neuroimaging studies with positron emission tomography (PET) have revealed increased binding of the 5-HT1A receptors in the pontine raphe nuclei, both in patients with depression and in patients with migraine. 36 , 37 Moreover, it has been suggested that damage to the raphe nuclei is associated with depressive symptoms in patients who have experienced brainstem strokes. 38 Furthermore, animal studies have implicated a neural circuit involving the dorsal raphe nucleus in depressive behaviors.…”

Section: Discussionmentioning

confidence: 99%

Hypoechogenicity of the midbrain raphe detected by transcranial sonography: an imaging biomarker for depression in migraine patients

Zhang

Liu

Han

et al. 2021

Ther Adv Neurol Disord

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Background: The high comorbidity of migraine and depression is suggestive of shared risk factors or common mechanisms between the two diseases. In individuals with a depressive disorder, there is a high prevalence of altered midbrain raphe (MBR) echogenicity, detectable via transcranial sonography (TCS), that is suggested to be linked with a dysfunction of the serotoninergic system. In patients with migraine, this alteration has seldom been explored in earlier studies, and conclusions are often lacking. Our study aimed to elucidate whether this alteration is specific to migraine and to determine whether it is related with depression. Methods: This study enrolled patients with migraine ( n = 100, 72% female) and patients with tension-type headache disorders (TTH) ( n = 62, 78.5% female) from a headache clinic. In addition, 79 healthy subjects (79.7% female) were recruited as controls. All participants underwent a standard interview to evaluate headache information and an interview with psychiatrists for depression evaluation. TCS examinations were performed on all participants. Results: Patients with migraine had a higher rate of MBR hypoechogenicity (28%) compared with that of healthy controls (15.2%) and that of patients with TTH (12.9%). In patients with migraine, reduced MBR echogenicity was associated with depressive symptoms assessed using the Hamilton Depression Rating Scale (HAM-D). No association between migraine self-medication and MBR echogenicity was found. Conclusion: Reduced-echoic MBR detected by TCS is prevalent in migraine patients and is associated with depressive symptoms. TCS-detected hypoechogenic MBR abnormality could be an imaging biomarker of depressive symptoms in patients with migraine.

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“…Sinogram data were back-projected with filtering onto a 344x344 matrix with scatter correction and no smoothing. Participant motion was corrected by rigid body registration to a reference frame ( Pillai et al, 2018 ) with subsequent coregistration of MRI to the average PET image.…”

Section: Methodsmentioning

confidence: 99%

“…This RN atlas, in MNI space, was created from parametric 5-HT 1A average binding potential maps generated with the 5-HT 1A tracer [ 11 C]-WAY100635. These maps were then thresholded in the midbrain ( Pillai et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Measuring brain glucose metabolism in order to predict response to antidepressant or placebo: A randomized clinical trial

Hill

Gardus

Bartlett

et al. 2021

NeuroImage: Clinical

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Highlights A clinically relevant method of predicting MDD treatment efficacy is needed. The present investigation applies dynamic FDG-PET using blood as a reference. FDG-PET was assessed in the raphe nuclei, ventral prefrontal cortex and insula. Regional pretreatment metabolism does not relate to symptom severity decrease. Predictive FDG-PET signal may not be generalizable to heterogeneous MDD cohorts.

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Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity?

Abstract: In agreement with postmortem studies, we found higher 5-HT autoreceptor binding in MDD selectively in the DRN. 5-HT autoreceptor binding in the combined DRN and MRN is a better biomarker for MDD than in the raphe as a whole.

Cited by 13 publications

References 59 publications

Brain 5-HT1A Receptor PET Binding, Cortisol Responses to Stress, and the Familial Transmission of Suicidal Behavior

Brain 5-HT1A Receptor PET Binding, Cortisol Responses to Stress, and the Familial Transmission of Suicidal Behavior

Hypoechogenicity of the midbrain raphe detected by transcranial sonography: an imaging biomarker for depression in migraine patients

Measuring brain glucose metabolism in order to predict response to antidepressant or placebo: A randomized clinical trial

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