Dorsolateral Prefrontal Cortex and Subcallosal Cingulate Connectivity Show Preferential Antidepressant Response in Major Depressive Disorder

Fatt, Cherise R. Chin; Cooper, Crystal; Jha, Manish K.; Aslan, Sina; Grannemann, Bruce D.; Kurian, Benji T.; Greer, Tracy L.; Fava, Maurizio; Weissman, Myrna M.; McGrath, Patrick J.; Parsey, Ramin V.; Etkin, Amit; Phillips, Mary L.

doi:10.1016/j.bpsc.2020.06.019

Cited by 13 publications

(13 citation statements)

References 47 publications

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“…Another limitation of this study is that, although abnormalities in the temporal lobe and visual cortex have been observed in MDD patients, 46 , 56 - 59 our findings did not show modulating effects on these regions. One explanation was that the dysregulation in some subcortical regions that appeared insensitive to treatment may act as trait vulnerability markers, and the relatively strict multiple-comparison correction makes our voxel-based analyses only reveal the most significant brain regions within potentially changed networks.…”

Section: Discussioncontrasting

confidence: 57%

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

He¹,

Li²,

Wang³

et al. 2023

Brazilian Journal of Psychiatry

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Introduction: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. Methods: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. Results: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. Conclusion: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

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Section: Discussioncontrasting

confidence: 57%

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

He¹,

Li²,

Wang³

et al. 2023

Brazilian Journal of Psychiatry

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“…They identified several areas that were potential moderators of response, including the right anterior insula which appeared to be the area most strongly associated with differential response (SMD = 1.43). Large multi-site studies have attempted to use biomarkers, including by identifying depression subtypes (n = 711) that may predict treatment response to transcranial magnetic stimulation (n = 154) (Drysdale et al, 2017) or using electroencephalography to identify responders to antidepressants vs. placebos (Fatt et al, 2020). Because these endeavours still task researchers with identifying interactions between pre-treatment variables (e.g., a specific genetic polymorphism) and treatment in Thus, many of the issues identifying on research on PTRs also apply to biomarkers.…”

Section: Biomarkersmentioning

confidence: 99%

Personalized Medicine and Cognitive Behavioral Therapies for Depression: Small Effects, Big Problems, and Bigger Data

et al. 2020

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Cognitive-behavioral therapies (CBTs) are the most widely studied form of psychotherapy for disorders like depression and anxiety. Nonetheless, there is heterogeneity in response to CBTs vs. other treatments. Researchers have become increasingly interested in using pre-treatment individual differences (i.e., moderators) to match patients to the most effective treatments for them. Several methods to combine multiple variables to create precision treatment rules (PTRs) that identify subgroups have been proposed. We review the rationale behind multivariable PTRs as well as the findings of studies that have used different PTRs. We identify conceptual and methodological issues in the literature. Multivariable treatment assignment is a promising avenue of research. Nonetheless, effect sizes appear to be small and most of the samples that have been used to study these questions have been grossly underpowered to detect small effects. We recommend researchers explore multivariable treatment selection strategies, particularly those resembling risk-stratification, in heterogeneous samples of patients undergoing low-intensity CBTs vs. realistic minimal controls.

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“…With respect to the AN and SMN, decreased AMYG functional connectivity with the left SMA and right precentral gyrus, as well as increased AMYG functional connectivity with the right central opercular cortex, have been found to reflect a favorable response to SSRI treatment ( 320 ). Previous research has also found that areas of the CEN with low functional connectivity, such as the DLPFC, are associated with a greater response to sertraline ( 321 ). In contrast, decreased functional connectivity of the right insula, a node of the SN, has been linked with insufficient antidepressant response ( 322 ).…”

Section: Intrinsic Connectivity Network and Slow-onset Monoaminergic ...mentioning

confidence: 99%

Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review

et al. 2022

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Conventional monoamine-based pharmacotherapy, considered the first-line treatment for major depressive disorder (MDD), has several challenges, including high rates of non-response. To address these challenges, preclinical and clinical studies have sought to characterize antidepressant response through monoamine-independent mechanisms. One striking example is glutamate, the brain's foremost excitatory neurotransmitter: since the 1990s, studies have consistently reported altered levels of glutamate in MDD, as well as antidepressant effects following molecular targeting of glutamatergic receptors. Therapeutically, this has led to advances in the discovery, testing, and clinical application of a wide array of glutamatergic agents, particularly ketamine. Notably, ketamine has been demonstrated to rapidly improve mood symptoms, unlike monoamine-based interventions, and the neurobiological basis behind this rapid antidepressant response is under active investigation. Advances in brain imaging techniques, including functional magnetic resonance imaging, magnetic resonance spectroscopy, and positron emission tomography, enable the identification of the brain network-based characteristics distinguishing rapid glutamatergic modulation from the effect of slow-acting conventional monoamine-based pharmacology. Here, we review brain imaging studies that examine brain connectivity features associated with rapid antidepressant response in MDD patients treated with glutamatergic pharmacotherapies in contrast with patients treated with slow-acting monoamine-based treatments. Trends in recent brain imaging literature suggest that the activity of brain regions is organized into coherent functionally distinct networks, termed intrinsic connectivity networks (ICNs). We provide an overview of major ICNs implicated in depression and explore how treatment response following glutamatergic modulation alters functional connectivity of limbic, cognitive, and executive nodes within ICNs, with well-characterized anti-anhedonic effects and the enhancement of “top-down” executive control. Alterations within and between the core ICNs could potentially exert downstream effects on the nodes within other brain networks of relevance to MDD that are structurally and functionally interconnected through glutamatergic synapses. Understanding similarities and differences in brain ICNs features underlying treatment response will positively impact the trajectory and outcomes for adults suffering from MDD and will facilitate the development of biomarkers to enable glutamate-based precision therapeutics.

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Dorsolateral Prefrontal Cortex and Subcallosal Cingulate Connectivity Show Preferential Antidepressant Response in Major Depressive Disorder

Cited by 13 publications

References 47 publications

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

Personalized Medicine and Cognitive Behavioral Therapies for Depression: Small Effects, Big Problems, and Bigger Data

Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review

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