Neuroimaging biomarkers as predictors of treatment outcome in Major Depressive Disorder

Fonseka, Trehani M.; MacQueen, Glenda; Kennedy, Sidney H.

doi:10.1016/j.jad.2017.10.049

Cited by 140 publications

(97 citation statements)

References 109 publications

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“…We also found a trend for decreased insula activity and anticipatory anhedonia during effort to avoid. The insula has been implicated in many studies of depression examining functional connectivity, volumetric analyses and biomarkers for treatment outcomes 32 . The insula is also involved in emotion processing, self-awareness and motor control 33 and also specifically in anticipatory cues and approach and avoidance behavior 34, 35 .…”

Section: Discussionmentioning

confidence: 99%

Dimensional Anhedonia and the Adolescent brain: Reward and Aversion Anticipation, Effort and Consummation: Anhedonia in adolescent depression

Rzepa

McCabe

2018

Preprint

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Given the heterogeneity of depression the Research Domain Criteria Framework suggests a dimensional approach to understanding the nature of mental health and illness. Neural reward function has been suggested as underpinning the symptom of anhedonia in depression but less is known about how anhedonia is related to aversion processing. We examined how anhedonia relates to neural activity during reward and aversion processing in adolescents and emerging adults (N=84) in the age range 13-21yrs. Using a dimensional approach we examined how anhedonia and depression severity correlated with an fMRI task measuring anticipation, effort and consummation of reward and aversion. We show for the first time that the dimensional experience of anhedonia correlated with neural responses during effort to avoid aversion in the precuneus with a trend in the insula and during aversive consummation in the caudate. Using a categorical approach we also examined how the neural responses during each phase of the task differed in those with depression symptoms compared to healthy controls. We found participants with depression symptoms invested less physical effort to gain reward than controls and had blunted neural anticipation of reward and aversion in the precuneus, insula, and prefrontal cortex and blunted neural effort for reward in the putamen. This work highlights blunted neural responses to reward and aversion in depression and how anticipatory and consummatory anhedonia may be enhanced via dysfunctional neural processing of aversion. Future work will assess if these neural mechanisms can be used to predict blunted behavioural approach to reward and avoidance of negative experiences in adolescents at risk of depression.

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Section: Discussionmentioning

confidence: 99%

Dimensional Anhedonia and the Adolescent brain: Reward and Aversion Anticipation, Effort and Consummation: Anhedonia in adolescent depression

Rzepa

McCabe

2018

Preprint

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“…Given that the amygdalae are involved in (in)effective emotion regulation in stress-related disorders (Gold & Chrousos, 2002;Perlman et al, 2012) and in particular the right amygdala is implicated when processing negative information stressful events (Baeken et al, 2010b;Mothersill & Donohoe, 2016), it is of interest to note that increased baseline and sustained amygdala activity to antidepressant treatment is associated with clinical nonresponse in major depression (Fonseka, Macqueen, & Kennedy, 2018). Given that the amygdalae are involved in (in)effective emotion regulation in stress-related disorders (Gold & Chrousos, 2002;Perlman et al, 2012) and in particular the right amygdala is implicated when processing negative information stressful events (Baeken et al, 2010b;Mothersill & Donohoe, 2016), it is of interest to note that increased baseline and sustained amygdala activity to antidepressant treatment is associated with clinical nonresponse in major depression (Fonseka, Macqueen, & Kennedy, 2018).…”

Section: Graph Measures As Biomarkermentioning

confidence: 99%

“…Furthermore, the degree in the right amygdala was significantly correlated with the clinical effects of verum aiTBS, suggesting that less connections to the right amygdala could be predictive for better clinical responses. Given that the amygdalae are involved in (in)effective emotion regulation in stress-related disorders (Gold & Chrousos, 2002;Perlman et al, 2012) and in particular the right amygdala is implicated when processing negative information stressful events (Baeken et al, 2010b;Mothersill & Donohoe, 2016), it is of interest to note that increased baseline and sustained amygdala activity to antidepressant treatment is associated with clinical nonresponse in major depression (Fonseka, Macqueen, & Kennedy, 2018).…”

Section: Graph Measures As Biomarkermentioning

confidence: 99%

Focal application of accelerated iTBS results in global changes in graph measures

Klooster

Franklin

Besseling

et al. 2018

Human Brain Mapping

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Graph analysis was used to study the effects of accelerated intermittent theta burst stimulation (aiTBS) on the brain's network topology in medication‐resistant depressed patients. Anatomical and resting‐state functional MRI (rs‐fMRI) was recorded at baseline and after sham and verum stimulation. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS). Using various graph measures, the different effects of sham and verum aiTBS were calculated. It was also investigated whether changes in graph measures were correlated to clinical responses. Furthermore, by correlating baseline graph measures with the changes in HDRS in terms of percentage, the potential of graph measures as biomarker was studied. Although no differences were observed between the effects of verum and sham stimulation on whole‐brain graph measures and changes in graph measures did not correlate with clinical response, the baseline values of clustering coefficient and global efficiency showed to be predictive of the clinical response to verum aiTBS. Nodal effects were found throughout the whole brain. The distribution of these effects could not be linked to the strength of the functional connectivity between the stimulation site and the node. This study showed that the effects of aiTBS on graph measures distribute beyond the actual stimulation site. However, additional research into the complex interactions between different areas in the brain is necessary to understand the effects of aiTBS in more detail.

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“…This study overcomes some of these limitations with a large sample size, specific treatment arms, and restriction to two analyzable MDD subtypes. Investigations into structural magnetic resonance imaging (MRI) biomarkers of MDD treatment response have further been limited to trials without placebo-control groups, preventing assessment of biomarker specificity [6,7,[28][29][30][31][32][33]. To support causal inferences regarding a treatment's effect on the brain and to control for nonspecific treatment effects, placebo and/or active treatment control arms are critical [34].…”

Section: Introductionmentioning

confidence: 99%

“…Based on these pretreatment and longitudinal neuroimaging studies, the a priori measures of interest: rostral ACC, caudal ACC, OFC, and RMF cortical thickness and volume, and hippocampal volume, were selected in the hopes that with EMBARC's large, placebo-controlled design, more conclusive evidence of their role in MDD treatment response may emerge. As these regions have been associated with executive functioning, cognition, memory formation, and emotional processing [29], these regions may be specifically implicated in the antidepressant effects of SSRIs. Our primary hypothesis was that individuals with a positive response to SSRI treatment, characterized by changes in a continuous measure of depression severity, would present with thicker/larger cortices pretreatment and would further display cortical thickening/enlargening in the acute phase of treatment, relative to those with a nonresponse to SSRI treatment.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment and early-treatment cortical thickness is associated with SSRI treatment response in major depressive disorder

Bartlett

DeLorenzo

Sharma

et al. 2018

Neuropsychopharmacol

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To date, there are no biomarkers for major depressive disorder (MDD) treatment response in clinical use. Such biomarkers could allow for individualized treatment selection, reducing time spent on ineffective treatments and the burden of MDD. In search of such a biomarker, multisite pretreatment and early-treatment (1 week into treatment) structural magnetic resonance (MR) images were acquired from 184 patients with MDD randomized to an 8-week trial of the selective serotonin reuptake inhibitor (SSRI) sertraline or placebo. This study represents a large, multisite, placebo-controlled effort to examine the association between pretreatment differences or early-treatment changes in cortical thickness and treatment-specific outcomes. For standardization, a novel, robust site harmonization procedure was applied to structural measures in a priori regions (rostral and caudal anterior cingulate, lateral orbitofrontal, rostral middle frontal, and hippocampus), chosen based on previously published reports. Pretreatment cortical thickness or volume did not significantly associate with SSRI response. Thickening of the rostral anterior cingulate cortex in the first week of treatment was associated with better 8-week responses to SSRI (p = 0.010). These findings indicate that frontal lobe structural alterations in the first week of treatment may be associated with long-term treatment efficacy. While these associational findings may help to elucidate the specific neural targets of SSRIs, the predictive accuracy of pretreatment or early-treatment structural alterations in classifying treatment remitters from nonremitters was limited to 63.9%. Therefore, in this large sample of adults with MDD, structural MR imaging measures were not found to be clinically translatable biomarkers of treatment response to SSRI or placebo.

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Neuroimaging biomarkers as predictors of treatment outcome in Major Depressive Disorder

Cited by 140 publications

References 109 publications

Dimensional Anhedonia and the Adolescent brain: Reward and Aversion Anticipation, Effort and Consummation: Anhedonia in adolescent depression

Dimensional Anhedonia and the Adolescent brain: Reward and Aversion Anticipation, Effort and Consummation: Anhedonia in adolescent depression

Focal application of accelerated iTBS results in global changes in graph measures

Pretreatment and early-treatment cortical thickness is associated with SSRI treatment response in major depressive disorder

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