Major depressive disorder (MDD) is considered the current leading cause of disability worldwide (Friedrich, 2017), yet the recovery process in MDD, including neurobiological underpinnings, clinical features and optimal approaches to treatment remains ambiguous. Current definitions of recovery are disputed and involve measures considered subjective in nature, such as thresholds for questionnaires and clinical interviews of symptoms and their duration (De Zwart and Jeronimus, 2019; Fava et al., 2007; Keller, 2003, 2004). Symptom-based measures, although informative of clinical presentation, are not informative of neurobiological underpinnings that may persist even when symptoms are reduced. Indeed, even after treatment, persistent residual symptoms, impairments in quality of life, and vulnerabilities for future return to more severe psychopathology persist (Gotlib and Hammen, 2008; IsHak et al., 2011; Judd et al., 1998a; Kennedy et al., 2004; Kennedy and Foy, 2005; Kennedy and Paykel, 2004). Without assessment of neural mechanisms of recovery in MDD, efforts toward developing novel treatment approaches that are able to address neural processes of illness and to provide sustained remission are slowed. The following collection of studies provide neural and clinical insights into MDD recovery and relate findings to potential treatment approaches that are optimized to individual differences in symptoms and neural functioning and able to address neural vulnerabilities to provide sustained remission. In pursuit of individualized treatment selection in MDD, study one involved a meta-analysis of prior prognostic fMRI studies of response to cognitive behavioral therapy (CBT) or a selective serotonin reuptake inhibitor (SSRI) in MDD. Study one also reported on the application of
resulting meta-analytic regions (subgenual and perigenual anterior cingulate cortex) in a confirmatory MDD sample. Although regions showed some predictive potential in the confirmatory sample, when predicting SSRI response, effects were inconsistent with prior studies, suggesting methodological confounds may hinder ready translation. In an assessment of the course of MDD, the second study documented depression symptoms and quality of life across 9-14 years after acute treatment (CBT or SSRI) and found that persistent residual depression symptoms and quality of life deficits were common. In light of the normality of chronic symptoms and impairment, the third study evaluated neural features of treatment (CBT) resistance in MDD within the context of neural mechanisms of change. The third study found a vermis-centered cerebellar cluster that was unresponsive to CBT, whereas prefrontal and parietal cortical regions were responsive, providing support of prior theories that CBT directly affects cognitive control and cortical regulatory processes in contrast to salience-driven subcortical functioning (Clark and Beck, 2010; DeRubeis et al., 2008; Frewen et al., 2008; Mayberg, 2003). In consideration of findings, clinical recommendations that pertain to treating residual symptoms and associated neural features toward asymptomatic remission are provided. Future research directions are also provided regarding neuroscience informed precision medicine, current therapy and medication practices, and the larger picture of MDD chronicity broadly. / Doctor of Philosophy / Major depressive disorder (MDD) is considered the leading cause of disability worldwide (Friedrich, 2017), yet there are many aspects of MDD recovery that are unclear such as neural and clinical features and optimal treatment approaches. Current definitions of recovery involve questionnaires and interviews, which may not accurately represent all aspects of recovery (De Zwart and Jeronimus, 2019; Fava et al., 2007; Keller, 2003, 2004). For example, they do not assess neural or biological features of recovery that may continue even if symptoms improve. Indeed, even after treatment, often some minimal depression symptoms, impairments in quality of life, and risks for future more severe symptoms continue (Gotlib and Hammen, 2008; IsHak et al., 2011; Judd et al., 1998a; Kennedy et al., 2004; Kennedy and Foy, 2005; Kennedy and Paykel, 2004). Without assessing neural features of MDD and recovery, developing treatments that can address illness- related neural features and provide sustained recovery are slowed. The following studies report on neural and clinical features of MDD recovery to approach treatment and sustained recovery with consideration of individual differences in symptoms and neural functioning. Pursuing neuroimaging measures of individual differences to inform treatment selection, study one involved a statistical review of prior neuroimaging prediction studies of MDD treatment. Study one also reported on whether the regions suggested by the statistical review to inform treatment selection would be useful when applied to a prior MDD treatment study. Findings suggested functioning of the identified brain regions can help inform treatment selection, but method differences among studies included in the review hinder application of resulting regions. In an assessment of the course of MDD, the second study documented depression symptoms and quality of life across 9-14 years after treatment and found at least minimal depression symptoms as well as impairments in quality life commonly continued after treatment. In light of persistent symptoms and impairment, the third study aimed to identify neural features of MDD that did not respond to treatment, as well as neural features that were responsive to treatment. The third study found that therapy directly affects cognitive control processes, but may not affect brain regions associated more with emotion-driven processes. Clinical recommendations pertain to treating depression symptoms that continue after treatment toward asymptomatic recovery. Future research directions pertain to neuroscience informed treatment selection, current therapy and medication practices, and the larger picture of persistent depression symptoms broadly.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/112938 |
| Date | 24 June 2021 |
| Creators | Strege, Marlene Vernette |
| Contributors | Psychology, Richey, John A., Kim-Spoon, Jungmeen, Siegle, Greg, Lee, Tae-Ho, Chiu, Pearl H. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf, application/msword |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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