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Major Depressive Disorder Across Development and Course of Illness: A Functional Neuroimaging Meta-Analysis
- C. Baten, A. M. Klassen, J. H. Shepherd, G. Zamora, E. Pritchard, S. Saravia, Z. Ali, J. Jordan, S. K. Kahlon, G. Maly, M. Duran, S. Santos, A. F. Nimarko, D. W. Hedges, P. Hamilton, I. H. Gotlib, M. D. Sacchet, C. H. Miller
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S345-S346
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Introduction
Functional magnetic resonance imaging (fMRI) has been used to identify the neural activity of both youth and adults diagnosed with major depressive disorder (MDD) in comparison to healthy age-matched controls. Previously reported abnormalities in depressed youth appear to mostly align with those found in depressed adults; however, some of the reported aberrant brain activity in youth has not been consistent with what is observed in adults, and to our knowledge there has not yet been a formal, quantitative comparison of these two groups. In addition, it is not known whether these observed differences between youth and adults with depression are attributable to developmental age or length-of-illness.
ObjectivesThe aim of this study is to elucidate the similarities and differences in patterns of abnormal neural activity between adults and youth diagnosed with MDD and to then determine whether these observed differences are due to either developmental age or length-of-illness.
MethodsWe used multilevel kernel density analysis (MKDA) with ensemble thresholding and triple subtraction to separately determine neural abnormalities throughout the whole brain in primary studies of depressed youth and depressed adults and then directly compare the observed abnormalities between each of those age groups. We then conducted further comparisons between multiple subgroups to control for age and length-of-illness and thereby determine the source of the observed differences between youth and adults with depression.
ResultsAdults and youth diagnosed with MDD demonstrated reliable, differential patterns of abnormal activation in various brain regions throughout the cerebral cortex that are statistically significant (p < .05; FWE-corrected). In addition, several of these brain regions that exhibited differential patterns of neural activation between the two age groups can be reliably attributed to either developmental age or length-of-illness.
ConclusionsThese findings indicate that there are common and disparate patterns of brain activity between youth and adults with MDD, several of which can be reliably attributed to developmental age or length-of-illness. These results expand our understanding of the neural basis of depression across development and course of illness and may be used to inform the development of new, age-specific clinical treatments as well as prevention strategies for this disorder.
Disclosure of InterestNone Declared
Major Depressive Disorder in Youth: A Meta-Analysis of Functional Magnetic Resonance Imaging Studies
- G. Zamora, C. Baten, A. M. Klassen, J. H. Shepherd, E. Pritchard, S. Saravia, Z. Ali, J. Jordan, S. K. Kahlon, G. Maly, M. Duran, S. L. Santos, A. F. Nimarko, D. W. Hedges, J. P. Hamilton, I. H. Gotlib, M. D. Sacchet, C. H. Miller
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S219-S220
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Introduction
Major depressive disorder (MDD) is a highly prevalent mental illness that frequently originates in early development and is pervasive during adolescence. Despite its high prevalence and early age of onset, our understanding of the potentially unique neural basis of MDD in this age group is still not well understood, and the existing primary literature on the topic includes many new and divergent results. This limited understanding of MDD in youth presents a critical need to further investigate its neural basis in youth and presents an opportunity to also improve clinical treatments that target its neural abnormalities.
ObjectivesThe present study aims to advance our understanding of the neural basis of MDD in youth by identifying abnormal functional activation in various brain regions compared with healthy controls.
MethodsWe conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of MDD by using a well-established method, multilevel kernel density analysis (MKDA) with ensemble thresholding, to quantitatively combine all existing whole-brain fMRI studies of MDD in youth compared with healthy controls. This method involves a voxel-wise, whole-brain approach, that compares neural activation of patients with MDD to age-matched healthy controls across variations of task-based conditions, which we subcategorize into affective processing, executive functioning, positive valence, negative valence, and symptom provocation tasks.
ResultsYouth with MDD exhibited statistically significant (p<0.05; FWE-corrected) hyperactivation and hypoactivation in multiple brain regions compared with age-matched healthy controls. These results include significant effects that are stable across various tasks as well as some that appear to depend on task conditions.
ConclusionsThis study strengthens our understanding of the neural basis of MDD in youth and may also be used to help identify possible similarities and differences between youth and adults with depression. It may also help inform the development of new treatment interventions and tools for predicting unique treatment responses in youth with depression.
Disclosure of InterestNone Declared
The Neural Basis of Major Depressive Disorder in Adults: A Meta-Analysis of Functional Magnetic Resonance Imaging Activation Studies
- A. M. Klassen, C. Baten, J. H. Shepherd, G. Zamora, S. Saravia, E. Pritchard, Z. Ali, J. Jordan, S. K. Kahlon, G. Maly, M. Duran, S. L. Santos, A. F. Nimarko, D. W. Hedges, J. P. Hamilton, I. H. Gotlib, M. D. Sacchet, C. H. Miller
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S158
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Introduction
Major depressive disorder (MDD) is a highly prevalent mental illness that often first occurs or persists into adulthood and is considered the leading cause of disability and disease burden worldwide. Unfortunately, individuals diagnosed with MDD who seek treatment often experience limited symptom relief and may not achieve long-term remission, which is due in part to our limited understanding of its underlying pathophysiology. Many studies that use task-based functional magnetic resonance imaging (fMRI) have found abnormal activation in brain regions in adults diagnosed with MDD, but those findings are often inconsistent; in addition, previous meta-analyses that quantitatively integrate this large body literature have found conflicting results.
ObjectivesThis meta-analysis aims to advance our understanding of the neural basis of MDD in adults, as measured by fMRI activation studies, and address inconsistencies and discrepancies in the empirical literature.
MethodsWe employed multilevel kernel density analysis (MKDA) with ensemble thresholding, a well-established method for voxel-wise, whole-brain meta-analyses, to conduct a quantitative comparison of all relevant primary fMRI activation studies of adult patients with MDD compared to age-matched healthy controls.
ResultsWe found that adults with MDD exhibited a reliable pattern of statistically significant (p<0.05; FWE-corrected) hyperactivation and hypoactivation in several brain regions compared to age-matched healthy controls across a variety of experimental tasks.
ConclusionsThis study supports previous findings that there is reliable neural basis of MDD that can be detected across heterogenous fMRI studies. These results can be used to inform development of promising treatments for MDD, including protocols for personalized interventions. They also provide the opportunity for additional studies to examine the specificity of these effects among various populations-of-interest, including youth vs. adults with depression as well as other related mood and anxiety disorders.
Disclosure of InterestNone Declared
Neural correlates of emotion processing predict resilience in youth at familial risk for mood disorders
- Akua F. Nimarko, Amy S. Garrett, Gabrielle A. Carlson, Manpreet K. Singh
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- Journal:
- Development and Psychopathology / Volume 31 / Issue 3 / August 2019
- Published online by Cambridge University Press:
- 08 May 2019, pp. 1037-1052
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Aberrant face emotion processing has been demonstrated in youth with and at a familial risk for bipolar and major depressive disorders. However, the neurobiological factors related to emotion processing that underlie resilience from youth-onset mood disorders are not well understood. Functional magnetic resonance imaging data during an implicit emotion processing task were collected at baseline from a sample of 50 youth, ages 8–17, who were healthy but also familially at high risk for either bipolar disorder or major depressive disorder, and 24 healthy controls with no family history of psychopathology (HCL). Participants were reevaluated 3 years later and classified into three groups for analysis: high-risk youth who converted to a psychiatric diagnosis (CVT; N = 23), high-risk youth who were resilient from developing any psychopathology (RES; N = 27), and HCL youth (N = 24) who remained healthy at follow-up. For happy > calm faces, the CVT and RES groups had significantly lower activation in the left inferior parietal lobe (IPL), while the RES group had lower activation in the right supramarginal gyrus. For fear > calm faces, the RES group had lower activation in the right precuneus and inferior frontal gyrus (IFG) compared to the CVT group. Connectivity analyses revealed the RES group exhibited higher left IPL connectivity with visual cortical regions for happy > calm faces, and higher IFG connectivity with frontal, temporal, and limbic regions for fear > calm faces. These connectivities were correlated with improvements in prosocial behaviors and global functioning. Our findings suggest that differential activation and connectivity in the IPL, IFG, and precuneus in response to emotional stimuli may represent distinct resilience and risk markers for youth-onset mood disorders.