Cluster analysis with MOODS‐SR illustrates a potential bipolar disorder risk phenotype in young adults with remitted major depressive disorder

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147140/1/bdi12693_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147140/2/bdi12693.pd

Developmental changes in resting‐state functional networks among individuals with and without internalizing psychopathologies

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147755/1/da22864.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147755/2/da22864_am.pd

Stability of Networks in Young Adults in Remission from Major Depressive Disorder

Although neurobiological research has pushed for determining biomarkers of major depressive disorder (MDD), the test-retest reliability of functional connectivity resting-state magnetic resonance imaging (fc-rsMRI) has not been assessed. Individuals with MDD and those in remission from MDD typically show increased fc-rsMRI within the default mode network (DMN), characterized as a set of regions coordinated in activity during mind-wandering or rest. Evidence in MDD also suggests aberrant connectivity between the DMN and cognitive control network (CCN) responsible for task- and attention-switching. Thus, a reliable within-DMN and between-network connectivity may provide an opportune window for further exploring depression etiology. The current study examined correlations of spontaneous blood oxygen level dependent activity both within the DMN (ventral and core DMN subcomponents) and between-networks (DMN – CCN subcomponents) over two time points in 82 individuals either with remitted (r) MDD (n = 47) or as Healthy Controls (HC; n = 35) to further classify the reliability of the networks and abnormalities in MDD. Linear Mixed Effects (LMEs) models showed that rMDD have a stable hyperconnectivity within DMN subcomponents and between cDMN and CCN subcomponents, but show no abnormality between vDMN and CCN subcomponents. In addition, rMDD showed more reliable connectivity over time than healthy controls, suggesting these network correlations are stable disease markers. The specificity of these findings has implications for future examinations of malleable treatment targets (i.e., vDMN – CCN connectivity) and stable disease markers that can identify those most at risk for developing the disorder (i.e., cDMN – CCN connectivity)

Malleability of rumination: An exploratory model of CBT-based plasticity and long-term reduced risk for depressive relapse among youth from a pilot randomized clinical trial.

Clinical trials registrationNCT01905267, https://clinicaltrials.gov/ct2/show/NCT01905267

A lifespan model of interference resolution and inhibitory control: Risk for depression and changes with illness progression

The cognitive processes involved in inhibitory control accuracy (IC) and interference resolution speed (IR) or broadly - inhibition - are discussed in this review, and both are described within the context of a lifespan model of mood disorders. Inhibitory control (IC) is a binary outcome (success or no for response selection and inhibition of unwanted responses) for any given event that is influenced to an extent by IR. IR refers to the process of inhibition, which can be manipulated by task design in earlier and later stages through use of distractors and timing, and manipulation of individual differences in response proclivity. We describe the development of these two processes across the lifespan, noting factors that influence this development (e.g., environment, adversity and stress) as well as inherent difficulties in assessing IC/IR prior to adulthood (e.g., cross-informant reports). We use mood disorders as an illustrative example of how this multidimensional construct can be informative to state, trait, vulnerability and neuroprogression of disease. We present aggregated data across numerous studies and methodologies to examine the lifelong development and degradation of this subconstruct of executive function, particularly in mood disorders. We highlight the challenges in identifying and measuring IC/IR in late life, including specificity to complex, comorbid disease processes. Finally, we discuss some potential avenues for treatment and accommodation of these difficulties across the lifespan, including newer treatments using cognitive remediation training and neuromodulation

Multivariate imaging-genetics study of MRI gray matter volume and SNPs reveals biological pathways correlated with brain structural differences in Attention Deficit Hyperactivity Disorder

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder affecting children, adolescents, and adults. Its etiology is not well-understood, but it is increasingly believed to result from diverse pathophysiologies that affect the structure and function of specific brain circuits. Although one of the best-studied neurobiological abnormalities in ADHD is reduced fronto-striatal-cerebellar gray matter volume, its specific genetic correlates are largely unknown. Methods: In this study, T1-weighted MR images of brain structure were collected from 198 adolescents (63 ADHD-diagnosed). A multivariate parallel independent component analysis technique (Para-ICA) identified imaging-genetic relationships between regional gray matter volume and single nucleotide polymorphism data. Results: Para-ICA analyses extracted 14 components from genetic data and 9 from MR data. An iterative cross-validation using randomly-chosen sub-samples indicated acceptable stability of these ICA solutions. A series of partial correlation analyses controlling for age, sex, and ethnicity revealed two genotype-phenotype component pairs significantly differed between ADHD and non-ADHD groups, after a Bonferroni correction for multiple comparisons. The brain phenotype component not only included structures frequently found to have abnormally low volume in previous ADHD studies, but was also significantly associated with ADHD differences in symptom severity and performance on cognitive tests frequently found to be impaired in patients diagnosed with the disorder. Pathway analysis of the genotype component identified several different biological pathways linked to these structural abnormalities in ADHD. Conclusions: Some of these pathways implicate well-known dopaminergic neurotransmission and neurodevelopment hypothesized to be abnormal in ADHD. Other more recently implicated pathways included glutamatergic and GABA-eric physiological systems; others might reflect sources of shared liability to disturbances commonly found in ADHD such as sleep abnormalities

Cognitive control neuroimaging measures differentiate between those with and without future recurrence of depression

Background: Major Depressive Disorder (MDD) is a prevalent, disruptive illness. A majority of those with MDD are at high risk for recurrence and increased risk for morbidity and mortality. This study examined whether multimodal baseline (and retest) Cognitive Control performance and neuroimaging markers (task activation and neural connectivity between key brain nodes) could differentiate between those with and without future recurrence of a major depressive (MD) episode within one year. We hypothesized that performance and neuroimaging measures of Cognitive Control would identify markers that differ between these two groups. Methods: A prospective cohort study of young adults (ages 18–23) with history (h) of early-onset MDD (N = 60), now remitted, and healthy young adults (N = 49). Baseline Cognitive Control measures of performance, task fMRI and resting state connectivity (and reliability retest 4–12 weeks later) were used to compare those with future recurrence of MDD (N = 21) relative to those without future recurrence of MDD (N = 34 with resilience). The measures tested were (1) Parametric Go/No-Go (PGNG) performance, and task activation for (2) PGNG Correct Rejections, (3) PGNG Commission errors, and (4 & 5), resting state connectivity analyses of Cognitive Control Network to and from subgenual anterior cingulate. Results: Relative to other groups at baseline, the group with MDD Recurrence had less bilateral middle frontal gyrus activation during commission errors. MDD Recurrence exhibited greater connectivity of right middle frontal gyrus to subgenual anterior cingulate (SGAC). SGAC connectivity was also elevated in this group to numerous regions in the Cognitive Control Network. Moderate to strong ICCs were present from test to retest, and highest for rs-fMRI markers. There were modest, significant correlations between task, connectivity and behavioral markers that distinguished between groups. Conclusion: Markers of Cognitive Control function could identify those with early course MD who are at risk for depression recurrence. Those at high risk for recurrence would benefit from maintenance or preventative treatments. Future studies could test and validate these markers as potential predictors, accounting for sample selection and bias in feature detection

Reliability, Convergent Validity and Time Invariance of Default Mode Network Deviations in Early Adult Major Depressive Disorder

There is substantial variability across studies of default mode network (DMN) connectivity in major depressive disorder, and reliability and time-invariance are not reported. This study evaluates whether DMN dysconnectivity in remitted depression (rMDD) is reliable over time and symptom-independent, and explores convergent relationships with cognitive features of depression. A longitudinal study was conducted with 82 young adults free of psychotropic medications (47 rMDD, 35 healthy controls) who completed clinical structured interviews, neuropsychological assessments, and 2 resting-state fMRI scans across 2 study sites. Functional connectivity analyses from bilateral posterior cingulate and anterior hippocampal formation seeds in DMN were conducted at both time points within a repeated-measures analysis of variance to compare groups and evaluate reliability of group-level connectivity findings. Eleven hyper- (from posterior cingulate) and 6 hypo- (from hippocampal formation) connectivity clusters in rMDD were obtained with moderate to adequate reliability in all but one cluster (ICC's range = 0.50 to 0.76 for 16 of 17). The significant clusters were reduced with a principle component analysis (5 components obtained) to explore these connectivity components, and were then correlated with cognitive features (rumination, cognitive control, learning and memory, and explicit emotion identification). At the exploratory level, for convergent validity, components consisting of posterior cingulate with cognitive control network hyperconnectivity in rMDD were related to cognitive control (inverse) and rumination (positive). Components consisting of anterior hippocampal formation with social emotional network and DMN hypoconnectivity were related to memory (inverse) and happy emotion identification (positive). Thus, time-invariant DMN connectivity differences exist early in the lifespan course of depression and are reliable. The nuanced results suggest a ventral within-network hypoconnectivity associated with poor memory and a dorsal cross-network hyperconnectivity linked to poorer cognitive control and elevated rumination. Study of early course remitted depression with attention to reliability and symptom independence could lead to more readily translatable clinical assessment tools for biomarkers

Self-Injury in Adolescence Is Associated with Greater Behavioral Risk Avoidance, Not Risk-Taking

Strategies to link impulsivity and self-injurious behaviors (SIBs) show highly variable results, and may differ depending on the impulsivity measure used. To better understand this lack of consistency, we investigated correlations between self-report and behavioral impulsivity, inhibitory control, SIBs, and rumination. We included participants aged 13–17 years with either current or remitted psychopathology who have (n = 31) and who do not have (n = 14) a history of SIBs. Participants completed self-report measures of impulsivity, the Rumination Responsiveness Scale (RRS), and two behavioral measures of impulsivity: the Balloon Analogue Risk Task (BART) and Parametric Go/No-Go (PGNG). Lifetime SIBs were positively associated with self-reported impulsivity, specifically positive and negative urgency. However, individuals with greater lifetime SIBs demonstrated greater risk aversion (lower impulsivity) as measured by the BART, whereas there was no relation between lifetime SIBs and PGNG performance. There was no relation between rumination and behavioral impulsivity, although greater rumination was associated with higher negative urgency. Future research examining the role of SIBs in the context of active versus remitted psychopathology is warranted. Because most adolescents were remitted from major depressive disorder at the time of study, follow-up studies can determine if lower risk-taking may aid individuals with more prior SIBs to achieve and maintain a remitted state