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

Abstract

Objectives: Delays in the diagnosis and detection of bipolar disorder can lead to adverse consequences, including improper treatment and increased suicide risk. The Mood Spectrum Self-Report Measure (MOODS-SR) was designed to capture the full spectrum of lifetime mood symptomology with factor scores for depression and mania symptom constellations. The utility of the MOODS-SR as a tool to investigate homogenous subgroups was examined, with particular focus on a possible bipolar risk subgroup. Moreover, potential patterns of differences in MOODS-SR subtypes were probed using cognitive vulnerabilities, neuropsychological functioning, and ventral striatum connectivity. Methods: K-mean cluster analysis based upon factor scores of MOODS-SR was used to determine homogenous subgroupings within a healthy and remitted depressed young adult sample (N=86). Between-group comparisons (based upon cluster sub-groupings) were conducted on measures of cognitive vulnerabilities, neuropsychological functioning, and ventral striatum rs-fMRI connectivity. Results: Three groups of participants were identified: one with minimal symptomology, one with moderate primarily depressive symptomology, and one with more severe manic and depressive symptomology. Differences in impulsivity, neuroticism, conscientiousness, facial perception accuracy, and rs-fMRI connectivity exist between moderate and severe groups. Conclusions: Within a sample of people with and without depression histories, a severe subgroup was identified with potentially increased risk of developing bipolar disorder through use of the MOODS-SR. This small subgroup had higher levels of lifetime depression and mania symptoms. Additionally, differences in traits, affective processing, and connectivity exist between those with a more prototypic unipolar subgrouping and those with potential risk for developing bipolar disorder.

Cognitive Control as a 5-HT1A-Based Domain That Is Disrupted in Major Depressive Disorder

“…Those with higher/normative5-HT 1A BP ND 5-HT 1A BP ND levels tended to have worse Negative Memory Bias, Inhibitory Control, and increased BOLD recruitment for successful rejection of prepotent stimuli. Although the sample is quite small, these results reaffirm with other work that there likely many circuits, neurotransmitters, and behaviors associated with subtypes of MDD that are heretofore unclear (Webb et al, 2016; Kling et al, 2018).…”

Changes in Intrinsic Brain Connectivity in Family-Focused Therapy Versus Standard Psychoeducation Among Youths at High Risk for Bipolar Disorder

“…Studies comparing intrinsic connectivity in patients with unipolar and bipolar depression (or those at risk) support this finding, suggesting that increased DMN connectivity represents both a predictor of depression treatment response across mood disorders, 49 and a feature that distinguishes unipolar from bipolar risk in young adults with remitted depression. 54 Other studies have suggested that hyperactivity of VLPFC and stronger connectivity to other high-order networks important for emotion regulation and executive control may represent a biomarker of adaptation toward more resilient outcomes, buffering high-risk offspring from developing BD. 13,55 It is the interpretation of increased strength of VLPFC connectivity as compensatory for early mood symptoms in these HR youths that brings the treatment groupÀby-time interaction finding into context.…”

Patterns of Neural Network Functional Connectivity Associated With Mania/Hypomania and Depression Risk in 3 Independent Young Adult Samples

“… 11 , 12 , 13 The manic mood domain in particular discriminates between individuals with BD vs unipolar depression, 11 , 13 , 14 highlighting the potential of this scale to screen for mania/hypomania and thus BD-specific risk in young adults on the BD spectrum, some of whom might already be diagnosed with unipolar depression. 15 , 16 …”

“…The few studies assessing neural markers of mania/hypomania risk in young adults reported similar findings of reward-related striatal and SN (insula) and emotional regulation–related amygdala hyperactivity in individuals who were hypomania prone vs control individuals 36 , 37 ; positive associations between mania/hypomania risk (measured by the MOODS-SR) and SN activity during reward processing 38 , 39 ; and reduced resting-state functional connectivity between the ventral striatum and CEN regions in individuals at highest risk for BD. 15 Studies in familial at-risk populations (eg, offspring of individuals affected by BD) and youth affected by BD similarly reported altered amygdala, striatal, CEN, and VAN or SN activity and altered amygdala-VAN and amygdala-SN functional connectivity during emotion processing and emotional regulation. 40 , 41 , 42 , 43 Yet, although childhood-onset BD is a more severe form of BD, 44 it is less common than adult-onset BD.…”