Characterizing major depressive disorder and substance use disorder using heatmaps and variable interactions: The utility of operant behavior and brain structure relationships

PLoS One. 2024 Mar 11;19(3):e0299528. doi: 10.1371/journal.pone.0299528. eCollection 2024.

Abstract

Background: Rates of depression and addiction have risen drastically over the past decade, but the lack of integrative techniques remains a barrier to accurate diagnoses of these mental illnesses. Changes in reward/aversion behavior and corresponding brain structures have been identified in those with major depressive disorder (MDD) and cocaine-dependence polysubstance abuse disorder (CD). Assessment of statistical interactions between computational behavior and brain structure may quantitatively segregate MDD and CD.

Methods: Here, 111 participants [40 controls (CTRL), 25 MDD, 46 CD] underwent structural brain MRI and completed an operant keypress task to produce computational judgment metrics. Three analyses were performed: (1) linear regression to evaluate groupwise (CTRL v. MDD v. CD) differences in structure-behavior associations, (2) qualitative and quantitative heatmap assessment of structure-behavior association patterns, and (3) the k-nearest neighbor machine learning approach using brain structure and keypress variable inputs to discriminate groups.

Results: This study yielded three primary findings. First, CTRL, MDD, and CD participants had distinct structure-behavior linear relationships, with only 7.8% of associations overlapping between any two groups. Second, the three groups had statistically distinct slopes and qualitatively distinct association patterns. Third, a machine learning approach could discriminate between CTRL and CD, but not MDD participants.

Conclusions: These findings demonstrate that variable interactions between computational behavior and brain structure, and the patterns of these interactions, segregate MDD and CD. This work raises the hypothesis that analysis of interactions between operant tasks and structural neuroimaging might aide in the objective classification of MDD, CD and other mental health conditions.

MeSH terms

  • Brain / diagnostic imaging
  • Depressive Disorder, Major* / diagnostic imaging
  • Humans
  • Magnetic Resonance Imaging
  • Substance-Related Disorders* / psychology

Grants and funding

H.B. received funding from the Office of Naval Research (ONR award, N00014-21-1-2216; https://www.nre.navy.mil/work-with-us/funding-opportunities). H.B. and A.K. received funding from the Office of Naval Research (ONR award, N00014-23-1-2396. This funder had no roles in study design, data collection and analysis, decision to publish, or preparation of the manuscript. H.B. received funding from National Institute on Drug Abuse (#14118, 026002, 026104, 027804; https://nida.nih.gov/funding/nida-funding-opportunities). The funders had no roles in study design, data collection and analysis, decision to publish, or preparation of the manuscript. H.B. received funding from The Phenotype Genotype Project in Addiction and Mood Disorder from the Office of National Drug Control Policy - Counterdrug Technology Assessment Center (DABK39-03-0098 & DABK39-03-C-0098; https://www.whitehouse.gov/ondcp/). The funders had no roles in study design, data collection and analysis, decision to publish, or preparation of the manuscript.