In recent times, more effort has been devoted to ascertaining effective screening methods for the early detection of, and subsequent intervention for, psychiatric conditions in children. Recent findings by Whitfield-Gabrieli et al. (2019) have suggested that resting-state functional MRI (fMRI) of children at the age of 7 may be effective in predicting the trajectory of major depressive disorder (MDD) and attention deficit hyperactivity disorder (ADHD) at 11 years of age.
In a 4-year longitudinal cohort study of 7-year olds recruited by Vanderbilt University, the authors sought to use fMRI to assess patterns of brain connectivity and how they changed over time, and to link these imaging findings to the course of development and evolution of MDD and ADHD.
Why these two conditions were chosen in particular stems from the fact that they both often transpire during childhood and early adolescence. Moreover, they are known as being conditions in which connectivity between vital developing brain structures is altered, a phenomenon detectable on fMRI, manifesting as changes in hemodynamic activity.
For instance, ADHD has been associated with an abnormal balance of neural connectivity within the default mode network (DMN) and adjacent task-positive networks. Moreover, MDD has been associated with reduced connectivity between the subgenual anterior cingulate cortex (sgACC) and inferior parietal lobule (IPL) and between left and right dorsolateral prefrontal cortices, suggesting that something is at play regarding neural circuitry here (Sudre et al., 2017; Hirshfeld-Becker et al., 2019).
The authors, concurrent with fMRI resting-state analyses of brain connections, regularly administered the Child Behavior Checklist (CBCL). This is a caregiver report screening for behavioral and psychological problems, ranging from the internalization of behaviors (associated with depression and anxiety) to thought and attention problems (associated with ADHD and ADD); it may be predictive of psychiatric conditions as well. (Achenbach & Rescorla, 2000).
What the authors found in the cohort was that inability to decouple connections between the dorsolateral prefrontal cortex (DLPFC) and the medial prefrontal cortex (mPFC) detected at age 7 was significantly associated with reductions in attention 4 years later based on CBCL scores. This is in line with the prior literature looking at the DMN/task-positive network connectivity imbalance. The mPFC is the core node of the DMN, and the DLPFC is the core node of the central executive task-positive network mentioned above. Decoupling between these two regions is required to be able to regulate attention between internal and external foci.
In other words, to be able to focus optimally, and reduce distractibility, these two networks need to be decoupled. Otherwise, one can easily get in the way of the other. Hence, failure to decouple these two networks may be an early neural pathway alteration transpiring before the symptomatic attentional deficits of ADHD.
Conversely, reduced coupling between the DLPFC and the subgenual anterior cingulate cortex (sgACC) was associated with increases in internalizing behaviors, as measured on the CBCL, 4 years later. The latter structure (sgACC) is associated with modulation of emotional behavior, so intuitively, this structure would be implicated in a depressive disorder (Drevets, Savitz, & Trimble, 2008).
Therefore, there appear to be neural pathway alterations, and specific ones at that, which can be, and have been now been detected from early on in MDD and ADHD. Moreover, they seem to be effective predictors in the subsequent development of these psychiatric disorders.
Larger Implications of These Findings
MDD and ADHD are highly prevalent disorders in society, particularly among our juvenile population. Over 17.3 million Americans are or have been affected by major depressive episodes (Weinberger et al., 2015). ADHD affects at least 6 to 7 percent of adolescents nationwide (Willcutt, 2012). Therefore, being able to detect neurobiological precursor changes to these conditions would be greatly beneficial to society in terms of being able to make crucial interventions to combat these conditions and prevent them from impairing their potential victims.
Much more future research will be needed both to substantiate these findings for ADHD and MDD, as well as to detect other changes in neural circuitry, exhibited early in life, which are—or may also be—associated with other psychiatric conditions. However, these findings further corroborate the fact that neurobiology is at play in mental health, and being able to use our imaging modalities to detect neurobiological changes early will allow us to respond with early, timely preventative treatment.
These findings are exciting and provide a reason for optimism in our quest to address psychiatric conditions like and beyond ADHD and MDD, for which our treatment modalities still remain ineffective due to neurobiological changes being irreparable by the time we intervene. This use of neuroimaging in the early detection of psychiatric conditions will augur well for the future.
Achenbach, T.M., & Rescorla, L.A. (2000). Manual for the ASEBA Preschool forms and Profiles. Burlington, VT: University of Vermont Department of Psychiatry. ISBN 0-938565-68-0
Drevets, W. C., Savitz, J., & Trimble, M. (2008). The subgenual anterior cingulate cortex in mood disorders. CNS spectrums, 13(8), 663.
Hirshfeld-Becker, D. R., Gabrieli, J. D., Shapero, B. G., Biederman, J., Whitfield-Gabrieli, S., & Chai, X. J. (2019). Intrinsic Functional Brain Connectivity Predicts Onset of Major Depression Disorder in Adolescence: A Pilot Study. Brain connectivity, 9(5), 388-398.
Sudre, G., Szekely, E., Sharp, W., Kasparek, S., & Shaw, P. (2017). Multimodal mapping of the brain’s functional connectivity and the adult outcome of attention deficit hyperactivity disorder. Proceedings of the National Academy of Sciences, 114(44), 11787-11792.
Weinberger, A. H., Gbedemah, M., Martinez, A. M., Nash, D., Galea, S., & Goodwin, R. D. (2018). Trends in depression prevalence in the USA from 2005 to 2015: widening disparities in vulnerable groups. Psychological medicine, 48(8), 1308-1315.
Whitfield-Gabrieli, S., Wendelken, C., Nieto-Castañón, A., Bailey, S. K., Anteraper, S. A., Lee, Y. J., ... & Bunge, S. A. (2019). Association of Intrinsic Brain Architecture With Changes in Attentional and Mood Symptoms During Development. JAMA psychiatry.
Willcutt E. G. (2012). The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 9(3), 490–499. doi:10.1007/s13311-012-0135-8