Unlocking the Potential of Effective Connectivity as a Neuroimaging Biomarker: A Path Toward Personalized Depression Treatment in Youth

Depression is a common and devastating mental illness with a peak age at onset of 19.5 years ( 1 Solmi M. Radua J. Olivola M. Croce E. Soardo L. Salazar de Pablo G. et al. Age at onset of mental disorders worldwide: Large-scale meta-analysis of 192 epidemiological studies. Mol Psychiatry. 2022; 27: 281-295 Crossref PubMed Scopus (703) Google Scholar ) and is a leading contributor to the burden of disease in youth ages 10 to 24 years ( 2 Mokdad A.H. Forouzanfar M.H. Daoud F. Mokdad A.A. Bcheraoui C.E. Moradi-Lakeh M. et al. Global burden of diseases, injuries, and risk factors for young people’s health during 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2016; 387: 2383-2401 Abstract Full Text Full Text PDF PubMed Scopus (650) Google Scholar ). Adolescents with depression are at increased risk for suicidal thoughts and behaviors, and depression represents a top cause of death in adolescents ( 3 Thapar A. Collishaw S. Pine D.S. Thapar A.K. Depression in adolescence. Lancet. 2012; 379: 1056-1067 Abstract Full Text Full Text PDF PubMed Scopus (1422) Google Scholar ). Moreover, earlier onset of depression is associated with adverse psychosocial outcomes and more severe depressive symptomatology ( 4 Zisook S. Lesser I. Stewart J.W. Wisniewski S.R. Balasubramani G.K. Fava M. et al. Effect of age at onset on the course of major depressive disorder. Am J Psychiatry. 2007; 164: 1539-1546 Crossref PubMed Scopus (357) Google Scholar ). Alarmingly, over the past decade, rates of depression have increased by 52% in adolescents ages 12 to 17 and 63% in young adults ages 18 to 25, with corresponding increases in suicidal thoughts and behaviors ( 5 Twenge J.M. Cooper A.B. Joiner T.E. Duffy M.E. Binau S.G. Age, period, and cohort trends in mood disorder indicators and suicide-related outcomes in a nationally representative dataset, 2005–2017. J Abnorm Psychol. 2019; 128: 185-199 Crossref PubMed Scopus (661) Google Scholar ). Together, these data underscore the critical importance of timely and effective treatment of depression in youth. SEE CORRESPONDING ARTICLE ON PAGE 959 SEE CORRESPONDING ARTICLE ON PAGE 959 Frontoamygdalar Effective Connectivity in Youth Depression and Treatment ResponseBiological PsychiatryVol. 94Issue 12PreviewEmotion regulation deficits are characteristic of youth depression and are underpinned by altered frontoamygdalar function. However, the causal dynamics of frontoamygdalar pathways in depression and how these dynamics relate to treatment prognosis remain unexplored. This study aimed to assess frontoamygdalar effective connectivity during cognitive reappraisal in youths with depression and to test whether pathway dynamics are predictive of individual response to combined cognitive behavioral therapy plus treatment with fluoxetine or placebo. Full-Text PDF Open Access