脳構造の違いが薬物使用リスクに与える影響 (Brain structure differences provide clues to substance use risks)

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2025-01-07 ワシントン大学セントルイス校

ワシントン大学セントルイス校の研究者たちは、約10,000人の子供たちの脳スキャンを分析し、15歳未満で物質使用を開始した若者の脳構造に特定の特徴があることを発見しました。特に、前頭前野を含む皮質の構造に差異が見られ、これらが思春期の物質使用の開始に寄与している可能性が示唆されました。この研究は、物質使用障害の進行における脳の構造的要因の役割を再評価する必要性を強調しています。

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小児期後半から青年期前半における神経解剖学的変異と物質使用開始 Neuroanatomical Variability and Substance Use Initiation in Late Childhood and Early Adolescence

Alex P. Miller, PhD; David A. A. Baranger, PhD; Sarah E. Paul, MA; et al
JAMA Network Open  Published:December 30, 2024
DOI:10.1001/jamanetworkopen.2024.52027

脳構造の違いが薬物使用リスクに与える影響 (Brain structure differences provide clues to substance use risks)

Key Points

Question What are the neuroanatomical features associated with early substance use initiation, and do they precede initiation?

Findings In this cohort study of 9804 participants, variability in brain structure, including greater whole brain, cortical, and subcortical volumes, and thinner prefrontal cortex, but thicker cortex otherwise, was significantly associated with early (ie, age <15 years) substance use initiation (ie, alcohol, nicotine, cannabis, or other). The majority of brain structure features associated with substance use initiation were evident among substance-naive children at baseline who later initiated.

Meaning These findings suggest neurodevelopmental variability in brain structure may confer risk for early substance involvement.

Abstract

Importance The extent to which neuroanatomical variability associated with early substance involvement, which is associated with subsequent risk for substance use disorder development, reflects preexisting risk and/or consequences of substance exposure remains poorly understood.

Objective To examine neuroanatomical features associated with early substance use initiation and to what extent associations may reflect preexisting vulnerability.

Design, Setting, and Participants Cohort study using data from baseline through 3-year follow-up assessments of the ongoing longitudinal Adolescent Brain Cognitive Development Study. Children aged 9 to 11 years at baseline were recruited from 22 sites across the US between June 1, 2016, and October 15, 2018. Data were analyzed from February to September 2024.

Exposures Substance use initiation through 3-year follow-up (ie, age <15 years).

Main Outcomes and Measures Self-reported alcohol, nicotine, cannabis, and other substance use initiation and baseline magnetic resonance imaging (MRI)–derived estimates of brain structure (ie, global and regional cortical volume, thickness, surface area, sulcal depth, and subcortical volume). Covariates included family (eg, familial relationships), pregnancy (eg, prenatal exposure to substances), child (eg, sex and pubertal status), and MRI (eg, scanner model) variables.

Results Among 9804 children (mean [SD] baseline age, 9.9 [0.6] years; 5160 boys [52.6%]; 213 Asian [2.2%], 1474 Black [15.0%], 514 Hispanic/Latino [5.2%], 29 American Indian [0.3%], 10 Pacific Islander [0.1%], 7463 White [76.1%], and 75 other [0.7%]) with nonmissing baseline neuroimaging and covariate data, 3460 (35.3%) reported substance use initiation before age 15. Initiation of any substance or alcohol use was associated with thinner cortex in prefrontal regions (eg, rostral middle frontal gyrus, β = -0.03; 95% CI, -0.02 to -0.05; P = 6.99 × 10-6) but thicker cortex in all other lobes, larger globus pallidus and hippocampal volumes, as well as greater global indices of brain structure (eg, larger whole brain volume, β = 0.05; 95% CI, 0.03 to 0.06; P = 2.80 × 10-8) following Bonferroni or false discovery rate multiple testing correction. Cannabis use initiation was associated with lower right caudate volume (β = -0.03; 95% CI, -0.01 to -0.05; P = .002). Post hoc examinations restricting to postbaseline initiation suggested that the majority of associations, including thinner prefrontal cortex and greater whole brain volume, preceded initiation.

Conclusions and Relevance In this cohort study of children, preexisting neuroanatomical variability was associated with substance use initiation. In addition to putative neurotoxic effects of substance exposure, brain structure variability may reflect predispositional risk for initiating substance use earlier in life with potential cascading implications for development of later problems.

 

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