Mesial Prefrontal Cortex and Alcohol Misuse: Dissociating Cross-sectional and Longitudinal Relationships in UK Biobank.


BACKGROUND: Alcohol misuse is a major global public health issue. The disorder is characterized by aberrant neural networks interacting with environment and genetics. Dissecting the neural substrates and functional networks that relate to longitudinal changes in alcohol use from those that relate to alcohol misuse cross-sectionally is important to elucidate therapeutic approaches. METHODS: To assess how neuroimaging data, including T1, resting-state functional magnetic resonance imaging, and diffusion-weighted imaging, relate to alcohol misuse cross-sectionally and longitudinally in the UK Biobank, this study analyzed range of alcohol misuse in a population-based normative sample of 24,784 participants, ages 45 to 81 years old, in a cross-sectional analysis and a sample of 3070 participants in a longitudinal analysis 2 years later. RESULTS: Cross-sectional analysis showed that alcohol use is associated with a reduction in dorsal anterior cingulate cortex and dorsomedial prefrontal cortex gray matter concentration and functional resting-state connectivity (nodal degree: t24,422 = -12.99, p < 1 × 10-17). Reduced dorsal anterior cingulate cortex/dorsomedial prefrontal cortex functional connections to the ventrolateral prefrontal cortex, amygdala, and striatum relate to greater alcohol use. In a longitudinal analysis, higher resting-state nodal degree (t3036 = -3.27, p = .0011) and T1 gray matter concentration in the ventromedial prefrontal cortex relate to reduced alcohol intake frequency 2 years later. Higher ventromedial prefrontal cortex and frontoparietal executive network functional connectivity is associated with lower subsequent drinking longitudinally. CONCLUSIONS: Dorsal versus ventromedial prefrontal regions are differentially related to alcohol misuse cross-sectionally or longitudinally in a large UK Biobank normative dataset. Our study provides a comprehensive understanding of the neurobiological substrates of alcohol use as a state or prospectively, thereby providing potential targets for clinical treatment.