Differentiating the Effects of Familial Risk for Alcohol Dependence and Prenatal Exposure to Alcohol on Offspring Brain Morphology

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Abstract

<div class="section"> <a class="named-anchor" id="S1">  </a> <h5 class="section-title" id="d3704226e123">BACKGROUND</h5> <p id="P1">Offspring with a family history of alcohol dependence (AD) have been shown to have altered structural and functional integrity of corticolimbic brain structures. Similarly, prenatal exposure to alcohol is associated with a variety of structural and functional brain changes. The goal of this study was to differentiate the brain gray matter volumetric differences associated with familial risk and prenatal exposure to alcohol among offspring while controlling for lifetime personal exposures to alcohol and drugs. </p> </div><div class="section"> <a class="named-anchor" id="S2">  </a> <h5 class="section-title" id="d3704226e128">METHODS</h5> <p id="P2">A total of 52 high-risk (HR) offspring from maternal multiplex families with a high proportion of alcohol dependence were studied along with 55 low-risk (LR) offspring. Voxel based morphometric (VBM) analysis was performed using statistical parametric mapping (SPM8) software using 3T structural images from these offspring to identify gray matter volume differences associated with familial risk and prenatal exposure. </p> </div><div class="section"> <a class="named-anchor" id="S3">  </a> <h5 class="section-title" id="d3704226e133">RESULTS</h5> <p id="P3">Significant familial risk group differences were seen with HR males showing reduced volume of the left inferior temporal, left fusiform and left and right insula regions relative to LR males, controlling for prenatal exposure to alcohol drugs and cigarettes. High-risk females showed a reduction in the right fusiform but also showed a reduction in volume in portions of the cerebellum (left crus I and left lobe 8). Prenatal alcohol exposure effects, assessed within the familial high-risk group, was associated with reduced right middle cingulum and left middle temporal volume. Even low exposure resulting from mothers drinking in amounts less than the median of those who drank (53 drinks or less over the course of the pregnancy) showed a reduction of volume in the right anterior cingulum and in the left cerebellum (lobes 4 and 5). </p> </div><div class="section"> <a class="named-anchor" id="S4">  </a> <h5 class="section-title" id="d3704226e138">CONCLUSIONS</h5> <p id="P4">Familial risk for alcohol dependence and prenatal exposure to alcohol and other drugs show independent effects on brain morphology. </p> </div>

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Most cited references 38

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Martin M. Riccomagno, Alex Kolodkin (2015)

The assembly of functional neural circuits requires the combined action of progressive and regressive events. Regressive events encompass a variety of inhibitory developmental processes, including axon and dendrite pruning, which facilitate the removal of exuberant neuronal connections. Most axon pruning involves the removal of axons that had already made synaptic connections; thus, axon pruning is tightly associated with synapse elimination. In many instances, these developmental processes are regulated by the interplay between neurons and glial cells that act instructively during neural remodeling. Owing to the importance of axon and dendritic pruning, these remodeling events require precise spatial and temporal control, and this is achieved by a range of distinct molecular mechanisms. Disruption of these mechanisms results in abnormal pruning, which has been linked to brain dysfunction. Therefore, understanding the mechanisms of axon and dendritic pruning will be instrumental in advancing our knowledge of neural disease and mental disorders.

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The insula: a critical neural substrate for craving and drug seeking under conflict and risk.

Nasir H Naqvi, Natassia Gaznick, Daniel Tranel … (2014)

Drug addiction is characterized by the inability to control drug use when it results in negative consequences or conflicts with more adaptive goals. Our previous work showed that damage to the insula disrupted addiction to cigarette smoking-the first time that the insula was shown to be a critical neural substrate for addiction. Here, we review those findings, as well as more recent studies that corroborate and extend them, demonstrating the role of the insula in (1) incentive motivational processes that drive addictive behavior, (2) control processes that moderate or inhibit addictive behavior, and (3) interoceptive processes that represent bodily states associated with drug use. We then describe a theoretical framework that attempts to integrate these seemingly disparate findings. In this framework, the insula functions in the recall of interoceptive drug effects during craving and drug seeking under specific conditions where drug taking is perceived as risky and/or where there is conflict between drug taking and more adaptive goals. We describe this framework in an evolutionary context and discuss its implications for understanding the mechanisms of behavior change in addiction treatments. © 2014 New York Academy of Sciences.