<p>Objectives. Alcohol-use disorders in adolescents are associated with gray matter (GM) abnormalities suggesting neurotoxicity by alcohol. However, recently similar GM abnormalities were found in non-drinking children with a family history (FH) of alcohol dependence (AD). The question thus rises whether these abnormalities represent a transient delay in brain maturation or a persistent risk factor for developing neuropsychiatric disorders, rather than a (neurotoxic) consequence of AD. This study investigated whether a FH of AD in non-drinking adults is associated with abnormal GM-volumes similar to those observed in drinking and non-drinking adolescents with a FH of AD. Methods. GM-images were analyzed using Voxel-Based Morphometry in non-alcoholics with (FH+; N = 36) and without (FH-; N = 107) familial AD. Additionally we controlled for possible confounders: diagnosis of depression/anxiety, childhood trauma and familial depression/ anxiety. Results. Smaller GM-volumes were shown in the right parahippocampal gyrus in FH+ compared with FH-. Results were unaffected by confounders. Conclusions. We demonstrated an effect of familial AD in non-alcoholic adults on GM volume in the parahippocampal gyrus, similar to drinking and non-drinking FH+ adolescents. These findings suggest that GM abnormalities in the parahippocampal gyrus represent a persistent biological susceptibility for AD or related psychopathology and not neurotoxicity of alcohol or delayed brain maturation.</p>
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