Neurophysiological Correlates and Differential Drug Response in Subjects With a Family History of an Alcohol Use Disorder

Abstract

A family history of an alcohol use disorder (AUD) has been shown to increase one’s risk of developing an AUD. Additionally, a positive family history of AUD (family history positive (FHP)) has neurobiological and neuropsychopharmacological consequences, and this review summarizes differential drug response as well as neuroanatomical and neurocognitive correlates. FHP status is related to altered responses to a number of drugs, including substances with abuse liability like alcohol, opioids, amphetamines, and ketamine. FHP individuals demonstrate fewer aversive effects and more rewarding response to both alcohol and subanesthetic dose ketamine. Ketamine is a rapid-acting antidepressant, and several studies have reported that ketamine is more effective for FHP treatment-resistant depressed individuals. In short, the reviewed neurophysiological differences may contribute to ketamine’s enhanced antidepressant efficacy in FHP patients. Volumetric differences in the amygdala, nucleus accumbens, neocortex, and cerebellum are commonly reported. Furthermore, FHP has also been associated with altered neurocognitive performance, e.g., increased impulsivity. The imaging and psychological literature supports a neurodevelopmental lag hypothesis in FHP youth. The review will further discuss these findings in depth.

Alcohol use and grey matter structure: Disentangling predispositional and causal contributions in human studies

“…This study found evidence for lower whole‐brain cortical thickness, as well as local associations with lower thickness in the precentral and paracentral lobules, superior and inferior parietal lobules, precuneus, middle temporal gyrus, banks of the superior temporal sulcus, entorhinal cortex, and lateral occipital sulcus, as well as increased surface area of the precentral lobule and lateral occipital sulcus. This study, however, did not replicate prior findings that had been observed across multiple smaller samples, including smaller amygdala volume 55,56 and greater cerebellar volume 57–61 . The young age of the ABCD study participants relative to these samples may contribute to differential findings.…”

“…This study, however, did not replicate prior findings that had been observed across multiple smaller samples, including smaller amygdala volume 55,56 and greater cerebellar volume. [57][58][59][60][61] The young age of the ABCD study participants relative to these samples may contribute to differential findings.…”

Testing the consequences of alcohol, cannabis, and nicotine use on hippocampal volume: a quasi-experimental cotwin control analysis of young adult twins

“…The present study may help to clarify the relationship between familial risk and hippocampal deviations. Prior work in adolescents using the high-risk offspring design has been mixed on whether a family history of substance use disorder (primarily alcohol use disorder) is associated with structural hippocampal deviations (for narrative reviews, see Comstock, Vaidya, & Niciu, 2019 ; McPhee et al, 2018 ). The CTC design used in this report is an alternate, more stringent, approach for separating risk from exposure (McGue et al, 2010 ; Rutter, 2007 ; Thapar & Rutter, 2019 ), and future work using this design may help shed further light on associations between substance use familial risk and hippocampal volume deviations.…”

A Clinical Rationale for Assessing the Impact of Childhood Sexual Abuse on Adjunctive Subcutaneous Esketamine for Treatment-Resistant Depression

“…In our model, +FH of alcohol use disorder and sex were highlighted as sources of bias between CSA and symptoms trajectory. Being raised by an alcohol-abusing parent increases the likelihood of sexual abuse exposure (29), and esketamine has been reported to be more effective in treatment-resistant depressed patients with a first-degree relative with alcohol use disorder (30). Child sexual abuse and +FH of alcohol use disorder are related to long-lasting neurodevelopmental or genetic/epigenetic variations (30) that predispose to depression in later life.…”