Gender Effects in Alcohol Dependence: An fMRI Pilot Study Examining Affective Processing

Abstract

Background Alcohol dependence (AD) has global effects on brain structure and function, including frontolimbic regions regulating affective processing. Preliminary evidence suggests alcohol blunts limbic response to negative affective stimuli and increases activation to positive affective stimuli. Subtle gender differences are also evident during affective processing. Methods Fourteen abstinent AD individuals (8 F, 6 M) and 14 healthy controls (9 F, 5 M), ages 23 to 60, were included in this facial affective processing functional magnetic resonance imaging pilot study. Whole-brain linear regression analyses were performed, and follow-up analyses examined whether AD status significantly predicted depressive symptoms and/or coping. Results Fearful Condition—The AD group demonstrated reduced activation in the right medial frontal gyrus, compared with controls. Gender moderated the effects of AD in bilateral inferior frontal gyri. Happy Condition—AD individuals had increased activation in the right thalamus. Gender moderated the effects of AD in the left caudate, right middle frontal gyrus, left paracentral lobule, and right lingual gyrus. Interactive AD and gender effects for fearful and happy faces were such that AD men activated more than control men, but AD women activated less than control women. Enhanced coping was associated with greater activation in right medial frontal gyrus during fearful condition in AD individuals. Conclusions Abnormal affective processing in AD may be a marker of alcoholism risk or a consequence of chronic alcoholism. Subtle gender differences were observed, and gender moderated the effects of AD on neural substrates of affective processing. AD individuals with enhanced coping had brain activation patterns more similar to controls. Results help elucidate the effects of alcohol, gender, and their interaction on affective processing.

Continuous and Intermittent Alcohol Free-Choice from Pre-gestational Time to Lactation: Focus on Drinking Trajectories and Maternal Behavior

“…Accordingly, the saccharin preference test highlighted a greater reduction in sensitivity to natural reward in IAR than in CAR indicating that, although both alcohol-drinking patterns diverted motivational resources in female rats, a prominent drop in interest- or pleasure- into naturally rewarding stimuli occurred in IAR, in favor of a higher alcohol-related salience (Robinson and Berridge, 1993 ). The reduction in reward sensitivity is considered a core symptom of depression, although recent evidence highlights that the alteration of affective processing is not always associated with depressive symptoms in human alcoholics (Padula et al, 2015 ). Accordingly, continuous and intermittent alcohol exposures produce opposite effects in preclinical tests of depressive-like behavior, generating respectively increased immobility in the 1-day forced swim test in rats, and increased swimming in the re-exposure session of the Porsolt-test in mice (Getachew et al, 2010 ; Lee et al, 2015 ).…”

Alcohol's Unique Effects on Cognition in Women: A 2020 (Re)view to Envision Future Research and Treatment

“…A small fMRI study of airplane pilots—individuals with AUD (8 women, 6 men) and healthy controls (9 women, 5 men)—revealed an interactive effect of AUD and sex on brain activation during negative and positive facial affective processing, such that men with AUD demonstrated higher brain activation than control men, whereas women with AUD showed lower brain activation than control women. 103 By contrast, an fMRI study conducted in long-term abstinent individuals with AUD reported sex-related differences in the pattern of brain responsivity to emotional stimuli, with lower activation in the rostral middle and superior frontal cortex, precentral gyrus, and inferior parietal cortex in men with AUD than in control men, whereas higher activation in superior frontal and supramarginal cortices were observed in women with AUD compared to control women. 104 As suggested, these specificities in brain reactivity between men and women during emotional processing may reflect sex-related differences in the emotional mechanisms leading to the development of AUD.…”

Alcoholism gender differences in brain responsivity to emotional stimuli

“…Emotional processing is associated with activity within well-characterized network-based brain circuitries including prefrontal cortex, insula, cingulate cortex, and medial temporal lobe structures including the amygdala (Davidson et al, 1999; Proverbio et al, 2009). In functional magnetic resonance imaging (fMRI) studies measuring AUD-related abnormal brain responses during emotional processing (Beck et al, 2009; Chanraud-Guillermo et al, 2009; Gilman and Hommer, 2008; Heinz et al, 2007), abstinent ALC individuals showed reduced fMRI activation in the amygdala, hippocampus, anterior cingulate, and medial frontal regions in response to viewing stimuli with a negative affective valence, compared to nonalcoholic control (NC) participants (Marinkovic et al, 2009; Padula et al, 2015; Salloum et al, 2007); in response to viewing stimuli with a positive affective valence, the ALC individuals showed an increase in activation in the anterior cingulate cortex, prefrontal cortex, ventral striatum, and thalamus (Heinz et al, 2007). However, little is known about gender-specific persistent influences of alcoholism-related brain activation in response to affective materials, because little research has compared abstinent alcoholic men (ALC M ) and women (ALC W ) compared to nonalcoholic men (NC M ) and women (NC W ) (e.g., Salloum et al, 2007).…”

“…To engage the Emotional Integration and Evaluation System, we asked participants to view complex, emotionally meaningful pictures ( aversive , erotic , gruesome , happy – and neutral for comparison), and to rate how the pictures made them feel ( good , bad , or neutral ). We chose stimuli representing the contrasting valences, because findings from previous research indicated that one or more of those emotional categories were sensitive to deficits in emotional processing by abstinent ALC groups compared to NC groups (Heinz et al, 2007; Marinkovic et al, 2009; Padula et al, 2015; Salloum et al, 2007). It should be noted that the behavioral task is not, explicitly, either an emotion judgment task nor an emotion regulation measure.…”

“…We were especially interested in responses to happy and aversive stimuli, because (a) they have been shown to be sensitive to gender effects in brain activation levels in abstinent ALC participants who viewed faces with different emotional expressions (Padula et al, 2015), and (b) abnormalities in the evaluation of aversive stimuli (which are associated with negative feelings such as fear, pain, and stress), play a crucial role in the transition to AUD or alcohol relapse (Maleki and Oscar-Berman, 2019; Witkiewitz et al, 2015). Whereas brain activation alterations in emotional processes have been studied in relation to AUD (Beck et al, 2009; Chanraud-Guillermo et al, 2009; Gilman and Hommer, 2008; Heinz et al, 2007), gender differences have not been explored in depth, and there is a need for more research in this domain (Nixon et al, 2014; Ruiz and Oscar-Berman, 2013).…”