Resting-state connectivity subtype of comorbid PTSD and alcohol use disorder moderates improvement from integrated prolonged exposure therapy in Veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid and are associated with significant functional impairment and inconsistent treatment outcomes. Data-driven subtyping of this clinically heterogeneous patient population and the associated underlying neural mechanisms are highly needed to identify who will benefit from psychotherapy. METHODS: In 53 comorbid PTSD/AUD patients, resting-state functional magnetic resonance imaging was collected prior to undergoing individual psychotherapy. We used a data-driven approach to subgroup patients based on directed connectivity profiles. Connectivity subgroups were compared on clinical measures of PTSD severity and heavy alcohol use collected at pre- and post-treatment. RESULTS: We identified a subgroup of patients associated with improvement in PTSD symptoms from integrated-prolonged exposure therapy. This subgroup was characterized by lower insula to inferior parietal cortex (IPC) connectivity, higher pregenual anterior cingulate cortex (pgACC) to posterior midcingulate cortex connectivity and a unique pgACC to IPC path. We did not observe any connectivity subgroup that uniquely benefited from integrated-coping skills or subgroups associated with change in alcohol consumption. CONCLUSIONS: Data-driven approaches to characterize PTSD/AUD subtypes have the potential to identify brain network profiles that are implicated in the benefit from psychological interventions - setting the stage for future research that targets these brain circuit communication patterns to boost treatment efficacy.

Contribution of early-life unpredictability to neuropsychiatric symptom patterns in adulthood.

BACKGROUND: Recent studies in both human and experimental animals have identified fragmented and unpredictable parental and environmental signals as a novel source of early-life adversity. Early-life unpredictability may be a fundamental developmental factor that impacts brain development, including reward and emotional memory circuits, affecting the risk for psychopathology later in life. Here, we tested the hypothesis that self-reported early-life unpredictability is associated with psychiatric symptoms in adult clinical populations. METHODS: Using the newly validated Questionnaire of Unpredictability in Childhood, we assessed early-life unpredictability in 156 trauma-exposed adults, of which 65% sought treatment for mood, anxiety, and/or posttraumatic stress disorder (PTSD) symptoms. All participants completed symptom measures of PTSD, depression and anhedonia, anxiety, alcohol use, and chronic pain. Relative contributions of early-life unpredictability versus childhood trauma and associations with longitudinal outcomes over a 6-month period were determined. RESULTS: Early-life unpredictability, independent of childhood trauma, was significantly associated with higher depression, anxiety symptoms, and anhedonia, and was related to higher overall symptom ratings across time. Early-life unpredictability was also associated with suicidal ideation, but not alcohol use or pain symptoms. CONCLUSIONS: Early-life unpredictability is an independent and consistent predictor of specific adult psychiatric symptoms, providing impetus for studying mechanisms of its effects on the developing brain that promote risk for psychopathology.

Effects of Noninvasive Cervical Vagal Nerve Stimulation on Cognitive Performance But Not Brain Activation in Healthy Adults.

OBJECTIVES: While preliminary evidence suggests that noninvasive vagal nerve stimulation (nVNS) may enhance cognition, to our knowledge, no study has directly assessed the effects of nVNS on brain function and cognitive performance in healthy individuals. The aim of this study was therefore to assess whether nVNS enhances complex visuospatial problem solving in a normative sample. Functional magnetic resonance imaging (fMRI) was used to examine underlying neural substrates. MATERIAL AND METHODS: Participants received transcutaneous cervical nVNS (N = 15) or sham (N = 15) stimulation during a 3 T fMRI scan. Stimulation lasted for 2 min at 24 V for nVNS and at 4.5 V for sham. Subjects completed a matrix reasoning (MR) task in the scanner and a forced-choice recognition task outside the scanner. An analysis of variance (ANOVA) was used to assess group differences in cognitive performance. And linear mixed effects (LMEs) regression analysis was used to assess main and interaction effects of experimental groups, level of MR task difficulty, and recall accuracy on changes in blood oxygen level-dependent (BOLD) signal. RESULTS: Subjects who received nVNS showed higher accuracy for both easy (p = 0.017) and hard (p = 0.013) items of the MR task, slower reaction times for hard items (p = 0.014), and fewer false negative errors during the forced-choice recognition task (p = 0.047). MR task difficulty related to increased activation in frontoparietal regions (p < 0.001). No difference between nVNS and sham stimulation was found on BOLD response during performance of the MR task. CONCLUSIONS: We hypothesize that nVNS increased attention compared to sham, and that this effect led to enhanced executive functions, and consequently to better performance on visuospatial reasoning and recognition tasks. Results provide initial support that nVNS may be a low-risk, low-cost treatment for cognitive disorders.

Proactive engagement of cognitive control modulates implicit approach-avoidance bias.

Implicit social-affective biases-reflected in a propensity to approach positive and avoid negative stimuli-have been documented in humans with paradigms, such as the Approach-Avoidance Task (AAT). However, the degree to which preemptively engaging cognitive control can help to down-regulate those behavioral tendencies remains poorly understood. While undergoing functional magnetic resonance imaging (fMRI), 24 healthy participants completed a cued version of the AAT, in which they responded to pictures of happy or angry faces by pulling a joystick toward themselves (approach) or pushing the joystick away (avoidance) based on the color of the stimulus frame. On some trials, they were cued to reverse the frame color/joystick action instructions. Before stimulus onset, a reverse cue was associated with deactivation of a visuo-spatial and motor planning network and subsequent slowing down in response to stimuli. During the stimulus phase, a reverse cue was associated with a) activation of cognitive control areas, including the right inferior frontal gyrus (IFG) and right inferior parietal lobule (IPL); and b) reduced right precentral gyrus activation when having to push (avoid) a happy face. Overall, these results suggest that proactively engaging cognitive control can help fine-tune behavioral and neural adjustment to emotionally incongruent behavioral conditions.

Neurocomputational Changes in Inhibitory Control Associated With Prolonged Exposure Therapy.

Posttraumatic stress disorder (PTSD) is associated with inhibitory control dysfunction that extends beyond difficulties inhibiting trauma-related intrusions. Inhibitory learning has been proposed as a potential mechanism of change underlying the effectiveness of extinction-based therapies such as prolonged exposure (PE), a first-line treatment for PTSD. To identify neurocognitive markers of change in inhibitory learning associated with PE, we applied a Bayesian learning model to the analysis of neuroimaging data collected during an inhibitory control task, both before and after PE treatment. Veterans (N = 20) with combat-related PTSD completed a stop-signal task (SST) while undergoing fMRI at time points immediately before and after PE treatment. Participants exhibited a small, significant improvement in performance on the SST, as demonstrated by longer reaction times and improved inhibition accuracy. Amplitude of neural activation associated with a signed prediction error (SPE; i.e., the discrepancy between actual outcome and model-based expectation of needing to stop) in the right caudate decreased from baseline to posttreatment assessment. Change in model-based activation was modulated by performance accuracy, with a decrease in positive SPE activation observed on successful trials, d = 0.79, and a reduction in negative SPE activation on error trials, d = 0.74. The decrease in SPE-related activation on successful stop trials was correlated with PTSD symptom reduction. These results are consistent with the notion that PE may help broadly strengthen inhibitory learning and the development of more accurate model-based predictions, which may thus facilitate change in cognitions in response to trauma-related cues and help reduce PTSD symptoms.

Neural mechanisms of interference control in working memory capacity.

The extent to which one can use cognitive resources to keep information in working memory is known to rely on (1) active maintenance of target representations and (2) downregulation of interference from irrelevant representations. Neurobiologically, the global capacity of working memory is thought to depend on the prefrontal and parietal cortices; however, the neural mechanisms involved in controlling interference specifically in working memory capacity tasks remain understudied. In this study, 22 healthy participants completed a modified complex working memory capacity task (Reading Span) with trials of varying levels of interference control demands while undergoing functional MRI. Neural activity associated with interference control demands was examined separately during encoding and recall phases of the task. Results suggested a widespread network of regions in the prefrontal, parietal, and occipital cortices, and the cingulate and cerebellum associated with encoding, and parietal and occipital regions associated with recall. Results align with prior findings emphasizing the importance of frontoparietal circuits for working memory performance, including the role of the inferior frontal gyrus, cingulate, occipital cortex, and cerebellum in regulation of interference demands.

Neural measures associated with configural threat acquisition.

Contextual threat learning reflects two often competing processes: configural and elemental learning. Configural threat learning is a hippocampal-dependent process of forming a conjunctive representation of a context through binding of several multi-modal elements. In contrast, elemental threat-learning is governed by the amygdala and involves forming associative relationships between individual features within the context. Contextual learning tasks in humans however, rarely probe if a learned fear response is truly due to configural learning vs. simple elemental associations. The aim of the current study was to probe both constructs separately to enable a more refined interpretation of configural vs. elemental threat learning performance and mediating circuits. Subjects (n = 25) performed both a novel feature-identical contextual threat conditioning task and a discrete cue threat acquisition task while undergoing functional magnetic resonance imaging. Results demonstrated increased hippocampus activity for the threat configuration compared to the safe configuration. This pattern was not observed in the amygdala. In contrast, elemental threat learning was associated with increased amygdala, but not hippocampus activity. Whole-brain analyses revealed that both configural and elemental threat acquisition share neural circuitry related to fear expression. These results provide support for the importance of the hippocampus specifically in configural threat acquisition and fear expression.

A functional magnetic resonance imaging study of spatial working memory in children with prenatal alcohol exposure: contribution of familial history of alcohol use disorders.

BACKGROUND: Heavy prenatal alcohol exposure leads to widespread cognitive deficits, including problems with spatial working memory (SWM). Neuroimaging studies report structural and functional abnormalities in fetal alcohol spectrum disorders (FASD), but interpretations may be complicated by the co-occurrence of a family history of alcoholism. Since this history is also linked to cognitive deficits and brain abnormalities, it is difficult to determine the extent to which deficits are unique to prenatal alcohol exposure. METHODS: Age-matched subjects selected from 2 neuroimaging studies underwent functional imaging while engaging in a task assessing memory for spatial locations relative to a vigilance condition assessing attention. Pairwise comparisons were made for the following 3 groups: children with histories of heavy prenatal alcohol exposure (ALC, n = 18); those with no prenatal alcohol exposure, but a confirmed family history of alcoholism (FHP, n = 18); and nonexposed, family history negative controls (CON, n = 17). RESULTS: Relative to CON and FHP, the ALC group showed increased blood oxygen level dependent (BOLD) response in the left middle and superior frontal gyri for the SWM condition relative to the vigilance condition (SWM contrast). Additionally, the ALC group showed unique BOLD response increases in the left lingual gyrus and right middle frontal gyrus relative to CON, and left cuneus and precuneus relative to FHP. Both ALC and FHP showed greater activation compared to CON in the lentiform nucleus and insular region. CONCLUSIONS: These results confirm previous studies suggesting SWM deficits in FASD. Differences between the ALC group and the CON and FHP groups suggest the left middle and superior frontal region may be specifically affected in alcohol-exposed children. Conversely, differences from the CON group in the lentiform nucleus and insular region for the ALC and FHP groups may indicate this region is associated with family history of alcoholism rather than specifically with prenatal alcohol exposure.

Neurosubstrates of remission following prolonged exposure therapy in veterans with posttraumatic stress disorder.

BACKGROUND: Prolonged exposure (PE) therapy is the first-line treatment for posttraumatic stress disorder (PTSD) in combat veterans. The underlying brain changes of treatment effect in PTSD are currently unknown. METHODS: A total of 31 veterans with PTSD completed an fMRI scan performing an affective anticipation task at baseline and were enrolled in PE therapy. Of these, 7 prematurely terminated therapy, while 24 individuals completed PE therapy and an identical follow-up fMRI scan. At follow-up, 15 of the 24 completers still had diagnosable PTSD (NR-PTSD) and 9 of the 24 completers showed complete remission from PTSD (R-PTSD), i.e. they did not meet diagnostic criteria for PTSD. RESULTS: The left anterior insula showed a significant group by scan session interaction. Specifically, the R-PTSD group showed decreased activation during anticipation of negative images from pre- to posttreatment scans, while the NR-PTSD group showed increased activation during anticipation of positive images in this region. Furthermore, the change in functional activation in the insula co-occurred with increased connectivity between this insular region and the right cingulate and right mid-posterior insular region in R-PTSD. CONCLUSIONS: These findings suggest that the capacity to effectively remit from PTSD symptoms after PE treatment requires the ability to connect with physiological signals and moderate the discomfort of anticipatory anxiety of exposure therapy. These processes appear to be controlled by a network where the anterior insula is connected with the cingulate and the mid-posterior insula.

Family history of alcohol use disorders and neuromaturation: a functional connectivity study with adolescents.

BACKGROUND: A positive family history (FHP) of alcohol use disorders (AUD) is linked to increased risk for personal AUD, but the mechanisms behind this risk are unclear. Previous research suggests that a subtle neurodevelopmental lag in FHP adolescents may contribute to risk for future AUD. METHODS: Functional magnetic resonance imaging (fMRI) response to a spatial working memory (SWM) task was examined for markers of neuromaturational delay in 85 youth with and without FHP. It was hypothesized that FHP adolescents (n = 24, ages 12-14 years), as compared to matched FHN youth (n = 26, ages 12-14 years), would show less similarity to brain connectivity observed in older adolescents (n = 35, ages 16-20 years) and that statistical comparison of SWM functional connectivity models would differentiate FHN and FHP youth. Structural equation modeling tested the fit of brain response connectivity between FH groups and against the older-adolescent model. RESULTS: Patterns of connectivity were more similar between older adolescent and FHN than FHP adolescents; FHP youth demonstrated higher association between right posterior and left frontal brain regions than FHN and older adolescent youth. Comparison of FH groups indicated a significant difference on the pathway from the right superior parietal lobule to the left middle frontal gyrus. CONCLUSIONS: These findings provide additional support for the notion of a neuromaturational lag in FHP youth. Protracted neuromaturation may be a mechanism by which FH increases risk for alcohol dependence, and this less mature neural connectivity pattern may provide a novel endophenotype for identifying youth at risk for drinking problems.

Understanding Pain and Trauma Symptoms in Veterans From Resting-State Connectivity: Unsupervised Modeling.

Trauma and posttraumatic stress are highly comorbid with chronic pain and are often antecedents to developing chronic pain conditions. Pain and trauma are associated with greater utilization of medical services, greater use of psychiatric medication, and increased total cost of treatment. Despite the high overlap in the clinic, the neural mechanisms of pain and trauma are often studied separately. In this study, resting-state functional magnetic resonance imaging (rs-fMRI) scans were completed among a diagnostically heterogeneous sample of veterans with a range of back pain and trauma symptoms. Using Group Iterative Multiple Model Estimation (GIMME), an effective functional connectivity analysis, we explored an unsupervised model deriving subgroups based on path similarity in a priori defined regions of interest (ROIs) from brain regions implicated in the experience of pain and trauma. Three subgroups were identified by patterns in functional connection and differed significantly on several psychological measures despite similar demographic and diagnostic characteristics. The first subgroup was highly connected overall, was characterized by functional connectivity from the nucleus accumbens (NAc), the anterior cingulate cortex (ACC), and the posterior cingulate cortex (PCC) to the insula and scored low on pain and trauma symptoms. The second subgroup did not significantly differ from the first subgroup on pain and trauma measures but was characterized by functional connectivity from the ACC and NAc to the thalamus and from ACC to PCC. The third subgroup was characterized by functional connectivity from the thalamus and PCC to NAc and scored high on pain and trauma symptoms. Our results suggest that, despite demographic and diagnostic similarities, there may be neurobiologically dissociable biotypes with different mechanisms for managing pain and trauma. These findings may have implications for the determination of appropriate biotype-specific interventions that target these neurological systems.

Learning from addiction: Craving of prescription opioids in chronic pain sufferers.

Prescription opioids are a primary driver of opioid-related deaths. Although craving is a substantial component of OUD, the degree to which craving leads to misuse among chronic pain patients on long-term prescription opioids is unknown. A clear understanding of the factors that lead to misuse in this vulnerable population is needed for the development of safe and effective practices for opioid taper. This narrative review summarizes the relevant literature on the role of craving in addiction and chronic pain through epidemiological and behavioral studies. The first part of this review examines the role of craving in predicting opioid use/misuse in individuals with chronic pain with and without OUD. The second part covers methods on how craving is evaluated experimentally using both subjective and objective measures and provides related findings. The overall goal of this review is to facilitate the development of a population-specific description of craving in those who use opioids to control chronic pain and to describe how it may be mechanistically linked to patterns of opioid (mis)use.

Higher affective congruency in the approach-avoidance task is associated with insular deactivation to dynamic facial expressions.

Individuals exhibit a natural bias to approach positive social cues (e.g., smiling face) and to avoid negative ones, which may be altered in psychiatric conditions. Computerized approach/avoidance training to promote affectively congruent behavior has proven useful in modulating such biases. Here, we investigate how exposure to a higher rate of congruency impacts neural processing of social-affective cues. While undergoing functional magnetic resonance imaging (fMRI), twenty-four individuals completed two versions of the approach-avoidance task (AAT), in which they had to approach or avoid dynamic facial expressions of either happiness or disgust. In the high congruency condition, congruent responses (i.e. approaching happy faces, avoiding disgusted faces) were more frequent. The balanced condition had equal amounts of congruent and incongruent responses. Processing of congruent approach-avoidance actions towards social cues was associated with lower recruitment of the right anterior insula in the congruency-intensive relative to the balanced condition. Differential activation between the high congruency and balanced condition in the right hippocampus was negatively related to individuals' trait avoidance tendency. These findings are consistent with reduced affective neural processing of social cues when being exposed to congruent AAT contexts. These neural foci could be important targets when assessing the effectiveness of affective congruency training protocols.

Hippocampal volumes in adolescents with and without a family history of alcoholism.

BACKGROUND AND OBJECTIVES: The hippocampus may be vulnerable to the effects of heavy alcohol use during adolescence, which is a time of continued neurodevelopment. However, differences in hippocampal volume may be due to risk factors such as a family history (FH) of alcoholism. We examined hippocampal volumes in youth with and without a FH of alcoholism prior to the initiation of alcohol use. METHODS: Participants were demographically matched adolescents (aged 12-14) with positive (n = 15; FHP) and negative (n = 15; FHN) FH of alcoholism. Each group consisted of 10 males and 5 females with minimal previous substance use. Manual hippocampal tracings were completed on high-resolution magnetic resonance images by reliable raters, and intracranial volumes were controlled in analyses. RESULTS: FH groups did not differ on memory or hippocampal volumes, but group x gender interactions (p < .05) indicated that FHP males had larger left hippocampi than FHN males. Females showed greater left versus right hippocampal asymmetry, while males showed larger right versus left asymmetry. For all adolescents, larger right hippocampal volumes predicted poorer delayed visual memory (p < .01). CONCLUSION AND SIGNIFICANCE: Alcoholism risk factors, such as family history of alcoholism, may differentially influence adolescent hippocampal development for boys as compared to girls. Results suggest that FH does not account for prior findings of reduced left hippocampal volumes in heavy drinking youth. Findings are preliminary, but suggest that future studies examining the effects of alcohol use on the adolescent brain should consider the influence of FH, especially among boys.

Neural affective mechanisms associated with treatment responsiveness in veterans with PTSD and comorbid alcohol use disorder.

Post-traumatic stress disorder (PTSD) is associated with neuro-physiological abnormalities reflecting increased anticipatory anxiety and reactivity to traumatic cues. It remains unclear whether neural mechanisms associated with PTSD treatment responsiveness, i.e. hyperactivation of the affective salience network in the brain, extend to a comorbid PTSD and substance use disorder population. Thirty-one Veterans with PTSD and co-occurring alcohol use disorder (AUD) were randomly assigned to either prolonged exposure or a non-exposure based treatment. They completed an affective anticipation task while undergoing fMRI, immediately prior and after completing treatment. After controlling for type and length of treatment, larger reduction of PTSD symptoms was associated with decreased anticipatory activation to negative trauma-related cues in the right pre-Supplementary Motor Area (pre-SMA), a region associated with emotion regulation. Smaller reduction in PTSD severity was associated with enhanced anticipatory activation to those cues within the right para-hippocampal region, an affective processing region. Our findings suggest that post-treatment reductions in anticipatory reactivity to trauma-related cues in the pre-SMA and para-hippocampal area are associated with larger PTSD symptom reduction in individuals with co-occurring PTSD and AUD. These results may offer neurofeedback training targets as an alternative to or enhancement of other PTSD treatment modalities in this population.

BOLD response during spatial working memory in youth with heavy prenatal alcohol exposure.

BACKGROUND: Prenatal alcohol exposure has been consistently linked to neurocognitive deficits and structural brain abnormalities in affected individuals. Structural brain abnormalities observed in regions supporting spatial working memory (SWM) may contribute to observed deficits in visuospatial functioning in youth with fetal alcohol spectrum disorders (FASDs). METHODS: We used functional magnetic resonance imaging (fMRI) to assess the blood oxygen level dependent (BOLD) response in alcohol-exposed individuals during a SWM task. There were 22 young subjects (aged 10-18 years) with documented histories of heavy prenatal alcohol exposure (ALC, n = 10), and age- and sex-matched controls (CON, n = 12). Subjects performed a SWM task during fMRI that alternated between 2-back location matching (SWM) and simple attention (vigilance) conditions. RESULTS: Groups did not differ on task accuracy or reaction time to the SWM condition, although CON subjects had faster reaction times during the vigilance condition (617 millisecond vs. 684 millisecond, p = 0.03). Both groups showed similar overall patterns of activation to the SWM condition in expected regions encompassing bilateral dorsolateral prefrontal lobes and parietal areas. However, ALC subjects showed greater BOLD response to the demands of the SWM relative to the vigilance condition in frontal, insular, superior, and middle temporal, occipital, and subcortical regions. CON youth evidenced less increased brain activation to the SWM relative to the vigilance task in these areas (p < 0.05, clusters > 1,664 microl). These differences remained significant after including Full Scale IQ as a covariate. Similar qualitative results were obtained after subjects taking stimulant medication were excluded from the analysis. CONCLUSIONS: In the context of equivalent performance to a SWM task, the current results suggest that widespread increases in BOLD response in youth with FASDs could either indicate decreased efficiency of relevant brain networks, or serve as a compensatory mechanism for deficiency at neural and/or cognitive levels. In context of existing fMRI evidence of heightened prefrontal activation in response to verbal working memory and inhibition demands, the present findings may indicate that frontal structures are taxed to a greater degree during cognitive demands in individuals with FASDs.

Characterization of white matter microstructure in fetal alcohol spectrum disorders.

BACKGROUND: Exposure to alcohol during gestation is associated with CNS alterations, cognitive deficits, and behavior problems. This study investigated microstructural aspects of putative white matter abnormalities following prenatal alcohol exposure. METHODS: Diffusion tensor imaging was used to assess white matter microstructure in 27 youth (age range: 8 to 18 years) with (n = 15) and without (n = 12) histories of heavy prenatal alcohol exposure. Voxelwise analyses, corrected for multiple comparisons, compared fractional anisotropy (FA) and mean diffusivity (MD) between groups, throughout the cerebrum. RESULTS: Prenatal alcohol exposure was associated with low FA in multiple cerebral areas, including the body of the corpus callosum and white matter innervating bilateral medial frontal and occipital lobes. Fewer between-group differences in MD were observed. CONCLUSIONS: These data provide an account of cerebral white matter microstructural integrity in fetal alcohol spectrum disorders and support extant literature showing that white matter is a target of alcohol teratogenesis. The white matter anomalies characterized in this study may relate to the neurobehavioral sequelae associated with gestational alcohol exposure, especially in areas of executive dysfunction and visual processing deficits.

Expansion of hippocampal and amygdala shape in posttraumatic stress and early life stress.

OBJECTIVE: The aim of this study was to examine the effect of Posttraumatic Stress Disorder (PTSD) and childhood adversity on brain structure. We assessed hippocampal and amygdala shape in veterans with varying levels of PTSD symptom severity and exposure to early life stressors (ELS). METHODS: A total of 70 male veterans, who were deployed to a combat area during OIF/OEF/OND and who had been exposed to trauma during deployment, were included in the study. We applied a vertex-wise shape analysis of 3T MRI scans to measure indentation or expansion in hippocampal and amygdala shape. RESULTS: Analyses showed a positive correlation between number of ELS and vertices in the right amygdala and the right hippocampus, as well as a positive correlation between PTSD symptom severity and right hippocampal vertices. There were no significant interactions between PTSD symptoms, ELS, and brain shape. DISCUSSION: Results indicate a relationship between exposure to more childhood adversity and expansion in amygdala and hippocampal shape as well as between more severe PTSD symptoms and expansion in hippocampal shape. These findings may have important implications for the pathophysiology of trauma-related disorders.

Shared gray matter reductions across alcohol use disorder and posttraumatic stress disorder in the anterior cingulate cortex: A dual meta-analysis.

The considerable comorbidity of posttraumatic stress disorder (PTSD) and alcohol use disorders (AUD) poses a greater public health burden than either condition alone. Although there is a substantial body of evidence linking the direct neurotoxic effect of heavy drinking to gray matter (GM) deficits, as well as a growing body of literature supporting a strong association between PTSD and GM alterations, there is scant research interrogating the direct interaction of the two disorders. In order to generate data-driven, specific hypotheses regarding the overlapping neural substrates of PTSD and AUD, we conducted a meta-analysis of GM volumes in each disorder relative to healthy control subjects. We found shared GM deficits in the anterior cingulate cortex (ACC) across both disorders relative to healthy control participants. These findings suggest that reduced volumes of the ACC across PTSD and AUD may have implications for the development, expression, or treatment of symptoms linked to these frequently co-existing disorders. Recommendations are made for future work aimed at delineating the specific and shared effects of traumatic stress and alcoholism on neural integrity.

Effects of family history of alcohol use disorders on spatial working memory BOLD response in adolescents.

BACKGROUND: A positive family history (FH) of alcohol use disorders (AUD) has been linked to increased risk for the development of AUD, and neurocognitive factors have been postulated as important underlying mechanisms of familial alcoholism transmission. METHODS: We used functional magnetic resonance imaging (fMRI) during a spatial working memory (SWM) and vigilance paradigm to investigate potential neurodevelopmental differences linked to familial density of AUD in 72 adolescents aged 12 to 14 years. RESULTS: Youth with denser family histories of AUD showed less activation during a simple vigilance condition relative to SWM in cingulate and medial frontal gyri (beta = 0.28, p = 0.03), and a trend for more relative activity during rest (beta = -0.25, p = 0.07) in this cluster. CONCLUSIONS: Youth with greater familial densities of AUD may be less successful at modulating activity of the default network, potentially indicating a greater propensity for task-independent thought or reduced inhibition of task-irrelevant processing. Failure to moderate activation of the default network may have implications for cognitive efficiency and goal directed behavior in youth with dense FH. Further, aberrant activation in cingulate regions may be linked to genetic variation in GABA receptor units, suggesting a useful endophenotype for risk associated with alcohol dependence.