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Stress is proposed to be a crucial factor in the onset and presentation of psychosis. The early stage of psychosis provides a window into how stress interacts with the emergence of psychosis. Yet, how people with early psychosis respond to stress remains unclear. The current study examined how stress responses (brain, physiological, self-report) differ in early psychosis. Forty participants (20 early psychosis [EP], 20 healthy controls [HC]) completed a stress task in the scanner that involved viewing stressful and neutral-relaxing images. Physiological responses (cortisol, heart rate) and self-report of stress were also assessed. Region of Interest analyses were conducted with brain regions previously shown to be activated during the stress task (amygdala, hippocampus, striatum, hypothalamus, prefrontal cortex [dorsolateral, ventrolateral, medial orbital]). Linear mixed models were used to test for effects of group (EP, HC) and emotion (stress, neutral-relaxing). HC had higher hippocampus activation to stress versus neutral-relaxing conditions while EP did not show a difference (group x emotion interaction, p = 0.04). There were also significant main effects of group with EP having higher amygdala activation (p = 0.01), ventrolateral prefrontal cortex activation (vlPFC, p = 0.03), self-report of stress (p = 0.01), and heart rate (p < 0.001). Our study found preliminary evidence that people with early psychosis showed heightened response to stressful and non-threatening situations, across multiple levels of stress responses. Our findings suggest a novel perspective on stress alterations in early psychosis and highlight the importance of considering both stressful and non-stressful situations., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Anxiety during early alcohol abstinence, likely resulting from neural changes caused by chronic alcohol use, contributes to high relapse rates. Studies in rodents show heightened activation during early abstinence in the bed nucleus of the stria terminalis (BNST)-a neural hub for anxiety-and its extended anxiety-related corticolimbic network. Despite the clinical importance of early abstinence, few studies investigate the underlying neural mechanisms., Methods: To address this gap, we investigated brain function in early alcohol abstinence (EA = 20, 9 women) relative to controls (HC = 20, 11 women) using an unpredictable threat task shown to engage the BNST and corticolimbic brain regions involved in anxiety and alcohol use disorder (AUD). Group, anxiety, and sex were predictors used to determine whole-brain activation and BNST functional connectivity., Results: We found widespread interactions of group × anxiety and group × anxiety × sex for both activation and BNST connectivity during unpredictable threat. In the EA group, higher anxiety was correlated with activation in the BNST, rostral anterior cingulate cortex (ACC), insula (men only), and dorsal ACC (men only). In the HC group, higher anxiety was negatively correlated with activation in the BNST, nucleus accumbens, thalamus, and insula (men only). For connectivity, anxiety was positively correlated in EA and negatively correlated in HC, between the BNST and the amygdala, ventromedial prefrontal cortex (PFC), and dorsomedial PFC; EA men showed stronger BNST-vmPFC connectivity than HC men., Conclusions: These novel findings provide preliminary evidence for alterations in the BNST and anxiety-related corticolimbic brain regions in early alcohol abstinence, adding to growing literature in humans supporting the BNST's role in anxiety and sex-dependent effects of chronic alcohol use., (© 2024 The Author(s). Alcohol, Clinical and Experimental Research published by Wiley Periodicals LLC on behalf of Research Society on Alcohol.)

This article presents a unique framework that combines insights from neuroscience with clinical assessment to evaluate individuals who have co-occurring alcohol use disorder, anxiety, and trauma. Through the use of a case study, the authors demonstrate the practical application of this framework and contextualize the relevant neurocircuitry associated with alcohol withdrawal, maladaptive fear and anxiety, and chronic stress. By integrating these perspectives, they provide a comprehensive approach for assessing and treating patients with complex psychiatric histories, particularly those presenting with anxiety symptoms, offering valuable insights for practitioners., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Maintaining abstinence from alcohol use disorder (AUD) is extremely challenging, partially due to increased symptoms of anxiety and stress that trigger relapse. Rodent models of AUD have identified that the bed nucleus of the stria terminalis (BNST) contributes to symptoms of anxiety-like behavior and drug-seeking during abstinence. In humans, however, the BNST's role in abstinence remains poorly understood. The aims of this study were to assess BNST network intrinsic functional connectivity in individuals during abstinence from AUD compared to healthy controls and examine associations between BNST intrinsic functional connectivity, anxiety and alcohol use severity during abstinence., Methods: The study included resting state fMRI scans from participants aged 21-40 years: 20 participants with AUD in abstinence and 20 healthy controls. Analyses were restricted to five pre-selected brain regions with known BNST structural connections. Linear mixed models were used to test for group differences, with sex as a fixed factor given previously shown sex differences., Results: BNST-hypothalamus intrinsic connectivity was lower in the abstinent group relative to the control group. There were also pronounced sex differences in both the group and individual analyses; many of the findings were specific to men. Within the abstinent group, anxiety was positively associated with BNST-amygdala and BNST-hypothalamus connectivity, and men, not women, showed a negative relationship between alcohol use severity and BNST-hypothalamus connectivity., Conclusions: Understanding differences in connectivity during abstinence may help explain the clinically observed anxiety and depression symptoms during abstinence and may inform the development of individualized treatments., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Posttraumatic stress disorder (PTSD) significantly impacts many veterans. Although PTSD has been linked to alterations in the fear brain network, the disorder likely involves alterations in both the fear and anxiety networks. Fear involves responses to imminent, predictable threat and is driven by the amygdala, whereas anxiety involves responses to potential, unpredictable threat and engages the bed nucleus of the stria terminalis (BNST). The BNST has been implicated in PTSD, but the role of the BNST in combat veterans with PTSD has yet to be examined. Identifying alterations in BNST responses to unpredictable threat could provide important new targets for treatment. The current study examined whether veterans with PTSD have altered BNST or amygdala responses (function and connectivity) to unpredictable and predictable threat. The fMRI task involved viewing predictable threat cues followed by threat images, predictable neutral cues followed by neutral images, and unpredictable threat cues followed by either a threat or neutral image. Participants included 32 combat-exposed veterans with PTSD and 13 combat-exposed controls without PTSD. Across all conditions, veterans with PTSD had heightened BNST activation and displayed stronger BNST and amygdala connectivity with multiple fear and anxiety regions (hypothalamus, hippocampus, insula, ventromedial prefrontal cortex) relative to controls. In contrast, combat controls showed a pattern of stronger connectivity during neutral conditions (e.g., BNST-vmPFC), which may suggest a neural signature of resilience to developing PTSD, η p 2 = .087-.527, ps < .001. These findings have implications for understanding fear and anxiety networks that may contribute to the development and maintenance of PTSD., (© 2023 International Society for Traumatic Stress Studies.)

Substantial evidence from studies in humans suggests the amygdala is pivotal for anxiety. Findings from animal models and translational studies suggests the bed nucleus of the stria terminalis (BNST) is also critical for anxiety and the anticipation of unpredictable threat in adults. However, it remains unknown whether the BNST is involved in unpredictable threat anticipation in children. Forty-two 8-10-year-olds completed resting-state functional magnetic resonance imaging (fMRI) scans and an unpredictable threat fMRI task in which they were trained to associate cues with images. Intrinsic connectivity analyses were performed to establish functional BNST and amygdala networks. BNST and amygdala activation to cues and images was tested. Significant findings were followed by task-based functional connectivity analyses. Children showed evidence for BNST and amygdala intrinsic connectivity that was similar to previous patterns observed in adults. In response to unpredictable cues relative to neutral face cues, children had a significant amygdala response but no response in the BNST. The amygdala, but not the BNST, also showed a significantly greater response to fear face images relative to neutral images. Thus, unpredictable threat activated the amygdala, but not BNST, in children. This finding is contrary to studies showing robust BNST activation to unpredictable threat in adults and may suggest that the BNST's role in threat processing emerges later in development., (© 2021 Wiley Periodicals LLC.)