The Insidious Influence of Stress: An Integrated Model of Stress, Executive Control, and Psychopathology.

Although exposure to acute stress undoubtedly contributes to psychopathology, most individuals do not develop psychopathology following stress exposure. To explain this, biological, emotional, and cognitive responses to stress have been implicated, but individual differences in executive control (i.e., top-down control of cognition and behavior) measured in response to stress has only recently emerged as a potential factor contributing to psychopathology. In this review, we introduce a model-the integrated model of stress, executive control, and psychopathology-positing how the impairing effects of acute stress on executive control can contribute to psychopathology. We link to research on biological, emotional, and cognitive processes, all of which can be impacted by executive control, to propose a framework for how poorer executive control under conditions of acute stress can contribute to psychopathology. This integrated model is intended to further our understanding of who is more susceptible to the negative consequences of stress.

Relations among symptoms of depression over time in at-risk youth.

Depression consists of symptoms that may relate to each other in ways that go beyond simple co-occurrence. For example, some symptoms may precede and possibly contribute to the emergence of others. The present study examined several potential relations among the symptoms of depression. The overarching goals were to better understand how depression may unfold and to identify potential targets for intervention. The sample included 120 offspring of depressed parents. Youths' symptoms of depression were rated across 89 weeks. First, we investigated which symptoms preceded and potentially contributed to other symptoms 1 week later. This model revealed that sleep disturbance predicted the occurrence of other symptoms (e.g., sad mood, fatigue), and the occurrence of sad mood was predicted by other symptoms (e.g., worthlessness/guilt, psychomotor symptoms, sleep disturbance). Second, we investigated the within-person question of which symptoms tended to co-occur at the same time point. This model identified sad mood, irritability, and anhedonia as symptoms that tended to co-occur with each other and with many other depressive symptoms. Third, we investigated the between-person question of which symptoms tended to co-occur when averaged across time. This model identified worthlessness/guilt, fatigue, and anhedonia as symptoms strongly associated with other depressive symptoms across people irrespective of timing. Results indicate that the relations among the symptoms of depression vary, such that some symptoms preceded others by 1 week, some symptoms occurred at the same time, and other symptoms co-occurred in individuals. This more detailed view of the connections among depressive symptoms informs our understanding of depression as a dynamic set of unique indicators. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Intraindividual phenotyping of depression in high-risk youth: An application of a multilevel hidden Markov model.

BACKGROUND: Traditionally, depression phenotypes have been defined based on interindividual differences that distinguish between subgroups of individuals expressing distinct depressive symptoms often from cross-sectional data. Alternatively, depression phenotypes can be defined based on intraindividual differences, differentiating between transitory states of distinct symptoms profiles that a person transitions into or out of over time. Such within-person phenotypic states are less examined, despite their potential significance for understanding and treating depression. METHODS: The current study used intensive longitudinal data of youths (N = 120) at risk for depression. Clinical interviews (at baseline, 4, 10, 16, and 22 months) yielded 90 weekly assessments. We applied a multilevel hidden Markov model to identify intraindividual phenotypes of weekly depressive symptoms for at-risk youth. RESULTS: Three intraindividual phenotypes emerged: a low-depression state, an elevated-depression state, and a cognitive-physical-symptom state. Youth had a high probability of remaining in the same state over time. Furthermore, probabilities of transitioning from one state to another did not differ by age or ethnoracial minority status; girls were more likely than boys to transition from a low-depression state to either the elevated-depression state or the cognitive-physical symptom state. Finally, these intraindividual phenotypes and their dynamics were associated with comorbid externalizing symptoms. CONCLUSION: Identifying these states as well as the transitions between them characterizes how symptoms of depression change over time and provide potential directions for intervention efforts.

Eating Disorders in U.S. Active Duty Military Members and Veterans: A Systematic Review.

INTRODUCTION: Feeding and eating disorders can be difficult to treat and frequently co-occur with other mental health conditions. The last systematic review of eating disorders in a military and veteran population was published in 2015. An updated review is warranted to re-examine the current literature on eating disorders in the active duty and veteran populations. MATERIALS AND METHODS: A systematic review that described the prevalence, co-occurrence of other disorders and/or events, and health care utilization of U.S. active duty members and veterans was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Databases and Medical Subject Headings (MeSH) terms used are listed in Appendix A. Each category of the literature was extracted and graded using the Oxford Centre for Evidence-Based Medicine Levels of Evidence. RESULTS: Twenty-one studies revealed prevalence estimates with varying rates based on demographic information. Trauma exposure is consistently associated with eating disorder development. Individuals diagnosed with eating disorders had greater health care utilization. CONCLUSIONS: Research on eating disorders in the military and veteran populations has expanded in recent years. Limitations of the evidence included in this review stem from the use of self-reported questionnaires, changes to medical record systems, and limited generalizability to the overall population of patients with eating disorders. Further research should investigate the impact of demographic factors and trauma exposure on the development of an eating disorder within the military and veteran populations.

Training Military Psychiatrists to Adapt and Overcome: How COVID-19 Highlighted the Unique Flexibility of Military Psychiatry in Training and in the Fleet.

PURPOSE OF REVIEW: Born out of necessity, military medicine continues to find itself at the forefront of medical innovation. This generation of military physicians has never previously been challenged with continuing to provide top notch medical support to servicemembers in a variety of operational settings in the midst of a global pandemic. While military medicine has always been able to uniquely meet the educational goals of residency training, COVID-19 brought new challenges to the forefront. RECENT FINDINGS: While the threat presented by COVID-19 was different from the historical battlefield threats and challenges that have given birth to military medicine, it was nevertheless ready to pivot and adjust course, focusing on how to best meet the medical needs of the military patient population in an ever-changing geopolitical environment while continuing to meet and exceed the educational standards that training programs are held to. Historically and currently, mental health remains one of the most common reasons that servicemembers are evacuated from combat zones. The COVID-19 pandemic provided an opportunity for modern military psychiatry to showcase its ability to adjust the educational focus in certain areas of residency training to prepare the next generation of military psychiatrists to be able to face the newest threat to force wellness.

Executive control under stress: Relation to reappraisal ability and depressive symptoms.

Depression is characterized by difficulties regulating emotions, which may result from executive control impairment. For some individuals, stress exposure leads to executive control impairment. The current study examined whether executive control measured under conditions of acute stress is associated with reappraisal ability and prospectively predicts symptoms of depression during a stressful time of life. Sixty-six participants completed either a laboratory stress induction or a control task. Executive control was measured before and after the stress induction or control task. Reappraisal ability was measured by self-reported negative emotion while viewing aversive images. Participants reported depressive symptoms at baseline and during a period of life stress. Lower levels of executive control under stress were associated with reduced reappraisal ability. Lower levels of executive control under stress also prospectively predicted higher depressive symptoms. Finally, reduced reappraisal ability prospectively predicted higher depressive symptoms. Findings suggest that level of executive control when under stress may contribute to reappraisal ability and symptoms of depression during a time of life stress.

Executive Control, Cytokine Reactivity to Social Stress, and Depressive Symptoms: Testing the Social Signal Transduction Theory of Depression.

Social Signal Transduction Theory of Depression hypothesizes that social stress upregulates inflammatory activity, which in turn contributes to depression for some individuals. However, the specific cognitive processes underlying social stress-induced increases in inflammatory activity remain unclear. We addressed this issue by examining two separate relations: (1) between executive control measured following a laboratory-based social stress induction and individuals' pro-inflammatory cytokine responses to the same stress induction and (2) between pro-inflammatory cytokine responses and participants' depressive symptom levels. Healthy young participants (Mage = 18.58 years old) were randomly assigned to either a stress condition or control condition. Executive control, and the inflammatory cytokines interleukin-1ß, interleukin-6, and tumor necrosis factor-α, were measured before and after the social stress induction or control task. Regression analyses (stress condition, n = 20; control condition, n = 16) demonstrated that in the stress condition only, greater increases in interleukin-6 were associated with more depressive symptoms. Additional analyses in the stress condition (n = 16) indicated that greater impairment in executive control following the social stress induction was related to greater social stress-induced increases in interleukin-6. These findings are consistent with Social Signal Transduction Theory of Depression and with the hypothesis that impairment in executive control during times of stress may be one process that contributes to stress-induced inflammatory activity, which may in turn increase risk for depression.Lay SummarySocial Signal Transduction Theory of Depression hypothesizes that social stress upregulates inflammatory activity, which in turn contributes to depression, and that cognitive processes play a role in structuring these effects. Consistent with this theory, greater social stress-induced increases in the inflammatory cytokine interleukin-6 were associated with more depressive symptoms. In addition, greater impairment in executive control following the social stress induction was related to greater social stress-induced increases in interleukin-6, highlighting potential links between social stress, cognition, inflammation, and depression.

Emotional content impacts how executive function ability relates to willingness to wait and to work for reward.

Research has demonstrated that better value-based decision making (e.g., waiting or working for rewards) relates to greater executive function (EF) ability. However, EF is not a static ability, but is influenced by the emotional content of the task. As such, EF ability in emotional contexts may have unique associations with value-based decision making, in which costs and benefits are explicit. Participants (N = 229) completed an EF task (with both negative and neutral task conditions) and two value-based decision-making tasks. Willingness to wait and to work were evaluated in separate path models relating the waiting and working conditions to the EF conditions. Willingness to wait and willingness to work showed distinct relationships with EF ability: Greater EF ability on a negative, but not on a neutral, EF task was related to a willingness to wait for a reward, whereas greater EF ability across both EF tasks was related to a greater willingness to work for a reward. EF ability on a negative EF task showed an inverted-U relationship to willingness to wait for reward, and was most related to willingness to wait at a 6-month delay. Greater EF, regardless of whether the task was negative or neutral, was related to a greater willingness to work when reward was uncertain (50%) or was likely (88%), but not when reward was unlikely (12%). This study suggests that the emotional content of value-based decisions impacts the relationship between EF ability and willingness to wait or to work for reward.

Comparing cognitive styles in social anxiety and major depressive disorders: An examination of rumination, worry, and reappraisal.

OBJECTIVE: Social anxiety disorder (SAD) and major depressive disorder (MDD) are commonly occurring and frequently comorbid disorders. Though individuals with SAD and MDD are more likely to engage in rumination and worry, relatively few studies have compared individuals with SAD, MDD, or both disorders on their use of these cognitive styles. Similarly, the extent to which the disorders differ in their use of reappraisal remains unclear. Thus, the current study sought to systematically examine rumination, worry, and reappraisal in individuals with and without SAD, MDD, or both disorders. METHODS: The study comprised 330 participants recruited from the community (n = 54 with SAD, n = 61 with MDD, n = 69 with comorbid SAD/MDD, and n = 146 healthy controls). Following confirmation of diagnostic status via clinical interview, participants completed measures of rumination, worry, and reappraisal. RESULTS: Healthy controls reported less use of rumination (i.e., brooding and reflection) and worry than individuals with a psychiatric diagnosis. Individuals with SAD or MDD did not differ from each other, but participants in both groups reported less rumination, particularly brooding, than individuals with comorbid SAD/MDD. Diagnostic group differences in reappraisal only emerged when reappraisal was considered alongside other cognitive styles. Further, moderation analyses indicated that reappraisal was only associated with SAD or MDD when participants also reported high levels of rumination and worry. CONCLUSIONS: Results support transdiagnostic conceptualizations of rumination and worry. They also suggest that reappraisal is only useful when it is used by people who experience frequent and habitual negative cognitions. PRACTITIONER POINTS: Individuals with SAD or MDD report more rumination and worry than healthy controls, but do not differ from each other in their reliance on these cognitive styles. Individuals with comorbid SAD/MDD endorse more rumination than individuals with SAD or MDD alone, even after adjusting for differences in symptom severity. Reappraisal may only predict diagnostic group status when considered alongside other cognitive styles. In particular, high reappraisal may be associated with reduced risk of psychiatric disorder, but only when rumination and worry are also high. LIMITATIONS: The study was limited by its cross-sectional design and reliance on self-report measures. Participants were diagnosed using DSM-IV-TR criteria for SAD and MDD.

Cognitive control and network disruption in remitted depression: a correlate of childhood adversity.

Individuals in a major depressive episode often display impairment in cognitive control, and this impairment exists outside of the acute phase of illness. Impairment in cognitive control also has been associated with exposure to childhood adversity (CA). The current study examined whether exposure to CA can explain variance in a component of cognitive control-inhibitory control-independent of diagnostic status in young adults with and without a history of depression. Healthy control individuals (n = 40) and individuals with remitted major depressive disorder (n = 53) completed a task measuring inhibitory control, reported level of CA and completed a scanning session to assess gray matter volume and resting state connectivity in regions associated with cognitive control. The results demonstrate that higher levels of CA were associated with poorer inhibitory control, reduced right middle frontal gyrus gray matter, decreased connectivity of salience and emotion networks and increased connectivity in cognitive control networks, even after controlling for diagnostic status, residual depression symptoms and current stressors. Together, the results suggest that inhibitory control impairment and intrinsic connectivity changes may be characterized as developmental sequelae of early stress exposure.

Negative cognitive style and cortisol recovery accentuate the relationship between life stress and depressive symptoms.

When exposed to stressful life events, a significant number of adolescents will experience depressive symptoms. One model of depression suggests that individuals with a negative cognitive style are most vulnerable to depression following life stress. Alternatively, altered activation of the hypothalamic-pituitary-adrenal axis may explain vulnerability to depression following life stress. Each of these models plausibly explains the emergence of depressive symptoms during adolescence and have been investigated largely independently. The current study recruited a sample of urban adolescents (N = 179) to evaluate whether cortisol response to a laboratory stress induction and negative cognitive style are related and whether they independently interact with exposure to stressful life events to predict symptoms of depression. Negative cognitive style was not associated with cortisol response to the laboratory stressor. Rather, negative cognitive style and cortisol recovery independently interacted with stressful life events to predict current symptoms of depression. Results support a heterogeneous etiology of depression.

Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia.

BACKGROUND AND AIMS: Pain is the hallmark of sickle cell anemia (SCA), presenting as recurrent acute events or chronic pain. Central sensitization, or enhanced excitability of the central nervous system, alters pain processing and contributes to the maintenance of chronic pain. Individuals with SCA demonstrate enhanced sensitivity to painful stimuli however central mechanisms of pain have not been fully explored. We hypothesized that adults with SCA would show evidence of central sensitization as observed in other diseases of chronic pain. METHODS: We conducted a prospective study of static and dynamic quantitative sensory tests in 30 adults with SCA and 30 matched controls. RESULTS: Static thermal testing using cold stimuli showed lower pain thresholds (p=0.04) and tolerance (p=0.04) in sickle cell subjects, but not for heat. However, SCA subjects reported higher pain ratings with random heat pulses (p<0.0001) and change in scores with temporal summation at the heat pain threshold (p=0.002). Similarly, with the use of pressure pain stimuli, sickle cell subjects reported higher pain ratings (p=0.04), but not higher pressure pain tolerance/thresholds or allodynia to light tactile stimuli. Temporal summation pain score changes using 2 pinprick probes (256 and 512mN) were significantly greater (p=0.004 and p=0.008) with sickle cell, and delayed recovery was associated with lower fetal hemoglobin (p=0.002 and 0.003). CONCLUSIONS: Exaggerated temporal summation responses provide evidence of central sensitization in SCA. IMPLICATIONS: The association with fetal hemoglobin suggests this known SCA modifier may have a therapeutic role in modulating central sensitization.

Diurnal cortisol slopes and mental and physical health outcomes: A systematic review and meta-analysis.

Changes in levels of the stress-sensitive hormone cortisol from morning to evening are referred to as diurnal cortisol slopes. Flatter diurnal cortisol slopes have been proposed as a mediator between chronic psychosocial stress and poor mental and physical health outcomes in past theory and research. Surprisingly, neither a systematic nor a meta-analytic review of associations between diurnal cortisol slopes and health has been conducted to date, despite extensive literature on the topic. The current systematic review and meta-analysis examined associations between diurnal cortisol slopes and physical and mental health outcomes. Analyses were based on 179 associations from 80 studies for the time period up to January 31, 2015. Results indicated a significant association between flatter diurnal cortisol slopes and poorer health across all studies (average effect size, r=0.147). Further, flatter diurnal cortisol slopes were associated with poorer health in 10 out of 12 subtypes of emotional and physical health outcomes examined. Among these subtypes, the effect size was largest for immune/inflammation outcomes (r=0.288). Potential moderators of the associations between diurnal cortisol slopes and health outcomes were examined, including type of slope measure and study quality indices. The possible roles of flatter slopes as either a marker or a mechanism for disease etiology are discussed. We argue that flatter diurnal cortisol slopes may both reflect and contribute to stress-related dysregulation of central and peripheral circadian mechanisms, with corresponding downstream effects on multiple aspects of biology, behavior, and health.

Genome-Wide Search for Host Association Factors during Ovine Progressive Pneumonia Virus Infection.

Ovine progressive pneumonia virus (OPPV) is an important virus that causes serious diseases in sheep and goats with a prevalence of 36% in the USA. Although OPPV was discovered more than half of a century ago, little is known about the infection and pathogenesis of this virus. In this report, we used RNA-seq technology to conduct a genome-wide probe for cellular factors that are associated with OPPV infection. A total of approximately 22,000 goat host genes were detected of which 657 were found to have been significantly up-regulated and 889 down-regulated at 12 hours post-infection. In addition to previously known restriction factors from other viral infections, a number of factors which may be specific for OPPV infection were uncovered. The data from this RNA-seq study will be helpful in our understanding of OPPV infection, and also for further study in the prevention and intervention of this viral disease.

Control when it counts: Change in executive control under stress predicts depression symptoms.

Individual differences in the ability to regulate affect following stressful life events have been associated with an increased risk for experiencing depression symptoms. Research further suggests that emotion regulation may depend on executive control which, in turn, has been shown to decline following stress exposure. Whether individual differences in stress-induced change in executive control predict depression symptoms, however, remains unknown. The current study examined whether trait executive control as well as stress-induced change in executive control predicts depression symptoms during a stressful time of life. The current study recruited 43 individuals during their first year of college. Participants completed an executive control task before and after a laboratory stress induction. Participants reported baseline depression symptoms during the laboratory session and follow-up depression symptoms during the final weeks of the semester. Results demonstrate that stress-induced change in executive control predicted an increase in depression symptoms at the end of the semester. The findings suggest that individual differences in the degree of decline in executive control following stress exposure may be a key factor in explaining why some individuals are vulnerable to depression during a stressful time of life.

Escherichia coli surface display of single-chain antibody VRC01 against HIV-1 infection.

Human immunodeficiency virus type 1 (HIV-1) transmission and infection occur mainly via the mucosal surfaces. The commensal bacteria residing in these surfaces can potentially be employed as a vehicle for delivering inhibitors to prevent HIV-1 infection. In this study, we have employed a bacteria-based strategy to display a broadly neutralizing antibody VRC01, which could potentially be used to prevent HIV-1 infection. The VRC01 antibody mimics CD4-binding to gp120 and has broadly neutralization activities against HIV-1. We have designed a construct that can express the fusion peptide of the scFv-VRC01 antibody together with the autotransporter ß-barrel domain of IgAP gene from Neisseria gonorrhoeae, which enabled surface display of the antibody molecule. Our results indicate that the scFv-VRC01 antibody molecule was displayed on the surface of the bacteria as demonstrated by flow cytometry and immunofluorescence microscopy. The engineered bacteria can capture HIV-1 particles via surface-binding and inhibit HIV-1 infection in cell culture.

Cognitive processes and emotion regulation in depression.

Sustained negative affect and diminished positive affect are hallmark features of Major Depressive Disorder (MDD). Difficulties in emotion regulation have been proposed to be at the core of these cardinal symptoms of MDD. It remains unclear, however, what underlies emotion regulation difficulties. Cognitive theories of depression have focused on cognitive processes and recent studies suggest that cognitive biases and deficits in cognitive control may help explain affective symptoms of this disorder. Specifically, it is proposed that cognitive biases and deficits affect emotion regulation ability thereby setting the stage for maintained negative affect and diminished levels of positive affect. The article reviews empirical studies that speak to these links and closes with a discussion of novel treatment approaches that are inspired by these ideas.

Mammalian alteration/deficiency in activation 3 (Ada3) is essential for embryonic development and cell cycle progression.

Ada3 protein is an essential component of histone acetyl transferase containing coactivator complexes conserved from yeast to human. We show here that germline deletion of Ada3 in mouse is embryonic lethal, and adenovirus-Cre mediated conditional deletion of Ada3 in Ada3(FL/FL) mouse embryonic fibroblasts leads to a severe proliferation defect which was rescued by ectopic expression of human Ada3. A delay in G(1) to S phase of cell cycle was also seen that was due to accumulation of Cdk inhibitor p27 which was an indirect effect of c-myc gene transcription control by Ada3. We further showed that this defect could be partially reverted by knocking down p27. Additionally, drastic changes in global histone acetylation and changes in global gene expression were observed in microarray analyses upon loss of Ada3. Lastly, formation of abnormal nuclei, mitotic defects and delay in G(2)/M to G(1) transition was seen in Ada3 deleted cells. Taken together, we provide evidence for a critical role of Ada3 in embryogenesis and cell cycle progression as an essential component of HAT complex.

Breast cancer subtypes: two decades of journey from cell culture to patients.

Recent molecular profiling has identified six major subtypes of breast cancers that exhibit different survival outcomes for patients. To address the origin of different subtypes of breast cancers, we have now identified, isolated, and immortalized (using hTERT) mammary stem/progenitor cells which maintain their stem/progenitor properties even after immortalization. Our decade long research has shown that these stem/progenitor cells are highly susceptible to oncogenesis. Given the emerging evidence that stem/progenitor cells are precursors of cancers and that distinct subtypes of breast cancer have different survival outcome, these cellular models provide novel tools to understand the oncogenic process leading to various subtypes of breast cancers and for future development of novel therapeutic strategies to treat different subtypes of breast cancers.