Risk Factor For Psychopathology Research Articles

Adolescent Alcohol Exposure Epigenetically Suppresses Amygdala Arc Enhancer RNA Expression to Confer Adult Anxiety Susceptibility

BackgroundAdolescent intermittent ethanol (AIE) exposure is an emerging risk factor for adult psychopathology, such as anxiety disorders. Enhancer RNAs (eRNAs) are short noncoding RNAs transcribed from enhancer regions that regulate synaptic plasticity–associated gene expression, including Arc, but their role in AIE-induced susceptibility to anxiety in adulthood is unknown. MethodsRats were exposed to AIE (ethanol exposure 2 days on/off) or intermittent normal saline during postnatal days 28 to 41 and allowed to grow to adulthood for analysis of behavior and biochemical measures. Some AIE rats and rats with intermittent normal saline exposure were exposed to an acute challenge with ethanol in adulthood. Cohorts of alcohol-naïve adult rats were cannulated in the central nucleus of amygdala and infused with either Kdm6b small interfering RNA or an antisense locked nucleic acid oligonucleotide specific to Arc eRNA before behavioral and biochemical analysis. ResultsAIE adult rats displayed heightened anxiety and decreased Arc eRNA expression, which is regulated epigenetically through decreased Kdm6b expression. This triggered condensed chromatin at the synaptic activity response element site and promoter of the Arc gene, facilitating increased negative elongation factor binding to the Arc promoter and decreasing Arc expression in the amygdala. Knockdown of Kdm6b or Arc eRNA expression in the central nucleus of amygdala provoked anxiety in alcohol-naïve adult rats and recapitulated the molecular and epigenetic phenotypes of AIE. ConclusionsThese data suggest that eRNA regulation via epigenetic reprogramming in the amygdala, particularly at the Arc synaptic activity response element site, contributes to adult anxiety after adolescent alcohol exposure.

F117EVALUATING THE IMPACT OF NON-RANDOM MATING: PSYCHIATRIC OUTCOMES AMONG THE OFFSPRING OF PAIRS DIAGNOSED WITH SCHIZOPHRENIA AND BIPOLAR DISORDER

22q11.2 Deletion Syndrome (22q11DS) confers strongly increased genetic risk for multiple psychiatric disorders. Similarly to the general population, rates of psychiatric comorbidity suggest that common disease mechanisms are shared across dimensions of psychopathology. Such pleiotropic disease mechanisms remain however currently unknown. We hypothesized that pituitary dysmaturation, indicative of HPA-axis dysregulation, could correlate to reduced tolerance to daily life stressors and reflect pleiotropic risk factor for psychopathology. Moreover HPA-axis dysregulation could affect atypical cortical and hippocampal development previously described in 22q11DS.Pituitary volume, hippocampal volume and cortical thickness measures were obtained from T1-weighted MRI images in a large longitudinal cohort of youth with 22q11DS (115 subjects, 260 scans, age-range = 5.4–31.6) and healthy controls (151 subjects, 280 scans, age-range = 5.1–32.3). We explored effects of pituitary dysmaturation on tolerance to stress, psychopathology and neurodevelopment employing mixed-models linear regression. Associations of pituitary and cortical development were correlated with the expression pattern of glucocorticoid receptor gene NR3C1 obtained from the Allen-Human-Brain-Atlas.We observed aberrant pituitary developmental trajectories in 22q11DS, with volumetric reductions emerging by young-adulthood (P = 0.0006). Longitudinal pituitary decline was associated with to reduced tolerance to stress (P = 0.04), higher overall psychopathology (P = 0.0003) and increased risk of psychiatric comorbidity (P = 0.02). Moreover, pituitary decline correlated with blunted growth of the right hippocampus (P = 0.03) and to increased cortical thinning of mostly temporal and orbitofrontal regions mediated by NR3C1 gene expression.Atypical pituitary development could reflect progressive extinction of HPAA due to chronic hyper-activation, in agreement with existing biochemical evidence in 22q11DS. HPAA dysregulation could represent and endophenotype that confers pleiotropic vulnerability to psychopathology and atypical neurodevelopment in 22q11DS.

Approach/avoidance personality traits as predictors of psychopathology in convicted offenders

This study examined the role of approach and avoidance personality traits as temperamental risk factors for psychopathology using the revised Reinforcement Sensitivity Theory as theoretical framework. Self-report measures were administered to male convicted offenders (N = 162) and controls matched for age, education, and ethnicity (N = 162). The results show higher approach and passive avoidance tendencies in the forensic sample, as well as higher psychological distress relative to controls. In the forensic sample, both approach and avoidance traits can account for a high degree of psychopathology vulnerability. However, higher behavioral inhibition system sensitivity is the primary risk factor both for general distress and various dimensions of psychopathology, while lower behavioral approach system sensitivity predicts internalizing psychopathology, paranoid, and psychoticism symptoms. The findings are discussed both in the general context of personality-psychopathology links, as well as in the forensic context of potential mental health interventions as part of rehabilitation prison programs.

Supplemental Material for Are Rumination and Neuroticism Genetically or Environmentally Distinct Risk Factors for Psychopathology?

Supplemental Material for Are Rumination and Neuroticism Genetically or Environmentally Distinct Risk Factors for Psychopathology?

The influence of stressful life events, psychopathy, and their interaction on internalizing and externalizing psychopathology

Exposure to stressful life events increases risk for both internalizing and externalizing psychopathology, but less is known about moderators of the association between stressful life events and psychopathology. The present study examined the influence of stressful life events, psychopathy, and their interaction on internalizing and externalizing psychopathology in 3877 individuals from the community. We hypothesized that (1) exposure to stressful life events would be a transdiagnostic risk factor for psychopathology, (2) primary and secondary psychopathy would be differentially associated with internalizing psychopathology, and (3) primary psychopathy would moderate the association between stressful life events and internalizing psychopathology. Confirming existing findings, our results were consistent with the first and second hypotheses. In contrast to our third hypothesis, primary psychopathy was not associated with stressful life events in childhood, inconsistently associated with stressful life events in adolescence, and did not moderate the association between stressful life events and internalizing psychopathology. Furthermore, stressful life events across development were associated with secondary psychopathy and internalizing and externalizing psychopathology. We also found similar associations between stressful life events, psychopathy, and psychopathology in females and males. Future studies investigating the impact of stressful life events on psychopathology should include psychopathic traits and stress-reactivity.

Resilience Against Traumatic Stress: Current Developments and Future Directions.

Given the high prevalence of stress-related mental disorders, their impact on person, family, and society and the paucity of treatment options for most of these disorders, there is currently a pressing need for innovative approaches to deal with these issues and enhance well-being. One approach which has received increasing attention over the last decade is to shift our scientific and clinical focus from risk factors for psychopathology to factors promoting resilience and mental well-being. In order to summarize and evaluate the current state of scientific affairs on the biological basis of resilience, we provide an overview of the literature on animal and human studies of resilience. Because resilience can only truly be operationalized through longitudinal data collection and analyses, we focus primarily on longitudinal studies. This review shows that the concept of resilience is currently being operationalized, measured and even defined in widely variable manners, both within animal and human studies. We further provide an overview of existing and new strategies that could help promote resilience and which are proposed to be implemented more often in clinical situations. Finally, we summarize the challenges the field is facing and provide recommendations for future research.

Practitioner Review: Mental health problems of refugee children and adolescents and their management.

Since 2010, the numbers of refugees have increased and around half are under 18years of age. It is known that experience of organised violence, displacement and resettlement increases the risk for psychiatric disorders and psychosocial impairment. This review integrates recent research into the risk and protective factors for psychopathology with service and treatment issues. We draw on and critically evaluate key systematic reviews in the selected areas, innovative robust studies and relevant government reports. Many refugee children show resilience and function well, even in the face of substantial adversities. The most robust findings for psychopathology are that PTSD, and posttraumatic and depressive symptoms are found at higher prevalence in those who have been exposed to war experiences. Their severity may decrease over time with resettlement, but PTSD in the most exposed may show higher continuity. More severe psychiatric disorders including psychosis may also occur. Service delivery needs to take into account socioeconomic and cultural influences but, given the high level of unmet need even in high-income countries, stepped care delivery is required. The evaluation of psychological interventions, often delivered in group settings, suggests that they can be effective for many distressed children; however, for the more impaired, a greater range of disorder-specific therapies will be required. Child and adolescent mental health clinicians and service providers need to be aware of the specific needs of this population and systems for service delivery. There are significant knowledge gaps in understanding risk and vulnerability, service delivery and treatment effectiveness.

Childhood trauma and negative memory bias as shared risk factors for psychopathology and comorbidity in a naturalistic psychiatric patient sample.

Background Both childhood trauma and negative memory bias are associated with the onset and severity level of several psychiatric disorders, such as depression and anxiety disorders. Studies on these risk factors, however, generally use homogeneous noncomorbid samples. Hence, studies in naturalistic psychiatric samples are lacking. Moreover, we know little about the quantitative relationship between the frequency of traumatic childhood events, strength of memory bias and number of comorbid psychiatric disorders; the latter being an index of severity. The current study examined the association of childhood trauma and negative memory bias with psychopathology in a large naturalistic psychiatric patient sample. Methods Frequency of traumatic childhood events (emotional neglect, psychological-, physical- and sexual abuse) was assessed using a questionnaire in a sample of 252 adult psychiatric patients with no psychotic or bipolar-I disorder and no cognitive disorder as main diagnosis. Patients were diagnosed for DSM-IV Axis-I and Axis-II disorders using a structured clinical interview. This allowed for the assessment of comorbidity between disorders. Negative memory bias for verbal stimuli was measured using a computer task. Results Linear regression models revealed that the frequency of childhood trauma as well as negative memory bias was positively associated with psychiatric comorbidity, separately and above and beyond each other (all p < .01). Conclusions The results indicate that childhood trauma and negative memory bias may be of importance for a broader spectrum of psychiatric diagnoses, besides the frequently studied affective disorders. Importantly, frequently experiencing traumatic events during childhood increases the risk of comorbid psychiatric disorders.

Trois profils cliniques à risque de comportements violents dans une cohorte de patients présentant un premier épisode de psychose

ObjectiveThis study aims to determine whether it is possible to identify clinical profiles at risk of violent behaviors (VB) in the early phase of psychotic disorders, on the basis of the main dynamic psychopathological risk factors and describe characteristics of the groups with highest levels of violent behaviors. MethodA total of 265 patients, aged 18 to 35, treated at the Treatment and early Intervention in Psychosis Program (TIPP–Lausanne), a specialized early psychosis program, were included in this study. We conducted a latent-class analysis and a discriminative analysis on the basis of the main dynamic VB risk factors: substance use disorder, impulsivity, positive symptoms, insight, aggression, hostility, anger, emotional instability and adherence to treatment. These factors were evaluated by specialized scales and on the basis of the Positive and Negative Syndrome Scale (PANSS). VB were restricted to physical aggression against people, defined as “serious violence”. They were assessed on the basis of a questionnaire listing violent offenses (Swiss Criminal Code) and VB such as assault and battery, information through the forensic psychiatric services and on the basis of the Staff Observation Aggression Scale (SOAS-R scale) during inpatient treatment phase. ResultsFour heterogeneous subgroups were identified with respect to the studied clinical characteristics, including two groups with high rates of VB. The first group, comprising 46% of patients with VB, is distinguished by the prevalence of a range of dimensions related to hostility, impulsivity and emotional instability, associated with high levels of substance abuse and positive symptoms. These clinical dimensions are very significant at the statistical level, since they explain 70% of the construction of subgroups (discriminant analysis). The second group with 37% of patients with VB, is characterized by a lack of insight, lack of adherence to treatment and substance use. These two clinical profiles could increase the impairment of cognitive, functional and relational abilities and contribute to the development of VB in this early phase of psychosis. The third subgroup, with a violent behaviors rate of 28.6%, is distinguished by its high proportion of diagnoses of substance abuse (100%) and women (54%). A last subgroup of patients, the largest quantitatively, has a low proportion of VB (15%) and the lowest levels on the studied factors, suggesting that the majority of patients with this profile commit few VB. ConclusionOur results show that it is possible to identify groups at risk of violent behaviors during the early phase of psychosis on the basis of clinical characteristics that may evolve and therefore be the focus of preventive care. These results highlight the need to target substance use, impulsivity and lack of insight at follow-up in order to prevent VB.

Susceptibility or Resilience to Maltreatment Can Be Explained by Specific Differences in Brain Network Architecture

BackgroundChildhood maltreatment is a major risk factor for psychopathology. However, some maltreated individuals appear remarkably resilient to the psychiatric effects while manifesting the same array of brain abnormalities as maltreated individuals with psychopathology. Hence, a critical aim is to identify compensatory brain alterations that enable resilient individuals to maintain mental well-being despite alterations in stress-susceptible regions. MethodsNetwork models were constructed from diffusion tensor imaging and tractography in physically healthy unmedicated 18- to 25-year-old participants (N = 342, n = 192 maltreated) to develop network-based explanatory models. ResultsFirst, we determined that susceptible and resilient individuals had the same alterations in global fiber stream network architecture using two different definitions of resilience: 1) no lifetime history of Axis I or II disorders, and 2) no clinically significant symptoms of anxiety, depression, anger-hostility, or somatization. Second, we confirmed an a priori hypothesis that right amygdala nodal efficiency was lower in asymptomatic resilient than in susceptible participants or control subjects. Third, we identified eight other nodes with reduced nodal efficiency in resilient individuals and showed that nodal efficiency moderated the relationship between maltreatment and psychopathology. Fourth, we found that models based on global network architecture and nodal efficiency could delineate group membership (control, susceptible, resilient) with 75%, 82%, and 80% cross-validated accuracy. ConclusionsTogether these findings suggest that sparse fiber networks with increased small-worldness following maltreatment render individuals vulnerable to psychopathology if abnormalities occur in specific nodes, but that decreased ability of certain nodes to propagate information throughout the network mitigates the effects and leads to resilience.

The dynamics of persisting through distress: Development of a Momentary Distress Intolerance Scale using ecological momentary assessment.

Distress tolerance, or the ability to withstand uncomfortable states, is thought to be a transdiagnostic risk factor for psychopathology. Distress tolerance is typically measured using self-report questionnaires or behavioral tasks, both of which construe distress tolerance as a trait and downplay the potential variability in distress tolerance across time and situation. The aim of the current study was to provide a method for assessing momentary distress tolerance using ecological momentary assessment to capture both within- and between-individual information. Participants (n = 86) responded to random prompts on their cell phones seven times per day for one week, which included 10 momentary distress tolerance items as well as momentary emotion. After examining item distributions and interclass correlations, we conducted a multilevel exploratory factor analysis using both within-individual and between-individual data to arrive at a brief, 3-item measure we call the Momentary Distress Intolerance Scale. Model fit and reliability indices were good for both within- and between-individual approaches. We found that distress tolerance varied significantly over time, and that average momentary distress intolerance and instability in momentary distress intolerance were associated with trait distress tolerance, emotion dysregulation and tendencies to use experiential avoidance. Neither average momentary distress intolerance nor instability in momentary distress intolerance correlated with behavioral distress tolerance tasks. We discuss the importance of construing distress tolerance from a dynamic perspective and provide recommendations toward future research. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Emotion Reactivity and Regulation in Adolescent Girls Following an Interpersonal Rejection.

Failures in emotion regulation, especially as a result of interpersonal stress, are implicated as transdiagnostic risk factors for psychopathology. This study examines the effects of an experimentally timed targeted interpersonal rejection on emotion reactivity and regulation in typically developing adolescent girls. Girls ( n = 33, ages 9-16 years, M = 12.47, SD = 2.20) underwent fMRI involving a widely used emotion regulation task. The emotion task involves looking at negative stimuli and using cognitive reappraisal strategies to decrease reactions to negative stimuli. Participants also engaged in a social evaluation task, which leads participants to believe a preselected peer was watching and evaluating the participant. We subsequently told participants they were rejected by this peer and examined emotion reactivity and regulation before and after this rejection. Adolescent girls evidence greater reactivity via higher self-reported emotional intensity and greater amygdala activation to negative stimuli immediately after (compared with before) the rejection. Self-reported emotional intensity differences before and after rejection were not observed during regulation trials. However, on regulation trials, girls exhibited increased prefrontal activation in areas supporting emotion regulation after compared with before the rejection. This study provides evidence that a targeted rejection increases self-report and neural markers of emotion reactivity and that girls increase prefrontal activation to regulate emotions after a targeted rejection.

Maternal prenatal depressive symptoms and risk for early-life psychopathology in offspring: genetic analyses in the Norwegian Mother and Child Birth Cohort Study

Maternal prenatal depression is a known risk factor for early-life psychopathology among offspring; however, potential risk transmission mechanisms need to be distinguished. We aimed to test the relative importance of passive genetic transmission, direct exposure, and indirect exposure in the association between maternal prenatal depressive symptoms and early-life internalising and externalising psychopathology in offspring. We used structural equation modelling of phenotypic data and genetically informative relationships from the families of participants in the Norwegian Mother and Child Birth Cohort Study (MoBa). The analytic subsample of MoBa used in the current study comprises 22 195 mothers and 35 299 children. We used mothers' self-reported depressive symptoms during pregnancy, as captured by the Symptom Checklist, and their reports of symptoms of psychopathology in their offspring during the first few years of life (measured at 18, 36, and 60 months using the Child Behavior Checklist). Maternal prenatal depressive symptoms were found to be associated with early-life psychopathology primarily via intergenerationally shared genetic factors, which explained 41% (95% CI 36-46) of variance in children's internalising problems and 37% (30-44) of variance in children's externalising problems. For internalising problems, phenotypic transmission also contributed significantly, accounting for 14% (95% CI 5-19) of the association, but this contribution was found to be explained by exposure to concurrent maternal depressive symptoms, rather than by direct exposure in utero. Associations between maternal prenatal depressive symptoms and offspring behavioural outcomes in early childhood are likely to be at least partially explained by shared genes. This genetic confounding should be considered when attempting to quantify risks posed by in-utero exposure to maternal depressive symptoms. UK Economic and Social Research Council, Norwegian Research Council, Norwegian Ministries of Health and Care Services, and Education & Research, Wellcome Trust, Royal Society, and National Institute for Health Research.

Validation of the Prodromal Questionnaire-Brief in a representative sample of adolescents: Internal structure, norms, reliability, and links with psychopathology.

The main purpose of the present study was twofold: to validate the Prodromal Questionnaire-Brief (PQ-B) in a community-derived sample of adolescents and to examine the links between psychotic-like experiences and emotional and behavioral problems, prosocial behavior, suicidal ideation, and bipolar-like experiences. One thousand five hundred eighty-eight students selected by random sampling participated in a cross-sectional survey. The PQ-B, Paykel Suicide Scale, Strengths and Difficulties Questionnaire, Mood Disorder Questionnaire, Penn Matrix Reasoning Test, Family Affluence Scale-II, and Oviedo Infrequency Scale were used. The unidimensional factorial structure of the PQ-B items showed adequate goodness of fit index. This model also showed configural and strong invariance across gender. The internal consistency of the PQ-B total frequency score was 0.92. A high degree of overlap was found between psychotic-like experiences and emotional and behavioral problems, suicidal ideation, and bipolar-like experiences. The PQ-B is a brief, easy, and reliable tool for screening psychotic-like experiences in adolescents from the general population. The assessment of risk for psychosis and its relationship with other psychopathological risk factors in a close-in strategy or two-stage process model may help us to enhance the early identification for youths at heightened risk for serious mental disorders.

Avoidant/Restrictive Food Intake Disorder: A Longitudinal Study of Malnutrition and Psychopathological Risk Factors From 2 to 11 Years of Age.

Aim: To evaluate different types and degrees of malnutrition over time in a sample of children diagnosed with Infantile Anorexia (IA), based on the DC:0-3R criteria, and recently defined by DSM-5 as the first subtype of Avoidant/Restrictive Food Intake Disorder (ARFID), and to investigate the relationship between children’s severity of malnutrition and emotional/behavioral development, and mothers’ long-term psychopathological symptoms.Methods: A total of 113 children (58 boys, 55 girls), originally diagnosed with IA, and their mothers, were evaluated at four assessment points at the children’s mean age of 2, 5, 7, and 11 years. Several measures were used to assess the children’s growth and level of malnutrition, mothers’ psychopathological symptoms and eating attitudes, as well as their children’s emotional/behavioral functioning.Results: A steady improvement in the severity of malnutrition over time emerged, but 73% of children still had ongoing mild to moderate to severe malnutrition at 11 years of age. Moreover, the children showed increasing internalizing and externalizing emotional/behavioral problems, and their mothers’ psychopathological symptoms and eating problems worsened as well over time. At 11 years of age, the girls’ emotional/behavioral problems and their mothers’ psychopathology and disturbed eating attitudes were more severe than that of the boys and their mothers. Finally, during the last assessment, significant associations between the mothers’ psychopathology and disturbed eating attitudes, the severity of the children’s malnutrition, and their emotional/behavioral problems emerged.Discussion: Our longitudinal study points out that the developmental course of children, originally diagnosed with IA and who received limited psychosocial treatment, is characterized by an enduring risk of malnutrition and increasing psychopathological symptoms in both, the children and their mothers, up to the sensitive period of pre-puberty.

Risk factors for challenging behaviour and psychopathology in adults with Down syndrome.

This study explored the role of demographic, psychosocial, stress and life event-related risk factors for psychopathology and challenging behaviour in a clinical sample of adults with Down syndrome. A convenience sample of adults with Down syndrome seen through a specialised clinic was assessed through interviews and questionnaires specifically designed for use in people with intellectual disabilities. Recent negative life events and stressors were significantly correlated with mental and behavioural health, and significantly predicted irritability, lethargy and depressed mood. Social avoidance was predicted by stress related to anticipation and social-environmental stressors, and negatively predicted by verbal ability. Ritual-related stress predicted obsessive-compulsive behaviour. Participants who did not have a job or vocational placement were significantly more depressed than participants who did. Adults with Down syndrome should be provided increased supports for coping with negative life events and stressors. Interventions should also emphasise community engagement, such as employment, and access to psychosocial supports that teach coping and self-regulation skills when faced with stressors and negative life events.

Psychophysiological reactivity, coping behaviour and intrusive memories upon multisensory Virtual Reality and Script-Driven Imagery analogue trauma: A randomised controlled crossover study

BackgroundPeri- and post-traumatic factors predict the differential development of stress-associated mental disorders. Prospective designs assessing these risk factors in real-time under controlled experimental conditions can overcome limitations of retrospective designs. Therefore, we aimed to investigate multi-sensory, experimental analogues of a traumatic experience delivered in Virtual Reality (VR) or Script-Driven Imagery (SDI). MethodsIn a randomised controlled crossover design, differences in the induced analogue trauma symptoms between multi-sensory analogue trauma by either VR or SDI versus a neutral condition were assessed in 127 non-clinical participants. ResultsAnalogue symptoms (psychophysiological responses, coping behaviour and intrusive memories of the experimental trauma) increased following analogue trauma in both VR and SDI, with more analogue symptoms for VR. Psychophysiological arousal was in general higher in VR. LimitationsThe analogue trauma situation of a car park fire that was used may be infrequent in real life. ConclusionsMultisensory (vision, olfaction, hearing) analogue trauma in VR and SDI offers a useful tool for the induction and real-time assessment of peri- and post-traumatic risk factors for analogue stress-associated psychopathology. VR was more effective in inducing analogue symptoms than SDI, even though the latter might be more personalised. New experimental models for studying trauma exposure and responses may contribute to a better understanding of risk factors and help to identify and protect individuals at risk.

Extinction Learning as a Potential Mechanism Linking High Vagal Tone with Lower PTSD Symptoms among Abused Youth.

Childhood abuse is a potent risk factor for psychopathology, including posttraumatic stress disorder (PTSD). Research has shown high resting vagal tone, a measure of parasympathetic nervous system function, protects abused youth from developing internalizing psychopathology, but potential mechanisms explaining this effect are unknown. We explored fear extinction learning as a possible mechanism underlying the protective effect of vagal tone on PTSD symptoms among abused youth. We measured resting respiratory sinus arrhythmia (RSA) and skin conductance responses (SCR) during a fear conditioning and extinction task in youth with variability in abuse exposure (N = 94; aged 6-18years). High RSA predicted lower PTSD symptoms and enhanced extinction learning among abused youths. In a moderated-mediation model, extinction learning mediated the association of abuse with PTSD symptoms only among youth with high RSA. These findings highlight extinction learning as a possible mechanism linking high vagal tone to decreased risk for PTSD symptoms among abused youth.

A Cybernetic Theory of Psychopathology

Cybernetics, the study of principles governing goal-directed, self-regulating systems, offers a useful approach to understanding psychopathology or psychological dysfunction, overcoming limitations of other naturalistic approaches. Whereas influential theories of psychopathology have relied on definitions of dysfunction rooted in evolution and fitness, we define psychopathology in terms of cybernetic dysfunction, failure to make progress toward important goals. Cybernetic function in organisms is not identical to evolutionary function, despite their causal phylogenetic relationship. We define psychopathology as persistent failure to move toward one’s goals, due to failure to generate effective new goals, interpretations, or strategies when existing ones prove unsuccessful. This definition allows a thorough integration of dimensional approaches to psychopathology and personality and provides a new perspective on the nosology of mental disorder. We review evidence that the major dimensions of psychopathology correspond to major trait dimensions of personality, but we assert that extremity on these dimensions is neither necessary nor sufficient for psychopathology, which requires cybernetic dysfunction. Drawing from psychological and neurobiological research on personality and psychopathology, we present a theory of the mechanisms underlying the five major dimensions of psychopathology, some of their subdimensions, and the general risk factor for psychopathology. We conclude by discussing implications of our theory for research, diagnosis, and mental health interventions.

Dominance relationships in Syrian hamsters modulate neuroendocrine and behavioral responses to social stress

Stress is a well-known risk factor for psychopathology and rodent models of social defeat have strong face, etiological, construct and predictive validity for these conditions. Syrian hamsters are highly aggressive and territorial, but after an acute social defeat experience they become submissive and no longer defend their home territory, even from a smaller, non-aggressive intruder. This defeat-induced change in social behavior is called conditioned defeat (CD). We have shown that dominant hamsters show increased neural activity in the ventromedial prefrontal cortex (vmPFC) following social defeat stress and exhibit a reduced CD response at social interaction testing compared to subordinates. Although the vmPFC can inhibit the neuroendocrine stress response, it is unknown whether dominants and subordinates differ in stress-induced activity of the extended hypothalamic-pituitary-adrenal (HPA) axis. Here, we show that, following acute social defeat, dominants exhibit decreased submissive and defensive behavior compared to subordinates but do not differ from subordinates or social status controls (SSCs) in defeat-induced cortisol concentrations. Furthermore, both dominants and SSCs show greater corticotropin-releasing hormone (CRH) mRNA expression in the basolateral/central amygdala compared to subordinates, while there was no effect of social status on CRH mRNA expression in the paraventricular nucleus of the hypothalamus or bed nucleus of the stria terminalis. Overall, status-dependent differences in the CD response do not appear linked to changes in stress-induced cortisol concentrations or CRH gene expression, which is consistent with the view that stress resilience is not a lack of a physiological stress response but the addition of stress coping mechanisms.Lay summaryDominant hamsters show resistance to the behavioral effects of acute social defeat compared to subordinates, but it is unclear whether social status modulates the neuroendocrine stress response in Syrian hamsters. This study indicates that dominant social status does not alter stress-induced activity of the extended hypothalamic-pituitary-adrenal (HPA) axis, which suggests that the ability of dominants to cope with social defeat stress is not associated with changes in their neuroendocrine stress response.