Social stress in tree shrews as an animal model of depression: an example of a behavioral model of a CNS disorder

Animal models are invaluable in preclinical research on human psychopathology. Valid animal models to study the pathophysiology of depression and specific biological and behavioral responses to antidepressant drug treatments are of prime interest. In order to improve our knowledge of the causal mechanisms of stress-related disorders such as depression, we need animal models that mirror the situation seen in patients. One promising model is the chronic psychosocial stress paradigm in male tree shrews. Coexistence of two males in visual and olfactory contact leads to a stable dominant/subordinate relationship, with the subordinates showing obvious changes in behavioral, neuroendocrine, and central nervous activity that are similar to the signs and symptoms observed during episodes of depression in patients. To discover whether this model, besides its "face validity" for depression, also has "predictive validity," we treated subordinate animals with the tricyclic antidepressant clomipramine and found a time-dependent recovery of both endocrine function and normal behavior. In contrast, the anxiolytic diazepam was ineffective. Chronic psychosocial stress in male tree shrews significantly decreased hippocampal volume and the proliferation rate of the granule precursor cells in the dentate gyrus. These stress-induced changes can be prevented by treating the animals with clomipramine, tianeptine, or the selective neurokinin receptor antagonist L-760,735. In addition to its apparent face and predictive validity, the tree shrew model also has a "molecular validity" due to the degradation routes of psychotropic compounds and gene sequences of receptors are very similar to those in humans. Although further research is required to validate this model fully, it provides an adequate and interesting non-rodent experimental paradigm for preclinical research on depression.     

树鼩的社会挫败抑郁模型

创制理想的动物模型是突破抑郁症研究的技术难点之一。来自进化研究的证据提示, 树鼩属灵长类近缘的一种小型动物, 具有较为发达的神经系统和与人类相似的应激系统, 因而可能成为创制精神疾病行为模型的较佳选择。已有的研究表明, 树鼩社会挫败模型可能具有比啮齿类更好的表面效度、预测效度及结构效度。由于树鼩与人类的近缘关系, 对其抑郁行为的脑机制研究或药物评价可能更具潜在价值。但是, 该模型仍有待进一步利用、拓展和完善。     

焦虑和抑郁动物模型的研究方法和策略

焦虑和抑郁障碍是严重威胁人们健康的精神疾病。焦虑和抑郁动物模型是通过一定的心理社会应激使动物产生明显的焦虑和抑郁情绪,模拟人类焦虑和抑郁障碍,以探讨其细胞、分子和基因水平机制。情绪障碍动物模型通常通过表面效度、结构效度和预测效度进行评价。目前的动物模型虽然存在一定的缺点,但已经为临床和科研提供了巨大帮助。     

Attenuation of Hippocampal 11beta-Hydroxysteroid Dehydrogenase Type 1 by Chronic Psychosocial Stress in the Tree Shrew

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyses the interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone, thus regulating glucocorticoid access to intracellular receptors. In rats, chronic glucocorticoid excess or stress increases 11beta-HSD-1 in the hippocampus, producing suggestions that it may attenuate the deleterious effects of chronic glucocorticoid excess. However, 11beta-HSD-1 predominantly catalyses 11beta-reduction in the intact liver and hippocampal cells, thus regenerating active glucocorticoids from inert substrate. We studied 11beta-HSD activity in the tissues of male tree shrews following 28 days of sustained psychosocial stress or exogenous administration of cortisol. In the hippocampus, chronic psychosocial stress attenuated 11-HSD-1 activity (69 +/- 9% of control), whereas cortisol alone had no effect. In the liver, both chronic stress and cortisol administration decreased 11beta-HSD-1 activity (47 +/- 11% and 49 +/- 4% fall, resp.). Attenuation of 11beta-HSD-1 within tissues may reflect a homeostatic mechanism designed to minimise the adverse effects of prolonged stress and/or glucocorticoid excess.     

Catastrophizing as a Cognitive Vulnerability Factor Related to Depression in Workers’ Compensation Patients with Chronic Musculoskeletal Pain

The purpose of this study was to examine the role of catastrophizing as a mediator and moderator between life stress and depression in a sample of workers’ compensation patients with chronic musculoskeletal pain. Pain intensity, life stress (especially work and financial stress), and catastrophizing contributed significantly to depression. Catastrophizing was found to be partially mediating the relationship between life stress and depression and a moderator between social stress and depression. The results supported the role of catastrophizing as a cognitive vulnerability-stress factor related to depression in chronic pain patients. Screening for life stress and intervening early to prevent catastrophizing from occurring in the workers’ compensation rehabilitation process may reduce psychosocial distress and enhance the overall effectiveness of rehabilitation programming for workers’ compensation patients with chronic pain.     

The Effects of Spirituality and Religion on Outcomes in Patients with Chronic Heart Failure

Heart failure (HF) is a chronic progressive disease with marked morbidity and mortality. Patients enduring this condition suffer from fluctuations in symptom burden such as fatigue, shortness of breath, chest pain, sexual dysfunction, dramatic changes in body image and depression. As physicians, we often ask patients to trust in our ability to ameliorate their symptoms, but oftentimes we do not hold all of the answers, and our best efforts are only modestly effective. The suffering endured by these individuals and their families may even call into question one??s faith in a higher power and portends to significant spiritual struggle. In the face of incurable and chronic physical conditions, it seems logical that patients would seek alternative or ancillary methods, notably spiritual ones, to improve their ability to deal with their condition. Although difficult to study, spirituality has been evaluated and deemed to have a beneficial effect on multiple measures including global quality of life, depression and medical compliance in the treatment of patients with HF. The model of HF treatment incorporates a multidisciplinary approach. This should involve coordination between primary care, cardiology, palliative care, nursing, patients and, importantly, individuals providing psychosocial as well as spiritual support. This review intends to outline the current understanding and necessity of spirituality??s influence on those suffering from HF.     

The direct and interactive effects of neuroticism and life stress on the severity and longitudinal course of depressive symptoms

The direct and interactive effects of neuroticism and stressful life events (chronic and episodic stressors) on the severity and temporal course of depression symptoms were examined in 826 outpatients with mood and anxiety disorders, assessed on 3 occasions over a 1-year period (intake and 6- and 12-month follow-ups). Neuroticism, chronic stress, and episodic stress were uniquely associated with intake depression symptom severity. A significant interaction effect indicated that the strength of the effect of neuroticism on initial depression severity increased as chronic stress increased. Although neuroticism did not have a significant direct effect on the temporal course of depression symptoms, chronic stress significantly moderated this relationship such that neuroticism had an increasingly deleterious effect on depression symptom improvement as the level of chronic stress over follow-up increased. In addition, chronic stress (but not episodic stress) over follow-up was uniquely predictive of less depression symptom improvement. Consistent with a stress generation framework, however, initial depression symptom severity was positively associated with chronic stress during follow-up. The results are discussed in regard to diathesis-stress conceptual models of emotional disorders and the various roles of stressful life events in the onset, severity, and maintenance of depressive psychopathology.     

Effects of chronic social stress during lactation on maternal behavior and growth in rats

Maternal mood disorders such as depression and chronic anxiety can negatively affect the lives of not only mothers, but also of partners, offspring, and future generations. Chronic exposure to psychosocial stress is common in postpartum mothers, and one of the strongest predictors of postpartum depression is social conflict. The objective of the current study was to evaluate the effects of chronic social stress (CSS) during lactation on the maternal behavior (which consists of maternal care and aggression toward a novel conspecific) of lactating rats, as well as on the growth of the dams and their offspring. It was hypothesized that chronic daily exposure to a novel male intruder would alter the display of maternal behavior and impair growth in both the dam and offspring during lactation due to the potentially disruptive effects on maternal behavior and/or lactation. The data indicate that CSS during lactation attenuates maternal care and the growth of both dams and pups, and increases self-grooming and maternal aggression toward a novel male intruder. These results support the use of CSS as a relevant model for disorders that impair maternal behavior and attenuate growth of the offspring, such as postpartum depression and anxiety.     

Chronic psychosocial stress induces visceral hyperalgesia in mice

Experimental and clinical evidence has shown that chronic stress plays an important role in the onset and/or exacerbation of symptoms of functional gastrointestinal disorders. Here, we aimed to investigate whether exposure to a chronic and temporally unpredictable psychosocial stressor alters visceral and somatic nociception as well as anxiety-related behaviour. In male C57BL/6J mice, chronic stress was induced by repeated exposure to social defeat (SD, 2?h) and overcrowding (OC, 24?h) during 19 consecutive days. Visceral and somatic nociception was evaluated by colorectal distension and a hot plate, respectively. The social interaction test was used to assess social anxiety. Mice exposed to psychosocial stress developed visceral hyperalgesia and somatic hypoalgesia 24?h following the last stress session. SD/OC mice also exhibited social anxiety-like behaviour. All these changes were also associated with physiological alterations, measured as a decreased faecal pellet output and hypothalamic-pituitary-adrenal (HPA) axis disruption. Taken together, these data confirm that this mouse model of chronic psychosocial stress may be useful for studies on the pathophysiological mechanisms underlying such stress-associated disorders and to further test potential therapies.     

Self-esteem reconsidered: unstable self-esteem outperforms level of self-esteem as vulnerability marker for depression

Previous studies have built up evidence that an unstable self-esteem is associated with vulnerability to depression and that it outperforms level of self-esteem as a predictor for symptoms of depression. However, most of these studies have used student samples exclusively to investigate the role of self-esteem instability in depression vulnerability. Our present study used samples of currently depressed inpatients, formerly depressed individuals, and never-depressed controls to investigate the relationship between self-esteem instability and depression. In addition, we examined the predictive validity of self-esteem instability in predicting future depressive symptoms. The results indicate that self-esteem instability is associated with depression and vulnerability to depression. Furthermore, self-esteem instability interacted with perceived stress variability and depressed mood variability in predicting future depressive symptomatology at six months follow-up. These results are in line with the diathesis-stress model and support the hypothesis that self-esteem instability might be more important than level of self-esteem in predicting vulnerability to depression.     

Problem-Solving Appraisal and Psychological Adjustment of Persons with Chronic Low-Back Pain

To examine the role of self-appraised problem-solving ability in the prediction of psychosocial impairment, depression, hopelessness, average pain unpleasantness, and current pain ratings among persons with chronic low-back pain. A second purpose was to enhance theoretical understanding of the mechanisms by which problem-solving appraisal influences adjustment. Correlational and regression procedures were used to test the hypothesized relations procedures between elements of self-appraised problem-solving ability and each criterion variable. Seventy-eight persons enrolled in an inpatient multidisciplinary chronic pain management program. The psychosocial subscale of the Sickness Impact Profile, the Beck Depression Inventory, the Beck Hopelessness Scale, the McGill Pain Questionnaire, and Visual Analogue Scales of Pain Sensory Intensity and Affective Response were the main outcome measures. After first controlling demographic characteristics, elements of self-appraised problem-solving ability assessed by the Problem-Solving Inventory were significantly predictive of depression, hopelessness, psychosocial impairment, and average pain unpleasantness (accounting for 20, 26, 29, and 11% of the respective variance in these constructs). Results indicate complex relations among the elements of problem-solving appraisal, suggesting that the Approach–Avoidance link to psychological adjustment was mediated by Problem-Solving Confidence. Comprehensive problem-solving interventions may be beneficial to persons with chronic pain     

Fatigue Impact Scale: Its validation in patients with chronic obstructive pulmonary disease

The aim of this study was to investigate the reliability and validity of the Fatigue Impact Scale (FIS) among patients with chronic obstructive pulmonary disease (COPD) and shorten the questionnaire. The empirically developed FIS, which comprised three subscales (cognitive, physical and psychosocial), was tested originally on Pipers' theoretical framework of subjective manifestations of fatigue, including behavioural, physical, emotional and cognitive expressions. The data analysed here consisted of responses from 296 patients with COPD who reported fatigue. The dimensionality of the FIS was examined using confirmatory factor analysis. A reduction of 15 items from the original FIS was made based on theory, modification indices and factor loadings. The results indicate that a nested-factor model with one general behavioural factor and three specific factors, physical, emotional and cognitive, shows acceptable fit. A modified version of 25 items, FIS-25 was developed. The original FIS and the FIS-25 were able to discriminate between patients with differing duration of fatigue. Test - retest correlations ranged from .70 to .85 for items and .94 for the total scale. Due to modification, the FIS-25 needs to be validated on a new group of patients with COPD.     

Shame,Early Abuse,and Course of Depression in a Clinical Sample: A Preliminary Study

This study of 35 depressed patients was designed to replicate findings from a community sample of a relationship between childhood abuse and bodily shame, and bodily shame and chronic or recurrent depression. In addition, we investigated whether characterological and behavioural shame would also be related to early abuse and depression course. The relation between bodily shame and childhood abuse was replicated. When the other types of shame were considered, bodily shame was the most powerful correlate of early abuse, with behavioural shame showing no relationship. However, all three types of shame appeared to be related to chronic or recurrent course of depression.     

The relationship of appraisal and coping to chronic illness adjustment

There is evidence that adaptation to chronic illness may be affected by psychological factors, especially how patients appraise and cope with the stress of their illness. The purpose of the present study was to examine the relationship of stress appraisal and coping responses to multiple behavioral indices of illness adjustment among patients with diverse chronic medical conditions. One hundred and one patients admitted to a multidisciplinary medicine/psychiatry unit completed measures of functional impairment, depression, symptom severity, and the Ways of Coping Checklist--Revised. Hierarchical regression analyses indicated that emotion-focused coping was positively related to poor psychosocial adjustment and depression after controlling for physician rated disease severity. Appraising chronic illness as holding one back predicted greater emotion-focused coping responses and poorer adjustment to illness. The use of problem-focused coping strategies was generally unrelated to illness adjustment. These findings suggest the presence of an emotion-focused coping triad consisting of wishful thinking, self blame, and avoidance, all of which appear to be maladaptive strategies when coping with chronic medical conditions. Implications for coping skills training and the need for longitudinal research is discussed.     

Good and Bad Sides of Self-Compassion: A Face Validity Check of the Self-Compassion Scale and an Investigation of its Relations to Coping and Emotional Symptoms in Non-Clinical Adolescents

To demonstrate that the positive and negative subscales of Self-Compassion Scale (SCS) are very different in nature, we conducted a series of face validity checks on the items of this questionnaire among psychologists and psychology students (Study 1). Furthermore, a survey was administered to a convenience sample of non-clinical adolescents to examine the relations between various SCS subscales and symptoms of anxiety and depression as well as coping styles (Study 2). The results of the face validity checks revealed that the positive subscales seem to be well in line with the protective nature of self-compassion as they were mainly associated with cognitive coping and healthy functioning, whereas the negative subscales were chiefly associated with psychopathological symptoms and mental illness. The survey data demonstrated that the positive SCS subscales were positively correlated with adaptive coping (r’s between .22 and .50) and negatively correlated with symptoms of anxiety and depression (r’s between ?.19 and ?.53), while the negative subscales were positively correlated with symptoms (r’s between .49 and .61) and maladaptive coping strategies such as passive reacting (r’s between .53 and .56). Additional analyses indicated the negative subscales of the SCS accounted for a significant proportion of the variance in symptoms, whereas the unique contribution of the positive SCS subscales was fairly marginal. We caution to employ the total SCS score that includes the reversed negative subscales as such a procedure clearly inflates the relation between self-compassion and psychopathology.     

Development and validation of a measure of cognitive and behavioural social self-efficacy

Although social self-efficacy appears influential across a broad spectrum of human behaviour, existing adult measures of social self-efficacy have conceptual and psychometric limitations. The current research brought together the realms of trait social intelligence and self-efficacy to develop and evaluate a measure of social self-efficacy which for the first time included assessment of cognitive domains of social self-efficacy. Items were administered to 301 participants, along with measures of general self-efficacy, subjective wellbeing, social anxiety, depression, general anxiety, and stress. An exploratory factor analysis (Maximum Likelihood with Direct Oblimin extraction) revealed two interpretable factors that were labeled “Social Understanding Self-efficacy” (cognitive) and “Social Skill Self-efficacy” (behavioural). Construct and criterion validity were evident and internal consistency and test–retest reliability were good. It was concluded that the new 18-item measure has sound psychometric properties. As such, this measure may serve as a meaningful tool for researchers and clinicians. While theoretical and empirical frameworks informed the current research, given the exploratory nature of this study, future research should further investigate the psychometric properties of this measure using confirmatory factor analysis and by examining the predictive validity of this measure in a clinical context.     

Implicit but not explicit self-esteem predicts future depressive symptomatology

To date, research on the predictive validity of implicit self-esteem for depressive relapse is very sparse. In the present study, we assessed implicit self-esteem using the Name Letter Preference Task and explicit self-esteem using the Rosenberg self-esteem scale in a group of currently depressed patients, formerly depressed individuals, and never depressed controls. In addition, we examined the predictive validity of explicit, implicit, and the interaction of explicit and implicit self-esteem in predicting future symptoms of depression in formerly depressed individuals and never depressed controls. The results showed that currently depressed individuals reported a lower explicit self-esteem as compared to formerly depressed individuals and never depressed controls. In line with previous research, all groups showed a positive implicit self-esteem not different from each other. Furthermore, after controlling for initial depressive symptomatology, implicit but not explicit self-esteem significantly predicted depressive symptoms at six months follow-up. Although implicit self-esteem assessed with the Name Letter Preference Test was not different between formerly depressed individuals and never depressed controls, the findings suggest it is an interesting variable in the study of vulnerability for depression relapse.     

Concurrent Validity of the Strengths and Difficulties Questionnaire in an Indigenous Pre-School Population

The strengths and difficulties questionnaire (SDQ) is a frequently used tool for universal screening of pre-schoolers’ behavioural and emotional problems. However, evidence for its concurrent validity is equivocal and has not been tested in a Māori population. We aimed to evaluate the concurrent validity of the strengths and difficulties questionnaire (SDQ) in Māori pre-schoolers (tamariki), aged 4 and 5. We carried out a prospective study of 225 tamariki (46% female) for whom a recent SDQ was available from the New Zealand Ministry of Health’s Before School Check database. A trained nurse carried out a standardised wellbeing and behavioural assessment for these children. Sensitivity, specificity, positive predictive and negative predictive values were calculated, using optimal total difficulty scale threshold values published for the SDQ (parent version SDQ-P; teacher version SDQ-T). Primary outcome: an assessment-based child referral to Child and Adolescent Mental Health Services or to a Paediatric outpatient service. Secondary outcomes: assessment-based parental referral to a parenting programme and combined referral. The optimal thresholds for child referral were low for the SDQ-P (13) and SDQ-T (7). Child referral SDQ-P: sensitivity 62%, specificity 83%, positive predictive value 0.35, negative predictive value 0.94. Child referral SDQ-T: sensitivity 77%, specificity 78%, positive predictive value 0.31, negative predictive value 0.96. The findings demonstrate optimal threshold values for referral for Māori on the SDQ-P and SDQ-T are much lower when compared to published thresholds (17 vs. 16). Sensitivity values were also low. A surveillance approach for the assessment of psychosocial problems is recommended for pre-schoolers.     

The validity and clinical utility of the MMPI-2 Malingering Depression scale

In this study, we examined the validity and clinical utility of the MMPI-2 (Butcher, Graham, Tellegen, Dahlstrom, & Kaemmer, 2001) Malingering Depression scale (Md) in relation to the MMPI-2 F scales (F, F(B), F(P)) to detect feigned depression. Overall, the F(B) scale and the F/F(P) scale combination were the best single predictors, although the Md scale did discriminate successfully cases of feigned depression from patients with bona fide depression. The Md scale added predictive capacity over the F scales, and the F(B) scale and the F/F(P) scale combination added predictive capacity over the Md scale; however, the actual increase in the number of cases predicted was minimal in each instance. In sum, although the Md scale is able to detect accurately feigned depression on the MMPI-2 (predictive validity), it does not confer a distinct advantage (incremental validity) over the existing standard validity scales-F, F(B), and F(P).     

Comparison of DSM-III-R chronic major depression and major depression superimposed on dysthymia (double depression): validity of the distinction

The nosology of chronic depression has become increasingly complex since the publication of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987), but there are few data available to evaluate the validity of the distinctions between the subtypes of chronic depression. The validity of the distinction between DSM-III-R chronic major depression (CMD) and major depression superimposed on dysthymia (double depression, DD) was examined. Participants were 635 patients with chronic depression in a 12-week trial of antidepressant medications. Patients with CMD, DD, and a 3rd group with a chronic major depressive episode superimposed on dysthymia (DD/CMD) were compared on demographic and clinical characteristics, family history, and response to treatment. Few differences were evident, although the depression of patients with DD/CMD tended to be more severe.