The Evolving Nexus of Sleep and Depression.

Sleep disturbances and depression are closely linked and share a bidirectional relationship. These interconnections can inform the pathophysiology underlying each condition. Insomnia is an established and modifiable risk factor for depression, the treatment of which offers the critical opportunity to prevent major depressive episodes, a paradigm-shifting model for psychiatry. Identification of occult sleep disorders may also improve outcomes in treatment-resistant depression. Sleep alterations and manipulations may additionally clarify the mechanisms that underlie rapid-acting antidepressant therapies. Both sleep disturbance and depression are heterogeneous processes, and evolving standards in psychiatric research that consider the transdiagnostic components of each are more likely to lead to translational progress at their nexus. Emerging tools to objectively quantify sleep and its disturbances in the home environment offer great potential to advance clinical care and research, but nascent technologies require further advances and validation prior to widespread application at the interface of sleep and depression.

Abnormal nocturnal behavior due to hypoglycemia: A case report.

RATIONALE: Hypoglycemia, which is characterized mainly by palpitations, dizziness, and sweating, is common and easy to identify. However, some other symptoms, such as mental disorder or abnormal behavior, are atypical, which may lead to a misdiagnosis of epilepsy, sleepwalking, infarction, or mental disorder, among others. PATIENT CONCERNS: We report a case of a patient with type 2 diabetes who presented with abnormal nocturnal behavior due to hypoglycemia. DIAGNOSIS: Hypoglycemia was diagnosed based on a blood glucose level of 2.1 mmol/L when the patient turned up disoriented unresponsive, unable to understand what was said to him, and producing nonsensical speech. After the patient ate a piece of chocolate, his consciousness returned to normal and all mental symptoms disappeared. Polysomnography (PSG) was synchronously performed. The results of the PSG did not show any signs of abnormality during nonrapid eye movement (NREM) or rapid eye movement (REM) sleep. INTERVENTIONS: We regulated his dose of insulin. OUTCOMES: No additional episodes occurred during the 3-month follow-up. Therefore, the abnormal nocturnal behavior of this patient was determined to be due to hypoglycemia, while the cause of the hypoglycemia was insulin overuse. LESSONS: For physicians, if the cause of abnormal behavior cannot be detected, hypoglycemia should be suspected. Long-term persistent hypoglycemia may cause brain dysfunction and even result in permanent brain damage.

Evaluation of quality of sleep in women with stress urinary incontinence before and after surgical correction.

OBJECTIVE: To evaluate the quality of sleep in women with urinary incontinence before and after sling surgery. METHODS: A prospective study of case series of women with urodynamic diagnosis of stress urinary incontinence. To evaluate the subjective quality of sleep, two specific questionnaires were used and validated for the Portuguese Language: Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. The questionnaires were applied before and 6 months after surgical repair. RESULTS: When analyzing the Epworth Sleepiness Scale, there was an improvement in sleep quality (p=0.0401). For the Pittsburgh Sleep Quality Index, only for sleep disorder there was improvement in quality of sleep after surgery (p=0.0127). CONCLUSION: Women with urinary incontinence, submitted to surgery with sling, showed improvement in both quality of sleep and sleep disorder.

Correlation between allopregnanolone levels and depressive symptoms during late menopausal transition and early postmenopause.

OBJECTIVES: This observational, cross-sectional study included 140 women with climacteric symptoms. The aim of the study was to evaluate the correlation between the presence and severity of depressive symptoms and allopregnanolone levels in women during late menopausal transition and early postmenopause. METHODS: The study group was divided into two groups: 45 women in late menopausal transition and 95 early postmenopausal women. We evaluated Kupperman index, Hamilton scale and serum follicle-stimulating hormone, luteinizing hormone, 17ß-estradiol, prolactin, total testosterone, dehydroepiandrosterone sulfate and allopregnanolone levels. RESULTS: We found that serum allopregnanolone concentration was lower in early postmenopausal women compared to women in late menopausal transition; that there was a correlation between serum allopregnanolone levels in early postmenopausal women and time since last menstruation, intensity of climacteric symptoms, and intensity of depression symptoms and that there was a correlation between serum allopregnanolone levels and several depression symptoms presence (shallow sleep and symptoms of the digestive tract in women during late menopause transition; feelings of guilt, sleep disorders and general somatic symptoms in early postmenopausal women). CONCLUSION: We concluded that reproductive aging is characterized by a reduction of allopregnanolone circulating levels that correlate to Hamilton depression index in early postmenopause and presence of specific depressive symptoms during late menopausal transition and early postmenopause.

Evaluation of quality of sleep in women with stress urinary incontinence before and after surgical correction / Avaliação da qualidade do sono em mulheres com incontinência urinária antes e depois da correção cirúrgica

ABSTRACT Objective: To evaluate the quality of sleep in women with urinary incontinence before and after sling surgery. Methods: A prospective study of case series of women with urodynamic diagnosis of stress urinary incontinence. To evaluate the subjective quality of sleep, two specific questionnaires were used and validated for the Portuguese Language: Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. The questionnaires were applied before and 6 months after surgical repair. Results: When analyzing the Epworth Sleepiness Scale, there was an improvement in sleep quality (p=0.0401). For the Pittsburgh Sleep Quality Index, only for sleep disorder there was improvement in quality of sleep after surgery (p=0.0127). Conclusion: Women with urinary incontinence, submitted to surgery with sling, showed improvement in both quality of sleep and sleep disorder.

RESUMO Objetivo: Avaliar a qualidade do sono em mulheres com incontinência urinária antes e após correção cirúrgica do tipo sling. Métodos: Estudo prospectivo do tipo série de casos de mulheres com diagnóstico urodinâmico de incontinência urinária de esforço. Para avaliar a qualidade subjetiva do sono, utilizaram-se dois questionários específicos e validados para a língua portuguesa: Escala de Sonolência de Epworth e Índice de Qualidade do Sono de Pittsburgh. Os questionários foram aplicados antes e 6 meses após a correção cirúrgica. Resultados: Ao analisar a Escala de Sonolência de Epworth, houve melhora da qualidade do sono (p=0,0401). Para o Índice de Qualidade do Sono de Pittsburgh, apenas para o transtorno do sono, houve melhora da qualidade do sono após a cirurgia (p=0,0127). Conclusão: Mulheres com incontinência urinária, submetidas à correção cirúrgica por meio de sling, apresentaram melhora tanto na qualidade do sono como no transtorno do sono.

Sleep disruption in chronic rhinosinusitis.

INTRODUCTION: Chronic rhinosinusitis (CRS) is a common disease of the upper airways and paranasal sinuses with a marked decline in quality of life (QOL). CRS patients suffer from sleep disruption at a significantly higher proportion (60 to 75%) than in the general population (8-18 %). Sleep disruption in CRS causes decreased QOL and is linked to poor functional outcomes such as impaired cognitive function and depression. Areas covered: A systematic PubMed/Medline search was done to assess the results of studies that have investigated sleep and sleep disturbances in CRS. Expert commentary: These studies reported sleep disruption in most CRS patients. The main risk factors for sleep disruption in CRS include allergic rhinitis, smoking, and high SNOT-22 total scores. The literature is inconsistent with regard to the prevalence of sleep-related disordered breathing (e.g. obstructive sleep apnea) in CRS patients. Although nasal obstruction is linked to sleep disruption, the extent of sleep disruption in CRS seems to expand beyond that expected from physical blockage of the upper airways alone. Despite the high prevalence of sleep disruption in CRS, and its detrimental effects on QOL, the literature contains a paucity of studies that have investigated the mechanisms underlying this major problem in CRS.

A Comparison of DSM-5 and DSM-IV Diagnostic Criteria for Posttraumatic Stress Disorder in Traumatized Refugees.

The aim of this study was to compare the prevalence rate and factor structure of posttraumatic stress disorder (PTSD) based on the diagnostic criteria of the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; DSM-5; American Psychiatric Association, , ) in traumatized refugees. There were 134 adult treatment-seeking, severely and multiply traumatized patients from various refugee backgrounds were assessed in their mother tongue using a computerized set of questionnaires consisting of a trauma list, the Posttraumatic Diagnostic Scale, and the new PTSD items that had been suggested by the DSM-5 Task Force of the American Psychiatric Association. Using DSM-IV, 60.4% of participants met diagnostic criteria for PTSD; using DSM-5, only 49.3% fulfilled all criteria (p < .001). Confirmatory factor analysis of DSM-IV and DSM-5 items showed good and comparable model fits. Furthermore, classification functions in the DSM-5 were satisfactory. The new Cluster D symptoms showed relatively high sensitivity, specificity, positive predictive power, and negative predictive power. The DSM-5 symptom structure appears to be applicable to traumatized refugees. Negative alterations in cognitions and mood may be especially useful for clinicians, not only to determine the extent to which an individual refugee is likely to meet criteria for PTSD, but also in providing targets for clinical intervention.

The enduring effects of early-childhood adversities and troubled sleep among Canadian adults: a population-based study.

OBJECTIVE: Although many studies have consistently found that early-childhood adversities are important risk factors for physical and mental health problems later in adulthood, few have examined the association between early-childhood adversities and troubled sleep. The objective of this study was to examine the association between early-childhood adversities and troubled sleep among adult Canadians. METHODS: Data for this paper (N = 19,349) were obtained from Statistics Canada's 2012 Canadian Community Health Survey-Mental Health (CCHS-MH). Logistic regression analysis was conducted to examine the association between early childhood adversities and troubled sleep, while accounting for various sociodemographic, socioeconomic, health, and mental health factors. RESULTS: Of the 19,349 respondents examined, 2748 representing 14.2% had troubled sleep. Controlling for sociodemographic, socioeconomic, health, and mental health factors, it was observed that for each additional childhood adversity experienced, the odds of having troubled sleep increased by 10% (odds ratio = 1.10, p <0.001, 95% confidence interval = 1.07-1.13). In addition, psychological distress, older age, being female, being unmarried, being white, a lower annual income, chronic pain, poor perceived health, and mental health difficulties were associated with troubled sleep. CONCLUSION: The results of this paper provide population-based evidence for childhood adversities as a major predictor of troubled sleep in adulthood. The long-standing effects of these adversities on sleep highlight the importance of early detection, such as consistent assessment of sleep habits for children, adolescents, and adults, who have experienced childhood adversities, in health and mental health settings.

Sleep disturbance, disability, and posttraumatic stress disorder in utility workers.

OBJECTIVE: The objective of the present study was to examine the associations between sleep disturbance, posttraumatic stress disorder (PTSD), and functional disability in a population exposed to a singular traumatic event. METHOD: The participants were a population of 2,453 predominantly male utility workers who were deployed to the World Trade Center site in the aftermath of the 9/11 attack. They underwent psychiatric screenings comprising measures of sleep disturbance, PTSD, and functional disability. RESULTS: Analyses indicated that (a) rates of sleep disturbances were significantly higher among participants diagnosed with PTSD than those without, (b) PTSD severity was significantly associated with sleep disturbance, and (c) sleep disturbance moderated the relationship between PTSD and disability. CONCLUSION: Sleep disturbance is associated with occupational, social functioning, and PTSD severity, suggesting that ameliorating sleep may lead to increased occupational and social functioning, as well as better treatment responses in PTSD.

[Depressive phenomenology at the outset of neuropaediatric diseases]. / Fenomenología depresiva al inicio de enfermedades neuropediátricas.

INTRODUCTION: Depressive phenomenology, in its diverse nosological forms, affects 8-10% of children and adolescents of general population. Most frequently mood disorders have a primary origin, following poligenic multifactorial model. Moreover there is a non negligible proportion of cases in which depressive symptoms accompany neurological illnesses or they even constitute a part of predominant manifestations at the clinical start of neurologic disease, or mark a point of inflexion in its course. The aim of the present article is to review relevant literature dealing with this topic. DEVELOPMENT: A significative higher frequency of depressive phenomenology, not explainable by hazard, can be an early manifestation in children and adolescents with: epileptic syndromes, sleep disorders, chronic recurrent cephalalgias, several neurometabolic diseases, and intracranial tumors. Points of coincidence have been shown in dysequilibrium of brain neurotransmitters (serotonine, noradrenaline, hyperglutamatergic states) which could not be hypothesized as maintaining both neurological and mood conditions. CONCLUSIONS: The suspiction of a neurological disease should be adopted in cases of mood disorder not easily explainable by familial antecedents or clear biographical stressors. The search for a brain disorder by means of a meticulous anamnesis and neurological clinical and ancillary exams makes possible to discover the brain disorder at a very early stage and ameliorate the chances of accurately manage both the neurological and mood disorders. The simultaneous treatment of both dimension of the illness helps to improve the patients' quality of life.

TITLE: Fenomenologia depresiva al inicio de enfermedades neuropediatricas.Introduccion. La depresion, en sus diversas formas, afecta al 8-10% de niños y adolescentes y en la mayor parte de casos su origen es primario, siguiendo el modelo genetico multifactorial. Pero hay una proporcion de pacientes, no bien cuantificada todavia, en la que la depresion acompaña precozmente una enfermedad neurologica o marca un punto de inflexion en el curso de esta. El objetivo es revisar la bibliografia al respecto. Desarrollo. Se observa fenomenologia depresiva, con una frecuencia significativamente mayor que por azar, en niños y adolescentes afectos de epilepsia, trastornos del sueño, cefaleas primarias cronicas recurrentes, enfermedades neurometabolicas y tumores intracraneales. En varias de estas patologias neuropediatricas se hipotetizan puntos de coincidencia fisiopatologica con la depresion a traves de un deficit de disponibilidad cerebral de serotonina y noradrenalina. No se considera aqui la depresion disadaptativa a una neurodiscapacidad cronica. Conclusiones. En niños y adolescentes, los trastornos del animo sintomaticos de enfermedad neurologica deben sospecharse en ausencia de antecedentes familiares o de experiencias vitales que los expliquen. La busqueda sistematica de anomalias neurologicas y los examenes complementarios permitirian en estos casos abordar precozmente el tratamiento de la enfermedad cerebral causante del cuadro depresivo. A su vez, como ocurre en casos de epilepsia, cefaleas o trastorno del sueño, la terapia farmacologica y psicologica del cuadro depresivo contribuye a mejorar la calidad de vida de los afectados.

[Sleep disorders and quality of life in refractory partial epilepsy: results of the SLEEP study]. / Alteraciones del sueño y calidad de vida en la epilepsia parcial refractaria: resultados del estudio SLEEP.

INTRODUCTION: Sleep disorders are frequent among patients with epilepsy and are correlated with a poorer quality of life. AIMS: To evaluate the prevalence of sleep disorders in patients with refractory and non-refractory focal epilepsy, and to explore the influence of these alterations on the quality of life of these patients. PATIENTS AND METHODS: An epidemiological, controlled, cross-sectional study was conducted in 150 outpatient neurology services. Patients who had been treated with two antiepileptic drugs since the onset of the disease (18-55 years) were recruited for the study. RESULTS: The sample included 237 patients with non-refractory focal epilepsy and 264 patients with refractory focal epilepsy. Twenty-two per cent of the non-refractory epilepsy group and 45% of the group with refractory epilepsy (p < 0.0001) suffered from some sleep disorder. The patients with refractory epilepsy had a poorer quality of life (p < 0.001) as measured with the quality of life questionnaire QOLIE-10. A positive significant correlation was observed between quality of life and quality of sleep, in both chronic insomnia (r = 0.65; p < 0.0001) and excessive daytime sleepiness (r = 0.43; p < 0.0001). CONCLUSIONS: Sleep disorders are more frequent in refractory than in non-refractory epilepsy, and affect the patients' quality of life.

TITLE: Alteraciones del sueño y calidad de vida en la epilepsia parcial refractaria: resultados del estudio SLEEP.Introduccion. Las alteraciones del sueño son frecuentes en pacientes con epilepsia y se correlacionan con una peor calidad de vida. Objetivos. Evaluar la prevalencia de las alteraciones del sueño en pacientes con epilepsia focal refractaria y no refractaria y explorar la influencia de estas alteraciones en la calidad de vida de los pacientes. Pacientes y metodos. Estudio epidemiologico, controlado, transversal, realizado en 150 consultas ambulatorias de neurologia. Se reclutaron pacientes que habian sido tratados con dos farmacos antiepilepticos desde el inicio de la enfermedad (18-55 años). Resultados. Se incluyeron 237 pacientes con epilepsia focal no refractaria y 264 pacientes con epilepsia focal refractaria. El 22% del grupo con epilepsia no refractaria y el 45% del grupo con epilepsia refractaria (p < 0,0001) padecian alguna altera­cion del sueño. Los pacientes con epilepsia refractaria tenian peor calidad de vida (p < 0,001) medida con el cuestionario de calidad de vida QOLIE-10. Se observo una correlacion positiva y significativa entre la calidad de vida y la calidad del sue­ño, tanto en el insomnio cronico (r = 0,65; p < 0,0001) como en la somnolencia excesiva diurna (r = 0,43; p < 0,0001). Conclusion. Las alteraciones del sueño son mas frecuentes en la epilepsia refractaria que en la no refractaria, y afectan a la calidad de vida de los pacientes.

Cognition in perimenopause: the effect of transition stage.

OBJECTIVE: The aims of this cross-sectional study were to determine if cognitive function differs across stages of reproductive aging and to evaluate whether hormones or menopausal symptoms predict cognition in perimenopause. We hypothesized that women in late menopausal transition and early postmenopause would perform more poorly than those in the late reproductive stage on attention and verbal memory tasks, and that estradiol, depressive symptoms, anxiety symptoms, hot flashes, and sleep disturbance would predict cognitive performance on those tasks. METHODS: One hundred seventeen middle-aged women enrolled in the Rochester Investigation of Cognition Across Menopause were categorized into late reproductive stage (n = 34), early menopausal transition stage (n = 28), late menopausal transition stage (n = 41), or early postmenopause stage (n = 14) according to criteria from the Stages of Reproductive Aging Workshop +10. We administered a neuropsychological battery assessing six domains of cognition, assessed menopausal symptoms, and measured serum levels of estradiol and follicle-stimulating hormone. Multivariate regressions were conducted to determine the impact of menopausal stage and symptoms on cognition. RESULTS: Women in the first year of postmenopause performed significantly worse than women in the late reproductive and late menopausal transition stages on measures of verbal learning, verbal memory, and motor function. They also performed significantly worse than women in the late menopausal transition stage on attention/working memory tasks. CONCLUSIONS: Cognitive function does not change linearly across perimenopause. Decreases in attention/working memory, verbal learning, verbal memory, and fine motor speed may be most evident in the first year after the final menstrual period.

Preliminary identification of key clinical domains for outcome evaluation in fibromyalgia using the Delphi method: the Italian experience.

OBJECTIVE: Fibromyalgia (FM) is a complex syndrome that, in Italy, affects at least 2% of the adult population. It is characterized by chronic widespread musculoskeletal pain often accompanied by multiple other symptoms. The aim of this study was to identify a set of clinical domains for FM considered relevant by both clinicians and patients using a consensus process. METHODS: Consensus was achieved using the Delphi method based on questionnaires and systematic, controlled opinion feedback. The Delphi exercise involved a panel of 252 rheumatologists and 86 patients with FM as defined by the American College of Rheumatology criteria. All of the patients and clinicians were asked to rank the relative different domains of FM in order of priority. The content validity index (CVI) was used to establish the percentage agreement. The importance of each item was ranked on a 0-3 Likert scale. The frequency, mean relevance scores, and frequency importance product were also calculated. RESULTS: The Delphi exercise showed that the domains ranked highest by patients were similar to those of the clinicians, with the exception of tender point intensity (considered relevant by the clinicians but not by the patients) and environmental sensitivity (considered important by the patients but not by the clinicians). A final 8-item model was developed which was considered to demonstrate adequate validity. CONCLUSIONS: The Delphi exercises identified and ranked relevant key clinical domains that need to be assessed in FM research. On the basis of these results, a new patient-reported composite outcome index can be developed and used in clinical trials.

Impact of post-traumatic hypersomnia on functional recovery of cognition and communication.

PRIMARY OBJECTIVE: To assess aspects of cognition and communication, in response to the treatment of post-traumatic hypersomnia and mood disturbance. RESEARCH DESIGN: A single case study; pre-post intervention. METHODS AND PROCEDURES: The participant was a male with severe TBI and cognitive-communication impairments, who subsequently developed sleep and mood disturbance and excessive daytime sleepiness. The Daily Cognitive-Communication and Sleep Profile (D-CCASP), Clinical Interview, Epworth and Stanford Sleepiness Scales and polysomnography assessed sleep and wakefulness. Cognitive-communication was also assessed by the D-CCASP. His sleep, wake and mood difficulties were pharmacologically managed. MAIN OUTCOMES AND RESULTS: Baseline polysomnography indicated abnormal sleep. There was a clear positive relationship between quality of sleep, language processing, attention and memory, seen across the phases of the medication intervention (p < 0.01). CONCLUSIONS: A comprehensive pharmacological management programme addressing the multi-factorial underlying aetiology was successful in improving sleep, arousal and mood. The D-CCASP was found to be clinically and statistically sensitive to reported changes in cognitive-communication function in relation to improvements in sleep and daytime arousal. These findings suggest that management of sleep/wake disturbances and mood post-traumatic brain injury can potentially facilitate improvements in cognitive-communication function which may, in turn, facilitate participation in rehabilitation and community integration.

The impact of sleep and mood disorders on quality of life in Parkinson's disease patients.

Sleep disturbances are common and often severe in patients with Parkinson's disease (PD) and their symptoms can be present at any time of day. The purpose of our study was to examine how excessive daytime sleepiness or poor nocturnal sleep quality and mood disorders influence the quality of life (QoL) in PD patients. Ninety-three PD patients from eastern Slovakia were recruited (49.5% males, mean age 68.0 ± 9.5 years, mean disease duration 6.1 ± 5.9 years). Sleep disturbances were measured using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI); QoL with the Parkinson's Disease Quality of Life Questionnaire (PDQ-39); depression and anxiety with the Hospital Anxiety and Depression Scale (HADS) and disease severity with the Unified Parkinson's Disease Rating Scale (UPDRS). χ (2) test, bivariate correlations and multiple linear regressions were performed. PSQI and ESS had significant correlations with worse QoL (p < 0.01, p < 0.05, respectively). HADS-D (p < 0.01), HADS-A (p < 0.01), UPDRS (p < 0.01) and disease duration (p < 0.05) were also significantly related to worse QoL. In the linear regression analysis, however, only PSQI (p < 0.01), anxiety (p < 0.001) and UPDRS (p < 0.001) remained significant. The model with PSQI explained 74% of the variance, and the model with ESS explained 63% of the variance in PDQ-39 when analyses were performed separately. In an overall model, however, only PSQI remained significant, accounting for 82% of the variance in PDQ-39. Nighttime poor sleep and anxiety are important contributors leading to a worse QoL. As these are treatable conditions, they should be recognized by clinicians and managed properly.

Sleep and inflammation: psychoneuroimmunology in the context of cardiovascular disease.

BACKGROUND: Poor sleep is prospectively linked to all-cause and cardiovascular mortality. Inflammatory processes may be an important biological mechanism linking poor sleep to cardiovascular disease. Such processes involve active participation of signaling molecules called cytokines in development of atherosclerotic plaques. PURPOSE: I review evidence from experimental sleep deprivation and clinical observational studies suggesting a bidirectional relationship between sleep and inflammatory cytokines. RESULTS: Findings from sleep deprivation studies indicate that sleep loss is associated with increases in these cytokines. Similarly, studies in clinical populations with sleep problems, such as primary insomnia patients and those diagnosed with major depression, also show elevations in these same cytokines. CONCLUSIONS: Bidirectional communication between the brain and the immune system is carried out through a complex network of autonomic nerves, endocrine hormones, and cytokines. Disturbed sleep appears to perturb the functioning of this network and therefore contribute to elevations in inflammatory mediators linked to cardiovascular disease.

Surviving the Holocaust: a meta-analysis of the long-term sequelae of a genocide.

The current set of meta-analyses elucidates the long-term psychiatric, psychosocial, and physical consequences of the Holocaust for survivors. In 71 samples with 12,746 participants Holocaust survivors were compared with their counterparts (with no Holocaust background) on physical health, psychological well-being, posttraumatic stress symptoms, psychopathological symptomatology, cognitive functioning, and stress-related physiology. Holocaust survivors were less well adjusted, as apparent from studies on nonselected samples (trimmed combined effect size d = 0.22, 95% CI [0.13, 0.31], N = 9,803) and from studies on selected samples (d = 0.45, 95% CI [0.32, 0.59], N = 2,943). In particular, they showed substantially more posttraumatic stress symptoms (nonselect studies: d = 0.72, 95% CI [0.46, 0.98], N = 1,763). They did not lag, however, much behind their comparisons in several other domains of functioning (i.e., physical health, stress-related physical measures, and cognitive functioning) and showed remarkable resilience. The coexistence of stress-related symptoms and good adaptation in some other areas of functioning may be explained by the unique characteristics of the symptoms of Holocaust survivors, who combine resilience with the use of defensive mechanisms. In most domains of functioning no differences were found between Israeli samples and samples from other countries. The exception was psychological well-being: For this domain it was found that living in Israel rather than elsewhere can serve as a protective factor. A biopsychological stress-diathesis model is used to interpret the findings, and future directions for research and social policy are discussed.