Does old age reduce the risk of anxiety and depression? A review of epidemiological studies across the adult life span

BACKGROUND: There is considerable disagreement about what happens to the risk of anxiety and depression disorders and symptoms as people get older. METHODS: A search was made for studies that examine the occurrence of anxiety, depression or general distress across the adult life span. To be included, a study had to involve a general population sample ranging in age from at least the 30s to 65 and over and use the same assessment method at each age. RESULTS: There was no consistent pattern across studies for age differences in the occurrence of anxiety, depression or distress. The most common trend found was for an initial rise across age groups, followed by a drop. Two major factors producing this variability in results were age biases in assessment of anxiety and depression and the masking effect of other risk factors that vary with age. When other risk factors were statistically controlled, a more consistent pattern emerged, with most studies finding a decrease in anxiety, depression and distress across age groups. This decrease cannot be accounted for by exclusion of elderly people in institutional care from epidemiological surveys or by selective mortality of people with anxiety or depression. CONCLUSION: There is some evidence that ageing is associated with an intrinsic reduction in susceptibility to anxiety and depression. However, longitudinal studies covering the adult life span are needed to distinguish ageing from cohort effects. More attention needs to be given to understanding the mechanism behind any ageing-related reduction in risk for anxiety and depression with age. Possible factors are decreased emotional responsiveness with age, increased emotional control and psychological immunization to stressful experiences.     

Playing it safe: An examination of risk-avoidance in an anxious treatment-seeking sample

It has been argued that individuals who are anxious are less likely and willing to take perceived risks across multiple behavioral domains (e.g., social, recreational, financial etc.), and that this bias is likely implicated in the etiology of pathological anxiety. While evidence is accumulating, there has been minimal research investigating the characteristics of risk-avoidance across anxiety disorders and across the specific risk-taking domains. The current study investigated risk-avoidance across domains in an anxious treatment-seeking sample. We hypothesized that: (i) individuals with anxiety would be more risk averse across domains relative to healthy controls; and, (ii) risk-avoidance would predict unique variance in anxiety symptoms, above and beyond other vulnerability factors (e.g., neuroticism). Individuals diagnosed with one or more anxiety disorders (n=67) completed measures of risk-taking, anxiety and depression symptoms, personality, and psychological distress. Healthy controls (n=58) completed measures of risk-taking and psychological distress. Results partially confirmed our hypotheses, demonstrating that anxious individuals were significantly more risk averse relative to controls across most domains, even after controlling for age and psychological distress. Furthermore, specific domains were found to account for unique variance in specific anxiety symptoms, as well as symptoms of depression. The results of this study provide novel evidence to suggest that risk-aversion is a possible transdiagnostic factor contributing to anxiety pathology.     

Unique genetic and environmental determinants of prolonged fatigue: a twin study

BACKGROUND: Prolonged fatigue syndromes have been proposed as prevalent and disabling forms of distress that occur independently of conventional notions of anxiety and depression. METHODS: To investigate the genetic and environmental antecedents of common forms of psychological and somatic distress, we measured fatigue, anxiety, depression and psychological distress in 1004 normal adult twin pairs (533 monozygotic (MZ), 471 dizygotic (DZ)) over 50 years of age. RESULTS: Familial aggregation of psychological distress, anxiety and fatigue appeared to be due largely to additive genetic factors (MZ:DZ ratios of 2.12-2.69). The phenotypic correlations between the psychological measures (distress, anxiety and depression) were moderate (0.67-0.79) and higher than that between fatigue and psychological distress (0.38). Multivariate genetic modelling revealed a common genetic factor contributing to the development of all the observed phenotypes (though most strongly for the psychological forms), a second independent genetic factor also influenced anxiety and depression and a third independent genetic factor made a major contribution to fatigue alone. In total, 44% (95% CI 25-60%) of the genetic variance for fatigue was not shared by the other forms of distress. Similarly, the environmental factor determining psychological distress made negligible contributions to fatigue, which was underpinned largely by its own independent environmental factor. CONCLUSION: This study supports the aetiological independence of prolonged fatigue and, therefore, argues strongly for its inclusion in classification systems in psychiatry.     

Nightmare prevalence, nightmare distress, and self-reported psychological disturbance

STUDY OBJECTIVES: The relationship between nightmare prevalence, nightmare distress, and self-reported psychological disturbance was assessed prospectively. DESIGN: Differences in self-reported psychological disturbance as a function of nightmare prevalence was investigated by MANCOVA's with non-nightmare dreams as the covariate as well as Pearson correlations. The relative contribution of nightmare prevalence and distress to the prediction of psychological disturbance was investigated through multiple regression analyses. SETTING: N/A. PARTICIPANTS: 116 participants (mean age = 20 years) completed self-report indices of depression, anxiety, dissociation, psychosis-proneness, and a psychiatric symptom checklist and kept a nightmare log for 21 consecutive nights. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Frequent nightmares were associated with higher levels of psychological disturbance. Individuals who reported 3 or more nightmares across the 3 weeks reported more dissociation, psychosis-proneness and psychiatric symptoms than participants reporting 2 nightmares or less. However, nightmare prevalence and distress were not significantly correlated and differentially predicted to different types of waking psychological disturbance. Multiple regressions further indicated that nightmare distress accounted for much of the unique explanatory variance in predicting clinical states associated with high negative affect (anxiety and depression). Last, there was no evidence for a specific relationship between nightmares and psychosis-proneness. CONCLUSIONS: The findings suggest that it is not the incidence of nightmares which is associated with poorer waking psychological functioning, especially anxiety and depression states, but the reported distress associated with the nightmare experience which is the critical variable in predicting higher psychological disturbance.     

Body mass index in middle life and future risk of hospital admission for psychoses or depression: findings from the Renfrew/Paisley study

BACKGROUND: There is evidence that greater body mass index (BMI) protects against depression, schizophrenia and suicide. However, there is a need for prospective studies. METHOD: We examined the association of BMI with future hospital admissions for psychoses or depression/anxiety disorders in a large prospective study of 7036 men and 8327 women. Weight and height were measured at baseline (1972-76) when participants were aged 45-64. Follow-up was for a median of 29 years. RESULTS: Greater BMI and obesity were associated with a reduced risk of hospital admission for psychoses and depression/anxiety in both genders, with the magnitude of these associations being the same for males and females. With adjustment for age, sex, smoking and social class, a 1 standard deviation (s.d.) greater BMI at baseline was associated with a rate ratio of 0.91 [95% confidence interval (CI) 0.82-1.01] for psychoses and 0.87 (95% CI 0.77-0.98) for depression/anxiety. Further adjustment for baseline psychological distress and total cholesterol did not alter these associations. CONCLUSIONS: Our findings add to the growing body of evidence that suggests that greater BMI is associated with a reduced risk of major psychiatric outcomes. Long-term follow-up of participants in randomized controlled trials of interventions that effectively result in weight loss and the use of genetic variants that are functionally related to obesity as instrumental variables could help to elucidate whether these associations are causal.     

Psychological risk factors of incidence of breast cancer: a prospective cohort study in Finland

BACKGROUND: Belief that depression and other psychological factors predict breast cancer is common, but there have been few prospective epidemiological studies on this relationship. METHOD: The relationship between depression, personality traits, illness attitudes, life events and health history, and breast cancer risk was studied in a prospective, 6-9 year follow-up of a cohort study of 10892 Finnish women of 48-50 years of age at the baseline. Cancer cases were obtained from the Cancer Registry of Finland. Multivariate logistic regression analysis was performed controlling for socioeconomic factors, family history of cancer, parity, and health behaviours. RESULTS: Breast cancer incidence in the cohort was 1.15 times the average in age group 50-59. There was no evidence of depression, trait anxiety, cynical distrust, or coping being significant predictors of breast cancer incidence. CONCLUSION: In this cohort study with the 6-9 year follow-up, psychological factors such as depression, trait anxiety, cynical distrust, or coping did not increase breast cancer risk.     

Surviving childhood cancer, social support, and parents' psychological adjustment.

Assessed whether the continuing emotional strain of parenting a child cancer survivor is associated with elevated levels of psychological distress (depression and anxiety) in parents. The role of social support in moderating this relationship was also evaluated. When parents of cancer survivors (63 mothers and 49 fathers) were compared to a matched sample of parents (64 mothers and 62 fathers) with healthy children there were no differences in levels of depression or anxiety overall but among parents experiencing low levels of social support, parents of cancer survivors were more depressed and anxious than parents of healthy children. Perceived social support has a significant inverse relationship with psychological distress for both parents but seems to be more important for mothers. The elevated risk for psychological distress noted for those experiencing low levels of support appears to be more generalized for fathers than mothers.     

冠状病毒疫情对医务人员心理健康的影响与干预(综述)

三次冠状病毒疫情下医务人员心理问题发生率分别为SARS 29%~75%,MERS 64.1%,COVID-19 63%。疫情爆发流行期以急性应激反应为主;疫情结束1年,17.3%的医务人员存在心理问题;疫情结束3年,4%医务人员存在创伤后应激症状,并出现抑郁、焦虑和物质滥用等不良结局。直接接触患者、被隔离、自身感染、本职专业与传染病相关性小被安排一线工作者、女性、不成熟的心理防御方式、既往躯体疾病史、既往存在精神障碍病史的医务人员心理问题发生风险更高。线上和线下心理干预有助于促进医务人员心理健康恢复。     

Anxiety and depression in parents 4-9 years after the loss of a child owing to a malignancy: a population-based follow-up

BACKGROUND: Some consider the loss of a child as the most stressful life event. When the death is caused by a malignancy, the parents are commonly exposed not only to their own loss, but also to the protracted physical and emotional suffering of the child. We investigated parental risk of anxiety and depression 4-9 years after the loss of a child owing to a malignancy. METHOD: In 2001, we attempted to contact all parents in Sweden who had lost a child due to a malignancy during 1992--1997. We used an anonymous postal questionnaire and utilized a control group of non-bereaved parents with a living child. RESULTS: Participation among bereaved parents was 449/561 (80 %); among non-bereaved 457/659 (69%). We found an increased risk of anxiety (relative risk 1.5, 95 % confidence interval 1.1-1.9) and depression (relative risk 1.4, 95 % confidence interval 1.1-1.7) among bereaved parents compared with non-bereaved. The risk of anxiety and depression was higher in the period 4-6 years after bereavement than in the 7-9 years period, during which the average excess risks approached zero. Psychological distress was overall higher among bereaved mothers and loss of a child aged 9 years or older implied an increased risk, particularly for fathers. CONCLUSIONS: Psychological morbidity in bereaved parents decreases to levels similar to those among non-bereaved parents 7-9 years after the loss. Bereaved mothers and parents who lose a child 9 years or older have on average an excess risk for long-term psychological distress.     

Longitudinal assessment of anxiety,depression, and fatigue in people with multiple sclerosis

Objectives. No longitudinal studies have concurrently evaluated predictors of anxiety, depression, and fatigue in people with multiple sclerosis (PwMS). This study determined factors that best predicted anxiety, depression, and fatigue in MS patients from a large pool of disease, cognitive, life‐event stressor (LES), psychosocial, life‐style, and demographic factors. Design. A 2‐year prospective longitudinal study evaluated predictors of psychological distress and fatigue in PwMS. Methods. One hundred and one consecutive participants with MS were recruited from two MS clinics in Sydney, Australia. LES, anxiety, depression, and fatigue were assessed at baseline and at 3‐monthly intervals for 2‐years. Disease, cognitive, demographic, psychosocial, and life‐style factors were assessed at baseline. Patient‐reported relapses were recorded and corroborated by neurologists or evaluated against accepted relapse criteria. Results. Depression strongly predicted anxiety and fatigue, and anxiety and fatigue strongly predicted later depression. Psychological distress (i.e. anxiety, depression) was also predicted by a combination of unhealthy behaviours (e.g. drug use, smoking, no exercise, or relaxation) and psychological factors (e.g. low optimism, avoidance coping), similar to the results of community‐based studies. However, state‐anxiety and fatigue were also predicted by immunotherapy status, and fatigue was also predicted by LES and demographics. Conclusions. These results suggest that similar factors might underpin psychological distress and fatigue in MS patients and community‐well samples, although MS treatment factors may also be important. These results might assist clinicians in determining which MS patients are at greatest risk of developing anxiety, depression, or fatigue.     

Systematic review of depression, anxiety, and other indicators of psychological distress among U.S. and Canadian medical students.

PURPOSE: To systematically review articles reporting on depression, anxiety, and burnout among U.S. and Canadian medical students. METHOD: Medline and PubMed were searched to identify peer-reviewed English-language studies published between January 1980 and May 2005 reporting on depression, anxiety, and burnout among U.S. and Canadian medical students. Searches used combinations of the Medical Subject Heading terms medical student and depression, depressive disorder major, depressive disorder, professional burnout, mental health, depersonalization, distress, anxiety, or emotional exhaustion. Reference lists of retrieved articles were inspected to identify relevant additional articles. Demographic information, instruments used, prevalence data on student distress, and statistically significant associations were abstracted. RESULTS: The search identified 40 articles on medical student psychological distress (i.e., depression, anxiety, burnout, and related mental health problems) that met the authors' criteria. No studies of burnout among medical students were identified. The studies suggest a high prevalence of depression and anxiety among medical students, with levels of overall psychological distress consistently higher than in the general population and age-matched peers by the later years of training. Overall, the studies suggest psychological distress may be higher among female students. Limited data were available regarding the causes of student distress and its impact on academic performance, dropout rates, and professional development. CONCLUSIONS: Medical school is a time of significant psychological distress for physicians-in-training. Currently available information is insufficient to draw firm conclusions on the causes and consequences of student distress. Large, prospective, multicenter studies are needed to identify personal and training-related features that influence depression, anxiety, and burnout among students and explore relationships between distress and competency.     

Cerebrovascular risk factors and subsequent depression in older general practice patients

BACKGROUND: This general practice-based case-control study tested the association between cerebrovascular risk factors (CVRFs) and the development of later-life depression by focusing on the impact of exposure duration to CVRFs and the modifying influence of age at depression onset. METHODS: Cases were 286 patients aged > or = 50 years with a first diagnosis of depression at age > or = 50 years. Nondepressed controls (N=832) were individually matched for age, gender and practice. CVRF diagnoses (hypertension, diabetes mellitus, cardiovascular conditions) prior to depression were determined. Analyses controlled for education, somatic and nondepressive psychiatric disease. RESULTS: No CVRF variable examined was significantly associated with subsequent depression in the total sample. An unexpected impact of age at onset of depression was observed: the odds ratio associated with having any CVRF was smaller for patients with age at onset > or = 70 years than for patients with onset between ages 50-59 years (p=.002) and 60-69 years (p=.067). Subsequent analyses excluding patients with onset at age > or = 70 years revealed that CVRF variables, including long-term exposure to CVRFs, significantly increased the odds of subsequent depression with onset between ages 50 and 69 years. LIMITATIONS: Reliance on GPs' records of morbidity may have resulted in bias towards underestimation in patients with depression onset at age > or = 70 years. CONCLUSIONS: Our findings suggest that CVRFs play a relevant role in the development of depression with onset between ages 50 and 69 years, but no evidence was found that they contribute to the occurrence of depression with onset at age > or = 70 years. Replication is warranted to exclude the possibility of bias.     

Distress in MEN 2 family members and partners prior to DNA test disclosure

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant early‐onset cancer disorder. In the Netherlands presymptomatic genetic testing for MEN 2 is offered to testees from the age of five years. We report on adults requesting testing for themselves (n=90) and on parents who want an at‐risk child to be tested (n=26). Sociodemographic, personality, and attitude characteristics, and levels of psychological distress, were determined for applicants and their partners in the predisclosure phase of testing. These participants showed only mildly increased levels of psychological distress, defined as heightened scores on measures of general and test‐related anxiety, and of psychological complaints. Compared with a normal population, high levels of anxiety and health complaints were found in applicants who were younger than 25 years and single, and in persons who generally tended to react to distressful situations with anxiety or depression. These characteristics were particularly evident in young applicants (<25 years). Our study shows that people who feel ambivalent towards DNA testing and who are more vulnerable to psychological distress are more likely to agree to participate in the test as part of a collective application by members of a hereditary cancer family. Am. J. Med. Genet. 91:1–7, 2000. © 2000 Wiley‐Liss, Inc.     

Psychological distress in high-risk youth with asthma

OBJECTIVE: To examine the relationship between asthma and psychological distress among adolescents already at-risk for adjustment problems secondary to lower economic strata and educational or vocational failure. METHOD: Twenty-five high-risk adolescents with asthma and 25 high-risk controls without asthma 16 to 21 years old completed the Brief Symptom Inventory, the Beck Depression Inventory, and the Beck Anxiety Inventory. RESULTS: Adolescents with asthma had significantly higher scores on multiple measures of psychological distress. Specifically, adolescents with asthma evidenced higher levels of anxiety, depression, and global psychological distress than those without asthma. CONCLUSIONS: High-risk adolescents with asthma may be more likely to experience psychological distress than those without asthma. Our findings suggest that asthma constitutes an additional significant independent stressor or risk factor among adolescents who already are at high risk for multiple adjustment problems.     

Menopausal symptoms and psychological distress in women with and without tubal sterilization

Data from self-administered mailed questionnaires were used to examine the relationship between menopausal and psychological/psychiatric factors in women age 45-50 years with and without tubal sterilization. In multivariate logistic regression analysis, tubal sterilization was associated with current flushing (odds ratio = 8.78, 95% confidence interval [CI] = 1.58-48.67) and current symptoms of psychological distress (odds ratio = 3.37, 95% CI = 1.27-8.95); psychological distress was associated with tubal sterilization (odds ratio = 3.28, 95% CI = 1.28-8.42) and with being perimenopausal (odds ratio = 3.93, 95% CI = 1.08-14.34). Sterilization was marginally associated with a history of physician-diagnosed depression (univariate age-adjusted odds ratio = 2.24, 95% CI = 0.90-5.60). The menopausal and psychological symptoms of women with tubal sterilization should be taken seriously and treated appropriately.     

Deciding who gets treatment for depression and anxiety: a study of consecutive GP attenders

BACKGROUND: Most research has focused on recognition by GPs of the common mental disorders: depression and anxiety. However, less is known about the factors that determine whether patients with those disorders that are recognised receive any active treatment. AIM: To investigate factors associated with receiving active treatment among consecutive attenders identified by GPs as having a common mental disorder. SETTING: Data were collected as part of a cluster randomised controlled trial in 30 general practices in the south of Bristol, UK, on the impact of mental health guidelines in primary care. METHOD: We studied 439 consecutive general practice attenders aged 16-64 years who were given a diagnosis of depression, anxiety, or chronic mixed anxiety and depression by their GP. The main outcome measure was the provision of any active treatment, whether pharmacological or psychological, for these disorders. Patient, GP, and practice level data, including sociodemographic, clinical, and administrative data were explored as predictors in a logistic regression model. Huber White variance estimates were used to account for hierarchical clustering. RESULTS: Of those patients identified as having a common mental disorder by the GP, 54% were offered active treatment. Higher symptom score, as measured by the General Health Questionnaire (GHQ) (odds ratio [OR] = 1.09; 95% confidence interval [CI] = 1.06 to 1.13; P<0.001) and being male (OR = 1.54; 95% CI = 1.13 to 2.09; P = 0.006), were both associated with an increased likelihood of being offered active treatment. Patients with anxiety (OR = 0.24; 95% = CI 0.14 to 0.41; P<0.001), or chronic mixed anxiety/depression (OR = 0.41; 95% CI = 0.23 to 0.73; P = 0.003) were less likely to be offered active treatment than those considered to have depression. CONCLUSION: When deciding to offer active treatment for common mental disorders, GPs appear to be influenced by the severity of symptoms rather than their 'understandability' in relation to recent life stresses or the social context of distress. Further research is needed to investigate why men are more likely and those with an anxiety disorder less likely, to be offered active treatment.     

The COVID-19 anxiety syndrome and selective attentional bias towards COVID-19-related stimuli in UK residents during the 2020–2021 pandemic

The psychological and social effects of the COVID-19 pandemic are pervasive, and there is potential for a long-lasting impact on mental health. In the current study, we sought to provide, in a representative sample of UK residents during the third COVID-19 lockdown in February 2021, further evidence for the validation of the COVID-19 anxiety syndrome construct. We did this by evaluating the COVID-19 anxiety syndrome against measures of personality, health anxiety and COVID-19 anxiety in predicting levels of generalized anxiety and depression and by examining whether increased health anxiety and COVID-19 psychological distress (COVID-19 anxiety and COVID-19 anxiety syndrome) scores were associated with increased attentional bias to COVID-19-related stimuli. A series of correlation analyses revealed that neuroticism, health anxiety, COVID-19 anxiety and COVID-19 anxiety syndrome scores were positively and significantly correlated with generalized anxiety and depression scores and that the perseveration component of the COVID-19 anxiety syndrome predicted generalized anxiety and depression scores independently of age, gender, conscientiousness, openness, health anxiety and COVID-19 anxiety. Furthermore, results indicated that only the total COVID-19 anxiety syndrome score and the scores on the avoidance and perseveration components were positively and significantly correlated with attentional bias indices. More specifically, the general attentional bias index was only shown to be positively and significantly correlated with the total COVID-19 anxiety syndrome score and its perseveration component, while slowed disengagement was only shown to be negatively and significantly correlated with the total COVID-19 anxiety syndrome score and its avoidance component. The implications of these findings are discussed.     

Risk factors for anxiety and depression in the elderly: a review

BACKGROUND: Although a number of studies have examined risk factors for anxiety and depression at a later age, there have been no systematic comparisons of risk profiles across studies. Knowledge on such risk profiles may further our understanding of both the etiology and early recognition of these highly prevalent disorders. This paper gives a comprehensive overview and compares risk factors associated with anxiety and depression in the elderly. METHODS: The databases MEDLINE, PsycINFO and Sociological Abstracts were systematically searched, and relevant English-language articles from January 1995 to December 2005 were reviewed. Cross-sectional and longitudinal studies on risk factors in elderly from a community or primary care setting were included. The associations between risk factors and pure anxiety or depressive symptoms or disorders were summarized and compared. RESULTS: The abstracted risk factors from studies on anxiety (N=17) and depression (N=71) were clustered into the categories biological, psychological and social. Although risk factors for anxiety and depression showed many similarities, some differences were found. Biological factors may be more important in predicting depression, and a differential effect of social factors on depression and anxiety was found. LIMITATION: Due to a high heterogeneity between studies, no meta-analysis could be conducted. CONCLUSIONS: There is considerable overlap between the risk profiles for anxiety and depression in the elderly, which suggests a dimensional approach on the interrelationship between anxiety and depression is more appropriate. To improve the recognition and preventive mental health programs, a clearer understanding of differentiating etiological factors will be needed.     

HIV/AIDS患者负性情绪及其与外周血T细胞计数关系的探讨

目的 探讨HIV/AIDS患者负性情绪与外周血T淋巴细胞计数的相关性.方法 采用症状自评量表(SCL-90)、抑郁自评量表(SDS)、焦虑自评量表(SAS)对102例HIV/AIDS患者进行问卷测评,进行外周血CD3+、CD4+、CD8+T细胞计数.CD4+T细胞<0.2×109/L分为A组,≥0.2×109/L分为B组,分析A、B组负性情绪的差异性,CD4+细胞计数与SCL-90各项得分相关性,分别将CD3+、CD4+、CD8+T细胞计数作为因变量进行线形回归分析.结果 77例(75.49%)HIV/AIDS患者存在程度不同的心理卫生问题,除敌对情绪外,躯体化、强迫、人际关系、抑郁、焦虑、恐怖、偏执、精神病性等八项因子分均较常模明显异常(P均<0.05),抑郁和焦虑主观感受的发生率分别为67.65%(69/102)和43.13%(44/102),较正常人明显突出;A组患者的心理卫生问题、在抑郁、焦虑方面的主观感受较B组突出(P<0.05);CD4+T细胞数量与SCL-90总分及多项均分呈负相关,线性回归分析显示抑郁症状对CD3+、CD4+、CD8+T细胞的影响最大.结论 大部分HIV/AIDS患者心理卫生状况存在明显异常,HIV/AIDS人群的情绪表达与CD4+T细胞计数有一定的相关性,以抑郁症状最明显.     

Complex genetic and environmental relationships between psychological distress, fatigue and immune functioning: a twin study

BACKGROUND: Although there is considerable support for adverse relationships between states of psychological and somatic distress and immune response, there is little evidence in humans of the relative contribution of genetic and environmental factors. METHODS: This study utilized a twin methodology to examine the interplay between psychological distress, fatigue and immune function. We recorded a number of measures of distress, including conventional depression and anxiety as well as the somatic symptom of prolonged fatigue, and immune responsiveness (by delayed-type hypersensitivity skin response) in 124 normal adult twin pairs (79 monozygotic, 45 dizygotic). RESULTS: While there were strong genetic influences on the psychological distress and fatigue factors (only some of which are common to both), familial aggregation of immune responsiveness arose mainly from environmental factors shared by both members of a twin pair. Phenotypic correlations between psychological and immune measures were negligible, but multivariate genetic modelling revealed that these masked larger genetic and environmental correlations of opposite sign. Negative environmental effects of psychological distress and fatigue on immune responsiveness were countered by a positive genetic relationship between psychological distress and immune function. CONCLUSIONS: Our study suggests that current psychoneuroimmunological hypotheses in humans need to be modified to place increasing importance on the individual's genotype. In this cohort immune responsiveness varied in response to a complex interplay of genetic and environmental factors. Additionally, although psychological distress and fatigue had some shared genetic determinants, independent genetic and environmental risk factors for fatigue were also identified.