Effects of a brief intervention based on Acceptance and Commitment Therapy versus usual care for cardiac rehabilitation patients with coronary heart disease (ACTonHEART): a randomised controlled trial.

OBJECTIVES: The main objective of the study is to investigate the short-term efficacy of Acceptance and Commitment Therapy (ACT) on the simultaneous modification of biological indicators of risk and psychological well-being in patients with coronary heart disease attending cardiac rehabilitation (CR). DESIGN: This was a two-arm randomised controlled trial comparing a brief, manualised, ACT-based intervention with usual care (UC). SETTING: The study was conducted in an outpatient CR unit in Italy. Data collection took place from January 2016 to July 2017. PARTICIPANTS: Ninety-two patients were enrolled and randomised, following an unbalanced randomisation ratio of 2:1 to the ACT group (n=59) and the control group (n=33). Eighty-five patients completed the ACT (n=54) and the UC (n=31) interventions and were analysed. INTERVENTIONS: The control group received UC, a 6 weeks multidisciplinary outpatient CR programme, encompassing exercise training, educational counselling and medical examinations. The experimental group, in addition to UC, participated in the Acceptance and Commitment Therapy on HEART disease (ACTonHEART) intervention encompassing three group sessions based on ACT. OUTCOMES: The primary outcomes were Low Density Lipoproteins (LDL)cholesterol, resting systolic blood pressure, body mass index (BMI) and psychological well-being measured by the Psychological General Well-Being Index (PGWBI). Outcome measures were assessed at baseline and at the end of CR. RESULTS: Based on linear mixed models, no significant group × time interaction was observed for either the primary outcomes (ß, 95% CI: PGWBI =-1.13, -6.40 to -4.14; LDL cholesterol =-2.13, -11.02 to -6.76; systolic blood pressure =-0.50, -10.76 to -9.76; diastolic blood pressure =-2.73, -10.12 to -4.65; BMI =-0.16, -1.83 to -1.51, all p values >0.05) or the secondary outcomes (all p values >0.05). A significant time effect was found for the PGWBI total (beta=4.72; p=0.03). CONCLUSIONS: Although analyses revealed null findings, the results can inform the design of future ACT-based CR interventions and can help researchers to strike a balance between the idealised implementation of an ACT intervention and the structural limitations of existing CR programmes. TRIAL REGISTRATION NUMBER: NCT01909102.

Recognizing and Appreciating the Partner's Support Protects Relationship Satisfaction during Cardiac Illness.

BACKGROUND: This study aimed to examine whether dyadic coping (DC) is associated with relationship satisfaction (RS) among couples facing cardiac diseases. Furthermore, the moderating role of both partners' anxiety and depression was tested. METHODS: One hundred cardiac patients (81.5% men) and their partners (81.5% women) completed a self-report questionnaire during hospitalization. The Actor-Partner Interdependence Model (APIM) and moderation analyses were used to assess the above associations. RESULTS: Results showed that positive DC was significantly related to higher levels of RS, and negative DC was related to lower levels of RS. Furthermore, patient and partner psychological distress significantly moderated the link between DC and RS: patient-perceived positive DC was associated with higher partner RS when partner depression was high; partner-perceived positive DC was associated with higher patient RS when patient anxiety was low; patient-perceived negative DC has associated with lower patient RS when patient anxiety and depression were high. CONCLUSION: This study showed that positive DC is associated with a more satisfying relationship and identified under what conditions of cardiac-related distress this can happen. Furthermore, this study underlined the importance of examining DC in addition to the individual coping skills as a process pertaining to personal well-being and couple's outcomes.

ACTonFood. Acceptance and Commitment Therapy-Based Group Treatment Compared to Cognitive Behavioral Therapy-Based Group Treatment for Weight Loss Maintenance: An Individually Randomized Group Treatment Trial.

The purpose of this Individually Randomized Group Treatment Trial was to compare an Acceptance and Commitment Therapy-based (ACT) group intervention and a Cognitive Behavioral Therapy-based (CBT) group intervention for weight loss maintenance in a sample of adult patients with obesity seeking treatment for weight loss. One hundred and fifty-five adults (BMI: Kg/m2 = 43.8 [6.8]) attending a multidisciplinary rehabilitation program for weight loss were randomized into two conditions: ACT and CBT. Demographical, physical, and clinical data were assessed at the beginning of the program (t0), at discharge (t1), and at 6-month follow-up (t2). The following measures were administered: The Acceptance and Action Questionnaire-II (AAQ-II) and the Clinical Outcome in Routine Evaluation-Outcome Measure (CORE-OM). Generalized linear mixed models were performed to assess differences between groups. Moderation effects for gender and Eating Disorders (ED) have been considered. From baseline to discharge, no significant differences between interventions were found, with the only exception of an improvement in the CORE-OM total score and in the CORE-OM subjective wellbeing subscale for those in the CBT condition. From discharge to follow-up, ACT group participants showed significant results in terms of weight loss maintenance, CORE-OM total score, and CORE-OM and AAQ-II wellbeing, symptoms, and psychological problems subscales. Gender moderated the effects of time and intervention on the CORE-OM subscale reporting the risk for self-harm or harm of others. The presence of an eating disorder moderated the effect of time and intervention on the CORE-OM total score, on the CORE-OM symptoms and psychological problems subscales, and on the AAQ-II. Patients who received the ACT intervention were more likely to achieve a ≥5% weight loss from baseline to follow-up and to maintain the weight loss after discharge. The ACT intervention was thus effective in maintaining weight loss over time.

Cardiac-specific experiential avoidance predicts change in general psychological well-being among patients completing cardiac rehabilitation.

Previous studies have shown that experiential avoidance (EA) is associated with physical and psychological well-being in medical and non-medical samples. The aims of the present study were to evaluate the reciprocal association between psychological well-being and EA over time among cardiac rehabilitation (CR) patients with moderately to severely low levels of psychological well-being. Pre-CR data on demographic characteristics, measures of psychological well-being, and cardiac-specific EA were collected from 915 CR patients, as well as post-CR psychological well-being and EA data, from 800 of these patients. A cross-lagged model was estimated to examine the relationship between EA and psychological well-being among patients with moderately to severely low levels of psychological well-being based on questionnaire scores. Both EA and psychological well-being significantly changed during CR and were negatively associated with each other at both pre- and post-CR. Results from cross-lagged structural equation modeling supported a nonreciprocal association between EA and psychological well-being during CR. Pre-CR assessment of EA in patients showing low levels of well-being at the beginning of CR could help to identify patients at risk for worse psychological outcomes. EA could be a promising target of psychological treatments administered during CR.

ACTonHEALTH study protocol: promoting psychological flexibility with activity tracker and mHealth tools to foster healthful lifestyle for obesity and other chronic health conditions.

BACKGROUND: Obesity and the state of being overweight are increasing steadily and becoming a global epidemic. Recent research reports 64% of the adult population as overweight in Europe and the USA. The social and economic impacts are increasing, and most of the rehabilitation programs, while effective in the short term, do not produce long-lasting results. An explanatory model from a behavioral perspective can describe the phenomena with the lack of sources of reinforcement related to healthful habits in a daily life context. METHODS/DESIGN: A randomized clinical trial combining single-subject studies and a four-arm group design will be conducted to compare the effect of the current standard in obesity treatment to Acceptance and Commitment Therapy (ACT) and wearable technology at different times, before starting intervention, at the end, and at follow-up visits of 3, 6, and 12 months measuring changes over time of physical activity and psychological well-being. DISCUSSION: The goal of this project, combining ACT and wearable technology, is to develop an effective intervention, efficient and sustainable, which even after discharge can provide adequate contingencies of reinforcement in the natural environment, integrating systematic measurements, continuous feedback, and individualized, values-based objectives. The intervention is aimed to provide a contingent reinforcement for healthful behaviors instead of reinforcing only the achievement of a significant weight loss. The aim of the project, combining Acceptance and Commitment Therapy and Wearable Technology, is to develop an effective, efficient and sustainable intervention able to provide a contingent reinforcement for healthy behaviors. The intervention is aimed to promote adequate healthy behaviors in the natural environment, integrating systematic measurements, continuous feedback and individualized values-based objectives, instead of reinforcing only the achievement of a significant weight loss. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03351712 . Registered on 24 November 2017.

Cross-Lagged Relations Between Exercise Capacity and Psychological Distress During Cardiac Rehabilitation.

Background: Poorer mental health is associated with lower exercise capacity, above and beyond the effect of other cardiovascular risk factors. However, the directionality of this relationship remains unclear. Purpose: The main aim of the present study was to clarify, with a cross-lagged panel design, the relationship between psychological status and exercise capacity among patients in a cardiac rehabilitation (CR) program. Methods: A clinical sample of 212 CR patients completed exercise-capacity testing and measures of depression and anxiety (Hospital Anxiety and Depression Scale) pre-CR and post-CR. Demographic and clinical data, including BMI and smoking history, were also collected. Multivariate stepwise regression analysis was performed to identify the best predictors of exercise capacity at discharge. Structural equation modeling was utilized to quantify the cross-lagged effect between exercise capacity and psychological distress. Results: Multivariate regression analysis revealed that higher levels of psychological distress pre-CR are predictively associated with less improvement in exercise capacity post-CR, beyond the effects of age, sex, and baseline functional status. Results from structural equation modeling supported a 1-direction association, with psychological distress pre-CR predicting lower exercise capacity post-CR over and above autoregressive effects. Conclusions: Study results did not support the hypothesis of a bidirectional relationship between psychological distress and EC. High levels of psychological distress pre-CR appeared to be longitudinally associated with lower exercise capacity post-CR, but not vice versa. This finding highlights the importance of assessing and treating both anxiety and depression in the early phase of secondary prevention programs.

Psychological Considerations in the Assessment and Treatment of Pain in Neurorehabilitation and Psychological Factors Predictive of Therapeutic Response: Evidence and Recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation.

BACKGROUND: In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) aimed to collate the evidence available across these topics. OBJECTIVES: To determine the psychological factors which are associated with or predictive of pain secondary to neurological conditions and to assess the influence of these aspects on the outcome of neurorehabilitation. METHODS: Two reviews were performed. In the first, a PUBMED search of the studies assessing the association between psychological factors and pain or the predictive value of these aspects with respect to chronic pain was conducted. The included papers were then rated with regards to their methodological quality and recommendations were made accordingly. In the second study, the same methodology was used to collect the available evidence on the predictive role of psychological factors on the therapeutic response to pain treatments in the setting of neurorehabilitation. RESULTS: The first literature search identified 1170 results and the final database included 189 articles. Factors such as depression, anxiety, pain catastrophizing, coping strategies, and cognitive functions were found to be associated with pain across the various conditions. However, there are differences between chronic musculoskeletal pain, migraine, neuropathy, and conditions associated with complex disability with regards to the psychological aspects that are involved. The second PUBMED search yielded 252 studies, which were all evaluated. Anxiety, depression, pain catastrophizing, coping strategies, and pain beliefs were found to be associated to different degrees with the outcomes of multidisciplinary programs, surgery, physical therapies, and psychological interventions. Finally, sense of presence was found to be related to the effectiveness of virtual reality as a distraction tool. CONCLUSIONS: Several psychological factors are associated with pain secondary to neurological conditions and should be acknowledged and addressed in order to effectively treat this condition. These factors also predict the therapeutic response to the neurorehabilitative interventions.

Psychological Treatments and Psychotherapies in the Neurorehabilitation of Pain: Evidences and Recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation.

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the paper.

Development and initial validation of the Cardiovascular Disease Acceptance and Action Questionnaire (CVD-AAQ) in an Italian sample of cardiac patients.

Psychological inflexibility refers to the attempt to decrease internal distress even when doing so is inconsistent with life values, and has been identified as a potential barrier to making and maintaining health behavior changes that are consistent with a heart-healthy lifestyle. Disease- and behavior-specific measures of psychological inflexibility have been developed and utilized in treatment research. However, no specific measure has been created for patients with heart disease. Thus, the CardioVascular Disease Acceptance and Action Questionnaire (CVD-AAQ) was developed. The present study is aimed to evaluate the psychometric properties of the CVD-AAQ and to explore its association with measures of psychological adjustment and cardiovascular risk factors in an Italian sample of 275 cardiac patients. Exploratory factor analysis showed a structural one-factor solution with satisfactory internal consistency and test-retest reliability. The relation with other measures was in the expected direction with stronger correlations for the theoretically consistent variables, supporting convergent and divergent validity. CVD-AAQ scores were associated with general psychological inflexibility, anxiety and depression and inversely correlated with psychological well-being. Moreover, the results showed that CVD-AAQ scores are associated with two relevant risk factors for cardiac patients, namely low adherence to medication and being overweight. In sum, results suggest that the CVD-AAQ is a reliable and valid measure of heart disease-specific psychological inflexibility with interesting clinical applications for secondary prevention care.

Effectiveness of group reminiscence for improving wellbeing of institutionalized elderly adults: study protocol for a randomized controlled trial.

BACKGROUND: Group reminiscence therapy is a brief and structured intervention in which participants share personal past events with peers. This approach has been shown to be promising for improving wellbeing and reducing depressive symptoms among institutionalized older adults. However, despite the considerable interest in reminiscence group therapy, controlled studies to determine its specific benefits as compared to generic social interactions with peers (group conversations about everyday subjects) are still lacking. METHODS/DESIGN: We have designed a randomized controlled trial aimed at comparing the effects of group reminiscence therapy with those of group recreational activity on the psychological wellbeing of an institutionalized sample of older adults. The study includes two groups of 20 hospitalized elderly participants: the experimental group and the control group. Participants included in the experimental group will receive six sessions of group reminiscence therapy, while the control group will participate in a recreational group discussion. A repeated-measures design will be used post-intervention and three months post-intervention to evaluate changes in self-reported outcome measures of depressive symptoms, self-esteem, life satisfaction, and quality of life from baseline. DISCUSSION: The protocol of a study aimed at examining the specific effects of group reminiscence therapy on psychological wellbeing, depression, and quality of life among institutionalized elderly people is described. It is expected that the outcomes of this trial will contribute to our knowledge about the process of group reminiscence, evaluate its effectiveness in improving psychological wellbeing of institutionalized individuals, and identify the best conditions for optimizing this approach. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (registration number: NCT02077153) on 31 January 2014.

The ACTonHEART study: rationale and design of a randomized controlled clinical trial comparing a brief intervention based on Acceptance and Commitment Therapy to usual secondary prevention care of coronary heart disease.

BACKGROUND: Modifiable risk factors, including life-style habits and psychological variables, have been increasingly demonstrated to have an important role in influencing morbidity and mortality in cardiovascular patients, and to account for approximately 90% of the population risk for cardiac events.Acceptance and Commitment Therapy (ACT) has shown effectiveness in promoting healthy behaviors, and improving psychological well-being in patients with chronic physical conditions. Moreover, a first application of an acceptance-based program in cardiac patients has revealed high treatment satisfaction and initial evidences of effectiveness in increasing heart-healthy behaviour. However, no clinical trial to date has evaluated the efficacy of an acceptance-based program for the modification of cardiovascular risk factors and the improvement of psychological well-being, compared to usual secondary prevention care. METHODS: Approximately 168 patients will be recruited from an outpatient cardiac rehabilitation unit and randomly assigned to receive usual care or usual care + a brief ACT-based intervention. The ACT group will be administered five group therapy sessions integrating educational topics on heart-healthy behaviours with acceptance and mindfulness skills. Participants will be assessed at baseline, six weeks later (post treatment for the ACT condition), at six and twelve months follow-up.A partially-nested design will be used to balance effects due to clustering of participants into small therapy groups. Primary outcome measures will include biological indicators of cardiovascular risk and self-reported psychological well-being. Treatment effects will be tested via multilevel modeling after which the mediational role of psychological flexibility will be evaluated. DISCUSSION: The ACTonHEART study is the first randomized clinical trial designed to evaluate the efficacy of a brief group-administered, ACT-based program to promote health behavior change and psychological well-being among cardiac patients. Results will address the effectiveness of a brief treatment created to simultaneously impact multiple cardiovascular risk factors. Conducted in the context of clinical practice, this trial will potentially offer empirical support to alternative interventions to improve quality of life and reduce mortality and morbidity rates among cardiac patients. TRIAL REGISTRATION: clinicaltrials.gov/ (NCT01909102).

Unstable maternal environment, separation anxiety, and heightened CO2 sensitivity induced by gene-by-environment interplay.

BACKGROUND: In man, many different events implying childhood separation from caregivers/unstable parental environment are associated with heightened risk for panic disorder in adulthood. Twin data show that the occurrence of such events in childhood contributes to explaining the covariation between separation anxiety disorder, panic, and the related psychobiological trait of CO(2) hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO(2) through genetic control of sensitivity to the environment. METHODOLOGY: Having spent the first 24 hours after birth with their biological mother, outbred NMRI mice were cross-fostered to adoptive mothers for the following 4 post-natal days. They were successively compared to normally-reared individuals for: number of ultrasonic vocalizations during isolation, respiratory physiology responses to normal air (20%O(2)), CO(2)-enriched air (6% CO(2)), hypoxic air (10%O(2)), and avoidance of CO(2)-enriched environments. RESULTS: Cross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO(2)-enriched air and heightened aversion towards CO(2)-enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO(2) was present at 16-20, and 75-90 postnatal days, implying the trait's stability. Quantitative genetic analyses of unrelated individuals, sibs and half-sibs, showed that the genetic variance for tidal volume increment during 6%CO(2) breathing was significantly higher (Bartlett χ = 8.3, p = 0.004) among the cross-fostered than the normally-reared individuals, yielding heritability of 0.37 and 0.21 respectively. These results support a stress-diathesis model whereby the genetic influences underlying the response to 6%CO(2) increase their contribution in the presence of an environmental adversity. Maternal grooming/licking behaviour, and corticosterone basal levels were similar among cross-fostered and normally-reared individuals. CONCLUSIONS: A mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO(2) sensitivity and anxiety. Some non-inferential physiological measurements can enhance animal models of human neurodevelopmental anxiety disorders.

Gene-environment interactions in panic disorder and CO2 sensitivity: Effects of events occurring early in life.

Heterogeneous life events (LE) precede the onset of-and potentially increase the susceptibility to-panic disorder (PD). It remains unknown whether LE can act as moderators in the context of gene-by-environment interactions (G×E) that alter the susceptibility to PD and the related trait of CO2 sensitivity, nor it is known whether such moderation may depend on occurrence of events at different epochs in life. In 712 general population twins we analyzed by Maximum Likelihood analyses of ordinal data whether life (major- and stressful) events moderate the genetic risk for PD and CO2 sensitivity, as indexed by the 35% CO2 /65% O2 challenge. For CO2 sensitivity, best-fitting models encompassed both additive and interactional effects that increased linearly with the cumulative number and severity (SEV) of events in lifetime. By analyzing the moderation effect of cumulative SEV separately for events that had occurred in adulthood (between age 18 and 37) or during childhood-adolescence (before the 18th birthday), we found evidence of G×E only within the childhood-adolescence window of risk, although twins had rated the childhood-adolescence events as significantly (P = 0.001) less severe than those having occurred during adulthood. For PD, all interactional terms could be dropped without significant worsening of the models' fit. Consistently with a diathesis-stress model, LE appear to act as moderators of the genetic variance for CO2 sensitivity. Childhood-adolescence appears to constitute a sensitive period to the action of events that concur to alter the susceptibility to this panic-related trait.

Genetic and environmental influences upon the CBCL/6-18 DSM-oriented scales: similarities and differences across three different computational approaches and two age ranges.

Inasmuch as the newly established DSM-oriented CBCL/6-18 scales are to be increasingly employed to assess clinical/high-risk populations, it becomes important to explore their aetiology both within the normal- and the extreme range of variation in general population samples and to compare the results obtained in different age groups. We investigated by the Quantitative Maximum Likelihood, the De Fries-Fulker, and the Ordinal Maximum Likelihood methods the genetic and environmental influences upon the five DSM-oriented CBCL/6-18 scales in 796 twins aged 8-17 years belonging to the general population-based Italian Twin Registry. When children were analysed together regardless of age, most best-fitting solutions yielded genetic and non-shared environmental factors as the sole influences for DSM-oriented CBCL/6-18 behaviours, both for the normal and the extreme variations. When analyses were conducted separately for two age groups, shared environmental influences emerged consistently for Affective and Anxiety Problems in children aged 8-11. Oppositional-Defiant, Attention Deficit/Hyperactivity, and Conduct Problems appeared-with few exceptions-influenced only by genetic and non-shared environmental factors in both age groups, according to all three computational approaches. The De Fries-Fulker method appeared to be more sensitive in detecting shared environmental effects. Analysing the same set of data with different analytic approaches leads to better-balanced views on the aetiology of psychopathological behaviours in the developmental years.

A genetically informed study of the association between childhood separation anxiety, sensitivity to CO(2), panic disorder, and the effect of childhood parental loss.

CONTEXT: Childhood separation anxiety disorder can predate panic disorder, which usually begins in early adulthood. Both disorders are associated with heightened sensitivity to inhaled CO(2) and can be influenced by childhood parental loss. OBJECTIVES: To find the sources of covariation between childhood separation anxiety disorder, hypersensitivity to CO(2), and panic disorder in adulthood and to measure the effect of childhood parental loss on such covariation. DESIGN: Multivariate twin study. PARTICIPANTS: Seven hundred twelve young adults from the Norwegian Institute of Public Health Twin Panel, a general population cohort. MAIN OUTCOME MEASURES: Personal direct assessment of lifetime panic disorder through structured psychiatric interviews, history of childhood parental loss, and separation anxiety disorder symptoms. Subjective anxiety response to a 35% CO(2)/65% O(2) inhaled mixture compared with compressed air (placebo). RESULTS: Our best-fitting solution yielded a common pathway model, implying that covariation between separation anxiety in childhood, hypersensitivity to CO(2), and panic disorder in adulthood can be explained by a single latent intervening variable influencing all phenotypes. The latent variable governing the 3 phenotypes' covariation was in turn largely (89%) influenced by genetic factors and childhood parental loss (treated as an identified element of risk acting at a family-wide level), which accounted for the remaining 11% of covariance. Residual variance was explained by 1 specific genetic variance component for separation anxiety disorder and variable-specific unique environmental variance components. CONCLUSIONS: Shared genetic determinants appear to be the major underlying cause of the developmental continuity of childhood separation anxiety disorder into adult panic disorder and the association of both disorders with heightened sensitivity to CO(2). Inasmuch as childhood parental loss is a truly environmental risk factor, it can account for a significant additional proportion of the covariation of these 3 developmentally related phenotypes.

A twin study of the common vulnerability between heightened sensitivity to hypercapnia and panic disorder.

For unknown reasons the inhalation of CO(2)-enriched air mixtures evokes acute panic-like symptoms in people with panic disorder and in their unaffected relatives. This study was set to determine whether, and to what extent, CO(2)-induced acute anxiety and panic disorder share the same genetic and environmental determinants. Cholesky structural equation models were used to decompose into genetic and environmental elements the correlation between self-assessed anxiety post-35%CO(2)-65%O(2) inhalation and interview-based DSM-IV lifetime diagnoses of panic disorder in 346 young adult twin pairs of the Norwegian Institute of Health Panel, 12% of whom had been invited to take part into the CO(2) study on the basis of self-reported symptoms of anxiety gathered 4-7 years before the provocation challenge. A full model corrected for the partially selective ascertainment showed that the phenotypic correlation between post-CO(2) anxiety and DSM-IV panic was largely due to additive genetic influences, while shared and unique environmental agents concurred to explain a relatively minor proportion of the correlation between these two traits. According to the best-fitting model the genetic correlation between post-CO(2) anxiety and panic was 0.81 (0.50-0.98); a common genetic factor was sufficient to explain the traits' covariation and a further, specific genetic factor was necessary to account for the residual phenotypic variance. The genetic determinants that lead to overreact to a hypercapnic stimulus coincide at a considerable extent with those that influence liability to naturally occurring panic. Environmental factors provide a modest--or no--contribution to the covariation of CO(2)-provoked anxiety with naturally occurring panic.

The co-occurrence between internalizing and externalizing behaviors. A general population twin study.

Although Internalized and Externalized problem behaviors are described as separate phenomena at the psychometric and clinical levels, they frequently co-occur. Only few studies, however, have investigated the causes of such covariation. In a sample of 398 twin pairs aged 8-17 drawn from the general population-based Italian Twin Registry, we applied bivariate genetic analyses to parent-rated CBCL/6-18 Internalization and Externalization scores. Covariation of Internalizing and Externalizing problem behaviors was best explained by genetic and common environmental factors, while the influence of unique environmental factors upon covariance appeared negligible. Odds ratio values showed that a borderline/clinical level of Externalization is a robust predictor of co-existing Internalizing problems in the same child, or within a sibship. Our findings help to approximate individual risks (e.g., in clinical practice, predicting the presence of Internalization in an externalizing child, and vice-versa), and to recognize that several shared environmental and genetic factors can simultaneously affect a child's proneness to suffer from both types of problem behaviors.

A general population twin study of the CBCL/6-18 DSM-oriented scales.

OBJECTIVE: To explore the contributions of genetic and environmental influences to individual variation and covariation of the Child Behavior Checklist (CBCL) DSM-oriented scales (DOS) originally proposed by Achenbach and associates in 2001. METHOD: A classic twin study of 398 twin pairs ages 8 to 17 years belonging to the population-based Italian Twin Registry, assessed by parents using the CBCL for Ages 6 to 18 (CBCL/6-18). RESULTS: Univariate analyses showed that compared with the classic CBCL/6-18 empirical subscales, the DOS have higher heritability (lowest 0.54 for Anxiety Problems, highest 0.71 for Conduct Problems) and simpler causal structure in that the phenotypic variance was satisfactorily explained by additive genetic and unique environmental factors only. Multivariate analyses showed that the causes of phenotypic correlation among the different DOS can be attributed to one common genetic factor and to two idiosyncratic environmental factors, each loading differently on the Internalizing (Anxiety and Affective Problems) and the Externalizing (Attention-Deficit/Hyperactivity, Oppositional Defiant, and Conduct Problems) CBCL/6-18 DOS. CONCLUSIONS: Several common risk factors of both genetic and environmental nature can simultaneously affect a child's proneness to develop the psychopathological signs and symptoms captured by the CBCL/6-18 DOS.

A genetic study of the acute anxious response to carbon dioxide stimulation in man.

People with panic disorder-agoraphobia and their relatives often react anxiously to CO(2)-enriched gas mixtures. Available data are not suited to disentangle genetic from common environmental causes of familial aggregation of CO(2) reactivity, nor provide quantitative estimations of the sources of trait variation. Three-hundred-forty-six twin pairs belonging to the general population-based Norwegian NIPH Mental Health Study underwent self-assessments of anxiety and of DSM-IV panic symptoms after inhalation of a 35%CO(2)-65%O(2) mixture. Two thresholds were employed - at sample's 75th and 90th percentiles of responses - to define provoked panic attacks and to calculate polychoric correlations. Variance components were estimated by structural equation modelling (SEM). For definitions of responses based on the sum of all 13 panic symptoms, SEM could not discriminate between shared environmental versus genetic causes of familial resemblance for provoked attacks. For definitions of responses based on global anxiety, or on the sums of those symptoms (dyspnea, dizziness, palpitations) with highest variance post-CO(2), the best-fitting models indicated additive genetic factors as the sole causes for within-family resemblance. Best-fit heritability estimates ranged from 0.42 to 0.57. Genetic and idiosyncratic environmental factors explain most of individual differences in reactivity to hypercapnia. Within-family similarities for this trait are largely explained by genetic determinants.