BackgroundIn 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 CO2 hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO2 through genetic control of sensitivity to the environment.MethodologyHaving 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%O2), CO2-enriched air (6% CO2), hypoxic air (10%O2), and avoidance of CO2-enriched environments.ResultsCross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO2-enriched air and heightened aversion towards CO2-enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO2 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%CO2 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%CO2 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.ConclusionsA mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO2 sensitivity and anxiety. Some non-inferential physiological measurements can enhance animal models of human neurodevelopmental anxiety disorders.

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.

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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.

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.

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.

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.