HPA axis related genes and response to psychological therapies: genetics and epigenetics

Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Results Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Conclusions Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner.

Factors that influence the detection of psychological problems in adolescents attending general practices

Background Epidemiological studies indicate that the prevalence of psychological problems in patients attending primary care services may be as high as 25%. Aim To identify factors that influence the detection of psychological difficulties in adolescent patients receiving primary care in the UK. Design of study A prospective study of 13-16 year olds consecutively attending general practices. Setting General practices, Norfolk, UK. Method Information was obtained from adolescents and parents using the validated Strengths and Difficulties Questionnaire (SDQ) and from GF`s using the consultation assessment form. Results Ninety-eight adolescents were recruited by 13 GPs in Norfolk (mean age = 14.4 years, SD = 1.08; 38 males, 60 females). The study identified psychological difficulties in almost one-third of adolescents (31/98, 31.6%). Three factors significant to the detection of psychological disorders in adolescents were identified: adolescents' perceptions of difficulties according to the self-report SDQ, the severity of their problems as indicated by the self-report SDQ, and whether psychological issues were discussed in the consultation. GPs did not always explore psychological problems with adolescents, even if GPs perceived these to be present. Nineteen of 31 adolescents with psychological difficulties were identified by GPs (sensitivity = 61.2%, specificity = 85.1%). A management plan or follow-up was made for only seven of 19 adolescents identified, suggesting that ongoing psychological difficulties in many patients are not being addressed. Conclusions GPs are in a good position to identify psychological issues in adolescents, but GPs and adolescents seem reluctant to explore these openly. Open discussion of psychological issues in GP consultations was found to be the most important factor in determining whether psychological difficulties in adolescents are detected by GPs.

A genome-wide test of the differential susceptibility hypothesis reveals a genetic predictor of differential response to psychological treatments for child anxiety disorders

Background: The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to Cognitive Behavioural Therapy (CBT) in children with anxiety disorders. Methods: We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1026 monozygotic (MZ) twin pairs was examined as a function of the pairs’ genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders. Results: The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9%, 55.5% and 41.6% respectively). Conclusions: Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments, but also benefit more from the most intensive types of treatment.

Risks Associated With Tendinitis: Effects From Demographic, Socioeconomic, and Psychological Status Among Brazilian Workers

Background Self-reported tendinitis/tenosynovitis was evaluated by gender, age group, skin color, family income, and educational and psychological status. Methods The study was carried out in a representative sample of formally contracted Brazilian workers from a household survey. A total of 54,660 participants were included. Occupations were stratified according to estimated prevalences of self-reported injuries. Non-conditional logistic regression was performed, and all variables were analyzed in two occupational groups. Results The overall prevalence rate of tendinitis/tenosynovitis was 3.1%: 5.5% in high-prevalence occupations (n=10,726); and 2.5% in low-prevalence occupations (n=43,934). White female workers between the ages of 45 and 64 years and at a higher socioeconomic level were more likely to report tendinitis/tenosynovitis regardless of their occupational category. An adjusted OR = 3.59 [95% CI: 3.15-4.09] was found between tendinitis/tenosynovitis and psychological status. Conclusion Among formally contracted Brazilian workers, higher income can imply greater physical and psychological demands that, regardless of occupational stratum, increase the risk of tendinitis/tenosynovitis. Am. J. Ind. Med. 53:72-79, 2010. (C) 2009 Wiley-Liss, Inc.

Effects of physiotherapy on hemodynamic variables in newborns with Acute Respiratory Distress Syndrome

Background: Acute respiratory distress syndrome (ARDS) is a frequent respiratory disturbance in preterm newborns. Preceding investigations evaluated chronic physiotherapy effects on newborns with different lung diseases; however, no study analyzed acute physiotherapy treatment on premature newborns with ARDS. In this study we aimed to evaluate the acute effects of chest and motor physiotherapy treatment on hemodynamic variables in preterm newborns with ARDS. Methods: We evaluated heart rate (HR), respiratory rate (RR), systolic (SAP), mean (MAP) and diastolic arterial pressure (DAP), temperature and oxygen saturation (SO(2)%) in 44 newborns with ARDS. We compared all variables between six periods in one day: before first physiotherapy treatment vs. after first physiotherapy treatment vs. before second physiotherapy treatment vs. after second physiotherapy treatment vs. before third physiotherapy treatment vs. after third physiotherapy treatment. Variables were measured 2 minutes before and 5 minutes after each physiotherapy session. We applied Anova one way followed by post hoc Bonferroni test. Results: HR (147.5 +/- 9.5 bpm vs. 137.7 +/- 9.3 bpm; p<0.001), RR (45.5 +/- 8.7cpm vs. 41.5 +/- 6.7 cpm; p=0.001), SAP (70.3 +/- 10.4 mmHg vs. 60.1 +/- 7.1 mmHg; p=0.001) and MAP (55.7 +/- 10 mmHg vs. 46 +/- 6.6 mmHg; p=0.001) were significantly reduced after the third physiotherapy treatment compared to before the first session. There were no significant changes regarding temperature, DAP and SO(2) %. Conclusion: Chest and motor physiotherapy acutely improves HR, RR, SAP, MAP and SO(2) % in newborns with ARDS.

Psychological and biochemical mechanisms of schizoprenia

Schizophrenia is a disease whose physical cause is unknown despite the attempts of several research teams to discover a physical basis for it. Some success has been gained in genetic studies which indicate that schizophrenia is an inherited disability. However, since research tools are at present so sadly inadequate, the value of pursuing a genetic line of reasoning is questionable. To compensate for the lack of biochemical certainties in treating mental illness, psychological theories have been constructed to explain the schizophrenia syndrome. Normal personality is seen as the resultant of environmental and inherited influences. Involved in the formation of personality are the processes of differentiation and integration, maturation of inherited traits, and the learning processes. As personality develops. consciousness of the self, inferiority feelings, and compensatory mechanisms, and the transformation of interests into drives exert a decided influence upon personality growth. Finally, in the mature personality, an integrating philosophy of life, a large variety of interests, and the possibility of self-objectification become evident.