Enhanced automatic action imitation and intact imitation- inhibition in schizophrenia

Imitation plays a key role in social learning and in facilitating social interactions and likely constitutes a basic building block of social cognition that supports higher-level social abilities. Recent findings suggest that patients with schizophrenia have imitation impairments that could contribute to the social impairments associated with the disorder. However, extant studies have specifically assessed voluntary imitation or automatic imitation of emotional stimuli without controlling for potential confounders. The imitation impairments seen might therefore be secondary to other cognitive, motoric or emotional deficits associated with the disorder. To overcome this issue, we used an automatic imitation paradigm with nonemotional stimuli to assess automatic imitation and the top-down modulation of imitation where participants were required to lift one of two fingers according to a number shown on the screen whilst observing the same or the other finger movement. In addition, we used a control task with a visual cue in place of a moving finger, to isolate the effect of observing finger movement from other visual cueing effects. Data from 33 patients (31 medicated) and 40 matched healthy controls were analyzed. Patients displayed enhanced imitation and intact top-down modulation of imitation. The enhanced imitation seen in patients may have been medication induced as larger effects were seen in patients receiving higher antipsychotic doses. In sum, we did not find an imitation impairment in schizophrenia. The results suggest that previous findings of impaired imitation in schizophrenia might have been due to other cognitive, motoric and/or emotional deficits

Genome-wide DNA methylation profiling with MeDIP-seq using archived dried blood spots

Segment distribution along the repeat-rich gene SFI1. Visualization of 500 bp segments (250 bp sliding window) at the SFI1 locus for hDBS, rDBS and oDBS. (PDF 113 kb

A large population-based investigation into the genetics of susceptibility to gastrointestinal infections and the link between gastrointestinal infections and mental illness.

Gastrointestinal infections can be life threatening, but not much is known about the host's genetic contribution to susceptibility to gastrointestinal infections or the latter's association with psychiatric disorders. We utilized iPSYCH, a genotyped population-based sample of individuals born between 1981 and 2005 comprising 65,534 unrelated Danish individuals (45,889 diagnosed with mental disorders and 19,645 controls from a random population sample) in which all individuals were linked utilizing nationwide population-based registers to estimate the genetic contribution to susceptibility to gastrointestinal infections, identify genetic variants associated with gastrointestinal infections, and examine the link between gastrointestinal infections and psychiatric and neurodevelopmental disorders. The SNP heritability of susceptibility to gastrointestinal infections ranged from 3.7% to 6.4% on the liability scale. Significant correlations were found between gastrointestinal infections and the combined group of mental disorders (OR = 2.09; 95% CI: 1.82-2.4, P = 1.87 × 10-25). Correlations with autism spectrum disorder, attention deficit hyperactivity disorder, and depression were also significant. We identified a genome-wide significant locus associated with susceptibility to gastrointestinal infections (OR = 1.13; 95% CI: 1.08-1.18, P = 2.9 × 10-8), where the top SNP was an eQTL for the ABO gene. The risk allele was associated with reduced ABO expression, providing, for the first time, genetic evidence to support previous studies linking the O blood group to gastrointestinal infections. This study also highlights the importance of integrative work in genetics, psychiatry, infection, and epidemiology on the road to translational medicine

A functional variant in the serotonin receptor 7 gene (HTR7), rs7905446, is associated with good response to SSRIs in bipolar and unipolar depression.

Predicting antidepressant response has been a clinical challenge for mood disorder. Although several genome-wide association studies have suggested a number of genetic variants to be associated with antidepressant response, the sample sizes are small and the results are difficult to replicate. Previous animal studies have shown that knockout of the serotonin receptor 7 gene (HTR7) resulted in an antidepressant-like phenotype, suggesting it was important to antidepressant action. In this report, in the first stage, we used a cost-effective pooled-sequencing strategy to sequence the entire HTR7 gene and its regulatory regions to investigate the association of common variants in HTR7 and clinical response to four selective serotonin reuptake inhibitors (SSRIs: citalopram, paroxetine, fluoxetine and sertraline) in a retrospective cohort mainly consisting of subjects with bipolar disorder (n = 359). We found 80 single-nucleotide polymorphisms (SNPs) with false discovery rate < 0.05 associated with response to paroxetine. Among the significant SNPs, rs7905446 (T/G), which is located at the promoter region, also showed nominal significance (P < 0.05) in fluoxetine group. GG/TG genotypes for rs7905446 and female gender were associated with better response to two SSRIs (paroxetine and fluoxetine). In the second stage, we replicated this association in two independent prospective samples of SSRI-treated patients with major depressive disorder: the MARS (n = 253, P = 0.0169) and GENDEP studies (n = 432, P = 0.008). The GG/TG genotypes were consistently associated with response in all three samples. Functional study of rs7905446 showed greater activity of the G allele in regulating expression of HTR7. The G allele displayed higher luciferase activity in two neuronal-related cell lines, and estrogen treatment decreased the activity of only the G allele. Electrophoretic mobility shift assay suggested that the G allele interacted with CCAAT/enhancer-binding protein beta transcription factor (TF), while the T allele did not show any interaction with any TFs. Our results provided novel pharmacogenomic evidence to support the role of HTR7 in association with antidepressant response

Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis:randomised, superiority, parallel group trial in Denmark (OPUS II)

Objective To compare the effects of five years of specialised early intervention (SEI) treatment for first episode schizophrenia spectrum disorder with the standard two years of SEI plus three years of treatment as usual. Design Randomised, superiority, parallel group trial with blinded outcome assessment. Randomisation was centralised and computerised with concealed randomisation sequence carried out at an external site. Setting Participants were recruited from six OPUS teams in Denmark between 2009 and 2012. OPUS teams provide SEI treatment to all patients diagnosed with a schizophrenia spectrum disorder in Denmark. Participants 400 participants (51% women) with a mean age of 25.6 (standard deviation 4.3) were randomised to five years of SEI (experimental intervention; n=197) or to two years of SEI plus three years of treatment as usual (control; n=203). Interventions OPUS treatment consists of three core elements—modified assertive community treatment, family involvement, and social skill training—with a patient-case manager ratio of no more than 12:1. For participants randomised to five years of OPUS treatment, the treatment was largely unchanged. Participants randomised to the control group were mostly referred to community health centres after two years of SEI treatment. Main outcomes Follow-up assessments were conducted five years after start of OPUS treatment. Primary outcome was negative symptoms measured on the scale for assessment of negative symptoms (avolition-apathy, anhedonia, alogia, and affective blunting). Secondary outcomes were remission of both negative and psychotic symptoms, psychotic symptoms, suicidal ideation, substance abuse, compliance with medical treatment, adherence with treatment, client satisfaction, days in hospital care, and labour market affiliation. Results Levels of negative symptoms did not differ between the intervention group and control group (1.72 v 1.81 points; estimated mean difference −0.10 (95% confidence interval 0.33 to 0.13), P=0.39). Participants receiving five years of OPUS treatment were more likely to remain in contact with specialised mental health services (90.4% v 55.6%, P<0.001), had higher client satisfaction (estimated mean difference 2.57 points (95% confidence interval 1.36 to 3.79), P<0.001), and had a stronger working alliance (estimated mean difference 5.56 points (95% confidence interval 2.30 to 8.82), P=0.001) than the control group. Conclusions This trial tests SEI treatment for up to five years for patients with first episode schizophrenia spectrum disorder; previous trials have found treatment effects for programmes lasting from one to three years. The prolonged SEI treatment had few effects, which could be due to the high level of treatment provided to control participants and the late start of specialised treatment. Trial registration Clinicaltrial.gov NCT00914238

Doing Identity Work with Transgendered Women

Gender, sexuality and identity in relation to individual freedom and equality go to the core of who we are, as well as shape our actions. By offering a glimpse into the identity work processes of two transgendered women, I hope to make visible some of the forces and mechanisms that influence all of us, regardless of our gender or status. The transgendered are a group of people who have long been excluded, diagnosed, defined and oppressed by our current gender system. By making my interviewees’ stories heard, I hope to contribute to change in the prevailing hetero normative and dichotomic gender system. This thesis is a narrative analysis on identity work and gender. In this thesis I aim at answering how the two transgendered women engage in identity work during our consecutive discussions. I also try to identify what the role of gender is during these discussions and in identity work. I have conducted this thesis by interviewing both women in two consecutive in-depth interviews that took place a little over a year apart. After each interview I constructed a narrative that focused on the interviewee’s working life experiences regarding her gender reassignment process and career. Later on, these narratives have worked as background against which I have reflected the identity work and the practice of narrating identity that took place during our meetings. The concept of identity is based on multiple, always changing and socially constructed identities brought forward in popular queer theory literature. I have also used queer theory as a guide in identifying gender related identity work regarding my interviewees. I use the popular identity work literature and my data to name the dominant elements that are present during identity work. I also present a framework for identity work that shows how the previous identity work episode and the micro-level context have an effect on both: narrative identity practice and identity work. In addition I show how gender was present as a subject that was referred to and discussed about and a force that was always looming in the background when we were having our identity discussions. This thesis adds to current identity work literature and queer theory. By making the gender related identity work visible, it helps us to grasp on and change current gendered practices and to undo gender. It also helps us to see and identify some of the forces that contribute to shaping our identities and action

Психокоррекция коммуникативной формы сексуальной дезадаптации у мужчин с органическим расстройством личности и изменением полового предпочтения

Представлена разработанная автором система психотерапии коммуникативной формы сексуальной дезадаптации супругов при девиантном сексуальном поведении мужчин с органическим расстройством личности. Предложенная система апробирована с хорошим терапевтическим эффектом у дезадаптированных супружеских пар, в которых у мужей наблюдалось изменение полового предпочтения.The original system of psychotherapy for communicative sexual dysadaptation of spouses at deviant sexual behavior of men with organic personality disorders is presented. The proposed system was tested with a good therapeutic effect in dysadapted married couples, in which the husband had changes of sexual preference