N. Jovanovic

Increased BDNF Promoter Methylation in the Wernicke Area of Suicide Subjects

CONTEXTnBrain-derived neurotrophic factor (BDNF) plays a pivotal role in the pathophysiology of suicidal behavior and BDNF levels are decreased in the brain and plasma of suicide subjects. So far, the mechanisms leading to downregulation of BDNF expression are poorly understood.nnnOBJECTIVESnTo test the hypothesis that alterations of DNA methylation could be involved in the dysregulation of BDNF gene expression in the brain of suicide subjects.nnnDESIGNnThree independent quantitative methylation techniques were performed on postmortem samples of brain tissue. BDNF messenger RNA levels were determined by quantitative real-time polymerase chain reaction.nnnSETTINGnAcademic medical center.nnnPATIENTS OR OTHER PARTICIPANTSnForty-four suicide completers and 33 nonsuicide control subjects of white ethnicity.nnnMAIN OUTCOME MEASURESnThe DNA methylation degree at BDNF promoter IV and the genome-wide DNA methylation levels in the brains Wernicke area.nnnRESULTSnPostmortem brain samples from suicide subjects showed a statistically significant increase of DNA methylation at specific CpG sites in BDNF promoter/exon IV compared with nonsuicide control subjects (P < .001). Most of the CpG sites lying in the -300/+500 region, on both strands, had low or no methylation, with the exception of a few sites located near the transcriptional start site that had differential methylation, while genome-wide methylation levels were comparable among the subjects. The mean methylation degree at the 4 CpG sites analyzed by pyrosequencing was always less than 12.9% in the 33 nonsuicide control subjects, while in 13 of 44 suicide victims (30%), the mean methylation degree ranged between 13.1% and 34.2%. Higher methylation degree corresponded to lower BDNF messenger RNA levels.nnnCONCLUSIONSnBDNF promoter/exon IV is frequently hypermethylated in the Wernicke area of the postmortem brain of suicide subjects irrespective of genome-wide methylation levels, indicating that a gene-specific increase in DNA methylation could cause or contribute to the downregulation of BDNF expression in suicide subjects. The reported data reveal a novel link between epigenetic alteration in the brain and suicidal behavior.

The role of CYP2D6 and ABCB1 pharmacogenetics in drug-naïve patients with first-episode schizophrenia treated with risperidone.

PurposeTo evaluate the role of cytochrome 450 2D6 (CYP2D6) and ABCB1 variants on plasma risperidone concentrations and treatment response in 83 drug-naive patients experiencing a first episode of psychosis.MethodsAll patients were treated with risperidone for 8xa0weeks. The CYP2D6 genotyping was performed by allele-specific PCR–restriction fragment length polymorphism analysis (for alleles *3,*4,*6) and long-distance PCR (for duplications and allele *5), while real-time PCR analysis was used for the ABCB1 G2677T/A and C3435T variants. Plasma concentrations of risperidone and 9-OH risperidone were measured by high-performance liquid chromatography.ResultsThe number of patients with the CYP2D6 wild type (wt)/wt, wt/mutation (mut) and mut/mut genotype was 43, 32 and 8, respectively. The number of patients with the ABCB1 2677G/G, G/T and T/T variants was 29, 42 and 12, respectively; those with the 3435CC, C/T and T/T variants was 25, 37 and 21, respectively. The CYP2D6 genotype had a strong effect on the steady-state dose-corrected plasma levels (C/D) of risperidone, its 9-OH metabolite and the active moiety, while the ABCB1 2677xa0T/T and 3435xa0T/T genotypes has similarly strong effects on the active moiety C/D. The CYP2D6 poor metabolizers had a significantly higher risperidone C/D and active moiety C/D and lower 9-OH risperidone C/D. The ABCB1 3435xa0T allele and the ABCB1 2667xa0T-3435xa0T haplotype carriers were more frequent among subjects without extrapyramidal syndromes. Patients showed significant improvements in positive and general symptoms, but not in negative symptoms. These changes were not related to variations in genetic and drug concentration data.ConclusionOur findings suggest that CYP2D6 and ABCB1 G2677T and C3435T may be useful determinants of risperidone plasma concentrations, but the clinical implications of these associations in relation to treatment response and side-effects remain unclear.

The Picture of Mental Health/Illness in the Printed Media in Three Central European Countries

Even in the era of the Internet, printed media are still among the most frequently identified sources of mental health information. Many studies have shown that this information is frequently negative and contributes to stigmatization of people with mental illness. This international comparative study describes the content of media messages about mental health/illness in terms of stigma in three Central European countries. The study sample comprised all articles pertaining to the topic of mental health/illness (N = 450) identified during five week-long periods in 2007 chosen from the six most widely read newspapers and magazines in each country. The authors used content analysis methods to achieve quantitative and qualitative objectives. More than half of all articles contained negative statements reflecting stigma toward persons with mental illness. Substance abuse disorders are the most frequent mental conditions covered in all three countries (22%), and psychotic disorders are the most stigmatized. Countries significantly differ in length of articles, in the association of aggressive behavior with persons with mental illness, and in the use of a sensationalized style of writing. Coverage of mental health/illness issues differs to some extent across countries but is generally of poor quality. On the basis of the authors findings, practical recommendations for journalists can be tailored specifically for each country.

Psychiatric disorders and aggression in the printed media: is there a link? a central European perspective

BackgroundA content analysis was used to describe the association between psychiatric disorders and aggression in the printed media in the Czech Republic and Slovakia.MethodsArticles were chosen from the most widely read daily newspapers and magazines in both countries during five one-week periods in 2007. A coding manual was developed and a content analysis was performed. Aggressive behavior was assessed by two separate categories - the role of the mentally ill person in the violent act (perpetrator/victim) and the type of aggressive act (homicide, suicide).ResultsA total of 375 articles were analyzed. Main findings: 1) The proportion of articles depicting psychiatric disorders together with either self- or other-directed aggressive behavior is 31.2%; 2) Homicide was most frequently mentioned in the context of psychotic disorders and schizophrenia, while affective disorders were most frequently associated with both completed suicides and homicides; 3) Eating disorders and anxiety disorders were seldom associated with any kind of aggressive behavior, including self-harm; 4) The vast majority of articles presented mentally ill people as perpetrators, and these articles were more often coded as stigmatizing. 5) Articles with aggressive behavior mentioned on the cover are roughly as frequent as those with aggressive behavior in the later sections of the media (36.7% vs. 30.7%).ConclusionsThe results are similar to the findings in countries with longer histories of consistent advocacy for improved depiction of mental illness in the media. However, we have shown that persons with mental illness are still over-portrayed as perpetrators of violent crimes, especially homicides.

Burnout syndrome among psychiatric trainees in 22 countries: Risk increased by long working hours, lack of supervision, and psychiatry not being first career choice

BACKGROUNDnPostgraduate medical trainees experience high rates of burnout, but evidence regarding psychiatric trainees is missing. We aim to determine burnout rates among psychiatric trainees, and identify individual, educational and work-related factors associated with severe burnout.nnnMETHODSnIn an online survey psychiatric trainees from 22 countries were asked to complete the Maslach Burnout Inventory (MBI-GS) and provide information on individual, educational and work-related parameters. Linear mixed models were used to predict the MBI-GS scores, and a generalized linear mixed model to predict severe burnout.nnnRESULTSnThis is the largest study on burnout and training conditions among psychiatric trainees to date. Complete data were obtained from 1980 out of 7625 approached trainees (26%; range 17.8-65.6%). Participants were 31.9 (SD 5.3) years old with 2.8 (SD 1.9) years of training. Severe burnout was found in 726 (36.7%) trainees. The risk was higher for trainees who were younger (P<0.001), without children (P=0.010), and had not opted for psychiatry as a first career choice (P=0.043). After adjustment for socio-demographic characteristics, years in training and country differences in burnout, severe burnout remained associated with long working hours (P<0.001), lack of supervision (P<0.001), and not having regular time to rest (P=0.001). Main findings were replicated in a sensitivity analysis with countries with response rate above 50%.nnnCONCLUSIONSnBesides previously described risk factors such as working hours and younger age, this is the first evidence of negative influence of lack of supervision and not opting for psychiatry as a first career choice on trainees burnout.

Pharmaceutical industry interactions of psychiatric trainees from 20 European countries

BACKGROUNDnInteractions between the pharmaceutical industry (PI) and psychiatrists have been under scrutiny recently, though there is little empirical evidence on the nature of the relationship and its intensity at psychiatry trainee level. We therefore studied the level of PI interactions and the underlying beliefs and attitudes in a large sample of European psychiatric trainees.nnnMETHODSnOne thousand four hundred and forty-four psychiatric trainees in 20 European countries were assessed cross-sectionally, with a 62-item questionnaire.nnnRESULTSnThe total number of PI interactions in the preceding two months varied between countries, with least interactions in The Netherlands (M (Mean)=0.92, SD=1.44, range=0-12) and most in Portugal (M=19.06, SD=17.44, range=0-100). Trainees were more likely to believe that PI interactions have no impact on their own prescribing behaviour than that of other physicians (M=3.30, SD=1.26 vs. M=2.39, SD=1.06 on a 5-point Likert scale: 1 completely disagree to 5 completely agree). Assigning an educational role to the pharmaceutical industry was associated with more interactions and higher gift value (IRR (incidence rate ratio)=1.21, 95%CI=1.12-1.30 and OR=1.18, 95%CI=1.02-1.37).nnnCONCLUSIONSnThere are frequent interactions between European psychiatric trainees and the PI, with significant variation between countries. We identified several factors affecting this interaction, including attribution of an educational role to the PI. Creating alternative educational opportunities and specific training dedicated to PI interactions may therefore help to reduce the impact of the PI on psychiatric training.

Suicide ideators and attempters with schizophrenia – The role of 5-HTTLPR, rs25531, and 5-HTT VNTR Intron 2 variants

AIMnTo examine the role of 5-HTTLPR, rs25531 and 5-HTT VNTR Intron 2 variants in subjects with psychotic disorders manifesting suicide ideation and behaviour.nnnMETHODSnThe study included 519 subsequently hospitalized subjects who were genotyped for 5-HTTLPR, rs25531 and 5-HTT VNTR In2 variants. Clinical assessments included structured psychiatric interview, sociodemographic characteristics, suicide ideation and behaviour (SIBQ), severity of psychopathology (PANSS) and depression (CDSS).nnnRESULTSnThree subgroups were identified: suicide attempters (N = 161), suicide ideators (N = 174) and subjects who never reported suicide ideation or behaviour (comparative group, N = 184).nnnMAJOR FINDINGSn1) Suicide attempters scored highest on the CDSS, while no differences between the three clinical subgroups were detected in the PANSS scores; 2) Suicide attempters were more frequently the carriers of L(A) allele, while subjects in the comparative group were more frequently the carriers of low expression 5-HTTLPR/5-HTT rs25531 haplotype SL(G); 3) No difference was found between the three clinical groups in the 5-HTT VNTR In2 variants; 4) Subjects with 5-HTTLPR/5-HTT rs25531 intermediate expression haplotype (L(A)L(G,)SL(A)) scored higher on the PANSS general psychopathology subscale; 5) There was no association between suicide attempt or ideation and 5-HTTLPR/In2 or 5-HTTLPR/rs25531/In2 haplotype distribution.nnnCONCLUSIONnThe suicide ideators, attempters and controls did not differ significantly in 5-HTTLPR or 5-HTT VNTR In 2 variants, but 5-HTTLPR/5-HTT rs25531 haplotype might be a useful genetic marker in distinguishing these three clinical groups.

Association between psychopathology and suicidal behavior in schizophrenia. A cross-sectional study of 509 participants.

BACKGROUNDnSuicide in schizophrenia is a serious problem--ideation rates go up to 40%, and approximately one half of patients attempt suicide at least once. The distinction between attempters and ideators is vital in everyday clinical practice.nnnAIMnTo explore the association between psychopathology and suicidal behavior in a comparative study of three groups of patients with schizophrenia: suicide ideators, suicide attempters, and subjects without suicide ideation and behavior.nnnMETHODnThe study included 509 patients: suicide attempters (n = 159), ideators (n = 180), and a comparative group (n = 170). The clinical assessment consisted of a structured psychiatric interview and an evaluation of sociodemographics, suicidality (SIBQ), psychopathology (PANSS), and depression (CDSS).nnnRESULTSnSuicide attempters were more depressed than ideators, and both groups had higher CDSS scores than the comparative group. The overall contribution of positive, negative, and general PANSS symptoms was not statistically significant enough to differentiate ideators from attempters. A principal component analysis of the PANSS items revealed five components: disinhibition, withdrawal, anxiety and guilt, reality distortion, and disorganization. Two logistic regression analyses showed that suicide ideation or attempt was significantly related to depression, anxiety, guilt, gender, age, and number of previous hospitalizations. Compared to suicide ideators, attempters were more depressed, had a higher number of previous hospitalizations, and lower education.nnnCONCLUSIONnThe results indicate that clinicians should look for depression, anxiety, and guilt feelings, while positive and negative symptoms seem to be less relevant for suicide assessment in schizophrenia.

Scenarios for the future of mental health care: a social perspective

Social values and concepts have played a central role in the history of mental health care. They have driven major reforms and guided the development of various treatment models. Although social values and concepts have been important for mental health care in the past, this Personal View addresses what their role might be in the future. We (DG, PH, and SP) did a survey of professional stakeholders and then used a scenario planning technique in an international expert workshop to address this question. The workshop developed four distinct but not mutually exclusive scenarios in which the social aspect is central: mental health care will be patient controlled; it will target peoples social context to improve their mental health; it will become virtual; and access to care will be regulated on the basis of social disadvantage. These scenarios are not intended as fixed depictions of what will happen. They could, however, be useful in guiding further debate, research, and innovation.

Psychometric properties and factor structure of the Temperament and Character Inventory-Revised (TCI-R) in a Croatian psychiatric outpatient sample

OBJECTIVEnThe goal of this study was to investigate psychometric properties and factorial structure of the Croatian adaptation of the Temperament and Character Inventory-Revised (TCI-R) in a sample of psychiatric outpatients (n=328).nnnMETHODnThe participants filled out the TCI-R, as well as self-report measures of the Big-Five personality traits (IPIP-50), trait impulsivity (BIS-11), depression (BDI-II), suicidality (SBQ-R), and life satisfaction (SWLS). We explored the internal consistency of 7 domains and 29 subscales and compared it with the Croatian version of the original TCI used in prior studies. Principal component analysis with promax rotation was conducted on temperament and character subscales separately, while concurrent validity was examined through the TCI-Rs relations with the abovementioned psychological measures.nnnRESULTSnThe TCI-R scales showed adequate internal consistencies, with Cronbachs alpha values ranging from 0.77 to 0.93. The internal consistency showed to be higher in comparison with the Croatian version of the original TCI. The postulated four-factor structure of temperament and the three-factor structure of character were confirmed. The meaningful associations with other measures supported the concurrent validity of the TCI-R.nnnCONCLUSIONnThe Croatian adaptation of the TCI-R exhibited satisfactory reliability and validity in a sample of psychiatric outpatients. These findings support the use of the TCI-R in Croatian clinical settings over its predecessor (TCI).