Anti-neuroinflammatory microRNA-146a-5p as a potential biomarker for neuronavigation-guided rTMS therapy success in medication resistant depression disorder.

Treatment-resistant depression (TRD) is a challenging issue to address. Repetitive transcranial magnetic stimulation (rTMS) is commonly used but shows varying efficacy, necessitating a deeper understanding of depression physiology and rTMS mechanisms. Notably, an increasing amount of recent data has displayed the connection of TRD and its clinical outcome with chronic inflammatory processes. The current study included 19 TRD patients undergoing rTMS and 11 depressed patients responding to medication as a comparison group. We assessed therapeutic efficacy using MADRS, HAM-D-17, GAD-7, and PHQ-9 tests. Inflammatory markers, neurotrophins, and associated miRNAs were measured in patients blood serum before and during treatment. A control group of 18 healthy individuals provided baseline data. The results of our study showed significantly higher levels of pro-inflammatory interleukins-6 and - 8 in TRD patients compared to drug-responders, which also related to more severe symptoms before treatment. In addition, TRD patients, both before and during treatment, exhibited higher average blood serum concentrations of pro-inflammatory interleukin-18 and lower levels of anti-neuroinflammatory miR-146a-5p compared to healthy controls. We also observed that the expression of miR-16-5p, miR-93-5p, and especially miR-146a-5p correlated with clinical changes following rTMS. Our study confirmed that TRD patients possess a higher inflammatory status, while the anti-neuroinflammatory miR-146a-5p was demonstrated to have a considerable potential for predicting their rTMS treatment success.

Statistical Analysis of Graph-Theoretic Indices to Study EEG-TMS Connectivity in Patients With Depression.

AIM: The objective of this work was to demonstrate the usefulness of a novel statistical method to study the impact of transcranial magnetic stimulation (TMS) on brain connectivity in patients with depression using different stimulation protocols, i.e., 1 Hz repetitive TMS over the right dorsolateral prefrontal cortex (DLPFC) (protocol G1), 10 Hz repetitive TMS over the left DLPFC (G2), and intermittent theta burst stimulation (iTBS) consisting of three 50 Hz burst bundle repeated at 5 Hz frequency (G3). METHODS: Electroencephalography (EEG) connectivity analysis was performed using Directed Transfer Function (DTF) and a set of 21 indices based on graph theory. The statistical analysis of graph-theoretic indices consisted of a combination of the k-NN rule, the leave-one-out method, and a statistical test using a 2 × 2 contingency table. RESULTS: Our new statistical approach allowed for selection of the best set of graph-based indices derived from DTF, and for differentiation between conditions (i.e., before and after TMS) and between TMS protocols. The effects of TMS was found to differ based on frequency band. CONCLUSION: A set of four brain asymmetry measures were particularly useful to study protocol- and frequency-dependent effects of TMS on brain connectivity. SIGNIFICANCE: The new approach would allow for better evaluation of the therapeutic effects of TMS and choice of the most appropriate stimulation protocol.

Brain stimulation effects on serum BDNF, VEGF, and TNFα in treatment-resistant psychiatric disorders.

Resistance to pharmacological treatment poses a notable challenge for psychiatry. Such cases are usually treated with brain stimulation techniques, including repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT). Empirical evidence links treatment resistance to insufficient brain plasticity and chronic inflammation. Therefore, this study encompasses analysis of neurotrophic and inflammatory factors in psychiatric patients undergoing rTMS and ECT in order to refine the selection of patients and predict clinical outcomes. This study enrolled 25 drug-resistant depressive patients undergoing rTMS and 31 drug-resistant schizophrenia patients undergoing ECT. Clinical efficacy of brain stimulation therapies was gauged using MADRS and HAM-D scales in the depression group and PANSS scale in the schizophrenia group. Blood-derived BDNF, VEGF, and TNFα were analysed during the treatment course. For reference, 19 healthy control subjects were also enrolled. After statistical analysis, no significant differences were detected in BDNF, VEGF, and TNFα concentrations among healthy, depressive, and schizophrenic subject groups before the treatment. However, depressive patient treatment with rTMS has increased BDNF concentration, while schizophrenic patient treatment with ECT has lowered the concentration of TNFα. Our findings suggest that a lower initial TNFα concentration could be a marker for treatment success in depressed patients undergoing rTMS, whereas in schizophrenic patient group treated with ECT, a higher concentration of VEGF correlates to milder symptoms post-treatment, especially in the negative scale.

A blind spot on the global mental health map: a scoping review of 25 years' development of mental health care for people with severe mental illnesses in central and eastern Europe.

Just over 25 years have passed since the major sociopolitical changes in central and eastern Europe; our aim was to map and analyse the development of mental health-care practice for people with severe mental illnesses in this region since then. A scoping review was complemented by an expert survey in 24 countries. Mental health-care practice in the region differs greatly across as well as within individual countries. National policies often exist but reforms remain mostly in the realm of aspiration. Services are predominantly based in psychiatric hospitals. Decision making on resource allocation is not transparent, and full economic evaluations of complex interventions and rigorous epidemiological studies are lacking. Stigma seems to be higher than in other European countries, but consideration of human rights and user involvement are increasing. The region has seen respectable development, which happened because of grassroots initiatives supported by international organisations, rather than by systematic implementation of government policies.

Are Mental Health Effects of Internet Use Attributable to the Web-Based Content or Perceived Consequences of Usage? A Longitudinal Study of European Adolescents.

BACKGROUND: Adolescents and young adults are among the most frequent Internet users, and accumulating evidence suggests that their Internet behaviors might affect their mental health. Internet use may impact mental health because certain Web-based content could be distressing. It is also possible that excessive use, regardless of content, produces negative consequences, such as neglect of protective offline activities. OBJECTIVE: The objective of this study was to assess how mental health is associated with (1) the time spent on the Internet, (2) the time spent on different Web-based activities (social media use, gaming, gambling, pornography use, school work, newsreading, and targeted information searches), and (3) the perceived consequences of engaging in those activities. METHODS: A random sample of 2286 adolescents was recruited from state schools in Estonia, Hungary, Italy, Lithuania, Spain, Sweden, and the United Kingdom. Questionnaire data comprising Internet behaviors and mental health variables were collected and analyzed cross-sectionally and were followed up after 4 months. RESULTS: Cross-sectionally, both the time spent on the Internet and the relative time spent on various activities predicted mental health (P<.001), explaining 1.4% and 2.8% variance, respectively. However, the consequences of engaging in those activities were more important predictors, explaining 11.1% variance. Only Web-based gaming, gambling, and targeted searches had mental health effects that were not fully accounted for by perceived consequences. The longitudinal analyses showed that sleep loss due to Internet use (ß=.12, 95% CI=0.05-0.19, P=.001) and withdrawal (negative mood) when Internet could not be accessed (ß=.09, 95% CI=0.03-0.16, P<.01) were the only consequences that had a direct effect on mental health in the long term. Perceived positive consequences of Internet use did not seem to be associated with mental health at all. CONCLUSIONS: The magnitude of Internet use is negatively associated with mental health in general, but specific Web-based activities differ in how consistently, how much, and in what direction they affect mental health. Consequences of Internet use (especially sleep loss and withdrawal when Internet cannot be accessed) seem to predict mental health outcomes to a greater extent than the specific activities themselves. Interventions aimed at reducing the negative mental health effects of Internet use could target its negative consequences instead of the Internet use itself. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 65120704; http://www.isrctn.com/ISRCTN65120704?q=&filters=recruitmentCountry:Lithuania&sort=&offset= 5&totalResults=32&page=1&pageSize=10&searchType=basic-search (Archived by WebCite at http://www.webcitation/abcdefg).

Differential diagnosis of depression and Alzheimer's disease with the Addenbrooke's Cognitive Examination-Revised (ACE-R).

BACKGROUND: One of the usual problems psychologists and clinicians face in clinical practice is differential diagnostics of Alzheimer's disease and depression. It has been reported that the ACE and ACE-R could discriminate the cognitive dysfunctions due to depression from that due to dementia, although this is not uniform in all studies. The current study aimed to evaluate the utility of the ACE-R to differentiate late-life onset depression (with severe episode) from mild-moderate Alzheimer's Disease (AD). METHODS: This study received approval from the Lithuanian Bioethics Committee. All participants were older than 50 years (mean age = 66.52 (±8.76) years). The study sample consisted of 295 individuals: 117 with severe depression, 85 with mild-moderate Alzheimer's disease (AD), and 94 age, gender and education matched participants of control group. RESULTS: The ACE-R had high sensitivity (100%) and specificity (81%) at detecting cognitive impairments related to AD. Patients with late-life onset depression (ACE-R mean 76.82, SD = 7.36) performed worse than controls (ACE-R mean 85.08, SD = 7.2), but better than the AD group (ACE-R mean 54.74, SD = 12.19). Participants with late-life onset depression were differentiated by mild impairment in the ACE-R total score with mild memory (13.79, SD = 6.29) and greater deficits in letter fluency (3.65, SD = 1.21) than in semantic fluency (4.68, SD = 1.23). Participants with AD were differentiated by severely impaired performance on attention and orientation (11.80, SD = 2.93), memory (8.25, SD = 3.47) and language subtests (17.21, SD = 4.04), and moderately impaired performance on verbal fluency (6.07, SD = 2.74). CONCLUSIONS: ACE-R has diagnostic accuracy in detecting people with AD and can be used in differential diagnostics of late-life onset depression (severe episode) and AD. Diagnostic accuracy may be improved by analyzing the neuropsychological profiles and using lower cutoffs for different age groups.

Global pattern of experienced and anticipated discrimination reported by people with major depressive disorder: a cross-sectional survey.

BACKGROUND: Depression is the third leading contributor to the worldwide burden of disease. We assessed the nature and severity of experienced and anticipated discrimination reported by adults with major depressive disorder worldwide. Moreover, we investigated whether experienced discrimination is related to clinical history, provision of health care, and disclosure of diagnosis and whether anticipated discrimination is associated with disclosure and previous experiences of discrimination. METHODS: In a cross-sectional survey, people with a diagnosis of major depressive disorder were interviewed in 39 sites (35 countries) worldwide with the discrimination and stigma scale (version 12; DISC-12). Other inclusion criteria were ability to understand and speak the main local language and age 18 years or older. The DISC-12 subscores assessed were reported discrimination and anticipated discrimination. Multivariable regression was used to analyse the data. FINDINGS: 1082 people with depression completed the DISC-12. Of these, 855 (79%) reported experiencing discrimination in at least one life domain. 405 (37%) participants had stopped themselves from initiating a close personal relationship, 271 (25%) from applying for work, and 218 (20%) from applying for education or training. We noted that higher levels of experienced discrimination were associated with several lifetime depressive episodes (negative binomial regression coefficient 0·20 [95% CI 0·09-0·32], p=0·001); at least one lifetime psychiatric hospital admission (0·29 [0·15-0·42], p=0·001); poorer levels of social functioning (widowed, separated, or divorced 0·10 [0·01-0·19], p=0·032; unpaid employed 0·34 [0·09-0·60], p=0·007; looking for a job 0·26 [0·09-0·43], p=0·002; and unemployed 0·22 [0·03-0·41], p=0·022). Experienced discrimination was also associated with lower willingness to disclose a diagnosis of depression (mean discrimination score 4·18 [SD 3·68] for concealing depression vs 2·25 [2·65] for disclosing depression; p<0·0001). Anticipated discrimination is not necessarily associated with experienced discrimination because 147 (47%) of 316 participants who anticipated discrimination in finding or keeping a job and 160 (45%) of 353 in their intimate relationships had not experienced discrimination. INTERPRETATION: Discrimination related to depression acts as a barrier to social participation and successful vocational integration. Non-disclosure of depression is itself a further barrier to seeking help and to receiving effective treatment. This finding suggests that new and sustained approaches are needed to prevent stigmatisation of people with depression and reduce the effects of stigma when it is already established. FUNDING: European Commission, Directorate General for Health and Consumers, Public Health Executive Agency.

Ageing and health status in adults with intellectual disabilities: results of the European POMONA II study.

BACKGROUND: POMONA II was a European Commission public health-funded project. The research questions in this article focus on age-specific differences relating to environmental and lifestyle factors, and the 17 medical conditions measured by the POMONA Checklist of Health Indicators (P15). METHOD: The P15 was completed in a cross-sectional design for a stratified sample of 1,253 adults with ID across 14 European member states. RESULTS: Older people (55+) were more likely to live in larger residential homes. Rates of smoking and use of alcohol were lower than in the general population but were higher with older age. More than 60% of older adults had a sedentary lifestyle. Cataract, hearing disorder, diabetes, hypertension, osteoarthritis/arthrosis, and osteoporosis were positively associated with advancing age; allergies and epilepsy, negatively associated. CONCLUSIONS: Some evidence of health disparities was found for older people with ID, particularly in terms of underdiagnosed or inadequately managed preventable health conditions.

Sampling and ethical issues in a multicenter study on health of people with intellectual disabilities.

OBJECTIVES: To study health inequalities in persons with intellectual disabilities, representative and unbiased samples are needed. Little is known about sample recruitment in this vulnerable group. This study aimed to determine differences in ethical procedures and sample recruitment in a multicenter research on health of persons with intellectual disabilities. Study questions regarded the practical sampling procedure, how ethical consent was obtained in each country, and which person gave informed consent for each study participant. STUDY DESIGN AND SETTING: Exploratory, as part of a multicenter study, in 14 European countries. After developing identical guidelines for all countries, partners collected data on health indicators by orally interviewing 1,269 persons with intellectual disabilities. Subsequently, semistructured interviews were carried out with partners and researchers. RESULTS: Identification of sufficient study participants proved feasible. Sampling frames differed from nationally estimated proportions of persons with intellectual disabilities living with families or in residential settings. Sometimes, people with intellectual disabilities were hard to trace. Consent procedures and legal representation varied broadly. Nonresponse data proved unavailable. CONCLUSION: To build representative unbiased samples of vulnerable groups with limited academic capacities, international consensus on respectful consent procedures and tailored patient information is necessary.

European network for promoting the physical health of residents in psychiatric and social care facilities (HELPS): background, aims and methods.

BACKGROUND: People with mental disorders have a higher prevalence of physical illnesses and reduced life expectancy as compared with the general population. However, there is a lack of knowledge across Europe concerning interventions that aim at reducing somatic morbidity and excess mortality by promoting behaviour-based and/or environment-based interventions. METHODS AND DESIGN: HELPS is an interdisciplinary European network that aims at (i) gathering relevant knowledge on physical illness in people with mental illness, (ii) identifying health promotion initiatives in European countries that meet country-specific needs, and (iii) at identifying best practice across Europe. Criteria for best practice will include evidence on the efficacy of physical health interventions and of their effectiveness in routine care, cost implications and feasibility for adaptation and implementation of interventions across different settings in Europe. HELPS will develop and implement a "physical health promotion toolkit". The toolkit will provide information to empower residents and staff to identify the most relevant risk factors in their specific context and to select the most appropriate action out of a range of defined health promoting interventions. The key methods are (a) stakeholder analysis, (b) international literature reviews, (c) Delphi rounds with experts from participating centres, and (d) focus groups with staff and residents of mental health care facilities.Meanwhile a multi-disciplinary network consisting of 15 European countries has been established and took up the work. As one main result of the project they expect that a widespread use of the HELPS toolkit could have a significant positive effect on the physical health status of residents of mental health and social care facilities, as well as to hold resonance for community dwelling people with mental health problems. DISCUSSION: A general strategy on health promotion for people with mental disorders must take into account behavioural, environmental and iatrogenic health risks. A European health promotion toolkit needs to consider heterogeneity of mental disorders, the multitude of physical health problems, health-relevant behaviour, health-related attitudes, health-relevant living conditions, and resource levels in mental health and social care facilities.

Perceptions of assertive community treatment in the UK and Lithuania.

BACKGROUND: There is current uncertainty over the future of assertive community and outreach teams in view of recent evidence suggesting that they no longer reduce hospital admissions. Despite this, assertive teams remain popular among practitioners. AIMS: To examine the views of assertive community team members and other mental health professionals in London (UK) and Vilnius (Lithuania) to determine important differences in attitudes. METHOD: A questionnaire, involving the assessment of statements giving common opinions on assertive community teams, was given to 62 staff in Vilnius, Lithuania and West London, UK, 33 from assertive community or outreach teams and 29 from other mental health professionals. RESULTS: The results of the questionnaire showed that personnel in experienced assertive outreach teams in London believed that they gave more intensive care (p < 0.001), felt it of greater value to see patients in the community (p < 0.001) and were not just well-resourced community teams with low caseloads (p < 0.01) than did other groups, but they placed lower value on assertiveness (p = 0.04) and comprehensive care (p < 0.04). These differences were less marked in Lithuania where staff regarded home treatment as similar to clinic treatment and were more supportive of comprehensive care. CONCLUSION: The results suggest that in experienced community teams the notion of assertiveness has become less important in planned intensive community care and so the term ACT may be outmoded. However, for countries such as Lithuania, somewhat similar to the United States in 1972 when ACT began, the original principles are still appropriate and 'assertive' is a major component of their effectiveness.

Lithuania mental health country profile.

As a part of international mental health policy, programmes and services project, the 'country profile' instrument was used for assessment of mental health policy and services in the Republic of Lithuania. Analysis of contextual factors revealed high levels of social pathology (including violence, suicide and other self-destructive behaviour) with stigmatizing approaches by the general population to mentally disturbed persons and other vulnerable groups. Analysis of existing data about resources invested in the mental health care system raises questions for policymakers about the effectiveness of this traditional way of investment. The largest proportion of physical and human capital is concentrated in psychiatric institutions, with large numbers of beds, psychiatrists and increasing funding for medications, while other components of care--such as housing, psychosocial and vocational rehabilitation, community-based child mental health services--are not being developed. Statistical accounts keep the tradition of presenting processes as outcomes, while modern assessment of outcomes of services, programmes and policies are lacking. The findings from this country profile may be very useful in the development of modern mental health policies in the countries of Eastern and Central Europe, which have been deprived for decades from the opportunity to introduce evidence-based mental health policies and services.