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Mutations in splicing factor 3B subunit 1 (SF3B1) frequently occur in patients with chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes (MDS). These mutations have different effects on the disease prognosis with beneficial effect in MDS and worse prognosis in CLL patients. A full-length transcriptome approach can expand our knowledge on SF3B1 mutation effects on RNA splicing and its contribution to patient survival and treatment options. We applied long-read transcriptome sequencing (LRTS) to 44 MDS and CLL patients, as well as two pairs of isogenic cell lines with and without SF3B1 mutations, and found >60% of novel isoforms. Splicing alterations were largely shared between cancer types and specifically affected the usage of introns and 3' splice sites. Our data highlighted a constrained window at canonical 3' splice sites in which dynamic splice site switches occurred in SF3B1-mutated patients. Using transcriptome-wide RNA binding maps and molecular dynamics simulations, we showed multimodal SF3B1 binding at 3' splice sites and predicted reduced RNA binding at the second binding pocket of SF3B1K700E Our work presents the hitherto most complete LRTS study of the SF3B1 mutation in CLL and MDS and provides a resource to study aberrant splicing in cancer. Moreover, we showed that different disease prognosis most likely results from the different cell types expanded during carcinogenesis rather than different mechanisms of action of the mutated SF3B1 These results have important implications for understanding the role of SF3B1 mutations in hematological malignancies and other related diseases.
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BACKGROUND: Alongside the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, the number of patients with persistent symptoms following acute infection with SARS-CoV-2 is of concern. It is estimated that at least 65 million people worldwide meet criteria for what the World Health Organization (WHO) defines as "post-COVID-19 condition" - a multisystem disease comprising a wide range of symptoms. Effective treatments are lacking. In the present review, we aim to summarize the current evidence for the effectiveness of non-invasive or minimally invasive brain stimulation techniques in reducing symptoms of post-COVID-19. METHODS: After pre-registration with PROSPERO, the review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA). The four electronic databases PubMed/MEDLINE, PsycINFO, Web of Science and Scopus were systematically searched for all relevant studies through April 2nd, 2024. Two independent investigators selected empirical papers that reported on the application of non- or minimally invasive brain stimulation in patients with post-COVID-19 conditions. RESULTS: A total of 19 studies were identified, one using transcutaneous vagus nerve stimulation (tVNS), another using transorbital alternating current stimulation (toACS), 6 studies on transcranial magnetic stimulation (TMS) and 11 studies on transcranial direct current stimulation (tDCS) for the treatment of post-COVID-19 symptoms. CONCLUSIONS: Existing studies report first promising results, illustrating improvement in clinical outcome parameters. Yet, the mechanistic understanding of post-COVID-19 and how brain stimulation techniques may be benefitial are limited. Directions for future research in the field are discussed.
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Borderline personality disorder (BPD) is an established diagnosis in adolescence with high comorbidity and psychosocial impairment. With the introduction of the alternative model for personality disorders in DSM-5 (AMPD), personality functioning is operationalized using the Level of Personality Functioning Scale (LPFS), which has been shown to be associated with severity of personality pathology. The present study aimed at examining differential psychopathological and psychosocial correlates of LPFS and BPD. A total of 526 adolescent in- and outpatients were interviewed with the STiP-5.1 (LPFS) and the SCID-II. Mixed linear regression was used to investigate the associations between the two interviews with measures of psychopathology and psychosocial impairment. 11.4% met the diagnostic threshold of both interviews, 16.1% only of the LPFS, and 64.1% were below the diagnostic threshold in both interviews (no PD). The BPD only group was larger than expected-8.4% of patients who met criteria for BPD did not fulfill criteria for significant impairment in the LPFS. The highest burden was found in individuals concurrently showing significant impairment in LPFS and fulfilling BPD diagnosis (LPFS + BPD). Differences between the LPFS only group and the BPD only group were found in risk behavior and traumatic experiences, with higher prevalence in the BPD group. Findings confirm the high psychopathological burden and psychosocial impairment associated with both BPD and LPFS. Those exceeding the diagnostic threshold of LPFS in combination with a BPD diagnosis are characterized by greatest disability. Not all adolescents fulfilling formal BPD diagnosis showed a clinically significant impairment in LPFS, which may refer to a distinct diagnostic group.
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Homeostasis models posit that nonsuicidal self-injury (NSSI) serves, in part, to upregulate the endogenous opioid system in order to compensate for an opioid deficiency. A few studies have demonstrated lower basal levels of beta-endorphin (BE), an endogenous opioid, in individuals with NSSI. However, longitudinal studies are missing. Hence, the present study aimed to investigate the longitudinal associations between NSSI, comorbid psychopathology (i.e., borderline personality disorder and depressive symptoms), pain sensitivity and basal BE levels in adolescents with NSSI. N = 53 adolescents with NSSI disorder undergoing specialized treatment participated in baseline and one-year follow-up assessments. BE was measured in plasma; pain sensitivity was assessed with a heat pain stimulation paradigm. Associations between BE and change in NSSI, borderline personality disorder and depressive symptoms as well as pain sensitivity were examined using negative binomial and linear regression analyses. We found that an increase in basal BE was significantly associated with a decrease in depressive symptoms. No associations between BE and NSSI, borderline personality disorder symptoms or pain sensitivity were observed. Our findings may confirm a role of plasma BE in the etiology of depressive symptoms but challenge current models of endogenous opioid homeostasis in NSSI.
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Transtorno da Personalidade Borderline , Comorbidade , Depressão , Comportamento Autodestrutivo , beta-Endorfina , Humanos , beta-Endorfina/sangue , Feminino , Masculino , Adolescente , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/sangue , Transtorno da Personalidade Borderline/epidemiologia , Transtorno da Personalidade Borderline/sangue , Estudos Longitudinais , Depressão/epidemiologia , Depressão/sangue , Limiar da Dor/fisiologiaRESUMO
Objective: The effects of Dialectical Behavioral Therapy for Adolescents (DBT-A) on emotional and interpersonal instability were explored in adolescents exhibiting Borderline Personality Disorder (BPD) features, using ecological momentary assessment (EMA) to reduce recall bias.Method: N = 28 help-seeking female adolescents were enrolled, meeting ≥ 3 DSM-IV BPD criteria. BPD criteria, non-suicidal self-injury (NSSI), and depressive symptoms were examined pre- and post-DBT-A treatment (mean duration: 42.74 weeks, SD = 7.46). Participants maintained e-diaries pre- and post-treatment, hourly rating momentary affect, attachment to mother and best friend, and self-injury urges.Results: Interview-rated BPD symptoms decreased (χ²(1) = 5.66, p = .017), alongside reduced self-rated depression severity (χ²(1) = 9.61, p = .002). EMA data showed decreased NSSI urges (χ²(1) = 9.05, p = .003) and increased mother attachment (χ²(1) = 6.03, p = .014). However, mean affect, affective instability, mean attachment to the best friend, and attachment instability showed no significant change over time.Conclusion: DBT-A yielded limited evidence for altering momentary affective states and instability in adolescents based on EMA. Nevertheless, significant effects were observed in reducing NSSI urges and enhancing interpersonal dynamics during treatment, as assessed via EMA.
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BACKGROUND: Neuroimaging studies suggest alterations in prefrontal cortex (PFC) activity in healthy adults under stress. Adolescents with non-suicidal self-injury (NSSI) report difficulties in stress and emotion regulation, which may be dependent on their level of borderline personality disorder (BPD). AIMS: The aim was to examine alterations in the PFC in adolescents with NSSI during stress. METHOD: Adolescents (13-17 years) engaging in non-suicidal self-injury (n = 30) and matched healthy controls (n = 29) performed a task with low cognitive demand and the Trier Social Stress Test (TSST). Mean PFC oxygenation across the PFC was measured with an eight-channel near-infrared spectroscopy system. Alongside self-reports on affect, dissociation and stress, BPD pathology was assessed via clinical interviews. RESULTS: Mixed linear-effect models revealed a significant effect of time on PFC oxygenation and a significant time×group interaction, indicating increased PFC activity in patients engaging in NSSI at the beginning of the TSST compared with healthy controls. Greater BPD symptoms overall were associated with an increase in PFC oxygenation during stress. In exploratory analyses, mixed models addressing changes in PFC connectivity over time as a function of BPD symptoms were significant only for the left PFC. CONCLUSIONS: Results indicate differences in the neural stress response in adolescents with NSSI in line with classic neuroimaging findings in adults with BPD. The link between PFC oxygenation and measures of BPD symptoms emphasises the need to further investigate adolescent risk-taking and self-harm across the spectrum of BPD, and maybe overall personality pathology, and could aid in the development of tailored therapeutic interventions.
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BACKGROUND: Youth with attention-deficit/hyperactivity disorder (ADHD) exhibit increased effort aversion, likely due to deficits in anticipatory dopamine firing. Previous research has shown that transcranial direct current stimulation (tDCS) targeting the right prefrontal cortex can enhance activity in dopaminergic meso-striatal regions. However, the extent to which this specific tDCS configuration effectively modulates effort behavior in anticipation of rewards in ADHD remains uncertain. HYPOTHESIS: We expected an increase of effort maintenance and invigoration during and following our tDCS set-up compared to sham in subjects with ADHD. METHODS: Twenty-four children and adolescents with ADHD (mean age: 11.6 years; 95 % CI [10.7, 12.4]) received 2 mA and sham tDCS for 20 min each. The anode was positioned over the ventromedial prefrontal cortex (PFC), while the cathode was placed over the right dorsolateral PFC, generating an electrical field with maximal strength in the right PFC. During and after the tDCS sessions, participants performed a button-pressing task aimed at earning delayed monetary rewards. Primary outcomes were effort maintenance (frequency of button presses) and invigoration (slopes of button presses), measuring motor task performance. RESULTS: We observed a significant increase in effort maintenance both during (b = 2.66; p < 0.001) and after tDCS (b = 2.04; p= .007) compared to sham. No significant difference was found for invigoration during stimulation, while after bonferroni correction (p = 0.025) a non-significant decrease was found after tDCS compared to sham (b = -5.18; p = 0.041). CONCLUSION: tDCS targeting the ventromedial PFC (anodal) and right dorsolateral PFC (cathodal) increases effort maintenance in children and adolescents with ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade , Córtex Pré-Frontal , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Masculino , Feminino , Criança , Adolescente , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/fisiopatologia , Recompensa , Desempenho Psicomotor/fisiologiaRESUMO
BACKGROUND: Non-suicidal self-injury (NSSI) is of high clinical relevance due to its high prevalence and negative long-term implications. In 2016, the German consensus-based clinical guidelines for diagnostic, assessment and treatment of NSSI in childhood and adolescence were published. However, research indicates that clinical guidelines are often poorly implemented in clinical practice. One crucial part of this process is the training of healthcare professionals to transfer knowledge and capacities to bring guideline recommendations into clinical practice. METHODS: The effect of three different dissemination strategies (printed educational material, e-learning, and blended-learning) on the NSSI guidelines´ recommendations was examined among 671 physicians and psychotherapists via an online-survey. The quasi-experimental study included three measurement points (before the training, after the training, 3-month follow-up) and mixed effects models were used to test for changes in knowledge, competences and attitudes toward NSSI and treatment. Moreover, the transfer of gained competences to practical work and user satisfaction were reviewed. RESULTS: With all three training formats, the intended changes of the outcome variables could be observed. Hereby, the printed educational material condition showed the lowest improvement in the scores for the 'negative attitudes toward NSSI and those who self-injure'. The training effect remained stable throughout the follow-up measurement. The highest application rate of acquired intervention techniques in clinical practice was reported for the blended-learning condition. For all three training strategies, user satisfaction was high and evaluation of training quality was positive, with printed educational material receiving the lowest and blended-learning the highest evaluations. CONCLUSIONS: In summary, all three training formats were perceived to be of high quality and seem to be suited to cover the needs of a heterogeneous group of physicians and psychotherapists. The choice of training method could be driven by considering which training goals are desired to be achieved and by the benefit-cost ratio allowing for tailored training approaches.
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This study investigated sociodemographic and clinical factors influencing help-seeking attitudes and behavior among adolescents with mental health problems. As part of the ProHEAD ("Promoting Help-seeking using E-technology for ADolescents") consortium a school-based, online assessment of sociodemographic information, psychopathology, risk-taking and self-harming behavior, help-seeking attitudes and behavior, and barriers to help-seeking was conducted in adolescents aged ≥ 12 years recruited from randomly selected schools in five regions of Germany. Linear regression analyses with the LMG formula were performed to explore predictors of help-seeking attitudes and behavior and assess their relative importance. Nine thousand five hundred and nine participants (95.5%) completed the online assessment (mean age: 15.1 years, 58.6% female). In total, 1606 participants (16.9%) showed relevant mental health problems (e.g., depressive and eating disorder symptoms, alcohol problems, and thoughts of self-harming behavior). Among them, 895 (55.7%) reported having sought help (lifetime), with higher rates for informal (n = 842, 52.4%) compared to professional (n = 380, 23.7%) sources. High help-seeking propensity emerged as the most important factor contributing to professional help-seeking, followed by elevated levels of psychopathology and perceived barriers, with sociodemographic factors being less impactful. Psychopathological severity also outweighed sociodemographic factors in predicting negative help-seeking attitudes. These findings indicate that attitudes towards seeking professional help, perceived barriers, and psychopathology severity critically influence limited adolescent help-seeking behavior. This emphasizes the need for initiatives that promote help-seeking, reduce negative attitudes, and address structural barriers in adolescent mental health care.
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BACKGROUND: Both low vagally-mediated heart rate variability (HRV) and depression have been shown to be risk factors for cardiovascular disease (CVD). We recently identified an HRV cutpoint below which persons have an increased risk for several cardiometabolic disorders. However, no cutpoint exists to identify those at risk for depression. METHODS: The association between daytime HRV and diagnostically validated depression cutoffs using the five-item World Health Organization Well-being Index (WHO-5) was examined in adults from the Mannheim Industrial Cohort Study (n = 9973; Mage = 41.9[10.9]; 20 % women [n = 1934]). The aim was to identify HRV cutpoints for individuals who may have clinical depression. RESULTS: Regression adjusting for age, sex, and linear trend showed a significant quadratic association between depression, indexed by WHO-5 scores and HRV, indexed by the root mean square successive differences (RMSSD) in milliseconds (ms) (p < 0.001). Logistic regression models adjusting for age, sex, and heart period (i.e., inter-beat intervals) compared the clinically depressed (WHO-5 ≤ 28) and those with a screening diagnosis of depression (WHO-5 ≤ 50) to the rest of the population. Significant odds ratios suggested two RMSSD values 25 ± 2 ms (OR = 1.39 [1.17, 1.64]) and 35 ± 2 ms (OR = 1.17 [1.02, 1.34]) that may be used to identify those with an elevated risk for depression. LIMITATIONS: The sample was primarily German men. Fitness and anti-depressant use were not available. CONCLUSIONS: As HRV is a brief measure that can be used in clinical settings, our HRV cutpoints have implications for the early detection of those at risk for psychological and cardiometabolic disorders.
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Depressão , Frequência Cardíaca , Humanos , Masculino , Feminino , Frequência Cardíaca/fisiologia , Adulto , Pessoa de Meia-Idade , Depressão/fisiopatologia , Depressão/diagnóstico , Nervo Vago/fisiopatologia , Nervo Vago/fisiologia , Fatores de Risco , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/diagnóstico , Alemanha , Estudos de Coortes , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnósticoRESUMO
PURPOSE: Memory plays an essential role in daily life and is one of the first functions to deteriorate in cognitive impairment and dementia. Transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic method; however, its ability to enhance memory is underexplored, especially considering long-term stimulation. We aimed to investigate the effect of a 2-week course of auricular tVNS (taVNS) on memory in a non-clinical population. METHODS: This single-blind randomized placebo-wait-list controlled trial recruited 76 participants (30 men; mean age 48.32 years) and randomized them into four groups: early active/sham taVNS and late active/sham taVNS. Participation in the study lasted 4 weeks; early groups underwent 2 weeks intervention immediately following the first study site visit (days 0-13) and late groups 2 weeks after the first study site visit (days 14-27). Active and sham taVNS included 2 weeks of daily 4-h neurostimulation at the tragus or earlobe, respectively. To assess memory, we used the Rey Auditory Verbal Learning Test. RESULTS: Two weeks of active taVNS, but not sham taVNS, improved immediate recall and short-term memory score both in early and late groups. Furthermore, the improvements persisted over subsequent follow-up in early active taVNS. Importantly, the effect of active taVNS was superior to sham for immediate recall in both early and late groups. There were no statistical differences in delayed recall. CONCLUSION: Our findings suggest that taVNS has potential to improve memory, particularly immediate recall, and may be an effective method in preventing memory loss and mitigating cognitive aging.
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Memória , Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estimulação do Nervo Vago/métodos , Estimulação Elétrica Nervosa Transcutânea/métodos , Método Simples-Cego , Adulto , Memória/fisiologiaRESUMO
BACKGROUND: Mental health problems, such as depression, have a high prevalence in young people. However, the majority of youths suffering from depression do not seek professional help. This study aimed to compare help-seeking behavior, intentions and perceived barriers between youthswith different levels of depressive symptoms. METHODS: This cross-sectional study is part of a large-scale, multi-center project. Participants were n = 9509 youths who were recruited in German schools and completed a baseline screening questionnaire. Based on their depressive symptoms, youths were allocated to the following three subgroups: (a) without depressive symptoms, (b) with subclinical symptoms, (c) with clinical symptoms (measured by PHQ-A). Quantitative analyses compared previous help-seeking behavior, help-seeking intentions and perceived barriers (Barriers questionnaire) between these subgroups. An additional exploratory qualitative content analysis examined text answers on other perceived barriers to help-seeking. RESULTS: Participants were mostly female (n = 5575, 58.6%) and 12 to 24 years old (M = 15.09, SD 2.37). Participants with different levels of depressive symptoms differed significantly in help-seeking behavior, intentions and perceived barriers. Specifically, participants with clinical depressive symptoms reported more previous help-seeking, but lower intentions to seek help compared to participants without symptoms (all p < 0.05). Participants with subclinical depressive symptoms reported a similar frequency of previous help-seeking, but higher intentions to seek help compared to participants without symptoms (all p < 0.05). Perception of barriers was different across subgroups: participants with clinical and subclinical depressive symptoms perceived the majority of barriers such as stigma, difficulties in accessibility, and family-related barriers as more relevant than participants without depressive symptoms. Across all subgroups, participants frequently mentioned intrapersonal reasons, a high need for autonomy, and a lack of mental health literacy as barriers to help-seeking. CONCLUSIONS: Youths with higher levels of depressive symptoms are more reluctant to seek professional help and perceive higher barriers. This underlines the need for effective and low-threshold interventions to tackle barriers, increase help-seeking, and lower depressive symptoms in adolescents and young adults differing in depression severity. TRIAL REGISTRATION: DRKS00014685.
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BACKGROUND: The current study evaluated the stepped care approach applied in AtR!Sk; a specialized outpatient clinic for adolescents with BPD features that offers a brief psychotherapeutic intervention (Cutting Down Program; CDP) to all patients, followed by a more intensive Dialectical Behavioral Therapy for Adolescents (DBT-A) for those whose symptoms persist. METHODS: The sample consisted of 127 patients recruited from two AtR!Sk clinics. The number of BPD criteria, psychosocial functioning, severity of overall psychopathology, number of days with non-suicidal self-injury (NSSI; past month), and the number of suicide attempts (last 3 months) were assessed at clinic entry (T0), after CDP (T1), and at 1- and 2-year follow-up (T2, T3). Based on the T1 assessment (decision criteria for DBT-A: ≥ 3 BPD criteria & ZAN-BPD ≥ 6), participants were allocated into three groups; CDP only (n = 74), CDP + DBT-A (eligible and accepted; n = 36), CDP no DBT-A (eligible, but declined; n = 17). RESULTS: CDP only showed significantly fewer BPD criteria (T2: ß = 3.42, p < 0.001; T3: ß = 1.97, p = 0.008), higher levels of psychosocial functioning (T2: ß = -1.23, p < 0.001; T3: ß = -1.66, p < 0.001), and lower severity of overall psychopathology (T2: ß = 1.47, p < 0.001; T3: ß = 1.43, p = 0.002) over two years compared with CDP no DBT-A, while no group differences were found with regard to NSSI and suicide attempts. There were no group differences between CDP + DBT-A and CDP no DBT-A, neither at T2 nor at T3. DISCUSSION: The findings support the decision criterion for the offer of a more intense therapy after CDP. However, there was no evidence for the efficacy of additional DBT-A, which might be explained by insufficient statistical power in the current analysis.
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BACKGROUND: Disordered eating behaviors (DEBs), a risk factor for the development of eating disorders (EDs), are prevalent in young people and different DEBs frequently co-occur. Previous studies on DEB-patterns have largely used traditional retrospective questionnaires to assess DEBs. In addition, most previous studies did not specifically exclude individuals with clinical EDs, which limits current knowledge concerning purely subclinical patterns of DEBs. In the present study, we aimed to explore phenotypes and group sizes of subclinical patterns of DEBs reported in everyday life via smartphone-based ecological momentary assessment (EMA) in adolescents and young adults from the general population without lifetime EDs. In secondary analyses, we further aimed to investigate whether DEB-patterns would be associated with additional previously identified risk factors for ED-development. METHODS: EMA was conducted in a community sample of 14-21-year-olds from Dresden, Germany, over four days for up to eight times a day and covered engagement in four DEBs: skipping eating, restrained eating, eating large amounts of food, and loss-of-control eating. Data were analyzed from N = 966 individuals without lifetime EDs with an EMA compliance rate of at least 50% (81.9% of the total sample; average compliance: 84.6%). Latent profile analyses were performed to identify subclinical patterns of DEBs, stratified by sex. Associations between symptomatic profiles and ED-risk factors were tested via regression analyses. RESULTS: Based on theoretical deliberations, statistical indices, interpretability, and parsimony, a three-profile solution, namely no DEBs, high-mixed DEBs, and low-mixed DEBs, was selected for both sexes. Both symptomatic profiles in both sexes were associated with more unfavorable manifestations in additional ED risk factors compared to the no DEBs profile, with the highest number of associations being observed in the female high-mixed profile. CONCLUSIONS: The present findings suggest that problematic manifestations of DEBs in young people may occur even in the absence of an ED diagnosis and that they are associated with additional risk factors for EDs, warranting increased efforts in targeted prevention, early identification and intervention in order to counteract symptom progression.
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BACKGROUND: Home treatment in child and adolescent psychiatry offers an alternative to conventional inpatient treatment by involving the patient's family, school, and peers more directly in therapy. Although several reviews have summarised existing home treatment programmes, evidence of their effectiveness remains limited and data synthesis is lacking. METHODS: We conducted a meta-analysis on the effectiveness of home treatment compared with inpatient treatment in child and adolescent psychiatry, based on a systematic search of four databases (PubMed, CINAHL, PsychINFO, Embase). Primary outcomes were psychosocial functioning and psychopathology. Additional outcomes included treatment satisfaction, duration, costs, and readmission rates. Group differences were expressed as standardised mean differences (SMD) in change scores. We used three-level random-effects meta-analysis and meta-regression and conducted both superiority and non-inferiority testing. RESULTS: We included 30 studies from 13 non-overlapping samples, providing data from 1795 individuals (mean age: 11.95 ± 2.33 years; 42.5% female). We found no significant differences between home and inpatient treatment for postline psychosocial functioning (SMD = 0.05 [- 0.18; 0.30], p = 0.68, I2 = 98.0%) and psychopathology (SMD = 0.10 [- 0.17; 0.37], p = 0.44, I2 = 98.3%). Similar results were observed from follow-up data and non-inferiority testing. Meta-regression showed better outcomes for patient groups with higher levels of psychopathology at baseline and favoured home treatment over inpatient treatment when only randomised controlled trials were considered. CONCLUSIONS: This meta-analysis found no evidence that home treatment is less effective than conventional inpatient treatment, highlighting its potential as an effective alternative in child and adolescent psychiatry. The generalisability of these findings is reduced by limitations in the existing literature, and further research is needed to better understand which patients benefit most from home treatment. TRIAL REGISTRATION: Registered at PROSPERO (CRD42020177558), July 5, 2020.
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Serviços de Assistência Domiciliar , Transtornos Mentais , Humanos , Transtornos Mentais/terapia , Adolescente , Criança , Resultado do Tratamento , Feminino , MasculinoRESUMO
AIM: Non-suicidal self-injury (NSSI) is a highly prevalent phenomenon during adolescence. Nonetheless, research on predictors of the clinical course of NSSI over time is still scarce. The present study aimed at investigating the impact of adverse childhood experiences (ACE) and hypothalamus-pituitary-adrenal (HPA) axis functioning on the longitudinal course of NSSI. METHODS: In a sample of n = 51 help-seeking adolescents engaging in NSSI, diurnal cortisol secretion (CAR, cortisol awakening response; DSL, diurnal slope), hair cortisol concentrations and ACE were assessed at baseline. Clinical outcome was defined by change in the frequency of NSSI in the past 6 months measured 12 and 24 months after the baseline assessments. Mixed-effects linear regression models were used to test for effects of ACE and HPA axis functioning on the course of NSSI. RESULTS: ACE and HPA axis functioning did not show main but interaction effects in the prediction of NSSI frequency over time: Adolescents with a low severity of ACE and either an increased CAR or a flattened DSL showed a steep decline of NSSI frequency in the first year followed by a subsequent increase of NSSI frequency in the second year. CONCLUSIONS: Our findings could be interpreted in the sense of high diurnal cortisol concentrations in the absence of ACE being favorable for clinical improvement on the short-term but bearing a risk of allostatic load and subsequent increase of NSSI frequency. In contrast, adolescents with severe ACE may benefit from elevated cortisol concentrations leading to slower but lasting decreases of NSSI frequency.
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Experiências Adversas da Infância , Cabelo , Hidrocortisona , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Comportamento Autodestrutivo , Humanos , Hidrocortisona/metabolismo , Hidrocortisona/análise , Adolescente , Masculino , Feminino , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Comportamento Autodestrutivo/metabolismo , Comportamento Autodestrutivo/fisiopatologia , Comportamento Autodestrutivo/psicologia , Cabelo/química , Cabelo/metabolismo , Estudos Longitudinais , Saliva/química , Saliva/metabolismo , Ritmo Circadiano/fisiologia , Estudos de Coortes , CriançaRESUMO
Study objective: African Americans (AAs) show early signs of vascular dysfunction paired with elevated blood pressure (BP) and total peripheral resistance (TPR), which is thought to underlie their increased rates of cardiovascular health complications relative to European Americans (EAs). AAs paradoxically have higher cardiac vagal tone, indexed by heart rate variability (HRV), which is cardio-protective. This paradox has been termed the Cardiovascular Conundrum. The physiological mechanism underlying this phenomenon is not well understood. We examined race differences in baroreflex function, which might be an important mechanism underlying the Cardiovascular Conundrum. Design: Participants completed a 5-minute baseline period where resting cardiac metrics were assessed. Setting: Laboratory. Participants: 130 college-aged individuals (54 women, 57 AAs). Main outcome measures: Baroreflex function was indexed as baroreflex sensitivity (BRS; the magnitude of changes in cardiovascular activity in accordance with BP changes) and effectiveness (BEI; the ratio of BP changes that elicit changes in cardiovascular activity) in the cardiac, vascular, and myocardial limbs. Results and conclusions: Results showed AAs to have higher HRV and cardiac BRS in comparison to EAs, suggesting the baroreflex is more sensitive to correcting the heart period for changes in BP among AAs compared to EAs. However, AAs showed lower vascular BEI relative to EAs, suggesting less effective control of TPR. In sum, lower BEI in the vascular branch might be an important mechanism underlying the Cardiovascular Conundrum (i.e., higher HRV and BP) and by extension, health disparities in cardiovascular diseases between AAs and EAs.
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INTRODUCTION: Stress affects many adolescents and is associated with physical and mental health symptoms that can have a negative impact on normative development. However, there are very few evidence-based, specific treatment approaches. The aim of the study was to investigate an eight-session group intervention using components of Acceptance and Commitment Therapy (ACT) enriched with elements of CBT (psychoeducation, problem solving) and art therapy, compared to a waitlist control (WLC) group, regarding its efficacy in reducing stress and associated symptoms. METHODS: We conducted a randomized controlled trial in eight cohorts. Eligible participants were 13-18 years old with elevated stress levels. Via block-randomization (n = 70), participants were allocated to receive ACT (n = 38) or WLC (n = 32) and subsequent ACT. We used a multimodal assessment (self-reports, interviews, ecological momentary assessment, physiological markers) before treatment (T1), after the training of the ACT group (T2) and after subsequent training in the WLC group (T3). Primary outcome was perceived stress at T2 assessed with the Perceived Stress Scale. The trial was preregistered at the German Clinical Trials Register (ID: DRKS00012778). RESULTS: Results showed significantly lower levels of perceived stress in the ACT group at T2, illustrating superiority of ACT compared to WLC with a medium to large effect size (d = 0.77). Furthermore, the training was effective in the reduction of symptoms of school burnout and physical symptoms associated with stress. CONCLUSION: Indicated prevention, especially when based on the principles of ACT and CBT, seems efficient in significantly decreasing stress in adolescents with increased stress.