European Society of Cardiology quality indicators for the care and outcomes of adults with pulmonary arterial hypertension. Developed in collaboration with the Heart Failure Association of the European Society of Cardiology.

AIMS: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults with pulmonary arterial hypertension (PAH). METHODS AND RESULTS: We followed the European Society of Cardiology (ESC) methodology for the development of QIs. This included (i) the identification of key domains of care for the management of PAH, (ii) the proposal of candidate QIs following systematic review of the literature, and (iii) the selection of a set of QIs using a modified Delphi method. The process was undertaken in parallel with the writing of the 2022 ESC/European Respiratory Society (ERS) guidelines for the diagnosis and treatment of pulmonary hypertension and involved the Task Force chairs, experts in PAH, Heart Failure Association (HFA) members and patient representatives. We identified five domains of care for patients with PAH: structural framework, diagnosis and risk stratification, initial treatment, follow-up, and outcomes. In total, 23 main and one secondary QIs for PAH were selected. CONCLUSION: This document presents the ESC QIs for PAH, describes their development process and offers scientific rationale for their selection. The indicators may be used to quantify and improve adherence to guideline-recommended clinical practice and improve patient outcomes.

[International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder]. / Internationale Konsenserklärung zu Screening, Diagnostik und Behandlung von Jugendlichen und Heranwachsenden mit Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung und gleichzeitigen Störungen durch Substanzgebrauch.

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder Abstract. Background: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. Objective: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. Method: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. Results: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. Conclusion: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.

Excessive and pathological Internet use - Risk-behavior or psychopathology?

Pathological Internet use (but only with respect to gaming) is classified as mental disorder in the ICD-11. However, there is a large group of adolescents showing excessive Internet use, which may rather be considered adolescent risk-behavior. The aim was to test whether pathological and excessive Internet use should be considered as "psychopathology" or "risk-behavior". A representative, cross-sectional sample of 11.110 students from 10 European Union countries was analyzed. Structural equation models, including the factors "risk-behavior" and "psychopathology" and the variables excessive and pathological Internet use, were tested against each other. "Risk-behavior" was operationalized by several risk-behaviors (e.g. drug abuse, truancy, etc). "Psychopathology" included measures of several mental disorders (e.g. depression, hyperactivity, etc). Excessive Internet use was assessed as the duration and frequency of Internet use. Pathological Internet use was assessed with the Young Diagnostic Questionnaire (i.e., presence of addiction criteria). Excessive Internet use loaded on "risk-behavior" (λ = 0.484, p < .001) and on "psychopathology" (λ = 0.071, p < .007). Pathological Internet use loaded on "risk-behavior" (λ = 0.333, p < .001) and on "psychopathology" (λ = 0.852, p < .001). Chi-square tests determined that the loadings of excessive Internet use (χ2 (1) = 81.98, p < .001) were significantly stronger on "risk-behavior" than "psychopathology". Vice versa, pathological Internet use loaded significantly stronger on "psychopathology" (χ2 (1) = 107.10, p < .001). The results indicate that pathological Internet use should rather be considered as psychopathology. Excessive Internet use on the other hand, should be classified as adolescent risk-behavior.

PH CARE COVID survey: an international patient survey on the care for pulmonary hypertension patients during the early phase of the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, most of the health care systems suspended their non-urgent activities. This included the cancellation of consultations for patients with rare diseases, such as severe pulmonary hypertension (PH), resulting in potential medication shortage and loss of follow-up. Thus, the aim of the study was to evaluate PH patient health status evolution, access to health care and mental health experience during the early phase of the pandemic. METHODS: We conducted an online patient survey, available in 16 languages, between 22/05/2020 and 28/06/2020. The survey included questions corresponding to demographic, COVID-19 and PH related information. RESULTS: 1073 patients (or relatives, 27%) from 52 countries all over the world participated in the survey. Seventy-seven percent (77%) of responders reported a diagnosis of pulmonary arterial hypertension and 15% of chronic thromboembolic PH. The COVID-19 related events were few: only 1% of all responders reported a diagnosis of COVID-19. However, 8% of patients reported health deterioration possibly related to PH, and 4% hospitalization for PH. Besides, 11% of the patients reported difficulties to access their PH expert centre, and 3% interruption of treatment due to shortage of medication. Anxiety or depression was reported by 67% of the participants. CONCLUSION: Although COVID-19 incidence in PH patients was low, PH related problems occurred frequently as the pandemic progressed, including difficulties to have access to specialized care. The importance of primary health care was emphasized. Further studies are needed to evaluate the long-term consequences of COVID-related PH care disruption.

The Association of Nonsuicidal Self-Injury with Quality of Life and Mental Disorders in Clinical Adolescents-A Network Approach.

Although earlier research has highlighted that psychiatric disorders significantly impair patients' quality of life (QoL), few studies have examined the relationship between nonsuicidal self-injury (NSSI) and QoL. Our aim was to investigate whether QoL mediates the mental disorder-NSSI relationship, and to study the QoL ratings agreement of self and parents in a clinical population of adolescents. We involved 202 adolescents from Vadaskert Child Psychiatric Hospital and Outpatient Clinic, Budapest, aged 13-18 years. All participants completed the Deliberate Self-Harm Inventory, Inventar zur Erfassung der Lebensqualität bei Kindern und Jugendlichen, and the Mini International Neuropsychiatric Interview Kid. To map the interrelationship between the NSSI, mental disorders, and QoL dimensions, Mixed Graphical Models were estimated. Adolescents with a history of NSSI rated their QoL to be significantly lower than adolescents without NSSI. Self and parents' QoL ratings are closer in the NSSI sample than in the no-NSSI sample. Among all QoL dimensions, only family problems had a direct significant association with NSSI engagement. Our results highlight that, contrary to our hypothesis, the presence of mental disorders mediates the relationship between most QoL dimensions and the occurrence of NSSI. Our results draw attention to the potential causal effect of environmental factors (e.g., peer problems) on mental disorders that, in turn, result in NSSI. The present paper highlights the importance of network modelling in clinical research.

ERS statement on chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels <500 µm, leads to increased pulmonary vascular resistance and progressive right heart failure. The mechanism responsible for the transformation of red clots into fibrotic material remnants has not yet been elucidated. In patients with pulmonary hypertension, the diagnosis is suspected when a ventilation/perfusion lung scan shows mismatched perfusion defects, and confirmed by right heart catheterisation and vascular imaging. Today, in addition to lifelong anticoagulation, treatment modalities include surgery, angioplasty and medical treatment according to the localisation and characteristics of the lesions.This statement outlines a review of the literature and current practice concerning diagnosis and management of CTEPH. It covers the definitions, diagnosis, epidemiology, follow-up after acute pulmonary embolism, pathophysiology, treatment by pulmonary endarterectomy, balloon pulmonary angioplasty, drugs and their combination, rehabilitation and new lines of research in CTEPH.It represents the first collaboration of the European Respiratory Society, the International CTEPH Association and the European Reference Network-Lung in the pulmonary hypertension domain. The statement summarises current knowledge, but does not make formal recommendations for clinical practice.

Synthesis and characterization of new fluorescent boro-ß-carboline dyes.

The first representatives of the new fluorescent boro-ß-carboline family were synthesized by the insertion of the difluoroboranyl group into the oxaza or diaza core. The resulting compounds showed good photophysical properties with fine Stokes-shifts in the range of 38-85 nm with blue and green emission. The energetics of the excitation states and molecular orbitals of two members were investigated by quantum chemical computations suggesting effects for the improved properties of diazaborinino-carbolines over oxazaborolo-carbolines. These properties nominated this chemotype as a new fluorophore for the development of fluorescent probes. As an example, diazaborinino-carbolines were used for the specific labeling of anti-Her2 antibody trastuzumab. The fluorescent conjugate showed a high fluorophore-antibody ratio and was confirmed as a useful tool for labeling and confocal microscopy imaging of tumour cells in vitro together with the ex vivo two-photon microscopy imaging of tumour slices.

[When is self-injury nonsuicidal? Reviewing the relationship between suicial and nonsuicidal self-injury].

BACKGROUND: The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders has included nonsuicidal self-injury (NSSI) as a proposed independent diagnostic category, emphasizing the nonsuicidal nature of the phenomenon. Nevertheless, this terminology and concept have provoked a still ongoing scientific debate among researchers and clinicians. AIMS: By extending a systematic search with a broader focus on the prevalence and psychopathological correlates of NSSI, the aim of the present study is to explore the relationships between NSSI and suicidal behavior. METHODS: A systematic literature search was conducted in five databases (PubMed, OVID Medline, OVID PsycINFO, Scopus, Web of Science) with the search terms "NSSI" and "prevalence" and "mental disorder" or "psychiatric disorder". The results were completed by manual searches. Inclusion criteria were for each publication to be an empirical study in English language that does not focus on a specific population. RESULTS: A total of 25 papers examined the relationship between NSSI and suicidality explicitly. Among these papers, fifteen focused on children/adolescents, five on young adults, four on adults, and one on participants from heteroge - neous age groups. According to the results reviewed, altogether 50-70% of those who engaged in NSSI also reported suicidal thoughts or attempts. Those who did not report suicidal ideation differed from those who reported both NSSI and suicidal ideation in certain intra- and interpersonal traits (e.g., less depressive and borderline personality disor der symptoms, fewer negative life events, more social support) and in some specific characteristics (e.g., higher frequency and higher number methods) of NSSI. DISCUSSION: Based on the publications reviewed, significant suicidal risk is associated with NSSI in both adolescence and adulthood. This risk may be even higher in the presence of certain comorbid disorders and other psychosocial factors as well as in the presence of certain NSSI patterns such as repetitiveness or multiple NSSI methods.

Nonsuicidal Self-Injury: Its Associations With Pathological Internet Use and Psychopathology Among Adolescents.

BACKGROUND/HYPOTHESES: As risk factors for nonsuicidal self-injury (NSSI), most studies highlight the importance of internalising disorders, while only a few researches show the connection between externalising disorders and NSSI. Although some papers have introduced the idea that increasing prevalence rates of NSSI are connected to the broader use of the internet, associations between NSSI and pathological internet use (PIU) are understudied. According to our hypothesis, there is a connection between PIU and NSSI, but this is mediated by psychopathological factors from both internalising and externalising dimensions. METHODS: In line with the dimensional approach of psychiatric disorders, participants (N = 363) were recruited from both clinical (N = 202 psychiatric inpatient) and nonclinical (N = 161 adolescents from secondary schools) settings. Measurements: Demographic Questionnaire; Strengths and Difficulties Questionnaire (SDQ); Deliberate Self-Harm Inventory (DSHI); Young Diagnostic Questionnaire for Internet Addiction (YDQ), Mini International Neuropsychiatric Interview Kid (M.I.N.I. Kid). RESULTS: There was high NSSI frequency (39.9%-71% of them were girls) in our sample. NSSI was significantly more frequent among those who showed threshold symptoms on SDQ than in the subthreshold group [H(3) = 53.293, p <.001]. In the NSSI frequency, there was also a significant difference between 'normal' internet users and both 'maladaptive' and 'pathological' internet users [H(2) = 10.039, p <.05 p = .007]. According to the mediator models, the relationship between PIU and NSSI is not a direct association; it is mediated by all examined psychopathological factors (M.I.N.I. kid diagnoses) except for obsessive-compulsive disorder (OCD), alcohol abuse and dependence, and adjustment disorder. CONCLUSIONS: We found a high frequency of NSSI. According to our results, PIU in itself is not a risk factor for NSSI but might become a risk factor in the presence of comorbid psychiatric disorders. All of these findings draw the attention of clinicians to the importance of careful screening of comorbid disorders with PIU.

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder.

BACKGROUND: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. OBJECTIVE: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. METHOD: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. RESULTS: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. CONCLUSION: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.

Nonsuicidal Self-Injury and Suicide: The Role of Life Events in Clinical and Non-Clinical Populations of Adolescents.

BACKGROUND: Nonsuicidal self-injury (NSSI) is highly prevalent in clinical and non-clinical populations of adolescents. Several studies have supported both the distinction and the strong association between NSSI and suicidal behavior. Although there is a great deal of data on the role of life events in both suicidal behavior and NSSI, few studies have assessed the role of life events in the NSSI-suicidal behavior relationship. Our aims were to explore the relationship between NSSI and suicidal behavior, and the possible moderating role of stressful life events in a clinical and non-clinical adolescent population. METHOD: A clinical (n = 202) and a nonclinical (n = 161) population of adolescents, aged 13-18 years were assessed. The Mini International Neuropsychiatric Interview Kid, Deliberate Self-Harm Inventory and the Life Events List were used. Group differences related to suicidal behavior, NSSI, and life events were tested with Wilcoxon tests. Two- and three-way interactions were tested with negative binomial regression models including zero-inflation parameter. RESULTS: The prevalence of suicidal behavior (W = 7,306, p < .001), NSSI (W = 9,652, p < .001) and life events (W = 10,410 p < .001) were significantly higher in the clinical than in the non-clinical group. Between number of life events and NSSI, a moderate effect size (.38, 95%CI [.28,.46]) was found. The main effect of NSSI (χ2 (1) = 109.65, p < .001) and group membership (χ2 (1) = 39.13, p < .001) predicted suicidal behavior; the main effect of quantity of life events did not explain suicidal behavior. The interaction between NSSI and number of life events (χ2 (1) = 10.49, p < .01) was associated with suicidal behavior. Among interpersonal, non-interpersonal events and adverse childhood circumstances, only interpersonal events were associated with both suicidal behavior (χ2 (1) = 6.08, p < .05) and had a moderating effect (χ2 (1) = 8.59, p < .01) on the NSSI-suicidal behavior relationship. Patterns of the effects of life events on the NSSI-suicidal behavior relationship did not differ in the two groups. CONCLUSION: Our results confirm the importance of prevention and intervention of NSSI, considering its high prevalence and frequent co-occurrence with suicidal behavior in both clinical and non-clinical adolescent populations. Moreover, to support NSSI and suicide prevention, we would like to highlight the importance of stressful life events, especially those associated with interpersonal conflicts, require special attention.

Direct Self-Injurious Behavior (D-SIB) and Life Events among Vocational School and High School Students.

Although several studies have recently assessed direct self-injurious behavior (D-SIB) among adolescents, it is still understudied in adolescents attending vocational schools: an educational setting generally associated with lower socioeconomic status. After extending the "Saving and Empowering Young Lives in Europe" (SEYLE) project to a vocational school population, we examined their D-SIB and life event characteristics compared to the high school population. SEYLE's Hungarian randomly selected high school sample (N = 995) was completed with a randomly selected vocational school sample (N = 140) in Budapest, Hungary. Participants aged 14⁻17 years completed the SEYLE project's self-administered questionnaires. D-SIB lifetime prevalence was significantly higher (29.4%) in the vocational school group compared to the high school group (17.2%) (Χ²(1) = 12.231, p< 0.001). D-SIB was associated with suicidal ideation in the vocational school group. Different life events were more frequent in the high school than in the vocational school group, and associations between D-SIB and life events differed in the vocational school group compared to the high school group. In conclusion, vocational school students are a vulnerable population with a higher prevalence of D-SIB compared to high school students. Life events and their association with D-SIB also differ in vocational school students compared to high school students. Taking all these into account might contribute to prevention/intervention designed for this population.

Attention-deficit hyperactivity disorder and nonsuicidal self-injury in a clinical sample of adolescents: the role of comorbidities and gender.

BACKGROUND: The aim of the present study was to investigate the possible association between attention-deficit hyperactivity disorder (ADHD) and non-suicidal self-injury (NSSI) with special focus on the role of comorbidities and gender in a clinical sample of adolescents with both a dimensional and a categorical approach to psychopathology. METHODS: Using a structured interview, the Mini International Neuropsychiatric Interview Kid and a self-rated questionnaire, the Deliberate Self-Harm Inventory, the authors examined 202 inpatient adolescents (aged: 13-18 years) in the Vadaskert Child and Adolescent Psychiatric Hospital and Outpatient Clinic, Budapest, Hungary. Descriptive statistics, Mann-Whitney U test, chi-square test and mediator model were used. RESULTS: Fifty-two adolescents met full criteria for ADHD and a further 77 showed symptoms of ADHD at the subthreshold level. From the 52 adolescents diagnosed with ADHD, 35 (67.30%) had NSSI, of whom there were significantly more girls than boys, boys: n = 10 (28.60%), girls: n = 25 (71.40%) ((χ2(1) = 10.643 p < .001 ϕ = .452). Multiple mediation analyses resulted in a moderated mediation model in which the relationship between symptoms of ADHD and the prevalence of current NSSI was fully mediated by the symptoms of comorbid conditions in both sex. Significant mediators were the symptoms of affective and psychotic disorders and suicidality in both sexes and the symptoms of alcohol abuse/dependence disorders in girls. CONCLUSIONS: ADHD symptoms are associated with an increased risk of NSSI in adolescents, especially in the case of girls. Our findings suggest that clinicians should routinely screen for the symptoms of ADHD and comorbidity, with a special focus on the symptoms of affective disorders and alcohol abuse/dependence psychotic symptoms to prevent NSSI.

[Cross-Informant Agreement Between Parent-Reported and Adolescent Self-Reported Quality of Life in children with externalising symptoms].

BACKGROUND: It is well-known phenomena both in clinical practice and research, that there is a discrepancy between the parents' and children's report about children's Quality of Life (QoL). The purpose of our research was to examine the differences in self and caregiver's proxy report of child's QoL. We also compared mothers', fathers' and other caregivers' reports of children's QoL. METHODS: Patients with externalizing symptoms in their history, aged 13-18 years were selected from the Vadaskert Child and Adolescent Psychiatry Hospital and Outpatient Clinic. We used the Inventory of Quality of Life in Children and Adolescents (QL), parent and children version to measure the children's QoL. We used F-factor analysis (Principal Component Analysis and direct oblimin rotation) and t-tests for data analysis. RESULTS: Altogether 138 caregiver-child dyads filled the QL. The adolescents mean age was 14.47 years (SD=.40). Seventy-four mothers, 37 fathers and 27 other caregivers were included into our study. The caregivers' ratings were settled sorted into three factors, the adolescents' ratings were settled sorted into two factors. We found significant differences between mothers, fathers and other caregivers' ratings in the following domains of QoL: school, loneliness, peer relations, physical health, mental health and problem/illness. The caregivers evaluated adolescents' QoL more positively then the adolescents did (t=761, df=139, p<0,0001). CONCLUSIONS: The caregivers and their children's reported different domains of QoL as problematic. Therefore, it is important to gain information from several sources about the adolescent's QoL.

Self-injury and externalizing pathology: a systematic literature review.

BACKGROUND: During the last decade there is a growing scientific interest in nonsuicidal self-injury (NSSI). The aim of the current paper was to review systematically the literature with a special focus on the associations between self-injurious behaviours and externalizing psychopathology. An additional aim was to review terminology and measurements of self-injurious behaviour and the connection between self-injurious behaviours and suicide in the included publications. METHODS: A systematic literature search was conducted on 31st December 2016 in five databases (PubMed, OVID Medline, OVID PsycINFO, Scopus, Web of Science) with two categories of search terms (1. nonsuicidal self-injury, non-suicidal self-injury, NSSI, self-injurious behaviour, SIB, deliberate self-harm, DSH, self-injury; 2. externalizing disorder, attention deficit hyperactivity disorder, ADHD, conduct disorder, CD, oppositional defiant disorder, OD, ODD). RESULTS: Finally 35 papers were included. Eleven different terms were found for describing self-injurious behaviours and 20 methods for measuring it. NSSI has the clearest definition. All the examined externalizing psychopathologies had strong associations with self-injurious behaviours according to: higher prevalence rates in externalizing groups than in control groups, higher externalizing scores on the externalizing scales of questionnaires, higher symptom severity in self-injurious groups. Eight studies investigated the relationship between suicide and self-injurious behaviours and found high overlap between the two phenomena and similar risk factors. CONCLUSIONS: Based on the current findings the association between externalizing psychopathology and self-injurious behaviours has been proven by the scientific literature. Similarly to other reviews on self-injurious behaviours the confusion in terminology and methodology was noticed. NSSI is suggested for use as a distinct term. Further studies should investigate the role of comorbid conditions in NSSI, especially when internalizing and externalizing pathologies are both presented.

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).

Potential salivary biomarkers and their genetic effects in a pilot study of adolescent boys with externalizing problems.

AIMS: Beside the well-known stress response marker cortisol, salivary alpha-amylase is receiving increasing attention. Numerous studies have investigated the potential biomarker properties of cortisol mirroring abnormal hypothalamic-pituitary-adrenal axis activity in connection to both internalizing and externalizing behavior problems. The other major physiological system involved in stress reactivity, the sympathetic nervous system activity can be also measured by the surrogate marker of salivary alpha-amylase. Most of the studies applied a stressful situation to obtain inter-individual differences in stress-reactivity, although differences in the baseline level of cortisol have been also shown in relation to externalizing problems. To test the relevance of another (easier) biomarker, we selected to study baseline circadian salivary cortisol and alpha-amylase levels among adolescent boys with externalizing problems. METHODS: Saliva samples were collected at 3 time-points (morning, noon, evening) during 3 consecutive days from 37 inpatient boys (mean age 12.4±1.0). Cortisol and alpha-amylase levels were measured by enzyme-linked immunosorbent and kinetic enzyme assays, respectively. Genetic variants in the hypothalamic-pituitary-adrenal axis and the norepinephrine transporter or catecholamine metabolizing enzymes were tested for potential moderating effects at these salivary biomarkers. RESULTS: Saliva cortisol showed the classical diurnal fluctuation in boys with externalizing problems (possibly from a lower morning level), but it was not modified by the presence of either conduct, oppositional defiant or attention-deficit/hyperactivity disorder. The diurnal fluctuation of the salivary alpha-amylase levels was also typical, but the presence of conduct disorder was associated with significantly lower alpha-amylase activity (p=0.024) among boys with externalizing problems. The catechol-O-methyltransferase Val158Met (rs4680) polymorphism had an additional effect on salivary alpha-amylase: boys with homozygote genotypes had lower alpha-amylase activity at all 3 time-points compared to Val/Met heterozygotes (p=0.045). CONCLUSIONS: Our preliminary data suggest that salivary alpha-amylase might be used to further characterize subgroups within externalizing problems, however, this biomarker might be modified by certain genetic polymorphisms.