INTRODUCTION:This study evaluated the effectiveness of a stepped-care approach - a staged model that escalates from lower- to higher-intensity treatments according to clinical response - for the treatment of adolescents and adults with ADHD, taking into account symptom severity and prior treatment response. METHODS:In a multicenter study, adolescents and adults with ADHD (16-45 years) participated in a two-step treatment program including randomized controlled trials (RCTs). In step 1, patients were (block-)randomized to 3 months of psychoeducation (PE), telephone-assisted self-help (TASH), or waiting control (WC). In step 2 based on step 1 response (full, partial, none), patients either received counseling or were randomized to counseling with/without neurofeedback (NF) or pharmacological treatment (with/without NF) for 6 months. The primary outcome was change in clinician-rated ADHD symptoms, analyzed using linear (mixed-)effects models for repeated measures to account for correlations within participants over time. RESULTS:Between January 2015, and September 2020, N = 299 (mean age = 28 years, 55.2% male) patients were randomized in step 1. The primary outcome showed no significant between-group differences (PE vs. TASH: d = -0.12, 95% CI: -3.18, 1.19, p = 0.64; PE vs. control: d = -0.26, 95% CI: -4.25, 0.05, p = 0.13; TASH vs. control: d = -0.14, 95% CI: -3.24, 1.04, p = 0.57). However, significant within-group effects emerged (PE: d = -0.60; TASH: d = -0.48; WC: d = -0.34; p < 0.001). Step 2 also showed no between-group differences but significant within-group effects (MPH: d = -0.59; MPH+NF: d = -0.76; counseling: d = -0.57/-1.35, p = 0.01/p < 0.001). Mixed models revealed symptom reduction in all step 1 responders and step 1 non-responders in step 2. CONCLUSIONS:The lack of step 1 RCT differences questions the specific effects of PE/TASH. Similar patterns emerged in step 2, but intensified treatment for step 1 non-responders improved outcomes in MPH groups. Step 1 response influenced later treatment success. Some stepped-care combinations did not further reduce symptoms, but no rebound effects occurred. The main limitations of this study are the two-step design complexity, limited information on certain (additional) psychosocial components, and the need to make assumptions about missing data. Nevertheless, findings support the feasibility and partial effectiveness of a stepped-care approach.

Attention-deficit/hyperactivity disorder (ADHD) has been associated with circadian rhythm disturbances, altered stress responses, and, in neural stem cells from ADHD patients, aberrant Wnt signaling. However, little is known about how these molecular pathways interact. This study aimed to investigate rhythmic expression of circadian, Wnt signaling, and stress-related genes in the context of ADHD. Human dermal fibroblasts were obtained via skin biopsy from participants diagnosed with ADHD (n = 13) and healthy controls (n = 13). Fibroblast cultures were synchronized using dexamethasone, with samples collected every 4 h over 28 h. Gene expression of Wnt signaling, stress-related, and circadian clock genes was quantified by qRT-PCR. Harmonic regression was applied to estimate rhythmicity (amplitude and phase), followed by mixed-effects modeling and likelihood ratio tests to assess between-group differences and gene–gene associations. Circular statistics (Rayleigh test, Watson two-sample test, circular correlations) were employed to test the uniformity and synchronicity of phase distributions. BMAL1, CRY1, PER2, PER3, and DKK1 exhibited significant rhythmicity within each group. DKK3 was rhythmic only in the ADHD group. Although between-group differences did not reach statistical significance, BMAL1 and CRY1 expression peaked later, while PER2 and PER3 expression peaked earlier in the ADHD group. Depending on data filtering, gene–gene rhythmicity associations included CRY1–SIRT1, PER3–FOXO1, and CLOCK–CTNNB1 in ADHD subjects, as well as CLOCK–DKK1 (ADHD) and BMAL1–DKK1 in controls. The phase and amplitude of core clock genes were correlated with donors’ ADHD symptoms and subjective sleep measures. Our data indicate ADHD is associated with subtly altered circadian gene expression and distinct integration of Wnt signaling and stress-related pathways, supporting the hypothesis of broader molecular dysregulation underlying ADHD.

Background: The objective of this study (registered under number 2020 006) was to assess the internal consistency of the revised Mental Health Professional Culture Inventory (MHPCI) scale, which comprises 15 items, among mental health service workers in Romania. Methods: To examine the psychometric properties of the MHPCI questionnaire within the Romanian population, we employed two main methods: The partial credit model (PCM) and Exploratory factor analysis (EFA). Results: A total of 94 individuals were interviewed, and among them, 71 provided complete responses to the questionnaire. All 15 items demonstrate a strong fit with the PCM, as indicated by mean-square (MSQ) outfit and MSQ infit values falling within the range of 0.5 to 1.5. But items 3 and 11 exhibit MSQ values greater than 1.5, suggesting that it may be challenging to predict individuals' responses to these items. The KMO index stands at 0.7, surpassing the recommended threshold of 0.6, signifying an acceptable level of suitability. Nevertheless, only 59.3% of the total variance is accounted for by the first four factors, and these factors do not align with the dimensions identified in the original article. Conclusion: The internal structure of the Romanian version of the MHPCI demonstrates satisfactory psychometric properties. These properties will need to be further validated through additional studies conducted in diverse socio-cultural contexts.

Circadian rhythms are biological oscillations, that perpetuate themselves even in the absence of "zeitgebers" (external time cues), with a period of approximately 24 hours. The master pacemaker is the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is entrained by environmental factors, particularly light, to the 24-hour light-dark cycle by the Earth's rotation. Peripheral circadian oscillators, located in multiple cell types and tissues, are controlled by signals arising from the SCN and from the environment, particularly food intake, hormonal signals and body-temperature fluctuations. Circadian rhythmicity is observable in almost every cell of living organisms including humans and, for example in cell cultures, these rhythms persist even without the SCN 1 2.

A number of psychiatric disorders are defined by persistent or recurrent sleep-wake disturbances alongside disruptions in circadian rhythm and altered clock gene expression. Circadian rhythms are present not only in the hypothalamic suprachiasmatic nucleus but also in peripheral tissues. In this respect, cultures of human derived dermal fibroblasts may serve as a promising new tool to investigate cellular and molecular mechanisms underlying the pathophysiology of mental illness. In this article, we discuss the advantages of fibroblast cultures to study psychiatric disease. More specifically, we provide an update on recent advances in modeling circadian rhythm disorders using human fibroblasts.

Introduction Hypoglycemia stimulates appetite and induces deterioration of cognitive function, e.g. attention. A key symptom of attention deficit hyperactivity disorder (ADHD) is – besides hyperactivity and/or impulsivity – inattention. Several studies reported about an association between glucose homeostasis and circadian rhythmicity. Thus, we investigate the influence of glucose on the expression of circadian genes in study participants with an ADHD diagnosis and healthy controls without a neuropsychiatric disorder in human dermal fibroblasts as in vitro model.

BACKGROUND:The COVID-19 pandemic has not only impacted intensive care units, but all healthcare services generally. This PsyGipo2C project specifically investigates how psychiatry and mental health professionals have been affected by the reorganizations and constraints imposed, which have reshaped their often already difficult working conditions. METHODS:Our research combined quantitative and qualitative methods, surveying and interviewing health professionals of all occupations working in psychiatric and mental health services. A questionnaire was completed by 1241 professionals from 10 European countries, and 13 group interviews were conducted across 5 countries. In addition to this, 31 individual interviews were conducted in Belgium and France. RESULTS:Among the questionnaire respondents, 70.2% felt that their workload had increased, particularly due to their tasks being diversified and due to increased complexity in the provision of care. 48.9% felt that finding a work-life balance had become more difficult, and 59.5% felt their health had been affected by the crisis. The impact of the health crisis nevertheless varied across professions: our data provides insight into how the health measures have had a differential impact on professional tasks and roles across the various categories of occupations, obliging professionals to make various adaptations. The distress incurred has been linked not only to these new constraints in their work, but also to the combination of these with other pressures in their personal lives, which has consequently compromised their well-being and their ability to cope with multiple demands. DISCUSSION:The COVID-19 health crisis has had varying impacts depending on the profession and access to remote work, sometimes leading to conflicts within the teams. The suffering expressed by the professionals was tied to their values and patterns of investment in work. Our research also highlights how these professionals made little use of the psychological supports offered, probably due to a reluctance to acknowledge that their mental health was affected.

Introduction Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder associated with changes in thyroid-stimulating hormone (TSH) and free triiodothyronine (T3). Thyroid hormones are associated with diurnal rhythms and reported to modulate circadian gene expression in a tissue-specific manor. Thus, we investigate the influence of T3 on circadian gene expression in human dermal fibroblasts from study participants diagnosed with ADHD and healthy controls without a neuropsychiatric disorder.

Introduction Attention deficit hyperactivity disorder (ADHD) is characterized by inattention and hyperactivity/impulsivity and is associated with alteration in circadian gene expression. Several studies reported an association between caffeine, sleep and attention. Thus, we investigate the influence of caffeine on the circadian gene expression in ADHD and healthy controls in a fibroblast model.

Attention deficit hyperactivity disorder (ADHD) is a very common disorder in children and adults. A connection with sleep disorders, and above all, disorders of the circadian rhythm are the subject of research and debate. The circadian system can be represented on different levels. There have been a variety of studies examining 24-h rhythms at the behavioral and endocrine level. At the molecular level, these rhythms are based on a series of feedback loops of core clock genes and proteins. In this paper, we compared the circadian rhythms at the behavioral, endocrine, and molecular levels between children with ADHD and age- and BMI-matched controls, complementing the previous data in adults. In a minimally invasive setting, sleep was assessed via a questionnaire, actigraphy was used to determine the motor activity and light exposure, saliva samples were taken to assess the 24-h profiles of cortisol and melatonin, and buccal mucosa swaps were taken to assess the expression of the clock genes BMAL1 and PER2. We found significant group differences in sleep onset and sleep duration, cortisol secretion profiles, and in the expression of both clock genes. Our data suggest that the analysis of circadian molecular rhythms may provide a new approach for diagnosing ADHD in children and adults.

Background: The internal clock is driven by circadian genes [e.g., Clock, Bmal1, Per1-3, Cry1-2], hormones [e.g., melatonin, cortisol], as well as zeitgeber [‘synchronisers’]. Chronic disturbances in the circadian rhythm in patients diagnosed with mood disorders have been recognised for more than 50 years. Objectives: The aim of this review is to summarise the current knowledge and literature regarding circadian rhythms in the context of mood disorders, focussing on the role of circadian genes, hormones, and neurotransmitters. Method: The review presents the current knowledge and literature regarding circadian rhythms in mood disorders using the Pubmed database. Articles with a focus on circadian rhythms and mood disorders [n=123], particularly from 1973 to 2020, were included. Results: The article suggests a molecular link between disruptions in the circadian rhythm and mood disorders. Circadian disturbances, caused by the dysregulation of circadian genes, hormones, and neurotransmitters, often result in a clinical picture resembling depression. Conclusion: Circadian rhythms are intrinsically linked to affective disorders, such as unipolar depression and bipolar disorder.

Background: The COVID-19 pandemic has required psychiatric and mental health professionals to change their practices to reduce the risk of transmission of SARS-CoV-2, in particular by favoring remote monitoring and assessment via digital technologies. Objective: As part of a research project that was cofunded by the French National Research Agency (ARN) and the Centre-Val de Loire Region, the aim of this systematic literature review was to investigate how such uses of digital technologies have been developing. Methods: This systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was carried out in the MEDLINE (ie, PubMed) and Cairn databases, as well as in a platform specializing in mental health, Ascodocpsy. The search yielded 558 results for the year 2020. After applying inclusion and exclusion criteria, first on titles and abstracts and then on full texts, 61 articles were included. Results: The analysis of the literature revealed a heterogeneous integration of digital technologies, not only depending on countries, contexts, and local regulations, but also depending on the modalities of care. Notwithstanding these variations, the use of videoconferencing has developed significantly, affecting working conditions and therapeutic relationships. For many psychiatric and mental health professionals, the pandemic has been an opportunity to build up their experience of remote care and, thus, better identify the possibilities and limits of these digital technologies. Conclusions: New uses of such technologies essentially consist of a transition from the classic consultation model toward teleconsultation and make less use of the specific potential of artificial intelligence. As professionals were not prepared for these uses, they were confronted with practical difficulties and ethical questions, such as the place of digital technology in care, confidentiality and protection of personal data, and equity in access to care. The COVID-19 health crisis questions how the organization of health care integrates the possibilities offered by digital technology, in particular to promote the autonomy and empowerment of mental health service users.

A The COVID-19 pandemic has had a considerable impact on the organization of psychiatric care. The present study examines how care professionals experienced this period and faced these new constraints weighing on their professional practices. Based on a qualitative research methodology, 13 group interviews with healthcare professionals working in psychiatric wards were conducted in five countries in western Europe. To complement this, 31 individual interviews were carried out in Belgium and France. Public health measures hindered certain therapeutic activities, jeopardized communication, and obliged healthcare professionals to modify and adapt their practices. Confronted with a transformation of their usual roles, healthcare professionals feared a deterioration in the quality of care. Impossible to continue in-person care practices, they resorted to online videoconferencing which went against their idea of care in which the encounter holds an essential place. The lockdown contradicted efforts to co-build care pathways toward readaptation, social reintegration, and recovery, thus reviving the perception of psychiatric hospitalization based on isolation.

Introduction Several studies reported about an association between vitamin D, circadian rhythmicity and physiological mechanisms, e.g. sleep. The aim of this study was to investigate the circadian gene expression in primary human dermal fibroblast cultures (HDF) from study participants with an ADHD diagnosis and healthy controls without a neuropsychiatric disorder after exposure to vitamin D.

Objective: The Covid-19 health crisis has disrupted the organization and functioning of European mental health and psychiatric services, impacting the working conditions -already difficult before the epidemic -of professionals working therein. The Psy-GIPO2C project investigated the impact of the pandemic on these professionals. The Psy-GIPOC2C project has been co-funded by the Agence Nationale de la Recherche francaise (ANR, French National Research Agency) and the Centre-Val de Loire region (France).Method: This research took the form of a collaborative mixed methods study. The data collected through qualitative and quantitative research were analyzed during a working session held by the research consortium, which resulted in the formulation of recommendations for action to optimize the occupational health of European mental health professionals.Results: This research made it possible to identify and explain the extent to which, and the ways in which, the reorganization of European mental health services has impacted the mental health of the professionals working therein, and, in particular, to highlight the fact that the unprecedented use of digital devices has generated stress, and even tension, within these services.Conclusions: It is important to promote well-being at work among European mental health professionals, by involving them in the development of ad hoc measures (in addition to the existing psychological support measures available) to enable them to recharge their batteries. It is also important to support current and future professionals in their appropriation of digital tools for professional use.

The increasing number of university students seeking diagnosis of attention-deficit/hyperactivity disorder (ADHD), and findings of an increased stimulant misuse among university students, has raised concerns regarding the credibility of the symptoms of those students. However, most of our current knowledge refers to university students in North America and less is known about this issue on European campuses. The present survey aimed to collect opinions on feigning ADHD and to estimate the prevalence of stimulant misuse among 1071 university students in the Netherlands. The majority of students expressed liberal attitudes towards feigning ADHD. Also, a substantial number of respondents considered feigning ADHD themselves or know someone who feigns ADHD. Furthermore, 68% of students assumed benefits of taking stimulants without prescription and 16% have indeed already taken stimulants without prescription. Feigning ADHD and misuse of prescription medication are prevalent issues among Dutch students. The results underline the need for a careful diagnostic evaluation of individuals for ADHD. Furthermore, efforts are required in order to prevent stimulant drug trafficking and misuse among university students.

Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value.

The circadian rhythm is essential for the interaction of all living organisms with their environments. Several processes, such as thermoregulation, metabolism, cognition and memory, are regulated by the internal clock. Disturbances in the circadian rhythm have been shown to lead to the development of neuropsychiatric disorders, including attention-deficit hyperactivity disorder (ADHD). Interestingly, the mechanism of the circadian rhythms has been conserved in many different species, and misalignment between circadian rhythms and the environment results in evolutionary regression and lifespan reduction. This review summarises the conserved mechanism of the internal clock and its major interspecies differences. In addition, it focuses on effects the circadian rhythm disturbances, especially in cases of ADHD, and describes the possibility of recombinant proteins generated by eukaryotic expression systems as therapeutic agents as well as CRISPR/Cas9 technology as a potential tool for research and therapy. The aim is to give an overview about the evolutionary conserved mechanism as well as the changes of the circadian clock. Furthermore, current knowledge about circadian rhythm disturbances and therapeutic approaches is discussed.