Bright light therapy versus physical exercise to prevent co-occurring depression in adolescents and young adults with attention-deficit/hyperactivity disorder: a multicentre, three-arm, randomised controlled, pilot phase-IIa trial.

Depression is common in attention-deficit/hyperactivity disorder (ADHD), but preventive behavioural interventions are lacking. This randomised controlled, pilot phase-IIa trial aimed to study a physical exercise intervention (EI) and bright light therapy (BLT)-both implemented and monitored in an individual, naturalistic setting via a mobile health (m-health) system-for feasibility of trial design and interventions, and to estimate their effects on depressive symptoms in young people with ADHD. Two hundred seven participants aged 14-45 years were randomised to 10-week add-on intervention of either BLT (10,000 lx; daily 30-min sessions) (n = 70), EI (aerobic and muscle-strengthening activities 3 days/ week) (n = 69), or treatment-as-usual (TAU) (n = 68), of whom 165 (80%) were retained (BLT: n = 54; EI: n = 52; TAU: n = 59). Intervention adherence (i.e. ≥ 80% completed sessions) was very low for both BLT (n = 13, 22%) and EI (n = 4, 7%). Usability of the m-health system to conduct interventions was limited as indicated by objective and subjective data. Safety was high and comparable between groups. Changes in depressive symptoms (assessed via observer-blind ratings, Inventory of Depressive Symptomatology) between baseline and end of intervention were small (BLT: -0.124 [95% CI: -2.219, 1.971], EI: -2.646 [95% CI: -4.777, -0.515], TAU: -1.428 [95% CI: -3.381, 0.526]) with no group differences [F(2,153) = 1.45, p = 0.2384]. These findings suggest that the m-health approach did not achieve feasibility of EI and BLT in young people with ADHD. Prior to designing efficacy studies, strategies how to achieve high intervention adherence should be specifically investigated in this patient group. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03371810, 13 December 2017.

Discontinuation of psychotropic medication: a synthesis of evidence across medication classes.

Pharmacotherapy is an effective treatment modality across psychiatric disorders. Nevertheless, many patients discontinue their medication at some point. Evidence-based guidance for patients, clinicians, and policymakers on rational discontinuation strategies is vital to enable the best, personalized treatment for any given patient. Nonetheless, there is a scarcity of guidelines on discontinuation strategies. In this perspective, we therefore summarize and critically appraise the evidence on discontinuation of six major psychotropic medication classes: antidepressants, antipsychotics, benzodiazepines, mood stabilizers, opioids, and stimulants. For each medication class, a wide range of topics pertaining to each of the following questions are discussed: (1) Who can discontinue (e.g., what are risk factors for relapse?); (2) When to discontinue (e.g., after 1 year or several years of antidepressant use?); and (3) How to discontinue (e.g., what's the efficacy of dose reduction compared to full cessation and interventions to mitigate relapse risk?). We thus highlight how comparing the evidence across medication classes can identify knowledge gaps, which may pave the way for more integrated research on discontinuation.

CLINICAL VIEW ON SUBSTANCE-INDUCED PSYCHOTIC SYMPTOMS IN A MEDICALLY SUPERVISED INJECTING ROOM: A DECADE OF EXPERIENCE.

Medically supervised injecting rooms (MSIRs) are extremely important facilities for people who inject drugs (PWID) as MSIRs provide a safe place for the consumption of street-sourced drugs, impacting overdose rates and viral transmitted infections.

The association between type 2 diabetes and attention- deficit/hyperactivity disorder: A systematic review, meta-analysis, and population-based sibling study.

We conducted a systematic review and a meta-analysis to quantitatively summarize evidence on the association between attention-deficit/hyperactivity disorder (ADHD) and type 2 diabetes (T2D). Moreover, a register-based sibling study was conducted to simultaneously control for confounding factors. A systematic search identified four eligible observational studies (N = 5738,287). The meta-analysis showed that individuals with ADHD have a more than doubled risk of T2D when considering adjusted estimates (OR=2.29 [1.48-3.55], d=0.46). Results from the register-based Swedish data showed a significant association between ADHD and T2D (HR=2.35 [2.14-2.58]), with substance use disorder, depression, and anxiety being the main drivers of the association, and cardiovascular and familiar risk playing a smaller role. While results from the meta-analysis provide evidence for an increased risk of T2D in individuals with ADHD, the register-based analyses show that the association between ADHD and T2D is largely explained by psychiatric comorbidities. Pending further evidence of causal association, our findings suggest that early identification and treatment of ADHD comorbidities might greatly reduce the risk of developing T2D in individuals with ADHD.

Confirmatory factor analysis of 20-item toronto alexithymia scale in spanish patients with substance use disorder.

Alexithymia is highly prevalent in patients with substance use disorders (SUDs) and has been implied in SUD pathogenesis and treatment outcomes. However, the psychometric properties of the most-used instrument for evaluating alexithymia (the 20-item Toronto Alexithymia Scale, TAS-20) have been scarcely studied in relation to SUD patients.

The dynamical association between physical activity and affect in the daily life of individuals with ADHD.

Exercise interventions in mental disorders have evidenced a mood-enhancing effect. However, the association between physical activity and affect in everyday life has not been investigated in adult individuals with ADHD, despite being important features of this disorder. As physical activity and affect are dynamic processes in nature, assessing those in everyday life with e-diaries and wearables, has become the gold standard. Thus, we used an mHealth approach to prospectively assess physical activity and affect processes in individuals with ADHD and controls aged 14-45 years. Participants wore accelerometers across a four-day period and reported their affect via e-diaries twelve times daily. We used multilevel models to identify the within-subject effects of physical activity on positive and negative affect. We split our sample into three groups: 1. individuals with ADHD who were predominantly inattentive (n = 48), 2. individuals with ADHD having a combined presentation (i.e., being inattentive and hyperactive; n = 95), and 3. controls (n = 42). Our analyses revealed a significant cross-level interaction (F(2, 135.072)=5.733, p = 0.004) of physical activity and group on positive affect. In details, all groups showed a positive association between physical activity and positive affect. Individuals with a combined presentation significantly showed the steepest slope of physical activity on positive affect (slope_inattentive=0.005, p<0.001; slope_combined=0.009, p<0.001; slope_controls=0.004, p = 0.008). Our analyses on negative affect revealed a negative association only in the individuals with a combined presentation (slope=-0.003; p = 0.001). Whether this specifically pronounced association in individuals being more hyperactive might be a mechanism reinforcing hyperactivity needs to be empirically clarified in future studies.

Neurodevelopmental disorders among Spanish school-age children: prevalence and sociodemographic correlates.

BACKGROUND: Prevalence estimates of neurodevelopmental disorders (ND) are essential for treatment planning. However, epidemiological research has yielded highly variable rates across countries, including Spain. This study examined the prevalence and sociodemographic correlates of ND in a school sample of Spanish children and adolescents. METHODS: The Child Behaviour Checklist/Teacher's Report Form/Youth Self-Report and the Conners' Rating Scales were administered for screening purposes. Additionally, teachers provided information on reading and writing difficulties. Subjects who screened positive were interviewed for diagnostic confirmation according to the Diagnostic and Statistical Manual of Mental Disorders criteria. The final population comprised 6834 students aged 5-17. Multivariate analyses were performed to determine the influence of gender, age, educational stage, school type, socioeconomic status (SES), and ethnicity on the prevalence estimates. RESULTS: A total of 1249 (18.3%) subjects met criteria for at least one ND, although only 423 had already received a diagnosis. Specifically, the following prevalence rates were found: intellectual disabilities (ID), 0.63%; communication disorders, 1.05%; autism spectrum disorder (ASD), 0.70%; attention-deficit/hyperactivity disorder (ADHD), 9.92%; specific learning disorder (SLD), 10.0%; and motor disorders, 0.76%. Students of foreign origin and from low SES evidenced higher odds of having ID. Boys were more likely to display ASD or a motor disorder. Age, SES, and ethnicity were significant predictors for SLD, while communication disorders and ADHD were also associated with gender. CONCLUSIONS: The prevalence of ND among Spanish students is consistent with international studies. However, a substantial proportion had never been previously diagnosed, which emphasise the need for early detection and intervention programmes.

Improvement of functional neurological disorder after administration of esketamine nasal spray: a case report.

Functional neurological disorder (FND) is a complex neuropsychiatric condition characterized by the presence of neurological symptoms and signs (either motor or sensory) that cannot be explained by any known medical or mental disease. It is frequently presented with psychiatric comorbidities, such as major depression. Its prognosis is poor, with low improvement or recovery rates at 1 year after their onset, and no particular treatment has demonstrated significant efficacy in this regard. Here, we describe the management of a patient affected by treatment-resistant depression (TRD) and FND characterized by mixed paralysis (sensory and motor) in the left arm, and who was successfully treated with esketamine nasal spray, achieving remission in both disorders. The US Food and Drug Administration and the European Medicines Agency recently approved esketamine, the S-enantiomer of ketamine, for treatment of TRD. It is a fast-acting drug that provides a rapid-onset improvement of depressive symptoms. We have presented the first case, to our knowledge, of functional neurological symptoms being successfully treated with esketamine in a patient with comorbid TRD. While the novelty of this data implies a clear need for further research, it is suggested that esketamine might be a useful tool for the treatment of FND, acting through different theorized mechanisms that are in tune with recent advances in knowledge of the etiopathology of FND.

Insomnia Disorder in Adult Attention-Deficit/Hyperactivity Disorder Patients: Clinical, Comorbidity, and Treatment Correlates.

Introduction: Several investigations have been performed on insomnia symptoms in adult attention-deficit/hyperactivity disorder (ADHD). However, the relationship between insomnia disorder and adult ADHD has been neglected in research. The main objective of the current study is to analyze the differences between adult ADHD patients with and without insomnia disorder, in terms of ADHD clinical severity, medical and psychiatric comorbidity, psychopharmacological treatment, and quality of life. Material and Methods: Two hundred and fifty-two adult patients with ADHD (mean age 37.60 ± 13.22 years; ADHD presentations-combined: 56.7%, inattentive: 39.7%, hyperactive/impulsive: 3.6%) were evaluated with an exhaustive clinical and psychological evaluation protocol including semistructured interviews (for comorbidities and ADHD assessment) and symptom rating scales for ADHD. The diagnosis of ADHD and insomnia disorder was made according to DSM-5 criteria. Furthermore, the Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Epworth Sleepiness Scale were administered. Results: Insomnia disorder was found in 44.4% of adult ADHD patients and was more common in combined presentation (64.3%) and in patients with more ADHD severity. Comorbidities (both medical and psychiatric), especially mood disorders (42%), anxiety disorder (26.8%), personality disorder (39.3%), and any substance use disorder (11.6%), were associated with a higher insomnia disorder prevalence. ADHD stimulant treatment was related to lower insomnia disorder compared to patients without medication, as well as ADHD stable treatment. Additionally, worse health-related quality of life was associated with insomnia disorder. Conclusion: Insomnia disorder is highly prevalent in adult ADHD and is related to higher ADHD severity and more psychiatric and medical comorbidities. Some stimulants and stable pharmacological ADHD treatment are associated with better outcomes of insomnia disorder.

Alexithymia in Patients With Substance Use Disorders and Its Relationship With Psychiatric Comorbidities and Health-Related Quality of Life.

Background: Alexithymia frequently correlates with several psychiatric disorders, including substance use disorder (SUD). However, most studies reporting the associations between alexithymia and psychiatric disorders have been performed in populations without SUD. This research, therefore, evaluates alexithymia in Spanish patients with SUD and the relationship among alexithymia, psychiatric comorbidities, psychological symptoms/traits, SUD variables, and health-related quality of life (HRQoL). Methodology: A cross-sectional study was conducted with 126 Spanish outpatients with SUD (75.4% males; mean age 43.72 ± 14.61 years), correlating their alexithymia levels (using the Toronto Alexithymia Scale 20 [TAS-20]) to their psychiatric comorbidities, psychological symptoms/traits, SUD variables, and HRQoL. Results: Alexithymia was significantly higher in patients who had cannabis use disorder. Higher alexithymia scores were also related to higher levels of depression, anxiety, impulsivity, and lower HRQoL. After multivariate analysis, trait anxiety, impulsivity, and the physical component summary of the HRQoL were found to be independently related to alexithymia. Conclusions: SUD patients with higher alexithymia levels have more frequently psychiatric comorbidities, present specific psychological features, and have worse HRQoL. Hence, it is important to evaluate these factors and offer more accurate psychotherapeutic approaches for this patient population.

Three-year prevalence of self-harm behaviors among the reasons for emergency visits of children and adolescents.

Self-harm in the paediatric population is an emerging problem that has been associated with disability and an increased risk of suicide. The objective of the study is to analyse the prevalence of self-harming behaviour as a reason for paediatric emergency consultations.

Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder.

Previous studies have shown that the gene encoding the adhesion G protein-coupled receptor L3 (ADGRL3; formerly latrophilin 3, LPHN3) is associated with Attention-Deficit/Hyperactivity Disorder (ADHD). Conversely, no studies have investigated the anatomical or functional brain substrates of ADGRL3 risk variants. We examined here whether individuals with different ADGRL3 haplotypes, including both patients with ADHD and healthy controls, showed differences in brain anatomy and function. We recruited and genotyped adult patients with combined type ADHD and healthy controls to achieve a sample balanced for age, sex, premorbid IQ, and three ADGRL3 haplotype groups (risk, protective, and others). The final sample (n = 128) underwent structural and functional brain imaging (voxel-based morphometry and n-back working memory fMRI). We analyzed the brain structural and functional effects of ADHD, haplotypes, and their interaction, covarying for age, sex, and medication. Individuals (patients or controls) with the protective haplotype showed strong, widespread hypo-activation in the frontal cortex extending to inferior temporal and fusiform gyri. Individuals (patients or controls) with the risk haplotype also showed hypo-activation, more focused in the right temporal cortex. Patients showed parietal hyper-activation. Disorder-haplotype interactions, as well as structural findings, were not statistically significant. To sum up, both protective and risk ADGRL3 haplotypes are associated with substantial brain hypo-activation during working memory tasks, stressing this gene's relevance in cognitive brain function. Conversely, we did not find brain effects of the interactions between adult ADHD and ADGRL3 haplotypes.

Strengths and Difficulties Questionnaire: Psychometric Properties and Normative Data for Spanish 5- to 17-Year-Olds.

The Strengths and Difficulties Questionnaire (SDQ) has been extensively used to measure common forms of psychopathology among children and adolescents. However, its psychometric properties vary across countries and several controversial issues warrant further investigation. This study aimed to evaluate whether the Spanish version of the SDQ is a reliable and valid tool for assessing emotional and behavioral problems in a sample of 6,775 students aged 5 to 17 years, as rated by parents, teachers, and youth. We examined the internal consistency of the questionnaire, its factor structure, and measurement invariance across child's gender and age. Criterion validity was tested against the Child Behavior Checklist (CBCL), Teacher's Report Form (TRF), and Youth Self-Report (YSR), and we measured the ability of the SDQ to identify children with specific psychiatric disorders. Finally, we provide, for the first time, Spanish normative data for children aged 5 to 10 and 11 to 17 years, according to gender and each informant. Our results revealed acceptable reliability estimates for all SDQ subscales. Confirmatory factor analysis supported the original five-factor model and full measurement invariance was found. Furthermore, SDQ scores showed a moderate to strong correlation with those on the equivalent CBCL/TRF/YSR scales, and were effective in discriminating individuals with and without clinical diagnoses.

Practical recommendations for the management of treatment-resistant depression with esketamine nasal spray therapy: Basic science, evidence-based knowledge and expert guidance.

OBJECTIVES: Despite the available therapies for treatment-resistant depression (TRD), there are a limited number that are evidence-based and effective in this hard-to-treat population. Esketamine nasal spray, an intranasal N-methyl-d-aspartate (NMDA) glutamate receptor antagonist, is a novel, fast-acting option in this patient population. This manuscript provides expert guidance on the practicalities of using esketamine nasal spray. METHODS: A group of six European experts in major depressive disorder (MDD) and TRD, with clinical experience of treating patients with esketamine nasal spray, first generated practical recommendations, before editing and voting on these to develop consensus statements during an online meeting. RESULTS: The final consensus statements encompass not only pre-treatment considerations for patients with TRD, but also specific guidelines for clinicians to consider during and post-administration of esketamine nasal spray. CONCLUSIONS: Esketamine nasal spray is a novel, fast-acting agent that provides an additional treatment option for patients with TRD who have previously failed several therapies. The guidance here is based on the authors' experience and the available literature; however, further real-world use of esketamine nasal spray will add to existing knowledge. The recommendations offer practical guidance to clinicians who are unfamiliar with esketamine nasal spray.

Quinolone-induced psychosis: an updated review.

Quinolones are an antibiotic group widely used due to their antimicrobial action and security profile, however, it has been described neuropsychiatric adverse effects, being induced-psychotic episodes one of the most clinically relevant. Nevertheless, this secondary effect has been scarcely studied. A literature search using PRISMA guidelines was performed between 01/01/1962 and 01/31/2019 on PubMed and ScienceDirect, including manuscripts which described substance-induced psychotic disorder according to DSM-5 and in which the symptomatology was not attributable to an acute confusional state (delirium) or to other induced psychiatric disorders. 459 articles were found, but only 27 manuscripts fulfilled inclusion criteria (n=27 patients, median age of 36.15±16.96 years). Ciprofloxacin, levofloxacin and ofloxacin were the main antibiotics implicated. Quinolone- induced psychosis is a clinical relevant issue due to the high prescription of these antibiotics and the severity of this clinical syndrome. In general, this syndrome can remit in a few days with the withdrawal of the quinolone and performing symptomatic support if it is necessary. Finally, it is important to perform further research on this issue. Keywords: Quinolones, Psychosis, Ciprofloxacin, Levofloxacinn, Psychotic Induced.

Attention Deficit Hyperactivity Disorder Increases Nicotine Addiction Severity in Adults Seeking Treatment for Substance Use Disorders: The Role of Personality Disorders.

AIMS: To examine the role of attention deficit/hyperactivity disorder (ADHD) and impulsive personality disorders in nicotine addiction severity among treatment-seeking substance use disorder (SUD) patients. METHODS: In a cross-sectional study, we examined data from the second International ADHD in Substance Use Disorders Prevalence Study (IASP-2) on 402 adults in SUD treatment from Puerto Rico, Hungary, and Australia using diagnostic interviews for ADHD, antisocial (ASP) and borderline (BPD) personality disorders, and the self-report Fagerström Test of Nicotine Dependence (FTND). We compared SUD patients with and without ADHD on nicotine addiction severity. We tested direct and indirect pathways from ADHD to nicotine addiction and mediation through ASP and BPD. RESULTS: Overall, 81.4% of SUD patients reported current cigarette smoking. SUD patients with ADHD had higher FTND scores and smoked more cigarettes than those without ADHD, with an earlier onset and more years of smoking. ASP mediated the effect of ADHD on all aspects of nicotine addiction severity, whereas BPD did so only on some aspects of nicotine addiction severity. CONCLUSIONS: SUD patients with comorbid ADHD show more severe nicotine addiction than those without, which is largely explained by comorbid impulsive personality disorders. In SUD patients, it is important to screen for adult ADHD and other psychiatric disorders, especially those with impulse control deficits such as ASP and BPD.

The role of environmental influences in the complex relationship between borderline personality disorder and attention-deficit/hyperactivity disorder: review of recent findings.

BACKGROUND: In recent years, the existence of possible developmental pathways from childhood Attention-Deficit/Hyperactivity Disorder (ADHD) to adult Borderline Personality Disorder (BPD) has been suggested. The existence of common genetic factors has been described but there is little evidence on the role of environmental factors in the possible transition from one disorder to another throughout life. The main goal of this work is to review the literature about the existing evidence on childhood traumas as factors that mediate the risk of developing BPD in children with ADHD. METHODS: A literature search was conducted using PubMed, Science Direct and PsychInfo databases. Criteria included studies of BPD and ADHD relationships and childhood traumas as environmental influences from epidemiological or clinical samples. RESULTS: The review only identified 4 studies that matched the search criteria. All studies retrospectively analyzed childhood traumas, and adult patients with BPD, with or without comorbid ADHD, were the most frequently mentioned. The analyzed evidence reinforces the relationship between the number of childhood traumas and higher clinical severity. Three of these analyzed studies describe an increased the risk of children with ADHD who report emotional and sexual traumatic experiences to develop BPD in adulthood. CONCLUSIONS: The experience of traumatic childhood events, especially those of an emotional type, may have a mediating effect of an increased risk of developing adult BPD in childhood ADHD patients. However, to consider them as risk factors, more studies, and especially longitudinal studies, are necessary to clarify the probable transactional process between the two disorders. Evidence from these studies may be helpful to develop early intervention programs to reduce the functional impairment associated with the two disorders.

Author Correction: GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability.

Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability," as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work.

ADGRL3 (LPHN3) variants predict substance use disorder.

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large sample of individuals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUD.

GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia.

Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.