Faculty Bibliography

We performed a scientometric analysis of the scientific literature on ADHD to evaluate key themes and trends over the past decades, informing future lines of research. We conducted a systematic search in Web of Science Core Collection up to 15 November, 2021 for scientific publications on ADHD. We retrieved 28,381 publications. We identified four major research trends: 1) ADHD treatment, risks factors and evidence synthesis; 2) neurophysiology, neuropsychology and neuroimaging; 3) genetics; 4) comorbidity. In chronological order, identified clusters of themes included: tricyclic antidepressants, ADHD diagnosis/treatment, bipolar disorder, EEG, polymorphisms, sleep, executive functions, pharmacology, genetics, environmental risk factors, emotional dysregulation, neuroimaging, non-pharmacological interventions, default mode network, Tourette, polygenic risk score, sluggish cognitive tempo, evidence-synthesis, toxins/chemicals, psychoneuroimmunology, Covid-19, and physical exercise. In conclusion, research on ADHD over the past decades has been driven mainly by a medical model. Whereas the neurobiological correlates of ADHD are undeniable and crucial, we look forward to further research on relevant psychosocial aspects related to ADHD, such as societal pressure, the concept of neurodiversity, and stigma.

OBJECTIVE:We meta-analyzed studies comparing perceptual timing abilities in the range of milliseconds to several seconds in individuals with ADHD and neurotypical participants, using the well-established time discrimination, time estimation, time production, and time reproduction paradigms. METHOD/METHODS:We searched Pubmed, OVID databases and WEB OF KNOWLEDGE through September 17, 2020. From 2,266 records, 55 studies were retained and meta-analyzed with random effects models. We conducted meta-regression analyses to explore moderating effects of task parameters and neuropsychological measures of working memory, attention, and inhibition on timing performance. RESULTS:Compared with those without ADHD, individuals with ADHD had significantly more severe difficulties in discriminating stimuli of very brief durations, especially in the sub-second range. They also had more variability in estimating the duration of stimuli lasting several seconds. Moreover, they showed deficits in time estimation and time production accuracy, indicative of an accelerated internal clock. Additional deficits in individual with ADHD were also found in the time reproduction paradigm, involving attentional (slower counting at short time intervals due to distraction) and motivational (faster counting at long time intervals due to increased delay aversion) functions. CONCLUSION/CONCLUSIONS:There is meta-analytic evidence of a broad range of timing deficits in individuals with ADHD. Results have implications for advancing our knowledge in the field (e.g., for refinement of recent timing models in ADHD) and clinical practice (e.g., testing timing functions to characterize the clinical phenotype of the patient and implementation of interventions to improve timing abilities).

OBJECTIVE:(1) investigate the associations of attention-deficit/hyperactivity disorder (ADHD) with systolic and diastolic blood pressure, resting heart rate, pulse pressure (PP), physical fitness, and BMI; (2) explore whether cardiovascular risk factors and ADHD share genetic and environmental influences; (3) assess if pharmacological treatment for ADHD influences these associations. METHODS:We identified 395,978 individuals born between 1973 and 1991 who had military conscription examinations at a mean age of 18.3 years (SD = 0.57) and their full-siblings within the same cohort (N = 208,060) by linking population-based registers in Sweden. RESULTS:Significantly increased risk of ADHD was observed in individuals with low systolic blood pressure (SBP) and PP, low physical fitness, and in those who had overweight or obesity after adjustments (adjusted Odds Ratio [OR] ranging from 1.10 to 1.45). Full siblings of individuals with low SBP, low physical fitness, and obesity were more likely to receive an ADHD diagnosis compared to full siblings without those risk factors (OR ranging from 1.17 to 1.31). Additionally, analyses showed robust associations between ADHD and low SBP, low physical fitness, and obesity, even in ADHD medication-naïve individuals. CONCLUSIONS:Individuals with several cardiovascular risk factors are more often diagnosed with ADHD, regardless of psychiatric comorbidity. These association are not explained by ADHD pharmacotherapy, rather, they are in part due to shared familial risk factors.

BACKGROUND:The mechanisms underlying placebo effects of psychotropic drugs remain poorly understood. We carried out the first systematic review of functional neuroimaging correlates of placebo response in adults with anxiety/depressive disorders. METHODS:We systematically searched a large set of databases up to February 2021 based on a pre-registered protocol (PROSPERO CRD42019156911). We extracted neuroimaging data related to clinical improvement following placebo or related to placebo mechanisms. We did not perform a meta-analysis due to the small number of included studies and significant heterogeneity in study design and outcome measures. RESULTS:We found 12 relevant studies for depressive disorders and four for anxiety disorders. Activity in the ventral striatum, rostral anterior cingulate cortex and other default mode network regions, orbitofrontal cortex, and dorsolateral prefrontal cortex correlated with placebo antidepressant responses. Activity in regions of the default mode network, including posterior cingulate cortex, was associated with placebo anxiolysis. There was also evidence for possible involvement of the endogenous opioid, dopamine and serotonin systems in placebo antidepressant and anxiolytic effects. CONCLUSIONS:Several brain regions and molecular systems may be involved in these placebo effects. Further adequately powered studies exploring causality and controlling for confounders are required.

We conducted the first systematic review and series of meta-analyses to assess the efficacy and tolerability of melatonin in children/adolescents or adults with sleep or mental health disorders, using the same set of criteria across disorders and ages. Based on a pre-registered protocol (PROPSPERO: CRD42021289827), we searched a broad range of electronic databases up to 02.02.2021 for randomized control trials (RCTs) of melatonin. We assessed study quality using the Risk of Bias tool, v2. We included a total of 34 RCTs (21 in children/adolescents: N = 984; 13 in adults: N = 1014). We found evidence that melatonin significantly improved sleep onset latency and total sleep time, but not sleep awaking, in children and adolescents with a variety of neurodevelopmental disorders, and sleep onset latency (measured by diary) as well as total sleep time (measured with polysomnography) in adults with delayed sleep phase disorder. No evidence of significant differences between melatonin and placebo was found in terms of tolerability. We discuss clinical and research implications of our findings.

Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS), is a potentially effective treatment strategy for a number of mental conditions. However, no quantitative evidence synthesis of randomized controlled trials (RCTs) of TMS or tDCS using the same criteria including several mental conditions is available. Based on 208 RCTs identified in a systematic review, we conducted a series of random effects meta-analyses to assess the efficacy of NIBS, compared to sham, for core symptoms and cognitive functioning within a broad range of mental conditions. Outcomes included changes in core symptom severity and cognitive functioning from pre- to post-treatment. We found significant positive effects for several outcomes without significant heterogeneity including TMS for symptoms of generalized anxiety disorder (SMD = -1.8 (95% CI: -2.6 to -1), and tDCS for symptoms of substance use disorder (-0.73, -1.00 to -0.46). There was also significant effects for TMS in obsessive-compulsive disorder (-0.66, -0.91 to -0.41) and unipolar depression symptoms (-0.60, -0.78 to -0.42) but with significant heterogeneity. However, subgroup analyses based on stimulation site and number of treatment sessions revealed evidence of positive effects, without significant heterogeneity, for specific TMS stimulation protocols. For neurocognitive outcomes, there was only significant evidence, without significant heterogeneity, for tDCS for improving attention (-0.3, -0.55 to -0.05) and working memory (-0.38, -0.74 to -0.03) in individuals with schizophrenia. We concluded that TMS and tDCS can benefit individuals with a variety of mental conditions, significantly improving clinical dimensions, including cognitive deficits in schizophrenia which are poorly responsive to pharmacotherapy.

This work aimed to review recent research on the characteristics of individuals who have both autism spectrum disorder and attention-deficit/hyperactivity disorder due to their high co-occurrence. Thirty-four studies were analyzed and main findings summarized in two content domains focusing on areas that could enhance our understanding of the cognitive and behavioral characteristics of individuals with autism spectrum disorder + attention-deficit/hyperactivity disorder (ASD+). Most of the results suggested that ASD+ is a co-occurring condition associated with more severe impairments in cognitive functioning, adaptive behavior, and increased likelihood to present more emotional/behavioral problems. These results will be helpful to provide improved care plans for individuals with both attention-deficit/hyperactivity disorder and autism spectrum disorder.

We mapped the evidence on the type and strength of associations between a broad range of mental and physical conditions in children and adolescents, by carrying out an umbrella review, i.e., a quantitative synthesis of previous systematic reviews and meta-analyses. We also assessed to which extent the links between mental and physical conditions vary across disorders or, by contrast, are transdiagnostic. Based on a pre-established protocol, we retained 45 systematic reviews/meta-analyses, encompassing around 12.5 million of participants. In analyses limited to the most rigorous estimates, we found evidence for the following associations: ADHD-asthma, ADHD-obesity, and depression-asthma. A transdiagnostic association was confirmed between asthma and anxiety/ASD/depression/bipolar disorder, between obesity and ADHD/ASD/depression, and between dermatitis and ASD/ADHD. We conclude that obesity and allergic conditions are likely to be associated with mental disorders in children and adolescents. Our results can help clinicians explore potential links between mental and physical conditions in children/adolescent and provide a road map for future studies aimed at shading light on the underlying factors.

Gambling in the modern era is pervasive owing to the variety of gambling opportunities available, including those that use technology (eg, online applications on smartphones). Although many people gamble recreationally without undue negative effects, a sizeable subset of individuals develop disordered gambling, which is associated with marked functional impairment including other mental health problems, relationship problems, bankruptcy, suicidality, and criminality. The National UK Research Network for Behavioural Addictions (NUK-BA) was established to promote understanding of, research into, and treatments for behavioural addictions including gambling disorder, which is the only formally recognised behavioural addiction. In this Health Policy paper, we outline the status of research and treatment for disordered gambling in the UK (including funding issues) and key research that should be conducted to establish the magnitude of the problem, vulnerability and resilience factors, the underlying neurobiology, long-term consequences, and treatment opportunities. In particular, we emphasise the need to: (1) conduct independent longitudinal research into the prevalence of disordered gambling (including gambling disorder and at-risk gambling), and gambling harms, including in vulnerable and minoritised groups; (2) select and refine the most suitable pragmatic measurement tools; (3) identify predictors (eg, vulnerability and resilience markers) of disordered gambling in people who gamble recreationally, including in vulnerable and minoritised groups; (4) conduct randomised controlled trials on psychological interventions and pharmacotherapy for gambling disorder; (5) improve understanding of the neurobiological basis of gambling disorder, including impulsivity and compulsivity, genetics, and biomarkers; and (6) develop clinical guidelines based on the best contemporary research evidence to guide effective clinical interventions. We also highlight the need to consider what can be learnt from approaches towards mitigating gambling-related harm in other countries.