Abstract Studies on animals and humans have demonstrated the importance of dopamine in modulating decision-making processes. In this work, we have tested dopaminergic modulation of economic ...decision-making and its neural correlates by administering either placebo or metoclopramide, a dopamine D2-receptor antagonist, to healthy subjects, during a functional MRI study. The decision-making task combined probability and time delay with a fixed monetary reward. For individual behavioral characterization, we used the Probability Time Trade-off (PTT) economic model, which integrates the traditional trade-offs of reward magnitude-time and reward magnitude-probability into a single measurement, thereby quantifying the subjective value of a delayed and probabilistic outcome. A regression analysis between BOLD signal and the PTT model index permitted to identify the neural substrate encoding the subjective reward-value. Behaviorally, medication reduced the rate of temporal discounting over probability, reflected in medicated subjects being more prone to postpone the reward in order to increase the outcome probability. In addition, medicated subjects showed less activity during the task in the postcentral gyrus as well as frontomedian areas, whereas there were no differences in the ventromedial orbitofrontal cortex (VMOFC) between groups when coding the subjective value. The present study demonstrates by means of behavior and imaging that dopamine modulation alters the probability-time trade-off in human economic decision-making.
Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poorly understood. According to the National Institute of Health RDoc programme, the pathophysiological ...basis of neuropsychiatric symptoms may be better understood in terms of dysfunction of underlying domains of neurocognition in a trans-diagnostic fashion. Abnormal cortico-striatal reward processing has been proposed as a key domain contributing to the pathogenesis of psychotic symptoms in schizophrenia. This theory has received empirical support in the study of schizophrenia spectrum disorders and preclinical models of psychosis, but has not been tested in the psychosis associated with PD. We, therefore, investigated brain responses associated with reward expectation and prediction error signaling during reinforcement learning in PD-associated psychosis. An instrumental learning task with monetary gains and losses was conducted during an fMRI study in PD patients with (
= 12), or without (
= 17), a history of psychotic symptoms, along with a sample of healthy controls (
= 24). We conducted region of interest analyses in the ventral striatum (VS), ventromedial prefrontal and posterior cingulate cortices, and whole-brain analyses. There was reduced activation in PD patients with a history of psychosis, compared to those without, in the posterior cingulate cortex and the VS during reward anticipation (
< 0.05 small volume corrected). The results suggest that cortical and striatal abnormalities in reward processing, a putative pathophysiological mechanism of psychosis in schizophrenia, may also contribute to the pathogenesis of psychotic symptoms in PD. The finding of posterior cingulate dysfunction is in keeping with prior results highlighting cortical dysfunction in the pathogenesis of PD psychosis.
Decision making can be regarded as the outcome of cognitive processes leading to the selection of a course of action among several alternatives. Borrowing a central measurement from information ...theory, Shannon entropy, we quantified the uncertainties produced by decisions of participants within an economic decision task under different configurations of reward probability and time. These descriptors were used to obtain blood oxygen level-dependent (BOLD) signal correlates of uncertainty and two clusters codifying the Shannon entropy of task configurations were identified: a large cluster including parts of the right middle cingulate cortex (MCC) and left and right pre-supplementary motor areas (pre-SMA) and a small cluster at the left anterior thalamus. Subsequent functional connectivity analyses using the psycho-physiological interactions model identified areas involved in the functional integration of uncertainty. Results indicate that clusters mostly located at frontal and temporal cortices experienced an increased connectivity with the right MCC and left and right pre-SMA as the uncertainty was higher. Furthermore, pre-SMA was also functionally connected to a rich set of areas, most of them associative areas located at occipital and parietal lobes. This study provides a map of the human brain segregation and integration (i.e., neural substrate and functional connectivity respectively) of the uncertainty associated to an economic decision making paradigm.
Intimate partner violence (IPV) and sexual violence (SV) are significant problems world-wide, and they affect women disproportionally. Whether individuals with attention-deficit/hyperactivity ...disorder (ADHD) are at an increased risk of being involved in these types of violence is unclear.
We carried out a systematic review and meta-analysis (PROSPERO registration CRD42022348165) of the associations between ADHD and being the victim or perpetrator of IPV and SV. Ratios of occurrence of violence were pooled in random-effects models and study risk of bias was evaluated using the Newcastle-Ottawa Scale.
A search on multiple databases, carried out on 7 October 2022, yielded 14 eligible studies (1 111 557 individuals). Analyses showed a higher risk of ADHD individuals being involved in IPV as perpetrators (six studies, OR 2.5, 95% CI 1.51-4.15) or victims (four studies, OR 1.78, 95% CI 1.06-3.0). Likewise, individuals with ADHD were at increased risk of being perpetrators (three studies, OR 2.73, 95% CI 1.35-5.51) or victims of SV (six studies, OR 1.84, 95% CI 1.51-2.24). Results were overall robust to different analytical choices.
Individuals with ADHD are at an increased risk of being involved in cases of violence, namely IPV and SV, either as victims or perpetrators. Although the causal path or mediating variables for these results are still unclear, this increased risk should inform evidence-based psychoeducation with individuals with ADHD, their families, and partners about romantic relationships and sexuality.
Evidence on the link between developmental coordination disorder (DCD) and obesity and overweight is mixed. Based on a pre-registered protocol (PROSPERO: CRD42023429432), we conducted the first ...systematic review/meta-analysis on the association between DCD and excessive weight. Web of Science, PubMed and an institutional database aggregator were searched until the 18th of December 2023. We assessed study quality using the Newcastle-Ottawa Scale and study heterogeneity using Q and I2 statistics. Data from 22 studies were combined, comprising 11,330 individuals out of which 1861 had DCD. The main analysis showed a significant association between DCD and higher body weight (OR:1.87, 95 % CI =1.43, 2.44). Meta-regression analyses indicated that the relationship was mediated by age, with stronger effects in studies with higher mean age (p 0.004). We conclude that DCD is associated with obesity and overweight, and this association increases with age. Our study could help to implement targeted prevention and intervention measures.
•Children and adolescents with Developmental Coordination Disorder (DCD) have a greater risk for obesity or overweight.•This heightened risk increases with age.•Individuals with DCD could be a high-risk target of obesity prevention programs.
•Risk of injury in children and adolescents with ADHD is increased.•ADHD medications reduce this risk.•Results were robust to sensitivity analyses.•Study was pre-registered in PROSPERO and reporting ...guidelines were followed.
A systematic review with meta-analyses was performed to: 1) quantify the association between ADHD and risk of unintentional physical injuries in children/adolescents (“risk analysis”); 2) assess the effect of ADHD medications on this risk (“medication analysis”). We searched 114 databases through June 2017. For the risk analysis, studies reporting sex-controlled odds ratios (ORs) or hazard ratios (HRs) estimating the association between ADHD and injuries were combined. Pooled ORs (28 studies, 4,055,620 individuals without and 350,938 with ADHD) and HRs (4 studies, 901,891 individuals without and 20,363 with ADHD) were 1.53 (95% CI=1.40,1.67) and 1.39 (95% CI=1.06,1.83), respectively. For the medication analysis, we meta-analysed studies that avoided the confounding-by-indication bias four studies with a self-controlled methodology and another comparing risk over time and groups (a “difference in differences” methodology). The pooled effect size was 0.879 (95% CI=0.838,0.922) (13,254 individuals with ADHD). ADHD is significantly associated with an increased risk of unintentional injuries and ADHD medications have a protective effect, at least in the short term, as indicated by self-controlled studies.
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.
•An umbrella review encompassing over 12 million participants was carried out.•Neurodevelopmental disorders were associated with several physical disorders.•There was also evidence of associations between physical and mood/anxiety disorders.•Obesity and allergic conditions have robust associations with mental disorders.
We aimed to quantify the clinical utility of continuous performance tests (CPTs) for the diagnosis of attention-deficit/hyperactivity disorder (ADHD) compared to a clinical diagnosis in children and ...adolescents.
Four databases (MEDLINE, PsycINFO, EMBASE, and PubMed) were screened until January 2023. Risk of bias of included results was judged with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We statistically pooled the area under the curve, the sensitivity, and the specificity of 3 commonly used CPTs subscales: omission/inattention, commission/impulsivity, and total number of errors/ADHD subscales (PROSPERO registration: CRD42020168091).
A total of 19 studies using commercially available CPTs were identified. Results from up to 835 control individuals and 819 cases were combined in the summary receiver operating characteristic (ROC) curve analyses (sensitivity and specificity pooling), and up to 996 cases and 1,083 control individuals in the area under the curve (AUC) analyses. Clinical utility as measured by AUCs could be considered as barely acceptable (between 0.7 and 0.8) for the most part, with the best results for the total/ADHD score, followed by omissions/inattention, and poorest for commission/impulsivity scores. A similar pattern was found when pooling sensitivity and specificity: 0.75 (95% CI = 0.66-0.82) and 0.71 (0.62-0.78) for the total/ADHD score; 0.63 (0.49-0.75) and 0.74 (0.65-0.81) for omissions; and 0.59 (0.38-0.77) and 0.66 (CI = 0.50-0.78) for commissions.
At the clinical level, CPTs as a stand-alone tool have only a modest to moderate ability to differentiate ADHD from non-ADHD samples. Hence, they should be used only within a more comprehensive diagnostic process.
A systematic review of screening tools for ADHD in children and adolescents; https://www.crd.york.ac.uk/prospero/; CRD42020168091.
Top‐tier evidence on the safety/tolerability of 80 medications in children/adolescents with mental disorders has recently been reviewed in this journal. To guide clinical practice, such data must be ...combined with evidence on efficacy and acceptability. Besides medications, psychosocial interventions and brain stimulation techniques are treatment options for children/adolescents with mental disorders. For this umbrella review, we systematically searched network meta‐analyses (NMAs) and meta‐analyses (MAs) of randomized controlled trials (RCTs) evaluating 48 medications, 20 psychosocial interventions, and four brain stimulation techniques in children/adolescents with 52 different mental disorders or groups of mental disorders, reporting on 20 different efficacy/acceptability outcomes. Co‐primary outcomes were disease‐specific symptom reduction and all‐cause discontinuation (“acceptability”). We included 14 NMAs and 90 MAs, reporting on 15 mental disorders or groups of mental disorders. Overall, 21 medications outperformed placebo regarding the co‐primary outcomes, and three psychosocial interventions did so (while seven outperformed waiting list/no treatment). Based on the meta‐analytic evidence, the most convincing efficacy profile emerged for amphetamines, methylphenidate and, to a smaller extent, behavioral therapy in attention‐deficit/hyperactivity disorder; aripiprazole, risperidone and several psychosocial interventions in autism; risperidone and behavioral interventions in disruptive behavior disorders; several antipsychotics in schizophrenia spectrum disorders; fluoxetine, the combination of fluoxetine and cognitive behavioral therapy (CBT), and interpersonal therapy in depression; aripiprazole in mania; fluoxetine and group CBT in anxiety disorders; fluoxetine/selective serotonin reuptake inhibitors, CBT, and behavioral therapy with exposure and response prevention in obsessive‐compulsive disorder; CBT in post‐traumatic stress disorder; imipramine and alarm behavioral intervention in enuresis; behavioral therapy in encopresis; and family therapy in anorexia nervosa. Results from this umbrella review of interventions for mental disorders in children/adolescents provide evidence‐based information for clinical decision making.
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