Maite Ferrin

Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments

OBJECTIVE Nonpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments. METHOD Using a common systematic search and a rigorous coding and data extraction strategy across domains, the authors searched electronic databases to identify published randomized controlled trials that involved individuals who were diagnosed with ADHD (or who met a validated cutoff on a recognized rating scale) and that included an ADHD outcome. RESULTS Fifty-four of the 2,904 nonduplicate screened records were included in the analyses. Two different analyses were performed. When the outcome measure was based on ADHD assessments by raters closest to the therapeutic setting, all dietary (standardized mean differences=0.21-0.48) and psychological (standardized mean differences=0.40-0.64) treatments produced statistically significant effects. However, when the best probably blinded assessment was employed, effects remained significant for free fatty acid supplementation (standardized mean difference=0.16) and artificial food color exclusion (standardized mean difference=0.42) but were substantially attenuated to nonsignificant levels for other treatments. CONCLUSIONS Free fatty acid supplementation produced small but significant reductions in ADHD symptoms even with probably blinded assessments, although the clinical significance of these effects remains to be determined. Artificial food color exclusion produced larger effects but often in individuals selected for food sensitivities. Better evidence for efficacy from blinded assessments is required for behavioral interventions, neurofeedback, cognitive training, and restricted elimination diets before they can be supported as treatments for core ADHD symptoms.

Cognitive Training for Attention-Deficit/Hyperactivity Disorder: Meta-Analysis of Clinical and Neuropsychological Outcomes From Randomized Controlled Trials

Objective The authors performed meta-analyses of randomized controlled trials to examine the effects of cognitive training on attention-deficit/hyperactivity disorder (ADHD) symptoms, neuropsychological deficits, and academic skills in children/adolescents with ADHD. Method The authors searched Pubmed, Ovid, Web of Science, ERIC, and CINAHAL databases through May 18, 2014. Data were aggregated using random-effects models. Studies were evaluated with the Cochrane risk of bias tool. Results Sixteen of 695 nonduplicate records were analyzed (759 children with ADHD). When all types of training were considered together, there were significant effects on total ADHD (standardized mean difference [SMD] = 0.37, 95% CI = 0.09–0.66) and inattentive symptoms (SMD = 0.47, 95% CI = 0.14–0.80) for reports by raters most proximal to the treatment setting (i.e., typically unblinded). These figures decreased substantially when the outcomes were provided by probably blinded raters (ADHD total: SMD = 0.20, 95% CI = 0.01–0.40; inattention: SMD = 0.32, 95% CI = −0.01 to 0.66). Effects on hyperactivity/impulsivity symptoms were not significant. There were significant effects on laboratory tests of working memory (verbal: SMD = 0.52, 95% CI = 0.24–0.80; visual: SMD = 0.47, 95% CI = 0.23–0.70) and parent ratings of executive function (SMD = 0.35, 95% CI = 0.08–0.61). Effects on academic performance were not statistically significant. There were no effects of working memory training, specifically on ADHD symptoms. Interventions targeting multiple neuropsychological deficits had large effects on ADHD symptoms rated by most proximal assessors (SMD = 0.79, 95% CI = 0.46–1.12). Conclusion Despite improving working memory performance, cognitive training had limited effects on ADHD symptoms according to assessments based on blinded measures. Approaches targeting multiple neuropsychological processes may optimize the transfer of effects from cognitive deficits to clinical symptoms.

Research Review: The role of diet in the treatment of attention-deficit/ hyperactivity disorder - An appraisal of the evidence on efficacy and recommendations on the design of future studies

BACKGROUND The efficacy of three dietary treatments for ADHD has been repeatedly tested in randomized controlled trials (RCTs). These interventions are restricted elimination diets (RED), artificial food colour elimination (AFCE) and supplementation with free fatty acids (SFFA). There have been three systematic reviews and associated meta-analyses of the RCTs for each of these treatments. SCOPE The aim of this review is to critically appraise the studies on the dietary treatments of ADHD, to compare the various meta-analyses of their efficacy that have been published and to identify where the design of such RCTs could be improved and where further investigations are needed. FINDINGS The meta-analyses differ in the inclusion and exclusion criteria applied to potentially eligible studies. The range of average effect sizes in standard deviation units is RED (0.29-1.2), AFCE (0.18-0.42) and SFFA (0.17-0.31). The methodology of many of the trials on which the meta-analyses are based is weak. CONCLUSIONS Nevertheless, there is evidence from well-conducted studies for a small effect of SFFA. Restricted elimination diets may be beneficial, but large-scale studies are needed on unselected children, using blind assessment and including assessment of long-term outcome. Artificial food colour elimination is a potentially valuable treatment but its effect size remains uncertain, as does the type of child for whom it is likely to be efficacious. There are additional dietary supplements that have been used with children with ADHD. A systematic search identified 11 RCTs that investigated the effects of these food supplements. Despite positive results for some individual trials, more studies are required before conclusions can be reached on the value in reducing ADHD symptoms of any of these additional supplements.

Dose–response effect between cannabis use and psychosis liability in a non-clinical population: Evidence from a snowball sample

This study aimed to explore the associations between daily cannabis use and the specific profiles of subclinical symptoms in a non-clinical population obtained through snowball sampling, taking into account alcohol use, other drug use, social exclusion and age at onset of cannabis use. We included 85 daily cannabis users and 100 non-daily cannabis users. Both the case and the control populations were identified by snowball sampling. Daily cannabis use was associated with more alcohol intake and other drug use, as well as with early onset in the use of cannabis. Daily cannabis use appeared to exert a dose-response effect on first-rank symptoms, mania symptoms and auditory hallucinations, even after adjusting for sex, age, other drug use, social exclusion and age at onset of cannabis use. The paranoid dimension was only associated with the heaviest consumption of cannabis. Initial age of cannabis use modified the effects of daily cannabis use on the first-rank and voices experiences. Daily cannabis use was associated with significantly more first-rank and voices experiences among those subjects who started to use cannabis before 17 years of age. Our study supports the association of psychotic experiences with cannabis use even among non-psychotic subjects.

Jumping to conclusions in psychosis: a faulty appraisal.

Schizophrenia patients, particularly those with current delusions, show a cognitive bias known as jumping to conclusions, defined as a decision made quickly on the basis of little evidence. The aim of this work was to examine the underlying mechanisms of this cognitive bias by means of the Picture To Decision Task, which allows one to analyse the effect of the context on decisions made. We compared the performance of this task by 42 psychotic patients, 21 siblings of these patients and 77 controls. The results of the current study suggest that, relative to siblings and controls, patients display a general tendency to jump to conclusions, characterised by overestimating the conviction in their choices at the beginning of the decision process and by a lowered threshold for making decisions in ambiguous contexts, where a greater amount of information is required. These results are interpreted in terms of faulty appraisal, which would be the first mechanism responsible for the Jumping To Conclusions bias. Theoretical and clinical implications are discussed.

Examination of Neurological Subtle Signs in ADHD as a Clinical Tool for the Diagnosis and Their Relationship to Spatial Working Memory.

BACKGROUND   Neurological subtle signs (NSS) are minor neurological abnormalities that have been shown to be increased in a number of neurodevelopmental conditions. For attention deficit/hyperactivity disorder (ADHD), it remains unclear whether NSS may aid the clinical diagnostic process. METHODS   This study explored the association of total and specific domains of NSS in 1,055 children and adolescents with ADHD compared to 130 age-matched typically developing participants; the relationship between NSS and Spatial Working Memory (SWM) as a cognitive process integrally involved in ADHD was also assessed. To determine the diagnostic and predictive efficiency of NSS, a receiver operating curve analysis was performed and the area under the curve (AUC) quantified. The best discriminant points for differentiating between ADHD and typically developing participants and the predictive power of NSS for SWM impairment in ADHD young people were also calculated. RESULTS   Area under the curves for total NSS, smoothness/accuracy, cerebellar signs and choreo-athetoid movements scores were considered good (.84, .79, .74 and .73 respectively), and the results remained after controlling for gender and IQ. A total score of 13 or over on the Scored Developmental Neurological Examination proved to be a good threshold point for differentiating between the ADHD and typically developing participants. For ADHD children, the AUC of total NSS to distinguish between those below 25th and above 75th percentile were .77 and .73 for Spatial Span and for Between Search Errors respectively (the two SWM-dependent measures examined). CONCLUSIONS   This study provides evidence suggesting that NSS may aid the clinical evaluation of a child or adolescent with ADHD. In children and adolescents with ADHD, NSS are associated with difficulties in SWM, specifically the Spatial Span and Between Search Error components.

Evaluation of attitudes towards treatment in adolescents with attention deficit hyperactivity disorder (ADHD)

A substantial proportion of adolescents with attention deficit hyperactivity disorder (ADHD) do not appropriately adhere to prescribed treatments, especially to pharmacological treatments. It is important to disentangle the specific attitudes that contribute to treatment adherence. A 33-item questionnaire was applied to 120 adolescents diagnosed with ADHD and their respective parents. Reliability of the scale was explored using factor analysis, Cronbach’s alpha, and test–retest. Validity was explored by face validity and the known-groups method. For the young people’s version, three main dimensions (preoccupations, insight and self-concept) emerged. The parents’ version showed six main dimensions (child’s personal attitudes, worries, social stigma, insight, future side effects and knowledge). The potential of this questionnaire to explore the attitudes of patients and their families towards treatments and for clinicians to predict treatment adherence is discussed.

Neurological Soft Signs in Patients with Psychosis and Cannabis Abuse: A Systematic Review and Meta-Analysis of Paradox

BACKGROUND Although neurological soft signs (NSSs) have been consistently associated with schizophrenia and a variety of risk factors, few studies have focused on the association between NSSs and environmental factors such as cannabis use, particularly in patients with first episode psychosis (FEP). AIMS To review studies that have specifically investigated the association between NSSs and cannabis use in subjects who suffer from psychosis, and more specifically in FEP. METHODS A review of studies investigating the associations between neurological function in psychotic patients and cannabis use. RESULTS A total of 5 studies met our inclusion criteria. Two of these included data only from patients with FEP. Four studies concluded that patients with psychosis and particularly FEP who consumed cannabis showed fewer NSSs. CONCLUSIONS Four possible explanations are suggested for the paradoxical relationship between cannabis use and NSSs in FEP. First, heavy cannabis users present with different acute responses to cannabis use than do occasional cannabis users. Second, the psychoses developed by patients who consume cannabis follow different physio-pathological pathways that include fewer neurodevelopmental abnormalities. Third, the direct effect of cannabis on the Central Nervous System (CNS) may be responsible for the paradox. Finally,severe NSSsare associated with other clinical characteristics that would limit a subjects personal access to cannabis.

The duration of untreated psychosis is associated with social support and temperament

The duration of untreated psychosis (DUP) has been suggested to be a modifiable factor influencing psychosis outcome. There are many studies on the factors that predict DUP, although with contradictory findings. Although temperament has been associated with seeking help in other pathologies, studies about how temperament influences DUP are lacking. This study explored the role of temperament (measured by the Eysenck Personality Inventory Questionnaire) on DUP and tested the hypothesis that social support modifies the effects of neuroticism and extraversion on DUP. We evaluated 97 first-episode psychosis patients. The effect of temperament, affective diagnosis and social support (measured by the Social Support Index) on DUP was explored through a multivariate analysis using Cox regression model. Once psychotic symptoms had started, a patient with affective psychosis was 76% more likely to start antipsychotic medications than a patient with non-affective psychosis of comparable time without treatment (adjusted hazard ratio, HR, 1.76; 95% CI, (1.07, 2.9)). There was a significant interaction between diffuse social support and neuroticism (p=0.04). Among patients who had a good diffuse social support, a patient with a high neuroticism score was 45% less likely to start antipsychotic medication than a time-comparable patient with a low neuroticism (HR, 0.55 (0.32, 0.95)). Among patients who had a low neuroticism score, a patient with poor diffuse social support was 56% less likely to start antipsychotic medication than a comparable patient with good support (HR, 0.44 (0.23, 0.86)). In conclusion, patients with affective psychosis had significantly shorter DUPs. In patients with a good diffuse social support, low neuroticism scores were significantly associated with decreased DUP. In patients with low neuroticism scores, a poor diffuse social support was associated with a significant increase in DUP.

Differential effects of anxiety and depressive symptoms on working memory components in children and adolescents with ADHD combined type and ADHD inattentive type

Abstract Working memory (WM) deficits have been shown to be associated with core ADHD symptoms, worse academic achievement and peer-relationship problems. Internalizing symptoms, such as anxiety and depression, have also been associated with impaired WM performance. However, the association of anxiety and depression and WM performance remains unclear for children and adolescents with ADHD. Further, it is unknown how these comorbid conditions might affect WM performance in the two main ADHD subtypes. The association of anxiety and depression and the specific components of spatial (SWM) and verbal working memory (VWM) were examined in 303 children and adolescents with ADHD, combined type (ADHD-CT) and 77 ADHD, inattentive type (ADHD-IA) compared to 128 age- and gender-matched typically developing participants. The relationship between anxiety and depression and WM was assessed using multiple linear regression analyses and separate simple regression analyses. Higher levels of anxiety/depression were associated with (1) increased between-search errors in the typically developing participants alone, (2) a better strategy performance in the ADHD-CT group, and (3) a better spatial span performance in the ADHD-IA group. VWM was equally impaired in the ADHD-CT and ADHD-IA groups, independent of the levels of anxiety and depression. The results suggest that the effects of internalizing symptoms on WM differ in typically developing children and adolescents compared to those with ADHD. Further, high levels of anxiety and depression modified WM performance differently according to the specific ADHD subtypes. This might help explain contradictory findings observed in previous studies of mixed samples of participants with ADHD-CT and ADHD-IA.