Catia Scassellati

Bio: Catia Scassellati is an academic researcher from University of Lausanne. The author has contributed to research in topics: Attention deficit hyperactivity disorder & Medicine. The author has an hindex of 20, co-authored 46 publications receiving 1189 citations.

Biomarkers and Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analyses

Abstract: Objective To determine whether peripheral biochemical markers (biomarkers) might differentiate patients with attention-deficit/hyperactivity disorder (ADHD) from non-ADHD individuals. Method We conducted a systematic search and a series of meta-analyses of case-control studies comprising studies from 1969 to 2011. Results We identified 210 studies in the following categories: 71 studies of the main metabolites and metabolism enzymes of monoaminergic neurotransmission pathway; 87 studies of environmental risk factors divided into heavy metals (18 studies), substance/chemical exposures (16 studies), and nutritional factors (trace elements: 29 studies; essential fatty acids: 24 studies); 22 studies of the hypothalamic–pituitary–adrenal axis (HPA) pathway; 31 studies indicated with "other." After screening for the availability for meta-analyses of drug naive/free case-control studies and Bonferroni correction, five comparisons were statistically significant (Norepinephrine [NE], 3-Methoxy-4-hydroxyphenylethylene glycol [MHPG], monoamine oxidase [MAO], Zinc [Zn], cortisol), five of the significant findings found support in studies of response to ADHD medications (NE, MHPG, MAO, b-phenylethylamine [PEA], cortisol), six in studies of symptoms severity (NE, MHPG, MAO, ferritin, Zn, cortisol) and three in studies of neurophysiological or cognitive functioning (lead–ferritin–Zn). No evidence of publication bias was found, whereas significant heterogeneity of effect sizes across studies was found for three of the five biomarkers that differentiated ADHD from control subjects. Suggestive associations were evidenced for neuropeptide Y (NPY), manganese, and dehydroepiandrosterone (DHEA). Conclusions This study provides evidence for several peripheral biomarkers as being associated with ADHD both in diagnosis and in treatment efficacy. Further studies are warranted to replicate these findings, to assess their specificity for ADHD, and to quantify the degree to which they are sufficiently precise to be useful in clinical settings.

Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies.

Abstract: The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug. Finally some peripheral biomarkers were identified in ADHD adult patients. We believe this work is the first systematic review and meta-analysis of candidate gene association studies, pharmacogenetic and biochemical (metabolomics) studies performed in adults with ADHD to identify potential genetic, predictive and peripheral markers linked specifically to ADHD in adults. After screening 5129 records, we selected 87 studies of which 61 were available for candidate gene association studies, 5 for pharmacogenetics and 21 for biochemical studies. Of these, 15 genetic, 2 pharmacogenetic and 6 biochemical studies were included in the meta-analyses. We obtained an association between adult ADHD and the gene BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), even after Bonferroni correction, with any heterogeneity in effect size and no publication bias. If we did not apply the Bonferroni correction, a trend was found for the carriers allele 9R of dopamine transporter SLC6A3 40 bp variable tandem repeat polymorphism (VNTR) and for 6/6 homozygotes of SLC6A3 30 bp VNTR. Negative results were obtained for the 9-6 haplotype, the dopamine receptor DRD4 48 bp VNTR, and the enzyme COMT SNP rs4680. Concerning pharmacogenetic studies, no association was found for the SLC6A3 40 bp and response to MPH with only two studies selected. For the metabolomics studies, no differences between ADHD adults and controls were found for salivary cortisol, whereas lower serum docosahexaenoic acid (DHA) levels were found in ADHD adults. This last association was significant even after Bonferroni correction and in absence of heterogeneity. Other polyunsaturated fatty acids (PUFAs) such as AA (arachidonic acid), EPA (eicosapentaenoic acid) and DyLA (dihomogammalinolenic acid) levels were not different between patients and controls. No publication biases were observed for these markers. Genes linked to dopaminergic, serotoninergic and noradrenergic signaling, metabolism (DBH, TPH1, TPH2, DDC, MAOA, MAOB, BCHE and TH), neurodevelopment (BDNF and others), the SNARE system and other forty genes/proteins related to different pathways were not meta-analyzed due to insufficient data. In conclusion, we found that there were not enough genetic, pharmacogenetic and biochemical studies of ADHD in adults and that more investigations are needed. Moreover we confirmed a significant role of BAIAP2 and DHA in the etiology of ADHD exclusively in adults. Future research should be focused on the replication of these findings and to assess their specificity for ADHD.

Biomarkers in the Diagnosis of ADHD – Promising Directions

Abstract: The etiology and pathogenesis of attention-deficit/hyperactivity disorder (ADHD) are unclear and a more valid diagnosis would certainly be welcomed. Starting from the literature, we built an hypothetical pyramid representing a putative set of biomarkers where, at the top, variants in DAT1 and DRD4 genes are the best candidates for their associations to neuropsychological tasks, activation in specific brain areas, methylphenidate response and gene expression levels. Interesting data come from the noradrenergic system (norepinephrine transporter, norepinephrine, 3-methoxy-4-hydroxyphenylglycol, monoamine oxidase, neuropeptide Y) for their altered peripheral levels, their association with neuropsychological tasks, symptomatology, drugs effect and brain function. Other minor putative genetic biomarkers could be dopamine beta hydroxylase and catechol-O-methyltransferase. In the bottom, we placed endophenotype biomarkers. A more deep integration of “omics” sciences along with more accurate clinical profiles and new high-throughput computational methods will allow us to identify a better list of biomarkers useful for diagnosis and therapies.

Common and specific genes and peripheral biomarkers in children and adults with attention-deficit/hyperactivity disorder

Abstract: Objectives: Elucidating the biological mechanisms involved in attention-deficit/hyperactivity disorder (ADHD) has been challenging. Relatively unexplored is the fact that these mechanisms can diffe...

ADHD Prevalence Estimates Across Three Decades: An Updated Systematic Review and Meta-Regression Analysis

Abstract: BACKGROUND Previous studies have identified significant variability in attention-deficit / hyperactivity disorder (ADHD) prevalence estimates worldwide, largely explained by methodological procedures. However, increasing rates of ADHD diagnosis and treatment throughout the past few decades have fuelled concerns about whether the true prevalence of the disorder has increased over time. METHODS We updated the two most comprehensive systematic reviews on ADHD prevalence available in the literature. Meta-regression analyses were conducted to test the effect of year of study in the context of both methodological variables that determined variability in ADHD prevalence (diagnostic criteria, impairment criterion and source of information), and the geographical location of studies. RESULTS We identified 154 original studies and included 135 in the multivariate analysis. Methodological procedures investigated were significantly associated with heterogeneity of studies. Geographical location and year of study were not associated with variability in ADHD prevalence estimates. CONCLUSIONS Confirming previous findings, variability in ADHD prevalence estimates is mostly explained by methodological characteristics of the studies. In the past three decades, there has been no evidence to suggest an increase in the number of children in the community who meet criteria for ADHD when standardized diagnostic procedures are followed.

Genetics of attention deficit hyperactivity disorder

Abstract: Decades of research show that genes play an vital role in the etiology of attention deficit hyperactivity disorder (ADHD) and its comorbidity with other disorders. Family, twin, and adoption studies show that ADHD runs in families. ADHD’s high heritability of 74% motivated the search for ADHD susceptibility genes. Genetic linkage studies show that the effects of DNA risk variants on ADHD must, individually, be very small. Genome-wide association studies (GWAS) have implicated several genetic loci at the genome-wide level of statistical significance. These studies also show that about a third of ADHD’s heritability is due to a polygenic component comprising many common variants each having small effects. From studies of copy number variants we have also learned that the rare insertions or deletions account for part of ADHD’s heritability. These findings have implicated new biological pathways that may eventually have implications for treatment development.

Translational Findings on Brain-Derived Neurotrophic Factor and Anxiety: Contributions from Basic Research to Clinical Practice

Abstract: Background/Aims: Anxious responses are evolutionarily adaptive, but excessive fear can become disabling and lead to anxiety disorders. Translational models of anxiety might be useful sources for understanding the neurobiology of fear and anxiety and can contribute to future proposals of therapeutic intervention for the disorders studied. Brain-derived neurotrophic factor (BDNF), which is known for its importance on neuroplasticity and contextual memory, has emerged as a relevant element for emotional memory. Recent studies show that the Val 66 Met BDNF polymorphism