scholarly journals Atomoxetine and circadian gene expression in human dermal fibroblasts from study participants with a diagnosis of attention-deficit hyperactivity disorder

2021 ◽  
Author(s):  
Frank Faltraco ◽  
Denise Palm ◽  
Adriana Uzoni ◽  
Frederick Simon ◽  
Oliver Tucha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Dermal Fibroblasts ◽  
Adhd Group ◽  
Healthy Controls ◽  
Circadian Gene ◽  
Hyperactivity Disorder ◽  
Circadian Preference ◽  
Study Participants

AbstractAtomoxetine (ATO) is a second line medication for attention-deficit hyperactivity disorder (ADHD). We proposed that part of the therapeutic profile of ATO may be through circadian rhythm modulation. Thus, the aim of this study was to investigate the circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after ATO exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with a diagnosis of ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different ATO concentrations in HDF cultures, the rhythmicity of circadian gene expression was analyzed via qRT-PCR. No statistical significant effect of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, sleep WASO and total number of wake bouts was observed. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. ATO induced the rhythmicity of Clock in the ADHD group. This effect, however, was not observed in HDF cultures of healthy controls. Bmal1 and Per2 expression showed a significant ZT × group interaction via mixed ANOVA. Strong positive correlations for chronotype and circadian genes were observed for Bmal1, Cry1 and Per3 among the study participants. Statistical significant different Clock, Bmal1 and Per3 expressions were observed in HDFs exposed to ATO collected from ADHD participants exhibiting neutral and moderate evening preference, as well as healthy participants with morning preferences. The results of the present study illustrate that ATO impacts on circadian function, particularly on Clock, Bmal1 and Per2 gene expression.

scholarly journals Norepinephrine influences the circadian clock in human dermal fibroblasts from study participants with a diagnosis of attention-deficit hyperactivity disorder

2021 ◽  
Author(s):  
Denise Palm ◽  
Adriana Uzoni ◽  
Frederick Simon ◽  
Oliver Tucha ◽  
Johannes Thome ◽  
...  
Keyword(s):  
Gene Expression ◽  
Attention Deficit Hyperactivity Disorder ◽  
Dermal Fibroblasts ◽  
Control Group ◽  
Adhd Group ◽  
Human Dermal Fibroblasts ◽  
Circadian Gene ◽  
Hyperactivity Disorder ◽  
Circadian Preference ◽  
Control Samples

AbstractAttention-deficit hyperactivity disorder (ADHD) is characterized by changes to the circadian process. Many medications used to treat the condition, influence norepinephrine levels. Several studies have, in addition, reported that norepinephrine itself has an effect on circadian function. The aim of this study was to investigate the circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after norepinephrine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with an ADHD diagnosis. Circadian preference was evaluated with German Morningness–Eveningness Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different norepinephrine concentrations in HDF cultures, the rhythmicity of circadian gene expression was analyzed via qRT-PCR. The exposure of 1 µM norepinephrine to confluent cultures of human dermal fibroblasts from participants with a diagnosis of ADHD, was shown to dampen Per1 rhythmicity. The expression of Bmal1, Per1 and Per3 in control subjects was also influenced by incubation with 1 µM norepinephrine. Cultures from the ADHD group revealed no statistically significant overall differences in circadian gene expression, between cultures with and without norepinephrine incubation. Per3 expression showed a significant ZT × group interaction via mixed ANOVA. Per3 expression at ZT4 was significant higher in the group of control samples incubated with 1 µM norepinephrine, compared to the control group without norepinephrine. This effect was also shown in the control samples incubated with 1 µM norepinephrine and cultures from subjects with ADHD without norepinephrine incubation. Per3 expression differed between the healthy control group and the ADHD group without norepinephrine incubation at ZT28. The results of the present study illustrate that norepinephrine impacts on circadian function. In both groups, control group and cultures taken from subjects with ADHD, the expression of the periodic genes (Per1–3) was significantly influenced by incubation with norepinephrine.

scholarly journals Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients

2021 ◽  
Author(s):  
Frank Faltraco ◽  
Denise Palm ◽  
Adriana Uzoni ◽  
Lena Borchert ◽  
Frederick Simon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dermal Fibroblast ◽  
Sleep Onset ◽  
Dermal Fibroblasts ◽  
Control Group ◽  
Adhd Group ◽  
Healthy Controls ◽  
Circadian Gene ◽  
Significant Difference ◽  
Circadian Preference

AbstractA link between dopamine levels, circadian gene expression, and attention deficit hyperactivity disorder (ADHD) has already been demonstrated. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after dopamine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with ADHD. Circadian preference was evaluated with German Morningness-Eveningness-Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different dopamine concentrations in human dermal fibroblast (HDF) cultures, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analyzed via qRT-PCR. We found no statistical significant effect in the actigraphy of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, wake after sleep onset, and total number of wake bouts. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. Dopamine has no effect on Per3 expression in healthy controls, but produces a significant difference in the ADHD group at ZT24 and ZT28. In the ADHD group, incubation with dopamine, either 1 µM or 10 µM, resulted in an adjustment of Per3 expression to control levels. A similar effect also was found in the expression of Per2. Statistical significant differences in the expression of Per2 (ZT4) in the control group compared to the ADHD group were found, following incubation with dopamine. The present study illustrates that dopamine impacts on circadian function. The results lead to the suggestion that dopamine may improve the sleep quality as well as ADHD symptoms by adjustment of the circadian gene expression, especially for Per2 and Per3.

scholarly journals Evaluation of estrogen and G protein-coupled estrogen receptor 1 (GPER) levels in drug-naïve patients with attention deficit hyperactivity disorder (ADHD)

2018 ◽  
Vol 18 (2) ◽  
pp. 126-131 ◽  
Author(s):  
Nilfer Sahin ◽  
Hatice Altun ◽  
Ergül Belge Kurutaş ◽  
Ebru Fındıklı
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Estrogen Receptor ◽  
G Protein ◽  
Attention Deficit ◽  
Adhd Group ◽  
Healthy Controls ◽  
Hyperactivity Disorder ◽  
Drug Naïve ◽  
G Protein Coupled ◽  
Estrogen Receptor 1

Estrogen has a crucial role in the regulation of reproductive and neuroendocrine function and exerts its effects through two classes of receptors, nuclear and membrane estrogen receptors (mERs). G protein-coupled estrogen receptor 1 (GPER) is a member of mERs, and despite limited research on the levels of GPER in patients with psychiatric diseases, a role of GPER in such conditions has been suggested. Here we evaluated serum estrogen and GPER levels in children with attention deficit hyperactivity disorder (ADHD) in relation to their age- and gender-matched healthy controls. A total of 82 children were included in the study, 47 drug- naïve patients with ADHD (age: 6–12 years; male/female: 34/13) and 35 healthy controls (age: 6–12 years; male/female: 19/16). The subgroups according to ADHD types were inattentive, hyperactive/impulsive, and combined. Serum estrogen was measured using an immunoassay system, while serum GPER was determined using a commercial sandwich enzyme-linked immunosorbent assay kit. Estrogen levels in children with ADHD were similar as in control group, while GPER levels were significantly lower in ADHD group compared to controls (p < 0.05). Logistic regression analysis showed a significant association between GPER levels and ADHD (p < 0.05), and no association between estrogen levels and ADHD (p > 0.05). No significant differences were found in GPER and estrogen levels between ADHD subgroups (p > 0.05). To the best of our knowledge, this study is the first to investigate estrogen and GPER levels in ADHD. Our preliminary findings suggest a relationship between serum GPER levels and ADHD, and this should be further investigated.

scholarly journals Gut microbiota signature in treatment-naïve attention-deficit/hyperactivity disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vanesa Richarte ◽  
Cristina Sánchez-Mora ◽  
Montserrat Corrales ◽  
Christian Fadeuilhe ◽  
Laura Vilar-Ribó ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Gut Microbiota ◽  
Relative Abundance ◽  
Attention Deficit ◽  
Gut Microbiome ◽  
Rating Scale ◽  
Small Sample ◽  
Adhd Group ◽  
Healthy Controls ◽  
Hyperactivity Disorder

AbstractCompelling evidence supports alterations in gut microbial diversity, bacterial composition, and/or relative abundance of several bacterial taxa in attention-deficit/hyperactivity disorder (ADHD). However, findings for ADHD are inconsistent among studies, and specific gut microbiome signatures for the disorder remain unknown. Given that previous studies have mainly focused on the pediatric form of the disorder and involved small sample sizes, we conducted the largest study to date to compare the gastrointestinal microbiome composition in 100 medication-naïve adults with ADHD and 100 sex-matched healthy controls. We found evidence that ADHD subjects have differences in the relative abundance of several microbial taxa. At the family level, our data support a lower relative abundance of Gracilibacteraceae and higher levels of Selenomonadaceae and Veillonellaceae in adults with ADHD. In addition, the ADHD group showed higher levels of Dialister and Megamonas and lower abundance of Anaerotaenia and Gracilibacter at the genus level. All four selected genera explained 15% of the variance of ADHD, and this microbial signature achieved an overall sensitivity of 74% and a specificity of 71% for distinguishing between ADHD patients and healthy controls. We also tested whether the selected genera correlate with age, body mass index (BMI), or scores of the ADHD rating scale but found no evidence of correlation between genera relative abundance and any of the selected traits. These results are in line with recent studies supporting gut microbiome alterations in neurodevelopment disorders, but further studies are needed to elucidate the role of the gut microbiota on the ADHD across the lifespan and its contribution to the persistence of the disorder from childhood to adulthood.

Attributions for School Success and Failure by Adolescent Students with and without Attention Deficit Hyperactivity Disorder

2008 ◽  
Vol 102 (2) ◽  
pp. 616-620 ◽  
Author(s):  
Helmut Niederhofer
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
School Success ◽  
Causal Attributions ◽  
Adhd Group ◽  
Healthy Controls ◽  
Adolescent Students ◽  
Hyperactivity Disorder

A study of possible differences in causal attributions between ADHD youth and non-ADHD controls is reported. 40 students (12 to 18 years of age), diagnosed with ADHD by a psychologist and a psychiatrist according to Conners' criteria were compared with healthy controls. Analyses confirmed that external attributions regarding luck were significantly higher for the ADHD group than for the 40 healthy controls. Implications of these findings for intervention in ADHD are discussed.

Neural correlates of visuospatial working memory in attention-deficit/hyperactivity disorder and healthy controls

2015 ◽  
Vol 233 (2) ◽  
pp. 233-242 ◽  
Author(s):  
Hanneke van Ewijk ◽  
Wouter D. Weeda ◽  
Dirk J. Heslenfeld ◽  
Marjolein Luman ◽  
Catharina A. Hartman ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Working Memory ◽  
Attention Deficit ◽  
Neural Correlates ◽  
Healthy Controls ◽  
Visuospatial Working Memory ◽  
Hyperactivity Disorder

Mainstream and Remedial School Attention Deficit Hyperactivity Disorder Boys: More Alike than Different

2005 ◽  
Vol 35 (1) ◽  
pp. 73-88
Author(s):  
J. B. Savitz ◽  
P. Jansen
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Control Group ◽  
Adhd Group ◽  
Hyperactivity Disorder ◽  
Significant Difference ◽  
Executive Deficits ◽  
Mainstream School ◽  
The Difference ◽  
Neuropsychological Tasks

The literature on the neuropsychology of Attention Deficit Hyperactivity Disorder (ADHD) is plagued by inconsistent findings, which are usually attributed to a variety of extraneous variables. One of the most inadequately explored of these variables is the difference between ADHD children attending remedial and mainstream schools. This study aimed to investigate whether the performance of remedial and mainstream school ADHD boys differs on relevant neuropsychological tasks. The sample consisted of three groups of 8- to 12-year-old boys. Two of these groups consisted of children with ADHD: one from remedial schools and one from mainstream schools. The third group was made up of participants without ADHD, who attended mainstream schools. The performance of the remedial school learners on the Stroop, Lurian and cancellation tasks was investigated and compared to a mainstream school ADHD sample. The performance of the ADHD group as a whole was compared with that of a control group. No significant difference in performance was found between the two ADHD groups, except for the length of time taken to read words in the control condition of the Stroop. The control group out-performed the ADHD samples on the Stroop, Lurian and cancellation tasks. The findings suggest that mainstream and remedial ADHD boys do not differ in the severity of their executive deficits, but that boys with ADHD attending remedial schools may be more likely to have another learning disorder than their counterparts at mainstream schools.

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Moreno-Alcázar ◽  
Josep A. Ramos-Quiroga ◽  
Marta Ribases ◽  
Cristina Sánchez-Mora ◽  
Gloria Palomar ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Working Memory ◽  
Attention Deficit ◽  
Temporal Cortex ◽  
Functional Brain Imaging ◽  
Brain Anatomy ◽  
Risk Haplotype ◽  
Healthy Controls ◽  
Functional Brain ◽  
Hyperactivity Disorder

AbstractPrevious 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.

Attention Deficit Hyperactivity Disorder, Creativity, and the Effects of Methylphenidate

PEDIATRICS ◽  
1993 ◽  
Vol 91 (4) ◽  
pp. 816-819
Author(s):  
Jeanne B. Funk ◽  
John B. Chessare ◽  
Michael T. Weaver ◽  
Anita R. Exley
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Repeated Measures ◽  
Creative Thinking ◽  
Adhd Group ◽  
Hyperactivity Disorder ◽  
Significant Difference ◽  
Quasi Experimental ◽  
The Difference ◽  
Clinically Significant

Given that children with attention deficit hyperactivity disorder (ADHD) are more impulsive than peers, this study explored whether they are correspondingly more creative, and whether creativity declines when impulsivity is decreased through methylphenidate (Ritalin) therapy. A repeated-measures quasi-experimental design was used to compare the performance of 19 boys with previously diagnosed ADHD and 21 comparison boys aged 8 through 11 on two administrations of alternate forms of the Torrance Tests of Creative Thinking-Figural (nonverbal). Boys with ADHD received prescribed methylphenidate only for the first session. Overall, mean Torrance summary scores for comparison boys (mean = 115.1, SD = 16.1) were higher than for boys with ADHD (mean = 107.6, SD = 12.7). However, the difference between means was small (7%) and did not meet the 25% criterion for a clinically significant difference. No changes in performance over time (comparison group) or medication state (ADHD group) were observed. These data suggest that, when measured nonverbally, the creative thinking performance of boys with ADHD is not superior to that of peers who do not have ADHD. Regarding the effects of methylphenidate, prescribed therapy did not influence performance on this measure of creative thinking.

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