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

Author(s):  
Denise Palm ◽  
Adriana Uzoni ◽  
Frederick Simon ◽  
Oliver Tucha ◽  
Johannes Thome ◽  
...  

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.

Author(s):  
Frank Faltraco ◽  
Denise Palm ◽  
Adriana Uzoni ◽  
Frederick Simon ◽  
Oliver Tucha ◽  
...  

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.


Author(s):  
Frank Faltraco ◽  
Denise Palm ◽  
Adriana Uzoni ◽  
Lena Borchert ◽  
Frederick Simon ◽  
...  

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.


2005 ◽  
Vol 35 (1) ◽  
pp. 73-88
Author(s):  
J. B. Savitz ◽  
P. Jansen

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.


2014 ◽  
Vol 29 (5) ◽  
pp. 316-323 ◽  
Author(s):  
H. Caci ◽  
M. Doepfner ◽  
P. Asherson ◽  
R. Donfrancesco ◽  
S.V. Faraone ◽  
...  

AbstractThe Lifetime Impairment Survey assessed impairment and symptoms of attention-deficit/hyperactivity disorder (ADHD) in children/adolescents from six European countries. Parents/caregivers of children/adolescents aged < 20 years with ADHD (ADHD group; n = 535) and without ADHD (control group; n = 424) participated in an online survey. History of ADHD diagnosis was self-reported. ADHD and control groups were compared using impairment and symptom scales; higher scores indicate greater impairment. Mean (SD) age at ADHD diagnosis was 7.0 (2.8) years, following consultation of 2.7 (2.6) doctors over 20.4 (23.9) months. Parents/caregivers (64%; 344/535) reported frustration with some aspect of the diagnostic procedure; 74% (222/298) were satisfied with their child's current medication. ADHD had a negative impact on children/adolescents in all aspects of life investigated. The ADHD group had a higher mean (SD) school impairment score (2.7 [0.7]) compared with the control group (2.1 [0.7]; P < 0.001) and were more likely to be in the bottom of their class (P < 0.001). These data provide insights into impairments associated with ADHD in childhood/adolescence, and identify areas for improvement in its management and treatment.


Author(s):  
Ali Ekhlasi ◽  
Ali Motie Nasrabadi ◽  
Mohammad Reza Mohammadi

Objective: This study aimed to investigate differences in brain networks between healthy children and children with attention deficit hyperactivity disorder (ADHD) during an attention test. Method: To fulfill this, we constructed weighted directed graphs based on Electroencephalography (EEG) signals of 61 children with ADHD and 60 healthy children with the same age. Nodes of graphs were 19 EEG electrodes, and the edges were phase transfer entropy (PTE) between each pair of electrodes. PTE is a measure for directed connectivity that determines the effective relationship between signals in linear and nonlinear coupling. Connectivity graphs of each sample were constructed using PTE in the five frequency bands as follows: delta, theta, alpha, beta, and gamma. To investigate the differences in connectivity strength of each node after the sparsification process with two values (0.5 and 0.25), the permutation statistical test was used with the statistical significance level of p<0.01. Results: The results indicate stronger inter-regional connectivity in the prefrontal brain regions of the control group compared to the ADHD group. However, the strength of inter-regional connectivity in the central regions of the ADHD group was higher. A comparison of the prefrontal regions between the two groups revealed that the areas of the Fp1 electrode (left prefrontal) in healthy individuals play stronger transmission roles. Conclusion: Our research can provide new insights into the strength and direction of connectivity in ADHD and healthy individuals during an attention task.


2014 ◽  
Author(s):  
Soyeon Kim ◽  
Tobias Banaschewski ◽  
Rosemary Tannock

Background: Individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) are reported to manifest visual problems (including ophthalmological and color perception problems, particularly for blue-yellow stimuli), but findings are inconsistent. Accordingly, this study investigated visual function and color perception in adolescents with ADHD using VEP. Method: Participants were 31 adolescents (aged 13-18); 16 with a confirmed diagnosis of ADHD, and 15 healthy peers, matched for age, gender, and IQ. All underwent ophthalmological exam, color vision testing (Mollon-Reffin Minimalist Colour Vision Test), as well as electrophysiological testing (color Visual Evoked Potentials; cVEP) which measured the latency and amplitude of the neural P1 response to chromatic stimuli (Blue-Yellow, Red-Green). Result: No group differences were found in clinical measure of color perception or opthalmological exam. However, significantly larger P1 amplitude was found for blue and yellow stimuli, but not red/green stimuli, in the ADHD group compared to controls. Discussion: Larger amplitude in the P1 component for blue-yellow in ADHD group compared to control group may account for no difference in colour perception task. Perhaps activating more resources in early sensory processing (P1) compensated for any underlying problems including compromised retinal input of s-cones due to hypo-dopaminergic tone.


2020 ◽  
Vol 17 (3) ◽  
pp. 256-261
Author(s):  
Ümit Is¸ ık ◽  
Faruk Kılıç ◽  
Arif Demirdas¸ ◽  
Evrim Aktepe ◽  
Pınar Aydog˘ an Avs¸ ar

Objective Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with underlying pathogenesis and etiological factors not fully understood. We assumed that galectin-3, which is also linked with inflammatory responses, may play an important role in the ethiopathogenesis of ADHD. In this study, we aimed to investigate whether serum galectin-3 levels are related to ADHD in childhood.Methods The current study consisted of 35 treatment-naive children with ADHD and 35 control subjects. The severities of ADHD and conduct disorder symptoms were assessed via parent- and teacher-rated questionnaires. The severity of anxiety and depression symptoms of the children were determined by the self-report scale. Venous blood samples were collected and serum galectin-3 levels were measured.Results The ADHD group had significantly higher serum Galectin-3 levels than the control group. To control confounding factors, including age, sex, and BMI percentile, one-way analysis of covariance (ANCOVA) test was also performed. Analyses revealed a significantly higher serum log- Galectin-3 levels in children with ADHD compared to controls. No association was found between the mean serum galectin-3 levels and sociodemographic characteristics and clinical test scores, except the oppositional defiant behavior scores.Conclusion Our research supports the hypothesis that serum levels of galectin-3 might be related to ADHD.


2018 ◽  
Vol 50 (3) ◽  
pp. 172-179 ◽  
Author(s):  
Julie Chi Chow ◽  
Chen-Sen Ouyang ◽  
Chin-Ling Tsai ◽  
Ching-Tai Chiang ◽  
Rei-Cheng Yang ◽  
...  

Diagnosis of attention-deficit hyperactivity disorder (ADHD) is currently based on core symptoms or checklists; however, the inevitability of practitioner subjectivity leads to over- and underdiagnosis. Although the Federal Drug Administration has approved an elevated theta/beta ratio (TBR) of the electroencephalogram (EEG) band as a tool for assisting ADHD diagnosis, several studies have reported no significant differences of the TBR between ADHD and control subjects. This study detailed the development of a method based on approximate entropy (ApEn) analysis of EEG to compare ADHD and control groups. Differences between ADHD presentation in boys and girls indicate the necessity of separate investigations. This study enrolled 30 girls with ADHD and 30 age-matched controls. The results revealed significantly higher ApEn values in most brain areas in the control group than in the ADHD group. Compared with TBR-related feature descriptors, ApEn-related feature descriptors can produce the higher average true positive rate (0.846), average true negative rate (0.814), average accuracy (0.817), and average area under the receiver operating characteristic curve value (0.862). Therefore, compared with TBR, ApEn possessed the better potential for differentiating between girls with ADHD and controls.


CNS Spectrums ◽  
2014 ◽  
Vol 20 (2) ◽  
pp. 112-121 ◽  
Author(s):  
Herve Caci ◽  
Philip Asherson ◽  
Renato Donfrancesco ◽  
Stephen V. Faraone ◽  
Amaia Hervas ◽  
...  

IntroductionThe Lifetime Impairment Survey, conducted in Europe, assessed impairment and symptoms of attention-deficit/hyperactivity disorder (ADHD) in childhood, and experiences of ADHD diagnosis and treatment, as recalled by adults.MethodsAdults with ADHD and without ADHD (control group) were invited to participate in an internet-based survey and report on their childhood experiences. History of ADHD diagnosis was self-reported. Groups were compared using impairment and symptom scales.ResultsOverall, 588 adults with ADHD and 736 without ADHD participated. Mean (standard deviation [SD]) age at diagnosis of ADHD was 20.0 (12.6) years (median 18.0) following consultation with 3.8 (5.1) doctors (median 2) over 44.6 (69.3) months (median 17.0). A total of 64.1% (377/588) of adults with ADHD reported frustration or difficulties during the diagnostic process. The ADHD group had a higher mean (SD) score versus control for general (3.3 [1.2] vs 2.1 [1.2]; p < 0.001) and school impairment (2.8 [0.7] vs 2.3 [0.6]; p < 0.001) but not home impairment (2.1 [0.5] for both groups).DiscussionThe survey demonstrated that ADHD had a negative impact on all aspects of childhood investigated, as recalled by adults.ConclusionsThese data provide insights into childhood impairments and identify areas for improvement in the management and treatment of ADHD.


2014 ◽  
Author(s):  
Soyeon Kim ◽  
Tobias Banaschewski ◽  
Rosemary Tannock

Background: Individuals with Attention-Deficit/Hyperactivity Disorder (ADHD) are reported to manifest visual problems (including ophthalmological and color perception problems, particularly for blue-yellow stimuli), but findings are inconsistent. Accordingly, this study investigated visual function and color perception in adolescents with ADHD using VEP. Method: Participants were 31 adolescents (aged 13-18); 16 with a confirmed diagnosis of ADHD, and 15 healthy peers, matched for age, gender, and IQ. All underwent ophthalmological exam, color vision testing (Mollon-Reffin Minimalist Colour Vision Test), as well as electrophysiological testing (color Visual Evoked Potentials; cVEP) which measured the latency and amplitude of the neural P1 response to chromatic stimuli (Blue-Yellow, Red-Green). Result: No group differences were found in clinical measure of color perception or opthalmological exam. However, significantly larger P1 amplitude was found for blue and yellow stimuli, but not red/green stimuli, in the ADHD group compared to controls. Discussion: Larger amplitude in the P1 component for blue-yellow in ADHD group compared to control group may account for no difference in colour perception task. Perhaps activating more resources in early sensory processing (P1) compensated for any underlying problems including compromised retinal input of s-cones due to hypo-dopaminergic tone.


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