Affective-cognitive-behavioral heterogeneity of Attention-Deficit/Hyperactivity Disorder (ADHD): Emotional dysregulation as a sentinel symptom differentiating “ADHD-simplex” and “ADHD-complex” syndromes?

Yue, Xinxin; Liu, Lu; Chen, Wai; Preece, David A.; Liu, Qianrong; Li, Haimei; Wang, Yufeng; Qian, Qiujin

doi:10.1016/j.jad.2022.03.065

Cited by 11 publications

(5 citation statements)

References 39 publications

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“…We found that perinatal lesions increased pain sensitivity to thermal and mechanical stimulus in two-month-old female but not male mice. Although sensory over-responsiveness [67,68] and emotional alterations [69,70] are often found in ADHD children, altered pain sensitivity has been reported mostly in women [33]. Other clinical studies have shown evidence of an association between higher pain sensitivity and ADHD in boys [71] and adults with ADHD [35,36,72].…”

Section: Discussionmentioning

confidence: 99%

Targeting Neuroinflammation with Abscisic Acid Reduces Pain Sensitivity in Females and Hyperactivity in Males of an ADHD Mice Model

Meseguer-Beltrán

Sánchez-Sarasúa

Landry

et al. 2023

Cells

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Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental syndrome characterized by dopaminergic dysfunction. In this study, we aimed to demonstrate that there is a link between dopaminergic deficit and neuroinflammation that underlies ADHD symptoms. We used a validated ADHD mice model involving perinatal 6-OHDA lesions. The animals received abscisic acid (ABA), an anti-inflammatory phytohormone, at a concentration of 20 mg/L (drinking water) for one month. We tested a battery of behavior tests, learning and memory, anxiety, social interactions, and pain thresholds in female and male mice (control and lesioned, with or without ABA treatment). Postmortem, we analyzed microglia morphology and Ape1 expression in specific brain areas related to the descending pain inhibitory pathway. In females, the dopaminergic deficit increased pain sensitivity but not hyperactivity. In contrast, males displayed hyperactivity but showed no increased pain sensitivity. In females, pain sensitivity was associated with inflammatory microglia and lower Ape1 levels in the anterior cingulate cortex (ACC) and posterior insula cortex (IC). In addition, ABA treatment alleviated pain sensitivity concomitant with reduced inflammation and normalized APE1. In males, ABA reduced hyperactivity but had no significant effect on inflammation in these areas. This is the first study proving a sex-dependent association between dopamine dysfunction and inflammation in specific brain areas, hence leading to different behavioral outcomes in a mouse model of ADHD. These findings provide new clues for potential treatments for ADHD.

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Section: Discussionmentioning

confidence: 99%

Targeting Neuroinflammation with Abscisic Acid Reduces Pain Sensitivity in Females and Hyperactivity in Males of an ADHD Mice Model

Meseguer-Beltrán

Sánchez-Sarasúa

Landry

et al. 2023

Cells

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“…Emotional dysregulation or sensory over-responsiveness is often found in ADHD children [67], [68]. These features can be used as predictors of ADHD and other psychiatric disorders [69].…”

Section: Discussionmentioning

confidence: 99%

Targeting neuroinflammation with Abscisic Acid reduces pain sensitivity in females and hyperactivity in males of an ADHD mice model

Meseguer-Beltrán

Sánchez-Sarasúa

Landry

et al. 2022

Preprint

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Aims: Attention deficit/ hyperactivity disorder (ADHD) is a neurodevelopmental syndrome characterized by dopaminergic dysfunction. In this study, we aimed to demonstrate the link between dopaminergic deficit and neuroinflammation underlying ADHD symptoms. Subjects and Treatment: We used a validated ADHD mice model, that involves perinatal 6-OHDA lesion. Animals were treated with 20mg/L (drinking water) of Abscisic acid (ABA) for one month. We tested behaviour (learning and memory, anxiety, social interactions, and pain) in both females and male mice, in all eight groups (control and lesioned, with/without ABA). Postmortem, we analyzed microglia morphology and Ape1 expression in specific brain areas related to the descending pain inhibitory pathway. Results: In females, dopaminergic deficit increased pain sensitivity, but not hyperactivity, in contrast to males. This behaviour was associated with inflammatory microglia and lower Ape1 levels in the anterior cingulate cortex (ACC) and posterior insula cortex (IC). ABA treatment reduced inflammation and alleviated pain. In males, ABA reduced hyperactivity, but had no significant effect on inflammation. Conclusions: This is the first study proving a sex-dependent association between dopamine dysfunction and inflammation in specific brain areas, leading to different behavior outcomes in a mouse model of ADHD. These findings provide new clues for potential treatments.

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“…Second, we only included 18 items of ADHD symptoms in our analyses based on the current DSM-5 criteria. In addition to the inattentive, hyperactive and impulsive domains, other important features such as emotion dysregulation, internalizing and externalizing symptoms are potential informative candidates for inclusion in the future analyses, given emotion dysregulation symptoms have been proposed to be a core component of ADHD symptoms (42), or sentinel features demarcating ADHD "complex" and "simplex" subtypes (43). Third, certain comorbidities were not excluded in our present study, and the extents to which existing common comorbidities may influence the network patterns or vice versus were adjusted as covariates in our analyses.…”

Section: Discussionmentioning

confidence: 99%

Network analysis of 18 attention-deficit/hyperactivity disorder symptoms suggests the importance of “Distracted” and “Fidget” as central symptoms: Invariance across age, gender, and subtype presentations

et al. 2022

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The network theory of mental disorders conceptualizes psychiatric symptoms as networks of symptoms that causally interact with each other. Our present study aimed to explore the symptomatic structure in children with attention-deficit/hyperactivity disorder (ADHD) using network analyses. Symptom network based on 18 items of ADHD Rating Scale-IV was evaluated in 4,033 children and adolescents with ADHD. The importance of nodes was evaluated quantitatively by examining centrality indices, including Strength, Betweenness and Closeness, as well as Predictability and Expected Influence (EI). In addition, we compared the network structure across different subgroups, as characterized by ADHD subtypes, gender and age groups to evaluate its invariance. A three-factor-community structure was identified including inattentive, hyperactive and impulsive clusters. For the centrality indices, the nodes of “Distracted” and “Fidget” showed high closeness and betweenness, and represented a bridge linking the inattentive and hyperactive/impulsive domains. “Details” and “Fidget” were the most common endorsed symptoms in inattentive and hyperactive/impulsive domains respectively. On the contrary, the “Listen” item formed a peripheral node showing weak links with all other items within the inattentive cluster, and the “Loss” item as the least central node by all measures of centrality and with low predictability value. The network structure was relatively invariant across gender, age and ADHD subtypes/presentations. The 18 items of ADHD core symptoms appear not equivalent and interchangeable. “Distracted” and “Fidget” should be considered as central, or core, symptoms for further evaluation and intervention. The network-informed differentiation of these symptoms has the potentials to refine the phenotype and reduce heterogeneity.

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Affective-cognitive-behavioral heterogeneity of Attention-Deficit/Hyperactivity Disorder (ADHD): Emotional dysregulation as a sentinel symptom differentiating “ADHD-simplex” and “ADHD-complex” syndromes?

Cited by 11 publications

References 39 publications

Targeting Neuroinflammation with Abscisic Acid Reduces Pain Sensitivity in Females and Hyperactivity in Males of an ADHD Mice Model

Targeting Neuroinflammation with Abscisic Acid Reduces Pain Sensitivity in Females and Hyperactivity in Males of an ADHD Mice Model

Targeting neuroinflammation with Abscisic Acid reduces pain sensitivity in females and hyperactivity in males of an ADHD mice model

Network analysis of 18 attention-deficit/hyperactivity disorder symptoms suggests the importance of “Distracted” and “Fidget” as central symptoms: Invariance across age, gender, and subtype presentations

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