Systematic review of mitochondrial genetic variation in attention-deficit/hyperactivity disorder

Giannoulis, Stavroula V; Müller, Daniel J.; Kennedy, James L.; Gonçalves, Vanessa F.

doi:10.1007/s00787-022-02030-6

Cited by 6 publications

(3 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondrial dysfunction contributes to a variety of neurodegenerative and neurodevelopmental disorders, including ADHD, suggesting that mitochondria are a promising therapeutic target (Li et al, 2017;Ogutlu et al, 2020;Giannoulis et al, 2022). Indeed, several recent studies have found that induction of mitochondrial biogenesis using PIO can mitigate abnormalities in various neurological disorder models (Miglio et al, 2009;Corona and Duchen, 2016;Li et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…These side effects may stem from the induction of oxidative stress and altered antioxidant enzyme activity (Martins et al, 2006;Gray et al, 2007;Gomes et al, 2008), potentially disrupting the activity of brain regions regulating psychological stress, cognition, appetite and motivation. While alterations in dopaminergic neurotransmission are strongly implicated in the pathophysiology of ADHD (Prince, 2008;Del Campo et al, 2011;Gold et al, 2014;Corona, 2018), there is accumulating evidence that mitochondrial dysfunction and oxidative stress also contribute (Verma et al, 2016;Corona, 2020;Ogutlu et al, 2020;Giannoulis et al, 2022). Therefore, improving mitochondrial metabolism and enhancing neural antioxidant capacity may be an effective adjunct therapeutic strategy for ADHD and other neurodevelopmental diseases.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pioglitazone enhances brain mitochondrial biogenesis and phase II detoxification capacity in neonatal rats with 6-OHDA-induced unilateral striatal lesions

Vázquez-González

Corona

2023

Front. Neurosci.

View full text Add to dashboard Cite

The psychostimulant methylphenidate (MPH) is the first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), but has numerous adverse side effects. The PPARγ receptor agonist pioglitazone (PIO) is known to improve mitochondrial bioenergetics and antioxidant capacity, both of which may be deficient in ADHD, suggesting utility as an adjunct therapy. Here, we assessed the effects of PIO on ADHD-like symptoms, mitochondrial biogenesis and antioxidant pathways in multiple brain regions of neonate rats with unilateral striatal lesions induced by 6-hydroxydopamine (6-OHDA) as an experimental ADHD model. Unilateral striatal injection of 6-OHDA reduced ipsilateral dopaminergic innervation by 33% and increased locomotor activity. This locomotor hyperactivity was not altered by PIO treatment for 14 days. However, PIO increased the expression of proteins contributing to mitochondrial biogenesis in the striatum, hippocampus, cerebellum and prefrontal cortex of 6-OHDA-lesioned rats. In addition, PIO treatment enhanced the expression of the phase II transcription factor Nrf2 in the striatum, prefrontal cortex and cerebellum. In contrast, no change in the antioxidant enzyme catalase was observed in any of the brain regions analyzed. Thus, PIO may improve mitochondrial biogenesis and phase 2 detoxification in the ADHD brain. Further studies are required to determine if different dose regimens can exert more comprehensive therapeutic effects against ADHD neuropathology and behavior.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pioglitazone enhances brain mitochondrial biogenesis and phase II detoxification capacity in neonatal rats with 6-OHDA-induced unilateral striatal lesions

Vázquez-González

Corona

2023

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Most genes that regulate mitochondrial functioning are encoded by nuclear DNA (nDNA). 42 The systematic review by Giannoulis et al 43 included a wide variety of studies, ranging from large sample genome-wide association studies to human-induced pluripotent stem cells (hiPSCs) and rat models, examining the relationship of nuclear mitochondrial genes with ADHD. By adding genes or proteins, hiPSCs are created from somatic cells by artificial reprogramming.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Dysfunction in Attention Deficit Hyperactivity Disorder

Öğütlü¹,

Kaşak²,

Tabur³

2023

Eurasian J Med

View full text Add to dashboard Cite

Attention deficit hyperactivity disorder is a neurodevelopmental disorder with primary symptoms of inattention, hyperactivity, and impulsivity, beginning in early childhood. Attention deficit hyperactivity disorder has a complex etiology based on neurobiological foundations, involving genetic, environmental, and biological factors in the early development process. The etiology of attention deficit hyperactivity disorder has not been completely clarified yet, but it has been suggested that increased oxidative stress is one of the possible common etiologies in attention deficit hyperactivity disorder. Oxidative stress can cause cellular damage, DNA repair system malfunction, and mitochondrial dysfunction. Mitochondrial dysfunction is thought to be a susceptibility factor in the development of psychiatric diseases. This article aims to review the research conducted to evaluate the possible relationship between attention deficit hyperactivity disorder and mitochondrial dysfunction and systematically examine the data obtained from these studies. Although studies considering the relationship between attention deficit hyperactivity disorder and mitochondrial dysfunction are less than those of autism spectrum disorder, schizophrenia, and mood disorders, studies on attention deficit hyperactivity disorder are increasing. A compensating system against mitochondrial dysfunction caused by hereditary and environmental factors may be generated by an increase in mitochondrial DNA copy number. Mitochondrial DNA copies may decrease with the reduction of attention deficit hyperactivity disorder severity and attention deficit in patients receiving treatment and may positively affect mitochondrial functions. The literature data of this review show that mitochondrial dysfunction could be a crucial factor in the pathophysiology of attention deficit hyperactivity disorder. Understanding mitochondrial contributions in the pathogenesis of attention deficit hyperactivity disorder may result in new diagnostic tools and the development of new therapeutic strategies for attention deficit hyperactivity disorder treatment.

show abstract

Neurodevelopmental Aspects of Behavioural Differences: I. Attention Deficit Hyperactivity Disorder (ADHD)

Stevenson

2023

Developmental Psychopathology

View full text Add to dashboard Cite

Systematic review of mitochondrial genetic variation in attention-deficit/hyperactivity disorder

Cited by 6 publications

References 59 publications

Pioglitazone enhances brain mitochondrial biogenesis and phase II detoxification capacity in neonatal rats with 6-OHDA-induced unilateral striatal lesions

Pioglitazone enhances brain mitochondrial biogenesis and phase II detoxification capacity in neonatal rats with 6-OHDA-induced unilateral striatal lesions

Mitochondrial Dysfunction in Attention Deficit Hyperactivity Disorder

Neurodevelopmental Aspects of Behavioural Differences: I. Attention Deficit Hyperactivity Disorder (ADHD)

Contact Info

Product

Resources

About