Table 2.

Description and outcome of the included studies.

No.	Study Ref.	Author/Year	Disease	Aim	Sample used	Method of mtDNA-cn assessment	mtDNA gene	nDNA gene	Finding	Conclusion
1	Giulivi et al.(37)	Giulivi/2010	ASD	mtDNA-cn and deletions, and mitochondrial activity	White blood cells	qPCR	ND1, ND4	PK, APP	Higher mtDNA-cn and mtDNA deletions in ASD patients compared to controls; low NADH, low activity of complex I, high plasma pyruvate levels and lower pyruvate dehydrogenase activity; higher oxidative stress in ASD patients compared to controls	Mitochondrial dysfunction, mtDNA overreplication, and mtDNA deletions are more likely to occur in ASD have than typically developing children
2	Gu et al. (38)	Gu/2013	ASD	mtDNA-cn and mitochondrial activity	Frontal cortex tissue	qPCR	ND1, ND4, CYTB	PK	Higher mtDNA-cn in ASD patients than in controls; defects in complexes I, III and V, and reduced PDH activity in ASD patients compared to controls	Mitochondrial dysfunction in the brain is associated with ASD
3	Tang et al. (29)	Tang/2013	ASD	mtDNA-cn and mitochondrial activity	Temporal cortex tissue	qPCR	12S rRNA	RNAseP	No differences in either mtDNA-cn or levels of the mitochondrial gene transcription factor TFAM or cofactor PGC1α in ASD patients and controls; altered mitochondrial dynamics, protein levels of mitochondria respiratory chain protein complexes, decreased Complex I and IV activities; decreased mitochondrial antioxidant enzyme SOD2; and increased oxidative DNA damage and mitochondrial membrane mass in ASD patients	Mitochondrial dysfunction in early childhood ASD
4	Napoli et al. (39)	Napoli/2014	ASD	mtDNA-cn and deletions, and mitochondrial activity	White blood cells	qPCR	ND1, ND4	PK, APP	Higher oxidative stress in patients with autism; higher rates of mitochondrial ROS production; higher mtDNA-cn; and increased mtDNA deletions	Molecular network linking mitochondrial function, OXPHOS and the inflammation/immune response in ASD
5	Chen et al. (40)	Chen/2015	ASD	mtDNA-cn	Peripheral blood	qPCR	mtDNA primers (L39, H475)	HBB	Higher mtDNA-cn in ASD patients compared to controls; no significant correlations between mtDNA-cn and clinical features including paternal age, maternal age, age of onset, illness of duration, CARS score and ABC score in childhood autism	Elevated mtDNA-cn is associated with ASD, indicating mitochondrial dysfunction in children with autism
6	Yoo et al. (26)	Yoo/2016	ASD	mtDNA-cn	Peripheral blood	qPCR	ND1, ND4, CYTB	PK	Higher mtDNA-cn in ASD patients than in unaffected sibs; significant correlations between mtDNA-cn and clinical phenotypes for language and communication in ASD	Mitochondrial dysfunction and elevated mtDNA-cn in ASD are related to the phenotype for communication
7	Wong et al. (41)	Wong/2016	ASD	mtDNA-cn and deletions, and p53 gene copy ratios	Peripheral blood mononuclear cell	qPCR	ND1, CYTB	PK	Higher mtDNA-cn in ASD patients than in controls; higher incidence of mtDNA deletions in ASD patients and their fathers	Genome instability and altered mtDNA-cn in ASD
8	Valiente-Palleja et al. (27)	Valiente-Palleja`/2018	ASD	mtDNA-cn and mtDNA mutations	White blood cells		ND1, ND4	NP	Lower mtDNA-cn in ASD and ID patients than in controls; a total of 28.6% of ASD and 30.5% of ID subjects carried at least one putative pathogenic mtDNA mutation	Mitochondrial dysfunction in ASD and ID
9	Carrasco et al. (42)	Carrasco/2019	ASD	mtDNA-cn, oxidative stress, complexes, polymorphisms and gene expression of mitochondrial SOD2	Buccal cells	qPCR	tRNA-Leu	B2M	Higher mtDNA-cn in ASD compared to controls, enhanced ROS generation; significantly lower levels of respiratory complex I and decreased complex I and IV activities; presence of C47T polymorphism in SOD2 gene results in Ala16Val change could affect the transport of the SOD2 enzyme to the mitochondrial matrix and increases oxidative stress	Involvement of mitochondrial biology in the development of ASD
10	Kim et al. (43)	Kim/2019	ADHD	mtDNA-cn, methylation ratio of the D-loop region and PPARGC1A	Peripheral blood	qPCR	CYTB	PK	Higher mtDNA-cn in ADHD patients than in controls; decreased methylation ratio of PPARGC1A in ADHD	Mitochondrial dysfunction plays a role in the pathophysiology of ADHD
11	Singh et al. (28)	Singh/2019	ASD	mtDNA-cn and mitochondrial activity	Peripheral blood mononuclear cell	qPCR	ND4, CYTB	PK	Lower mtDNA-cn in ASD than in controls; higher maximal oxygen consumption rate, maximal respiratory capacity and reserve capacity in ASD and DR children than in ASD without DR; association of Coupling Efficiency and Maximal Respiratory Capacity with disruptive behaviors	Mitochondrial function is related to ASD symptoms and a potential mitochondrial therapeutic target in ASD
12	Öğütlü et al. (30)	Öğütlü/2020	ADHD	mtDNA-cn	Peripheral blood	qPCR	ND1	HBB	Higher mtDNA-cn in ADHD patients than in controls	Mitochondrial dysfunction is related to the etiopathogenesis of ADHD
13	Bam et al. (44)	Bam/2021	ASD	mtDNA-cn, DNA methylation of PGC-1α and mtDNA deletion	Buccal cells	qPCR	ND1	B2M	Higher mtDNA-cn in ASD patients than in control; methylation at the PGC-1α promoter can lead to mtDNA deletion and associated with high mtDNA-cn	Mitochondrial dysfunction in ASD
14	Öğütlü et al. (31)	Öğütlü/2021	ADHD	mtDNA-cn	Peripheral blood	qPCR	ND1	HBB	High mtDNA-cn in ADHD patients regardless of treatment	Mitochondrial dysfunction plays a role in pathophysiology of ADHD

ASD, autism spectrum disorder; ADHD, attention deficit hyperactivity disorder; mtDNA-cn, mitochondrial DNA copy number; qPCR, quantitative PCR; nDNA, nuclear DNA; ND1, NADH dehydrogenase 1; ND4, NADH dehydrogenase 4, CYTB, cytochrome b; HBB, beta-globin; PK; pyruvate kinase; APP, amyloid β A4 precursor protein; B2M, beta-2-microglobulin; NP, not provided.