A study found a strong link between mitochondrial disorders and conditions like autism, ADHD, and various psychiatric issues.
Highlights:
- Common Link: Mitochondrial disorders are frequently found in people with autism, ADHD, and intellectual disabilities.
- ASD Emphasis: Most research focused on autism, suggesting it might be more strongly linked to mitochondrial issues or simply better funded.
- Psychiatric Impact: Mitochondrial problems are also connected to psychiatric conditions like schizophrenia, bipolar disorder, and depression.
- Research Gap: There is a lack of research on mitochondrial disorders beyond autism, indicating the need for broader studies.
- Mechanism: Mitochondrial dysfunction affects energy production in cells, which can lead to various neurodevelopmental and psychiatric disorders.
Source: Frontiers in Psychiatry (2024)
Major Findings: Mitochondrial Disorders in Neurodevelopmental Conditions (2024)
1. Prevalence of Mitochondrial Disorders in Neurodevelopmental Conditions
Mitochondrial disorders are found in about 1 in 5,000 people.
These disorders are particularly common in individuals with neurodevelopmental conditions such as autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and intellectual disabilities.
Mitochondrial dysfunction impacts high-energy demand tissues, including the brain, leading to these conditions.
2. Focus on Autism Spectrum Disorder (ASD)
The majority of the studies reviewed (100 out of 139) focused on the connection between mitochondrial dysfunction and ASD.
This strong focus suggests either a stronger correlation between ASD and mitochondrial issues or more research funding being directed towards studying ASD.
Children with ASD frequently have comorbid mitochondrial dysfunction, impacting their energy metabolism and contributing to the severity of their symptoms.
3. Connection to Psychiatric Disorders
Mitochondrial dysfunction is also linked to several psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder (MDD).
For instance, studies have found mitochondrial abnormalities, such as swelling and dysfunctional energy production, in individuals with schizophrenia.
In bipolar disorder, research has uncovered significant differences in mitochondrial size and distribution in the brain, alongside evidence of increased oxidative stress and altered energy production processes.
4. Lack of Research on Mitochondrial Dysfunction in Psychiatry
There is a noticeable lack of studies exploring the connection between mitochondrial dysfunction and conditions beyond ASD.
The limited research on other neurodevelopmental and psychiatric disorders suggests a need for broader investigation to understand the full impact of mitochondrial dysfunction on these conditions.
5. Mechanism of Mitochondrial Dysfunction
Mitochondrial dysfunction impairs the production of ATP, the cell’s energy currency, leading to energy deficits.
High-energy tissues like the brain are particularly affected, which can result in neurodevelopmental and psychiatric disorders.
Oxidative stress, caused by mitochondrial dysfunction, damages cells and contributes to the development and progression of these disorders.
Study Overview: Mitochondrial Disorders vs. Neurodevelopmental Disorders (2024)
The study aimed to investigate the connection between mitochondrial disorders and neurodevelopmental disorders (NDDs) and psychiatric/behavioral conditions through a comprehensive review of existing literature.
Sample
- The study reviewed 277 publications from databases including PubMed/MEDLINE, Scopus, and Cochrane Library.
- After removing duplicates and applying inclusion/exclusion criteria, 139 publications were included in the analysis.
Methods
- A systematic review of literature was conducted using specific search terms related to mitochondrial diseases, neurodevelopmental disorders, and behavioral/psychiatric conditions.
- Databases searched included PubMed/MEDLINE, Scopus, and Cochrane Library, up to November 2022.
- Inclusion criteria: Full-text articles in English, human subjects, and relevant cell studies.
- Exclusion criteria: Articles without full text, non-English articles, and animal studies.
- Publications were categorized based on type (e.g., review articles, case reports, clinical trials) and whether they mentioned neurodevelopmental or psychiatric/behavioral disorders.
Limitations
- Diagnostic Challenges: Diagnosing mitochondrial disorders is complex due to heterogeneous presentations and multiorgan system involvement.
- Research Bias: A significant portion of the reviewed literature focused on ASD, potentially due to more research funding and interest, leading to a research bias.
- Lack of Standardization: Variability in diagnostic criteria and research methodologies across studies complicates the comparison and synthesis of findings.
- Limited Research Beyond ASD: There is a noticeable gap in research on mitochondrial dysfunction in conditions other than ASD, indicating a need for broader studies.
Potential Reasons Mitochondrial Disorders & Neurodevelopmental Disorders Linked
Energy Deficits in High-Demand Tissues
Mitochondria are crucial for producing ATP, the main energy source for cells.
Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often affect the brain, which requires a significant amount of energy.
Mitochondrial dysfunction can lead to energy deficits in these high-demand tissues, impairing brain development and function, contributing to NDDs.
Oxidative Stress & Cellular Damage
Mitochondria are involved in managing reactive oxygen species (ROS).
When mitochondrial function is compromised, ROS can accumulate, causing oxidative stress and damaging cellular components like DNA, proteins, and lipids.
This oxidative damage can disrupt normal brain development and function, potentially leading to neurodevelopmental disorders.
Shared Genetic Architecture
Both mitochondrial disorders and NDDs can have a genetic basis.
Mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) affecting mitochondrial function can be inherited and may predispose individuals to both mitochondrial disorders and NDDs.
Some studies have found specific genetic variants and single nucleotide polymorphisms (SNPs) in mtDNA that are associated with both mitochondrial dysfunction and conditions like ASD.
Neuroinflammation
Mitochondrial dysfunction can trigger neuroinflammation, which has been implicated in the pathology of various neurodevelopmental disorders.
Chronic inflammation in the brain can disrupt normal neuronal signaling and connectivity, contributing to the symptoms of NDDs.
Disrupted Calcium Homeostasis
Mitochondria play a key role in regulating calcium levels within cells.
Disruption of calcium homeostasis due to mitochondrial dysfunction can affect neuronal activity and synaptic function, which are critical for brain development and cognitive processes.
Impact on Neurotransmitter Synthesis
Mitochondria are involved in the synthesis of neurotransmitters, which are essential for communication between neurons.
Mitochondrial dysfunction can impair the production of neurotransmitters, leading to imbalances that are often seen in neurodevelopmental disorders like ADHD and ASD.
Conclusion: Mitochondrial Disorders & Neurodevelopmental Disorders Linked
The study highlights a significant link between mitochondrial disorders and neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).
Mitochondrial dysfunction, through mechanisms like energy deficits, oxidative stress, and disrupted neurotransmitter synthesis, appears to play a crucial role in the development and progression of these conditions.
The strong focus on ASD in the reviewed literature suggests either a stronger correlation or more research funding directed towards this condition, but also reveals a gap in research on other NDDs and psychiatric disorders.
Understanding the shared genetic architecture and underlying mechanisms can provide valuable insights into potential therapeutic targets.
Further research is needed to explore the full impact of mitochondrial dysfunction on a broader range of neurodevelopmental and psychiatric conditions, paving the way for more comprehensive diagnostic and treatment approaches.
References
- Study: A systematic review on the role of mitochondrial dysfunction/disorders in neurodevelopmental disorders and psychiatric/behavioral disorders (2024)
- Authors: Daniela V Pinto Payares
