In this manuscript, we highlight the evolutionary origins of mitochondria from bacterial endosymbionts and explore their contributions to health, energy metabolism, and neural-immune communication. Mitochondrial adaptability and the roles played by these organelles in promoting oxygen-dependent ATP production provide critical regulation of cognition, motivation, and inflammation. Hypoxia has been identified as an important initiator of inflammation, neurodegeneration, and mitochondrial dysfunction, emphasizing the overall importance of oxygen homeostasis to health and well-being. The Behavior, Exercise, Relaxation, and Nutrition framework highlights these observations as tools that can be used to optimize mitochondrial efficiency. Interestingly, mitochondrial dysfunction may also be linked to psychiatric disorders (e.g., schizophrenia), a hypothesis that focuses on energy dynamics, a proposal that may extend our understanding of these disorders beyond traditional neurotransmitter-focused concepts. Collectively, these perspectives underscore the critical contributions of mitochondria to health and disease and offer a novel framework that may help to explain the connections featured in mind-body medicine.

• Keywords
• BERN, CNS pathways and networks, evolution, hypoxia, mind–body medicine, mitochondria, motivation,
• MeSH
• Biological Evolution MeSH
• Pain * metabolism   physiopathology   MeSH
• Exercise * physiology   MeSH
• Energy Metabolism * MeSH
• Cognition * physiology   MeSH
• Humans MeSH
• Mitochondria metabolism   MeSH
• Motivation * MeSH
• Pleasure * physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Background: Mind-body medicine (MBM) focuses on improving our understanding of how the interactions between the brain, mind, body, and behavior can be used to promote health. In this narrative review, we present the basic principles of MBM, including the introduction of a rational framework for the implementation of MBM-based interventions. We also discuss the contributions of MBM to motivation and reward systems in the brain including those that may specifically involve the mitochondria. Results: MBM can be used to promote health in patients with chronic diseases, especially conditions identified as lifestyle-related. MBM builds on salutogenesis, which is a paradigm that focuses on health (as opposed to disease) determinants and the development of individual resilience and coherence factors as a means to reduce stress, decrease the burden of disease, and improve the quality of life. This approach involves several well-known principles of self-healing and self-care. MBM interventions typically include behavioral modification techniques in conjunction with cognitive work focused on stress regulation, exercise, relaxation, meditation, and nutrition. We suggest the use of the acronym "BERN" (Behavior, Exercise, Relaxation, and Nutrition) to summarize the operational framework of this approach. Discussion: Different BERN techniques act via shared autoregulatory central nervous system (CNS) reward and motivation circuitries. These systems rely on numerous neurobiological signaling pathways with overlapping effector molecules that converge, e.g., on nitric oxide (NO) as a common effector molecule. NO is critically coupled to reward physiology, stress reduction, and self-regulation as it modulates the responses of various mitochondrial, nuclear, and chromosomal processes within brain cells. NO has also been implicated in relevant outcomes (e.g., the placebo response). Conclusions: MBM interventions typically follow the BERN model and aim to strengthen health and resilience, and reduce stress. The mechanisms of action of these processes involve the CNS reward systems and correlate with placebo and self-healing pathways.

• Keywords
• behavioral medicine, integrative medicine, meditation, mitochondria, placebo, salutogenesis, self-healing, stress management,
• Publication type
• Journal Article MeSH
• Review MeSH

Mitochondria are complex endosymbionts that evolved from primordial purple nonsulfur bacteria. The incorporation of bacteria-derived mitochondria facilitates a more efficient and effective production of energy than what could be achieved based on previous processes alone. In this case, endosymbiosis has resulted in the seamless coupling of cytochrome c oxidase and F-ATPase to maximize energy production. However, this mechanism also results in the generation of reactive oxygen species (ROS), a phenomenon that can have both positive and negative ramifications on the host. Recent studies have revealed that neuropsychiatric disorders have a pro-inflammatory component in which ROS is capable of initiating damage and cognitive malfunction. Our current understanding of cognition suggests that it is the product of a neuronal network that consumes a substantial amount of energy. Thus, alterations or perturbations of mitochondrial function may alter not only brain energy supply and metabolite generation, but also thought processes and behavior. Mitochondrial abnormalities and oxidative stress have been implicated in several well-known psychiatric disorders, including schizophrenia (SCZ) and bipolar disorder (BPD). As cognition is highly energy-dependent, we propose that the neuronal pathways underlying maladaptive cognitive processing and psychiatric symptoms are most likely dependent on mitochondrial function, and thus involve brain energy translocation and the accumulation of the byproducts of oxidative stress. We also hypothesize that neuropsychiatric symptoms (e.g., disrupted emotional processing) may represent the vestiges of an ancient masked evolutionary response that can be used by both hosts and pathogens to promote self-repair and proliferation via parasitic and/or symbiotic pathways.

• Keywords
• HIV-1, SARS-CoV-2, bipolar disorder, depression, mitochondria, reactive nitrogen species, reactive oxygen species, schizophrenia,
• Publication type
• Journal Article MeSH
• Review MeSH

Persistent comorbidities occur in patients who initially recover from acute coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 'Long COVID' involves the central nervous system (CNS), resulting in neuropsychiatric symptoms and signs, including cognitive impairment or 'brain fog' and chronic fatigue syndrome. There are similarities in these persistent complications between SARS-CoV-2 and the Ebola, Zika, and influenza A viruses. Normal CNS neuronal mitochondrial function requires high oxygen levels for oxidative phosphorylation and ATP production. Recent studies have shown that the SARS-CoV-2 virus can hijack mitochondrial function. Persistent changes in cognitive functioning have also been reported with other viral infections. SARS-CoV-2 infection may result in long-term effects on immune processes within the CNS by causing microglial dysfunction. This short opinion aims to discuss the hypothesis that the pathogenesis of long-term neuropsychiatric COVID-19 involves microglia, mitochondria, and persistent neuroinflammation.

• MeSH
• Central Nervous System pathology   MeSH
• COVID-19 complications   pathology   MeSH
• Cognitive Dysfunction etiology   pathology   MeSH
• Humans MeSH
• Microglia pathology   MeSH
• Mitochondria pathology   MeSH
• Neurons pathology   MeSH
• SARS-CoV-2 MeSH
• Inflammation pathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Editorial MeSH

Alterations in brain functioning, especially in regions associated with cognition, can result from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and are predicted to result in various psychiatric diseases. Recent studies have shown that SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) can directly or indirectly affect the central nervous system (CNS). Therefore, diseases associated with sequelae of COVID-19, or 'long COVID', also include serious long-term mental and cognitive changes, including the condition recently termed 'brain fog'. Hypoxia in the microenvironment of select brain areas may benefit the reproductive capacity of the virus. It is possible that in areas of cerebral hypoxia, neuronal cell energy metabolism may become compromised after integration of the viral genome, resulting in mitochondrial dysfunction. Because of their need for constant high metabolism, cerebral tissues require an immediate and constant supply of oxygen. In hypoxic conditions, neurons with the highest oxygen demand become dysfunctional. The resulting cognitive impairment benefits viral spread, as infected individuals exhibit behaviors that reduce protection against infection. The effects of compromised mitochondrial function may also be an evolutionary advantage for SARS-CoV-2 in terms of host interaction. A high viral load in patients with COVID-19 that involves the CNS results in the compromise of neurons with high-level energy metabolism. Therefore, we propose that selective neuronal mitochondrial targeting in SARS-CoV-2 infection affects cognitive processes to induce 'brain fog' and results in behavioral changes that favor viral propagation. Cognitive changes associated with COVID-19 will have increasing significance for patient diagnosis, prognosis, and long-term care.

• MeSH
• COVID-19 complications   metabolism   physiopathology   psychology   transmission   MeSH
• Energy Metabolism MeSH
• Cognitive Dysfunction metabolism   physiopathology   psychology   MeSH
• Humans MeSH
• Microbial Viability MeSH
• Mitochondria metabolism   MeSH
• Hypoxia, Brain metabolism   physiopathology   psychology   MeSH
• Neurons metabolism   MeSH
• Post-Acute COVID-19 Syndrome MeSH
• Virus Replication MeSH
• SARS-CoV-2 physiology   MeSH
• Viral Load MeSH
• Health Behavior * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Editorial MeSH

Current critical thinking has displaced the elaborated beta amyloid theory as the underlying unitary mechanism of Alzheimer disease (AD) in favor of concerted, long-term disruption or dysregulation of broad-based physiological processes. We present a critical discussion in which a chronic state of systemic proinflammation sustained over the course of several decades and engendered by ongoing metabolic or autoimmune disease is predicted to promote severe disruptions of central neurological processes. Specifically, long-term functional rundown of microglial-mediated phagocytic activity in concert with aberrant expression and cellular deposition of beta amyloid and tau protein facilitates formation of senile plaques and neurofibrillary tangles. Within this functional context, we hypothesize that early initiation events in the pathophysiology of AD may operationally involve a convergence of dysregulated peripheral and central constitutive nitric oxide signaling pathways resulting from a chronic state of systemic proinflammation and leading to severely dysfunctional "hyperactivated" microglia.

• MeSH
• Alzheimer Disease * metabolism   pathology   physiopathology   MeSH
• Humans MeSH
• Microglia * metabolism   pathology   MeSH
• Nitric Oxide metabolism   MeSH
• Signal Transduction * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Editorial MeSH
• Names of Substances
• Nitric Oxide MeSH