Copper, Iron, and Manganese Toxicity in Neuropsychiatric Conditions

Abstract

Copper, manganese, and iron are vital elements required for the appropriate development and the general preservation of good health. Additionally, these essential metals play key roles in ensuring proper brain development and function. They also play vital roles in the central nervous system as significant cofactors for several enzymes, including the antioxidant enzyme superoxide dismutase (SOD) and other enzymes that take part in the creation and breakdown of neurotransmitters in the brain. An imbalance in the levels of these metals weakens the structural, regulatory, and catalytic roles of different enzymes, proteins, receptors, and transporters and is known to provoke the development of various neurological conditions through different mechanisms, such as via induction of oxidative stress, increased α-synuclein aggregation and fibril formation, and stimulation of microglial cells, thus resulting in inflammation and reduced production of metalloproteins. In the present review, the authors focus on neurological disorders with psychiatric signs associated with copper, iron, and manganese excess and the diagnosis and potential treatment of such disorders. In our review, we described diseases related to these metals, such as aceruloplasminaemia, neuroferritinopathy, pantothenate kinase-associated neurodegeneration (PKAN) and other very rare classical NBIA forms, manganism, attention-deficit/hyperactivity disorder (ADHD), ephedrone encephalopathy, HMNDYT1-SLC30A10 deficiency (HMNDYT1), HMNDYT2-SLC39A14 deficiency, CDG2N-SLC39A8 deficiency, hepatic encephalopathy, prion disease and “prion-like disease”, amyotrophic lateral sclerosis, Huntington’s disease, Friedreich’s ataxia, and depression.

Ferritin, transferrin, and transferrin receptor in relation to metabolic obesity phenotypes: Findings from the China Health and Nutrition Survey

“…People's hematological capacity and liver function deteriorated with age, which might lead to more ferritin release and transferrin inhibition (34). Cellular dystrophy, iron homeostasis dysregulation, and other factors due to aging may also play an important role in elevated ferritin and decreased transferrin (35,36).…”

A Review of the Association of Blue Food Coloring With Attention Deficit Hyperactivity Disorder Symptoms in Children

“…One of these other options is changing components of a child’s diet to see if there is a change in behavioral symptoms. Dietary elements that have been implicated in the symptom onset of ADHD include deficiencies in iron, copper, and manganese [ 8 ] fatty acids, and artificial food coloring. The growing interest in the role of diet in ADHD management has led to an increase in restriction diet studies, a type of study in which one component is removed from the participant’s diet and any resulting behavior change is noted.…”

Cognitive and Physical Intervention in Metals’ Dysfunction and Neurodegeneration

“…It has been found in ALS patients in the spinal cord, brainstem and motor cortex [21]. In all these neurodegenerational disorders, metal dyshomeostatis is proposed as a pathological pattern leading to neurodegeneration [5,19,24]. Iron and copper can induce oxidative stress and may stimulate DNA damage and the mitochondria and lipid membranes' impairment.…”

“…Manganism is characterized by different tremors and speech impediments and lethargy, with the occasional accompaniment of psychosis. Psychiatric symptoms are common signs in disorders with metal accumulation, and can also precede neurological signs or be the first sign of disease [24,52]. Intellectual impairment is recognized in PKAN, particularly in children with young onset.…”