Biomarkers for High Metabolic Burden in Neurologic Disease

Neurologic diseases are recognized to have multifactorial origins well beyond mere genetic predisposition. Nutritional burdens have been identified to contribute to neurodegeneration. Healthy diets are becoming increasingly appreciated to potentially play key roles in both the developing and developed world of reducing incidences of neurologic diseases, while unhealthy diets are acknowledged to be contributing to their rise.

Biomarkers may have utility in diagnosing and treating, as well as in predicting and preventing, many neurologic diseases, such as bipolar disorder, major depressive disorder, and schizophrenia [1,2]. Biomarkers may be particularly useful when information on psychiatric symptoms is unavailable, as in underreporting, and for assessing intermediate treatment thresholds, as well as for evaluating uncertain diagnoses, such as typical in accurately identifying those presenting with symptoms of mania as a component of bipolar disorder [3,4].

Nutritional burdens

While we typically focus on the role of nutritional deficits contributing to neurologic diseases, excessive levels of substances, including respective nutrients, may be problematic as well. For instance, high levels of oleic acid, a type of omega-9 monounsaturated fatty acid (MUFA) that comprises about 80% of all MUFAs in blood plasma, may be associated with disorder pathogenesis as fatty acids can impact neurotransmission, neuroinflammation, and neuronal survival, thereby altering immune response regulation and metabolism, both of which have been implicated as risks for major depressive disorder and bipolar disorder [5]. Peripheral cholesterol levels, as linked to nutritionally-based conditions like diabetes [6] and obesity, have been associated with the risk of neurologic diseases such as Alzheimer’s [7] and Parkinson’s disease [8]. Overnutrition, generally, is recognized as contributing to cognitive impairment [9]. Alcohol consumption increases the risks of chronic diseases and mental health problems by escalating anxiety and depression, as well as suppressing immune system response [10,11], as does tobacco use [12,13] and exposure to secondhand and thirdhand tobacco smoke [14]. A better understanding of these sorts of associations can potentially lead to the use of new biomarkers to enhance preventive and therapeutic approaches. Biomarkers, like, for instance, sirtuin 1, are progressively becoming crucial to the prevention and treatment of neurodegenerative diseases [15]. Further, inter-professional healthcare team members should consider assessing high metabolic burdens, such as serum oleic acid levels, at least when clinically relevant in patients.

Lead toxicity

Lead toxicity has been speculated to have contributed to the fall of the Roman Empire. As lead has no physiological role in the human body its presence disrupts multiple enzyme systems, such as those involved in heme synthesis, like ferro-chelatase, and with antioxidants, like catalase, glutathione peroxide, and superoxide dismutase. Lead binds to calcium-activated proteins, which can cause abnormally high calcium levels impacting calcium-dependent functions, particularly the release of neurotransmitter substances as implicated in myriad psychiatric conditions. Lead also disrupts an array of cellular, intracellular, and molecular neurological functions [16], such as cortical synaptogenesis, dendrite density, myelin deposition, and synaptic pruning; all implicated in numerous neurologic diseases and generalized neurodegeneration, such as decreased volume of neurologic aspects like frontal and total gray matter, parietal white matter, and total brain volume [17]. Lead poisoning has traditionally been associated with neuromuscular motor neuropathy, such as results initially in weakness of wrist and finger extensions and then spreads to other muscular areas [18]. Lead levels have been associated with certain dietary habits, such as fish consumption [19,20].

More focused use of biomarkers of high metabolic burdens has potential to dramatically improve prevention and treatment of neurologic diseases, like major depressive disorder and bipolar depression [21]. There is also the additional benefit of such practices aiding in identifying and addressing associated comorbidities, such as diabetes mellitus and Alzheimer’s disease [22-24]. It is recognized that high metabolic burdens can result from multiple factors, including unhealthy lifestyles [25], lack of access to quality healthcare, and adverse pharmacological effects. Nevertheless, additional research that will enable wider utilization of biomarkers to prevent and treat neurologic diseases is highly encouraged and promises to be more valid and reliable than self-report and clinician-assessed evaluative approaches.

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