Papers by George Anderson
The role of melatonin in post-partum psychosis and depression associated with bipolar disorder
Journal of Perinatal Medicine, 2010
Recent data has highlighted the association of a bipolar disorder (BD) with an increased risk of ... more Recent data has highlighted the association of a bipolar disorder (BD) with an increased risk of post-partum psychosis and depression. It is suggested that genetic- and environmental-induced decrease in the levels of melatonin in BD contributes to post-partum disorders. Melatonin may also have some efficacy in the treatment of BD, especially in decreasing the side-effects associated with lithium and the neuroleptics. It is proposed that the optimization of melatonin levels, perhaps in conjunction with optimized vitamin D3 level, would decrease post-partum psychosis and depression associated with BD.
Melatonin research, Dec 15, 2019
This article reviews the recent proposed model of Reiter and colleagues in this journal on the ro... more This article reviews the recent proposed model of Reiter and colleagues in this journal on the role of circadian, pineal gland-derived melatonin in driving mitochondria melatonin production in the pathoetiology and pathophysiology of breast cancers. This uptake of melatonin is proposed to inhibit pyruvate dehydrogenase kinase, thereby increasing the production of acetyl-CoA from pyruvate, with acetyl-CoA being a necessary co-factor for the initiation of the melatonergic pathway within mitochondria. Consequently, this proposed model suggests that a circadian shift in metabolic regulation occurs in breast cancers, from daytime cytosolic glycolysis to a night-time, melatonin-driven mitochondria oxidative phosphorylation, with relevance to the early pathoetiology of breast cancers. This has a number of consequences and links well to wider breast cancer data showing a pathophysiological role for the aryl hydrocarbon receptor, cytochrome P450 (CYP)1B1, 14-3-3 protein, and microRNAs. The current article overviews such data in the context of pineal gland-derived melatonin's circadian regulation of the mitochondria melatonergic pathways in breast cancer cells as proposed by Reiter and colleagues, suggesting that daytime, wake promoting orexin and stress-induced gut dysregulation contribute to mitochondria dysfunction in wider breast cancer symptomatology.
Düşünen adam psikiyatri ve nörolojik bilimler dergisi, 2020
Why Do Anti-Amyloid Beta Antibodies not work? Time to reconceptualize Dementia Pathophysiology by incorporating astrocyte melatonergic pathway desynchronization from amyloid-beta production
Revista Brasileira de Psiquiatria, 2022
Melatonin research, Jun 15, 2020
As data emerges on the pathophysiological underpinnings of severe acute respiratory syndrome coro... more As data emerges on the pathophysiological underpinnings of severe acute respiratory syndrome coronavirus (SARS-CoV)-2, it is clear that there are considerable variations in its susceptibility and severity/fatality, which give indications as to its pathophysiology and treatment. SARS-CoV-2 modulatory factors include age, vitamin D levels, cigarette smoking, gender and ethnicity as well as premorbid medical conditions, including diabetes, cancer, obesity, cardiovascular disease, and immune-compromised conditions. A complex picture is emerging, with an array of systemic physiological processes interacting including circadian, immune, intestinal, CNS and coagulation factors. This article reviews data on SARS-CoV-2 pathoetiology and pathophysiology. It is proposed that a decrease in pineal and systemic melatonin is an important driver of SARS-CoV-2 susceptibility and severity, with the loss of pineal melatonin's induction of the alpha 7 nicotinic acetylcholine receptor (α7nAChR) in pulmonary epithelial cells and immune cells being a powerful regulator of susceptibility and severity, respectively. Stress, including discrimination stress, and decreased vitamin D also regulate SARS-CoV-2, including via gut dysbiosis and permeability, with a resultant decrease in the short-chain fatty acid, butyrate, and increase in circulating lipopolysaccharide. Stress and cytokine induction of the kynurenine pathways, leads to aryl hydrocarbon receptor activation, which primes platelets for heightened activity, coagulation and thrombin production, thereby driving elevations in thrombin that underpin many SARS-CoV-2 fatalities. On the basis of these pathophysiological changes, prophylactic and symptomatic treatments are proposed, including the use of melatonin and α7nAChR agonism.
Disrupted nocturnal melatonin in autism: Association with tumor necrosis factor and sleep disturbances
Journal of Pineal Research, 2021
Sleep disturbances, abnormal melatonin secretion, and increased inflammation are aspects of autis... more Sleep disturbances, abnormal melatonin secretion, and increased inflammation are aspects of autism spectrum disorder (ASD) pathophysiology. The present study evaluated the daily urinary 6‐sulfatoxymelatonin (aMT6s) excretion profile and the salivary levels of tumor necrosis factor (TNF) and interleukin‐6 (IL‐6) in 20 controls and 20 ASD participants, as well as correlating these measures with sleep disturbances. Although 60% of ASD participants showed a significant night‐time rise in aMT6s excretion, this rise was significantly attenuated, compared to controls (P < .05). The remaining 40% of ASD individuals showed no significant increase in nocturnal aMT6s. ASD individuals showed higher nocturnal levels of saliva TNF, but not IL‐6. Dysfunction in the initiation and maintenance of sleep, as indicated by the Sleep Disturbance Scale for Children, correlated with night‐time aMT6s excretion (r = −.28, P < .05). Dysfunction in sleep breathing was inversely correlated with aMT6s (r =...
J. Neuroinflammation, 2012
Background: Emergent seizures are common in Alzheimer’s disease (AD) in both humans and animal mo... more Background: Emergent seizures are common in Alzheimer’s disease (AD) in both humans and animal models [1,2], although the mechanisms mediating this are unknown. It seems that about 1.5% to 10% of AD patients experience seizure activity, with the highest prevalence in early onset AD [3]. This raises the question as to whether there is a subtype of AD that is seizure associated and may be linked to differential changes and possibly to differential treatment. Induction of kynurenine pathway member indoleamine 2,3-dioxygenase (IDO) in the brain can lead subsequent quinolinic acid (QA) production (Fig. 1). QA mediates neuronal excitotoxicity via the N-methyl-D-aspartate receptor (NMDAr) [6] and thus is a possible mediator of both seizures and neuronal loss [4,5]. IDO is induced at least by interferon-γ (IFNγ), but other inflammatory factors may also contribute to its increase [7,8]. One such factor is Interleukin-18 (IL-18; former IFNγ inducing factor IGIF, IL-1γ). IL-18 is induced by st...
Psychotherapy and psychosomatics, 2012
ABSTRACT No abstract available.
The role of melatonin in post-partum psychosis and depression associated with bipolar disorder
Journal of Perinatal Medicine, 2010
Recent data has highlighted the association of a bipolar disorder (BD) with an increased risk of ... more Recent data has highlighted the association of a bipolar disorder (BD) with an increased risk of post-partum psychosis and depression. It is suggested that genetic- and environmental-induced decrease in the levels of melatonin in BD contributes to post-partum disorders. Melatonin may also have some efficacy in the treatment of BD, especially in decreasing the side-effects associated with lithium and the neuroleptics. It is proposed that the optimization of melatonin levels, perhaps in conjunction with optimized vitamin D3 level, would decrease post-partum psychosis and depression associated with BD.
Prenatal Corticosteroids: Pretermer Outcomes, Stress, Schizophrenia, Multiple Sclerosis and the Developmental Role of Melatonin and Vitamin D3
Journal of Pediatric and Adolescent Gynecology, 2010
Cortisol has a long history of use in women at risk of having a preterm birth, and has proven val... more Cortisol has a long history of use in women at risk of having a preterm birth, and has proven value in lung maturation [1]. This seems crucial to increase the likelihood of survival of pretermers [2]. However, a number of side-effects are known to arise from such ante-natal corticosteroids. These include an increase in the levels of blood pressure in childhood [3] and adulthood [4], with an increased risk of later hypertension and associated disorders. Prenatal corticosteroids are also associated with a decrease in the levels of I.Q. [5] and some wider cognitive deficits [6]. Data also suggests changes in the levels of emotional reactivity, linking to an increased risk of psychiatric classification and perhaps in drug abuse [7, 8].
Melatonin Research, 2019
Two important hubs have emerged as cutting edge areas of research across a diverse array of medic... more Two important hubs have emerged as cutting edge areas of research across a diverse array of medical conditions, the gut microbiome and mitochondria. This article highlights the role of melatonin in modulating changes in both the gut and mitochondria. The gut microbiome, especially via its production of the small chain fatty acid, butyate, can have a significant impact on immune inflammatory processes. Lower levels of butyrate producing bacteria can increase gut permeability, thereby increasing immune-inflammatory activity. Butyrate may also modulate immune and other cells via the regulation of the content of exosomes from intestinal epithelial cells. Butyrate also induces N-acetylserotonin and melatonin synthesis in the gut, suggesting that some of the effects of butyrate may be mediated via its induction of the melatonergic pathway. The induction of melatonin by butyrate may feed back on the microbiome via melatonin increasing gut bacteria swarming, as well as melatonin optimizing ...
Academia Biology, Jan 29, 2026
There is a growing frustration regarding the lack of progress in the prevention and treatment of ... more There is a growing frustration regarding the lack of progress in the prevention and treatment of Parkinson’s disease (PD). This article reviews wide bodies of data on PD pathophysiology and proposes that this lack of progress arises from a failure to investigate the role of the mitochondrial melatonergic pathway in enteric glial cells (PD pathogenesis) and astrocytes (PD ongoing pathophysiology). Recent work indicates that the melatonergic pathway is powerfully regulated by the interactions of canonical (nuclear translocating) and noncanonical (mitochondria translocating) STAT3 with NF-κB dimer composition. As both STAT3 and NF-κB have been extensively investigated in PD and shown to have significant etiological and pathophysiological importance, the incorporation of their interactions in the regulation of enteric glial cell and astrocyte melatonergic pathway provides a novel conceptualization of PD etiology and pathophysiology. Incorporating the mitochondrial melatonergic pathway in enteric glial cells and astrocytes has significant future research and treatment implications and better integrates wider bodies of data linked to PD, including the effects of type 2 diabetes; methylglyoxal; and why PD susceptibility is associated with a wide array of diverse medical conditions, including autism, bipolar disorder, schizophrenia, and depression. The suppression of the enteric glial cell melatonergic pathway is proposed to attenuate trophic support for enteroendocrine cells, thereby initiating α-synuclein upregulation in enteroendocrine cells and wider gut cells, which is transported via the vagal nerve to the CNS. Gut α-synuclein and/or mitochondrial antigens are proposed to prime CD8+ t cells for substantia nigra pars compacta (SNpc) dopamine neuron elimination. Suppression of the enteric glial cell melatonergic pathway also prevents vagal nerve stimulation from dampening gut inflammatory activity, which requires local gut melatonin production. Within the CNS, maintained astrocyte reactivity is associated with an attenuated capacity to upregulate the melatonergic pathway, which is proposed to arise from altered STAT3 phosphorylation interacting with NF-κB dimer composition. Reactive astrocytes expressing CD44 are proposed to guide gut-primed CD8+ t cells to eliminate SNpc dopamine neurons. The investigation of the astrocyte and enteric glial cell melatonergic pathway is an important future research direction that should better integrate wider bodies of previous disparate data pertaining to PD pathoetiology and pathophysiology and provide a conceptual framework for both prevention and symptom treatment.
Molecular Neurobiology, 2016
Abstract
Background: There is evidence that immune-inflammatory and oxidative and nitrosative st... more Abstract
Background: There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of chronic fatigue spectrum disorders, including chronic fatigue syndrome (CFS) and Myalgic Encephalomyelitis (ME). There is also evidence that these neuro-immune diseases are accompanied by hypothalamic pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline levels ofglucocorticoids.
Aims: This paper aims to review the bidirectional communications between immune
inflammatory and O&NS pathways and HPA axis hypoactivity in chronic fatigue spectrum disorders, considering two possibilities: a) activation of immune-inflammatory pathways is secondary to HPA axis hypofunction via attenuated negative feedback mechanisms; or b) chronic activated immune-inflammatory and O&NS pathways play a causative role in HPAaxis hypoactivity.
Methods: Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as
sources for this narrative review using keywords: CFS, ME, cortisol, ACTH, CRH, HPA-axis, glucocorticoid receptor, cytokines, immune, immunity, inflammation, O&NS.
Results: Findings show that activation of immune-inflammatory and O&NS pathways in chronic fatigue spectrum disorders are probably not secondary to HPA-axis hypoactivity and that activation of immune pathways may underpin HPA-axis hypofunction in ME/CFS. Mechanistic explanations comprise: increased levels of tumor necrosis factor-; T regulatory responses with elevated levels of interleukin-10 and transforming growth factor-; elevated levels of nitric oxide; and viral/bacterial mediated mechanisms.
Conclusions: HPA-axis hypoactivity in chronic fatigue spectrum disorders is most likely a consequence and not a cause of a wide variety of immune-inflammatory and O&NS
pathways
Journal of breastfeeding biology, Jul 22, 2016
The biological underpinnings that drive the plethora of breastfeeding benefits over formula-feedi... more The biological underpinnings that drive the plethora of breastfeeding benefits over formula-feeding is an area of intense research, given the cognitive and emotional benefits as well as the offsetting of many childhood-and adult-onset medical conditions that breast-feeding provides. In this article, we review the research on the role of melatonin in driving some of these breastfeeding benefits. Melatonin is a powerful antioxidant, antiinflammatory and antinociceptive as well as optimizing mitochondrial function. Melatonin is produced by the placenta and, upon parturition, maternal melatonin is passed to the infant upon breastfeeding with higher levels in night-time breast milk. As such, some of the benefits of breastfeeding may be mediated by the higher levels of maternal circulating night-time melatonin, allowing for circadian and antioxidant effects, as well as promoting the immune and mitochondrial regulatory aspects of melatonin; these actions may positively modulate infant development. Herein, it is proposed that some of the benefits of breastfeeding may be mediated by melatonin's regulation of the infant's gut microbiota and immune responses. As such, melatonin is likely to contribute to the early developmental processes that affect the susceptibility to a range of adult onset conditions. Early research on animal models has shown promising results for the regulatory role of melatonin.
Advances in integrative medicine, Apr 1, 2015
Depression and neuroprogression: Sirtuins and mitochondria as crucial hubs
Oxford University Press eBooks, Feb 1, 2019
Neuroprogressive processes in major depressive disorder (MDD) can occur in association with recur... more Neuroprogressive processes in major depressive disorder (MDD) can occur in association with recurrent episodes. The primary biological underpinnings are mediated by increases in the levels of immune-inflammation, tryptophan catabolites, mitochondrial dysfunction, and oxidative and nitrosative stress. Such biochemical alterations may be driven by changes in many peripheral and central sites, including in the gut, as well as by early developmental priming, such as prenatal stressors and breastfeeding consequences. As such, the conceptualization of MDD is shifted from simple psychological and central biochemical models to one that includes whole body processes over a developmental timescale. This provides a model that better integrates wider bodies of data relevant to the aetiology and course of MDD, and which therefore underpins the neuroprogressive processes that can occur over the course of MDD. This also significantly challenges current MDD (and wider psychiatric) classification by shifting classification to one based on biological processes rather than one based on subjective phenomenology.
A Role for the Regulation of the Melatonergic Pathways in Alzheimer’s Disease and Other Neurodegenerative and Psychiatric Conditions
When tryptophan is taken up by the body, some is used for the synthesis of sero-tonin. As well as... more When tryptophan is taken up by the body, some is used for the synthesis of sero-tonin. As well as having neuroregulatory effects, serotonin is also the precursor for the synthesis of N-acetylserotonin (NAS) and melatonin, which form the melatonergic pathways. The melatonergic pathways are associated with many of the changes that are thought to be important in the pathophysi-ology of Alzheimer&#39;s disease, Parkinson&#39;s disease, multiple sclerosis, and major depressive disorder. As well as being produced by the pineal gland at night, and thereby contributing to the circadian rhythm, melatonin is also very highly produced in other organs and tissues, including the gut, where CONTENTS
Reactive Oxygen Species, 2018
In stroke, increased oxidative stress (OS), mediated by reactive oxygen species (ROS) including H... more In stroke, increased oxidative stress (OS), mediated by reactive oxygen species (ROS) including H2O2 release, can induce changes that lead to neural production of amyloid-β (Aβ), a hallmark protein in the brains of Alzheimer's disease (AD) patients. Aβ peptide can also induce OS by itself or by activating microglia to release ROS. Estrogenic compounds can protect neurons against Aβ-and OS-induced cell death. Aβ-and OS-induced cell death is another hallmark of AD. We have studied OS-related cell damage by exposing rat primary hippocampal neurons and differentiated human SH-SY5Y neuroblastoma cells to H2O2 or Aβ1-42 and evaluated the neuroprotective potential of 17β-estradiol (E2), estrone (E1), tamoxifen (Tam), 4-OH-tamoxifen (4-OH-Tam), diethylstilbestrol (Des) and genistein (Gen) against OS. These compounds have differences in estrogen receptor (ER) binding affinities and their number of antioxidative-OH groups varies. The cell damage indicator was the lactate dehydrogenase release into culture medium. Treatment with 5 nM E2, Gen, or 4-OH-Tam for 24 h before and after the H2O2 insult was neuroprotective in both hippocampal and SH-SY5Y cultures. E2 and Gen were neuroprotective against Aβ1-42-mediated toxicity. Protection by E2 was partially mediated by Bcl-2, Bcl-xL, and BAG-1. Tam also increased Bcl-2 and Bcl-xL but was much less neuroprotective. Gen increased amyloid precursor protein (APP) synthesis, but γ-secretase component PS-1 was reduced, suggesting that Gen can increase the production of neurotrophic soluble APP. Des increased Aβ production. In conclusion, Gen shows comparable neuroprotective efficacy to E2, and seems also to reduce Aβ production in our study. However, other neuroprotective mechanisms may exist, and further studies on this subject will enhance our understanding in this respect.
Neuroprotective potential of estrogens and estrogenic compounds against amyloid-beta and oxidative stress
Journal of Neuroimmunology, 2012
Neuroprotective potential of estrogens and estrogenic compounds against amyloid-beta and oxidativ... more Neuroprotective potential of estrogens and estrogenic compounds against amyloid-beta and oxidative stress
Metabolic Syndrome, Alzheimer Disease, Schizophrenia, and Depression: Role for Leptin, Melatonin, Kynurenine Pathways, and Neuropeptides
John Wiley & Sons, Ltd eBooks, Oct 11, 2013
Metabolic dysregulation is intimately associated with a wide array of seemingly unrelated disorde... more Metabolic dysregulation is intimately associated with a wide array of seemingly unrelated disorders, including schizophrenia, Alzheimer disease, and depression. Genetic susceptibility genes show significant overlap between Alzheimer disease and schizophrenia, suggesting overlap in underlying biological processes, including metabolic. The high levels of depression in both disorders is linked to these shared processes. This chapter reviews the data suggesting that changes in leptin levels and leptin resistance mediate many of these metabolic changes, including the regulation of tryptophan catabolites (TRYCATs) and neuropeptides, which in turn drives alterations in cognition, neurogenesis, and apoptotic pathways. On the basis of this, treatment implications are proposed including the use of melatonin, together with leptin, in the prevention and treatment of these poorly managed disorders.
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Papers by George Anderson
Background: There is evidence that immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways play a role in the pathophysiology of chronic fatigue spectrum disorders, including chronic fatigue syndrome (CFS) and Myalgic Encephalomyelitis (ME). There is also evidence that these neuro-immune diseases are accompanied by hypothalamic pituitary-adrenal (HPA) axis hypoactivity as indicated by lowered baseline levels ofglucocorticoids.
Aims: This paper aims to review the bidirectional communications between immune
inflammatory and O&NS pathways and HPA axis hypoactivity in chronic fatigue spectrum disorders, considering two possibilities: a) activation of immune-inflammatory pathways is secondary to HPA axis hypofunction via attenuated negative feedback mechanisms; or b) chronic activated immune-inflammatory and O&NS pathways play a causative role in HPAaxis hypoactivity.
Methods: Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as
sources for this narrative review using keywords: CFS, ME, cortisol, ACTH, CRH, HPA-axis, glucocorticoid receptor, cytokines, immune, immunity, inflammation, O&NS.
Results: Findings show that activation of immune-inflammatory and O&NS pathways in chronic fatigue spectrum disorders are probably not secondary to HPA-axis hypoactivity and that activation of immune pathways may underpin HPA-axis hypofunction in ME/CFS. Mechanistic explanations comprise: increased levels of tumor necrosis factor-; T regulatory responses with elevated levels of interleukin-10 and transforming growth factor-; elevated levels of nitric oxide; and viral/bacterial mediated mechanisms.
Conclusions: HPA-axis hypoactivity in chronic fatigue spectrum disorders is most likely a consequence and not a cause of a wide variety of immune-inflammatory and O&NS
pathways