PUFAs, Sugar Restriction and Social Isolation.

RatTaTat “The psychopathology of social isolation has been studied in a variety of animals, and many features are similar across species, including humans. Aggression, helplessness, and reduced ability to learn are typically produced in animals…and…certain kinds of family environment produce the same conditions in children.” – Ray Peat PhD

When it comes to harming the body and the brain, there’s probably something even worse than social isolation, and that’s social isolation when combined with any of a long list of metabolism interfering, stress promoting things. In fact, without additional anti-metabolic influences, social isolation isn’t necessarily always so bad.

But seriously, chronic biological stress, which can easily arise due to unavoidably stressful social circumstances, is also promoted by lack of light or too much of the wrong light, not enough relaxation and play, poor sleep quality, starvation or insufficient fuel intake, protein and other nutritional deficiencies, toxic culture and trauma, radiation of various kinds, as well as excessive exposure to poisonous chemicals, heavy metals and numerous environmental estrogens.

These and other anti-metabolism things, interact with biological/biochemical processes which (particularly in the context of a high polyunsaturated fat, sugar restricted diet), lead to increased levels of cortisol, and other stress related hormones and inflammatory substances.

Social isolation and high cortisol have been shown to be linked, and there is evidence demonstrating that rising cortisol is involved in the progression of mood dysregulation. Reducing cortisol is known to be an effective method for treating serious depression.

“Boys whose cortisol levels rose most between the ages of 8 and 10 were also those whose aggressive behavior increased most during the same timeframe.” (Azurmendi A, et al., 2016)

“A group (17%) with both high levels of cortisol and depressive symptoms of both sexes had more depressed thinking…” (Matthew Owens, et al., 2014)

“…treatment was defined by a reduction of at least 50% in the Hamilton Rating Scale for Depression after 3 weeks of therapy…tests…revealed a significant reduction of cortisol concentrations already after 1 day of…treatment…” (Laakmann G, et al., 2003)

Ongoing or excessive exposure to adrenaline and cortisol, interferes with energy systems and thyroid function, promoting the release of polyunsaturated fats (PUFAs) from storage, and all of the above has been shown to interfere with digestive processes, causing many inflammatory and stressful effects.

An under active digestive system can promote the overgrowth of bacteria, allowing them to move further and further up the intestine where they are not intended to be, increasing endotoxin secretion and circulation. Endotoxin is inflammatory, and promotes serotonin, estrogen and nitric oxide, and all of these substances inhibit oxidative metabolism, and add to the stress placed on the liver, interfering with detoxification capabilities.

When the liver and digestive system is overburdened, serotonin and estrogen levels start to be able to rise systemically, and this has the potential to feed a vicious circle of inflammation and stress, promoting chronically high cortisol, and the heightened release of the harmful polyunsaturated free fatty acids into the blood.

Most people intuitively understand that there is a close connection between digestive function and state of mind, and there is plenty of good quality evidence available, demonstrating the significance of this relationship in both directions.

What is probably less well known is the fact that working to improve metabolism and digestive function (reducing the potential for exposure to endotoxin and the consequent systemic rise in circulation of inflammatory things like estrogen, serotonin and nitric oxide) is a tactic which can be used to effectively reduce the negative impact of socially isolating and stressful conditions.

Increased circulation and exposure to bacterial endotoxin, has been shown to have a direct impact upon metabolic function as well as mood.

“Endotoxin-administration in human subjects…induces specific dose-dependent symptoms…These symptoms are similar to symptoms seen in idiopathic depression.” (DellaGioia N, Hannestad J, 2010)

Although testosterone often gets blamed for aggressive, anti-social behavior, studies show that exposure to chronic stress (interfering with sugar availability, and leading to increased contact with the breakdown products of PUFAs in the blood), is a big part of what is responsible for rising endotoxin and serotonin exposure, chronic inflammation, and greater conversion of testosterone (via aromatization) to estrogen.

“We suggest that individual differences in central aromatase activity and steroid receptor expression within the brain may be factors that may partially account for the inconsistent relationship between T and aggression in humans…Recent studies suggest that estrogens may influence components of aggression in humans, such as hostility.” (Trainor BC, et al., 2006)

Both serotonin and estrogen have been demonstrated to promote aggressive and violent behavior (in animals and humans), and are known to be involved in the processes which increase learned helplessness and depression. Social stress has been shown to raise estrogen and serotonin levels. Their rising levels can be seen as the result of exposure to stressful conditions and environments, but also as a factor which can worsen the perception and impact of any particular circumstances faced.

“Reduction of estrogen production resulted in a decrease in aggressive behavior, suggesting that estrogen acts to increase aggression.” (Greiwe, Kelly, 2006)

“…lower socioeconomic status during adolescence is associated with an increase in methylation of the proximal promoter of the serotonin transporter gene, which predicts greater increases in threat-related amygdala reactivity…” (Swartz JR, et al., 2017)

“…evidence for direct estrogenic regulation of CRF gene expression provides a compelling mechanism for sexual dimorphism of stress reactivity and prevalence of stress-related psychopathology in women…” (Bangasser DA, et al., 2010)

The breakdown products of the highly unstable PUFAs (including fish oils) have been closely associated with depression as well as other mood dysregulation symptoms.

“Concentrations of malondialdehyde (MDA) were…significantly higher during depressive episodes.” (Gałecki P, et al., 2009)

“This meta-analysis suggests an association between increased lipid peroxidation in peripheral blood samples and the presence of MDD [major depressive disorder].” (Mazereeuw G, et al., 2015)

“MDA status is used as biomarker for oxidative stress….elevated MDA was related with…auditory-verbal working memory, impairment of visualspatial, and, short-term and delayed declarative memory…MDA levels have been found to be increased in depression…we found significantly increased levels of MDA in patients of major depressive disorder…Increased MDA levels implicate increased lipid peroxidation products in major depressive disorder.” (Bajpai A, et al., 2014)

When stress is high, blood sugar (and glycogen in storage) gets used up at a faster rate, and the combination of stress and low sugar availability, promote the release of the inflammatory stress substances that are known to interfere with energy production.

Low blood sugar and suppression of thyroid metabolism, interferes with brain function, and has been shown to increase aggressive behavior as well as many other mood disorder symptoms.

“The results of this study demonstrate another important physiological variable that influences aggressive tendencies and behaviors, namely glucose. Glucose levels are an important influence on self-control and aggression, and glucose levels stand as a physiological factor that can be actively targeted and influenced.” (Brad J. Bushman, et al., 2014)

The stress promoting inflammatory effects of the breakdown products of PUFAs, are known to be able to inhibit thyroid function in a number of ways, and to cause chronic interference with the ability of all kinds of cells, to use sugar for energy production.

Interference with oxidative metabolism can promote aggressive behavior, and it not surprising that there is a correlation between depression and aggression, and the progression of disease states like cancer and diabetes.

“Aerobic glycolysis (AG) is characterized by elevated glycolysis relative to oxidative phosphorylation despite adequate oxygen availability to completely metabolize glucose to carbon dioxide…Our data suggest a shift toward brain AG in high aggression states.” (Chandrasekaran S, et al., 2015)

Brain function in general (including learning capability and mood states), are powerfully influenced by energy availability. A lack of availability of sugar for the brain can promote degeneration and disease in a number of different ways.

“In humans, the brain accounts for ~2% of the body weight, but it consumes ~20% of glucose-derived energy making it the main consumer of glucose…Neurons are largely intolerant of inadequate energy supply, and thus the high energy demand of the brain predisposes it to a variety of diseases if energy supplies are disrupted.” (Mergenthaler P, et al., 2013)

Social isolation has been proven to be able to interfere with brain oxidative metabolism, and to raise levels of the anti-metabolic stress substances, including estrogen, cortisol and nitric oxide.

“Our data suggest that inhibition of mitochondrial oxidative metabolism…and compensatory elevation of glycolysis in hippocampus occurs during social isolation…” (Zhuravliova E, et al., 2009)

“…data suggest that social isolation may enhance de novo estradiol synthesis in the hippocampus.” (Munetsuna E, et al., 2009)

“Independently of multiple behavioural and psychosocial correlates, recent onset of social isolation is related to diurnal cortisol patterns that increase the risk of morbidity and mortality.” (Stafford M, et al., 2013)

“In contrast to the acute stress, chronic social isolation compromised hypothalamic-pituitary-adrenal axis functioning…Changes in redox-status…enabled NF-κB translocation into the nucleus, causing increased cytosolic nNOS and iNOS protein expression…” (Zlatković J, Filipović D, 2013)

Sugar restriction (or interference with sugar usability), and excessive exposure to the breakdown products of the PUFAs, can also interfere with cholesterol production, and low cholesterol has been associated with violence, suicide and aggression.

Cholesterol protects against bacterial toxins, and so low cholesterol can potentially increase exposure to the inflammatory anti-metabolic effects of endotoxin, adding stress onto the liver, and eventually causing estrogen and other stress related substances to rise systemically.

On top of this, when thyroid energy metabolism is suppressed for any of these reasons, this can get in the way of the normal conversion of cholesterol into the highly protective, anti-stress, anti-inflammatory substances, including pregnenolone, progesterone and testosterone, all of which have been shown to protect against mood disorders, as well as brain dysfunction and inflammatory disease in general.

When cholesterol is unable to be converted in sufficient quantities, this can also directly lead to a build up of estrogen throughout the system (trapped and produced inside tissue), which in and of itself promotes all of the issues being discussed, including inflammatory disease, thyroid suppression, as well as mood dysregulation and aggression.

All these kinds of issues, can be approached in a variety of different ways, including by attempting to change or improve the environment you are exposed to, by finding better relationships or improving existing ones, or with psychological or spiritual development in general. An improvement in one area has the potential to be a helpful inroad into overall improvement.

Of course aggression is not always unwarranted, and may well be an appropriate response depending on the particular circumstances. But irritation or stimulation in combination with interference with energy systems, can promote the release of substances that have been shown to change how the brain perceives various kinds of  potential threats.

Also, there is an obvious relationship (even if it doesn’t hold true in every case) between depression and helplessness, and an increased susceptibility to aggressive or violent behavior, and the development of certain types of learning disabilities.

If environmental or psychological conditions are likely to remain challenging, greater protection from the effects of chronic stress, can be provided via dietary measures, with the effective provision of energy for the maintenance of metabolic performance.

Am I suggesting that getting PUFAs out of your diet and system, and swallowing kilos of sugar, will automatically solve all human problems? No. But there are things that need to be considered, that are simply not being considered, in almost every case, and with the vast majority of popular treatment approaches.

Unfortunately there is no great demand (or financial support) for the encouragement of studies or experiments which look at the emotional and physiological impact of social hardship, in the context of interference with thyroid function and energy metabolism. My personal experience is that the difference in impact, can be like night and day.

Although stress substances like estrogen, cortisol, serotonin, nitric oxide and lactate, each have their basic physiological role to play, systemic and chronically high levels, can have many dangerous disease promoting consequences, and it’s hard to deny that the results of excessive exposure, can dramatically change behavior and reduce enjoyment of life, regardless of external, more objective circumstances.

The stressful nature of an environment (whether that be emotional stress or any other stress) can powerfully influence metabolic, biochemical outcomes (proven to influence mind states and behavior), but nutritional/biochemical factors, play an important part here.

I’m not a doctor, and this is not intended as medical advice, but no matter which approach to health is taken, a better understanding of the relationship between the stress substances, thyroid energy metabolism, blood sugar regulation, and how they can be manipulated in order to improve overall stress resilience and well-being, can be a powerful thing.

One way I know of, which can effectively reduce overall stress, is focusing on improving digestion, and attempting to stabilize blood sugar, whilst ensuring the continued provision of energy. Some tools which have been shown to be useful, include activated charcoal, raw carrot salad, minocycline, aspirin, methylene blue, cyproheptidine, famotidine, sodium bicarb, pulse and temperature tracking, regular bag breathing, and various other pro-metabolic things.

Avoiding PUFAs, and increasing consumption of sugar from sweet ripe juicy fruits, fruit juice, white sugar and honey, combined with a diet consisting of sufficient protein and other nutrients from milk, cheese and gelatin, is one possible approach to protecting against the anti-metabolic effects of socially isolating environments and behaviors, hopefully providing the capacity to discover new avenues for improving outlook and mood, and overall learning capability.

Although some people are better equipped to withstand – at least for a while – the stress promoted by the consumption of lots of PUFAs and seeds and grains and raw vegetable matter (combined with the avoidance of good quality sources of protein, vitamins, minerals and sugar), if you are suffering due to social circumstances, it may well be worth experimenting with different ways of eating.

Why is it so hard for so many people to believe that dietary (and other) changes (such as greater restriction of PUFAs and increased sugar consumption), known to promote a non-stressful metabolism via the improvement of energy systems, helps to protect against the impact of stress, and improve state of mind and behavior?

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Pharmacol Biochem Behav. 1976. The role of serotonergic pathways in isolation-induced aggression in mice. Malick JB, et al.

Front Neuroendocrinol. 2006. Estrogenic encounters: how interactions between aromatase and the environment modulate aggression. Trainor BC, et al.

Mol Psychiatry. 2017 Feb;22(2):209-214. An epigenetic mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents. Swartz JR, Hariri AR, Williamson DE.

PLoS One. 2015 Oct 7;10(10):e0138904. A Meta-Analysis of Oxidative Stress Markers in Depression. Liu T, Zhong S, Liao X, Chen J, He T, Lai S, Jia Y.

Biochem J. 1992 Mar 1;282 ( Pt 2):487-94. Inhibition of protein synthesis in intact mammalian cells by arachidonic acid. Rotman EI, Brostrom MA, Brostrom CO.

Biol Psychiatry. 1993 Sep 15;34(6):373-9. The cortisol response to clonidine in acute and remitted depressed men. Trestman RL, Coccaro EF, Mitropoulou V, Gabriel SM, Horvath T, Siever LJ.

Psychiatry Res. 2010 May 15;177(1-2):109-13. Antidepressant treatment with mirtazapine, but not venlafaxine, lowers cortisol concentrations in saliva: a randomised open trial. Scharnholz B, Weber-Hamann B, Lederbogen F, Schilling C, Gilles M, Onken V, Frankhauser P, Kopf D, Deuschle M.

J Clin Diagn Res. 2014 Dec;8(12):CC04-7. Oxidative Stress and Major Depression. Bajpai A, Verma AK, Srivastava M, Srivastava R.

Neurosci Lett. 2017 Aug 24;656:131-137. Depletion of 5 hydroxy-triptamine (5-HT) affects the antidepressant-like effect of neuronal nitric oxide synthase inhibitor in mice. da Silva Leal VM, Bonassoli VT, Soares LM, Milani H, de Oliveira RMW.

J Nutr. 2016 Dec;146(12):2461-2467. Glycine Regulates Protein Turnover by Activating Protein Kinase B/Mammalian Target of Rapamycin and by Inhibiting MuRF1 and Atrogin-1 Gene Expression in C2C12 Myoblasts.  Sun K, Wu Z, Ji Y, Wu G.

Clin Lymphoma Myeloma Leuk. 2013 Oct;13(5):534-40. Aggressive behavior and elevated lactate dehydrogenase at baseline confer inferior prognosis in patients with primary cutaneous lymphoma. Liu WP, Song YQ, Zheng W, Wang XP, Ding N, Zhu J.

Biochem Biophys Res Commun. 2009 Feb 6;379(2):480-4. Social isolation stimulates hippocampal estradiol synthesis. Munetsuna E, Hattori M, Komatsu S, Sakimoto Y, Ishida A, Sakata S, Hojo Y, Kawato S, Yamazaki T.

Neuropsychobiology. 2003;47(1):31-6. Influence of mirtazapine on salivary cortisol in depressed patients. Laakmann G, Hennig J, Baghai T, Schüle C.

Physiol Behav. 2015 Jun 1;145:38-44. Co-occurrence of anxiety and depressive-like behaviors following adolescent social isolation in male mice; possible role of nitrergic system. Amiri S, Haj-Mirzaian A, Rahimi-Balaei M, Razmi A, Kordjazy N, Shirzadian A, Ejtemaei Mehr S, Sianati H, Dehpour AR.

Trends Neurosci. 2013 Oct;36(10):587-97. Sugar for the brain: the role of glucose in physiological and pathological brain function. Mergenthaler P, Lindauer U, Dienel GA, Meisel A.

Perspect Psychol Sci. 2015 Mar;10(2):227-37. Loneliness and social isolation as risk factors for mortality: a meta-analytic review. Holt-Lunstad J, Smith TB, Baker M, Harris T, Stephenson D.

Genes Brain Behav. 2015 Feb;14(2):158-66. Aggression is associated with aerobic glycolysis in the honey bee brain1. Chandrasekaran S, Rittschof CC, Djukovic D, Gu H, Raftery D, Price ND, Robinson GE.

J Neural Transm (Vienna). 2005 Aug;112(8):1083-96. Salivary cortisol and aggression in a population-based longitudinal study of adolescent males. van Bokhoven I, Van Goozen SH, van Engeland H, Schaal B, Arseneault L, Séguin JR, Nagin DS, Vitaro F, Tremblay RE.

Psychoneuroendocrinology. 2016 Sep;71:102-9. Executive functioning and diabetes: The role of anxious arousal and inflammation. Murdock KW, LeRoy AS, Lacourt TE, Duke DC, Heijnen CJ, Fagundes CP.

Semin Clin Neuropsychiatry. 1997 Jan;2(1):57-65. The Emotional, Social, and Behavioral Implications of Insulin-Induced Hypoglycemia. Gonder-Frederick LA, Clarke WL, Cox DJ.

Neurochem Int. 2013 Sep;63(3):172-9. Chronic social isolation induces NF-κB activation and upregulation of iNOS protein expression in rat prefrontal cortex. Zlatković J, Filipović D.

J Affect Disord. 2003 Mar;74(1):85-96. Estrogen-mediated effects on depression and memory formation in females. Shors TJ, Leuner B.

Socially responsive effects of brain oxidative metabolism on aggression. Hongmei Li-Byarlay, Clare C. Rittschof, Jonathan H. Massey, Barry R. Pittendrigh, and Gene E. Robinson

Funct Neurol. 1989 Apr-Jun. Psychopathology and aggressive behaviour in cancer pain perception. Orsolini GC, et al.

. Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms. Matthew Owens, Joe Herbert, Peter B. Jones, Barbara J. Sahakian, Paul O. Wilkinson, Valerie J. Dunn, Timothy J. Croudace, and Ian M. Goodyer

Psychoneuroendocrinology. 2013 Nov;38(11):2737-45. Social isolation and diurnal cortisol patterns in an ageing cohort. Stafford M, Gardner M, Kumari M, Kuh D, Ben-Shlomo Y.

Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation. Steven W. Cole, John P. Capitanio, Katie Chun, Jesusa M. G. Arevalo, Jeffrey Ma, and John T. Cacioppo

Br J Pharmacol. 2000 Jul;130(6):1385-93. Antidepressant drugs inhibit glucocorticoid receptor-mediated gene transcription – a possible mechanism. Budziszewska B, Jaworska-Feil L, Kajta M, Lasoń W.

. Low glucose relates to greater aggression in married couples. Brad J. Bushman, C. Nathan DeWall, Richard S. Pond Jr., and Michael D. Hanus

Med Hypotheses. 2015 Dec;85(6):947-52. Why May Allopregnanolone Help Alleviate Loneliness? Cacioppo S, Cacioppo JT.

J Interpers Violence. 2012 Jul;27(11):2163-82. Violent behavior in cancer patients–a rarely addressed phenomenon in oncological treatment. Grube M.

Personality and Social Psychology Bulletin June 13, 2017. Reciprocal Influences Between Loneliness and Self-Centeredness: A Cross-Lagged Panel Analysis in a Population-Based Sample of African American, Hispanic, and Caucasian Adults. John T. Cacioppo, Hsi Yuan Chen, Stephanie Cacioppo

J Nutr. 2006 Jun;136(6 Suppl):1722S-1725S. Toxicity of methionine in humans. Garlick PJ.

Science  25 Nov 2016:Vol. 354, Issue 6315, pp. 1041-1045. Social status alters immune regulation and response to infection in macaques. Noah Snyder-Mackler, Joaquín Sanz, Jordan N. Ko.

J Eval Clin Pract. 2016 Jun;22(3):421-4. Study of the relationship between aggression and chronic diseases (diabetes and hypertension). Tilov B, Semerdzhieva M, Bakova D, Tornyova B, Stoyanov D.

Int Sch Res Notices. 2014 Nov 26;2014:690950. Metabolic Effects of Social Isolation in Adult C57BL/6 Mice. Sun M, Choi EY, Magee DJ, Stets CW, During MJ, Lin EJ.

Clinics (Sao Paulo). 2010;65(11):1175-81. Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth. Hosseini M, Dastghaib SS, Rafatpanah H, Hadjzadeh MA, Nahrevanian H, Farrokhi I.

PLoS One. 2012;7(3):e32023. The effects of acute tryptophan depletion on reactive aggression in adults with attention-deficit/hyperactivity disorder (ADHD) and healthy controls. Zimmermann M, Grabemann M, Mette C, Abdel-Hamid M, Uekermann J, Kraemer M, Wiltfang J, Kis B, Zepf FD.

Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22393-8. Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors. Hermes GL, Delgado B, Tretiakova M, Cavigelli SA, Krausz T, Conzen SD, McClintock MK.

Psychoneuroendocrinology. 2017 Apr;78:76-84. Dual-hormone stress reactivity predicts downstream war-zone stress-evoked PTSD. Josephs RA, Cobb AR, Lancaster CL, Lee HJ, Telch MJ.

Am J Hum Biol. 2016 Jan-Feb;28(1):90-7. Developmental trajectories of aggressive behavior in children from ages 8 to 10: The role of sex and hormones. Azurmendi A, Pascual-Sagastizabal E, Vergara AI, Muñoz JM, Braza P, Carreras R, Braza F, Sánchez-Martín JR.

Cureus. 2017 Jan 24;9(1):e994. The Pathophysiology of Perceived Social Isolation: Effects on Health and Mortality. Bhatti AB, Haq AU.

ACS Chem Neurosci. 2014 Oct 15;5(10):908-19. Mice Genetically Depleted of Brain Serotonin Do Not Display a Depression-like Behavioral Phenotype. Angoa-Pérez M, Kane MJ, Briggs DI, Herrera-Mundo N, Sykes CE, Francescutti DM, Kuhn DM.

BMJ Open Diabetes Res Care. 2015 May 16;3(1):e000063. Association of severe hypoglycemia with depressive symptoms in patients with type 2 diabetes: the Fukuoka Diabetes Registry. Kikuchi Y, Iwase M, Fujii H, Ohkuma T, Kaizu S, Ide H, Jodai T, Idewaki Y, Nakamura U, Kitazono T.

Ukr Biokhim Zh (1999). 2011 May-Jun;83(3):85-90. Russian. Tissue specificity of lipid peroxidation under emotional stress in rats. Menabde KO, Burdzhanadze GM, Chachua MV, Kuchukashvili ZT, Koshoridze NI.

Integr Comp Biol. 2015 Aug;55(2):281-93. Rapid Effects of Estradiol on Aggression in Birds and Mice: The Fast and the Furious. Heimovics SA, Trainor BC, Soma KK.

J Affect Disord. 2010 Feb;121(1-2):184-8. Severe affective and behavioral dysregulation in youth is associated with increased serum TSH. Holtmann M, Duketis E, Goth K, Poustka L, Boelte S.

Cancer Prev Res (Phila). 2013 Jul;6(7):634-45. Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue. Volden PA, Wonder EL, Skor MN, Carmean CM, Patel FN, Ye H, Kocherginsky M, McClintock MK, Brady MJ, Conzen SD.

Behav Brain Res. 2009 Dec 28;205(2):377-83. Social isolation in rats inhibits oxidative metabolism, decreases the content of mitochondrial K-Ras and activates mitochondrial hexokinase. Zhuravliova E, Barbakadze T, Zaalishvili E, Chipashvili M, Koshoridze N, Mikeladze D.

Behav Brain Res. 2001 Jun;121(1-2):95-102. Serotonin reverses dominant social status. Larson ET, Summers CH.

Epilepsy Behav. 2014 Dec;41:158-63. Involvement of the nitrergic system in the proconvulsant effect of social isolation stress in male mice. Amiri S, Shirzadian A, Haj-Mirzaian A, Imran-Khan M, Rahimi Balaei M, Kordjazy N, Dehpour AR, Mehr SE.

J Clin Invest. 1993 Oct;92(4):1896-902. Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction. Vamvakopoulos NC, Chrousos GP.

Neurosci Biobehav Rev. 2010 Jan;34(1):130-43. A critical review of human endotoxin administration as an experimental paradigm of depression. DellaGioia N, Hannestad J.

Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):5797-801. Social isolation, loneliness, and all-cause mortality in older men and women. Steptoe A, Shankar A, Demakakos P, Wardle J.

Crit Care Med. 2008 Oct;36(10):2726-33. Intensive Care Unit Hypoglycemia Predicts Depression during Early Recovery from Acute Lung Injury. Dowdy DW, Dinglas V, Mendez-Tellez PA, Bienvenu OJ, Sevransky J, Dennison CR, Shanholtz C, Needham DM.

Heart. 2016 Jul 1;102(13):1009-16. Loneliness and social isolation as risk factors for coronary heart disease and stroke: systematic review and meta-analysis of longitudinal observational studies. Valtorta NK, Kanaan M, Gilbody S, Ronzi S, Hanratty B.

Physiol Behav. 2014. The effects of social isolation on wound healing mechanisms in female mice. Pyter LM, et al.

Neuropsychiatr Dis Treat. 2015 Sep 29;11:2479-91. A meta-analysis of lipid peroxidation markers in major depression. Mazereeuw G, Herrmann N, Andreazza AC, Khan MM, Lanctôt KL.

Biochim Biophys Acta. 2015 Dec;1850(12):2464-75. Tropisetron attenuated the anxiogenic effects of social isolation by modulating nitrergic system and mitochondrial function. Amiri S, Amini-Khoei H, Haj-Mirzaian A, Rahimi-Balaei M, Naserzadeh P, Dehpour A, Mehr SE, Hosseini MJ.

Molecular Psychiatry volume 15, pages 896–904 (2010) Sex differences in corticotropin-releasing factor receptor signaling and trafficking: potential role in female vulnerability to stress-related psychopathology. D A Bangasser, A Curtis, B A S Reyes, T T Bethea, I Parastatidis, H Ischiropoulos, E J Van Bockstaele & R J Valentino

Pharmacol Rep. 2009 May-Jun;61(3):436-47. Lipid peroxidation and antioxidant protection in patients during acute depressive episodes and in remission after fluoxetine treatment. Gałecki P, Szemraj J, Bieńkiewicz M, Florkowski A, Gałecka E.

Cerebral Cortex, Volume 27, Issue 4, April 2017, Pages 2607–2616. Multivariate Associations of Fluid Intelligence and NAA. Aki Nikolaidis, Pauline L. Baniqued, Michael B. Kranz, Claire J. Scavuzzo, Aron K. Barbey, Arthur F. Kramer, Ryan J. Larsen

Biol Pharm Bull. 2005 Aug;28(8):1389-93. Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin. Huong NT, Murakami Y, Tohda M, Watanabe H, Matsumoto K.

Biol Psychiatry. 2013 May 15;73(10):1024-34. Social Isolation Exacerbates Schizophrenia-like Phenotypes via Oxidative Stress in Cortical Interneurons. Jiang Z, Rompala GR, Zhang S, Cowell RM, Nakazawa K.

Ann Fam Med. 2013 May-Jun;11(3):245-50. Association of depression with increased risk of severe hypoglycemic episodes in patients with diabetes. Katon WJ, Young BA, Russo J, Lin EH, Ciechanowski P, Ludman EJ, Von Korff MR.

J Am Heart Assoc. 2017 Nov 29;6(12). pii: e007016. Role of Depression and Social Isolation at Time of Waitlisting for Survival 8 Years After Heart Transplantation. Spaderna H, Zittermann A, Reichenspurner H, Ziegler C, Smits J, Weidner G.

Horm Behav. 2012 Nov;62(5):553-62. Estrogenic plant consumption predicts red colobus monkey (Procolobus rufomitratus) hormonal state and behavior. Wasserman MD, Chapman CA, Milton K, Gogarten JF, Wittwer DJ, Ziegler TE.

Behav Brain Res. 2015 Jan 1;276:111-7. Endotoxaemia resulting from decreased serotonin tranporter (5-HTT) function: a reciprocal risk factor for depression and insulin resistance? Pomytkin IA, Cline BH, Anthony DC, Steinbusch HW, Lesch KP, Strekalova T.

Brain Struct Funct. 2017 Jan;222(1):1-20. Oxidative and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxiety-like symptoms. Filipović D, Todorović N, Bernardi RE, Gass P.

Int J Neurosci. 2006 Aug;116(8):895-906. Memory improvement with treatment of hypothyroidism. Miller KJ, Parsons TD, Whybrow PC, van Herle K, Rasgon N, van Herle A, Martinez D, Silverman DH, Bauer M.

J Pharmacol Exp Ther. 2011 Dec;339(3):790-8. Serotonin receptor type 3 antagonists improve obesity-associated fatty liver disease in mice. Haub S, Ritze Y, Ladel I, Saum K, Hubert A, Spruss A, Trautwein C, Bischoff SC.

The Ohio State University Department of Psychology Honors Theses; 2006. Effects of Estrogen on Aggressive Behavior. Greiwe, Kelly

J Psychiatry Neurosci. 2016 Jan;41(1):56-69. Serum lipid levels and suicidality: a meta-analysis of 65 epidemiological studies. Wu S, Ding Y, Wu F, Xie G, Hou J, Mao P.


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