# Introduction euroscience research has become crucial to understand the complexity of neuropsychiatry disorders and assist with the diagnosis and treatment of the various disorders [1]. Neuropsychiatric disorders such as schizophrenia, depression, bipolar disease, autism, attention deficit hyperactivity disorder and neurodegenerative diseases such as Parkinson's disease, Huntington's disease, and Alzheimer's disease have increased in various communities. The global chronic disease epidemic has indicated that nonalcoholic fatty liver disease (NAFLD) and diabetes (Figure 1) will reach epidemic levels with 30% of the population affected with complications such as cardiovascular disease, kidney disease and neurodegenerative diseases [2,3]. Neuropsychiatric disorders may now be connected to the global chronic disease epidemic [2] with early diagnosis essential to prevent accelerated neurodegeneration and to improve medical therapy in neuropsychiatric patients [4][5][6]. Insulin resistance in NAFLD, obesity, and diabetes involve autoimmune alterations in various tissues such as the adipose tissue, heart, liver and kidney that may determine accelerated brain aging and lifespan with relevance to neuropsychiatric disorders (Figure 1) [7][8][9][10][11][12][13]. The role of nutrition, lifestyle and environmental factors on increased oxidative stress, overactive immune system, and inactivation of anti-aging genes [14] has increased interest in the treatment, care, and diagnosis of neuropsychiatric disorders-early diagnosis with relevance to anti-aging genesis critical to prevent autoimmune reactions [3,7,14] associated withmajor subcellular alterations such as mitochondrial apoptosis and endoplasmic reticulum (ER) stress in neurons [15][16][17][18][19][20][21] that may lead to accelerated programmed cell death in neuropsychiatric conditions and global chronic disease. # a) Sirtuin 1 and Global chronic disease with relevance to ER stress and mitophagy in neuropsychiatric disorders Specific genes and novel mutations were identified in neuropsychiatric conditions with gene variants involved in cognitive disorders in these patients [22][23][24]. These genes may not allow early diagnosis and N Author: School of Medical Sciences, Edith Cowan University, Western Australia 6009, Australia. e-mail: i.martins@ecu.edu.au A reversal of the complications of these neuropsychiatric disorders. In recent years the discovery of anti-aging genes and their inactivation [25,26] may now be relevant to the epigenetics of neuropsychiatric disorders [27,28]. The anti-aging gene Sirtuin 1 (Sirt 1) has become important to neuropsychiatric conditions with its connections to schizophrenia, depression, bipolar disease and autism [29][30][31][32][33][34][35][36]. Sirt 1 dysregulation is critical to the development of global chronic disease with Sirt 1 effects on chromatin alterations (modeling) that influence the DNA sequence, DNA repair, DNA methylation and histone modifications [25,26]. Sirt 1 is a nicotinamide adenine dinucleotide dependent-class III histone deacetylase that targets transcription factors such as peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC 1-), mitochondrial biogenesis, p53, pregnane X receptor (PXR) to adapt gene expression to metabolic activity, insulin resistance and inflammation [25,26]. Sirt 1 mediated deacetylation of the transcriptional factor FoxO3a represses Rho-associated protein kinase-1 gene expression was associated with the reduction of amyloid beta generation [14]. In mammalian cells, Sirt 1 is linked to autoimmune disease [3,7] and the regulation of telomere maintenance and length [26]. Sirt 1 and its association with neuron senescence [37] was connected to Alzheimer's disease and other neurodegenerative diseases. Inactivation of anti-aging genes such as Sirt 1 may supersede the genetic findings in neuropsychiatric disorders and the Sirt 1 gene now associated with cell Mitochondrial alterations and ER stress in global chronic disease have become of principal concern to neuroinflammation in neuropsychiatric conditions and neurodegenerative diseases. The repression of Sirt 1 in global illness [2,3] and ER stress-induced mitophagy (Figure 2) [38][39][40][41][42] may be relevant to the diagnosis and treatment of neuropsychiatric patients in various global communities. Sirt 1 in neurons is critical for the prevention of cholesterol dyshomeostasis with toxic amyloid beta formation (Figure 2) involved in ER stressinduced mitophagy and neuron survival [43]. The connections between Sirt 1 and neuropsychiatric conditions are relevant to Sirt 1's role in autoimmune disease and amyloid beta aggregation [3,7,43]. In the developing with increased plasma bacterial lipopolysaccharides (LPS), Sirt 1 may be repressed [44] with relevance to LPS in cell membranes that bind to cholesterol/sphingomyelin domain with an acceleration of toxic amyloid beta oligomerization in neuropsychiatric disorders [45][46][47]. In neuropsychiatric disorders [12,13,48, 49] alterations in neuron membranes have become of prime concern with relevance to defective phospholipid metabolism in these patients. Lipid membrane abnormalities may affect dopamine signaling in schizophrenia and phospholipase A2 abnormalities responsible for altered brain membranes. The defective neuron amyloid beta pathway (Figure 2) is now relevant to neuropsychiatric disorders such as schizophrenia, depression and bipolar disease and applicable to disturbed membrane cholesterol homeostasis and toxic amyloid beta oligomer formation in neurons (Figure 2). In chronic diseases such as NAFLD, obesity, and diabetes alterations in membrane phospholipids are connected to the defective amyloid beta clearance pathway [43,47] with effects on neuron membranes with toxic amyloid beta oligomerization associated with neuron cell apoptosis (Figure 2). Phospholipid composition such as phosphatidylinositol lower membrane cholesterol (Figure 2) and amyloid beta with prevention of toxic amyloid beta aggregation [50]. © 2018 Global Journals A Nitric oxide (NO) is now a crucial player in neuropsychiatric disease and associated with schizophrenia, bipolar disorder and major depression [51,52]. NO as a lipophile acts as an intracellular and intercellular messenger that is critically regulated by cellular Sirt 1 [53,54] with NO involved in cell communication between neuron cells in the brain. The connections between the immune system and neuropsychiatric diseases involve NO and implicate Sirt 1 regulation of NO in autoimmune disease [51]. The importance of Sirt 1 in neuropsychiatric disorders is relevant to NO homeostasis as the primary defect (Figure 2) with connections to secondary subcellular and membrane alterations in neuropsychiatric disturbances [51,52]. # b) Diagnosis of mitophagy in neuropsychiatric patients with global chronic disease The criteria are allowing reliable diagnostic identification of schizophrenia, bipolar disease and depression are defined by subjective experiences (symptoms), loss of function (behavioral impairments) and variable patterns of the disease. Some biological markers (genomics, proteomics, metabolomics) were associated with the disorder, but to date, these markers do not have the sensitivity/specificity of a diagnostic test [55][56][57][58][59][60]. The early diagnosis of neuropsychiatric disorders now involves measurements of nuclear, cellular and plasma Sirt 1 levels (Figure 3) [43,61]. Measurements of magnesium [62,63] and zinc may be vital to prevent inactivation of brain Sirt 1 activity. Sirt 1 nuclear receptor control of ER-mitochondria interaction may need to assess plasma LPS levels to avoid complete repression of Sirt 1 and induction of mitophagy induced ER stress in neuropsychiatry diseases. Figure 3: Biomarker tests for mitophagy and ER stress in neuropsychiatric disorders were required for reversal and stabilization of the disease. Genomic, proteomic and lipidomic experiments are critical to assess the induction of mitophagy with relevance Sirt 1 and lipid binding protein analysis in plasma and tissues. Plasma lipid measurements of cholesterol, ceramide, sphingolipids, and phospholipids (phosphatidylinositol) are essential to determine early mitophagy-ER stress disorders in neuropsychiatric disorders. Lipidomic analysis [64] of plasma lipids (sphingolipids/ceramides) may reflect changes in the periphery and central nervous system and correlation with plasma Sirt 1, ceramide binding proteins and sphingolipid transfer proteins may be important in neuropsychiatric diseases. Measurements of micro RNA (mir-34a, mir-122, mir-132) may indicate repression of Sirt 1 [3] and relevant to the lipidomic analysis. The levels of plasma heat shock protein (Figure 3) may reflect inhibition of Sirt 1 activity and pertinent to activation of autoimmune disease [43]. These biomarker tests (Figure 3) that are relevant to global chronic illness [65,66] are now appropriate to the early diagnosis and treatment of neuropsychiatric disturbances. # c) Nutritional Biotherapy and Management of neuropsychiatric114 patients In neuropsychiatric disorders such as schizophrenia, a healthy and low carbohydrate diet with careful nutritional assessment [67,68] is required to prevent obesity, diabetes, and NAFLD and stabilize complications of the disease. A systematic review of the literature indicates that metabolic abnormalities were linked to schizophrenia [69]. In depression and mental illness a complete nutritional diet [70] is required to improve behavior, emotion, and cognition with consumption of low carbohydrates, proteins (amino acids/brain function, essential fatty acids (omega-3), vitamins (B, B12, folate) and minerals (calcium, chromium, iodine, iron, lithium, selenium, zinc). Diets that contain functional foods such as biologically active Sirt 1 activator are now essential to maintain patients with neuropsychiatric disorders [64]. Nutritional biotherapy is now critical to the maintenance of the calorie sensitive gene Sirt 1 with excessive glucose and fatty acid that is involved in Sirt 1 repression. Early interventions with the use of genomic A medicine [71,72] and Sirt 1 activatorsare essential to the treatment of autoimmune disease and neurodegeneration. Appropriate doses of Sirt 1 activators such as pyruvic acid, resveratrol, leucine, rutin, and alpha lipoic acid will prevent mitophagy and ER stress by modulation at the cellular level of neuropsychiatric disease. Phosphatidylinositol (4gm/day) should be consumed [50] to halt neuron membrane cholesterol and amyloid beta disturbances. Appetite control (Figure 4) with cautious nutrient (glucose/fatty acid) intake will maintain the calorie sensitive Sirt 1 activity and stabilize schizophrenia, depression and bipolar disease. The contents of caffeine (Figure 4) in the diet in neuropsychiatric patients should be carefully controlled to prevent caffeine associated neuron disturbances in the brain [63]. In the developing world with elevated LPS levels [44][45][46][47] nutritional biotherapy is critical to maintaining Sirt 1 activity and rapid hepatic drug and xenobiotic metabolism [14]. The use of anti-depressants, antipsychotics and other drug therapy in neuropsychiatric patients require intact hepatic and brain Sirt 1 activity. Sirt 1 inhibitors [43,63] may nullify drug therapy with drug-drug interactions (Figure 4) as complications of neuropsychiatric disorders. Prevention of stress and maintenance of core body temperature were required for the prevention of autoimmune disease [43,54] in these patients. II. # Conclusion Early diagnosis and the measurement of plasma/tissue Sirt 1 levels in neuropsychiatric disorders will allow treatment of schizophrenia, depression and bipolar disease. Plasma analysis of Sirt 1 with extensive lipidomic analysis may indicate the risk of mitophagy and ER stress with relevance to autoimmune disease in neuropsychiatric disorders. Nutritional biotherapy and genomic medicine that involves the activation of Sirt 1 at the nuclear receptor level may allow modulation/reversal of mitophagy and ER stress in psychiatric disorders and neurodegenerative diseases such as Alzheimer/s disease, Parkinson's disease, and Huntington's disease. 1![Figure 1: Connections between global chronic disease and neuropsychiatric disorders indicate insulin resistance and immune reactions interfere with the diagnosis and treatment of neuropsychiatric disturbances such as schizophrenia, depression, bipolar disorder, autism, and neurodegenerative diseases.Insulin resistance in NAFLD, obesity, and diabetes involve autoimmune alterations in various tissues such as the adipose tissue, heart, liver and kidney that may determine accelerated brain aging and lifespan with relevance to neuropsychiatric disorders (Figure1)[7][8][9][10][11][12][13]. The role of nutrition, lifestyle and environmental factors on increased oxidative stress, overactive immune system, and inactivation of anti-aging genes[14] has increased interest in the treatment, care, and diagnosis of neuropsychiatric disorders-early diagnosis with relevance to anti-aging genesis critical to prevent autoimmune reactions[3,7,14] associated withmajor subcellular alterations such as mitochondrial apoptosis and endoplasmic reticulum (ER) stress in neurons[15][16][17][18][19][20][21] that may lead to accelerated programmed cell death in neuropsychiatric conditions and global chronic disease.](image-2.png "Figure 1 :") 2![Figure 2: Inactivation of genes such as Sirtuin 1 (Sirt 1) is associated with ER stress and the induction of mitophagy in neuropsychiatric disorders. Cholesterol dysregulation and toxic amyloid beta formation are associated with Sirt 1 inactivation by LPS with relevance to neuropsychiatric diseases in the developing world. Phosphatidylinositol (PI) may reduce membrane cholesterol levels and amyloid beta oligomers to treat mitophagy and ER stress in liver and brain diseases (2). N-Nucleus.](image-3.png "Figure 2 :") 4![Figure 4: Appetite control is essential to maintain Sirt 1 activityand therapeutic drug metabolism with the prevention of drug-drug interactions in neuropsychiatric disorders. Nutrigenomic diets that contain Sirt 1 activators are vital for the treatment of neuropsychiatric disease and the prevention of mitophagy induced ER stress. Caffeine intake should be controlled to maintain therapeutic drug treatment. Excessive anxiety and pressure should be avoided to preserve nitric oxide homeostasis and immune reactions with relevance to autoimmune and neurodegenerative diseases.II.](image-4.png "Figure 4 :") ![](image-5.png "") Early Diagnosis and Nutritional Treatment Stabilizes Neuropsychiatric Disorders Year 2018 ## Acknowledgements * Diagnosis and treatment of neuropsychiatric disorders KHTaber RAHurley SCYudofsky Annu Rev Med 61 2010 * Diabetes and Organ Dysfunction in the Developing and Developed World IJMartins GJMR 15 2015 * Genomic medicine and acute cardiovascular disease progression in diabetes IJMartins Res Chron Dis 2 2018 * Neuropsychiatric screening in type 2 diabetes mellitus SKKota LKMeher SJammula SV SKrishna SKKota Indian J Endocrinol Metab 16 Suppl1 2012 * Diabetes and psychiatric disorders YP SBalhara Indian J Endocrinol Metab 15 2011 * Neuropsychiatric disorders at the presentation of type 2 diabetes mellitus in children LevittKatz LESwami SAbraham MMurphy KMJawad AF Pediatr Diabetes 6 2005 * Genomic Medicine and Endocrine Autoimmunity as Key to Mitochondrial Disease IJMartins Glob J Endocrinol Metab 2 2018 * The immune system and neuropsychiatric diseases DKerr CKrishnan MLPucak JCarmen Int Rev Psychiatry 17 2005 * AMRatnaseelan ITsilioni TCTheoharides Effects of Mycotoxins on Neuropsychiatric Symptoms and Immune Processes 2018 40 * The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders GMorris MBerk BMC Med 13 68 2015 * FARadtke GChapman JHall YASyed Modulating Neuroinflammation to Treat Neuropsychiatric Disorders 2017 * BioMed Res Int 2017 * The membrane hypothesis of schizophrenia DFHorrobin AIGlen KVaddadi Schizophr Res 13 1994 * Alterations of brain membranes in schizophrenia: impact of phospholipase A (2) ELSchaeffer WFGattaz GPEckert Curr Top Med Chem 12 2012 * Increased Risk for Obesity and Diabetes with Neurodegeneration in Developing Countries. Top 10 Contribution on IJMartins Genetics. Avid Science 1 2018 * Crosstalk between endoplasmic reticulum stress and oxidative stress in schizophrenia: The dawn of new therapeutic approaches SPatel DSharma KKalia VTiwari Neurosci Biobehav Rev 83 2017 * Endoplasmic reticulum stress and inflammation in the central nervous system NTSprenkle SGSims CLSánchez GPMeares Mol Neurodegener 12 42 2017 * Recent Insights into the Role of Unfolded Protein Response in ER Stress in Health and Disease DLindholm LKorhonen OEriksson SKõks Front Cell Dev Biol 5 48 2017 * Mitochondrial Etiology of Neuropsychiatric Disorders DC AWallace JAMA Psychiatry 74 2017 * Neuropsychiatric Features in Primary Mitochondrial Disease SEMarin RPSaneto Neurol Clin 34 2016 * Mitochondrial Etiology of Neuropsychiatric Disorders LPei DCWallace Biol Psychiatry 83 2018 * Mitochondrial alterations and neuropsychiatric disorders DMarazziti SBaroni MPicchetti PLandi SSilvestri Curr Med Chem 18 2011 * The genetics of neuropsychiatric diseases: looking in and beyond the exome ELHeinzen BMNeale SFTraynelis ASAllen DBGoldstein Annu Rev Neurosci 38 2015 * The cognitive genetics of neuropsychiatric disorders ACorvin GDonohoe AHargreaves LGallagher MGill Curr Top Behav Neurosci 12 2012 * Nature and nurture in neuropsychiatric genetics: where do we stand? DMDick BRiley KSKendler Dialogues Clin Neurosci 12 2010 * Anti-Aging Genes Improve Appetite Regulation and Reverse Cell Senescence and IJMartins Apoptosis in Global Populations. AAR 5 2016 * Single Gene Inactivation with Implications to Diabetes and Multiple Organ Dysfunction Syndrome IJMartins J Clin Epigenet 3 24 2017 * Epigenetic approaches to psychiatric disorders CPtak APetronis Dialogues Clin Neurosci 12 2010 * MMahgoub LMMonteggia Epigenetics and psychiatry 10 2013 Neurotherapeutics * TKishi YFukuo TKitajima TOkochi YYamanouchi SIRT1 gene, schizophrenia and bipolar disorder in the Japanese population: an association study 2011 10 * Role and Possible Mechanisms of Sirt1 in Depression GLu JLi HZhang XZhao L-JYan Oxidative Medicine and Cellular Longevity 2018 2018 * SIRT1 Mediates Depression-Like Behaviors in the Nucleus Accumbens H-DKim JHesterman TCall SMagazu EKeeley J Neurosci 36 2016 * To Stay Happy, Keep Your SIRT1 Active SChatterjee TAbel Biol Psychiatry 80 2016 * Role of Sirtuins in Linking Metabolic Syndrome with Depression JSong JKim Front Cell Neurosci 10 86 2016 * LLo Iacono FVisco-Comandini AValzania MTViscomi MCoviello Adversity in childhood and depression: linked through SIRT1 2015 5 e629 * NAbe-Higuchi SUchida HYamagata FHiguchi THobara Hippocampal Sirtuin 1 2016 * Signaling Mediates Depression-like Behavior Biol Psychiatry 80 * Role of SIRT1/PGC-1? in mitochondrial oxidative stress in autistic spectrum disorder XBu DWu XLu LYang XXu Neuropsychiatr Dis Treat 13 2017 * AZHerskovits LGuarente SIRT1 in neurodevelopment and brain senescence 2014 81 * The role of de novo protein synthesis and SIRT1 in ER stress-induced Atf4 and Chop mRNA expression in mammalian cells SM HChan XZhao AElfowiris CRatnam TPHerbert Biochimie 138 2017 * SIRT1 attenuates palmitate-induced endoplasmic reticulum stress and insulin resistance in HepG2 cells via induction of oxygen-regulated protein 150 TWJung KTLee MWLee KHKa Biochem Biophys Res Commun 422 2012 * Hepatic over expression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver YLi SXu AGiles KNakamura JWLee FASEB J 25 2011 * Endoplasmic Reticulum (ER) Stress Induces Sirtuin 1 (SIRT1) Expression via the PI3K-Akt-GSK3? Signaling Pathway and Promotes Hepatocellular Injury TKoga MASuico SShimasaki EWatanabe YKai J Biol Chem 290 2015 * SIRT1 protects the heart from ER stress-induced cell death through eIF2? deacetylation AProla JPires Da Silva AGuilbert LLecru JPiquereau Cell Death Differ 24 2017 * Heat Shock Gene Inactivation and Protein Aggregation with Links to Chronic Diseases IJMartins 2018 6 * The Future of Genomic Medicine Involves the Maintenance of Sirtuin 1 in Global Populations IJMartins Int J Mol Biol 2 13 2017 * Bacterial Lipopolysaccharides Change Membrane Fluidity with Relevance to Phospholipid and Amyloid Beta Dynamics in Alzheimer's Disease JMartinsi J Microb Biochem Technol 8 2016 * IJMartins LPS Regulates Apolipoprotein E and A? Interactions with Effects on Acute Phase Proteins and Amyloidosis. AAR 2015 4 * Appetite Regulation and the Peripheral Sink Amyloid beta Clearance Pathway in Diabetes and Alzheimer's Disease. Top 10 Commentaries in Alzheimer's Disease IJMartins Avid Science 2 2018 * Brain membrane lipids in major depression and anxiety disorders CPMüller MReichel CMühle CRhein EGulbins Biochim Biophys Acta 1851 2015 * Bipolar disorder and cell membrane dysfunction. Progress toward integrative management PMKidd Altern Med Rev 9 2004 * Over nutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases IJMartins Int J Mol Sci 16 2015 * The nitric oxide pathway: potential implications for treatment of neuropsychiatric disorders JKaratinos RBRosse SIDeutsch Clin Neuropharmacol 18 1995 * Nitric oxide as a physiopathological factor in neuropsychiatric disorders OAkyol SSZoroglu FArmutcu SSahin AGurel In Vivo 18 2004 * Antimicrobial activity inactivation and toxic immune reactions induce Epilepsy in human IJMartins J Med Discov 2 2017 * Nutritional diets accelerate amyloid beta metabolism and prevent the induction of chronic diseases and Alzheimer's disease. Photon ebooks IJMartins 2015 * PDHarvey RKHeaton WTCarpenter MFGreen JMGold Diagnosis of Schizophrenia: Consistency Across information Sources and Stability of the Condition 2012 140 * The diagnostic concept of schizophrenia: its history, evolution, and future prospects AJablensky Dialogues Clin Neurosci 12 2010 * Awareness, Diagnosis, and Treatment of Depression LSGoldman NHNielsen HCChampion J Gen Intern Med 14 1999 * Problems associated with the diagnosis of depression AJRush J Clin Psychiatry 51 1990 * The diagnosis of depression: current and emerging methods KMSmith PFRenshaw JBilello Compr Psychiatry 54 2013 * The Diagnosis and Treatment of Bipolar Disorder: Decision-Making in Primary Care LCulpepper PCC.13r01609 Prim Care Companion CNS Disord 16 2014 * Sirtuin 1, a Diagnostic Protein Marker and its Relevance to Chronic Disease and Therapeutic Drug Interventions IJMartins 2018 * Magnesium Therapy Prevents Senescence with the Reversal of Diabetes and Alzheimer's Disease. Health IJMartins 2016 8 * Nutrition Therapy Regulates Caffeine Metabolism with Relevance to NAFLD and Induction of Type 3 Diabetes IJMartins J Diabetes Metab Disord 4 19 2017 * Membrane lipidomics in schizophrenia patients: a correlational study with clinical and cognitive manifestations CTessier KSweers AFrajerman HBergaoui FFerreri Transl Psychiatry 6 e906 2016 * The Future of Biomarkers Tests and Genomic Medicine in Global Organ Disease IJMartins Microbiology and Infectious Diseases 1 2017 * IJMartins Biomarker Tests and Ageing Science 2017 1 * Dietary Intake of Patients with Schizophrenia MStrassnig JSBrar RGanguli Psychiatry (Edgmont) 2 2005 * The dietary pattern of patients with schizophrenia: a systematic review SDipasquale CMPariante PDazzan EAguglia PMcguire J Psychiatr Res 47 2013 * Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature BDKraft ECWestman 6:10 Nutr Metab 2009 * Understanding nutrition, depression and mental illnesses SathyanarayanaRao TSAsha MRRamesh BN JagannathaRao KS Indian J Psychiatry 50 2008 * Functional Foods and Active molecules with relevance to Health and Chronic disease IJMartins FFHD 7 2017 * Unhealthy Nutrigenomic Diets Accelerate NAFLD and Adiposity in Global communities IJMartins J Mol Genet Med 9 2015