The promise of biological markers for treatment response in first-episode psychosis: A systematic review

Schizophrenia Bulletin

Volumn 41, Issue 3, 2015, Pages 559-573

  Fond, Guillaume ^a,b,c   D'Albis, Marc Antoine ^a,b,c   Jamain, Stéphane ^a,b,c   Tamouza, Ryad ^d   Arango, Celso ^e   Fleischhacker, W Wolfgang ^f   Glenthøj, Birte ^g   Leweke, Markus ^h   Lewis, Shôn ⁱ   McGuire, Phillip ^j   Meyer Lindenberg, Andreas ^h   Sommer, Iris E ^k   Winter Van Rossum, Inge ^k   Kapur, Shitij ^j   Kahn, René S ^k   Rujescu, Dan ^l   Leboyer, Marion ^a,b,c  

^a INSERM U955   (France)

^b UNIVERSITÉ PARIS EST CRÉTEIL   (France)

^c FONDATION FONDAMENTAL   (France)

^d SAINT LOUIS HOSPITAL   (France)

^e UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^f INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^g UNIVERSITY OF COPENHAGEN   (Denmark)

^h UNIVERSITY OF HEIDELBERG   (Germany)

ⁱ UNIVERSITY OF MANCHESTER   (United Kingdom)

^j KING'S COLLEGE LONDON   (United Kingdom)

^k UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^l MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

more..

Author keywords

Antipsychotic response; Biomarker; Cortisol; First episode psychosis; Hormonal; Infla mmation; Oxidative stress; Pharmacogenetic

Indexed keywords

ANTIOXIDANT; BIOLOGICAL MARKER; CATALASE; CORTICOTROPIN; DOPAMINE 2 RECEPTOR; GAMMA INTERFERON; GLUTATHIONE; HYDROCORTISONE; INTERLEUKIN 12; INTERLEUKIN 17; INTERLEUKIN 1BETA; INTERLEUKIN 6; MONOAMINE DERIVATIVE; NEUROLEPTIC AGENT; POLYUNSATURATED FATTY ACID; SUPEROXIDE DISMUTASE; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA;

DOPAMINERGIC TRANSMISSION; DRUG METABOLISM; EXPERIMENTAL THERAPY; FEMALE; GENE TARGETING; GENETIC CODE; HUMAN; HYPOPHYSIS ADRENAL SYSTEM; IMMUNE RESPONSE; INFECTION; MALE; OXIDATIVE STRESS; PHARMACOGENETICS; PRIORITY JOURNAL; PROGNOSIS; PSYCHOSIS; REVIEW; SENSITIVITY ANALYSIS; SIGNAL TRANSDUCTION; STRESS; SYSTEMATIC REVIEW; TREATMENT RESPONSE; URINE LEVEL; METABOLISM; OUTCOME ASSESSMENT; PSYCHOTIC DISORDERS;

ANTIPSYCHOTIC AGENTS; BIOMARKERS; HUMANS; OUTCOME ASSESSMENT (HEALTH CARE); PSYCHOTIC DISORDERS;

EID: 84949452821     PISSN: 05867614     EISSN: 17451701     Source Type: Journal    
DOI: 10.1093/schbul/sbv002     Document Type: Review

References (144)

1. Insel TR, Voon V, Nye JS, et al. Innovative solutions to novel drug development in mental health. Neurosci Biobehav Rev. 2013;37:2438-2444.
2. Kapur S, Phillips AG, Insel TR. Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it? Mol Psychiatry. 2012;17:1174-1179.
3. Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation. 2006;113:2335-2362.
4. Birchwood M, Todd P, Jackson C. Early intervention in psychosis. The critical period hypothesis. Br J Psychiatry Suppl. 1998;172:53-59.
5. Chiliza B, Asmal L, Emsley R. Early intervention in schizophrenia in developing countries: focus on duration of untreated psychosis and remission as a treatment goal. Int Rev Psychiatry. 2012;24:483-488.
6. Drancourt N, Etain B, Lajnef M, et al. Duration of untreated bipolar disorder: missed opportunities on the long road to optimal treatment. Acta Psychiatr Scand. 2013;127:136-144.
7. Fraguas D, Merchán-Naranjo J, del Rey-Mejías Á, et al. A longitudinal study on the relationship between duration of untreated psychosis and executive function in early-onset first-episode psychosis. Schizophr Res. 2014;158:126-133.
8. Subotnik KL, Ventura J, Gretchen-Doorly D, et al. The impact of second-generation antipsychotic adherence on positive and negative symptoms in recent-onset schizophrenia. Schizophr Res. 2014;159:95-100.
9. Lieberman JA, Tollefson G, Tohen M, et al. Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Am J Psychiatry. 2003;160:1396-1404.
10. Lieberman JA. Prediction of outcome in first-episode schizophrenia. J Clin Psychiatry. 1993;54(suppl):13-17.
11. Capdevielle D, Norton J, Jaussent I, et al. Extended duration of hospitalization in first episode psychosis: an evaluation of its clinical justification. Psychiatry Res. 2013;209:160-166.
12. Reininghaus U, Dutta R, Dazzan P, et al. Mortality in schizophrenia and other psychoses: a 10-year follow-up of the SOP first-episode cohort [published online ahead of print September 27, 2014]. Schizophr Bull. doi: 10.1093/schbul/sbu138.
13. Kahn RS, Sommer IE. The neurobiology and treatment of first-episode schizophrenia [published online ahead of print July 22, 2014]. Mol Psychiatry. doi: 10.1038/mp.2014.66.
14. Tansella M, Balestrieri A. The choice of neuroleptics in the treatment of schizophrenia: a critical review. Arzneimittelforschung. 1976;26:943-945.
15. Luykx JJ, Bakker SC, Lentjes E, et al. Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid. Mol Psychiatry. 2014;19:228-234.
16. Nagaoka S, Iwamoto N, Arai H. First-episode neurolepticfree schizophrenics: concentrations of monoamines and their metabolites in plasma and their correlations with clinical responses to haloperidol treatment. Biol Psychiatry. 1997;41:857-864.
17. Koreen AR, Lieberman J, Alvir J, et al. Plasma homovanillic acid levels in first-episode schizophrenia. Psychopathology and treatment response. Arch Gen Psychiatry. 1994;51:132-138.
18. Baeza I, Castro-Fornieles J, Deulofeu R, et al. Plasma homovanillic acid differences in clinical subgroups of first episode schizophrenic patients. Psychiatry Res. 2009;168:110-118.
19. Howes OD, Kapur S. A neurobiological hypothesis for the classification of schizophrenia: type A (hyperdopaminergic) and type B (normodopaminergic). Br J Psychiatry. 2014;205:1-3.
20. Howes OD, Kambeitz J, Kim E, et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry. 2012;69:776-786.
21. Howes OD, Egerton A, Allan V, McGuire P, Stokes P, Kapur S. Mechanisms underlying psychosis and antipsychotic treatment response in schizophrenia: insights from PET and SPECT imaging. Curr Pharm Des. 2009;15:2550-2559.
22. Egerton A, Brugger S, Raffin M, et al. Anterior cingulate glutamate levels related to clinical status following treatment in first-episode schizophrenia. Neuropsychopharmacology. 2012;37:2515-2521.
23. Demjaha A, Murray RM, McGuire PK, Kapur S, Howes OD. Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. Am J Psychiatry. 2012;169:1203-1210.
24. Demjaha A, Egerton A, Murray RM, et al. Antipsychotic treatment resistance in schizophrenia associated with elevated glutamate levels but normal dopamine function. Biol Psychiatry. 2014;75:e11-e13.
25. Yoshimura R, Ueda N, Shinkai K, Nakamura J. Plasma levels of homovanillic acid and the response to risperidone in first episode untreated acute schizophrenia. Int Clin Psychopharmacol. 2003;18:107-111.
26. Condray R, Dougherty GG Jr, Keshavan MS, et al. 3-Hydroxykynurenine and clinical symptoms in first-episode neuroleptic-naive patients with schizophrenia. Int J Neuropsychopharmacol. 2011;14:756-767.
27. Mohr P, Horácek J, Motlová L, Libiger J, Czobor P. Prolactin response to D-fenfluramine challenge test as a predictor of treatment response to haloperidol in acute schizophrenia. Schizophr Res. 1998;30:91-99.
28. van der Heijden FM, Tuinier S, Fekkes D, Sijben AE, Kahn RS, Verhoeven WM. Atypical antipsychotics and the relevance of glutamate and serotonin. Eur Neuropsychopharmacol. 2004;14:259-265.
29. Rasmussen H, Ebdrup BH, Oranje B, Pinborg LH, Knudsen GM, Glenthøj B. Neocortical serotonin2A receptor binding predicts quetiapine associated weight gain in antipsychotic- naive first-episode schizophrenia patients. Int J Neuropsychopharmacol. 2014;17:1729-1736.
30. Cai HL, Li HD, Yan XZ, et al. Metabolomic analysis of biochemical changes in the plasma and urine of first-episode neuroleptic-naïve schizophrenia patients after treatment with risperidone. J Proteome Res. 2012;11:4338-4350.
31. Brandl EJ, Kennedy JL, Müller DJ. Pharmacogenetics of antipsychotics. Can J Psychiatry. 2014;59:76-88.
32. Reynolds GP, Yao Z, Zhang X, Sun J, Zhang Z. Pharmacogenetics of treatment in first-episode schizophrenia: D3 and 5-HT2C receptor polymorphisms separately associate with positive and negative symptom response. Eur Neuropsychopharmacol. 2005;15:143-151.
33. Ikeda M, Yamanouchi Y, Kinoshita Y, et al. Variants of dopamine and serotonin candidate genes as predictors of response to risperidone treatment in first-episode schizophrenia. Pharmacogenomics. 2008;9:1437-1443.
34. Lencz T, Robinson DG, Xu K, et al. DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients. Am J Psychiatry. 2006;163:529-531.
35. Zalsman G, Frisch A, Lev-Ran S, et al. DRD4 exon III polymorphism and response to risperidone in Israeli adolescents with schizophrenia: a pilot pharmacogenetic study. Eur Neuropsychopharmacol. 2003;13:183-185.
36. Pelayo-Terán JM, Pérez-Iglesias R, Vázquez-Bourgon J, et al. Catechol-O-methyltransferase Val158Met polymorphism and negative symptoms after acute antipsychotic treatment in first-episode non-affective psychosis. Psychiatry Res. 2011;185:286-289.
37. Vázquez-Bourgon J, Arranz MJ, Mata I, et al. Serotonin transporter polymorphisms and early response to antipsychotic treatment in first episode of psychosis. Psychiatry Res. 2010;175:189-194.
38. Reynolds GP, Arranz B, Templeman LA, Fertuzinhos S, San L. Effect of 5-HT1A receptor gene polymorphism on negative and depressive symptom response to antipsychotic treatment of drug-naive psychotic patients. Am J Psychiatry. 2006;163:1826-1829.
39. Ravyn D, Ravyn V, Lowney R, Nasrallah HA. CYP450 pharmacogenetic treatment strategies for antipsychotics: a review of the evidence. Schizophr Res. 2013;149:1-14.
40. Jovanović N, Božina N, Lovrić M, Medved V, Jakovljević M, Peleš AM. The role of CYP2D6 and ABCB1 pharmacogenetics in drug-naïve patients with first-episode schizophrenia treated with risperidone. Eur J Clin Pharmacol. 2010;66:1109-1117.
41. Barteček R, Juřica J, Zrůstová J, Kašpárek T, Pindurová E, Žourková A. Relevance of CYP2D6 variability in first-episode schizophrenia patients treated with risperidone. Neuro Endocrinol Lett. 2012;33:236-244.
42. Zhang JP, Malhotra AK. Pharmacogenetics of antipsychotics: recent progress and methodological issues. Expert Opin Drug Metab Toxicol. 2013;9:183-191.
43. Lencz T, Robinson DG, Napolitano B, et al. DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia. Pharmacogenet Genomics. 2010;20:569-572.
44. Reynolds GP, Zhang ZJ, Zhang XB. Association of antipsychotic drug-induced weight gain with a 5-HT2C receptor gene polymorphism. Lancet. 2002;359:2086-2087.
45. Reynolds GP, Zhang Z, Zhang X. Polymorphism of the promoter region of the serotonin 5-HT(2C) receptor gene and clozapine-induced weight gain. Am J Psychiatry. 2003;160:677-679.
46. Templeman LA, Reynolds GP, Arranz B, San L. Polymorphisms of the 5-HT2C receptor and leptin genes are associated with antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode psychosis. Pharmacogenet Genomics. 2005;15:195-200.
47. Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry. 2011;70:663-671.
48. Song X, Fan X, Song X, et al. Elevated levels of adiponectin and other cytokines in drug naïve, first episode schizophrenia patients with normal weight. Schizophr Res. 2013;150:269-273.
49. Severance EG, Gressitt KL, Halling M, et al. Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia. Neurobiol Dis. 2012;48:447-453.
50. Borovcanin M, Jovanovic I, Radosavljevic G, et al. Elevated serum level of type-2 cytokine and low IL-17 in first episode psychosis and schizophrenia in relapse. J Psychiatr Res. 2012;46:1421-1426.
51. Di Nicola M, Cattaneo A, Hepgul N, et al. Serum and gene expression profile of cytokines in first-episode psychosis. Brain Behav Immun. 2013;31:90-95.
52. Upthegrove R, Manzanares-Teson N, Barnes NM. Cytokine function in medication-naive first episode psychosis: a systematic review and meta-analysis. Schizophr Res. 2014;155:101-108.
53. Ramsey JM, Schwarz E, Guest PC, et al. Distinct molecular phenotypes in male and female schizophrenia patients. PLoS One. 2013;8:e78729.
54. Tourjman V, Kouassi É, Koué MÈ, et al. Antipsychotics' effects on blood levels of cytokines in schizophrenia: a metaanalysis. Schizophr Res. 2013;151:43-47.
55. Crespo-Facorro B, Pérez-Iglesias R, Mata I, et al. Longterm (3-year) effectiveness of haloperidol, risperidone and olanzapine: results of a randomized, flexible-dose, openlabel comparison in first-episode nonaffective psychosis. Psychopharmacology (Berl). 2012;219:225-233.
56. MacDowell KS, García-Bueno B, Madrigal JL, et al. Risperidone normalizes increased inflammatory parameters and restores anti-inflammatory pathways in a model of neuroinflammation. Int J Neuropsychopharmacol. 2013;16:121-135.
57. Kubistova A, Horacek J, Novak T. Increased interleukin-6 and tumor necrosis factor alpha in first episode schizophrenia patients versus healthy controls. Psychiatr Danub. 2012;24(suppl 1):S153-S156.
58. de Witte L, Tomasik J, Schwarz E, et al. Cytokine alterations in first-episode schizophrenia patients before and after antipsychotic treatment. Schizophr Res. 2014;154:23-29.
59. Ding M, Song X, Zhao J, et al. Activation of Th17 cells in drug naïve, first episode schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2014;51:78-82.
60. Duffy D, Rouilly V, Libri V, et al. Functional analysis via standardized whole-blood stimulation systems defines the boundaries of a healthy immune response to complex stimuli. Immunity. 2014;40:436-450.
61. Fond G, Hamdani N, Kapczinski F, et al. Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review. Acta Psychiatr Scand. 2014;129:163-179.
62. Müller N, Krause D, Dehning S, et al. Celecoxib treatment in an early stage of schizophrenia: results of a randomized, double-blind, placebo-controlled trial of celecoxib augmentation of amisulpride treatment. Schizophr Res. 2010;121:118-124.
63. Berger GE, Proffitt TM, McConchie M, et al. Ethyleicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial. J Clin Psychiatry. 2007;68:1867-1875.
64. Liu F, Guo X, Wu R, et al. Minocycline supplementation for treatment of negative symptoms in early-phase schizophrenia: a double blind, randomized, controlled trial. Schizophr Res. 2014;153:169-176.
65. Levkovitz Y, Mendlovich S, Riwkes S, et al. A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry. 2010;71:138-149.
66. Brown AS. Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism. Dev Neurobiol. 2012;72:1272-1276.
67. Brown AS, Begg MD, Gravenstein S, et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry. 2004;61:774-780.
68. Canetta SE, Bao Y, Co MD, et al. Serological documentation of maternal influenza exposure and bipolar disorder in adult offspring. Am J Psychiatry. 2014;171:557-563.
69. Brown AS, Schaefer CA, Quesenberry CP Jr, Liu L, Babulas VP, Susser ES. Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring. Am J Psychiatry. 2005;162:767-773.
70. Mortensen PB, Nørgaard-Pedersen B, Waltoft BL, Sørensen TL, Hougaard D, Yolken RH. Early infections of Toxoplasma gondii and the later development of schizophrenia. Schizophr Bull. 2007;33:741-744.
71. Buka SL, Tsuang MT, Torrey EF, Klebanoff MA, Bernstein D, Yolken RH. Maternal infections and subsequent psychosis among offspring. Arch Gen Psychiatry. 2001;58:1032-1037.
72. Mortensen PB, Pedersen CB, Hougaard DM, et al. A Danish National Birth Cohort study of maternal HSV-2 antibodies as a risk factor for schizophrenia in their offspring. Schizophr Res. 2010;122:257-263.
73. Torrey EF, Bartko JJ, Yolken RH. Toxoplasma gondii and other risk factors for schizophrenia: an update. Schizophr Bull. 2012;38:642-647.
74. Bachmann S, Schröder J, Bottmer C, Torrey EF, Yolken RH. Psychopathology in first-episode schizophrenia and antibodies to Toxoplasma gondii. Psychopathology. 2005;38:87-90.
75. Strobl JS, Cassell M, Mitchell SM, Reilly CM, Lindsay DS. Scriptaid and suberoylanilide hydroxamic acid are histone deacetylase inhibitors with potent anti-Toxoplasma gondii activity in vitro. J Parasitol. 2007;93:694-700.
76. Jones-Brando L, Torrey EF, Yolken R. Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii. Schizophr Res. 2003;62:237-244.
77. Goodwin DG, Strobl JS, Lindsay DS. Evaluation of five antischizophrenic agents against Toxoplasma gondii in human cell cultures. J Parasitol. 2011;97:148-151.
78. Fond G, Macgregor A, Tamouza R, et al. Comparative analysis of anti-toxoplasmic activity of antipsychotic drugs and valproate. Eur Arch Psychiatry Clin Neurosci. 2014;264:179-183.
79. Wang HL, Xiang YT, Li QY, et al. The effect of artemether on psychotic symptoms and cognitive impairment in firstepisode, antipsychotic drug-naive persons with schizophrenia seropositive to Toxoplasma gondii. J Psychiatr Res. 2014;53:119-124.
80. Leweke FM, Gerth CW, Koethe D, et al. Antibodies to infectious agents in individuals with recent onset schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2004;254:4-8.
81. Yao Y, Schröder J, Nellåker C, et al. Elevated levels of human endogenous retrovirus-W transcripts in blood cells from patients with first episode schizophrenia. Genes Brain Behav. 2008;7:103-112.
82. Amminger GP, McGorry PD, Berger GE, et al. Antibodies to infectious agents in individuals at ultra-high risk for psychosis. Biol Psychiatry. 2007;61:1215-1217.
83. Stefansson H, Ophoff RA, Steinberg S, et al. Common variants conferring risk of schizophrenia. Nature. 2009;460:744-747.
84. Shi J, Levinson DF, Duan J, et al. Common variants on chromosome 6p22.1 are associated with schizophrenia. Nature. 2009;460:753-757.
85. Purcell SM, Wray NR, Stone JL, et al.; International Schizophrenia Consortium. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009;460:748-752.
86. Drago A, Giegling I, Schäfer M, et al. Genome-wide association study supports the role of the immunological system and of the neurodevelopmental processes in response to haloperidol treatment. Pharmacogenet Genomics. 2014;24:314-319.
87. Fournier M, Ferrari C, Baumann PS, et al. Impaired metabolic reactivity to oxidative stress in early psychosis patients. Schizophr Bull. 2014;40:973-983.
88. Yao JK, Dougherty GG, Reddy RD, Matson WR, Kaddurah- Daouk R, Keshavan MS. Associations between purine metabolites and monoamine neurotransmitters in first-episode psychosis. Front Cell Neurosci. 2013;7:90.
89. Mukherjee B, Ghosh S, Chatterjee M. Chemopreventive efficacy of selenomethionine and its role in the antioxidant defense system in 2-acetylaminofluorene-induced hepatocarcinogenesis in rats. J Exp Ther Oncol. 1996;1:209-217.
90. Fraguas D, Gonzalez-Pinto A, Micó JA, et al. Decreased glutathione levels predict loss of brain volume in children and adolescents with first-episode psychosis in a two-year longitudinal study. Schizophr Res. 2012;137:58-65.
91. Martínez-Cengotitabengoa M, Micó JA, Arango C, et al. Basal low antioxidant capacity correlates with cognitive deficits in early onset psychosis. A 2-year follow-up study. Schizophr Res. 2014;156:23-29.
92. Micó JA, Rojas-Corrales MO, Gibert-Rahola J, et al. Reduced antioxidant defense in early onset first-episode psychosis: a case-control study. BMC Psychiatry. 2011;11:26.
93. Reddy R, Keshavan M, Yao JK. Reduced plasma antioxidants in first-episode patients with schizophrenia. Schizophr Res. 2003;62:205-212.
94. Raffa M, Atig F, Mhalla A, Kerkeni A, Mechri A. Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive first-episode schizophrenic patients. BMC Psychiatry. 2011;11:124.
95. Mössner R, Schuhmacher A, Wagner M, et al. DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis. Eur Arch Psychiatry Clin Neurosci. 2010;260:209-215.
96. Reddy RD, Keshavan MS, Yao JK. Reduced red blood cell membrane essential polyunsaturated fatty acids in first episode schizophrenia at neuroleptic-naive baseline. Schizophr Bull. 2004;30:901-911.
97. Kale A, Naphade N, Sapkale S, et al. Reduced folic acid, vitamin B12 and docosahexaenoic acid and increased homocysteine and cortisol in never-medicated schizophrenia patients: implications for altered one-carbon metabolism. Psychiatry Res. 2010;175:47-53.
98. Smesny S, Schmelzer CE, Hinder A, et al. Skin ceramide alterations in first-episode schizophrenia indicate abnormal sphingolipid metabolism. Schizophr Bull. 2013;39:933-941.
99. Smesny S, Milleit B, Hipler UC, et al. Omega-3 fatty acid supplementation changes intracellular phospholipase A2 activity and membrane fatty acid profiles in individuals at ultra-high risk for psychosis. Mol Psychiatry. 2014;19:317-324.
100. Khan MM, Evans DR, Gunna V, Scheffer RE, Parikh VV, Mahadik SP. Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first-episode of psychosis and after years of treatment with antipsychotics. Schizophr Res. 2002;58:1-10.
101. Amminger GP, McGorry PD. Update on ω-3 polyunsaturated fatty acids in early-stage psychotic disorders. Neuropsychopharmacology. 2012;37:309-310.
102. Peters BD, Machielsen MW, Hoen WP, et al. Polyunsaturated fatty acid concentration predicts myelin integrity in earlyphase psychosis. Schizophr Bull. 2013;39:830-838.
103. Mahadik SP, Mukherjee S, Scheffer R, Correnti EE, Mahadik JS. Elevated plasma lipid peroxides at the onset of nonaffective psychosis. Biol Psychiatry. 1998;43:674-679.
104. Amminger GP, Schäfer MR, Papageorgiou K, et al. Longchain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010;67:146-154.
105. Wood SJ, Cocchi L, Proffitt TM, et al. Neuroprotective effects of ethyl-eicosapentaenoic acid in first episode psychosis: a longitudinal T2 relaxometry pilot study. Psychiatry Res. 2010;182:180-182.
106. Fond G, Macgregor A, Attal J, et al. Treating patients with schizophrenia deficit with erythropoietin? Psychiatry Clin Neurosci. 2012;66:375-382.
107. Sivrioglu EY, Kirli S, Sipahioglu D, Gursoy B, Sarandöl E. The impact of omega-3 fatty acids, vitamins E and C supplementation on treatment outcome and side effects in schizophrenia patients treated with haloperidol: an open-label pilot study. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:1493-1499.
108. Okusaga OO. Accelerated aging in schizophrenia patients: the potential role of oxidative stress. Aging Dis. 2014;5:256-262.
109. Peters A, Conrad M, Hubold C, Schweiger U, Fischer B, Fehm HL. The principle of homeostasis in the hypothalamuspituitary- adrenal system: new insight from positive feedback. Am J Physiol Regul Integr Comp Physiol. 2007;293:R83-R98.
110. Wolkowitz OM, Epel ES, Reus VI. Stress hormone-related psychopathology: pathophysiological and treatment implications. World J Biol Psychiatry. 2001;2:115-143.
111. Morley JE, Kaiser F, Raum WJ, et al. Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci USA. 1997;94:7537-7542.
112. Kimonides VG, Spillantini MG, Sofroniew MV, Fawcett JW, Herbert J. Dehydroepiandrosterone antagonizes the neurotoxic effects of corticosterone and translocation of stressactivated protein kinase 3 in hippocampal primary cultures. Neuroscience. 1999;89:429-436.
113. Kimonides VG, Khatibi NH, Svendsen CN, Sofroniew MV, Herbert J. Dehydroepiandrosterone (DHEA) and DHEAsulfate (DHEAS) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity. Proc Natl Acad Sci USA. 1998;95:1852-1857.
114. Walsh P, Spelman L, Sharifi N, Thakore JH. Male patients with paranoid schizophrenia have greater ACTH and cortisol secretion in response to metoclopramide-induced AVP release. Psychoneuroendocrinology. 2005;30:431-437.
115. Mondelli V, Pariante CM, Navari S, et al. Higher cortisol levels are associated with smaller left hippocampal volume in first-episode psychosis. Schizophr Res. 2010;119:75-78.
116. Mondelli V, Dazzan P, Hepgul N, et al. Abnormal cortisol levels during the day and cortisol awakening response in firstepisode psychosis: the role of stress and of antipsychotic treatment. Schizophr Res. 2010;116:234-242.
117. Ryan MC, Sharifi N, Condren R, Thakore JH. Evidence of basal pituitary-adrenal overactivity in first episode, drug naïve patients with schizophrenia. Psychoneuroendocrinology. 2004;29:1065-1070.
118. Walker EF, Trotman HD, Pearce BD, et al. Cortisol levels and risk for psychosis: initial findings from the North American prodrome longitudinal study. Biol Psychiatry. 2013;74:410-417.
119. Cullen AE, Zunszain PA, Dickson H, et al. Cortisol awakening response and diurnal cortisol among children at elevated risk for schizophrenia: relationship to psychosocial stress and cognition. Psychoneuroendocrinology. 2014;46:1-13.
120. Girshkin L, Matheson SL, Shepherd AM, Green MJ. Morning cortisol levels in schizophrenia and bipolar disorder: a metaanalysis. Psychoneuroendocrinology. 2014;49:187-206.
121. Aas M, Dazzan P, Mondelli V, et al. Abnormal cortisol awakening response predicts worse cognitive function in patients with first-episode psychosis. Psychol Med. 2011;41:463-476.
122. Garner B, Phassouliotis C, Phillips LJ, et al. Cortisol and dehydroepiandrosterone-sulphate levels correlate with symptom severity in first-episode psychosis. J Psychiatr Res. 2011;45:249-255.
123. Beyazyüz M, Albayrak Y, Beyazyüz E, Unsal C, Göka E. Increased serum dehydroepiandrosterone sulfate in the first episode but not in subsequent episodes in male patients with schizophrenia. Neuropsychiatr Dis Treat. 2014;10:687-693.
124. Strous RD, Maayan R, Kaminsky M, Blumensohn R, Weizman A, Spivak B. DHEA and DHEA-S levels in hospitalized adolescents with first-episode schizophrenia and conduct disorder: a comparison study. Eur Neuropsychopharmacol. 2009;19:499-503.
125. Strous RD, Maayan R, Lapidus R, et al. Increased circulatory dehydroepiandrosterone and dehydroepiandrosterone- sulphate in first-episode schizophrenia: relationship to gender, aggression and symptomatology. Schizophr Res. 2004;71:427-434.
126. Oades RD, Schepker R. Serum gonadal steroid hormones in young schizophrenic patients. Psychoneuroendocrinology. 1994;19:373-385.
127. Weitzman RE, Kleeman CR. The clinical physiology of water metabolism. Part I: The physiologic regulation of arginine vasopressin secretion and thirst. West J Med. 1979;131:373-400.
128. Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M. Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci. 2011;12:524-538.
129. Strupp B, Weingartner H, Goodwin FK, Gold PW. Neurohypophyseal hormones and cognition. Pharmacol Ther. 1983;23:267-279.
130. Carter CS. Neuroendocrine perspectives on social attachment and love. Psychoneuroendocrinology. 1998;23:779-818.
131. Heinrichs M, Domes G. Neuropeptides and social behaviour: effects of oxytocin and vasopressin in humans. Prog Brain Res. 2008;170:337-350.
132. Gutkowska J, Jankowski M. Oxytocin revisited: its role in cardiovascular regulation. J Neuroendocrinol. 2012;24:599-608.
133. Ferris CF. Functional magnetic resonance imaging and the neurobiology of vasopressin and oxytocin. Prog Brain Res. 2008;170:305-320.
134. Rubin LH, Carter CS, Bishop JR, et al. Peripheral vasopressin but not oxytocin relates to severity of acute psychosis in women with acutely-ill untreated first-episode psychosis. Schizophr Res. 2013;146:138-143.
135. Rubin LH, Carter CS, Bishop JR, et al. Reduced levels of vasopressin and reduced behavioral modulation of oxytocin in psychotic disorders. Schizophr Bull. 2014;40:1374-1384.
136. Wu X, Huang Z, Wu R, et al. The comparison of glycometabolism parameters and lipid profiles between drug-naïve, first-episode schizophrenia patients and healthy controls. Schizophr Res. 2013;150:157-162.
137. Verma SK, Subramaniam M, Liew A, Poon LY. Metabolic risk factors in drug-naive patients with first-episode psychosis. J Clin Psychiatry. 2009;70:997-1000.
138. Verma S, Liew A, Subramaniam M, Poon LY. Effect of treatment on weight gain and metabolic abnormalities in patients with first-episode psychosis. Aust N Z J Psychiatry. 2009;43:812-817.
139. Ryan MC, Collins P, Thakore JH. Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry. 2003;160:284-289.
140. Arranz B, Rosel P, Ramírez N, et al. Insulin resistance and increased leptin concentrations in noncompliant schizophrenia patients but not in antipsychotic-naive first-episode schizophrenia patients. J Clin Psychiatry. 2004;65:1335-1342.
141. Sengupta S, Parrilla-Escobar MA, Klink R, et al. Are metabolic indices different between drug-naïve first-episode psychosis patients and healthy controls? Schizophr Res. 2008;102:329-336.
142. Holmes E, Tsang TM, Huang JT, et al. Metabolic profiling of CSF: evidence that early intervention may impact on disease progression and outcome in schizophrenia. PLoS Med. 2006;3:e327.
143. Jiang P, Zhu MQ, Li HD, Liu YP, Cai HL, Zhang LM. Effects of vitamin D receptor polymorphisms on the risk of schizophrenia and metabolic changes caused by risperidone treatment. Psychiatry Res. 2014;215:806-807.
144. Wu TH, Chiu CC, Shen WW, et al. Pharmacokinetics of olanzapine in Chinese male schizophrenic patients with various smoking behaviors. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:1889-1893.