Skip to main content

Abstract

Psychiatric illnesses are cognitive and behavioral disorders of the brain. At present, psychiatric diagnosis is based on DSM-5 criteria. Even if endophenotype specificity for psychiatric disorders is discussed, it is difficult to study and identify psychiatric biomarkers to support diagnosis, prognosis, or clinical response to treatment. This chapter investigates the innovative biomarkers of psychiatric diseases for diagnosis and personalized treatment, in particular post-genomic data and proteomic analyses.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Katahira K, Yamashita Y (2017) A theoretical framework for evaluating psychiatric research strategies. Comput Psychiatr 1:184–207

    Article  PubMed  PubMed Central  Google Scholar 

  2. Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69(3):89–95

    Article  Google Scholar 

  3. Biomarkers and risk assessment: concepts and principles/published under the joint sponsorship of the United Nations environment Programme, the International Labour Organisation, and the World Health Organization (1993) http://www.who.int/iris/handle/10665/39037

  4. Boksa P (2013) A way forward for research on biomarkers for psychiatric disorders. J Psychiatry Neurosci 38(2):75–77

    Article  PubMed  PubMed Central  Google Scholar 

  5. Quevedo J, Yatham LN (2018) Biomarkers in mood disorders: are we there yet? J Affect Disord 233:1–2

    Article  PubMed  Google Scholar 

  6. Scarr E, Millan MJ, Bahn S, Bertolino A, Turck CW, Kapur S et al (2015) Biomarkers for psychiatry: the journey from fantasy to fact, a report of the 2013 CINP Think Tank. Int J Neuropsychopharmacol 18(10):pyv042. https://doi.org/10.1093/ijnp/pyv042

    Article  PubMed  PubMed Central  Google Scholar 

  7. Singh I, Rose N (2009) Biomarkers in psychiatry. Nature 460(7252):202–207

    Article  CAS  PubMed  Google Scholar 

  8. Dean B (2011) Dissecting the syndrome of schizophrenia: progress toward clinically useful biomarkers. Schizophr Res Treat 2011:614730. https://doi.org/10.1155/2011/614730

    Article  Google Scholar 

  9. McGorry P, Keshavan M, Goldstone S, Amminger P, Allott K, Berk M et al (2014) Biomarkers and clinical staging in psychiatry. World Psychiatry 13(3):211–223

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lydon-Staley DM, Bassett DS (2018) Network neuroscience: a framework for developing biomarkers in psychiatry. Curr Top Behav Neurosci 40:79-109

    Google Scholar 

  11. Bora E, Yucel M, Pantelis C (2009) Cognitive endophenotypes of bipolar disorder: a meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. J Affect Disord 113(1–2):1–20

    Article  PubMed  Google Scholar 

  12. Snyder HR (2013) Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review. Psychol Bull 139(1):81–132

    Article  PubMed  Google Scholar 

  13. Porcelli S, Van Der Wee N, van der Werff S, Aghajani M, Glennon JC, van Heukelum S et al (2018) Social brain, social dysfunction and social withdrawal. Neurosci Biobehav Rev Sep 20. doi: 10.1016/j.neubiorev.2018.09.012. [Epub ahead of print]

    Google Scholar 

  14. Lozupone M, Panza F, Piccininni M, Copetti M, Sardone R, Imbimbo BP et al (2018) Social dysfunction in older age and relationships with cognition, depression, and apathy: the GreatAGE Study. J Alzheimers Dis 65(3):989–1000

    Article  PubMed  Google Scholar 

  15. Tansey KE, Guipponi M, Perroud N, Bondolfi G, Domenici E, Evans D et al (2012) Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis. PLoS Med 9(10):e1001326. https://doi.org/10.1371/journal.pmed.1001326

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rabinowitz J, Werbeloff N, Caers I, Mandel FS, Stauffer V, Ménard F et al (2014) Determinants of antipsychotic response in schizophrenia: implications for practice and future clinical trials. J Clin Psychiatry 75(4):e308–e316

    Article  CAS  PubMed  Google Scholar 

  17. Panza F, Lozupone M, Stella E, Lofano L, Gravina C, Urbano M (2016) Psychiatry meets pharmacogenetics for the treatment of revolving door patients with psychiatric disorders. Expert Rev Neurother 16(12):1357–1369

    Article  CAS  PubMed  Google Scholar 

  18. Panza F, Lozupone M, Stella E, Miscio G, La Montagna M, Daniele A (2016) The pharmacogenetic road to avoid adverse drug reactions and therapeutic failures in revolving door patients with psychiatric illnesses: focus on the CYP2D6 isoenzymes. Expert Rev Precis Med Drug Dev 1(5):431–442

    Article  Google Scholar 

  19. Hurko O (2009) The uses of biomarkers in drug development. Ann N Y Acad Sci 1180:1–10

    Article  CAS  PubMed  Google Scholar 

  20. Lozupone M, Seripa D, Stella E, La Montagna M, Solfrizzi V, Quaranta N et al (2017) Innovative biomarkers in psychiatric disorders: a major clinical challenge in psychiatry. Expert Rev Proteomics 14(9):809–824

    Article  CAS  PubMed  Google Scholar 

  21. Petterson RF (1990) Mapping and sequencing the human genome. Ann Med 22(6):371–373

    Article  Google Scholar 

  22. Higa GS, De Sousa E, Walter LT, Kinjo ER, Resende RR, Kihara AH (2014) MicroRNAs in neuronal communication. Mol Neurobiol 49(3):1309–1326

    CAS  PubMed  Google Scholar 

  23. Mohammadi A, Rashidi E, Amooeian VG (2018) Brain, blood, cerebrospinal fluid, and serum biomarkers in schizophrenia. Psychiatry Res 265:25–38

    Article  CAS  PubMed  Google Scholar 

  24. Sigitova E, FiÅ¡ar Z, HroudovĂ¡ CT, Raboch J (2017) Biological hypotheses and biomarkers of bipolar disorder. Psychiatry Clin Neurosci 71(2):77–103

    Article  PubMed  Google Scholar 

  25. Hacimusalar Y, Eşel E (2018) Suggested biomarkers for major depressive disorder. Noro Psikiyatr Ars 55(3):280–290

    PubMed  PubMed Central  Google Scholar 

  26. Strawbridge R, Young AH, Cleare AJ (2017) Biomarkers for depression: recent insights, current challenges and future prospects. Neuropsychiatr Dis Treat 13:1245–1262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Alawieh A, Zaraket FA, Li JL, Mondello S, Nokkari A, Razafsha M et al (2012) Systems biology, bioinformatics, and biomarkers in neuropsychiatry. Front Neurosci 6:187. https://doi.org/10.3389/fnins.2012.00187

    Article  PubMed  PubMed Central  Google Scholar 

  28. Han KM, Kim YK (2018) Promising neural diagnostic biomarkers and predictors of treatment outcomes for psychiatric disorders: novel neuroimaging approaches. Prog Neuropsychopharmacol Biol Psychiatry. pii: S0278-5846(18)30773-5. https://doi.org/10.1016/j.pnpbp.2018.10.001

  29. Pasternak O, Kelly S, Sydnor VJ (2018) Advances in microstructural diffusion neuroimaging for psychiatric disorders. NeuroImage 182:259–282. https://doi.org/10.1016/j.neuroimage.2018.04.051

    Article  PubMed  Google Scholar 

  30. Shenton ME, Javadpour A, Mohammadi A (2016) Improving brain magnetic resonance image (MRI) segmentation via a novel algorithm based on genetic and regional growth. J Biomed Phys Eng 6(2):95–108

    Google Scholar 

  31. Zipursky RB (2007) Imaging mental disorders in the 21st century. Can J Psychiatr 52(3):133–134

    Article  Google Scholar 

  32. Bailey DL, Pichler BJ, GĂ¼ckel B, Barthel H, Beer AJ, Botnar R et al (2016) Combined PET/MRI: from Status Quo to Status Go. Summary report of the fifth international workshop on PET/MR imaging, February 15–19, 2016, TĂ¼bingen, Germany. Mol Imaging Biol 18(5):637–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ngounou Wetie AG, Sokolowska I, Wormwood K, Beglinger K, Michel TM, Thome J (2013) Mass spectrometry for the detection of potential psychiatric biomarkers. J Mol Psychiatry 1(1):8. https://doi.org/10.1186/2049-9256-1-8

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ross CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT (2006) Neurobiology of schizophrenia. Neuron 52(1):139–153

    Article  CAS  PubMed  Google Scholar 

  35. Niznikiewicz MK, Kubicki M, Shenton ME (2003) Recent structural and functional imaging findings in schizophrenia. Curr Opin Psychiatry 16:123–147

    Article  Google Scholar 

  36. Cannon TD, Glahn DC, Kim J, Van Erp TG, Karlsgodt K, Cohen MS et al (2005) Dorsolateral prefrontal cortex activity during maintenance and manipulation of information in working memory in patients with schizophrenia. Arch Gen Psychiatry 62:1071–1080

    Article  PubMed  Google Scholar 

  37. Wang L, Metzak PD, Honer WG, Woodward TS (2010) Impaired efficiency of functional networks underlying episodic memory-for-context in schizophrenia. J Neurosci 30(39):13171–13179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Anderson A, Cohen MS (2013) Decreased small-world functional network connectivity and clustering across resting state networks in schizophrenia: an fMRI classification tutorial. Front Hum Neurosci 7:520. https://doi.org/10.3389/fnhum.2013.00520

    Article  PubMed  PubMed Central  Google Scholar 

  39. Liu Y, Liang M, Zhou Y, He Y, Hao Y, Song M et al (2008) Disrupted small-world networks in schizophrenia. Brain 131(4):945–961

    Article  PubMed  Google Scholar 

  40. Fornito A, Yoon J, Zalesky A, Bullmore ET, Carter CS (2011) General and specific functional connectivity disturbances in first-episode schizophrenia during cognitive control performance. Biol Psychiatry 70(1):64–72

    Article  PubMed  PubMed Central  Google Scholar 

  41. He H, Sui J, Yu Q, Turner JA, Ho BC, Sponheim SR et al (2012) Altered small-world brain networks in schizophrenia patients during working memory performance. PLoS One 7(6):e38195. https://doi.org/10.1371/journal.pone.0038195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. DemirtaÅŸ M, Tornador C, Falcon C, LĂ³pez-SolĂ  M, HernĂ¡ndez-Ribas R, Pujol J et al (2016) Dynamic functional connectivity reveals altered variability in functional connectivity among patients with major depressive disorder. Hum Brain Mapp 37(8):2918–2930

    Article  PubMed  PubMed Central  Google Scholar 

  43. Lawrie SM, Abukmeil SS (1998) Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies. Br J Psychiatry 172:110–120

    Article  CAS  PubMed  Google Scholar 

  44. Nelson MD, Saykin AJ, Flashman LA, Riordan HJ (1998) Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study. Arch Gen Psychiatry 55:433–440

    Article  CAS  PubMed  Google Scholar 

  45. Honea R, Crow TJ, Passingham D, Mackay CE (2005) Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. Am J Psychiatry 162:2233–2245

    Article  PubMed  Google Scholar 

  46. Van Horn JD, Mcmanus IC (1992) Ventricular enlargement in schizophrenia. A metaanalysis of studies of the ventricle: brain ratio (VBR). Br J Psychiatry 160:687–697

    Article  PubMed  Google Scholar 

  47. Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, Bullmore ET (2000) Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 157:16–25

    Article  CAS  PubMed  Google Scholar 

  48. Penttila M, Jaaskelainen E, Hirvonen N, Isohanni M, Miettunen J (2014) Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis. Br J Psychiatry 205(2):88–94

    Article  PubMed  Google Scholar 

  49. Goff DC, Zeng B, Ardekani BA, Diminich ED, Tang Y, Fan X et al (2018) Association of hippocampal atrophy with duration of untreated psychosis and molecular biomarkers during initial antipsychotic treatment of first-episode psychosis. JAMA Psychiat 75(4):370–378

    Article  Google Scholar 

  50. Kubicki M, Mccarley R, Westin CF, Park HJ, Maier S, Kikinis R et al (2007) A review of diffusion tensor imaging studies in schizophrenia. J Psychiatr Res 41:15–30

    Article  PubMed  Google Scholar 

  51. Mayberg HS (2003) Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimized treatment. Br Med Bull 65:193–207

    Article  PubMed  Google Scholar 

  52. Dong D, Ming Q, Zhong X, Pu W, Zhang X, Jiang Y et al (2018) State-independent alterations of intrinsic brain network in current and remitted depression. Prog Neuropsychopharmacol Biol Psychiatry 89:475-480

    Article  PubMed  Google Scholar 

  53. Ressler KJ, Mayberg HS (2007) Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci 10:1116–1124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yang J, Zhang M, Ahn H, Zhang Q, Jin TB, Li IA (2018) Development and evaluation of a multimodal marker of major depressive disorder. Hum Brain Mapp 39(11):4420–4439

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lorenzetti V, Allen NB, Fornito A, Yucel M (2009) Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. J Affect Disord 117:1–17

    Article  PubMed  Google Scholar 

  56. Fu CH, Steiner H, Costafreda SG (2012) Predictive neural biomarkers of clinical response in depression: a meta-analysis of functional and structural neuroimaging studies of pharmacological and psychological therapies. Neurobiol Dis 52:75–83

    Article  PubMed  CAS  Google Scholar 

  57. Strakowski SM, DelBello MP, Zimmerman ME, Getz GE, Mills NP, Ret J et al (2002) Ventricular and periventricular structural volumes in first- versus multiple-episode bipolar disorder. Am J Psychiatry 159(11):1841–1847

    Article  PubMed  Google Scholar 

  58. Moorhead TW, McKirdy J, Sussmann JE, Hall J, Lawrie SM, Johnstone EC et al (2007) Progressive gray matter loss in patients with bipolar disorder. Biol Psychiatry 62(8):894–900

    Article  PubMed  Google Scholar 

  59. Bora E, Fornito A, YĂ¼cel M, Pantelis C (2010) Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder. Biol Psychiatry 67:1097–1105

    Article  PubMed  Google Scholar 

  60. Hibar DP, Westlye LT, van Erp TG, Rasmussen J, Leonardo CD, Faskowitz J et al (2016) Subcortical volumetric abnormalities in bipolar disorder. Mol Psychiatry 21(12):1710–1171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Maletic V, Raison C (2014) Integrated neurobiology of bipolar disorder. Front Psych 5:98. https://doi.org/10.3389/fpsyt.2014.00098

    Article  Google Scholar 

  62. Cerullo MA, Adler CM, Delbello MP, Strakowski SM (2009) The functional neuroanatomy of bipolar disorder. Int Rev Psychiatry 21:314–322

    Article  PubMed  Google Scholar 

  63. Vargas C, LĂ³pez-Jaramillo C, Vieta E (2013) A systematic literature review of resting state network—functional MRI in bipolar disorder. J Affect Disord 150:727–735

    Article  PubMed  Google Scholar 

  64. Li L, Ji E, Han X, Tang F, Bai Y, Peng D et al (2018) Cortical thickness and subcortical volumes alterations in euthymic bipolar I patients treated with different mood stabilizers. Brain Imaging Behav Aug 25. https://doi.org/10.1007/s11682-018-9950-9. [Epub ahead of print]

  65. Alda M (2015) Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics. Mol Psychiatry 20(6):661–670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Fleck DE, Ernest N, Adler CM, Cohen K, Eliassen JC, Norris M et al (2017) Prediction of lithium response in first-episode mania using the LITHium Intelligent Agent (LITHIA): pilot data and proof-of-concept. Bipolar Disord 19(4):259–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Houenou J, Boisgontier J, Henrion A, d’Albis MA, Dumaine A, Linke J et al (2017) A multilevel functional study of a SNAP25 at-risk variant for bipolar disorder and schizophrenia. J Neurosci 37(43):10389–10397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Keener MT, Phillips ML (2007) Neuroimaging in bipolar disorder: a critical review of current findings. Curr Psychiatry Rep 9(6):512–520

    Article  PubMed  PubMed Central  Google Scholar 

  69. De Witte L, Tomasik J, Schwarz E, Guest PC, Rahmoune H, Kahn RS et al (2014) Cytokine alterations in first episode schizophrenia patients before and after antipsychotic treatment. Schizophr Res 154(1–4):23–29

    Article  PubMed  Google Scholar 

  70. Bauer IE, Pascoe MC, Wollenhaupt-Aguiar B, Kapczinski F, Soares JC (2014) Inflammatory mediators of cognitive impairment in bipolar disorder. J Psychiatr Res 56:18–27

    Article  PubMed  PubMed Central  Google Scholar 

  71. Nikkila H, MĂ¼ller K, Ahokas A, Miettinen K, Andersson LC, RimĂ³n R (1995) Abnormal distributions of T-lymphocyte subsets in the cerebrospinal fluid of patients with acute schizophrenia. Schizophr Res 14:215–221

    Article  CAS  PubMed  Google Scholar 

  72. MĂ¼ller N, Ackenheil M (1995) Immunoglobulin and albumin content of cerebrospinal fluid in schizophrenic patients: relationship to negative symptomatology. Schizophr Res 14:223–228

    Article  PubMed  Google Scholar 

  73. Howren MB, Lamkin DM, Suls J (2009) Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 71:171–186

    Article  CAS  PubMed  Google Scholar 

  74. Haapakoski R, Mathieu J, Ebmeier KP, Alenius H, Kivimäki M (2015) Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factorα and C-reactive protein in patients with major depressive disorder. Brain Behav Immun 49:206–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Ripke S, Neale BM, Corvin A, Walters JTR, Farh K-H, Holmans PA et al (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:421–427

    Article  CAS  PubMed Central  Google Scholar 

  76. Miller BJ, Culpepper N, Rapaport MH (2014) C-reactive protein levels in schizophrenia: a review and meta-analysis. Clin Schizophr Relat Psychoses 7(4):223–230

    Article  PubMed  Google Scholar 

  77. Wan C, La Y, Zhu H, Yang Y, Jiang L, Chen Y et al (2007) Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene. Amino Acids 32:101–108

    Article  CAS  PubMed  Google Scholar 

  78. Van Kammen DP, Mcallister-Sistilli CG, Kelley ME, Gurklis JA, Yao JK (1999) Elevated interleukin-6 in schizophrenia. Psychiatry Res 87:129–136

    Article  PubMed  Google Scholar 

  79. Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY (2002) Decreased production of interleukin-2 (IL-2), IL-2 secreting cells and CD4+ cells in medication-free patients with schizophrenia. J Psychiatr Res 36:331–336

    Article  PubMed  Google Scholar 

  80. Asevedo E, Rizzo LB, Gadelha A, Mansur RB, Ota VK, Berberian AA et al (2014) Peripheral interleukin-2 level is associated with negative symptoms and cognitive performance in schizophrenia. Physiol Behav 129:194–198

    Article  CAS  PubMed  Google Scholar 

  81. Nawa H, Takahashi M, Patterson PH (2000) Cytokine and growth factor involvement in schizophrenia–support for the developmental model. Mol Psychiatry 5:594–603

    Article  CAS  PubMed  Google Scholar 

  82. Wang AK, Miller BJ (2018) Meta-analysis of cerebrospinal fluid cytokine and tryptophan catabolite alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder, and depression. Schizophr Bull 44(1):75–83

    Article  CAS  PubMed  Google Scholar 

  83. Chen J, Huang C, Song Y, Shi H, Wu D, Yang Y et al (2015) Comparative proteomic analysis of plasma from bipolar depression and depressive disorder: identification of proteins associated with immune regulatory. Protein Cell 6(12):908–911

    Article  PubMed  PubMed Central  Google Scholar 

  84. Orlovska-Waast S, Köhler-Forsberg O, Brix SW, Nordentoft M, Kondziella D, Krogh J et al (2018) Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis. Mol Psychiatry. https://doi.org/10.1038/s41380-018-0220-4. [Epub ahead of print]

  85. Benros ME, Mortensen PB, Eaton WW (2012) Autoimmune diseases and infections as risk factors for schizophrenia. Ann N Y Acad Sci 1262:56–66

    Article  PubMed  Google Scholar 

  86. Kirch DG, Alexander RC, Suddath RL, Papadopoulos NM, Kaufmann CA, Daniel DG et al (1992) Blood-CSF barrier permeability and central nervous system immunoglobulin G in schizophrenia. J Neural Transm 89:219–232

    Article  CAS  Google Scholar 

  87. Stich O, Andres TA, Gross CM, Gerber SI, Rauer S, Langosch JM (2015) An observational study of inflammation in the central nervous system in patients with bipolar disorder. Bipolar Disord 17:291–302

    Article  CAS  PubMed  Google Scholar 

  88. Endres D, Perlov E, Baumgartner A, Hottenrott T, Dersch R, Stich O et al (2015) Immunological findings in psychotic syndromes: a tertiary care hospital’s CSF sample of 180 patients. Front Hum Neurosci 9:476. https://doi.org/10.3389/fnhum.2015.00476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Kirch DG, Kaufmann CA, Papadopoulos NM, Martin B, Weinberger DR (1985) Abnormal cerebrospinal fluid protein indices in schizophrenia. Biol Psychiatry 20:1039–1046

    Article  CAS  PubMed  Google Scholar 

  90. MĂ¼ller N, Dobmeier P, Empl M, Riedel M, Schwarz M, Ackenheil M (1997) Soluble IL-6 receptors in the serum and cerebrospinal fluid of paranoid schizophrenic patients. Eur Psychiatry 12:294–299

    Article  PubMed  Google Scholar 

  91. Pazzaglia PJ, Post RM, Rubinow D, Kling MA, Huggins TS, Sunderland T (1995) Cerebrospinal fluid total protein in patients with affective disorders. Psychiatry Res 57:259–266

    Article  CAS  PubMed  Google Scholar 

  92. Kern S, Skoog I, Börjesson-Hanson A, Blennow K, Zetterberg H, Östling S et al (2014) Higher CSF interleukin-6 and CSF interleukin-8 in current depression in older women. Results from a population-based sample. Brain Behav Immun 41:55–58

    Article  CAS  PubMed  Google Scholar 

  93. Janelidze S, Ventorp F, Erhardt S, Hansson O, Minthon L, Flax J et al (2013) Altered chemokine levels in the cerebrospinal fluid and plasma of suicide attempters. Psychoneuroendocrinology 38:853–862

    Article  CAS  PubMed  Google Scholar 

  94. Teixeira AL, Barbosa IG, Machado-Vieira R, Rizzo LB, Wieck A, Bauer ME (2013) Novel biomarkers for bipolar disorder. Expert Opin Med Diagn 7(2):147–159

    Article  CAS  PubMed  Google Scholar 

  95. Baghai TC, Varallo-Bedarida G, Born C, Häfner S, SchĂ¼le C, Eser D et al (2018) Classical risk factors and inflammatory biomarkers: one of the missing biological links between cardiovascular disease and major depressive disorder. Int J Mol Sci 19(6):E1740. https://doi.org/10.3390/ijms19061740

    Article  CAS  PubMed  Google Scholar 

  96. Cheng Y, Li Z, He S, Tian Y, He F, Li W (2018) Elevated heat shock proteins in bipolar disorder patients with hypothalamic pituitary adrenal axis dysfunction. Medicine (Baltimore) 97(27):e11089. https://doi.org/10.1097/MD.0000000000011089

    Article  CAS  Google Scholar 

  97. Kuipers SD, Bramham CR (2006) Brain-derived neurotrophic factor mechanisms and function in adult synaptic plasticity: new insights and implications for therapy. Curr Opin Drug Discov Devel 9:580–586

    CAS  PubMed  Google Scholar 

  98. Neves-Pereira M, Cheung JK, Pasdar A, Zhang F, Breen G, Yates P et al (2005) BDNF gene is a risk factor for schizophrenia in a Scottish population. Mol Psychiatry 10:208–212

    Article  CAS  PubMed  Google Scholar 

  99. Numata S, Ueno S, Iga J, Yamauchi K, Hongwei S, Ohta K et al (2006) Brain derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms. Neurosci Lett 401:1–5

    Article  CAS  PubMed  Google Scholar 

  100. Rybakowski JK, Borkowska A, Skibinska M, Szczepankiewicz A, Kapelski P, Leszczynska-Rodziewicz A et al (2006) Prefrontal cognition in schizophrenia and bipolar illness in relation to Val66Met polymorphism of the brain-derived neurotrophic factor gene. Psychiatry Clin Neurosci 60:70–76

    Article  CAS  PubMed  Google Scholar 

  101. Spalletta G, Morris DW, Angelucci F, Rubino IA, Spoletini I, Bria P et al (2010) BDNF Val66Met polymorphism is associated with aggressive behavior in schizophrenia. Eur Psychiatry 25:311–313

    Article  CAS  PubMed  Google Scholar 

  102. Issa G, Wilson C, Terry AV Jr, Pillai A (2010) An inverse relationship between cortisol and BDNF levels in schizophrenia: data from human postmortem and animal studies. Neurobiol Dis 39:327–333

    Article  CAS  PubMed  Google Scholar 

  103. Thompson Ray M, Weickert CS, Wyatt E, Webster MJ (2011) Decreased BDNF, trkBTK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders. J Psychiatry Neurosci 36:195–203

    Article  PubMed  Google Scholar 

  104. Durany N, Michel T, Zochling R, Boissl KW, Cruz-Sanchez FF, Riederer P et al (2001) Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses. Schizophr Res 52:79–86

    Article  CAS  PubMed  Google Scholar 

  105. Fulzele S, Pillai A (2009) Decreased VEGF mRNA expression in the dorsolateral prefrontal cortex of schizophrenia subjects. Schizophr Res 115:372–373

    Article  PubMed  Google Scholar 

  106. Kale A, Joshi S, Pillai A, Naphade N, Raju M, Nasrallah H et al (2009) Reduced cerebrospinal fluid and plasma nerve growth factor in drug-naive psychotic patients. Schizophr Res 115:209–214

    Article  PubMed  Google Scholar 

  107. Zakharyan R, Atshemyan S, Gevorgyan A, Boyajyan A (2014) Nerve growth factor and its receptor in schizophrenia. BBA Clin 1:24–29

    Article  PubMed  PubMed Central  Google Scholar 

  108. Lee BH, Hong JP, Hwang JA, Ham BJ, Na KS, Kim WJ et al (2015) Alterations in plasma vascular endothelial growth factor levels in patients with schizophrenia before and after treatment. Psychiatry Res 228:95–99

    Article  CAS  PubMed  Google Scholar 

  109. Rao S, Martinez-Cengotitabengoa M, Yao Y, Guo Z, Xu Q, Li S et al (2017) Peripheral blood nerve growth factor levels in major psychiatric disorders. J Psychiatr Res 86:39–45

    Article  PubMed  Google Scholar 

  110. Toyooka K, Asama K, Watanabe Y, Muratake T, Takahashi M, Someya T et al (2002) Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients. Psychiatry Res 110:249–257

    Article  CAS  PubMed  Google Scholar 

  111. Pirildar S, Gonul AS, Taneli F, Akdeniz F (2004) Low serum levels of brain-derived neurotrophic factor in patients with schizophrenia do not elevate after antipsychotic treatment. Prog Neuropsychopharmacol Biol Psychiatry 28:709–713

    Article  CAS  PubMed  Google Scholar 

  112. Tan YL, Zhou DF, Cao LY, Zou YZ, Zhang XY (2005) Decreased BDNF in serum of patients with chronic schizophrenia on long-term treatment with antipsychotics. Neurosci Lett 382:27–32

    Article  CAS  PubMed  Google Scholar 

  113. Grillo RW, Ottoni GL, Leke R, Souza DO, Portela LV, Lara DR (2007) Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics. J Psychiatr Res 41:31–35

    Article  PubMed  Google Scholar 

  114. Xiu MH, Hui L, Dang YF, Hou TD, Zhang CX, Zheng YL et al (2009) Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics. Prog Neuropsychopharmacol Biol Psychiatry 33:1508–1512

    Article  CAS  PubMed  Google Scholar 

  115. Rizos EN, Papadopoulou A, Laskos E, Michalopoulou PG, Kastania A, Vasilopoulos D et al (2010) Reduced serum BDNF levels in patients with chronic schizophrenic disorder in relapse, who were treated with typical or atypical antipsychotics. World J Biol Psychiatry 11:251–255

    Article  PubMed  Google Scholar 

  116. Li C, Tao H, Yang X, Zhang X, Liu Y, Tang Y et al (2018) Assessment of a combination of Serum Proteins as potential biomarkers to clinically predict Schizophrenia. Int J Med Sci 15(9):900–906

    Article  PubMed  PubMed Central  Google Scholar 

  117. Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatr 122(5):509–522

    Article  CAS  PubMed  Google Scholar 

  118. Hashimoto K, Bruno D, Nierenberg J, Marmar CR, Zetterberg H, Blennow K et al (2016) Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study. Transl Psychiatry 6:e744. https://doi.org/10.1038/tp.2016.8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Hattori K, Ota M, Sasayama D, Yoshida S, Matsumura R, Miyakawa T et al (2015) Increased cerebrospinal fluid fibrinogen in major depressive disorder. Sci Rep 5:11412. https://doi.org/10.1038/srep11412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Ogawa S, Hattori K, Sasayama D, Yokota Y, Matsumura R, Matsuo J et al (2015) Reduced cerebrospinal fluid ethanolamine concentration in major depressive disorder. Sci Rep 5:7796. https://doi.org/10.1038/srep07796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Hyland K (2007) Inherited disorders affecting dopamine and serotonin: critical neurotransmitters derived from aromatic amino acids. J Nutr 137(6 Suppl 1):1568S–1572S; discussion 1573S–1575S

    Article  CAS  PubMed  Google Scholar 

  122. Bowers MB (1974) Lumbar CSF 5-hydroxyindoleacetic acid and homovanillic acid in affective syndromes. J Nerv Ment Dis 158(5):325–330

    Article  PubMed  Google Scholar 

  123. Ren J, Zhao G, Sun X, Liu H, Jiang P, Chen J et al (2017) Identification of plasma biomarkers for distinguishing bipolar depression from major depressive disorder by iTRAQ-coupled LC-MS/MS and bioinformatics analysis. Psychoneuroendocrinology 86:17–24

    Article  CAS  PubMed  Google Scholar 

  124. Pan JX, Xia JJ, Deng FL, Liang WW, Wu J, Yin BM et al (2018) Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: a targeted metabolomics study. Transl Psychiatry 8(1):130. https://doi.org/10.1038/s41398-018-0183-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Dean B, Kulkarni J, Copolov DL, Shrikanthan P, Malone V, Hill C (1992) Dopamine uptake by platelets from subjects with schizophrenia: a correlation with the delusional state of the patient. Psychiatry Res 41:17–24

    Article  CAS  PubMed  Google Scholar 

  126. Liu L, Jia F, Yuan G, Chen Z, Yao J, Li H et al (2010) Tyrosine hydroxylase, interleukin-1beta and tumor necrosis factor-alpha are overexpressed in peripheral blood mononuclear cells from schizophrenia patients as determined by semi-quantitative analysis. Psychiatry Res 176:1–7

    Article  CAS  PubMed  Google Scholar 

  127. Liu L, Yuan G, Cheng Z, Zhang G, Liu X, Zhang H (2013) Identification of the mRNA expression status of the dopamine D2 receptor and dopamine transporter in peripheral blood lymphocytes of schizophrenia patients. PLoS One 8:e75259. https://doi.org/10.1371/journal.pone.0075259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Boneberg EM, Von Seydlitz E, Propster K, Watzl H, Rockstroh B, Illges H (2006) D3 dopamine receptor mRNA is elevated in T cells of schizophrenic patients whereas D4 dopamine receptor mRNA is reduced in CD4+-T cells. J Neuroimmunol 173:180–187

    Article  CAS  PubMed  Google Scholar 

  129. Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS et al (2000) Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci U S A 97:8104–8109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Laruelle M, Abi-Dargham A, Van Dyck CH, Gil R, D’souza CD, Erdos J et al (1996) Single photon emission computerized tomography imaging of amphetamine induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci U S A 93:9235–9240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Ogawa S, Tsuchimine S, Kunugi H (2018) Cerebrospinal fluid monoamine metabolite concentrations in depressive disorder: a meta-analysis of historic evidence. J Psychiatr Res 105:137–146

    Article  PubMed  Google Scholar 

  132. Farde L, Gustavsson JP, Jönsson E (1997) D2 dopamine receptors and personality traits. Nature 385:590. https://doi.org/10.1038/385590a0

    Article  CAS  PubMed  Google Scholar 

  133. Farde L, Plavén-Sigray P, Borg J, Cervenka S (2018) Brain neuroreceptor density and personality traits: towards dimensional biomarkers for psychiatric disorders. Philos Trans R Soc Lond Ser B Biol Sci 373(1744). https://doi.org/10.1098/rstb.2017.0156

    Article  CAS  Google Scholar 

  134. Woodward ND, Cowan RL, Park S, Ansari MS, Baldwin RM, Li R et al (2011) Correlation of individual differences in schizotypal personality traits with amphetamine induced dopamine release in striatal and extrastriatal brain regions. Am J Psychiatry 168:418–426

    Article  PubMed  Google Scholar 

  135. Breier A, Su TP, Saunders R, Carson RE, Kolachana BS, de Bartolomeis A et al (1997) Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci U S A 94(6):2569–2574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Howes OD, Montgomery AJ, Asselin MC, Murray RM, Valli I, Tabraham P et al (2009) Elevated striatal dopamine function linked to prodromal signs of schizophrenia. Arch Gen Psychiatry 66(1):13–20

    Article  PubMed  Google Scholar 

  137. Joyce JN, Shane A, Lexow N, Winokur A, Casanova MF, Kleinman JE (1993) Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics. Neuropsychopharmacology 8:315–336

    Article  CAS  PubMed  Google Scholar 

  138. Gurevich EV, Joyce JN (1997) Alterations in the cortical serotonergic system in schizophrenia: a postmortem study. Biol Psychiatry 42:529–545

    Article  CAS  PubMed  Google Scholar 

  139. Laruelle M, Abi-Dargham A, Casanova MF, Toti R, Weinberger DR, Kleinman JE (1993) Selective abnormalities of prefrontal serotonergic receptors in schizophrenia. A postmortem study. Arch Gen Psychiatry 50:810–818

    Article  CAS  PubMed  Google Scholar 

  140. Sumiyoshi T, Stockmeier CA, Overholser JC, Dilley GE, Meltzer HY (1996) Serotonin1A receptors are increased in postmortem prefrontal cortex in schizophrenia. Brain Res 708:209–214

    Article  CAS  PubMed  Google Scholar 

  141. Lopez-Figueroa AL, Norton CS, Lopez-Figueroa MO, Armellini-Dodel D, Burke S, Akil H et al (2004) Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia. Biol Psychiatry 55:225–233

    Article  CAS  PubMed  Google Scholar 

  142. Muck-Seler D, Pivac N, Jakovljevic M (1999) Sex differences, season of birth and platelet 5-HT levels in schizophrenic patients. J Neural Transm 106(3–4):337–347

    CAS  PubMed  Google Scholar 

  143. Tuominen L, Salo J, Hirvonen J, NĂ¥gren K, Laine P, Melartin T et al (2013) Temperament, character and serotonin activity in the human brain: a positron emission tomography study based on a general population cohort. Psychol Med 43(4):881–894

    Article  CAS  PubMed  Google Scholar 

  144. Kim JS, Kornhuber HH, Schmid-Burgk W, HolzmĂ¼ller B (1980) Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci Lett 20:379–382

    Article  CAS  PubMed  Google Scholar 

  145. Neeman G, Blanaru M, Bloch B, Kremer I, Ermilov M, Javitt DC et al (2005) Relation of plasma glycine, serine, and homocysteine levels to schizophrenia symptoms and medication type. Am J Psychiatry 162:1738–1740

    Article  PubMed  Google Scholar 

  146. Hashimoto K, Engberg G, Shimizu E, Nordin C, Lindstrom LH, Iyo M (2005) Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry 29:767–769

    Article  CAS  PubMed  Google Scholar 

  147. Haaf M, Leicht G, Curic S, Mulert C (2018) Glutamatergic deficits in schizophrenia - biomarkers and pharmacological interventions within the ketamine model. Curr Pharm Biotechnol 19(4):293–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Duncan CE, Webster MJ, Rothmond DA, Bahn S, Elashoff M, Shannon Weickert C (2010) Prefrontal GABA(A) receptor alpha-subunit expression in normal postnatal human development and schizophrenia. J Psychiatr Res 44:673–681

    Article  PubMed  Google Scholar 

  149. Arrue A, Davila R, Zumarraga M, Basterreche N, Gonzalez-Torres MA, Goienetxea B et al (2010) GABA and homovanillic acid in the plasma of Schizophrenic and bipolar I patients. Neurochem Res 35:247–253

    Article  CAS  PubMed  Google Scholar 

  150. Lo WS, Harano M, Gawlik M, Yu Z, Chen J, Pun FW et al (2007) GABRB2 association with schizophrenia: commonalities and differences between ethnic groups and clinical subtypes. Biol Psychiatry 61:653–660

    Article  CAS  PubMed  Google Scholar 

  151. Pinna G (2018) Biomarkers for PTSD at the interface of the endocannabinoid and neurosteroid axis. Front Neurosci 12:482. https://doi.org/10.3389/fnins.2018.00482

    Article  PubMed  PubMed Central  Google Scholar 

  152. Rasmusson AM, King M, Gregor K, Scioli-Salter E, Pineles S, Valovski I et al (2018) GABAergic neurosteroids in cerebrospinal fluid are negatively associated with PTSD severity in men. Biol Psychiatry 83:S15–S16

    Article  Google Scholar 

  153. Nemeroff CB (2008) Understanding the pathophysiology of postpartum depression: implications for the development of novel treatments. Neuron 59:185–186

    Article  CAS  PubMed  Google Scholar 

  154. Lovick T (2013) SSRIs and the female brain–potential for utilizing steroid-stimulating properties to treat menstrual cycle-linked dysphorias. J Psychopharmacol 27:1180–1185

    Article  PubMed  CAS  Google Scholar 

  155. Trivisano M, Lucchi C, Rustichelli C, Terracciano A, Cusmai R, Ubertini GM et al (2017) Reduced steroidogenesis in patients with PCDH19-female limited epilepsy. Epilepsia 58:e91–e95

    Article  CAS  PubMed  Google Scholar 

  156. Dichtel LE, Lawson EA, Schorr M, Meenaghan E, Paskal ML, Eddy KT et al (2018) Neuroactive steroids and affective symptoms in women across the weight spectrum. Neuropsychopharmacology 43(6):1436–1444

    Article  CAS  PubMed  Google Scholar 

  157. Belelli D, Lambert JJ (2005) Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat Rev Neurosci 6:565–575

    Article  CAS  PubMed  Google Scholar 

  158. Pineles SL, Nillni YI, Pinna G, Irvine J, Webb A, Hall A et al (2018) PTSD in women is associated with a block in conversion of progesterone to the GABAergic neurosteroids allopregnanolone and pregnanolone: confirmed in plasma. Psychoneuroendocrinology 93:133–141

    Article  CAS  PubMed  Google Scholar 

  159. Wilker S, Pfeiffer A, Elbert T, Ovuga E, Karabatsiakis A, Krumbholz A et al (2016) Endocannabinoid concentrations in hair are associated with PTSD symptom severity. Psychoneuroendocrinology 67:198–206

    Article  CAS  PubMed  Google Scholar 

  160. Court J, Spurden D, Lloyd S, Mckeith I, Ballard C, Cairns N et al (1999) Neuronal nicotinic receptors in dementia with Lewy bodies and schizophrenia: alpha-bungarotoxin and nicotine binding in the thalamus. J Neurochem 73:1590–1597

    Article  CAS  PubMed  Google Scholar 

  161. Guan ZZ, Zhang X, Blennow K, Nordberg A (1999) Decreased protein level of nicotinic receptor alpha7 subunit in the frontal cortex from schizophrenic brain. Neuroreport 10:1779–1782

    Article  CAS  PubMed  Google Scholar 

  162. Mancama D, Arranz MJ, Landau S, Kerwin R (2003) Reduced expression of the muscarinic 1 receptor cortical subtype in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 119b:2–6

    Article  CAS  PubMed  Google Scholar 

  163. Rozek LS, Dolinoy DC, Sartor MA, Omenn GS (2014) Epigenetics: relevance and implications for public health. Annu Rev Public Health 35:105–122

    Article  PubMed  PubMed Central  Google Scholar 

  164. Zhang TY, Labonte B, Wen XL, Turecki G, Meaney MJ (2013) Epigenetic mechanisms for the early environmental regulation of hippocampal glucocorticoid receptor gene expression in rodents and humans. Neuropsychopharmacology 38(1):111–123

    Article  PubMed  CAS  Google Scholar 

  165. Daskalakis NP, Cohen H, Nievergelt CM, Baker DG, Buxbaum JD, Russo SJ et al (2016) New translational perspectives for blood-based biomarkers of PTSD: from glucocorticoid to immune mediators of stress susceptibility. Exp Neurol 284(Pt B):133–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Watson S, Gallagher P, Ritchie JC, Ferrier IN, Young AH (2004) Hypothalamic-pituitary adrenal axis function in patients with bipolar disorder. Br J Psychiatry 184:496–502

    Article  PubMed  Google Scholar 

  167. Pariante CM, Dazzan P, Danese A, Morgan KD, Brudaglio F, Morgan C et al (2005) Increased pituitary volume in antipsychotic-free and antipsychotic-treated patients of the Aesop first-onset psychosis study. Neuropsychopharmacology 30(10):1923–1931

    Article  CAS  PubMed  Google Scholar 

  168. Ryan MC, Sharifi N, Condren R, Thakore JH (2004) Evidence of basal pituitary adrenal overactivity in first episode, drug naive patients with schizophrenia. Psychoneuroendocrinology 29(8):1065–1070

    Article  CAS  PubMed  Google Scholar 

  169. Perkins DO, Jeffries CD, Jarskog LF, Thomson JM, Woods K, Newman MA et al (2007) microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol 8(2):R27. https://doi.org/10.1186/gb-2007-8-2-r27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Kim AH, Reimers M, Maher B, Williamson V, McMichael O, McClay JL et al (2010) MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders. Schizophr Res 124(1–3):183–191

    Article  PubMed  PubMed Central  Google Scholar 

  171. Moreau MP, Bruse SE, David-Rus R, Buyske S, Brzustowicz LM (2011) Altered microRNA expression profiles in postmortem brain samples from individuals with schizophrenia and bipolar disorder. Biol Psychiatry 69(2):188–193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Beveridge NJ, Tooney PA, Carroll AP, Gardiner E, Bowden N, Scott RJ et al (2008) Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Hum Mol Genet 17(8):1156–1168

    Article  CAS  PubMed  Google Scholar 

  173. Xu Y, Yue W, Yao Shugart Y, Li S, Cai L, Li Q et al (2016) Exploring transcription factors-microRNAs co-regulation networks in schizophrenia. Schizophr Bull 42:1037–1045

    Article  PubMed  Google Scholar 

  174. Burmistrova OA, Goltsov AY, Abramova LI, Kaleda VG, Orlova VA, Rogaev EI (2007) MicroRNA in schizophrenia: genetic and expression analysis of miR-130b (22q11). Biochemistry (Mosc) 72:578–582

    Article  CAS  Google Scholar 

  175. Beveridge NJ, Gardiner E, Carroll AP, Tooney PA, Cairns MJ (2010) Schizophrenia is associated with an increase in cortical microRNA biogenesis. Mol Psychiatry 15(12):1176–1189

    Article  CAS  PubMed  Google Scholar 

  176. Santarelli DM, Beveridge NJ, Tooney PA, Cairns MJ (2011) Upregulation of dicer and microRNA expression in the dorsolateral prefrontal cortex Brodmann area 46 in schizophrenia. Biol Psychiatry 69(2):180–187

    Article  CAS  PubMed  Google Scholar 

  177. Miller BH, Zeier Z, Xi L, Lanz TA, Deng S, Strathmann J et al (2012) MicroRNA-132 dysregulation in schizophrenia has implications for both neurodevelopment and adult brain function. Proc Natl Acad Sci U S A 109(8):3125–3130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Shi W, Du J, Qi Y, Liang G, Wang T, Li S et al (2012) Aberrant expression of serum miRNAs in schizophrenia. J Psychiatr Res 46(2):198–204

    Article  PubMed  Google Scholar 

  179. Banigan MG, Kao PF, Kozubek JA, Winslow AR, Medina J, Costa J et al (2013) Differential expression of exosomal microRNAs in prefrontal cortices of schizophrenia and bipolar disorder patients. PLoS One 8(1):e48814. https://doi.org/10.1371/journal.pone.0048814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Fan HM, Sun XY, Niu W, Zhao L, Zhang QL, Li WS et al (2015) Altered microRNA expression in peripheral blood mononuclear cells from young patients with schizophrenia. J Mol Neurosci 56(3):562–571

    Article  CAS  PubMed  Google Scholar 

  181. Sun XY, Lu J, Zhang L, Song HT, Zhao L, Fan HM et al (2015) Aberrant microRNA expression in peripheral plasma and mononuclear cells as specific blood-based biomarkers in schizophrenia patients. J Clin Neurosci 22(3):570–574

    Article  CAS  PubMed  Google Scholar 

  182. Lai CY, Lee SY, Scarr E, Yu YH, Lin YT, Liu CM (2016) Aberrant expression of microRNAs as biomarker for schizophrenia: from acute state to partial remission, and from peripheral blood to cortical tissue. Transl Psychiatry 6:e717. https://doi.org/10.1038/tp.2015.213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Yao Y, Schröder J, Karlsson H (2008) Verification of proposed peripheral biomarkers in mononuclear cells of individuals with schizophrenia. J Psychiatr Res 42:639–643

    Article  PubMed  Google Scholar 

  184. Liu S, Zhang F, Wang X, Shugart YY, Zhao Y, Li X et al (2017) Diagnostic value of blood-derived microRNAs for schizophrenia: results of a meta-analysis and validation. Sci Rep 7(1):15328. https://doi.org/10.1038/s41598-017-15751-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Wang X, Wang X (2006) Systematic identification of microRNA functions by combining target prediction and expression profiling. Nucleic Acids Res 34(5):1646–1652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M et al (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439(7074):283–289

    Article  CAS  PubMed  Google Scholar 

  187. Padula MC, Scariati E, Schaer M, Eliez S (2018) A mini review on the contribution of the anterior cingulate cortex in the risk of psychosis in 22q11.2 deletion syndrome. Front Psych 9:372. https://doi.org/10.3389/fpsyt.2018.00372

    Article  Google Scholar 

  188. Narahari A, Hussain M, Sreeram V (2017) MicroRNAs as biomarkers for psychiatric conditions: a review of current research. Innov Clin Neurosci 14(1–2):53–55

    PubMed  PubMed Central  Google Scholar 

  189. Seripa D, Lozupone M, Miscio G, Stella E, La Montagna M, Gravina C et al (2018) CYP2D6 genotypes in revolving door patients with bipolar disorders: a case series. Medicine (Baltimore) 97(37):e11998. https://doi.org/10.1097/MD.0000000000011998

    Article  CAS  Google Scholar 

  190. Seripa D, Lozupone M, Stella E, Paroni G, Bisceglia P, La Montagna M et al (2017) Psychotropic drugs and CYP2D6 in late-life psychiatric and neurological disorders. What do we know? Expert Opin Drug Saf 16(12):1373–1385

    Article  CAS  PubMed  Google Scholar 

  191. Moodithaya S, Avadhany ST (2012) Gender differences in age-related changes in cardiac autonomic nervous function. J Aging Res 2012:679345. https://doi.org/10.1155/2012/679345

    Article  PubMed  Google Scholar 

  192. Sztajzel J (2004) Heart rate variability: a noninvasive electrocardiographic method to measure the autonomic nervous system. Swiss Med Wkly 134(35–36):514–522

    PubMed  Google Scholar 

  193. Lin HP, Lin HY, Lin WL, Huang AC (2011) Effects of stress, depression, and their interaction on heart rate, skin conductance, finger temperature, and respiratory rate: sympathetic-parasympathetic hypothesis of stress and depression. J Clin Psychol 67(10):1080–1091

    Article  PubMed  Google Scholar 

  194. Shah LB, Torres S, Kannusamy P, Chng CM, He HG, Klainin-Yobas P (2015) Efficacy of the virtual reality-based stress management program on stress-related variables in people with mood disorders: the feasibility study. Arch Psychiatr Nurs 29(1):6–13

    Article  PubMed  Google Scholar 

  195. Barua S, Begum S, Ahmed MU (2015) Supervised machine learning algorithms to diagnose stress for vehicle drivers based on physiological sensor signals. Stud Health Technol Inform 211:241–248

    PubMed  Google Scholar 

  196. Teisala T, Mutikainen S, Tolvanen A, Rottensteiner M, Leskinen T, Kaprio J (2014) Associations of physical activity, fitness, and body composition with heart rate variability-based indicators of stress and recovery on workdays: a cross-sectional study. J Occup Med Toxicol 9:16. https://doi.org/10.1186/1745-6673-9-16

    Article  PubMed  PubMed Central  Google Scholar 

  197. Bootsma M, Swenne CA, Van Bolhuis HH, Chang PC, Cats VM, Bruschke AV (1994) Heart rate and heart rate variability as indexes of sympathovagal balance. Am J Phys 266(4 Pt 2):H1565–H1571

    CAS  Google Scholar 

  198. Alonso JF, Romero S, Ballester MR, Antonijoan RM, Mañanas MA et al (2015) Stress assessment based on EEG univariate features and functional connectivity measures. Physiol Meas 36(7):1351–1365

    Article  CAS  PubMed  Google Scholar 

  199. Valkonen-Korhonen M, Tarvainen MP, Ranta-Aho P, Karjalainen PA, Partanen J, Karhu J et al (2003) Heart rate variability in acute psychosis. Psychophysiology 40(5):716–726

    Article  PubMed  Google Scholar 

  200. Rachow T, Berger S, Boettger MK, Schulz S, Guinjoan S, Yeragani VK et al (2011) Nonlinear relationship between electrodermal activity and heart rate variability in patients with acute schizophrenia. Psychophysiology 48(10):1323–1332

    Article  PubMed  Google Scholar 

  201. Olbrich R, Kirsch P, Pfeiffer H, Mussgay L (2001) Patterns of recovery of autonomic dysfunctions and neurocognitive deficits in schizophrenics after acute psychotic episodes. J Abnorm Psychol 110(1):142–150

    Article  CAS  PubMed  Google Scholar 

  202. Yeragani VK, Rao KA, Smitha MR, Pohl RB, Balon R, Srinivasan K (2002) Diminished chaos of heart rate time series in patients with major depression. Biol Psychiatry 51(9):733–744

    Article  PubMed  Google Scholar 

  203. Yeragani VK (2000) Major depression and long-term heart period variability. Depress Anxiety 12(1):51–52

    Article  CAS  PubMed  Google Scholar 

  204. Won E, Kim YK (2016) Stress, the autonomic nervous system, and the immune-kynurenine pathway in the etiology of depression. Curr Neuropharmacol 14(7):665–673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Alvares GA, Quintana DS, Kemp AH, Van Zwieten A, Balleine BW, Hickie IB et al (2013) Reduced heart rate variability in social anxiety disorder: associations with gender and symptom severity. PLoS One 8(7):e70468. https://doi.org/10.1371/journal.pone.0070468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Pollatos O, Herbert BM, Wankner S, Dietel A, Wachsmuth C, Henningsen P et al (2011) Autonomic imbalance is associated with reduced facial recognition in somatoform disorders. J Psychosom Res 71(4):232–239

    Article  PubMed  Google Scholar 

  207. Kawachi I, Sparrow D, Vokonas PS, Weiss ST (1995) Decreased heart rate variability in men with phobic anxiety (data from the Normative Aging Study). Am J Cardiol 75(14):882–885

    Article  CAS  PubMed  Google Scholar 

  208. Karpyak VM, Romanowicz M, Schmidt JE, Lewis KA, Bostwick JM (2014) Characteristics of heart rate variability in alcohol-dependent subjects and nondependent chronic alcohol users. Alcohol Clin Exp Res 38(1):9–26

    Article  PubMed  Google Scholar 

  209. Garland EL, Franken IH, Sheetz JJ, Howard MO (2012) Alcohol attentional bias is associated with autonomic indices of stress-primed alcohol cue-reactivity in alcohol-dependent patients. Exp Clin Psychopharmacol 20(3):225–235

    Article  PubMed  Google Scholar 

  210. Frewen J, Finucane C, Savva GM, Boyle G, Coen RF, Kenny RA (2013) Cognitive function is associated with impaired heart rate variability in ageing adults: the Irish longitudinal study on ageing wave one results. Clin Auton Res 23(6):313–323

    Article  PubMed  Google Scholar 

  211. Sarlon J, Plaszczyk S, Engel S, Oertel-Knöchel V (2018) Electrophysiological parameters as biomarkers for psychiatry: intra-individual variability and influencing factors. Int J Psychophysiol 123:42–47

    Article  PubMed  Google Scholar 

  212. Boutros NN, Mucci A, Vignapiano A, Galderisi S (2014) Electrophysiological aberrations associated with negative symptoms in schizophrenia. Curr Top Behav Neurosci 21:129–156

    Article  PubMed  Google Scholar 

  213. Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S et al (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488(7410):178–184

    Article  CAS  PubMed  Google Scholar 

  214. Mayer EA (2011) Gut feelings: the emerging biology of gut–brain communication. Nat Rev Neurosci 12(8):453–466

    Article  CAS  PubMed  Google Scholar 

  215. Hoban AE, Stilling RM, Ryan FJ, Shanahan F, Dinan TG, Claesson MJ et al (2016) Regulation of prefrontal cortex myelination by the microbiota. Transl Psychiatry 6:e774. https://doi.org/10.1038/tp.2016.42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Ogbonnaya ES, Clarke G, Shanahan F, Dinan TG, Cryan JF, O’Leary OF (2015) Adult hippocampal neurogenesis is regulated by the microbiome. Biol Psychiatry 78(4):e7–e9. https://doi.org/10.1016/j.biopsych.2014.12.023

    Article  PubMed  Google Scholar 

  217. Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney RD, Shanahan F et al (2013) The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18(6):666–673

    Article  CAS  PubMed  Google Scholar 

  218. Cenit MC, Sanz Y, Codoñer-Franch P (2017) Influence of gut microbiota on neuropsychiatric disorders. World J Gastroenterol 23(30):5486–5498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Fabi E, Fusco A, Valiante M, Celli R (2013) Genetics and epigenetics of schizophrenia. Clin Ter 164:e319–e324

    CAS  PubMed  Google Scholar 

  220. Dinan TG, Borre YE, Cryan JF (2014) Genomics of schizophrenia: time to consider the gut microbiome? Mol Psychiatry 19:1252–1257

    Article  CAS  PubMed  Google Scholar 

  221. Dinan TG, Cryan JF (2013) Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol Motil 25:713–719

    Article  CAS  PubMed  Google Scholar 

  222. Aizawa E, Tsuji H, Asahara T, Takahashi T, Teraishi T, Yoshida S et al (2016) Possible association of Bifidobacterium and Lactobacillus in the gut microbiota of patients with major depressive disorder. J Affect Disord 202:254–257

    Article  PubMed  Google Scholar 

  223. Hughes C, Davoodi-Semiromi Y, Colee JC, Culpepper T, Dahl WJ, Mai V et al (2011) Galactooligosaccharide supplementation reduces stress-induced gastrointestinal dysfunction and days of cold or flu: a randomized, double-blind, controlled trial in healthy university students. Am J Clin Nutr 93:1305–1311

    Article  CAS  PubMed  Google Scholar 

  224. Kelly JR, Borre Y, O’Brien C, Patterson E, El Aidy S, Deane J et al (2016) Transferring the blues: depression-associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res 82:109–118

    Article  PubMed  Google Scholar 

  225. Solfrizzi V, Custodero C, Lozupone M, Imbimbo BP, Valiani V, Agosti P (2017) Relationships of dietary patterns, foods, and micro- and macronutrients with Alzheimer’s disease and late-life cognitive disorders: a systematic review. J Alzheimers Dis 59(3):815–849

    Article  CAS  PubMed  Google Scholar 

  226. Jørgensen BP, Hansen JT, Krych L, Larsen C, Klein AB, Nielsen DS et al (2014) A possible link between food and mood: dietary impact on gut microbiota and behavior in BALB/c mice. PLoS One 9(8):e103398. https://doi.org/10.1371/journal.pone.0103398

    Article  CAS  Google Scholar 

  227. Zhernakova A, Kurilshikov A, Bonder MJ, Tigchelaar EF, Schirmer M, Vatanen T et al (2016) Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352:565–569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Messaoudi M, Violle N, Bisson JF, Desor D, Javelot H, Rougeot C (2011) Beneficial psychological effects of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in healthy human volunteers. Gut Microbes 2:256–261

    Article  PubMed  Google Scholar 

  229. Schwensen HF, Kan C, Treasure J, Høiby N, Sjögren M (2018) A systematic review of studies on the faecal microbiota in anorexia nervosa: future research may need to include microbiota from the small intestine. Eat Weight Disord 23(4):399–418

    Article  PubMed  Google Scholar 

  230. Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K et al (2010) Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry 167(7):748–751

    Article  PubMed  Google Scholar 

  231. Wakefield JC (2014) Wittgenstein’s nightmare: why the RDoC grid needs a conceptual dimension. World Psychiatry 13(1):38–40

    Article  PubMed  PubMed Central  Google Scholar 

  232. Pratt J, Hall J (2018) Biomarkers in neuropsychiatry: a prospect for the twenty-first century? Curr Top Behav Neurosci 40:3-10

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Francesco Panza .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lozupone, M. et al. (2019). The Role of Biomarkers in Psychiatry. In: Guest, P. (eds) Reviews on Biomarker Studies in Psychiatric and Neurodegenerative Disorders. Advances in Experimental Medicine and Biology(), vol 1118. Springer, Cham. https://doi.org/10.1007/978-3-030-05542-4_7

Download citation

Publish with us

Policies and ethics