The Role of Biomarkers in Psychiatry

  • Madia Lozupone
  • Maddalena La Montagna
  • Francesca D’Urso
  • Antonio Daniele
  • Antonio Greco
  • Davide Seripa
  • Giancarlo Logroscino
  • Antonello Bellomo
  • Francesco PanzaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1118)


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.


Proteomics Biomarker Post-genomic diagnostics Psychiatric disease Epigenetics Microbiota Lifestyle Depressive disorder Schizophrenia Bipolar disorder 


  1. 1.
    Katahira K, Yamashita Y (2017) A theoretical framework for evaluating psychiatric research strategies. Comput Psychiatr 1:184–207PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69(3):89–95CrossRefGoogle Scholar
  3. 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)
  4. 4.
    Boksa P (2013) A way forward for research on biomarkers for psychiatric disorders. J Psychiatry Neurosci 38(2):75–77PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Quevedo J, Yatham LN (2018) Biomarkers in mood disorders: are we there yet? J Affect Disord 233:1–2PubMedCrossRefGoogle Scholar
  6. 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. Scholar
  7. 7.
    Singh I, Rose N (2009) Biomarkers in psychiatry. Nature 460(7252):202–207PubMedCrossRefGoogle Scholar
  8. 8.
    Dean B (2011) Dissecting the syndrome of schizophrenia: progress toward clinically useful biomarkers. Schizophr Res Treat 2011:614730. Scholar
  9. 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):211–223PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Lydon-Staley DM, Bassett DS (2018) Network neuroscience: a framework for developing biomarkers in psychiatry. Curr Top Behav Neurosci 40:79-109Google Scholar
  11. 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):1–20PubMedCrossRefGoogle Scholar
  12. 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):81–132PubMedCrossRefGoogle Scholar
  13. 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. 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):989–1000PubMedCrossRefGoogle Scholar
  15. 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. Scholar
  16. 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–e316PubMedCrossRefGoogle Scholar
  17. 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):1357–1369PubMedCrossRefGoogle Scholar
  18. 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):431–442CrossRefGoogle Scholar
  19. 19.
    Hurko O (2009) The uses of biomarkers in drug development. Ann N Y Acad Sci 1180:1–10PubMedCrossRefGoogle Scholar
  20. 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):809–824PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Petterson RF (1990) Mapping and sequencing the human genome. Ann Med 22(6):371–373CrossRefGoogle Scholar
  22. 22.
    Higa GS, De Sousa E, Walter LT, Kinjo ER, Resende RR, Kihara AH (2014) MicroRNAs in neuronal communication. Mol Neurobiol 49(3):1309–1326PubMedPubMedCentralGoogle Scholar
  23. 23.
    Mohammadi A, Rashidi E, Amooeian VG (2018) Brain, blood, cerebrospinal fluid, and serum biomarkers in schizophrenia. Psychiatry Res 265:25–38PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Sigitova E, Fišar Z, Hroudová CT, Raboch J (2017) Biological hypotheses and biomarkers of bipolar disorder. Psychiatry Clin Neurosci 71(2):77–103PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Hacimusalar Y, Eşel E (2018) Suggested biomarkers for major depressive disorder. Noro Psikiyatr Ars 55(3):280–290PubMedPubMedCentralGoogle Scholar
  26. 26.
    Strawbridge R, Young AH, Cleare AJ (2017) Biomarkers for depression: recent insights, current challenges and future prospects. Neuropsychiatr Dis Treat 13:1245–1262PubMedPubMedCentralCrossRefGoogle Scholar
  27. 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. Scholar
  28. 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.
  29. 29.
    Pasternak O, Kelly S, Sydnor VJ (2018) Advances in microstructural diffusion neuroimaging for psychiatric disorders. NeuroImage 182:259–282. Scholar
  30. 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):95–108Google Scholar
  31. 31.
    Zipursky RB (2007) Imaging mental disorders in the 21st century. Can J Psychiatr 52(3):133–134CrossRefGoogle Scholar
  32. 32.
    Bailey DL, Pichler BJ, Gückel 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, Tübingen, Germany. Mol Imaging Biol 18(5):637–650PubMedPubMedCentralCrossRefGoogle Scholar
  33. 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. Scholar
  34. 34.
    Ross CA, Margolis RL, Reading SA, Pletnikov M, Coyle JT (2006) Neurobiology of schizophrenia. Neuron 52(1):139–153PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Niznikiewicz MK, Kubicki M, Shenton ME (2003) Recent structural and functional imaging findings in schizophrenia. Curr Opin Psychiatry 16:123–147CrossRefGoogle Scholar
  36. 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 62:1071–1080PubMedCrossRefPubMedCentralGoogle Scholar
  37. 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):13171–13179PubMedCrossRefPubMedCentralGoogle Scholar
  38. 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. Scholar
  39. 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):945–961PubMedCrossRefPubMedCentralGoogle Scholar
  40. 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):64–72PubMedPubMedCentralCrossRefGoogle Scholar
  41. 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. Scholar
  42. 42.
    Demirtaş M, Tornador C, Falcon C, López-Solà M, Hernández-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):2918–2930PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Lawrie SM, Abukmeil SS (1998) Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies. Br J Psychiatry 172:110–120PubMedCrossRefPubMedCentralGoogle Scholar
  44. 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 55:433–440PubMedCrossRefGoogle Scholar
  45. 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 162:2233–2245PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Van Horn JD, Mcmanus IC (1992) Ventricular enlargement in schizophrenia. A metaanalysis of studies of the ventricle: brain ratio (VBR). Br J Psychiatry 160:687–697PubMedCrossRefGoogle Scholar
  47. 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 157:16–25PubMedCrossRefPubMedCentralGoogle Scholar
  48. 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):88–94PubMedCrossRefGoogle Scholar
  49. 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):370–378CrossRefGoogle Scholar
  50. 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 41:15–30PubMedCrossRefGoogle Scholar
  51. 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 65:193–207PubMedCrossRefGoogle Scholar
  52. 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 89:475-480PubMedCrossRefGoogle Scholar
  53. 53.
    Ressler KJ, Mayberg HS (2007) Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci 10:1116–1124PubMedPubMedCentralCrossRefGoogle Scholar
  54. 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):4420–4439PubMedCrossRefGoogle Scholar
  55. 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 117:1–17PubMedCrossRefGoogle Scholar
  56. 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 52:75–83PubMedCrossRefGoogle Scholar
  57. 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):1841–1847PubMedCrossRefGoogle Scholar
  58. 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):894–900PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Bora E, Fornito A, Yücel M, Pantelis C (2010) Voxelwise meta-analysis of gray matter abnormalities in bipolar disorder. Biol Psychiatry 67:1097–1105PubMedCrossRefPubMedCentralGoogle Scholar
  60. 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):1710–1171PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Maletic V, Raison C (2014) Integrated neurobiology of bipolar disorder. Front Psych 5:98. Scholar
  62. 62.
    Cerullo MA, Adler CM, Delbello MP, Strakowski SM (2009) The functional neuroanatomy of bipolar disorder. Int Rev Psychiatry 21:314–322PubMedCrossRefGoogle Scholar
  63. 63.
    Vargas C, López-Jaramillo C, Vieta E (2013) A systematic literature review of resting state network—functional MRI in bipolar disorder. J Affect Disord 150:727–735PubMedCrossRefGoogle Scholar
  64. 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. [Epub ahead of print]
  65. 65.
    Alda M (2015) Lithium in the treatment of bipolar disorder: pharmacology and pharmacogenetics. Mol Psychiatry 20(6):661–670PubMedPubMedCentralCrossRefGoogle Scholar
  66. 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):259–272PubMedPubMedCentralCrossRefGoogle Scholar
  67. 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):10389–10397PubMedCrossRefGoogle Scholar
  68. 68.
    Keener MT, Phillips ML (2007) Neuroimaging in bipolar disorder: a critical review of current findings. Curr Psychiatry Rep 9(6):512–520PubMedPubMedCentralCrossRefGoogle Scholar
  69. 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):23–29PubMedCrossRefGoogle Scholar
  70. 70.
    Bauer IE, Pascoe MC, Wollenhaupt-Aguiar B, Kapczinski F, Soares JC (2014) Inflammatory mediators of cognitive impairment in bipolar disorder. J Psychiatr Res 56:18–27PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Nikkila H, Müller K, Ahokas A, Miettinen K, Andersson LC, Rimón R (1995) Abnormal distributions of T-lymphocyte subsets in the cerebrospinal fluid of patients with acute schizophrenia. Schizophr Res 14:215–221PubMedCrossRefGoogle Scholar
  72. 72.
    Müller N, Ackenheil M (1995) Immunoglobulin and albumin content of cerebrospinal fluid in schizophrenic patients: relationship to negative symptomatology. Schizophr Res 14:223–228PubMedCrossRefGoogle Scholar
  73. 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 71:171–186PubMedCrossRefGoogle Scholar
  74. 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 49:206–215PubMedPubMedCentralCrossRefGoogle Scholar
  75. 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 511:421–427PubMedCentralCrossRefPubMedGoogle Scholar
  76. 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):223–230PubMedCrossRefGoogle Scholar
  77. 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 32:101–108PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Van Kammen DP, Mcallister-Sistilli CG, Kelley ME, Gurklis JA, Yao JK (1999) Elevated interleukin-6 in schizophrenia. Psychiatry Res 87:129–136PubMedCrossRefGoogle Scholar
  79. 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 36:331–336PubMedCrossRefGoogle Scholar
  80. 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 129:194–198PubMedCrossRefGoogle Scholar
  81. 81.
    Nawa H, Takahashi M, Patterson PH (2000) Cytokine and growth factor involvement in schizophrenia–support for the developmental model. Mol Psychiatry 5:594–603PubMedCrossRefGoogle Scholar
  82. 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):75–83PubMedCrossRefGoogle Scholar
  83. 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):908–911PubMedPubMedCentralCrossRefGoogle Scholar
  84. 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. [Epub ahead of print]
  85. 85.
    Benros ME, Mortensen PB, Eaton WW (2012) Autoimmune diseases and infections as risk factors for schizophrenia. Ann N Y Acad Sci 1262:56–66PubMedCrossRefGoogle Scholar
  86. 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 89:219–232CrossRefGoogle Scholar
  87. 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 17:291–302PubMedCrossRefGoogle Scholar
  88. 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. Scholar
  89. 89.
    Kirch DG, Kaufmann CA, Papadopoulos NM, Martin B, Weinberger DR (1985) Abnormal cerebrospinal fluid protein indices in schizophrenia. Biol Psychiatry 20:1039–1046PubMedCrossRefGoogle Scholar
  90. 90.
    Müller 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 12:294–299PubMedCrossRefGoogle Scholar
  91. 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 57:259–266PubMedCrossRefGoogle Scholar
  92. 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 41:55–58PubMedCrossRefGoogle Scholar
  93. 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 38:853–862PubMedCrossRefGoogle Scholar
  94. 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):147–159PubMedCrossRefGoogle Scholar
  95. 95.
    Baghai TC, Varallo-Bedarida G, Born C, Häfner S, Schüle 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. Scholar
  96. 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. Scholar
  97. 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 9:580–586PubMedGoogle Scholar
  98. 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 10:208–212PubMedCrossRefGoogle Scholar
  99. 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 401:1–5PubMedCrossRefGoogle Scholar
  100. 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 60:70–76PubMedCrossRefPubMedCentralGoogle Scholar
  101. 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 25:311–313PubMedCrossRefPubMedCentralGoogle Scholar
  102. 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 39:327–333PubMedCrossRefPubMedCentralGoogle Scholar
  103. 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 36:195–203PubMedCrossRefPubMedCentralGoogle Scholar
  104. 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 52:79–86PubMedCrossRefPubMedCentralGoogle Scholar
  105. 105.
    Fulzele S, Pillai A (2009) Decreased VEGF mRNA expression in the dorsolateral prefrontal cortex of schizophrenia subjects. Schizophr Res 115:372–373PubMedCrossRefPubMedCentralGoogle Scholar
  106. 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 115:209–214PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Zakharyan R, Atshemyan S, Gevorgyan A, Boyajyan A (2014) Nerve growth factor and its receptor in schizophrenia. BBA Clin 1:24–29PubMedPubMedCentralCrossRefGoogle Scholar
  108. 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 228:95–99PubMedCrossRefPubMedCentralGoogle Scholar
  109. 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 86:39–45PubMedCrossRefPubMedCentralGoogle Scholar
  110. 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 110:249–257PubMedCrossRefPubMedCentralGoogle Scholar
  111. 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 28:709–713PubMedCrossRefPubMedCentralGoogle Scholar
  112. 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 382:27–32PubMedCrossRefPubMedCentralGoogle Scholar
  113. 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 41:31–35PubMedCrossRefPubMedCentralGoogle Scholar
  114. 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 33:1508–1512PubMedCrossRefPubMedCentralGoogle Scholar
  115. 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 11:251–255PubMedCrossRefPubMedCentralGoogle Scholar
  116. 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):900–906PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatr 122(5):509–522PubMedCrossRefGoogle Scholar
  118. 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. Scholar
  119. 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. Scholar
  120. 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. Scholar
  121. 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–1575SPubMedCrossRefGoogle Scholar
  122. 122.
    Bowers MB (1974) Lumbar CSF 5-hydroxyindoleacetic acid and homovanillic acid in affective syndromes. J Nerv Ment Dis 158(5):325–330PubMedCrossRefGoogle Scholar
  123. 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 86:17–24PubMedCrossRefGoogle Scholar
  124. 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. Scholar
  125. 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 41:17–24PubMedCrossRefGoogle Scholar
  126. 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 176:1–7PubMedCrossRefGoogle Scholar
  127. 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. Scholar
  128. 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 173:180–187PubMedCrossRefGoogle Scholar
  129. 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 97:8104–8109PubMedPubMedCentralCrossRefGoogle Scholar
  130. 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 93:9235–9240PubMedPubMedCentralCrossRefGoogle Scholar
  131. 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 105:137–146PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    Farde L, Gustavsson JP, Jönsson E (1997) D2 dopamine receptors and personality traits. Nature 385:590. Scholar
  133. 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). Scholar
  134. 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 168:418–426PubMedCrossRefPubMedCentralGoogle Scholar
  135. 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):2569–2574PubMedPubMedCentralCrossRefGoogle Scholar
  136. 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):13–20PubMedCrossRefPubMedCentralGoogle Scholar
  137. 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 8:315–336PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Gurevich EV, Joyce JN (1997) Alterations in the cortical serotonergic system in schizophrenia: a postmortem study. Biol Psychiatry 42:529–545PubMedCrossRefPubMedCentralGoogle Scholar
  139. 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 50:810–818PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Sumiyoshi T, Stockmeier CA, Overholser JC, Dilley GE, Meltzer HY (1996) Serotonin1A receptors are increased in postmortem prefrontal cortex in schizophrenia. Brain Res 708:209–214PubMedCrossRefPubMedCentralGoogle Scholar
  141. 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 55:225–233PubMedCrossRefPubMedCentralGoogle Scholar
  142. 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):337–347PubMedPubMedCentralGoogle Scholar
  143. 143.
    Tuominen L, Salo J, Hirvonen J, Någren 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):881–894PubMedCrossRefPubMedCentralGoogle Scholar
  144. 144.
    Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmüller B (1980) Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci Lett 20:379–382PubMedCrossRefPubMedCentralGoogle Scholar
  145. 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 162:1738–1740PubMedCrossRefPubMedCentralGoogle Scholar
  146. 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 29:767–769PubMedCrossRefPubMedCentralGoogle Scholar
  147. 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):293–307PubMedPubMedCentralCrossRefGoogle Scholar
  148. 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 44:673–681PubMedCrossRefPubMedCentralGoogle Scholar
  149. 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 35:247–253PubMedCrossRefPubMedCentralGoogle Scholar
  150. 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 61:653–660PubMedCrossRefPubMedCentralGoogle Scholar
  151. 151.
    Pinna G (2018) Biomarkers for PTSD at the interface of the endocannabinoid and neurosteroid axis. Front Neurosci 12:482. Scholar
  152. 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–S16CrossRefGoogle Scholar
  153. 153.
    Nemeroff CB (2008) Understanding the pathophysiology of postpartum depression: implications for the development of novel treatments. Neuron 59:185–186PubMedCrossRefPubMedCentralGoogle Scholar
  154. 154.
    Lovick T (2013) SSRIs and the female brain–potential for utilizing steroid-stimulating properties to treat menstrual cycle-linked dysphorias. J Psychopharmacol 27:1180–1185PubMedCrossRefPubMedCentralGoogle Scholar
  155. 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–e95PubMedCrossRefPubMedCentralGoogle Scholar
  156. 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):1436–1444PubMedCrossRefPubMedCentralGoogle Scholar
  157. 157.
    Belelli D, Lambert JJ (2005) Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat Rev Neurosci 6:565–575PubMedCrossRefPubMedCentralGoogle Scholar
  158. 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 93:133–141PubMedCrossRefPubMedCentralGoogle Scholar
  159. 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 67:198–206PubMedCrossRefPubMedCentralGoogle Scholar
  160. 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 73:1590–1597PubMedCrossRefPubMedCentralGoogle Scholar
  161. 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 10:1779–1782PubMedCrossRefPubMedCentralGoogle Scholar
  162. 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:2–6PubMedCrossRefPubMedCentralGoogle Scholar
  163. 163.
    Rozek LS, Dolinoy DC, Sartor MA, Omenn GS (2014) Epigenetics: relevance and implications for public health. Annu Rev Public Health 35:105–122PubMedPubMedCentralCrossRefGoogle Scholar
  164. 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):111–123PubMedCrossRefPubMedCentralGoogle Scholar
  165. 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):133–140PubMedPubMedCentralCrossRefGoogle Scholar
  166. 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 184:496–502PubMedCrossRefPubMedCentralGoogle Scholar
  167. 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):1923–1931PubMedCrossRefPubMedCentralGoogle Scholar
  168. 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):1065–1070PubMedCrossRefPubMedCentralGoogle Scholar
  169. 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. Scholar
  170. 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):183–191PubMedPubMedCentralCrossRefGoogle Scholar
  171. 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):188–193PubMedPubMedCentralCrossRefGoogle Scholar
  172. 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):1156–1168PubMedCrossRefPubMedCentralGoogle Scholar
  173. 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 42:1037–1045PubMedCrossRefPubMedCentralGoogle Scholar
  174. 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) 72:578–582CrossRefGoogle Scholar
  175. 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):1176–1189PubMedCrossRefGoogle Scholar
  176. 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):180–187PubMedCrossRefGoogle Scholar
  177. 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):3125–3130PubMedPubMedCentralCrossRefGoogle Scholar
  178. 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):198–204PubMedCrossRefGoogle Scholar
  179. 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. Scholar
  180. 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):562–571PubMedCrossRefGoogle Scholar
  181. 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):570–574PubMedCrossRefGoogle Scholar
  182. 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. Scholar
  183. 183.
    Yao Y, Schröder J, Karlsson H (2008) Verification of proposed peripheral biomarkers in mononuclear cells of individuals with schizophrenia. J Psychiatr Res 42:639–643PubMedCrossRefGoogle Scholar
  184. 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. Scholar
  185. 185.
    Wang X, Wang X (2006) Systematic identification of microRNA functions by combining target prediction and expression profiling. Nucleic Acids Res 34(5):1646–1652PubMedPubMedCentralCrossRefGoogle Scholar
  186. 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):283–289PubMedCrossRefGoogle Scholar
  187. 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. Scholar
  188. 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):53–55PubMedPubMedCentralGoogle Scholar
  189. 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. Scholar
  190. 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):1373–1385PubMedCrossRefGoogle Scholar
  191. 191.
    Moodithaya S, Avadhany ST (2012) Gender differences in age-related changes in cardiac autonomic nervous function. J Aging Res 2012:679345. Scholar
  192. 192.
    Sztajzel J (2004) Heart rate variability: a noninvasive electrocardiographic method to measure the autonomic nervous system. Swiss Med Wkly 134(35–36):514–522PubMedGoogle Scholar
  193. 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):1080–1091PubMedCrossRefGoogle Scholar
  194. 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):6–13PubMedCrossRefGoogle Scholar
  195. 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 211:241–248PubMedGoogle Scholar
  196. 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. Scholar
  197. 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–H1571Google Scholar
  198. 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):1351–1365PubMedCrossRefGoogle Scholar
  199. 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):716–726PubMedCrossRefGoogle Scholar
  200. 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):1323–1332PubMedCrossRefPubMedCentralGoogle Scholar
  201. 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):142–150PubMedCrossRefPubMedCentralGoogle Scholar
  202. 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):733–744PubMedCrossRefPubMedCentralGoogle Scholar
  203. 203.
    Yeragani VK (2000) Major depression and long-term heart period variability. Depress Anxiety 12(1):51–52PubMedCrossRefPubMedCentralGoogle Scholar
  204. 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):665–673PubMedPubMedCentralCrossRefGoogle Scholar
  205. 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. Scholar
  206. 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):232–239PubMedCrossRefPubMedCentralGoogle Scholar
  207. 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):882–885PubMedCrossRefPubMedCentralGoogle Scholar
  208. 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):9–26PubMedCrossRefPubMedCentralGoogle Scholar
  209. 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):225–235PubMedCrossRefPubMedCentralGoogle Scholar
  210. 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):313–323PubMedCrossRefPubMedCentralGoogle Scholar
  211. 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 123:42–47PubMedCrossRefPubMedCentralGoogle Scholar
  212. 212.
    Boutros NN, Mucci A, Vignapiano A, Galderisi S (2014) Electrophysiological aberrations associated with negative symptoms in schizophrenia. Curr Top Behav Neurosci 21:129–156PubMedCrossRefPubMedCentralGoogle Scholar
  213. 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):178–184PubMedPubMedCentralCrossRefGoogle Scholar
  214. 214.
    Mayer EA (2011) Gut feelings: the emerging biology of gut–brain communication. Nat Rev Neurosci 12(8):453–466PubMedCrossRefGoogle Scholar
  215. 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. Scholar
  216. 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. Scholar
  217. 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):666–673PubMedCrossRefGoogle Scholar
  218. 218.
    Cenit MC, Sanz Y, Codoñer-Franch P (2017) Influence of gut microbiota on neuropsychiatric disorders. World J Gastroenterol 23(30):5486–5498PubMedPubMedCentralCrossRefGoogle Scholar
  219. 219.
    Fabi E, Fusco A, Valiante M, Celli R (2013) Genetics and epigenetics of schizophrenia. Clin Ter 164:e319–e324PubMedPubMedCentralGoogle Scholar
  220. 220.
    Dinan TG, Borre YE, Cryan JF (2014) Genomics of schizophrenia: time to consider the gut microbiome? Mol Psychiatry 19:1252–1257PubMedCrossRefPubMedCentralGoogle Scholar
  221. 221.
    Dinan TG, Cryan JF (2013) Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol Motil 25:713–719PubMedCrossRefPubMedCentralGoogle Scholar
  222. 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 202:254–257PubMedCrossRefPubMedCentralGoogle Scholar
  223. 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 93:1305–1311PubMedCrossRefPubMedCentralGoogle Scholar
  224. 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 82:109–118PubMedCrossRefPubMedCentralGoogle Scholar
  225. 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):815–849PubMedCrossRefPubMedCentralGoogle Scholar
  226. 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. Scholar
  227. 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 352:565–569PubMedPubMedCentralCrossRefGoogle Scholar
  228. 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 2:256–261PubMedCrossRefPubMedCentralGoogle Scholar
  229. 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):399–418PubMedCrossRefPubMedCentralGoogle Scholar
  230. 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):748–751PubMedCrossRefPubMedCentralGoogle Scholar
  231. 231.
    Wakefield JC (2014) Wittgenstein’s nightmare: why the RDoC grid needs a conceptual dimension. World Psychiatry 13(1):38–40PubMedPubMedCentralCrossRefGoogle Scholar
  232. 232.
    Pratt J, Hall J (2018) Biomarkers in neuropsychiatry: a prospect for the twenty-first century? Curr Top Behav Neurosci 40:3-10Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Madia Lozupone
    • 1
  • Maddalena La Montagna
    • 2
  • Francesca D’Urso
    • 2
  • Antonio Daniele
    • 3
    • 4
  • Antonio Greco
    • 5
  • Davide Seripa
    • 5
  • Giancarlo Logroscino
    • 1
    • 6
  • Antonello Bellomo
    • 2
  • Francesco Panza
    • 1
    • 5
    • 6
    Email author
  1. 1.Neurodegenerative Disease Unit, Department of Basic Medical Sciences, Neuroscience and Sense OrgansUniversity of Bari Aldo MoroBariItaly
  2. 2.Psychiatric Unit, Department of Clinical and Experimental MedicineUniversity of FoggiaFoggiaItaly
  3. 3.Institute of NeurologyCatholic University of Sacred HeartRomeItaly
  4. 4.Fondazione Policlinico Universitario A. Gemelli IRCCSRomeItaly
  5. 5.Geriatric Unit, Fondazione IRCCS Casa Sollievo della SofferenzaFoggiaItaly
  6. 6.Department of Clinical Research in NeurologyUniversity of Bari Aldo MoroLecceItaly

Personalised recommendations