Top

Published in:

01-04-2018 | ORIGINAL ARTICLE

In Schizophrenia, Depression, Anxiety, and Physiosomatic Symptoms Are Strongly Related to Psychotic Symptoms and Excitation, Impairments in Episodic Memory, and Increased Production of Neurotoxic Tryptophan Catabolites: a Multivariate and Machine Learning Study

Authors: Buranee Kanchanatawan, Supaksorn Thika, Sunee Sirivichayakul, André F. Carvalho, Michel Geffard, Michael Maes

Published in: Neurotoxicity Research | Issue 3/2018

Abstract

The depression, anxiety and physiosomatic symptoms (DAPS) of schizophrenia are associated with negative symptoms and changes in tryptophan catabolite (TRYCAT) patterning. The aim of this study is to delineate the associations between DAPS and psychosis, hostility, excitation, and mannerism (PHEM) symptoms, cognitive tests as measured using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) and IgA/IgM responses to TRYCATs. We included 40 healthy controls and 80 participants with schizophrenia. Depression and anxiety symptoms were measured with The Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales, respectively. Physiosomatic symptoms were assessed with the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale (FF). Negative symptoms as well as CERAD tests, including Verbal Fluency Test (VFT), Mini-Mental State Examination (MMSE), Word List Memory (WLM), and WL Delayed Recall were measured, while ratios of IgA responses to noxious/protective TRYCATs (IgA NOX_PRO) were computed. Schizophrenia symptoms consisted of two dimensions, a first comprising PHEM and negative symptoms, and a second DAPS symptoms. A large part of the variance in DAPS was explained by psychotic symptoms and WLM. Of the variance in HAM-D, 58.9% was explained by the regression on excitement, IgA NOX_PRO ratio, WLM, and VFT; 29.9% of the variance in HAM-A by psychotic symptoms and IgA NOX/PRO; and 45.5% of the variance in FF score by psychotic symptoms, IgA NOX/PRO, and WLM. Neural network modeling shows that PHEM, IgA NOX_PRO, WLM, and MMSE are the dominant variables predicting DAPS. DAPS appear to be driven by PHEM and negative symptoms coupled with impairments in episodic memory, especially false memory creation, while all symptom dimension and cognitive impairments may be driven by an increased production of noxious TRYCATs, including picolinic, quinolinic, and xanthurenic acid.

Available only for authorised users

American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders: DSM-IV-TR. American Psychiatric Association, Washington, DC

Amtmann D, Askew RL, Kim J, Chung H, Ehde DM, Bombardier CH, Kraft GH, Jones SM, Johnson KL (2015) Pain affects depression through anxiety, fatigue, and sleep in multiple sclerosis. Rehabil Psychol 60(1):81–90. https://doi.org/10.1037/rep0000027 CrossRefPubMedPubMedCentral

Anderson G, Maes M (2013) Schizophrenia: linking prenatal infection to cytokines, the tryptophan catabolite (TRYCAT) pathway, NMDA receptor hypofunction, neurodevelopment and neuroprogression. Prog Neuro-Psychopharmacol Biol Psychiatry 42:5–19. https://doi.org/10.1016/j.pnpbp.2012.06.014 CrossRef

Anderson G, Maes M, Berk M (2013) Schizophrenia is primed for an increased expression of depression through activation of immuno-inflammatory, oxidative and nitrosative stress, and tryptophan catabolite pathways. Prog Neuro-Psychopharmacol Biol Psychiatry 42:101–114. https://doi.org/10.1016/j.pnpbp.2012.07.016 CrossRef

Beeri MS, Schmeidler J, Sano M, Wang J, Lally R, Grossman H, Silverman JM (2006) Age, gender, and education norms on the CERAD neuropsychological battery in the oldest old. Neurology 67(6):1006–1010. https://doi.org/10.1212/01.wnl.0000237548.15734.cd CrossRefPubMedPubMedCentral

Burton N (2012) Living with schizophrenia. Acheron Press, Oxford

Cavicchioli FL, Maes M, Roomruangwong C, Bonifacio KL, Barbosa DS, Anderson G, Vargas HO, Nunes SOV (2017) Associations between severity of anxiety and clinical and biological features of major affective disorders. Psychiatry Res 260:17–23. https://doi.org/10.1016/j.psychres.2017.11.024 CrossRefPubMed

CERAD (1986) CERAD—an overview: the consortium to establish a registry for Alzheimer’s disease. http://cerad.mc.duke.edu/

Corlett PR, Honey GD, Fletcher PC (2007) From prediction error to psychosis: ketamine as a pharmacological model of delusions. J Psychopharmacol (Oxford) 21(3):238–252. https://doi.org/10.1177/0269881107077716 CrossRef

Crow TJ (1985) The two-syndrome concept: origins and current status. Schizophr Bull 11(3):471–486. https://doi.org/10.1093/schbul/11.3.471 CrossRefPubMed

Cuesta MJ, Peralta V (1995) Cognitive disorders in the positive, negative, and disorganization syndromes of schizophrenia. Psychiatry Res 58(3):227–235. https://doi.org/10.1016/0165-1781(95)02712-6 CrossRefPubMed

Davis J, Eyre H, Jacka FN, Dodd S, Dean O, McEwen S, Debnath M, McGrath J, Maes M, Amminger P, McGorry PD, Pantelis C, Berk M (2016) A review of vulnerability and risks for schizophrenia: beyond the two hit hypothesis. Neurosci Biobehav Rev 65:185–194. https://doi.org/10.1016/j.neubiorev.2016.03.017 CrossRefPubMedPubMedCentral

Duleu S, Mangas A, Sevin F, Veyret B, Bessede A, Geffard M (2010) Circulating antibodies to IDO/THO pathway metabolites in Alzheimer’s disease. Int J Alzheimers Dis. https://doi.org/10.4061/2010/501541

Emsley RA, Oosthuizen PP, Joubert AF, Roberts MC, Stein DJ (1999) Depressive and anxiety symptoms in patients with schizophrenia and schizophreniform disorder. J Clin Psychiatry 60(11):747–751. https://doi.org/10.4088/JCP.v60n1105 CrossRefPubMed

Ferrando PJ, Lorenzo-Seva U (2013) Unrestricted item factor analysis and some relations with item response theory. Technical report. Department of Psychology, Universitat Rovira i Virgili, Tarragona

Ferrando PJ, Lorenzo-Seva U (2017) Manual of the program: FACTOR, Windows 7 / Windows 8 / Windows 10

Grillon ML, Krebs MO, Gourevitch R, Giersch A, Huron C (2010) Episodic memory and impairment of an early encoding process in schizophrenia. Neuropsychology 24(1):101–108. https://doi.org/10.1037/a0015544 CrossRefPubMed

Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32(1):50–55. https://doi.org/10.1111/j.2044-8341.1959.tb00467.x CrossRefPubMed

Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23(1):56–62. https://doi.org/10.1136/jnnp.23.1.56 CrossRefPubMedPubMedCentral

Harvey PD, Koren D, Reihenberg A, Bowie CR (2006) Negative symptoms and cognitive deficits: what is the nature of their relationship? Schizophr Bull 32(2):250–258. https://doi.org/10.1093/schbul/sbj011 CrossRefPubMed

Hubbard NA, Hutchison JL, Hambrick DZ, Rypma B (2016) The enduring effects of depressive thoughts on working memory. J Affect Disord 190:208–213. https://doi.org/10.1016/j.jad.2015.06.056 CrossRefPubMed

Jablensky A (2010) The diagnostic concept of schizophrenia: its history, evolution, and future prospects. Dialogues Clin Neurosci 12(3):271–287PubMedPubMedCentral

Janssens KA, Zijlema WL, Joustra ML, Rosmalen JG (2015) Mood and anxiety disorders in chronic fatigue syndrome, fibromyalgia, and irritable bowel syndrome: results from the LifeLines cohort study. Psychosom Med 77(4):449–457. https://doi.org/10.1097/PSY.0000000000000161 CrossRefPubMed

Kanchanatawan B, Sirivichayakul S, Thika S, Ruxrungtham K, Carvalho AF, Geffard M, Anderson G, Noto C, Ivanova R, Maes M (2017a) Physio-somatic symptoms in schizophrenia: association with depression, anxiety, neurocognitive deficits and the tryptophan catabolite pathway. Metab Brain Dis 32(4):1003–1016. https://doi.org/10.1007/s11011-017-9982-7 CrossRefPubMed

Kanchanatawan B, Hemrungrojn S, Thika S, Sirivichayakul S, Ruxrungtham K, Carvalho AF, Geffard M, Anderson G, Maes M (2017b) Changes in tryptophan catabolite (TRYCAT) pathway patterning are associated with mild impairments in declarative memory in schizophrenia and deficits in semantic and episodic memory coupled with increased false-memory creation in deficit schizophrenia. Mol Neurobiol. https://doi.org/10.1007/s12035-017-0751-8

Kanchanatawan B, Sirivichayakul S, Carvalho AF, Anderson G, Galecki P, Maes M (2018a) Depressive, anxiety and hypomanic symptoms in schizophrenia may be driven by tryptophan catabolite (TRYCAT) patterning of IgA and IgM responses directed to TRYCATs. Prog Neuro-Psychopharmacol Biol Psychiatry 80(Pt C):205–216. https://doi.org/10.1016/j.pnpbp.2017.06.033 CrossRef

Kanchanatawan B, Thika S, Anderson G, Galecki P, Maes M (2018b) Affective symptoms in schizophrenia are strongly associated with neurocognitive deficits indicating disorders in executive functions, visual memory, attention and social cognition. Prog Neuro-Psychopharmacol Biol Psychiatry 80(Pt C):168–176. https://doi.org/10.1016/j.pnpbp.2017.06.031 CrossRef

Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13(2):261–276. https://doi.org/10.1093/schbul/13.2.261 CrossRefPubMed

Keefe RS, Harvey PD (2012) Cognitive impairment in schizophrenia. Handb Exp Pharmacol 213:11–37. https://doi.org/10.1007/978-3-642-25758-2_2 CrossRef

Kirkpatrick B, Buchanan RW, McKenney PD, Alphs LD, Carpenter WT Jr (1989) The schedule for the deficit syndrome: an instrument for research in schizophrenia. Psychiatry Res 30(2):119–123. https://doi.org/10.1016/0165-1781(89)90153-4 CrossRefPubMed

Kirschner M, Aleman A, Kaiser S (2017) Secondary negative symptoms — A review of mechanisms, assessment and treatment. Schizophr Res 186:29–38. https://doi.org/10.1016/j.schres.2016.05.003

Kittirathanapaiboon P, Khamwongpin M (2005) The validity of the Mini International Neuropsychiatric Interview (M.I.N.I.) Thai Version: Suanprung Hospital, Department of Mental Health

Kizilbash AH, Vanderploeg RD, Curtiss G (2002) The effects of depression and anxiety on memory performance. Arch Clin Neuropsychol 17(1):57–67. https://doi.org/10.1093/arclin/17.1.57 CrossRefPubMed

Li J, Yu L, Long Z, Li Y, Cao F (2015) Perceived cognitive impairment in Chinese patients with breast cancer and its relationship with post-traumatic stress disorder symptoms and fatigue. Psychooncology 24(6):676–682. https://doi.org/10.1002/pon.3710 CrossRefPubMed

Lysaker PH, Davis LW, Lightfoot J, Hunter N, Stasburger A (2005) Association of neurocognition, anxiety, positive and negative symptoms with coping preference in schizophrenia spectrum disorders. Schizophr Res 80(2-3):163–171. https://doi.org/10.1016/j.schres.2005.07.005 CrossRefPubMed

Maes M (2009) “Functional” or “psychosomatic” symptoms, e.g. a flu-like malaise, aches and pain and fatigue, are major features of major and in particular of melancholic depression. Neuro Endocrinol Lett 30(5):564–573PubMed

Maes M (2011) An intriguing and hitherto unexplained co-occurrence: depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways. Prog Neuro-Psychopharmacol Biol Psychiatry 35(3):784–794. https://doi.org/10.1016/j.pnpbp.2010.06.023 CrossRef

Maes M, Meltzer HY, Cosyns P, Schotte C (1994) Evidence for the existence of major depression with and without anxiety features. Psychopathology 27(1–2):1–13. https://doi.org/10.1159/000284842 CrossRefPubMed

Maes M, Mihaylova I, Kubera M, Leunis JC, Twisk FN, Geffard M (2012a) IgM-mediated autoimmune responses directed against anchorage epitopes are greater in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) than in major depression. Metab Brain Dis 27(4):415–423. https://doi.org/10.1007/s11011-012-9316-8 CrossRefPubMed

Maes M, Twisk FN, Ringel K (2012b) Inflammatory and cell-mediated immune biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome and depression: inflammatory markers are higher in myalgic encephalomyelitis/chronic fatigue syndrome than in depression. Psychother Psychosom 81(5):286–295. https://doi.org/10.1159/000336803 CrossRefPubMed

Marneros A, Deister A, Rohde A (1991) Long-term monomorphism of negative and positive schizophrenic episodes. In: negative symptoms in schizophrenia: relationship to positive symptoms and outcome. In: Marneros A, Andreasen N, Tsuang MT (eds) Negative versus positive schizophrenia. Springer-Verlag, Berlin, pp 183–196. https://doi.org/10.1007/978-3-642-76841-5_12 CrossRef

Mellor CS (1991) Methodological problems in identifying and measuring first-rank symptoms of schizophrenia. In: Marneros A, Andreasen N, Tsuang MT (eds) Negative symptoms in schizophrenia: relationship to positive symptoms and outcome. Springer-Verlag, Berlin, pp 71–78. https://doi.org/10.1007/978-3-642-76841-5_5 CrossRef

Möser C, Krieg JC, Zihl J, Lautenbacher S (2006) Attention and memory deficits in schizophrenia: the role of symptoms of depression. Cogn Behav Neurol 19(3):150–156 wnn.0000213910.41901.1aPubMed

Myhre SR (2015) False memories in depression: vulnerability factor or symptom? Thesis, North Dakota State University of Agriculture and Applied Science. Fargo, North Dakota

Overall JE, Gorham DR (1962) The brief psychiatric rating scale. Psychol Rep 10(3):799–812. https://doi.org/10.2466/pr0.1962.10.3.799 CrossRef

Reichenberg A (2010) The assessment of neuropsychological functioning in schizophrenia. Dialogues Clin Neurosci 12(3):383–392PubMed

Seidman LJ, Lanca M, Kremen WS, Faraone SV, Tsuang MT (2003) Organizational and visual memory deficits in schizophrenia and bipolar psychoses using the Rey-Osterrieth complex figure: effects of duration of illness. J Clin Exp Neuropsychol 25(7):949–964. https://doi.org/10.1076/jcen.25.7.949.16482 CrossRefPubMed

So WK, Marsh G, Ling WM, Leung FY, Lo JC, Yeung M, Li GK (2009) The symptom cluster of fatigue, pain, anxiety, and depression and the effect on the quality of life of women receiving treatment for breast cancer: a multicenter study. Oncol Nurs Forum 36(4):E205–E214. https://doi.org/10.1188/09.ONF.E205-E214 CrossRefPubMed

Tamminga CA, Buchanan RW, Gold JM (1998) The role of negative symptoms and cognitive dysfunction in schizophrenia outcome. Int Clin Psychopharmacol Suppl 3:S21–S26CrossRef

Welsh KA, Butters N, Mohs RC, Beekly D, Edland S, Fillenbaum G, Heyman A (1994) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part V. A normative study of the neuropsychological battery. Neurology 44(4):609–614. https://doi.org/10.1212/WNL.44.4.609 CrossRefPubMed

Yu M, Tang X, Wang X, Zhang X, Zhang X, Sha W, Yao S, Shu N, Zhang X, Zhang Z (2015) Neurocognitive impairments in deficit and non-deficit schizophrenia and their relationships with symptom dimensions and other clinical variables. PLoS One 10(9):e0138357. https://doi.org/10.1371/journal.pone.0138357 CrossRefPubMedPubMedCentral

Zachrisson O, Regland B, Jahreskog M, Kron M, Gottfries CG (2002) A rating scale for fibromyalgia and chronic fatigue syndrome (the FibroFatigue scale). J Psychosom Res 52(6):501–509. https://doi.org/10.1016/S0022-3999(01)00315-4 CrossRefPubMed

Title: In Schizophrenia, Depression, Anxiety, and Physiosomatic Symptoms Are Strongly Related to Psychotic Symptoms and Excitation, Impairments in Episodic Memory, and Increased Production of Neurotoxic Tryptophan Catabolites: a Multivariate and Machine Learning Study
Authors: Buranee Kanchanatawan
Supaksorn Thika
Sunee Sirivichayakul
André F. Carvalho
Michel Geffard
Michael Maes
Publication date: 01-04-2018
Publisher: Springer US
Published in: Neurotoxicity Research / Issue 3/2018
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-018-9868-4

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

In Schizophrenia, Depression, Anxiety, and Physiosomatic Symptoms Are Strongly Related to Psychotic Symptoms and Excitation, Impairments in Episodic Memory, and Increased Production of Neurotoxic Tryptophan Catabolites: a Multivariate and Machine Learning Study

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2018

Experimental Evidence that In Vivo Intracerebral Administration of L-2-Hydroxyglutaric Acid to Neonatal Rats Provokes Disruption of Redox Status and Histopathological Abnormalities in the Brain

Atorvastatin Prevents Early Oxidative Events and Modulates Inflammatory Mediators in the Striatum Following Intranasal 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Administration in Rats

Neurochemical and Neurotoxic Effects of MDMA (Ecstasy) and Caffeine After Chronic Combined Administration in Mice

Chronic Mild Hyperhomocysteinemia Alters Inflammatory and Oxidative/Nitrative Status and Causes Protein/DNA Damage, as well as Ultrastructural Changes in Cerebral Cortex: Is Acetylsalicylic Acid Neuroprotective?

Differential Alterations in Metabolism and Proteolysis-Related Proteins in Human Parkinson’s Disease Substantia Nigra

Add-on Treatment with Curcumin Has Antidepressive Effects in Thai Patients with Major Depression: Results of a Randomized Double-Blind Placebo-Controlled Study