Relationship Between Exposure to Emotional Neglect and the Inflammatory Biomarkers Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, and Platelet-to-Lymphocyte Ratios in Patients With First-Episode Psychosis

Oriol Cuñat, MD; Belén Arranz, MD; Regina Vila-Badia, PhD; Clara Serra-Arumí, MS; Nuria Del Cacho, MD, PhD; Anna Butjosa, PhD; Alicia Colomer-Salvans, MS; Montse Dolz, MD; Marta Pardo, MD; PROFEP Group; Judith Usall, MD, PhD

J Clin Psychiatry. 2024;85(2):23m15141

Abstract

Aim: To assess whether exposure to childhood traumatic experiences is linked to the inflammatory markers neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in people with a first-episode psychosis.

Methods: A cross-sectional study was performed in 83 patients (21 females and 62 males) with a diagnosis of a first psychotic episode. All participants completed the self-reported Spanish version of the Childhood Trauma Questionnaire (CTQ). NLR, MLR, and PLR were calculated in each patient.

Results: Highest CTQ scores were noted on the emotional neglect and abuse domains (mean ± SD = 10.92 ± 4.41; mean ± SD = 10.93 ± 4.78, respectively), being lowest for the sexual abuse domain (mean ± SD = 6.12 ± 2.41). Backward stepwise linear regressions showed that high emotional neglect significantly predicted increased PLR (β = 0.452, P = .036), older age and high emotional neglect predicted increased NLR (β = 0.483, P = .036; β = 0.442, P = .06, respectively), and high emotional neglect, low physical neglect, high total Positive and Negative Syndrome Scale (PANSS) score, and cannabis and alcohol use predicted increased MLR (β = 0.698, P = .003; β = 0.672, P = .033; β = 0.296, P = .027; β = 0.390, P = .069; β = 0.560, P = .078, respectively).

Conclusions: Our results highlight the relationship between the exposure to emotional neglect and the inflammatory biomarkers NLR, MLR, and PLR in patients with a first-episode psychosis. This study has benefitted from controlling for confounders such as body mass index, smoking status, symptom severity, and alcohol and cannabis use.

J Clin Psychiatry 2024;85(2):23m15141

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References (69)

Edwards VJ, Holden GW, Felitti VJ, et al. Relationship between multiple forms of childhood maltreatment and adult mental health in community respondents: results from the Adverse Childhood Experiences Study. Am J Psychiatry. 2003;160(8):1453–1460. PubMed CrossRef
Goodwin RD, Stein MB. Association between childhood trauma and physical disorders among adults in the United States. Psychol Med. 2004;34(3):509–520. PubMed CrossRef
Matheson SL, Shepherd AM, Pinchbeck RM, et al. Childhood adversity in schizophrenia: a systematic meta-analysis. Psychol Med. 2013;43(2):225–238. PubMed CrossRef
McGrath JJ, Saha S, Lim CCW, et al. Trauma and psychotic experiences: transnational data from the World Mental Health survey. Br J Psychiatry. 2017;211(6):373–380. PubMed CrossRef
Varese F, Smeets F, Drukker M, et al. Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective-and cross-sectional cohort studies. Schizophr Bull. 2012;38(4):661–671. PubMed CrossRef
Mayo D, Corey S, Kelly LH, et al. The role of trauma and stressful life events among individuals at clinical high risk for psychosis: a review. Front Psychiatry. 2017;8:55. PubMed
Aas M, Dieset I, Hope S, et al. Childhood maltreatment severity is associated with elevated C-reactive protein and body mass index in adults with schizophrenia and bipolar diagnoses. Brain Behav Immun. 2017;65:342–349. PubMed CrossRef
Baumeister D, Akhtar R, Ciufolini S, et al. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Mol Psychiatry. 2016;21(5):642–649. PubMed CrossRef
Chase KA, Melbourne JK, Rosen C, et al. Traumagenics: at the intersect of childhood trauma, immunity and psychosis. Psychiatry Res. 2019;273:369–377. PubMed CrossRef
Coelho R, Viola TW, Walss-Bass C, et al. Childhood maltreatment and inflammatory markers: a systematic review. Acta Psychiatr Scand. 2014;129(3):180–192. PubMed CrossRef
Hepgul N, Pariante CM, Dipasquale S, et al. Childhood maltreatment is associated with increased body mass index and increased C-reactive protein levels in first-episode psychosis patients. Psychol Med. 2012;42(9):1893–1901. PubMed CrossRef
Di Nicola M, Cattaneo A, Hepgul N, et al. Serum and gene expression profile of cytokines in first-episode psychosis. Brain Behav Immun. 2013;31:90–95. PubMed
Dennison U, McKernan D, Cryan J, et al. Schizophrenia patients with a history of childhood trauma have a pro-inflammatory phenotype. Psychol Med. 2012;42(9):1865–1871. PubMed CrossRef
Mondelli V, Cattaneo A, Murri MB, et al. Stress and inflammation reduce brain derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume. J Clin Psychiatry. 2011;72(12):1677–1684. PubMed CrossRef
Braehler C, Holowka D, Brunet A, et al. Diurnal cortisol in schizophrenia patients with childhood trauma. Schizophr Res. 2005;79(2–3):353–354. PubMed CrossRef
Cicchetti D, Walker EF. Editorial: stress and development: biological and psychological consequences. Dev Psychopathol. 2001;13(3):413–418. PubMed
Read J, Perry BD, Moskowitz A, et al. The contribution of early traumatic events to schizophrenia in some patients: a traumagenic neurodevelopmental model. Psychiatry Interpers Biol Process. 2001;64(4):319–345. PubMed CrossRef
Aiello G, Horowitz M, Hepgul N, et al. Stress abnormalities in individuals at risk for psychosis: a review of studies in subjects with familial risk or with “at risk” mental state. Psychoneuroendocrinology. 2012;37(10):1600–1613. PubMed CrossRef
Baumeister D, Russell A, Pariante CM, et al. Inflammatory biomarker profiles of mental disorders and their relation to clinical, social and lifestyle factors. Soc Psychiatry Psychiatr Epidemiol. 2014;49(6):841–849. PubMed CrossRef
Zunszain PA, Anacker C, Cattaneo A, et al. Interleukin-1β: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis. Neuropsychopharmacology. 2012;37(4):939–949. PubMed CrossRef
Šagud M, Madžarac Z, Nedic Erjavec G, et al. The associations of neutrophil–lymphocyte, platelet–lymphocyte, monocyte–lymphocyte ratios and immune-inflammation index with negative symptoms in patients with schizophrenia. Biomolecules. 2023;13(2):297. PubMed
Faria SS, Fernandes PC Jr., Silva MJB, et al. The neutrophil-to-lymphocyte ratio: a narrative review. Ecancermedicalscience. 2016;10:702. PubMed CrossRef
Tahto E, Jadric R, Pojskic L, et al. Neutrophil-to-lymphocyte ratio and its relation with markers of inflammation and myocardial necrosis in patients with acute coronary syndrome. Med Arch. 2017;71(5):312–315. PubMed CrossRef
Song M, Graubard BI, Rabkin CS, et al. Neutrophil-to-lymphocyte ratio and mortality in the United States general population. Sci Rep. 2021;11(1):464. PubMed
Brinn A, Stone J. Neutrophil-lymphocyte ratio across psychiatric diagnoses: a cross sectional study using electronic health records. BMJ Open. 2020;10(7):e036859. PubMed CrossRef
Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl Lek Listy. 2021;122(7):474–488. PubMed CrossRef
Lee JS, Kim NY, Na SH, et al. Reference values of neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South Korea. Medicine. 2018;97(26):e11138. PubMed CrossRef
Mazza MG, Lucchi S, Rossetti A, et al. Neutrophil-lymphocyte ratio, monocyte lymphocyte ratio and platelet-lymphocyte ratio in non-affective psychosis: a meta analysis and systematic review. World J Biol Psychiatry. 2020;21(5):326–338. PubMed CrossRef
Karageorgiou V, Milas GP, Michopoulos I. Neutrophil-to-lymphocyte ratio in schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2019;206:4–12. PubMed CrossRef
Gercek HG, Citir BG, Bukulme A. Neutrophil-to-lymphocyte and platelet-to lymphocyte ratios as inflammation markers for early-onset schizophrenia. Bratisl Lek Listy. 2023;124(7):503–507. PubMed
Garcia-Rizo C, Casanovas M, Fernandez-Egea E, et al. Blood cell count in antipsychotic-naive patients with non-affective psychosis. Early Interv Psychiatry. 2019;13(1):95–100. PubMed CrossRef
World Health Organization. ICD-10: International Statistical Classification of Diseases and Related Health Problems. World Health Organization; 2004.
Del Cacho N, Vila-Badia R, Butjosa A, et al. Sexual dysfunction in drug- naïve first episode nonaffective psychosis patients. Relationship with prolactin and psychotic symptoms. Gender differences. Psychiatry Res. 2020;289:112985. PubMed CrossRef
Bernstein DP, Stein JA, Newcomb MD, et al. Development and validation of a brief screening version of the childhood trauma questionnaire. Child Abuse Negl. 2003;27(2):169–190. PubMed CrossRef
Hernandez A, Gallardo-Pujol D, Pereda N, et al. Initial validation of the Spanish childhood trauma questionnaire-short form: factor structure, reliability and association with parenting. J Interpers Violence. 2013;28(7):1498–1518. PubMed CrossRef
Bernstein DP, Fink L. Childhood Trauma Questionnaire: A Retrospective Self Report. Pearson; 1998.
Üçok A, Bıkmaz S. The effects of childhood trauma in patients with first-episode schizophrenia. Acta Psychiatr Scand. 2007;116(5):371–377. PubMed
Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261–276. PubMed CrossRef
Peralta Martín V, Cuesta Zorita MJ. [Validation of positive and negative symptom scale (PANSS) in a sample of Spanish schizophrenic patients]. Actas Luso Esp Neurol Psiquiatr Cienc Afines. 1994;22(4):171–177. PubMed
Donnadieu-Rigole H, Mura T, Portales P, et al. Effects of alcohol withdrawal on monocyte subset defects in chronic alcohol users. J Leukoc Biol. 2016;100(5):1191–1199. PubMed CrossRef
Suárez-Pinilla P, López-Gil J, Crespo-Facorro B. Immune system: a possible nexus between cannabinoids and psychosis. Brain Behav Immun. 2014;40:269–282. PubMed
Riecher-Rössler A, Butler S, Kulkarni J. Sex and gender differences in schizophrenic psychoses-a critical review. Arch Womens Ment Health. 2018;21(6):627–648. PubMed
Bailey T, Alvarez-Jimenez M, Garcia-Sanchez AM, et al. Childhood trauma is associated with severity of hallucinations and delusions in psychotic disorders: a systematic review and meta-analysis. Schizophr Bull. 2018;44(5):1111–1122. PubMed CrossRef
Kahn RS, Sommer IE. The neurobiology and treatment of first-episode schizophrenia. Mol Psychiatry. 2015;20(1):84–97. PubMed CrossRef
Braehler C, Valiquette L, Holowka D, et al. Childhood trauma and dissociation in first-episode psychosis, chronic schizophrenia and community controls. Psychiatry Res. 2013;210(1):36–42. PubMed CrossRef
Trauelsen AM, Bendall S, Jansen JE, et al. Childhood adversity specificity and dose-response effect in non-affective first-episode psychosis. Schizophr Res. 2015;165(1):52–59. PubMed CrossRef
Salokangas RKR, Schultze-Lutter F, Schmidt SJ, et al. Childhood physical abuse and emotional neglect are specifically associated with adult mental disorders. J Ment Health. 2020;29(4):376–384. PubMed CrossRef
Zhang X, Zhang M, Zeng M, et al. Childhood emotional neglect predicts empathic accuracy in social inclusion and exclusion contexts. Psych J. 2022;11(4):481–491. PubMed CrossRef
Aas M, Andreassen OA, Aminoff SR, et al. A history of childhood trauma is associated with slower improvement rates: findings from a one-year follow up study of patients with a first-episode psychosis. BMC Psychiatry. 2016;16:126. PubMed CrossRef
Garcia M, Montalvo I, Creus M, et al. Sex differences in the effect of childhood trauma on the clinical expression of early psychosis. Compr Psychiatry. 2016;68:86–96. PubMed CrossRef
Mills P, Newman EF, Cossar J, et al. Emotional maltreatment and disordered eating in adolescents: testing the mediating role of emotion regulation. Child Abuse Negl. 2015;39:156–166. PubMed CrossRef
Chmielewski PP, Strzelec B. Elevated leukocyte count as a harbinger of systemic inflammation, disease progression, and poor prognosis: a review. Folia Morphol. 2018;77(2):171–178. PubMed CrossRef
Gibson PH, Croal BL, Cuthbertson BH, et al. Preoperative neutrophil-lymphocyte ratio and outcome from coronary artery bypass grafting. Am Heart J. 2007;154(5):995–1002. PubMed CrossRef
Varsak N, Aydin M, Eren İ. The evaluation of neutrophil-lymphocyte ratio in patients with first episode psychosis İlk atak psikoz hastalarında nötrofil lenfosit oranının değerlendirilmesi. Fam Pract Palliat Care. 2016;1(3):65–69.
Moody G, Miller BJ. Total and differential white blood cell counts and hemodynamic parameters in first-episode psychosis. Psychiatry Res. 2018;260:307–312. PubMed CrossRef
Steiner J, Frodl T, Schiltz K, et al. Innate immune cells and C-reactive protein in acute first-episode psychosis and schizophrenia: relationship to psychopathology and treatment. Schizophr Bull. 2020;46(2):363–373. PubMed CrossRef
Bustan Y, Drapisz A, Ben Dor DH, et al. Elevated neutrophil to lymphocyte ratio in non-affective psychotic adolescent inpatients: evidence for early association between inflammation and psychosis. Psychiatry Res. 2018;262:149–153. PubMed CrossRef
Danese A, Tan M. Childhood maltreatment and obesity: systematic review and meta-analysis. Mol Psychiatry. 2014;19(5):544–554. PubMed CrossRef
Min MO, Minnes S, Kim H, et al. Pathways linking childhood maltreatment and adult physical health. Child Abuse Negl. 2013;37(6):361–373. PubMed CrossRef
Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011;29(1):415–445. PubMed CrossRef
Song G-M, Tian X, Shuai T, et al. Treatment of adults with treatment-resistant depression: electroconvulsive therapy plus antidepressant or electroconvulsive therapy alone? Evidence from an indirect comparison meta-analysis. Medicine. 2015;94(26):e1052. PubMed CrossRef
Li J, Chen Q, Luo X, et al. Neutrophil-to-lymphocyte ratio positively correlates to age in healthy population. J Clin Lab Anal. 2015;29(6):437–443. PubMed CrossRef
Myles H, Myles N, Large M. Cannabis use in first episode psychosis: meta analysis of prevalence, and the time course of initiation and continued use. Aust N Z J Psychiatry. 2016;50(3):208–219. PubMed CrossRef
Quigley H, MacCabe JH. The relationship between nicotine and psychosis. Ther Adv Psychopharmacol. 2019;9:2045125319859969. PubMed CrossRef
Hosseinzadeh A, Thompson PR, Segal BH, et al. Nicotine induces neutrophil extracellular traps. J Leukoc Biol. 2016;100(5):1105–1112. PubMed CrossRef
Myles N, Newall HD, Curtis J, et al. Tobacco use before, at, and after first-episode psychosis: a systematic meta-analysis. J Clin Psychiatry. 2012;73(4):468–475. PubMed CrossRef
Andersen SL, Tomada A, Vincow ES, et al. Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development. J Neuropsychiatry Clin Neurosci. 2008;20(3):292–301. PubMed CrossRef
Fisher HL, Craig TK, Fearon P, et al. Reliability and comparability of psychosis patients’ retrospective reports of childhood abuse. Schizophr Bull. 2011;37(3):546–553. PubMed CrossRef
Davis JS, Lee HY, Kim J, et al. Use of non-steroidal anti-inflammatory drugs in US adults: changes over time and by demographic. Open Heart. 2017;4(1):e000550. PubMed CrossRef