Hostname: page-component-8448b6f56d-gtxcr Total loading time: 0 Render date: 2024-04-23T06:07:15.102Z Has data issue: false hasContentIssue false
  • English
  • Français

Childhood trauma and being at-risk for psychosis are associated with higher peripheral endocannabinoids

Published online by Cambridge University Press:  19 August 2019

E. Appiah-Kusi Open the ORCID record for E. Appiah-Kusi [Opens in a new window] ,
R. Wilson ,
M. Colizzi ,
E. Foglia ,
E. Klamerus ,
A. Caldwell ,
M. G. Bossong ,
P. McGuire  and
S. Bhattacharyya
E. Appiah-Kusi
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Box PO 63, De Crespigny Park, Denmark Hill, LondonSE5 8AF, UK
R. Wilson
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Box PO 63, De Crespigny Park, Denmark Hill, LondonSE5 8AF, UK
M. Colizzi
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Box PO 63, De Crespigny Park, Denmark Hill, LondonSE5 8AF, UK Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Policlinico ‘G. B. Rossi’, P.le L.A. Scuro 10, 37134, Verona, Italy
E. Foglia
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Box PO 63, De Crespigny Park, Denmark Hill, LondonSE5 8AF, UK
E. Klamerus
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Box PO 63, De Crespigny Park, Denmark Hill, LondonSE5 8AF, UK
A. Caldwell
Affiliation:
King's College London, Mass Spectometry Facility, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
M. G. Bossong
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Box PO 63, De Crespigny Park, Denmark Hill, LondonSE5 8AF, UK Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands
P. McGuire
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Box PO 63, De Crespigny Park, Denmark Hill, LondonSE5 8AF, UK
S. Bhattacharyya*
Affiliation:
Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), Box PO 63, De Crespigny Park, Denmark Hill, LondonSE5 8AF, UK
*
Author for correspondence: Sagnik Bhattacharyya, E-mail: sagnik.2.bhattacharyya@kcl.ac.uk
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Evidence has been accumulating regarding alterations in components of the endocannabinoid system in patients with psychosis. Of all the putative risk factors associated with psychosis, being at clinical high-risk for psychosis (CHR) has the strongest association with the onset of psychosis, and exposure to childhood trauma has been linked to an increased risk of development of psychotic disorder. We aimed to investigate whether being at-risk for psychosis and exposure to childhood trauma were associated with altered endocannabinoid levels.

Method

We compared 33 CHR participants with 58 healthy controls (HC) and collected information about previous exposure to childhood trauma as well as plasma samples to analyse endocannabinoid levels.

Results

Individuals with both CHR and experience of childhood trauma had higher N-palmitoylethanolamine (p < 0.001) and anandamide (p < 0.001) levels in peripheral blood compared to HC and those with no childhood trauma. There was also a significant correlation between N-palmitoylethanolamine levels and symptoms as well as childhood trauma.

Conclusions

Our results suggest an association between CHR and/or childhood maltreatment and elevated endocannabinoid levels in peripheral blood, with a greater alteration in those with both CHR status and history of childhood maltreatment compared to those with either of those risks alone. Furthermore, endocannabinoid levels increased linearly with the number of risk factors and elevated endocannabinoid levels correlated with the severity of CHR symptoms and extent of childhood maltreatment. Further studies in larger cohorts, employing longitudinal designs are needed to confirm these findings and delineate the precise role of endocannabinoid alterations in the pathophysiology of psychosis.

Keywords

Anandamidechildhood traumaclinical high-riskendocannabinoid
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 11 , August 2020 , pp. 1862 - 1871
Check for updates
Copyright
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Addington, J, Stowkowy, J, Cadenhead, KS, Cornblatt, BA, Mcglashan, TH, Perkins, DO, Seidman, LJ, Tsuang, MT, Walker, EF and Woods, SW (2013) Early traumatic experiences in those at clinical high risk for psychosis. Early Intervention in Psychiatry 7, 300–305.CrossRefGoogle ScholarPubMed
Appiah-Kusi, E, Leyden, E, Parmar, S, Mondelli, V, Mcguire, P and Bhattacharyya, S (2016) Abnormalities in neuroendocrine stress response in psychosis: the role of endocannabinoids. Psychological Medicine 46(1), 1–19.CrossRefGoogle ScholarPubMed
Appiah-Kusi, E, Fisher, H, Petros, N, Wilson, R, Mondelli, V, Garety, P, Mcguire, P and Bhattacharyya, S (2017) Do cognitive schema mediate the association between childhood trauma and being at ultra-high risk for psychosis? Journal of Psychiatric Research 88, 89–96.CrossRefGoogle ScholarPubMed
Barkus, EJ, Stirling, J, Hopkins, RS and Lewis, S (2006) Cannabis-induced psychosis-like experiences are associated with high schizotypy. Psychopathology 39, 175–178.CrossRefGoogle ScholarPubMed
Bebbington, P, Jonas, S, Kuipers, E, King, M, Cooper, C, Brugha, T, Meltzer, H, Mcmanus, S and Jenkins, R (2011) Childhood sexual abuse and psychosis: data from a cross-sectional national psychiatric survey in England. The British Journal of Psychiatry 199, 29–37.CrossRefGoogle ScholarPubMed
Bechdolf, A, Thompson, A, Nelson, B, Cotton, S, Simmons, M, Amminger, G, Leicester, S, Francey, S, Mcnab, C and Krstev, H (2010) Experience of trauma and conversion to psychosis in an ultra-high-risk (prodromal) group. Acta Psychiatrica Scandinavica 121, 377–384.CrossRefGoogle Scholar
Bernstein, DP and Fink, L (1998) Childhood Trauma Questionnaire: A Retrospective Self-Report: Manual. San Antonio: Harcourt Brace & Company.Google Scholar
Bhattacharyya, S, Wilson, R, Appiah-Kusi, E, O'neill, A, Brammer, M, Perez, J, Murray, R, Allen, P, Bossong, MG and Mcguire, P (2018) Effect of cannabidiol on medial temporal, midbrain, and striatal dysfunction in people at clinical high risk of psychosis: a randomized clinical trial. JAMA Psychiatry 75, 1107–1117.CrossRefGoogle ScholarPubMed
Bioque, M, García-Bueno, B, Macdowell, KS, Meseguer, A, Saiz, PA, Parellada, M, Gonzalez-Pinto, A, Rodriguez-Jimenez, R, Lobo, A, Leza, JC and Bernardo, M (2013) Peripheral endocannabinoid system dysregulation in first-episode psychosis. Neuropsychopharmacology 38, 2568.CrossRefGoogle ScholarPubMed
Borgan, F, Veronese, M, O'daly, O, Marques, TR, Rogdaki, M and Howes, O (2018) Cannabinoid 1 receptor availability & memory function in first episode psychosis: a multi-modal PET fMRI study. Schizophrenia Bulletin 44, S291.CrossRefGoogle Scholar
Ceccarini, J, De Hert, M, Van Winkel, R, Peuskens, J, Bormans, G, Kranaster, L, Enning, F, Koethe, D, Leweke, FM and Van Laere, K (2013) Increased ventral striatal CB1 receptor binding is related to negative symptoms in drug-free patients with schizophrenia. Neuroimage 79, 304–312.CrossRefGoogle ScholarPubMed
Cohen, S, Kamarck, T and Mermelstein, R (1983) A global measure of perceived stress. Journal of Health and Social Behavior 24(4), 385–396.CrossRefGoogle ScholarPubMed
Coid, J, Petruckevitch, A, Feder, G, Chung, W-S, Richardson, J and Moorey, S (2001) Relation between childhood sexual and physical abuse and risk of revictimisation in women: a cross-sectional survey. The Lancet 358, 450–454.CrossRefGoogle ScholarPubMed
De Marchi, N, De Petrocellis, L, Orlando, P, Daniele, F, Fezza, F and Di Marzo, V (2003) Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids in Health and Disease 2, 5.CrossRefGoogle ScholarPubMed
Di, S, Malcher-Lopes, R, Halmos, KC and Tasker, JG (2003) Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. The Journal of Neuroscience 23, 4850–4857.CrossRefGoogle ScholarPubMed
Di, S, Malcher-Lopes, R, Marcheselli, VL, Bazan, NG and Tasker, JG (2005 a) Rapid glucocorticoid-mediated endocannabinoid release and opposing regulation of glutamate and gamma-aminobutyric acid inputs to hypothalamic magnocellular neurons. Endocrinology 146, 4292–4301.CrossRefGoogle ScholarPubMed
Di, S, Malcher-Lopes, R, Marcheselli, VL, Bazan, NG and Tasker, JG (2005 b) Rapid glucocorticoid-mediated endocannabinoid release and opposing regulation of glutamate and γ-aminobutyric acid inputs to hypothalamic magnocellular neurons. Endocrinology 146, 4292–4301.CrossRefGoogle ScholarPubMed
Dlugos, A, Childs, E, Stuhr, KL, Hillard, CJ and De Wit, H (2012) Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans. Neuropsychopharmacology 37, 2416–2427.CrossRefGoogle ScholarPubMed
D'souza, DC, Cortes-Briones, JA, Ranganathan, M, Thurnauer, H, Creatura, G, Surti, T, Planeta, B, Neumeister, A, Pittman, B and Normandin, MD (2016) Rapid changes in cannabinoid 1 receptor availability in cannabis-dependent male subjects after abstinence from cannabis. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 1, 60–67.Google ScholarPubMed
Eggan, SM, Hashimoto, T and Lewis, DA (2008) Reduced cortical cannabinoid 1 receptor messenger RNA and protein expression in schizophrenia. Archives of General Psychiatry 65, 772–784.CrossRefGoogle Scholar
Eggan, SM, Stoyak, SR, Verrico, CD and Lewis, DA (2010) Cannabinoid CB1 receptor immunoreactivity in the prefrontal cortex: comparison of schizophrenia and major depressive disorder. Neuropsychopharmacology 35, 2060–2071.CrossRefGoogle ScholarPubMed
Fisher, HL, Appiah-Kusi, E and Grant, C (2012) Anxiety and negative self-schemas mediate the association between childhood maltreatment and paranoia. Psychiatry Research 196, 323–324.CrossRefGoogle ScholarPubMed
Giuffrida, A, Parsons, L, Kerr, T, De Fonseca, FR, Navarro, M and Piomelli, D (1999) Dopamine activation of endogenous cannabinoid signaling in dorsal striatum. Nature Neuroscience 2, 358.CrossRefGoogle ScholarPubMed
Giuffrida, A, Leweke, FM, Gerth, CW, Schreiber, D, Koethe, D, Faulhaber, J, Klosterkötter, J and Piomelli, D (2004) Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology 29, 2108.CrossRefGoogle ScholarPubMed
Hill, M and Tasker, J (2012) Endocannabinoid signaling, glucocorticoid-mediated negative feedback, and regulation of the hypothalamic-pituitary-adrenal axis. Neuroscience 204, 5–16.CrossRefGoogle ScholarPubMed
Hill, MN, Miller, GE, Carrier, EJ, Gorzalka, BB and Hillard, CJ (2009) Circulating endocannabinoids and N-acyl ethanolamines are differentially regulated in major depression and following exposure to social stress. Psychoneuroendocrinology 34, 1257–1262.CrossRefGoogle ScholarPubMed
Howes, OD and Kapur, S (2009) The dopamine hypothesis of schizophrenia: version III – the final common pathway. Schizophrenia Bulletin 35, 549–562.CrossRefGoogle ScholarPubMed
Koethe, D, Giuffrida, A, Schreiber, D, Hellmich, M, Schultze-Lutter, F, Ruhrmann, S, Klosterkötter, J, Piomelli, D and Leweke, FM (2009) Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis. The British Journal of Psychiatry 194, 371–372.CrossRefGoogle Scholar
Koethe, D, Pahlisch, F, Hellmich, M, Rohleder, C, Mueller, JK, Meyer-Lindenberg, A, Torrey, EF, Piomelli, D and Leweke, FM (2018) Familial abnormalities of endocannabinoid signaling in schizophrenia. The World Journal of Biological Psychiatry 20(2), 1–9.Google Scholar
Leweke, FM, Giuffrida, A, Wurster, U, Emrich, HM and Piomelli, D (1999) Elevated endogenous cannabinoids in schizophrenia. Neuroreport 10, 1665–1669.CrossRefGoogle Scholar
Leweke, FM, Giuffrida, A, Koethe, D, Schreiber, D, Nolden, BM, Kranaster, L, Neatby, MA, Schneider, M, Gerth, CW and Hellmich, M (2007) Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: impact of cannabis use. Schizophrenia Research 94, 29–36.CrossRefGoogle ScholarPubMed
Leweke, F, Piomelli, D, Pahlisch, F, Muhl, D, Gerth, C, Hoyer, C, Klosterkötter, J, Hellmich, M and Koethe, D (2012) Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Translational Psychiatry 2, e94.CrossRefGoogle ScholarPubMed
Leweke, FM, Mueller, JK, Lange, B and Rohleder, C (2016) Therapeutic potential of cannabinoids in psychosis. Biological Psychiatry 79, 604–612.CrossRefGoogle ScholarPubMed
Malcher-Lopes, R, Di, S, Marcheselli, VS, Weng, F-J, Stuart, CT, Bazan, NG and Tasker, JG (2006) Opposing crosstalk between leptin and glucocorticoids rapidly modulates synaptic excitation via endocannabinoid release. The Journal of Neuroscience 26, 6643–6650.CrossRefGoogle ScholarPubMed
Mizrahi, R (2015) Social stress and psychosis risk: common neurochemical substrates? Neuropsychopharmacology 41, 666.CrossRefGoogle ScholarPubMed
Moore, TH, Zammit, S, Lingford-Hughes, A, Barnes, TR, Jones, PB, Burke, M and Lewis, G (2007) Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. The Lancet 370, 319–328.CrossRefGoogle ScholarPubMed
Müller-Vahl, KR and Emrich, HM (2008) Cannabis and schizophrenia: towards a cannabinoid hypothesis of schizophrenia. Expert Review of Neurotherapeutics 8, 1037–1048.CrossRefGoogle ScholarPubMed
Petros, N, Foglia, E, Klamerus, E, Beards, S, Murray, R and Bhattacharyya, S (2016) Impact of childhood trauma on risk of relapse requiring psychiatric hospital admission for psychosis. British Journal of Psychiatry 209(2), 169–170. doi:10.1192/bjp.bp.115.176636.CrossRefGoogle Scholar
Pruessner, M, Cullen, AE, Aas, M and Walker, EF (2017) The neural diathesis-stress model of schizophrenia revisited: an update on recent findings considering illness stage and neurobiological and methodological complexities. Neuroscience & Biobehavioral Reviews 73, 191–218.CrossRefGoogle ScholarPubMed
Radua, J, Ramella-Cravaro, V, Ioannidis, JP, Reichenberg, A, Phiphopthatsanee, N, Amir, T, Yenn Thoo, H, Oliver, D, Davies, C and Morgan, C (2018) What causes psychosis? An umbrella review of risk and protective factors. World Psychiatry 17, 49–66.CrossRefGoogle ScholarPubMed
Ranganathan, M, Cortes-Briones, J, Radhakrishnan, R, Thurnauer, H, Planeta, B, Skosnik, P, Gao, H, Labaree, D, Neumeister, A, Pittman, B, Surti, T, Huang, Y, Carson, RE and D'souza, DC (2016) Reduced brain cannabinoid receptor availability in schizophrenia. Biological Psychiatry 79, 997–1005.CrossRefGoogle Scholar
Read, J (1997) Child abuse and psychosis: a literature review and implications for professional practice. Professional Psychology: Research and Practice 28, 448.CrossRefGoogle Scholar
Read, J, Os, JV, Morrison, A and Ross, CA (2005) Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications. Acta Psychiatrica Scandinavica 112, 330–350.CrossRefGoogle ScholarPubMed
Reuter, AR, Bumb, JM, Mueller, JK, Rohleder, C, Pahlisch, F, Hanke, F, Arens, E, Leweke, FM, Koethe, D and Schwarz, E (2017) Association of anandamide with altered binocular depth inversion illusion in schizophrenia. The World Journal of Biological Psychiatry 18, 483–488.CrossRefGoogle Scholar
Sami, MB and Bhattacharyya, S (2018) Are cannabis-using and non-using patients different groups? Towards understanding the neurobiology of cannabis use in psychotic disorders. Journal of Psychopharmacology 32(8), 825–849.CrossRefGoogle ScholarPubMed
Schoeler, T, Monk, A, Sami, MB, Klamerus, E, Foglia, E, Brown, R, Camuri, G, Altamura, AC, Murray, R and Bhattacharyya, S (2016 a) Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis. The Lancet Psychiatry 3(3), 215–225.CrossRefGoogle ScholarPubMed
Schoeler, T, Petros, N, Di Forti, M, Klamerus, E, Foglia, E, Ajnakina, O, Gayer-Anderson, C, Colizzi, M, Quattrone, D and Behlke, I (2016 b) Effects of continuation, frequency, and type of cannabis use on relapse in the first 2 years after onset of psychosis: an observational study. The Lancet Psychiatry 3, 947–953.CrossRefGoogle ScholarPubMed
Schoeler, T, Petros, N, Di Forti, M, Pingault, J-B, Klamerus, E, Foglia, E, Small, A, Murray, R and Bhattacharyya, S (2016 c) Association between continued cannabis use and risk of relapse in first-episode psychosis: a quasi-experimental investigation within an observational study. JAMA Psychiatry 73, 1173–1179.CrossRefGoogle ScholarPubMed
SPSS, I (2012) IBM SPSS Statistics Version 21. Boston, Mass: International Business Machines Corp.Google Scholar
Tzavara, ET, Li, DL, Moutsimilli, L, Bisogno, T, Di Marzo, V, Phebus, LA, Nomikos, GG and Giros, B (2006) Endocannabinoids activate transient receptor potential vanilloid 1 receptors to reduce hyperdopaminergia-related hyperactivity: therapeutic implications. Biological Psychiatry 59, 508–515.CrossRefGoogle ScholarPubMed
Varese, F, Smeets, F, Drukker, M, Lieverse, R, Lataster, T, Viechtbauer, W, Read, J, Van Os, J and Bentall, RP (2012) Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective- and cross-sectional cohort studies. Schizophrenia Bulletin 38(4), 661–671.CrossRefGoogle ScholarPubMed
Volk, DW, Eggan, SM, Horti, AG, Wong, DF and Lewis, DA (2014) Reciprocal alterations in cortical cannabinoid receptor 1 binding relative to protein immunoreactivity and transcript levels in schizophrenia. Schizophrenia Research 159(1), 124–129.CrossRefGoogle Scholar
Walker, EA, Unutzer, J, Rutter, C, Gelfand, A, Saunders, K, VonKorff, M, Koss, MP and Katon, W (1999) Costs of health care use by women hmo members with a history of childhood abuse and neglect. Archives of General Psychiatry 56, 609–613.CrossRefGoogle ScholarPubMed
Wong, DF, Kuwabara, H, Horti, AG, Raymont, V, Brasic, J, Guevara, M, Ye, W, Dannals, RF, Ravert, HT and Nandi, A (2010) Quantification of cerebral cannabinoid receptors subtype 1 (CB1) in healthy subjects and schizophrenia by the novel PET radioligand [11C] OMAR. Neuroimage 52, 1505–1513.CrossRefGoogle ScholarPubMed
Yung, AR, Phillips, LJ, Mcgorry, PD, Mcfarlane, CA, Francey, S, Harrigan, S, Patton, GC and Jackson, HJ (1998) Prediction of psychosis: a step towards indicated prevention of schizophrenia. The British Journal of Psychiatry 172(S33), 14–20.CrossRefGoogle ScholarPubMed
Yung, AR, Yung, AR, Pan Yuen, H, Mcgorry, PD, Phillips, LJ, Kelly, D, Dell'olio, M, Francey, SM, Cosgrave, EM and Killackey, E (2005) Mapping the onset of psychosis: the comprehensive assessment of at-risk mental states. Australian & New Zealand Journal of Psychiatry 39, 964–971.CrossRefGoogle ScholarPubMed