Multimodaler Ansatz zum Verständnis des Zusammenspiels zwischen dem endokrinen und dem Endocannabinoidsystem, nicht suizidalem selbstverletzendem Verhalten und der Borderline-Persönlichkeitsstörung

ZUSAMMENFASSUNG

Die Borderline-Persönlichkeitsstörung (BPS) und, unabhängig davon, nicht suizidales selbstverletzendes Verhalten (NSSV) sind äußerst prävalente psychiatrische Störungsbilder, welche häufig mit weiteren psychischen Komorbiditäten einhergehen. Dennoch gibt es wenige wissenschaftliche Untersuchungen zu den zugrunde liegenden Mechanismen, die zudem der Verbesserung derzeitiger Behandlungsmöglichkeiten dienen können. Da Cannabiskonsum häufig zur Selbstmedikation bei Patienten mit BPS und NSSV eingesetzt wird und Cannabismissbrauch vermehrt vorkommt, liegt die Untersuchung des Endocannabinoidsystems (ECS) als potenziellen Modulator der Psychopathologie nahe. Des Weiteren sind die Stressverarbeitung als zugrunde liegender Faktor und die Funktionsfähigkeit des endokrinologischen Systems, welches eine zentrale Rolle in der Entwicklung und Aufrechterhaltung der BPS und NSSV spielt, eng mit dem ECS verbunden, welches unter anderem für die Modulation der Hypothalamus-Hypophysen-Nebennierenrinden (HPA)-Achse bekannt ist. Auch wenn mehr Forschung nötig ist, hat das ECS großes Potenzial die Behandlungsmöglichkeiten zu erweitern.

ABSTRACT

Borderline personality disorder (BPD) and independently non-suicidal self-injury (NSSI) are highly prevalent in psychiatric care and often linked to other mental disorders. However, research investigating the underlying neurobiological mechanisms, which could also be beneficial in the enhancement of current treatment options, remains scarce. Since cannabis use as a self-medication and cannabis use disorders are common in patients with BPD and NSSI, investigating the mechanisms of the endocannabinoid system (ECS) as a potential modulator of psychopathology seems plausible. Further, the processing of stress as an underlying factor and the functioning of the endocrinological system, which plays a central role in the development and manifestation of BPD and NSSI, are closely linked to the ECS, which is well known to modulate the hypothalamic-pituitary-adrenal axis (HPA)-axis. Even though more research is needed, the ECS might offer great potential to stimulate and expand current treatment options.

Schlüsselwörter

Endocannabinoidsystem - Borderline-Persönlichkeitsstörung - Immunsystem - nicht suizidal selbstverletzendes Verhalten

Key words

Endocannabinoid system - borderline personality disorder - immune system - non-suicidal self-injurious

Publication History

Article published online:
03 March 2023

• Literatur

• 1 Guilé JM, Boissel L, Alaux-Cantin S. et al Borderline personality disorder in adolescents: prevalence, diagnosis, and treatment strategies. Adolesc Health Med Ther 2018; 09: 199-210 DOI: 10.2147/AHMT.S156565.
• 2 Bell CC. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders. JAMA: The Journal of the American Medical Association 1994; 272: 828 DOI: 10.1001/jama.1994.03520100096046.
• 3 Swannell S v., Martin GE, Page A. et al Prevalence of Nonsuicidal Self-Injury in Nonclinical Samples: Systematic Review, Meta-Analysis and Meta-Regression. Suicide Life Threat Behav 2014; 44: 273-303 DOI: 10.1111/sltb.12070.
• 4 Levine AZ, Aljabari R, Dalrymple K. et al Nonsuicidal Self-Injury and Suicide: Differences Between Those With and Without Borderline Personality Disorder. J Pers Disord 2020; 34: 131-144 DOI: 10.1521/pedi_2018_32_385.
• 5 Reichl C, Kaess M. Self-harm in the context of borderline personality disorder. Curr Opin Psychol 2021; 37: 139-144 DOI: 10.1016/j.copsyc.2020.12.007.
• 6 Zetterqvist M, Lundh L-G, Dahlström Ö. et al Prevalence and Function of Non-Suicidal Self-Injury (NSSI) in a Community Sample of Adolescents, Using Suggested DSM-5 Criteria for a Potential NSSI Disorder. J Abnorm Child Psychol 2013; 41: 759-773 DOI: 10.1007/s10802-013-9712-5.
• 7 Wagner T, Fydrich T, Stiglmayr C. et al Societal cost-of-illness in patients with borderline personality disorder one year before, during and after dialectical behavior therapy in routine outpatient care. Behaviour Research and Therapy 2014; 61: 12-22 DOI: 10.1016/j.brat.2014.07.004.
• 8 Nitkowski D, Petermann F. Selbstverletzendes Verhalten und komorbide psychische Störungen: ein Überblick. Fortschritte der Neurologie · Psychiatrie 2011; 79: 9-20 DOI: 10.1055/s-0029-1245772.
• 9 Brunner R, Kaess M, Parzer P. et al Life-time prevalence and psychosocial correlates of adolescent direct self-injurious behavior: A comparative study of findings in 11 European countries. Journal of Child Psychology and Psychiatry 2014; 55: 337-348 DOI: 10.1111/jcpp.12166.
• 10 Hawton K, Witt KG, Taylor Salisbury TL. et al Interventions for self-harm in children and adolescents. Cochrane Database of Systematic Reviews. 2015: 2021 DOI: 10.1002/14651858.CD012013
• 11 Kothgassner OD, Robinson K, Goreis A. et al Does treatment method matter? A meta-analysis of the past 20 years of research on therapeutic interventions for self-harm and suicidal ideation in adolescents. Borderline Personal Disord Emot Dysregul 2020; 07: 9 DOI: 10.1186/s40479-020-00123-9.
• 12 Liu RT, Walsh RFL, Sheehan AE. et al Prevalence and Correlates of Suicide and Nonsuicidal Self-injury in Children. JAMA Psychiatry 2022; 79: 718 DOI: 10.1001/jamapsychiatry.2022.1256.
• 13 Dick B, Ferguson BJ. Health for the World’s Adolescents: A Second Chance in the Second Decade. Journal of Adolescent Health 2015; 56: 3-6 DOI: 10.1016/j.jadohealth.2014.10.260.
• 14 Nock MK, Park JM, Finn CT. et al Measuring the Suicidal Mind. Psychol Sci 2010; 21: 511-517 DOI: 10.1177/0956797610364762.
• 15 Whitlock J, Knox KL. The Relationship Between Self-injurious Behavior and Suicide in a Young Adult Population. Arch Pediatr Adolesc Med 2007; 161: 634 DOI: 10.1001/archpedi.161.7.634.
• 16 Brown RC, Fischer T, Goldwich AD. et al #cutting: Non-suicidal self-injury (NSSI) on Instagram. Psychol Med 2018; 48: 337-346 DOI: 10.1017/S0033291717001751.
• 17 Young R, Sproeber N, Groschwitz RC. et al Why alternative teenagers self-harm: exploring the link between non-suicidal self-injury, attempted suicide and adolescent identity. BMC Psychiatry 2014; 14: 137 DOI: 10.1186/1471-244X-14-137.
• 18 Ghinea D, Fuchs A, Parzer P. et al Psychosocial functioning in adolescents with non-suicidal self-injury: the roles of childhood maltreatment, borderline personality disorder and depression. Borderline Personal Disord Emot Dysregul 2021; 08: 21 DOI: 10.1186/s40479-021-00161-x.
• 19 Golier JA, Yehuda R, Bierer LM. et al The Relationship of Borderline Personality Disorder to Posttraumatic Stress Disorder and Traumatic Events. American Journal of Psychiatry 2003; 160: 2018-2024 DOI: 10.1176/appi.ajp.160.11.2018.
• 20 Sansone RA, Sansone LA. Borderline personality and criminality. Psychiatry 2009; 06: 16-20
• 21 Kaess M, Hooley JM, Klimes-Dougan B. et al Advancing a temporal framework for understanding the biology of nonsuicidal self- injury: An expert review. Neurosci Biobehav Rev 2021; 130: 228-239 DOI: 10.1016/j.neubiorev.2021.08.022.
• 22 Koenig J, Rinnewitz L, Warth M. et al Psychobiological response to pain in female adolescents with nonsuicidal self-injury. Journal of Psychiatry & Neuroscience 2017; 42: 189-199 DOI: 10.1503/jpn.160074.
• 23 Schmahl C, Bohus M, Esposito F. et al Neural Correlates of Antinociception in Borderline Personality Disorder. Arch Gen Psychiatry 2006; 63: 659 DOI: 10.1001/archpsyc.63.6.659.
• 24 Schmahl C, Greffrath W, Baumgärtner U. et al Differential nociceptive deficits in patients with borderline personality disorder and self-injurious behavior: laser-evoked potentials, spatial discrimination of noxious stimuli, and pain ratings. Pain 2004; 110: 470-479 DOI: 10.1016/j.pain.2004.04.035.
• 25 Degasperi G, Cristea IA, di Rosa E. et al Parsing variability in borderline personality disorder: a meta-analysis of neuroimaging studies. Transl Psychiatry 2021; 11: 314 DOI: 10.1038/s41398-021-01446-z.
• 26 Ho W, Kolla NJ. The endocannabinoid system in borderline personality disorder and antisocial personality disorder: A scoping review. Behavioral Sciences & the Law 2022; 40: 331-350 DOI: 10.1002/bsl.2576.
• 27 Weld KP, Mench JA, Woodward RA. et al Effect of Tryptophan Treatment on Self-Biting and Central Nervous System Serotonin Metabolism in Rhesus Monkeys (Macaca mulatta). Neuropsychopharmacology 1998; 19: 314-321 DOI: 10.1016/S0893-133X(98)00026-8.
• 28 Tiefenbacher S. The physiology and neurochemistry of self-injurious behavior: a nonhuman primate model. Frontiers in Bioscience 2005; 10: 1 DOI: 10.2741/1500.
• 29 Garland MR, Hallahan B, McNamara M. et al Lipids and essential fatty acids in patients presenting with self-harm. British Journal of Psychiatry 2007; 190: 112-117 DOI: 10.1192/bjp.bp.105.019562.
• 30 Roaldset JO, Bakken AM, Bjørkly S. A prospective study of lipids and serotonin as risk markers of violence and self-harm in acute psychiatric patients. Psychiatry Res 2011; 186: 293-299 DOI: 10.1016/j.psychres.2010.07.029.
• 31 Blasco-Fontecilla H, Fernández-Fernández R, Colino L. et al The Addictive Model of Self-Harming (Non-suicidal and Suicidal) Behavior. Front Psychiatry. 2016: 7 DOI: 10.3389/fpsyt.2016.00008
• 32 Kasim S, Jinnah HA. Self-Biting Induced by Activation of L-Type Calcium Channels in Mice: Dopaminergic Influences. Dev Neurosci 2003; 25: 20-25 DOI: 10.1159/000071464.
• 33 Stanley B, Sher L, Wilson S. et al Non-suicidal self-injurious behavior, endogenous opioids and monoamine neurotransmitters. J Affect Disord 2010; 124: 134-140 DOI: 10.1016/j.jad.2009.10.028.
• 34 Koenig J, Thayer JF, Kaess M. A meta-analysis on pain sensitivity in self-injury. Psychol Med 2016; 46: 1597-1612 DOI: 10.1017/S0033291716000301.
• 35 Störkel LM, Karabatsiakis A, Hepp J. et al Salivary beta-endorphin in nonsuicidal self-injury: an ambulatory assessment study. Neuropsychopharmacology 2021; 46: 1357-1363 DOI: 10.1038/s41386-020-00914-2.
• 36 van der Venne P, Balint A, Drews E. et al Pain sensitivity and plasma beta-endorphin in adolescent non-suicidal self-injury. J Affect Disord 2021; 278: 199-208 DOI: 10.1016/j.jad.2020.09.036.
• 37 Klimes-Dougan B, Begnel E, Almy B. et al Hypothalamic-pituitary-adrenal axis dysregulation in depressed adolescents with non-suicidal self-injury. Psychoneuroendocrinology 2019; 102: 216-224 DOI: 10.1016/j.psyneuen.2018.11.004.
• 38 Kaess M, Hille M, Parzer P. et al Alterations in the neuroendocrinological stress response to acute psychosocial stress in adolescents engaging in nonsuicidal self-injury. Psychoneuroendocrinology 2012; 37: 157-161 DOI: 10.1016/j.psyneuen.2011.05.009.
• 39 Plener PL, Zohsel K, Hohm E. et al Lower cortisol level in response to a psychosocial stressor in young females with self-harm. Psychoneuroendocrinology 2017; 76: 84-87 DOI: 10.1016/j.psyneuen.2016.11.009.
• 40 Koenig J, Brunner R, Fischer-Waldschmidt G. et al Prospective risk for suicidal thoughts and behaviour in adolescents with onset, maintenance or cessation of direct self-injurious behaviour. Eur Child Adolesc Psychiatry 2017; 26: 345-354 DOI: 10.1007/s00787-016-0896-4.
• 41 Reichl C, Heyer A, Brunner R. et al Hypothalamic-pituitary-adrenal axis, childhood adversity and adolescent nonsuicidal self-injury. Psychoneuroendocrinology 2016; 74: 203-211 DOI: 10.1016/j.psyneuen.2016.09.011.
• 42 Reichl C, Brunner R, Bender N. et al Adolescent nonsuicidal self-injury and cortisol response to the retrieval of adversity: A sibling study. Psychoneuroendocrinology 2019; 110 104460 DOI: 10.1016/j.psyneuen.2019.104460.
• 43 Aleknaviciute J, Tulen JHM, Kamperman AM. et al Borderline and cluster C personality disorders manifest distinct physiological responses to psychosocial stress. Psychoneuroendocrinology 2016; 72: 131-138 DOI: 10.1016/j.psyneuen.2016.06.010.
• 44 Duesenberg M, Wolf OT, Metz S. et al Psychophysiological stress response and memory in borderline personality disorder. Eur J Psychotraumatol 2019; 10 1568134 DOI: 10.1080/20008198.2019.1568134.
• 45 Walter M, Bureau J-F, Holmes BM. et al Cortisol Response To Interpersonal Stress in Young Adults With Borderline Personality Disorder: A Pilot Study. European Psychiatry 2008; 23: 201-204 DOI: 10.1016/j.eurpsy.2007.12.003.
• 46 Jogems-Kosterman BJM, de Knijff DWW, Kusters R. et al Basal cortisol and DHEA levels in women with borderline personality disorder. J Psychiatr Res 2007; 41: 1019-1026 DOI: 10.1016/j.jpsychires.2006.07.019.
• 47 Thomas N, Gurvich C, Hudaib AR. et al Systematic review and meta-analysis of basal cortisol levels in Borderline Personality Disorder compared to non-psychiatric controls. Psychoneuroendocrinology 2019; 102: 149-157 DOI: 10.1016/j.psyneuen.2018.12.009.
• 48 Hill MN, Tasker JG. Endocannabinoid signaling, glucocorticoid-mediated negative feedback, and regulation of the hypothalamic-pituitary-adrenal axis. Neuroscience 2012; 204: 5-16 DOI: 10.1016/j.neuroscience.2011.12.030.
• 49 Micale V, Drago F. Endocannabinoid system, stress and HPA axis. Eur J Pharmacol 2018; 834: 230-239 DOI: 10.1016/j.ejphar.2018.07.039.
• 50 Morena M, Patel S, Bains JS. et al Neurobiological Interactions Between Stress and the Endocannabinoid System. Neuropsychopharmacology 2016; 41: 80-102 DOI: 10.1038/npp.2015.166.
• 51 Hillard CJ, Beatka M, Sarvaideo J. Endocannabinoid Signaling and the Hypothalamic-Pituitary-Adrenal Axis. In: Comprehensive Physiology. London: Wiley; 2016: 1-15
• 52 Viveros MP, Marco EM, File SE.. Endocannabinoid system and stress and anxiety responses. In: Pharmacology Biochemistry and Behavior. 2005
• 53 Berardi A, Schelling G, Campolongo P. The endocannabinoid system and Post Traumatic Stress Disorder (PTSD): From preclinical findings to innovative therapeutic approaches in clinical settings. Pharmacol Res 2016; 111: 668-678 DOI: 10.1016/j.phrs.2016.07.024.
• 54 Marsicano G, Wotjak CT, Azad SC. et al The endogenous cannabinoid system controls extinction of aversive memories. Nature 2002; 418: 530-534 DOI: 10.1038/nature00839.
• 55 Woodhams SG, Chapman V, Finn DP. et al The cannabinoid system and pain. Neuropharmacology 2017; 124: 105-120 DOI: 10.1016/j.neuropharm.2017.06.015.
• 56 McLaughlin RJ, Hill MN, Gorzalka BB. A critical role for prefrontocortical endocannabinoid signaling in the regulation of stress and emotional behavior. Neurosci Biobehav Rev 2014: 42
• 57 Lutz B, Marsicano G, Maldonado R. et al The endocannabinoid system in guarding against fear, anxiety and stress. Nat Rev Neurosci. 2015: 16
• 58 Kano M, Ohno-Shosaku T, Hashimotodani Y. et al Endocannabinoid-Mediated Control of Synaptic Transmission. Physiol Rev 2009; 89: 309-380 DOI: 10.1152/physrev.00019.2008.
• 59 Clapper JR, Mangieri RA, Piomelli D. The endocannabinoid system as a target for the treatment of cannabis dependence. Neuropharmacology 2009; 56: 235-243 DOI: 10.1016/j.neuropharm.2008.07.018.
• 60 Chiang KP. Reduced cellular expression and activity of the P129T mutant of human fatty acid amide hydrolase: evidence for a link between defects in the endocannabinoid system and problem drug use. Hum Mol Genet 2004; 13: 2113-2119 DOI: 10.1093/hmg/ddh216.
• 61 Dincheva I, Drysdale AT, Hartley CA. et al FAAH genetic variation enhances fronto-amygdala function in mouse and human. Nat Commun 2015: 6 DOI: 10.1038/ncomms7395
• 62 Lutz B, Marsicano G, Maldonado R. et al The endocannabinoid system in guarding against fear, anxiety and stress. Nat Rev Neurosci 2015; 16: 705-718
• 63 The 1000 Genomes Project Consortium An integrated map of genetic variation from 1,092 human genomes. Nature 2012; 491: 56-65 DOI: 10.1038/nature11632.
• 64 Spohrs J, Ulrich M, Grön G. et al FAAH polymorphism (rs324420) modulates extinction recall in healthy humans: an fMRI study. Eur Arch Psychiatry Clin Neurosci. 2021 DOI: 10.1007/s00406-021-01367-4
• 65 Crombie KM, Privratsky AA, Schomaker CM. et al The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD. Neuroimage Clin 2022; 33: 102922 DOI: 10.1016/j.nicl.2021.102922.
• 66 Spohrs J, Ulrich M, Grön G. et al Fear extinction learning and anandamide: an fMRI study in healthy humans. Transl Psychiatry 2021: 11 DOI: 10.1038/s41398-020-01177-7
• 67 Mayo LM, Asratian A, Lindé J. et al Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial. Biol Psychiatry 2020; 87: 538-547 DOI: 10.1016/j.biopsych.2019.07.034.
• 68 Coccaro EF, McCloskey MS, Fitzgerald DA. et al Amygdala and Orbitofrontal Reactivity to Social Threat in Individuals with Impulsive Aggression. Biol Psychiatry 2007; 62: 168-178 DOI: 10.1016/j.biopsych.2006.08.024.
• 69 Lee TMC, Chan SC, Raine A. Strong limbic and weak frontal activation to aggressive stimuli in spouse abusers. Mol Psychiatry 2008; 13: 655-656 DOI: 10.1038/mp.2008.46.
• 70 New AS, Hazlett EA, Buchsbaum MS. et al Amygdala–Prefrontal Disconnection in Borderline Personality Disorder. Neuropsychopharmacology 2007; 32: 1629-1640 DOI: 10.1038/sj.npp.1301283.
• 71 Schmitt R, Winter D, Niedtfeld I. et al Effects of Psychotherapy on Neuronal Correlates of Reappraisal in Female Patients With Borderline Personality Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging 2016; 01: 548-557 DOI: 10.1016/j.bpsc.2016.07.003.
• 72 Siep N, Tonnaer F, van de Ven V. et al Anger provocation increases limbic and decreases medial prefrontal cortex connectivity with the left amygdala in reactive aggressive violent offenders. Brain Imaging Behav 2019; 13: 1311-1323 DOI: 10.1007/s11682-018-9945-6.
• 73 Hariri AR, Gorka A, Hyde LW. et al Divergent Effects of Genetic Variation in Endocannabinoid Signaling on Human Threat- and Reward-Related Brain Function. Biol Psychiatry 2009; 66: 9-16 DOI: 10.1016/j.biopsych.2008.10.047.
• 74 Bossong MG, van Hell HH, Jager G. et al The endocannabinoid system and emotional processing: A pharmacological fMRI study with ∆9-tetrahydrocannabinol. European Neuropsychopharmacology 2013; 23: 1687-1697 DOI: 10.1016/j.euroneuro.2013.06.009.
• 75 Phan KL, Angstadt M, Golden J. et al Cannabinoid Modulation of Amygdala Reactivity to Social Signals of Threat in Humans. Journal of Neuroscience 2008; 28: 2313-2319 DOI: 10.1523/JNEUROSCI.5603-07.2008.
• 76 Schaefer C, Enning F, Mueller JK. et al Fatty acid ethanolamide levels are altered in borderline personality and complex posttraumatic stress disorders. Eur Arch Psychiatry Clin Neurosci 2014; 264: 459-463 DOI: 10.1007/s00406-013-0470-8.
• 77 Wingenfeld K, Dettenborn L, Kirschbaum C. et al Reduced levels of the endocannabinoid arachidonylethanolamide (AEA) in hair in patients with borderline personality disorder – a pilot study. Stress 2018; 21: 366-369 DOI: 10.1080/10253890.2018.1451837.
• 78 Kolla NJ, Mizrahi R, Karas K. et al Elevated fatty acid amide hydrolase in the prefrontal cortex of borderline personality disorder: a [11 C]CURB positron emission tomography study. Neuropsychopharmacology 2020; 45: 1834-1841 DOI: 10.1038/s41386-020-0731-y.
• 79 Compton WM, Conway KP, Stinson FS. et al Prevalence, Correlates, and Comorbidity of DSM-IV Antisocial Personality Syndromes and Alcohol and Specific Drug Use Disorders in the United States. J Clin Psychiatry 2005; 66: 677-685 DOI: 10.4088/JCP.v66n0602.
• 80 Regier DA. Comorbidity of Mental Disorders With Alcohol and Other Drug Abuse. JAMA 1990; 264: 2511 DOI: 10.1001/jama.1990.03450190043026.
• 81 Vest NA, Murphy KT, Tragesser SL. Borderline personality disorder features and drinking, cannabis, and prescription opioid motives: Differential associations across substance and sex. Addictive Behaviors 2018; 87: 46-54 DOI: 10.1016/j.addbeh.2018.06.015.
• 82 Gillespie NA, Aggen SH, Neale MC. et al Associations between personality disorders and cannabis use and cannabis use disorder: a population-based twin study. Addiction 2018; 113: 1488-1498 DOI: 10.1111/add.14209.
• 83 Escelsior A, Belvederi Murri M, Corsini G. pietro et al Cannabinoid use and self-injurious behaviours: A systematic review and meta-analysis. J Affect Disord 2021; 278: 85-98 DOI: 10.1016/j.jad.2020.09.020.
• 84 Fontanella CA, Steelesmith DL, Brock G. et al Association of Cannabis Use With Self-harm and Mortality Risk Among Youths With Mood Disorders. JAMA Pediatr 2021; 175: 377 DOI: 10.1001/jamapediatrics.2020.5494.
• 85 Giacobbe J, Marrocu A, di Benedetto MG. et al A systematic, integrative review of the effects of the endocannabinoid system on inflammation and neurogenesis in animal models of affective disorders. Brain Behav Immun 2021; 93: 353-367 DOI: 10.1016/j.bbi.2020.12.024.
• 86 Sayd A, Anton M, Alen F. et al Systemic Administration of Oleoylethanolamide Protects from Neuroinflammation and Anhedonia Induced by LPS in Rats. International Journal of Neuropsychopharmacology. 2015 18. pyu111–pyu111 DOI: 10.1093/ijnp/pyu111
• 87 Scarante FF, Vila-Verde C, Detoni VL. et al Cannabinoid Modulation of the Stressed Hippocampus. Front Mol Neurosci. 2017: 10 DOI: 10.3389/fnmol.2017.00411
• 88 Kerr DM, Burke NN, Ford GK. et al Pharmacological inhibition of endocannabinoid degradation modulates the expression of inflammatory mediators in the hypothalamus following an immunological stressor. Neuroscience 2012; 204: 53-63 DOI: 10.1016/j.neuroscience.2011.09.032.
• 89 Schmahl C, Arvastson L, Tamm JA. et al Gene Expression Profiles in Relation to Tension and Dissociation in Borderline Personality Disorder. PLoS One 2013; 08: e70787 DOI: 10.1371/journal.pone.0070787.
• 90 MacDowell KS, Marsá MD, Buenache E. et al Inflammatory and antioxidant pathway dysfunction in borderline personality disorder. Psychiatry Res 2020; 284: 112782 DOI: 10.1016/j.psychres.2020.112782.
• 91 Kindler J, Koenig J, Lerch S. et al Increased immunological markers in female adolescents with non-suicidal self-injury. J Affect Disord 2022; 318: 191-195 DOI: 10.1016/j.jad.2022.08.125.
• 92 Saccaro LF, Schilliger Z, Dayer A. et al Inflammation, anxiety, and stress in bipolar disorder and borderline personality disorder: A narrative review. Neurosci Biobehav Rev 2021; 127: 184-192 DOI: 10.1016/j.neubiorev.2021.04.017.
• 93 Bedse G, Bluett RJ, Patrick TA. et al Therapeutic endocannabinoid augmentation for mood and anxiety disorders: comparative profiling of FAAH, MAGL and dual inhibitors. Transl Psychiatry 2018; 08: 92 DOI: 10.1038/s41398-018-0141-7.
• 94 Mayo LM, Rabinak CA, Hill MN. et al Targeting the Endocannabinoid System in the Treatment of Posttraumatic Stress Disorder: A Promising Case of Preclinical-Clinical Translation?. Biol Psychiatry 2022; 91: 262-272 DOI: 10.1016/j.biopsych.2021.07.019.
• 95 Stoffers-Winterling JM, Völlm BA, Rücker G. et al Psychological therapies for people with borderline personality disorder. Cochrane Database of Systematic Reviews 2012: 2020 DOI: 10.1002/14651858.CD005652.pub2
• 96 Zanarini MC, Frankenburg FR, Reich DB. et al Treatment Rates for Patients With Borderline Personality Disorder and Other Personality Disorders: A 16-Year Study. Psychiatric Services 2015; 66: 15-20 DOI: 10.1176/appi.ps.201400055.
• 97 Gartlehner G, Crotty K, Kennedy S. et al Pharmacological Treatments for Borderline Personality Disorder: A Systematic Review and Meta-Analysis. CNS Drugs 2021; 35: 1053-1067 DOI: 10.1007/s40263-021-00855-4.
• 98 Lieb K, Stoffers-Winterling J. Die neuen S3-Leitlinien: Borderline Persönlichkeitsstörung. Psychotherapie Forum 2020; 24: 87-88 DOI: 10.1007/s00729-020-00162-1.
• 99 Rivera P, Fernández-Arjona M del M, Silva-Peña D. et al Pharmacological blockade of fatty acid amide hydrolase (FAAH) by URB597 improves memory and changes the phenotype of hippocampal microglia despite ethanol exposure. Biochem Pharmacol 2018; 157: 244-257 DOI: 10.1016/j.bcp.2018.08.005.
• 100 Yamakawa K, Matsunaga M, Isowa T. et al Transient responses of inflammatory cytokines in acute stress. Biol Psychol 2009; 82: 25-32 DOI: 10.1016/j.biopsycho.2009.05.001.
• 101 Cattaneo A, Gennarelli M, Uher R. et al Candidate Genes Expression Profile Associated with Antidepressants Response in the GENDEP Study: Differentiating between Baseline ‘Predictors’ and Longitudinal ‘Targets’. Neuropsychopharmacology 2013; 38: 377-385 DOI: 10.1038/npp.2012.191.
• 102 Passos IC, Vasconcelos-Moreno MP, Costa LG. et al Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression. Lancet Psychiatry 2015; 02: 1002-1012 DOI: 10.1016/S2215-0366(15)00309-0.
• 103 Spohrs J, Prost M, Ulrich M. et al Endocannabinoid system reactivity during stress processing in healthy humans. Biol Psychol 2022: 169 DOI: 10.1016/j.biopsycho.2022.108281
• 104 Chang C-H, Liu Y-C, Sun C-Y. et al Regulation of stress-provoked aggressive behavior using endocannabinoids. Neurobiol Stress 2021; 15: 100337 DOI: 10.1016/j.ynstr.2021.100337.
• 105 Kolla NJ, Mishra A. The Endocannabinoid System, Aggression, and the Violence of Synthetic Cannabinoid Use, Borderline Personality Disorder, Antisocial Personality Disorder, and Other Psychiatric Disorders. Front Behav Neurosci 2018: 12 DOI: 10.3389/fnbeh.2018.00041
• 106 Martin M, Ledent C, Parmentier M. et al Involvement of CB1 cannabinoid receptors in emotional behaviour. Psychopharmacology (Berl) 2002; 159: 379-387 DOI: 10.1007/s00213-001-0946-5.
• 107 Desai S, Borg B, Cuttler C. et al A Systematic Review and Meta-Analysis on the Effects of Exercise on the Endocannabinoid System. Cannabis Cannabinoid Res 2022; 07: 388-408 DOI: 10.1089/can.2021.0113.
• 108 Vaughn LK, Denning G, Stuhr KL. et al Endocannabinoid signalling: has it got rhythm?. Br J Pharmacol 2010; 160: 530-543 DOI: 10.1111/j.1476-5381.2010.00790.x.
• 109 Gatta-Cherifi B, Matias I, Vallée M. et al Simultaneous postprandial deregulation of the orexigenic endocannabinoid anandamide and the anorexigenic peptide YY in obesity. Int J Obes 2012; 36: 880-885 DOI: 10.1038/ijo.2011.165.
• 110 Aguilera Vasquez N, Nielsen DE The Endocannabinoid System and Eating Behaviours: a Review of the Current State of the Evidence. Curr Nutr Rep. 2022 DOI: 10.1007/s13668-022-00436-x
• 111 Fanelli F, Mezzullo M, Repaci A. et al Profiling plasma N-Acylethanolamine levels and their ratios as a biomarker of obesity and dysmetabolism. Mol Metab 2018; 14: 82-94 DOI: 10.1016/j.molmet.2018.06.002.
• 112 Bilkei-Gorzo A. The endocannabinoid system in normal and pathological brain ageing. Philosophical Transactions of the Royal Society B: Biological Sciences 2012; 367: 3326-3341 DOI: 10.1098/rstb.2011.0388.
• 113 Simone JJ, Green MR, McCormick CM. Endocannabinoid system contributions to sex-specific adolescent neurodevelopment. Prog Neuropsychopharmacol Biol Psychiatry 2022; 113: 110438 DOI: 10.1016/j.pnpbp.2021.110438.
• 114 Peters KZ, Zlebnik NE, Cheer JF.. Cannabis exposure during adolescence: A uniquely sensitive period for neurobiological effects. 2021: 95-120
• 115 Meyer HC, Lee FS, Gee DG. The Role of the Endocannabinoid System and Genetic Variation in Adolescent Brain Development. Neuropsychopharmacology 2018; 43: 21-33 DOI: 10.1038/npp.2017.143.