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September 12, 2004
Autoimmune Phenomena in Schizophrenia: Psychodynamic Speculations
I would very much like to comment on a previous posting to our listserve, “Abnormal gene expression in schizophrenia & bipolar disorder” taken from a piece in the Lancet. Thank you to whoever posted this update. For readers unfamiliar with molecular biological processes, especially in relation to the immune system, the following speculations may be a bit tedious.
When I read the posting, I wondered if the connection between the downregulation of myelin-related genes (neuregulin,transferrin, etc. and their relationship to glia, in particular, oligodendrocytes) and severe mental illness (schizophrenia & bipolar disorders) is through autoimmune mechanisms/processes. Oligodendrocytes in the CNS produce and ensheath axons with myelin which plays a critical role in nerve conduction in the CNS. Damage to this myelin sheath can lead to marked deficits in nerve conduction (information transfer -- what neurons do). The field of psychoneuroimmunoendocrinology studies the relation between CNS function and the immune system. Psychological/psychosocial stress (e.g., inescapable, or anticipated inescapable, pain/shock/etc.) suppresses immune function (the pathways are too complex to detail here), but also, can disrupt the regulatory influence of the brain on the immune system, and lead to increased immune activity which if directed against the body’s own tissues and organs, leads to greater susceptibility to inflammatory and autoimmune disease (e.g. some forms of diabetes, rheumatoid arthritis, Graves disease, MS, psoriasis, systemic lupus erythematosis, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, etc).
Psychosocial stress can increase the risk of autoimmune disease or adversely affect its course by impairing the regulatory component of the immune system responsible for controlling excessive immune reactivity. The immune system forms antibodies to healthy tissue which can result in autoimmune disease. It has long been suggested that schizophrenia shares clinical, epidemiological and genetic characteristics with the classic autoimmune diseases (Strauss & Printz 1996). A critical question is whether the autoimmune phenomena arise secondary to non-immune CNS damage or alternative pathways (for an excellent review of autoimmune phenomena and neuronal stress in schizophrenia see David Strauss & David Printz 1996 in “Schizophrenia: New Directions for Clinical Research and Treatment” edited by Charles Kaufmann & Jack Gorman -- Mary Ann Liebert Publishers). Research has demonstrated an overexpression of cytokines and antibodies to heat shock proteins (HSP are expressed at low levels in all cells and function in protein assembly and transport-they are increased in response to a range of insults including infection, trauma, cytokines, etc.) in schizophrenia. I believe that these are downstream reactions to profound stress and anxieties.
I will quote from my own thoughts on this that I published in my Mind/Brain column of the ISPS-US Newsletter Spring-Summer 2000(Volume #2 Issue #2):
“Autoimmune phenomena observed in schizophrenia (Strauss & Printz, 1996) are also seen in stress (Watkins & Maier, 1998). Perhaps, the later evolutionary development of the body’s stress response made use of the phylogenetically earlier biological machinery mediating the bodily response of inflammation or infection to a pathogen. Watkins and Maier (1998) hypothesized that the “stress response redirected the sickness machinery to a new purpose: all that was necessary was to now activate the machinery from a new source - external threat rather than a pathogen” (p. 192). I sometimes wonder, could other persons [from which the person with schizophrenia feels she/he has no protection, i.e., remains permeable, vulnerable to ‘colonization’] be unconsciously reacted to as threatening non - self pathogens [antigens] particularly in poorly differentiated or interpersonally traumatized individuals? If this is partly the case, we may have a kind of psychodynamics of neuroimmunomodulation or a neurobiology [psychoneuroimmunology] of the paranoid-schizoid position. The issue of the massive and complex neural effects of stress and anxiety are beyond the scope of this piece.”
The metaphor of psychosis as being a psychic analogue to autoimmune illness may seem at first glance unwarranted. However, the more I have reflected upon my patients’ symptomatology and narratives, I began to see a clinical relevance to this association. I understand the schizophrenias, as well as severe mental illness in general, as the person’s being under serious threat from without (whether from, as the excellent research of John Read and other investigators have demonstrated, real external traumas, often suffered in isolation in childhood) or within (sometimes as a result of the person’s attempts to cope with external trauma, or as Searles has pointed out, awareness of mortality in a person who feels she/he has not really formed a viable sense of identity to begin with, or as Shakespeare phrased it so eloquently in Hamlet, from “the slings and arrows of outrageous fortune”).
Severe and terrifying separation anxieties are intertwined with omnipotent destructive feelings and phantasies. Dangers and threats to the integrity of the self (in addition to Searles’ viewpoint on the fear of mortality, Franco De Masi points to fear and sense of psychic death -- a fragile sense of insubstantiability at the core of the psychotic patient’s being -- see his 2004 volume “Making Death Thinkable” published by Free Association Books) which are felt to be uncontrollable could, theoretically, initiate a psychobiological cascade (for a review of the neuroimmunology of the stress response see “New Fronteirs in Stress Research: Modulation of Brain Function” edited by Aharon Levy et al in 1998 for Harwood Academic Publishers) including immunological responses designed to distinguish between self/and non-self. The latter become problematic in the autoimmune disorders. Could such psychotic symptoms as unremitting auditory hallucinations and persecutory delusions be usefully conceptualized as autoprotective processes (e.g., providing needed resonance that one exists especially when alone, serving hypervigilance functions against dissociated relational traumas, such as sexual and physical abuse, as well as emotional neglect, etc) against ‘foreign’ non-self invaders? Or we may have a situation in which the self, due to the boundary confusion and permeability often seen in schizophrenia, becomes ‘non-self’ (similar to Arieti’s position that the severe anxiety observed in psychosis is intimately associated with an unlivable, unbearable vision of oneself) a state of depersonalization in which the self is experienced to be altered in strange and threatening ways (perhaps some cases of suicide in schizophrenia could be partly accounted for by this phenomena).
Gaetano Benedetti (1987), based on his long-term clinical experience, usefully speculated on this: “Schizophrenia can be conceptualized as psychosomatic disease, in which the brain itself is the target organ...schizophrenia has the terrible merit of confronting us with the deepest psychosomatic problem of all” (p. 196). I would prefer to say, that because of significant failures in the symbolization process, e.g., metaphorical processes are experienced as concrete reality, as pointed out by Arieti, Hanna Segal, Andrew Lotterman and many others (e.g., one of my patient’s experience of his body being delusionally transformed into a female body is a concrete rendering of earlier experiences of social and interpersonal humiliation, sense of himself as being weak and impotent, etc). Psychic reality (self) is equivalent to concrete physical reality (body), perhaps arising from, as pointed out by Segal, intolerance of separation. In this state thoughts are equivalent to external reality and vice versa. Benedetti and many others, including Searles, have provided some roadmaps in which the threatening, persecutory ‘non-self’ or negative ‘self,’ can be transformed, through a process of therapeutic symbiosis, identification and counter-identification processes, mutually arrived at insight through the medium of ‘transforming images’ in which interpretations are not experienced as narcissistically ‘wounding,,’ etc., into a ‘matrix’ of integration which is life-sustaining. This often requires the therapist’s survival of the same ‘attacks’ the patients formerly directed solely against her or his self. To step into this “I of the vortex’ (apologies to R. Llinas for using his metaphor of the neurobiological ‘self’), results in painful and intense countertransference phenomena (I know of one psychoanalyst who developed an autoimmune disorder which she attributed to her long-term work with a very self-and other destructive patient) which may be one of the significant reasons we prefer to fall back upon physico-chemical ‘explanations’ in place of risking encounter with the depth of suffering and destructiveness our psychotic patients are struggling with.
Interested readers are referred to the following sources:
Benedetti, G. (1987). Psychotherapy of Schizophrenia. NY: New York University Press.
Daruna, J. H. (2004). Introduction to Psychoneuroimmunology. NY: Elsevier Academic Press.
Levy, A., Graver, E., Ben-Nathan, D., & deKloet, E. R. (Eds.). (1998). New Frontiers in Stress Research: Modulation of Brain Function. The Netherlands: Harwood Academic Publishers.
Friedman, M., Charney, D., & Deutch, A. (Eds.). (1995). Neurobiological and Clinical Consequences of Stress: From Normal Adaptation to Post-Traumatic Stress Disorder. Philadelphia: Lippincott-Raven Publishers.
Yehuda, R., & McFarlane, E. (Eds.). (1997). Psychobiology of Post-Traumatic Stress Disorder. Annals of the NY Academy of Sciences-Volume 821.
Brian Koehler PhD
80 East 11th Street #339
New York NY 10003
212 533-5687
brian_koehler@psychoanalysis.net
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