Schizophrenia: A Psychobiological Self DisorderGlucocorticoid hormones play a key role in the regulation of an organism’s response to threat and challenge. In humans and other mammals, the stress response is characterized by an activation of the HPA axis by the release of corticotrophin-releasing factor/hormone (CRF/CRH) from the paraventricular nucleus of the hypothalamus into the portal-venous circulation. CRF/CRH acts together with arginine vasopressin (AVP) to release adrenocorticotrophin (ACTH) from the anterior pituitary gland. Circulating ACTH leads to release of cortisol from the cortex of the adrenal glands. Glucocorticoid hormones represent a core component of adaptive responsivity to environmental threat. Cortisol promotes gluconeogenesis and lipolysis, processes which help increase the availability of energy reserves to facilitate activity (e.g., flight/fight). The degree of limbic-hypothalamic-pituitary-adrenal axis (LHPA) activity is finely regulated through a series of homeostatic negative-feedback processes, including glucocorticoid (cortisol) receptors situated in the cortex, hippocampus, hypothalamus, and pituitary. These same hormones are involved in early neural development, exerting permanent effects on tissue growth and differentiation (De Kloet et al. 1988). In rats, glucocorticoids have been shown to regulate the phenotypic expression of certain neuronal types, impacting on the genomic and environmentally influenced processes that shape the developing brain. It is quite plausible that disruption in the development of the glucocorticoid hormone systems could result in altered neural development and to altered stress vulnerability to the effects of threat/stress later in adult life (see Keith Matthews “Social separation models of depression” in Maria Ron & Trevor Robbins edited volume, “Disorders of Brain and Mind: Volume 2” published in 2003 by Cambridge University Press). During ontogenetic development, differential components of the LHPA system evidence characteristic patterns of development. Immediately prior and post-birth, cortisol levels are very high in the rat. From post-natal day 2 through postnatal 12-14, the rat enters what is known by neuroscientists as the “stress-hyporesponsive phase” (SHRP). It has been theorized that the SHRP acts as a neuroprotective period, to prevent the adverse effects of excessive cortisol on neural development. Neuroscientists have identified the thermal (e.g., provision of warmth) and tactile (ventral contact, licking, grooming, etc.) cues provided by the mother to be the main regulatory influences over the maintenance of the SHRP. The one experimental manipulation which appears to be capable of disrupting the SHRP and promoting the release of significant quantities of ACHT and cortisol is physical separation of the neonate from its dam (mother). Maternal separation results in acute cortisol secretion which increases with repeated episodes of separation, as well as chronic effects on LHPA responsivity into adulthood. These research results have been confirmed in other species, e.g., nonhuman primates. Glucocorticoids exert primarily catabolic effects in that they inhibit cell division and protein synthesis. Neurally, glucocorticoids inhibit the rate of cell proliferation as well as cell division in some types of stem cells (Bohn 1980). When cells have ceased dividing, glucocorticoids impair myelination, synaptogenesis (synaptic growth) and the formation of dendritic spines. The hippocampus (a neural region particularly implicated in the neuropathology of the schizophrenias) appears particularly susceptible to high glucocorticoid levels. Matthews (2003) noted: “If an extremely adverse early environment, such as maternal separation, overpowers the SHRP, it is possible that high circulating levels of glucocorticoids penetrate the developing brain, irreversibly altering the optimal neuronal and dendritic sculpting processes. These neonatal manipulations certainly lead to altered HPA function in adulthood...and may impact on other developing systems and structures” (p.355). Repeated maternal separations (RMS), result in the following neural research findings (Matthews et al. 2001) across neurochemical systems:
Increased levels of dopamine in both dorsal and ventral striatum Developmental psychobiology, which provides a link between psychological-developmental experience and the structure and function of the brain, has addressed the nature of the psychobiological effects of disruption of early attachments. Myron Hofer (see his recent article “Developmental psychobiology of early attachment” in B. J. Casey’s edited volume “Developmental Psychobiology” published in 2004 by American Psychiatric Publishing, Inc.) has detailed, in meticulous research with rats, how attachment patterns interact with the genome to influence long-term neural functioning. He and his colleagues identified the “hidden regulators” mediating the attachment bond between pup and dam. Separation from the mother resulted in a loss of these ‘hidden regulators” which leads to psychobiological dysregulation across multiple biological systems. In humans, we see the formation of mental representations arising from these earlier regulatory interactions. Hofer noted: “Once formed, it seems likely that these organized mental structures come to act as superordinate regulators of behavioral and biological systems underlying motivation and affect, gradually supplanting the sensorimotor, thermal, and nutrient regulatory systems found in younger infants. These developmental processes would link biological systems with internal object representations in humans and would account for the remarkable upheavals of biological as well as psychological systems that occur in adults in response to cues signaling impending separation or in response to losses established simply on hearing of a death, for example, by telephone” (pp. 21-22). The above research findings offer us a form of understanding of the neuroscience and phenomenology of the schizophrenias: the neuroscience of profound stress/fear is, for the most part, the neuroscience of the schizophrenias and should there be severe disruption in the achievement of the mental structures which Hofer refers to, the person is tied to concrete modes of experiencing internal-psychic reality, in which self-constancy depends upon the physical presence and emotional relatedness of the other. This would entail grave difficulty in differentiating thoughts from objects. The positive symptoms of psychosis, as well as the negative symptoms, could be explained in a proportion of patients by the state of separations arousing significant fear/stress (annihilation anxiety) as reflected in neuroscience and neuroimaging research, as well as the relative failure of metacognitive processes and the establishment of mental structures which differentiate internal from external realities as reflected in the clinical phenomenology of these heterogeneous disorders. The above is a partial account of a more complex model delineated in my volume in progress “The Schizophrenias: Brain, Mind and Culture.” It, like the model of disordered self-monitoring of Chris Frith and colleagues, is an attempt to relate the neuroscience research with clinical phenomenology. However, unlike that of Frith and colleagues, this model privileges relational developmental experience, attachment processes and the significant role of anxiety and self-other development. Anxiety, particulary the type of annihilatory anxiety arising from the sense of self-loss, plays a central role in this model, as does the nature of differentiation of the self leading to metacognitive competence. The psychopharmacologists have long recognized the need to modify the affective dysregulation apparent in acute and chronic psychotic states. The cognitive-behavioral theorists, particularly in the UK, are gradually coming to terms with the significance of affect in cognitive dysfunction and the nature of self-other relatedness reflected in specific psychotic symptoms such as hallucinations and delusions.The various psychoanalytic schools have attempted to describe the self-disorder within the language of their own theoretical perspective, often with similar themes: the Lacanians refer to the self of the patient being constiuted by the jouissance of the Other; the existentialists refer to dasein becoming prey to that which it encounters; the object relations theorists speak of impaired self- and object constancy; the Jungians point to a disintegration of the very foundations of the personality; the Kleinians refer to the ego/self weakening due to excessive splitting (schizoid anxieties), projective identification, destructive narcissism and the dominance of the omnipotent psychotic part of the personality; the British independents describe various kinds of trauamtic impingements on the developing self/ego root; the Freudians emphasize withdrawal of emotional investment in objects and their representations as well as failure of primary identifications; the interpersonalists underscore dissociative processes, abysmally low self-esteem and the patient’s fear/terror of one’s own omnipotently experienced destructiveness; the self psychologists point to fragmentation of the self due to failed self-object functioning and the intersubjectivists of self-annihilating/negating relational contexts. Gaetano Benedetti and Maurizio Peciccia describe the psychotic patient’s difficulty in separating self from non-self and the threat of self-loss either in states of loneliness/isolation or within a relationship. The neuroscience of a proportion of the schizophrenias from the above perspectives, is the neuroscience of the annihilation anxiety, as well as the defenses against this disintegration anxiety, arising from and contributing to, the precariously established self, both relational and private. This model of the schizophrenias, unlike more reductionistic models which attempt to isolate the genome of the individual from the multiple environments in which it unfolds, allows an etiological significance to cultural and developmental experience and to the individual’s handling and shaping of such experience. Brian Koehler PhD |