It is proposed that the extraordinary sensory bombardment of excruciating painful stimuli associated with genital mutilation in infancy has deleterious effects upon the normal structural and functional development of those brain structures associated with genital sensory stimulation/function and the normative experiences of pain and pleasure. Such early trauma upon the pleasure systems of the brain is proposed to have a deleterious impact upon the development of affectional bonds that depends upon those intact brain structures that are essential for the formation of affectional bonds in human relationships, particularly, the development of intimacy in sexual affectional bonding.
It is further proposed that these early traumatic experiences of genital mutilation, particularly, if they are uncorrected by subsequent positive pleasure experiences , are very likely to be expressed later in life in personal and intrapersonal dysfunction involving depression, alienation, anger, self-destructive and socially destructive behaviors. These hypotheses are based upon the well established effects of early somatosensory stimulation and deprivation upon the developing brain and behavior (Cannon, 1939; Cannon & Rosenbleuth, 1949; Berman, Berman and Prescott, 1974; Coleman, 1971; Essman, 1971; Floeter & Greenough, 1979; Heath, 1968,1972ab, 1975, 1977; Higley, Suomi, Linnoila, 1991; Higley, Hasert, Suomi, Linnoila,1991; Laudenslager, M.L., Reite, M., & Harbeck, 1982; Laudenslager and Reite, 1984; Laudenslager, Capitanio and Reite, 1985; Melzack and Scott, 1957; Melzack and Burns, 1965; Prescott, 1967, 1968, 1971, 1975ab, 1976, 1977, 1979, 1980, 1990; Reite, et. al., 1982; Riesen, Dickerson & Struble, 1977; Rosenzweig, Krech, Bennett & Diamond 1968; Saltzberg, Lustick and Heath, 1971; Struble and Riesen,1978; Sharpless, 1969, 1975; Snider & Maiti, 1976; and Tassinari, 1968; and from the known effects of prenatal, perinatal and early infant trauma upon later adult functioning (Anand & Hickey, 1987; Diamond, 1990; Faro & Windle, 1969; Jacobson, Eklund, Hamberger, Linnarsson, Sedvall & Valverius, 1987; Jacobson, Nyberg, Eklund, Bygdeman & Rydberg, 1988; Jacobson, Nyberg, Gronbladh, Edlund, Bygdeman & Rydberg;, 1990; Levy, 1945; Porter, Miller & Marshall, 1986; and Salk, Lipsitt, Sturner, Reilly & Levat, 1985) and others.
1. Consequences of Failure to Provide Effective Pain Relief During Surgical Procedures Upon Physiology, Behavior and Health Status. There is now incontrovertible evidence that the failure to provide effective pain relief during surgical procedures in neonates results in such stress to the neonate that the psychophysiological integrity of the neonate is so severely compromised that it results in enhanced morbidity and mortality in such neonates. It is now informed medical opinion that "the response of newborns to the stress of cardiac (Anand, Hansen and Hickey, 1990) and noncardiac (Anand, Sippell & Aynsley-Green, 1987; Anand, Sippell, Schonfield & Aynsley-Green, 1988) operations is substantially greater than that of adults " (Anand and Hickey, 1992). Specifically, Anand and Hickey (1987) have previously proposed a physiologic basis "for the use of deep levels of anesthesia and postoperative analgesia to attenuate the extreme responses of newborns to perioperative pain and stress" (Anand & Hickey, 1992).
The findings of Anand & Hickey (1992) upon variations in the effectiveness of anesthesia and postoperative analgesia in neonatal cardiac surgery are so dramatic and relevant to the study proposed herein that direct quotations from their Results and Conclusions are particularly warranted:
Results. The neonates who received deep anesthesia (with sufentanil) had significantly reduced responses of beta-endorphin, norepinephrine, epinephrine, glucagon, aldosterone, cortisol, and other steroid hormones; their insulin responses and rations of insulin to glucagon were greater during the operation. The neonates who received lighter anesthesia (with halothane plus morphine) had more severe hyperglycemia and lactic acidemia during more severe hyperglycemia and lactic acidemia during surgery and higher lactate and acetoacetate concentrations postoperatively (P<0.025). The group that received deep anesthesia had a decreased incidence of sepsis (P=0.03), metabolic acidosis (P<0.01), and disseminated intravascular coagulation (P=0 .03) and fewer postoperative deaths (none of 30 given sufentanil vs. 4 of 15 given halothane plus morphine, P<0.01).
Conclusions. In neonates undergoing cardiac surgery, the physiologic responses to stress are attenuated by deep anesthesia and postoperative analgesia with high doses of opioids. Deep anesthesia continued postoperatively may reduce the vulnerability of these neonates to ;complications and may reduce mortality. (N Engl J Med 1992; 326: 1-9). In the above study, the authors were particular to note and describe the mechanisms of increased stress and its relationship to sepsis:
The increased incidence of sepsis in the halothane group may have been related to postoperative changes in immune function; such changes have been correlated with hormonal stress responses in adult patients. Beta-endorphins, glucocorticoids, catecholamines, and prolactin are important regulators of immune responses; such interactions may be integrated by the hypothalamus (p.7). The consequences of significantly increased release of stress hormones upon the developing brain and later behaviors have yet to be fully appreciated. The finding of extended periods of non-rapid-eye-movement sleep in neonates undergoing circumcision without anesthesia by Emde, et al (1971) is a case in point. The findings of Porter, Miller and Marshall (1966) demonstrated that spectrographic analyses of neonatal pain cries could distinguish between cries to circumcision and other stressors and that these neonatal cries could also be distinguished by listening adults.
It takes no leap of faith or evidence to recognize that such pain states will interfere with the maternal-infant bonding process which is known to have its own adverse consequences upon brain structure, function and behavior (supra; and Marshal, et. al, 1982).
Although, it is beyond the scope of this introductory review to systematically cite numerous animal studies on the effects of maternal stress upon fetal and neonatal brain development, function and behavior, the study of Peters (1990) is illustrative of these kind of studies. Peters (1990) reviewed earlier findings that maternal stress modifies 5-hydroxytryptamine (5-HT) receptor binding in several brain regions of the adult offspring and alters the intensity of behavioral responses to 5-HT receptor agonists. In a further study of the same maternal stressor (crowding combined with daily saline injections during the final week of pregnancy), an elevated maternal plasma free tryptophan level without significantly affecting total tryptophan was reported. The increased maternal plasma tryptophan was associated with significantly increased fetal brain levels of tryptophan, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA, a metabolite of 5-HT). These increases were found to be maintained at 10 days postnatal life.
Since 5-HT is recognized to have a role in the control of neuron development during the perinatal period, it was suggested that the stress-induced increase in fetal brain 5-HT synthesis may play a part in the mechanisms by which prenatal stress influences adult behavior.
Similar arguments can be made for the flooding of the neonatal brain with adrenal corticosteroids and other stress hormones from the hypothalamic-pituitary-adrenal system consequent to circumcision stress which have unknown long-term consequences for "encoding" and influencing the developing brain with a possible permanent induction of a psychobiological substrate or pattern of psychophysiological stress that interacts with, influences and confounds all subsequent experiences of pain and pleasure.
This is to say that such profound neonatal pain involving the unique sensory-brain systems that are designed to mediate pleasure may be contributory to the establishment of "sado-masochistic" processes at a most fundamental neurobiolgical level that is beyond the normative range of conscious awareness. Additionally, the possible enhancement of "androgenization" of the developing brain due to excessive output of adrenal androgens consequent to perinatal and postnatal stress, e.g. circumcision, is a possible contributory mechanism to such later behaviors.
Another consideration. What extent, if any, are the mechanisms that convert androgens to estrogens within the brain affected or impaired by perinatal and postnatal trauma? And what are the long term behavioral implications of such a possibility? (Baum, 1979; Phoenix, Goy and Resko, 1968; Diamond, Liacuna & Wong, 1973). What are the long-term consequences of a "hyperandrogenization" of the developing brain for enhanced aggression; quality of male-female relationships; and the capacity for intimacy in sexual relationships? Although, these questions are not directly related to the immediate objectives of this proposal they do reflect issues that are related to the overall consequences of perinatal and neonatal trauma, as it is reflected in acts of circumcision, particularly, as these procedures have been conducted without analgesics or anesthetics.