Jarrett Barnhill, M.D.
Self-injurious behavior (SIB) is a heterogeneous group of behaviors reported in between 10-15% of individuals with severe intellectual disabilities, brain dysfunction, and comorbid autism (Schroeder et al., 1995). Because of this heterogeneity, SIB can be classified in several ways. Most SIB is "nonspecific" and often difficult to classify. Classification based on severity, typology, topography and observational data are the most common methods. SIB is classified under "Stereotypic Movement Disorder" under current DSM-IV criteria (American Psychiatric Association, 2000). Another model of SIB includes etiological factors such as self-injury associated with pain, premenstrual changes, seizure disorder, and communication disorders (Buitelaar, 1993). A second subgroup of SIB is associated with the behavioral phenotypes of specific genetic disorders such as Lesch-Nyhan Syndrome (Breese et al., 1995; Denckla, 2000). A third subgroup represents state-related SIB that accompanies primary psychiatric disorders. In this subgroup, SIB emerges or intensifies in relation to the onset of mood, anxiety, and psychotic disorders (Herpetz, 1995).
Because of this heterogeneity, it is apparent that SIB represents a final common pathway with many possible etiologies. As such, each individual with SIB must be assessed based on the diversity of variables associated with environmental, bio-behavioral, and conditioned factors. It is often the case that in spite of this diversity, many clinicians continue to rely on single theoretical models to diagnose and plan behavioral or pharmacological interventions. These reductionistic approaches result in a literature that is littered with contradictory and difficult to replicate studies and once promising treatments. In order to make sense of this cacophony, clinicians need to develop models that integrate behavioral observations and neurobiology. This paper proposes that a subset of severe SIB shares a common neurobiological substrate with chronic addiction. Based on this model, common treatment approaches may exist and need to be explored.
SIB- Differential Diagnosis
The evaluation of SIB is an individualized process of elimination that begins with behavioral analysis. It is essential to define the trigger events, severity, typology, topography, and behavioral "rules" for self-injury. This analysis should also include a careful assessment of affective state, temperamental factors (how the individuals reacts), level of adaptive behaviors, comorbid neurological and medical disorders, and possible iatrogenic causes. One goal of this process is to separate trait related factors such as generalized brain dysfunction and intellectual disability from state related changes (baseline exaggeration) from primary neuropsychiatric disorders. Another goal is to define treatable subgroups.
This process also includes a genetic evaluation that focuses on differentiating behavioral phenotypes associated with SIB. Examples of behavioral phenotypes include severe compulsive self-mutilation observed in Lesch-Nyhan Syndrome (Breese et al., 1995; Barnhill, 2000; Johnson & Patel, 1996); hand biting without severe tissue damage secondary to overarousal in individuals with Fragile-X Syndrome (Cohen, 1995; Mazzucco, 2000); Smith-Magenis (Finucane, Dirril, & Simon, 2001); Cornelia de Lange syndrome (Denckla, 2000); skin picking associated with Prader-Willi syndrome (Dimitopoulos et al., 2000) and other obsessive compulsive spectrum disorders (Swerdo, Zinner, & Farber, 1999; Lewis & Bodfish, 1998; Mace & Mauk, 1995). One of the most severe forms of SIB is associated with Lesch-Nyhan Syndrome (LNS). LNS is associated with compulsive self-mutilation, abnormal movements, intact pain perception, and a positive response to restraint (Barnhill, 2000). The neurobiology of LNS has been well studied although the link between the genotype, low levels of HGPRT, and hyperuricemia and SIB is more complex. Animal models of LNS suggest that hypersensitive DA1 receptors play a crucial role in the compulsive self-mutilation associated with LNS. A range of specific pharmacological probes that exacerbate self-mutilating behavior (Breese et al., 1995) supports this finding. As if to re-inforce the complexity of the neurochemical networks involved, serotonin and adenosine may also play modulatory roles (Johnson & Patel, 1996). In contrast to the severe self-mutilating SIB in LNS, individuals with FRAXA syndrome engage in repetitive hand biting. This behavior may occur predominantly in novel social settings and appears triggered by affective overaousal (Cohen, 1995). Although the exact mechanism of this overarousal is unclear, modulation of noradrenergic tone affects the frequency and severity of hand biting and motoric hyperactivity (Cohen, 1995). As expected serotonin may also regulate this arousal system, and play a role in these compulsive, but often low intensity SIB (Mazzucco, 2000).
SIB and Psychiatric Disorders
When compared to behavioral phenotypes or nonspecific SIB, self-injury associated with primary psychopathology occurs as state-related phenomena associated with syndrome specific changes in mood, activity level, perceptual disturbances, and thought processes. In a general sense, the SIB appears "time-locked" with the psychiatric disorder. The appearance, intensification, or changes in the behavioral characteristics accompany the psychiatric disorder. This relationship is frequently more complex than meets the eye. For example, individuals with mild intellectual disabilities have lower rates of SIB and psychiatric disorders when compared to those with severe disabilities. On the other hand, individuals with mild intellectual disabilities may be less likely to have severe organic brain disorders or behavioral phenotypes that may be associated severe SIB. As a result, SIB among individuals with mild intellectual disabilities may be more likely to be associated with a primary psychiatric disorder than nonspecific or phenotypic subtypes. This relationship may be reversed in individuals with severe intellectual disabilities. In this population, DSM-IV diagnoses are confounded by higher rates of brain diseases, and are often less reliable. This uncertainty is compounded by underdeveloped language and self-reporting skills, increased vulnerability to environmental disruption and severely limited adaptive capacities (Guess & Carr, 1991). As a result, there is a tendency to lump state-related changes in SIB into either "nonspecific" or "stereotypic movement disorder" categories. In this sense, the relationship between SIB and primary psychiatric disorders may relate to the level of intellectual disability as well as the capacity to make a reasonably accurate and reliable diagnosis. Perhaps in the future, better diagnostic assessment instruments and more intensive genetic analysis may improve this dilemma.
Individuals with schizophrenia may engage in a range of SIBs during acute exacerbation of disorganized thought and behavior, chronic hallucinations or delusions (Sweeny & Zamecnik, 1981). Chronically institutionalized schizophrenic patients present a different problem. These patients represent a treatment refractory subgroup with high rates of negative symptoms, cognitive impairments, self-stimulating or perseverative behaviors (Kraus, 2000). Ritualistic manipulation of body parts or self-mutilation may result in severe tissue damage.
SIB in individuals with mood disorders may result from suicide attempts that may include command hallucinations, somatic delusions and dysmorphophobic obsessions (Burgess, 1991; Matthew et al., 2001). In severe depression, psychotic delusions may focus on defective body parts and the need to remove the sinful part. Dysphoric or rapid cycling bipolar disorder may also increase the risk for suicide. The cyclical nature of mood disorders, periods of symptomatic behaviors alternating with a relative absence of SIB, is characteristic of mood disorders.
Obsessive compulsive disorder (OCD) may also produce tissue damage through constant washing to avoid contamination. These individuals may be quite distressed by obsessive thoughts and attempt to suppress or inhibit their repetitive behaviors. "Giving in" to the obsession or urge may provide only temporary release. Others may experience a growing "urge" but few obsessions (Hollander & Benzaquen, 1996; ). Repetitive skin picking or rubbing are common and may result in injury damage due to high frequency or prolonged bouts of repetitive behavior. For others, SIB can be relentless and potentially tissue damaging. The "rules" that guide this severe form of SIB differ from milder, high frequency/low intensity self-injury. The severe forms of SIB may occur in "binges" and may continue to intensify until it "feels right" or hurts "just so" (Hollander & Benzaquen, 1996). Other OCD spectrum disorders are more perplexing. Body Dysmorphic Disorders (BDD) and dysmorphophobias (Delusion disorders) are association with misperceptions of body imperfections. The compulsion to remove or correct these "imperfections" may result in tissue damage caused by repetitive cleansing, or manipulation (Phillips, gunderson, Mallay, McElroy, & Carter, 1998).
Individuals with intellectual disabilities and panic attacks may self-injure during outbursts or while attempting to escape "panicogenic" situations. Individuals with post-traumatic stress disorder (PTSD) may also self-injure during periods of intense autonomic arousal, dissociation, and re-experiencing phenomena such as flashbacks (Yehuda, 1998). These symptoms are associated with personal histories of severe physical or sexual abuse and emotional neglect. Borderline Personality Disorder (BPD) is also associated with chronic abuse (Russ et al., 1992). Individuals with BPD experience affective instability, intense reactivity, dysfunctional attachment behaviors, and impulsive reactions to distress. This combination may lead to repetitive self-destructive behaviors and parasuicidal behaviors. In addition self-reports of relative analgesia, or calmness produced by the injury suggest a reinforcing property to the self-injurious behaviors. Addiction is also more common.
Drug Addiction and Addiction behavior
Addiction behaviors include a group of repetitive, self-defeating or potentially self-destructive behaviors that appear to follow the behavioral "rules" of drug addiction. Addiction behaviors are frequently activated by increasing tension or urge to act (craving); engaging in the behavior and resolution of the urge (drug seeking and consumption); and a temporary sense of relief or mild euphoria ("high" or reduced tension). The temporary relief afforded by engaging in the behavior provides intrinsic, contingent, positive re-enforcement (Goldstein, 2001; Koob & Roberts, 1999; Kupferman, Kandel, & Iverson, 2000). Over time the "high" may wane in a subgroup of individuals. This process appears akin to tolerance. At this point the individual can abandon the behavior as no longer "thrilling", or begin the process of overriding tolerance by increasing the frequency or intensity of the behavior. This step is analogous to the transition from drug "use" (pleasure) to "abuse"(use with declining effects and increasing negative consequences) in which the motivation changes form self-reinforcement to a need to escape the negative affective states. This step sets the stage for more malignant forms of addiction behaviors. During this process the behavior becomes increasingly "ingrained" or automatic response to negative affective states. Conditioning experiences may also change form positive to negative reinforcement contingencies. At this point the biological similarities between these compulsive spectrum disorders and addiction is more apparent and recent functional neuroimaging studies underscore this relationship (Gianoulakis, 1996).
Drug addiction involves tolerance, craving and high rates of drug seeking, loss of control over use, withdrawal states, and continued use in spite of progressive psychosocial, and legal consequences and medical and neurological complications. Addiction also includes the compulsive search for and use of the substance irrespective of potentially life-threatening consequences. In addition, continued abuse frequently results in a worsening of psychiatric disorders, high rates of suicidal behavior, and eventual CNS injury (London, Grant, Morgan, & Zukin, 1995).
Tolerance results in the need to increase doses of the agent in order to maintain the desired state. Although the exact mechanism is still subject to debate, there is a consistent reduction in the reinforcing properties of the drug. For vulnerable individuals, the attenuated "high" is accompanied by symptoms of withdrawal and an increased urgency to avoid withdrawal. Craving is intensified during withdrawal states, setting in motion a compulsive urge to use the drug and a range of acquisition behaviors (drug seeking). Unfortunately drug consumption only temporarily satiates craving. Although re-using resolves the abstinence symptoms (dysphoria and intense discomfort), it also establishes a negative reinforcement loop by pairing reduced distress with the episode of drug use (Gianoulaakis, 1996). Drug ingestion allows the individual to escape the discomfort of withdrawal and may play a major role in the maintenance of abuse.
The pattern of drug use changes in individuals genetically vulnerable to addiction. At this addiction stage, binge use predominates in conjunction with a loss of control over consumption. Craving sets the stage eventual drug use triggers out of control consumption that terminates because of exhaustion or when no drugs available. At this point, drug withdrawal, environmental stress, conditioned cues, and brief episodes of drug may readily initiate uncontrollable compulsive use (Commings, 1996). This pattern suggests a lowered threshold for the entire process.
In addition to tolerance and withdrawal symptoms, chronic, binge drug abuse also contributes to sensitization. In contrast to tolerance, sensitization is characterized by an increased sensitivity or lowered threshold for some effects of the drug. Cocaine addiction illustrates this point. Chronic cocaine abuse leads to the development of tolerance to the euphorigenic effects of the stimulant. Due to eventual changes in several neurotransmitter systems, attempts to reproduce the "high" by increasing the dose of cocaine eventually begin to fail. The end result is a change towards binge-use. Escalating rates of noncontinuous use seem to lock in bingeing (periods of intense use), craving (increasing urge to use) and loss of control over consumption. Over time, high dose bingeing contributes to the emergence of stereotypies/ritualistic behaviors (punding), tactile hallucinosis, excoriation to eliminate the cocaine "bugs", increasing paranoia and risk for psychosis. These changes suggest a different neurochemical process and the "taking over" of intrinsic reinforcement pathways by more malignant forms of craving, compulsive behavior, or deleterious drug effects. This process resembles kindling in chemically or electrically induced seizures (Kraus, 2000). In kindling models, the stimulus is required to trigger a seizure. With repeated stimulation, the threshold for stimulus-induced seizures decrease to the point that an eventual spontaneous ictus occurs. In essence the neural pathways in the limbic system are altered and inhibitory controls are overridden by the epileptic focus. Kindling-like phenomena are suggested in chronic poorly controlled seizure disorders , affective disorders, addictions (both craving and withdrawal), and perhaps forms of self-injurious behaviors (Kraus, 2000).
SIB shares many features with drug use and other compulsive spectrum disorders- trichotillomania (O'Sullivan et al., 1998), or compulsions associated with Tourette disorder (Robertson, 2000; Sreingard & Dillon-Sout, 1992; Swerdo et al., 1999). Clinically milder forms of SIB (high frequency/low intensity) overlap stereotypies and other intrinsically or self-reinforced behaviors. Tissue damage may eventually result from the high frequency of repetition rather than intensity or severity. These milder forms of self-injury appear analogous to early drug use behavior. The drug-induced "high" resembles self-stimulation and contributes to a positive affective state and intrinsic reinforcement. For most, the process may stop here. Individuals genetically or temperamentally vulnerable to addiction start to behave differently. These individuals may be more prone to develop tolerance to these intrinsically reinforcing properties. They may also be more likely to shift towards the use of self-stimulatory behaviors towards escape behaviors. The threshold for sensitization may also differ in genetically vulnerable individuals. In these individuals, there may be a lowered threshold for transformation towards severe self-injury (Clonninger, Svrakic, & Przybeck, 1993; Commings, 1996; Herpetz, 1995; Kaye & Wisniewski, 1996; King & Flowers, 1996; Zimmerman, Jinnah, & Lockhart, 1998).
More severe forms of SIB present with an intense compulsion to tissue damaging self-injury. At this stage, once SIB is initiated, it will continue until exhaustion or restraint is applied. Analgesia may be difficult to prove but it is apparent that pain may not terminate the process. This process suggests either faulty production or decreased sensitivity to endorphins, but the role of corticotrophic releasing factor (CRF) and other peptides may have larger role than anticipated. At this stage, the process suggests that the compulsion to injure overrides pain or pleasure and proceeds in a relentless fashion until satiation occurs.
Severe SIB may be analogous to chronic severe, addiction where loss of control and compulsive self-injury continue on a binge regardless of consequences. As in addiction, the pattern of uncontrollable SIB can be triggered by conditioned social cues, pain or dyphoric, affective states, psychiatric disorders, or periods of non self-injurious stereotypies (similar to re-exposure to small doses of the abused drug). Once the ritualistic behavior is started, SIB will continue "out of control" until restraint, or satiation switches it off. Sensitization or kindling may also result in a process in which the more the individual self-injures, the more likely he or she is to continue to self-injure. In such a case , the threshold for self-injury is progressively lowered, while the probability of self-injury binges increases. The behaviors become "too easy", suggesting over-committed pathways or circuits that supercede and dominate other behavioral options.
Conclusion and Questions
This paper offers a model for a subset of SIB that is based on the neurobehavioral aspects of addiction and addiction behaviors. Milder forms of SIB may occur in compulsive spectrum disorders and other addiction behaviors. In this context, self-reinforcement rules may apply. This pattern resembles the early phases of drug use in which the motivation is to experience a "high" or positive affective state. The frequency of these self-reinforcing behaviors may fluctuate according to affective state or environmental stresses. Over time the pattern of behaviors may change in individuals with comorbid psychiatric disorders to ameliorate psychological distress.
A subset of individuals progress to chronic forms of SIB that seem to parallel the transition from drug use to abuse (Becker, 1999). Over time, tolerance emerges to either the intrinsically reinforcing or stress reducing (escape) properties of the behavior (less effective as escape behaviors). Tolerance may change the rate of reinforcement (variable rate of positive or negative reinforcing effects) as well as resistance to extinction. At this stage, interrupting the addiction behavior may produce increased dysphoria, irritability, agitation or aggression. This pattern of behavior may analogous to withdrawal states. Further repetition develops into a vicious cycle in which engaging in the behavior, like the continued abuse of a drug, now serves to minimize withdrawal states. The role of conditioned environmental factors also plays an increasing role in maintenance. This transformation adds another layer of negative reinforcement or escape behaviors to the mix.
Restrictions on SIB begin to increase distress (withdrawal) and an increased urge to engage in self-injury (craving). At this point, a smaller subset of vulnerable individuals are beginning to "cross the wall" and move towards SIB that resemble chronic addiction behaviors. At this stage there is a loss of control and changes in the patterns of SIB (increased intensity and bingeing) as well as increased vulnerability to further sensitization. As a result, the behavior (or addiction) takes on a life of its own, and becomes increasingly malignant and destructive.
For this model to be valid, the clinician needs to demonstrate a developmental convergence of SIB and addiction. This process involves delineating a developmental sequence for SIB as well as a typology of the transformation from low intensity/high frequency repetitive behavior (stereotypy) to self-injury. This transformation begin in childhood and intensify as the result of genetic vulnerability, temperamental differences, adverse ecological events or settings, and the emergence of some psychiatric disorders. It is unclear if this model will apply to specific behavioral phenotypes of SIB.
From a clinical perspective, the chain of evidence that connects severe forms of SIB to addiction behaviors leaves us with the following questions:
1.Is there any relationship between a positive family history of drug/alcohol abuse and dependency among mentally retarded clients with severe, compulsive SIB? To the author's knowledge studies that look at the genetic vulnerability to addiction and SIB are not widely available. Such a study might need to focus on fathers in order to minimize the effects of fetal exposure. Nicotine would also need to be included in the list of drugs of abuse, since in utero exposure is associated with learning disabilities, impulse control disorder, possible addiction and aggressive/disruptive behaviors in children.
2.Does the relationship between temperamental factors and addiction play also apply to some forms of SIB? Clonninger and others (1993) have addressed temperamental factors as risk factors for addiction. Clonninger has also addressed the role of temperament in personality development and risk for other psychopathologies. These findings suggest a dimensional quality to temperament, personality and psychopathology, addictions and perhaps SIB. Early SIB associated with abuse and neglect, irritability, low frustration tolerance or affective instability. The "traits" may increase the likelihood self-injury in response to rage or distress. These factors may also be associated with the risk for addiction
3.Does the age of onset of SIB determine the severity of adult behavior?
During childhood, self-injury appears to follow a developmental course similar to other repetitive and other ritualistic behaviors. In each behavior, the usual course and typology differ from less adaptive forms. For example emerging OCD differentiates from the usual childhood worries and rituals. Hall and group (2001) has demonstrated a similar developmental course and differentiation for SIB. What are the factors that shape this aberrant developmental course? SIB associated with behavioral phenotypes and primary neuropsychiatric disorders may offer tantalizing clues, but the author suspects that other genetic factors such as the risk addictions may play a key role. A vulnerability to addiction may increase the likelihood of a rapid transformation from stereotypic or self-reinforcing precursors into severe compulsive SIB. In this sense, compulsive SIB may be a behavioral equivalent to severe addiction behavior. Genetic vulnerability may increase the probability or accelerate the pace of transformation. In addition, these individuals may have a lower threshold for sensitization that contributes to a progressive loss of control.
Most SIB begins in childhood but most individuals do not progress to severe self-mutilating or compulsive SIB. In addictions, early use may increase the probability of drug abuse but a smaller subset will progress to chronic addiction. Perhaps SIB is the culmination of several risk factors including level of intellectual impairment, comorbid neurological disorders, temperament, abuse/neglect, institutionalization, and ecological factors. The progression towards severe SIB may require another set of factors. One of these factors may be the genetic vulnerability to addiction. One set of factors may initiate the process while genetic vulnerability may increase the probability of progression in severity.
4.Where do SIB that accompanies behavioral phenotypes such as Prader-Willi of SIB fit into this scheme? A reasonable starting point is comparing addiction behaviors to behavioral phenotypes associated with compulsions, affective instability, and other forms of "craving" behaviors. In the animal literature, neuropeptide Y (NPY) stimulates feeding. Chronic exposure to alcohol shifts the role of NPY to craving and drug ingestion rather than feeding (Brown, Coscina, & Fletcher, 2000). Perhaps a similar "kidnapping" of function occurs during sensitization and progression to chronic, severe SIB. This process has moved beyond intrinsic reinforcement and predictable naltrexone response since opiates may play a less direct role at this stage of the behavior. Other peptides and CNS changes through sensitization or kindling are now operative.
5.Does a family history of addiction allow clinician to predict which group of early onset stereotypies (low intensity/high frequency SIB) will progress during childhood? Although the timetable of this process may vary, the genetic vulnerability to addiction may define a subgroup of children who demonstrate the transition from self-reinforcing use to progressively more malignant forms of destructive/compulsive SIB.
6.Would the compulsion to self-injure be comparable to craving on functional neuroimaging studies? Two issues may be germane. Stereotypies and milder forms of SIB may have a PET/fMRI signature that more closely resembles compulsive spectrum disorders (e.g. trichotillomania, or compulsive gambling). More severe SIB may be associated with functional images that more closely resemble chronic addictions. To my knowledge neither of these comparisons have been made.
7.Is there evidence of a biphasic course of SIB that suggests a similar progression of drug use that accompanies addiction behaviors? Self-reinforcing behaviors (positive effects of endorphins/DA/5HT activation) resemble the early phases of drug use or self-stimulation. This pattern is eventually replaced by negatively conditioned experiences (withdrawal states). Later in the history of SIB/stereotypies the pattern of eventual binge SIB emerges that suggests tolerance and sensitization. Sensitization may alter the conditioning experience so that emotional states, environmental events, engagement in repetitive behaviors or SIB may now unleash a more malignant escalation of SIB. This subgroup should display a pattern of "binge-like' self-injury, that once initiated persists until reaching satiation. This episodic SIB may be followed by a refractory period of decreased SIB that may resemble bipolar illness.
8.Do the pharmacological approaches to craving, binge use, or withdrawal significantly improve this subtype of SIB?
a.The response to SSRIs in persons with addictions suggest consistent improvement in a subset of patients with affective and anxiety disorders, obsessive compulsive symptoms, irritability and impulsivity. The response to SSRIs is less predictable in a subset of individuals with impulse dyscontrol, obsessive-compulsive spectrum disorders and addiction behaviors. Although the initial excitement over the anticraving effects of SSRIs has waned, long term studies suggest that improvement in mood and impulsivity may have a significant impact on addiction. Acute reductions in craving may occur shortly after the introduction of SSRIs, but the effect wanes quickly. Rapid improvement in SIB suggests a similar mechanism to craving. A delayed response would support the relationship to mood disorders or other compulsive disorders. Unfortunately improvement in mood may not necessarily result in a reduction in psychological craving.
b.Mood stabilizers have also been used in both SIB and addiction, but it appears that treating the underlying mood disorder may be the key factor in reducing drug abuse. Drugs that affect glutamate activity may have a greater effect on chronic SIB.
c.Atypical antipsychotic drugs have demonstrated efficacy in bipolar disorder, but may worsen OCD. In contrast to this mixed picture, DA1/DA3 antagonistic effects of some of the drugs may be helpful in the treatment of addictions. The drugs have some usefulness in OC spectrum disorders, especially when related to tic disorders, and stereotypies/SIB in persons with severe intellectual deficiencies. The DA1 blocking effects of clozapine, and olanzapine are helpful, but have not demonstrated any clear superiority to risperidone, a 5HT2/DA2 blocker. There are reports that DA1/DA3 effects of clozapine may reduce alcohol use among schizophrenics with comorbid drug dependency (Drake, Xie, McHugo, & Green, 2000).
d.Recent studies of novel 5-HT3 antagonists suggests that these drugs may have significant effects on psychosis, and addiction behaviors. The efficacy of 5-HT3 blockers (mitirzapine included) needs to be addressed.
e.To date there is no available literature on the clinical SIB use of calcium channel blockers, long-term opiate antagonism (nalmefene), and NMDA and excitatory modulators (acomprosate). Most of these drugs have not been used clinically for individuals with SIB or intellectual disabilities. The efficacy of opiate antagonists is complex in both addiction and SIB. In contrast to other positive studies (Garbutt, West, Carey, Lohr, & Crews, 1999), Krystal and group (2001) reported that naltrexone was less effective in long term alcoholics within the VA system. The individuals were chronic long-standing abusers. A similar conflicting literature exists regarding the effects of opiate antagonists on SIB. Perhaps chronicity implicates other neurochemical factors in severe forms of both disorders. For example, animal models suggest that chronic "addiction" is associated with changes in glutamate and other peptides (neuropeptide Y, corticotrophin releasing factor, vasopressin). These changes may decrease the likelihood of responding to naltrexone. SIB has also been associated with alterations in opiate receptors (downregulation), exaggerated opiate response, altered pain sensitivity, and variations in the formation of endorphins from its parent peptide (POMC) (Sandman, Hetrick, Taylor, & Chicz-DeMet, 1997). Perhaps naltrexone is more effective early in the course of SIB, but, as in alcohol addiction, this pattern may change over time. In this context, DA1 and 5-HT3 antagonists, drugs that affect NMDA/glutamate receptor activity (perhaps acomprosate) or novel peptide antagonists may turn out to be more effective in chronic, addiction-like SIB.
In summary, a clinical comparison between a subset of SIB, addiction behaviors and substance dependency offers tantalizing clues into the perplexing world of severe self-injury. Recent evidence does suggest that SIB may be preceded by a developmental history of stereotypies and temperamental factors (Buitelaar, 1993; Gedeye, 1992). Perhaps tolerance, withdrawal and increased "craving" play a role in the early evolution of SIB. Sensitization however may be crucial in this transformation to more malignant forms of SIB. There are striking parallels between the derivative of chronic addiction behavior, treatment resistant drug dependency and SIB. There appears to be a connection between long term potentiation (LTP) and the conditioned "hyperconnectedness" of SIB to trigger stimuli. Sensitization or kindling may result in a transition from clear-cut environmental triggers to endogenous factors such internal, state-related changes (craving or spontaneous events that may be seizure or tic-like phenomena). Sensitization may also play a role in the rapid escalation of compulsive self-injury in the face of pain and tissue mutilation (loss of control).
This convergence of typology suggests a common neurobehavioral substrate and may open the door to the applications of anti-addiction and anti-SIB drug treatments. To date, it is unfortunate that SIB has no "cure" and that reliable palliative treatments are still often empirically based. Defining a subgroup that resembles drug dependency may be helpful from an evidenced-based perspective as well as spurn more clinically relevant treatment research. .
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Other Suggested Reading
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For further information:
Jarrett Barnhill, M. D., University of North Carolina School of Medicine,
CB 7160, Chapel Hill, NC 27599-7160;