L Jarrett Barnhill, M.D.
Anxiety is a universal human experience. As an affective state, the symptoms of anxiety include a sense of discomfort and uneasiness, arousal, fear and need to escape. Anxiety disorders are characterized by symptoms of sufficient intensity to disrupt social functioning (Fahs,1989). Within this framework, social phobia represents discomfort in unfamiliar interpersonal or performance situations (Kessler, Stein, and Berglund, 1998). Generalized anxiety disorder represents an exaggeration of uncertainty about competency, or future threat ( Bell-Dolan and Brazeal, 1993). Panic disorder involves activation of fear responses and flight or fight arousal ( Moreau and Follet, 1993). Post traumatic stress disorders represent a reaction to extreme distress, intrusive re-experiencing of traumatic events, sense of learned helplessness, and subsequent need to avoid re-exposure (Amaya-Jackson and March, 1993). Obsessive-compulsive disorder involves intrusive, disturbing thoughts and urges, as well as, repetitive or compulsive behaviors. Compulsions diminish underlying threat or sense of incompleteness (Leonard, Lenane, and Swedo, 1993).
Agoraphobia is often associated with panic disorder (APA, 1997). This form of avoidance behavior represents a response to conditioned fear. Avoidance develops when intense arousal and negative cognitive states are paired with neutral or non-threatening stimuli (Black, 1993). A client who experiences a panic attack in the mall may eventually generalize to avoid any large space or choose to remain at home. Clients may also anticipate the danger and become anxious before exposure. Generalization of this anxiety response may expand to include a variety of environmental settings, life situations, or context cues (Drobes and Strauss, 1993).
Anxiety may also relate to organic brain disease, seizure disorders, endocrine disorders, and other medical conditions (Insel and Winslow, 1992) Central nervous system injuries involving the left prefrontal cortex may be associated with catastrophic anxiety. Clients may experience intense dysphasia in response to novel or unpredictable environmental demands. Repetitive or compulsive behaviors occur in the basal ganglia and non-dominant frontal lobe lesions. Perseverative behaviors may present without accompanying overt anxiety or psychological discomfort (Fuster, 1996). In clients with epilepsy, complex partial seizures may occasionally be difficult to distinguish from panic attacks, especially when there is a combination of epileptic and nonepileptic seizures (pseudo-seizures) (Charney, Nagy et al, l996). Endocrinopathies, especially thyroid disorders may present with anxiety or increased moodiness. Cardiovascular disorders such as mitral valve prolapse share a special relationship with panic disorders (Katon, 1989).
Anxiety Disorders in Persons with Mental Retardation
Anxiety disorders are present in 15 to 20% of the general population (APA, 1997). With such a large distribution, comorbidity with other psychiatric disorders becomes the rule rather than the exception (APA 1997) Anxiety disorders are seen in affective disorders, attention deficit hyperactivity disorder, developmental disorders, and some disruptive behavior disorders. Among persons with developmental disorders, anxiety may result from cognitive impairment, reduced adaptive behaviors, and increased vulnerability to environmental demands (Ollinek and Ollinek, 1982; Gualtieri, and Matson, 1989). Decreased social skills, and dependency on familiar others may also lay the ground work for reported high rates of anxiety (Parsons, 1984). As a result, nearly 25% of persons with mild mental retardation experience clinically significant levels of anxiety (Menolascino et al, 1986, Fahs, 1989). This high prevalence may relate not only to poorly resolved stresses, but also genetic vulnerability to anxiety disorders. Among severely/profoundly retarded persons, the actual rates of anxiety disorders are subject to diagnostic misinterpretations, cognitive disintegration, or confounded by the effects of anxiety on baseline rates of other target behaviors (Sovner, 1986). As a result, the recognition of anxiety disorders is also complicated by a lack of skills for reporting symptoms. The clinician may have to rely on reports from staff or family members, or descriptions of arousal state. Observations may also yield information about the paroxysmal nature of associated physiologic expressions of affect. The clinician will often have to rely on a high index of suspicion for anxiety disorders.
The expression of anxiety, as well as, clinical syndromes follows a developmental course (Black, 1993). Infants may react to novel, or unexpected events with overarousal. Brain systems that regulate arousal involve gaze aversion, stereotypic behaviors, and intensified attachment behaviors (Harum and Johnston, 1998). Later, separation anxiety, stranger wariness, emotional referencing, and behavioral inhibition may result from brain maturation as well as temperamental vulnerabilities (REF). Behavior inhibition represents a state of overarousal and withdrawal from novel or unexpected environmental stimuli. Kagan and others (Beiderman et al 1993) have linked behavioral inhibition in infancy to later social phobias, panic disorders and risk for agoraphobia. Behavioral inhibition may represent the earliest manifestation of a neurophysiological diathesis to panic disorder and subsequent avoidance behaviors. Later forms of anxiety include fears of body integrity, natural environmental events, school performance, and increasing concern with social adequacy.(Allen, Heston, et al, l998).
These developmental manifestations of anxiety disorders are also linked to the maturation of neurotransmitter systems. For example, the incidence of panic disorder is less common in prepubescent children; increases during the late teens or early adulthood; and then decreases with aging (Moreau and Follet, 1993). This developmental sequence may parallel the maturation and regulation of the noradrenergic or sympathetic nervous system. (Charney, Bremer, and Redmond, 1994) Other forms of anxiety disorders may increase with aging, possibly reflecting life experience, as well as progressive declines in cognitive abilities. Neuropsychiatric disorders have been associated with anxiety. Complex partial seizures, Alzheimer's disease and Parkinson's disease are examples.
The diagnosis of anxiety disorders requires a careful evaluation of setting, set, and the behavioral repertoire of the individual. The setting may provide clues to specific triggers, level of complexity in environment, demands for novelty, and requirements for behavioral adaptation. This approach is a common part of any behavioral analysis. Set factors include temperament, intensity of physiological arousal, threshold for repetitive/stereotypic behaviors, and genetic vulnerability to anxiety disorders. Among higher functioning patients the DSM-IV and clinically based rating scales are often sufficient. There are circumstances when even the experienced clinician is frustrated by diagnostic uncertainty. This uncertainty is based on the categorical nature of DSM-IV criteria and reliance on patient generated description of symptoms. The clinician may struggle to determine the intensity level of symptoms or degree of social impairment in a low functioning client (Szymanski and Kaplan, 1997). As a result, many clients fail to meet criteria for specific anxiety disorders, and receive a diagnosis of Anxiety Disorder NOS or Atypical Anxiety Disorder. In these subsyndromal forms of anxiety disorders, it may be more useful to obtain a careful history of individualized, operationalized descriptions of symptoms, than to be immobilized by a need for diagnostic rigor.
Persons with severe/profound mental retardation create even more uncertainty and reliability concerns (Sovner, 1986). As a result, a modification of the diagnostic schema may be improved by descriptions of physiologic arousal, fear response, reactions to novelty, and threshold for repetitive or stereotypic behaviors (Perry and Pollard, 1998). Such an observation approach reflects the state of the individual, as well as level reactivity, adaptability, and proneness to repetitive behavior. Since limitations in adaptability may force the client with SPMR to depend on caretakers, an assessment of attachment behaviors is necessary. In stressful situations, attachments may be intensified, while loss or disruption may promote severe separation anxiety or symptoms of learned helplessness (Ratey and Dymek, 1996).
The diagnosis of post traumatic stress disorder (PTSD) is often overlooked in persons with mental retardation (King, et al 1998; States et al 1998). Many clients are exposed to overwhelming stresses as a result of impairments in adaptive behaviors ( Perry and Pollard, 1998) The symptoms associated with PTSD include avoidance behaviors, emotional constriction, dissociative states or explosive outbursts to perceived threats intrusive flashbacks or re-experiencing of traumatic events, and other disruptive behaviors (Pfefferbaum, 1998). Some aggressive behaviors in persons with SPMR may represent manifestations of PTSD in which the vulnerable client responds aggressively to situations reminiscent of earlier abuse or severe stress. Panic disorder, on the other hand, may represent spontaneous arousal, fear conditioning and generalization to other avoidant behaviors (Moreau and Follet, 1993; APA 1997). A common neurophysiological mechanism underlies PTSD and panic disorder involving affective dysregulation, and overarousal as a result of noradrenergic overactivation, faulty GABAergic, or serotonin modulation (Charney, et al 1996). Klein and others have also proposed that some forms of panic disorder, but not PTSD, may result from an overly sensitive CNS suffocation reflex. The result is low threshold for activation of the fear response system (Charney et al 1996) These two models apply to the subgroup of fear-related anxiety disorders and have implications for treatment.
Generalized anxiety may represent wariness to potential environmental threat (Charney, et al 1996). Such anxiety can involve conditioning to situation or environmental specific stimuli, or a sense of threat. The levels of activation fail to reach panic threshold, but avoidance and other forms of anxiety reducing behaviors may emerge (Black, 1993). For some clients, stereotypic behaviors may be generated by overarousal, and the stereotypy restores affective homeostasis (Schroeder, 1989). For other clients, specific environmental triggers may activate a generalized sense of discomfort. This form of anxiety may include conditioned experiences and an overactive behavioral inhibitory system (Rogeness, 1994). The BIS, or behavioral inhibitory system results in behavioral arrest in reactions to novelty, unexpected change, or previous negative experiences (Gray, et al l982). In persons with developmental disabilities, multiple demands may overwhelm adaptive capacities and trigger fearfulness or inhibition. This form of anxiety appears to integrate past life experiences with behavioral inhibition (Clonninger, et al 1993).
Social anxieties manifest increased adrenergic arousal in novel interpersonal settings (Black, Leonard, and Rapoport, 1997). Neurobiologically, social anxiety may represent an extreme sensitivity to signals of disrupted attachment, or vulnerability to threat from unfamiliar social settings (Allen, et al, 1998). Social phobias are characterized by intense fear, discomfort in autonomic arousal in the context of, performance demands. Social phobia falls onto a continuum with temperamental style (slow to adapt) behavioral inhibition and exaggerated forms of performance anxiety (Biedel and Morris, 1993,) This group of disorders include some forms of separation anxiety, avoidant disorder or elective mutism (Leonard and Topol, 1993) In each situation, fearful behaviors are less apparent with family or familiar staff, and may emerge with the entrance of a new person or trip to a setting with unfamiliar people.
Repetitive behaviors, stereotypies, and self-injurious behaviors are common in persons with SPMR (Schroeder, 1989) Obsessive-compulsive disorder has received increasing attention in persons with developmental disorders. Classically, compulsive symptoms represent an attempt to manage obsessions or intrusive thoughts. Clients may describe a sense of discomfort, and note that their compulsions relieve the anxiety. Inhibition of or failure to carry out the compulsion may lead to increasing anxiety (Marazatti, 1998; Schwartz, 1997) As such, OCD appears to operate under rules of negative reinforcement where escape from anxiety is the key outcome (Drobes and Strauss, 1993).
Recently the concept of obsessive-compulsive spectrum disorders has included clients with few if any obsessions, but impulse control disorders, comorbid movement disorders, and addiction behaviors (Cohen, Hollander, Simeon and Stein, 1997). For these clients, there is no urge to inhibit their repetitive behaviors. These behaviors occur in association with positive affects and seem to be intrinsically reinforcing. On occasion, attempts to interrupt these repetitive behaviors may lead to distress or aggression (Gedeye, 1996). The relationship between OC spectrum disorder and addiction behaviors include: arousal (craving) repetitive behaviors that reduces arousal (drug seeking and consumption), positive affective state (euphorigenic or escape from dysphoria with consumption), and relative lack of self-motivated inhibition (compulsive use) (Mazaratti, 1998; Cohen, Hollander, and Stein, 1998).
The treatment of anxiety disorders requires an ecological analysis. When prominent, changes in environmental stimulation or antecedent stresses may be sufficient triggers. Clients with associated neurological impairments may be especially vulnerable to overstimulation and overuse of escape/avoidance behaviors. These clients may respond to simplification of demands, or decreases in levels of novelty. Temperamental characteristics should also be included. Slow to adapt clients may tolerate fewer novel experiences, limitations on social contact, and a gradual introduction to these "normalizing experiences" (Perry and Pollard, 1998). Cognitive Behavioral Therapy (CBT) can be very helpful for higher functioning clients. Clients with SPMR are inappropriate for CBT, but can be helped by behavioral and pharmacological treatments (Schwartz, 1997).
The treatment of panic disorder, simple phobia, and PTSD involves behavioral desensitization, graduated exposure, and medications when needed (Drobes and Strauss, 1993). Pharmacological approaches focus on altering the threshold or intensity of fear reactions (Charney, et al 1996). The tricyclic antidepressants (TCAs) have been quite effective, but require a significant latency of response. Although relatively high doses of TCAs may be required, most clients can only tolerate low starting doses and a gradual titration. Due to potential cardiovascular side effects, the use of TCAs should be carefully weighed, especially in patients with associated anatomical or electrical cardiovascular anomalies (Allen, et al 1993). The Monamine Oxidase Inhibitors (MAO-Is) are perhaps the most effective treatments for panic disorder. Unfortunately, misperceived dangerousness, dietary restrictions on tyramine, and risky interactions with other medications have limited their usefulness (Slater and Greenblatt, 1994). The SSRI's (Prozac, Paxil, Zoloft) have revolutionized the treatment of panic disorder. Like the TCAs, many patients have low starting doses, gradual titration to clinically effective dose, and prolonged trials to determine efficacy (Dougherty and Rausch, 1997). The minimal effective doses may be relatively high, and increase the risk for behavioral toxicity or disinhibition. High potency benzodiazepines (Xanax and Klonopin) have also been beneficial in the management of anxiety disorders. In high doses, these drugs probably effect not only neurotransmitters but neuropeptides involved in panic disorder (Slater and Greenblatt, 1994). Irritability and concerns about dependency have limited the use of the medications in clients with mental retardation (King; States et al, 1998).
The treatment of chronic PTSD has focused on attempts to reduce autonomic arousal. Clonidine, beta blockers, buspirone, low dose SSRIs, occasional benzodiazepines, and anticonvulsants have been of limited usefulness (Amaya-Jackson and March, 1993; Pfefferbaum, 1998). Among persons with developmental disabilities, a lack of recognition or index of suspicion for PTSD has often delayed treatment. The aggressive treatment of clients with PTSD with tricyclics, may produce an exacerbation of agitation, flashbacks, hallucinations or fear (APA, 1997). This reaction often leads to a misdiagnosis of psychosis, and unnecessary use of neuroleptics (Hurley, 1996). As a result, the treatment of PTSD requires the cautious introduction pharmacologic agents with ongoing behavioral interventions. Pharmacotherapy may help to reduce autonomic reactivity, but has little impact on previous learning or experience (Charney, et al 1996). Behavioral programs that focus on fear tolerance, and avoidant behaviors may have a synergistic treatment effect with medications (Drobes and Strauss, 1993). As in panic disorder, such a careful integration may eventually allow fading or eventual elimination of the pharmacotherapy. Unfortunately, many clients with chronic PTSD tend to be more treatment resistant and prone to symptomatic relapse.
Autonomic arousal in social phobias seems to involve the beta adrenergic system (Black and Leonard, 1997). Treatment focuses on this interconnected system. Clients improve on beta blockers, low dose SSRI's, and on occasion, low dose tricyclics. Each agent may down-regulate beta adrenergic activity (APA, 1997). The relative lack of habituation is also an interesting feature of social phobia. Many patients report a worsening of symptoms with repeated exposure, and have evolved elaborate counter rituals to minimize anxiety (Kessler, et al, 1998). Among persons with developmental disabilities, social phobia may be unrecognized because of pre-existing compromised adaptive functioning. As a result the clinician needs to be wary of changes in tolerance for novel social settings, as well as associated fearfulness, oppositional behavior, intense anxiety, stress-induced urination or defecation, or situation specific increases in stereotypies. Social phobia may be associated with other anxiety disorders and comorbid mood disorders and symptoms may improve with treatment of the primary or comorbid condition (Kessler, et al, 1998) .
Obsessive-compulsive spectrum disorders include symptoms ranging from recurring thoughts to repetitive behaviors. The classic obsessive-compulsive disorder manifests intrusive thoughts, or repetitive behaviors. The individual finds these intrusions disruptive, and often attempts to inhibit or ignore these symptoms. The attempts at inhibition produces anxiety (Rasmussen and Eisen, 1992). At the other end of the OCD spectrum are patients with repetitive behaviors that seem associated with positive affect, and are carried out until it "feels right" and may produce irritability when interrupted (Cohen, et al, 1997). OC Spectrum overlaps addiction behavior, repetitive disorders such as trichotillomania or even gambling. Among persons with developmental disabilities, there is a substantial overlap with stereotypies, compulsions and self-injurious behaviors (Bodfish, et al, 1995; Gedeye, 1996; Zimmerman, Jinnah and Lockhart, 1998). This linkage and recent reports of decreased eye blink rates suggest abnormalities in both dopaminergic and serotonergic systems (Bodfish, et al, 1995). Tic disorders have also been associated with obsessive-compulsive spectrum, SIB, and stereotypic behaviors, but increased rates of eye blinking (Robertson, 1992). This finding may suggest different subtypes among the OC spectrum in which the neuropeptides, vasopressin and oxytocin, may play differing roles (Stein, Simeon, and Hollander, 1997).
The treatment of obsessive-compulsive symptoms depends on the probable subtype. Clinically, classic OCD has been associated with recurring thoughts. These are difficult to delineate in mentally retarded patients, although in higher functioning clients these can be perceived as intrusive, disruptive and occasionally frightening. These thoughts may be confused with "voices" associated with schizophrenia (Hurley, 1996). Compulsive behaviors tend to be more common than obsessions. Common compulsions associated with OCD involve washing, cleaning, checking and even obsessive slowness. Compulsive spectrum behaviors include hoarding, touching, arranging, and need for symmetry (Gedeye, 1996).
Treatment of OCD has been revolutionized with the introduction of serotonin reuptake inhibitors. Clomipramine is oldest and perhaps the best studied. In the majority of studies, 50 to 60% of patients experience significant improvements. Clomipramine is a TCA and is associated with cardiovascular risk. Additionally, some patients are rapid metabolizers, and produce increased levels of a demethylated metabolite (norclomipramine). The metabolite may be less effective in obsessive-compulsive disorder (Jenike, 1992). The SSRI's including Luvox, Prozac, Paxil, and Zoloft have been as effective in high doses. Like clomipramine, there is a latency of response of up to 12 weeks (Dougherty and Rausch, 1997). Treatment non-responders may include those with associated motor tics, or spectrum disorders. Often augmentation is required, with beta blocker (pindolol), and buspirone. Among patients with tic disorders, concomitant use of neuroleptics, atypical neuroleptics, or clonazepam may be helpful (McDougal and Goodman, 1997).
There is an enhancement of benefit when SSRI's are combined with response prevention programs. The OC spectrum disorders show a less predictable response pattern (Dar and Greist, 1992). Among persons with SPMR, pica, hair-pulling, skin picking, and other repetitive behaviors may be less responsive. Clinically, some clients experience behavioral disinhibition or increased restlessness at higher doses. Disinhibition is often difficult to distinguish from hypomania, and many times can only be clarified by discontinuing the drug and monitoring (Hewlett, 1997). Based on these limitations, some clients may require the addition of atypical neuroleptics, high potency benzodiazepines (McDougal and Goodman, 1997) or Naltrexone (Lewis and Bodfish, 1997) Clinically, Naltrexone has been beneficial in reducing repetitive behaviors without overt associated anxiety (Gedeye, 1996, Szymanski and Kaplan, 1997).
Some clients have periodic exacerbation of tics, obsessive-compulsive symptoms, and mood changes following streptococcal infections. This subgroup of clients may have a variant of Sydenham's chorea or PANDAS (pediatric autoimmune neurological disorders associated with beta hemolytic streptococcal infections). These clients manifest an abrupt onset of time limited symptoms associated with an elevation in streptococcal antibodies and a plasma cell surface antigen marker, D8/17. The spectrum of behaviors can resemble mania, schizophrenia, acute psychosis, or delirium. Milder forms may show seasonal variation in symptoms. At present, treatment of this subgroup involves short-term trials of antibiotics, plasmapheresis, benzodiazepines, valproic acid, and neuroleptics (Leonard, Rapoprt, and Swedo, 1997).
The treatment of anxiety disorders requires a careful integration of both behavioral and pharmacological therapy. Among higher functioning clients, cognitive psychotherapy can be beneficial. Among persons with SPMR, the recognition of anxiety disorders is complicated by neurological disease and brain dysfunction, deficits in communication, symptom expression, and sensitivity to traumatization. Pharmacotherapy only affects the hardwiring for autonomic reactivity, but does little to alter past experiences (Clonninger, 1995) or cognitive limitations. The overlap between drug treatments for various anxiety disorders suggests that there is a complex interrelationship among brain systems. Similarly, the complexity of neurotransmitter systems should humble the clinician and limit oversimplified, medication-only strategies. Although this paper has focused on neurobiologic factors, many of these findings are incompletely understood and are subject to constant revision.
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For further information contact:
L. Jarret Barnhil, MD
University of NC at Chapel Hill
campus Box #7160
chapel Hill, NC 27599-7160