Impulse Control and Serotonin

Impulse Control Disorders Introduction Impulsivity is a fundamental aspect of the human personality in addition to being a prominent feature of many psychiatric disorders. Defined broadly, impulsivity can refer to: 1. acting on the spur of the moment without previous planning 2. rapid decision making without consideration of alternative action 3. carefreeness, taking each day as it comes. Other authors place impulsivity in a class of action oriented personality predispositions that includes extroversion, sensation seeking, and a lack of inhibitory controls. Difficulties with impulse control are present in a number of Axis I disorders, including intermittent explosive disorder (IED), kleptomania, pyromania, pathological gambling and trichotillomania. With the exception of IED, these impulse control disorders have the diagnostic feature of a tension release cycle and/or gratification after engaging in the behavior. Compulsive shopping falls within the DSM-IV category of Impulse-Control Disorders Not Otherwise Specified. Preoccupation with, and inability to resist purchasing unneeded items characterize compulsive shopping. There are many other disorders where impulsive behavior is secondary to a more primary problem. For example patients with dementia, psychosis, mania, and organic brain syndromesoften exhibit impulsive behavior but both pathological conceptualization as well as treatment focus on the primary disorder. In addition Cluster B personality disorders (borderline, antisocial, histrionic and narcissistic) also have prominent impulsive traits. For the purpose of this lecture we will concentrate on those conditions where impulse control is a core feature. Neurobiology The emerging view is that the serotonin system is important in the expression of impulsivity. Research over the past twenty years has been fairly consistent in finding lowered indices of serotonin function associated with behaviors characterized by impulsivity. One conceptualization of the function of serotonin is that it serves in a capacity of behavioral restraint checking for signals of nonreward, punishment and uncertainty. Pharmacologic manipulations support this model. For example, animals with impaired serotonin levels (due to blockade of serotonin synthesis or lesion of raphe nuclei) exhibit behavior described as hyperirritable and hyperexciteable. Approaches for studying serotonin function in this population have included measuring the serotonin metabolite 5-HIAA in CSF, neuroendocrine challenge studies, and studies of serotonin receptors and transporters on platelets. More recent methods have focused on second messenger signaling, genetic polymorphisms associated with important serotonin related proteins (eg. tryptophan hydroxylase) and application of brain imaging techniques. These studies have been generally consistent in finding low serotonin function in populations with impulsive behavior. It is not surprising that biologic factors may be important in this dimension of behavior as at least two studies support a heritable component of impulsiveness and aggressive behavior. Intermittent Explosive Disorder (IED) Diagnostic Criteria 1. Several discrete episodes of failure to resist aggressive impulses that result in serious assaultive acts or destruction of property. 2. The degree of aggressiveness expressed during the episodes is grossly out of proportion to any precipitating psychosocial stressors. 3. The aggressive episodes are not better accounted for by another mental disorder. Clinical Features IED is characterized by aggressive outbursts that typically have a rapid onset, are short lived (less than 30 minutes) and can involve verbal assault , assault against property or physical assault. The episode can be associated with a provocation but the response is out of proportion. This pattern of behavior leads to significant distress and impairment in the interpersonal and occupational spheres. In addition, legal or financial problems may result. Epidemiology Although IED can occur in childhood, the mean age of onset is 15. It is more common in males (3:1). The lifetime prevalence has been estimated to be about 2.4%. Differential Diagnosis 1. Substance Intoxication or Withdrawal: Aggressive outbursts can be associated with alcohol, cocaine, PCP, barbiturate and inhalant use. 2. Personality Change Due to a General Medical Condition: This diagnosis is made when behavior is associated with a diagnosable medical condition (eg. traumatic brain injury). 3. Oppositional Defiant Disorder, Conduct Disorder, Cluster B personality disorders: IED should be distinguished from the aggressive behavior associated with these disorders. 4. Purposeful behavior: In this case the aggressive behavior has a clear primary gain. 5. Malingering: Individuals may try to feign IED to avoid responsibility for their aggressive behavior. Treatment Serotonin reuptake inhibitors are a logical first choice in treating IED. Clinical trials indicate their efficacy in decreasing verbal and non-assaultive physical aggression in personality disordered subjects as well as in IED. Trials have generally used doses higher than what are typically used for treatment of depression. Among the anticonvulsants, valproate has been studied the most extensively. There is evidence, that like SSRIs, that valproate can reduce impulsive aggression in a variety of diagnostic categories. A number of studies have demonstrated efficacy of lithium in reducing impulsive aggressive acts in prison populations. Side-effects, however, have limited its use. There is some evidence that treatment response is maximized when pharmacological treatment is combined with psychological interventions. Psychological interventions center primarily on cognitive-behavioral group therapy. Specific treatments include relaxation training, problem-solving, negative thought reduction, cognitive therapy alone or in various combinations. While combination approaches appear to be more effective, there has been little ability to discriminate which specific treatment is superior to others. Kleptomania Diagnostic Criteria 1. Recurrent failure to resist impulses to steal objects that are not needed for personal use or for their monetary value. 2. Increasing sense of tension immediately before committing the theft. 3. Pleasure, gratification, or relief at the time of committing the theft. 4. The stealing is not committed to express anger or vengeance and is not in response to a delusion or a hallucination. 5. The stealing is not better accounted for by Conduct Disorder, Mania, or Antisocial Personality Disorder. Clinical Features & Epidemiology The diagnosis of kleptomania is reserved for a relatively rare group of individuals who engage in shoplifting of items they neither want nor need. Fewer than 5% of shoplifters are thought to represent this disorder. The diagnosis is made most frequently in women and the average age at presentation is about 35 years, although the age of onset is much younger (~20 years old). Patients with this disorder appear to have high rates of depression and social isolation. Bulimia also is associated with this disorder. Differential Diagnosis Ordinary theft, which is deliberate and motivated by primary gain (usefulness or monetary value of the object), should be distinguished from Kleptomania. Treatment Cognitive behavioral therapy has been used often in conjunction with medications such as lithium and antidepressants including SSRIs. Systematic long-term treatment studies are lacking. This disorder can have a chronic course despite repeated convictions for shoplifting. Pyromania Diagnostic Criteria 1. Deliberate and purposeful fire setting on more than one occasion. 2. Tension or affective arousal before the act 3. Fascination with, interest in, curiosity about, or attraction to fire and its situational contexts. 4. The fire setting is not done for monetary gain, as an expression of sociopolitical ideology, to conceal criminal activity, to express anger of vengeance, to improve one's living circumstances, in response to a delusion or hallucination, or as a result of impaired judgment. 5. The fire setting is not better accounted for by Conduct Disorder, Mania or Antisocial Personality Disorder. Little is known about this relatively rare disorder. While arson is a major source of property damage, studies indicate that patients with pyromania represent a small fraction of perpetrators, as little as 1%. Similarly, while childhood fire setting is quite common, rarely is the diagnosis of pyromania made. This suggests that efforts should be directed towards evaluating fire setters first for other diagnoses such as conduct disorder, antisocial personality disorder, substance abuse, or other conditions where judgement can be impaired (mental retardation, psychosis, etc). Because of its low prevalence, there is insufficient data in regard to treatment and outcome. Trichotillomania Diagnostic Criteria 1. Recurring pulling out of one's hair resulting in noticeable hair loss.\ 2. An increasing sense of tension immediately before pulling out the hair or when attempting to resist the behavior. 3. Pleasure, gratification, or relief when pulling out the hair. 4. The disturbance is not better accounted for by another mental disorder and is not due to a general medical condition. 5. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. Clinical Features While hair pulling can occur at any site on the body, and frequently at multiple sites, the most common sites are the scalp, eyelashes, eye brows and pubic hair. This behavior can be prompted by stressful circumstances, depressed mood or contemplative states (such as may occur during reading, driving, or lying in bed). Of particular note is the impact trichotillomania has on social functioning. Feelings of shame and embarrassment lead to avoidance behavior and the use of wigs, hats and scarves to disguise hair loss. Case reports describe patients that eat hair (trichophagia) resulting in the development of bezoars (hairballs) that can lead to abdominal pain, bowel obstruction, and vomiting. Patients with trichotillomania are more likely to suffer from mood, anxiety and substance abuse disorders. Eating disorders and body dysmorphic disorder have also been reported to occur at a higher frequency in this population. Epidemiology Available literature suggests the prevalence in the United States to be less than 1%. The prevalence, however, of chronic hair pulling that does not meet criteria for the disorder may be as high as 10%. Surveys suggest that it is more common in women than men. The mean age of onset is estimated to be 13 years. Hair pulling in children is typically considered a benign "habit" and is self-limited. Etiology In contrast to the current DSM-IV classification of trichotillomania as an impulse control disorder, there is an alternate view that it more closely resembles OCD in its phenomenology, pathophysiology, and reported response to serotonergic agents. Others focus on the reinforcing, anxiety-reducing aspects of the behavior and suggest that trichotillomania might be related to anxiety disorders. A third interesting view is that trichotillomania is best viewed as part of a spectrum of biologically determined "pathological 'grooming' behaviors" such as compulsive feather-picking in birds and acral lick dermatitis in dogs. Treatment Antidepressants with prominent serotonergic effects (such as clomipramine and SSRIs) are most often prescribed. There is not, however, a consistent literature supporting efficacy. Combination approaches with atypical antipsychotics have been used with some success. Evidence suggests that even in those patients who show a good response initially to medication treatment, the potential for relapse is quite high. A variety of behavioral techniques have been applied to treating this population. Habit reversal training is designed to increase awareness of the behavior and teach alternative coping skills. Cognitive behavioral therapy is also used. There is a lack of systematic studies to determine efficacy of these interventions. The course of trichotillomania is highly variable without a consistent pattern. Pathological Gambling 1. Persistent and recurrent maladaptive gambling behavior as indicated by five (or more) of the following: 1. preoccupation with gambling 2. needs to gamble with increasing amounts of money 3. has repeated unsuccessful efforts to control, cut back, or stop gambling 4. is restless or irritable when attempting to cut down or stop gambling 5. gambles as a way of escaping from problems or of relieving a dysphoric mood 6. after losing money gambling, often returns another day to get even 7. lies to others to conceal extent of involvement with gambling 8. has committed illegal acts to finance gambling (forgery, fraud, theft, etc) 9. has jeopardized or lost a significant relationship, job, or educational or career opportunity because of gambling 10. relies on others to provide money to relieve a desperate financial situation caused by gambling 2. The gambling behavior is not better accounted for by a Manic Episode Clinical Features The gambling related costs in the United States of gambling are estimated to exceed $5 billion annually. While 86% of the general adult population was estimated (in 1998) to have gambled at some point in their lives, less than 10% of adult gamblers develop a gambling problem (as defined by impairment in occupational, interpersonal or financial functioning). Individuals with this disorder tend to be competitive, energetic, restless and easily bored. Pathological gambling is complicated by high rates of mood, psychotic, anxiety, attention-deficit, personality (antisocial), and substance use disorders (alchohol, nicotine, and stimulants). Rates of attempted suicide are higher than the general population (17% to 24%) Epidemiology The lifetime prevalence of pathological gambling in adults is estimated to be between 1.1-1.6%. Not surprisingly, these rates are much higher in patrons of gambling venues. Similarly states with increased access to legalized gambling have an even greater prevalence. The rates of pathological gambling also appear to be higher in populations receiving mental health or substance abuse treatment. Males outnumber females 2:1 with females being less likely to receive treatment (perhaps reflecting greater stigma in females). Of interest is that individuals with a family history of gambling are more at risk (a number of twin studies support this conclusion). Neurobiology In addition to a link with the serotonin system (as is generally seen with impulsive behavior) other studies of gambling behavior have focused on limbic brain regions, such as the anterior cingulate cortex, that are also thought to be involved in the underlying drug craving in cocaine dependence. Dopamine, involved in mediating the rewarding and reinforcing aspects of drugs of abuse, has been implicated in biochemical studies of pathological gambling, with cerebrospinal fluid levels of dopamine and its metabolites that are suggestive of increased dopamine neurotransmission. This overlap with substance abuse is supported by studies of decision making, neuroimaging, and neuropsychological testing. Treatment Behavioral treatments that have been effective in substance abuse have also been applied in treating pathological gambling. These include Gamblers Anonymous, motivational interviewing techniques, and cognitive behavioral therapy. There have not been many studies to convincingly establish their efficacy. Studies suggest that drop out rates as high as 90% occur with self-help groups. A number of well-controlled studies, however, have been completed showing benefit from SSRI treatment. While not definitive, these results are encouraging. SSRI doses higher than typically used for treating mood disorders were required. Other pharmacological approaches have been with the opiod antagonist naltrexone. Course Without intervention, there is generally a progression of in the frequency of gambling, the amount wagered, and the preoccupations with gambling. References American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC, American Psychiatric Association, 1994. Diefenbach, GJ; Reitman, D; Williamson, DA. Trichotillomania: a challenge to research and practice. Clinical Psychology Review. 20(3):289-309, 2000 Sarasalo, E; Bergman, B; Toth, J. Theft behaviour and its consequences among kleptomaniacs and shoplifters--a comparative study. Forensic Science International. 86(3):193-205, 1997 Potenza MN, Kosten TR, Rounsaville BJ. Pathological gambling. JAMA 11;286(2):141-144, 2001 Reist C. Serotonin and Impulsivity. Directions in Psychiatry. 17:297-301, 1997. Coccaro EF, Kavoussi RK. Fluoxetine and impulsive aggressive behavior in personality disordered subjects. Arch Gen Psychiatry 54: 1081-1088, 1997.