THE SPECTRUM OF COMPULSIVE, IMPULSIVE, AND AUTISTIC DISORDERS
From “Advances in Psychiatry: Breakthrough Developments in Psychiatric Treatments,” presented by Mount Sinai
School of Medicine, Department of Psychiatry
| UPDATE ON COMPULSIVE, IMPULSIVE, AND AUTISTIC DISORDERS —Eric Hollander, MD, Esther and Joseph
Klingenstein Professor and Chair of Psychiatry, and Director, Seaver and New York Autism Center of Excellence, Mount
Sinai School of Medicine, New York, NY
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| Repetitive thoughts and behaviors: can be symptom, syndrome, or part of behavioral symptom domain that “cuts
across and drives a broad range of different conditions”; groups of disorders share certain features, including one group
characterized by preoccupation with bodily sensations or appearance, one characterized by impulsive choices and behaviors
done for immediate reinforcement, and one characterized by neurologic disorders that often involve dysfunction of
basal ganglia
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| Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V): trying to incorporate “dimensional approach”
to understanding of mental disorders, including dimension that involves compulsivity vs impulsivity; on one end
of this spectrum are people who are risk aversive and perform rituals and routines to neutralize anxiety or perceived
threat; on other end are people who do things impulsively, seeking “some small immediate reinforcement despite long-
term negative consequences”; research-planning agenda for DSM-V proposes that if obsessive-compulsive-related disorders
share 3 of 5 criteria, and if one of those criteria addresses etiology or pathophysiology, then those disorders can be
grouped together; disorders that fall into same group include obsessive-compulsive disorder (OCD), obsessive-compulsive
personality disorder (OCPD), hoarding (which may be removed from OCD), Tourette’s syndrome, Sydenham’s chorea,
grooming disorders, body-image disorders, somatoform disorders, and eating disorders
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| Selective efficacy of selective serotonin reuptake inhibitors (SSRIs) in OCD: potent SSRIs given at high
doses over long periods seem to reduce obsessive and compulsive thoughts and behaviors (meeting treatment-response
criterion), but selective norepinephrine reuptake inhibitors (SNRIs) do not; ≈60% of patients respond to SSRIs, with 25%
to 35% improvement on Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)
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| New approaches to treatment: atypical antipsychotic medications—when added to SSRIs in dose ranges <3 mg,
yield “pretty robust” decrease in obsessions and compulsions in individuals who were resistant to early trials with SSRI; low
relative metabolic rate in striatum predicts good response to atypical antipsychotic medications; deep-brain stimulation
(DBS)—burr holes drilled bilaterally in skull and tip of electrodes placed in shell of nucleus accumbens to alter activity of
circuits
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| Body dysmorphic disorder: defined as distress of imagined ugliness; individual has obsessive preoccupation with
perceived defect in his or her appearance and practices compulsive rituals, including repeated cosmetic surgeries, to conceal
that defect; patients have higher rates of depression, social anxiety, and suicide than patients with OCD; onset in
childhood or adolescence; shows selective efficacy to SSRIs but not to SNRIs
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| Behavioral and substance addictions: National Institute on Drug Abuse may change name to National Institute of
Disorders of Addiction to reflect continuum of behavioral addictions and substance addictions; these conditions share impairment
and reward circuitry; have similar deficits in frontal lobe brake mechanism and perhaps in other key regions (eg,
nucleus accumbens) that influence impulsive choice, causing patient to engage in risky behaviors with immediate payoff
rather than planning for future rewards
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| Impulse-control disorders in current and future DSM systems: intermittent explosive disorder; kleptomania;
pyromania; pathologic gambling; trichotillomania; impulsive-compulsive shopping, sexual behavior, Internet use, and skin
picking; proposed that these be called impulsive-compulsive disorders because they start with level of pleasure, arousal, or
gratification that initiates behavior, but over time, persistent component develops; more common in men—pathologic gambling;
intermittent explosive disorder; pyromania; sexual compulsions; more common in women—kleptomania; trichotillomania;
self-injurious behavior; compulsive buying; binge eating
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| Autism: complex heterogeneous developmental disorder that presents before 3 yr of age; has marked impairment in 3 core
symptom domains; associated symptom domains shape expression and differ from person to person; has strongest genetic
heritability of all neuropsychiatric disorders; twin studies suggest no single gene with major effect; rare causal
deletions or duplications of chromosomal architecture sometimes lead directly to production of autism; currently, ≈1%
of boys have autism spectrum disorder (much more common than previously thought, which may be due to earlier intensive
screening); environmental factors may have epigenetic effects, playing role in turning on or off gene transcription
in vulnerable individuals
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 | To make diagnosis, the following features must be present: marked social deficits; speech and language problems; narrow
restricted interests and repetitive behaviors
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| Associated symptom domains: impulsivity and aggression; affective instability; electroencephalography (EEG) abnormalities;
seizure disorders; inattention and motor hyperactivity; symptom domains can be targeted for treatment to reduce
distress and improve functioning
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| Social deficits: people with autism deficient in empathy; patient does not understand that anyone has mind outside of his
or hers and cannot see situation from other’s perspective; does not understand what others think or feel; does not look
others in eyes, but usually focuses on mouth or periphery; deficient in reading nonverbal communications; does not interact
reciprocally with others
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| Repetitive behaviors: individuals with autism who have use of language describe intrusive, disturbing thoughts, impulses,
or images (ie, obsessions) involving contamination, aggression, sexual urges, blasphemous thoughts, hoarding, magical
thinking, and somatic concerns; they try to relieve anxiety about obsessions with compulsive behaviors such as putting
things in order, lining things up, rituals involving other individuals, bedtime rituals, asking for reassurance,
hoarding, checking things repeatedly, washing repeatedly, repeating, self-damaging behaviors, and counting rituals
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| Oxytocin trials: compared to placebo, intravenous oxytocin reduced repetitive behaviors and improved social cognition;
speaker now studying intranasal oxytocin to see whether same improvements can be achieved
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| SSRI trials: investigations suggest serotonin deficiency exists in autism, and when SSRIs in very low doses used to treat
autism in children, improvements seen in repetitive behaviors and possibly in global functioning (mean dose 9.5 mg;
higher doses result in activation); results replicated with “somewhat higher” doses in adults, with more robust response
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| Anticonvulsant trials: high rates of seizures and EEG abnormalities seen in people with autism; these patients show great
deal of impulsivity and aggression; large-scale studies show decreases in irritability with divalproex vs placebo
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| Pathologic gambling: study found less compulsive gambling in people who received lithium, especially people with
mood instability; question whether lithium works because it reduces mood instability, resulting in improvement in impulsivity?
or does it work because it reduces impulsivity, which results in improvement in mood stability?
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| THE ROLE AND TREATMENT OF IMPULSIVITY IN PSYCHIATRIC DISORDERS —Alan C. Swann, MD, Pat R.
Rutherford Jr Chair in Psychiatry, and Professor and Vice Chair for Research, Department of Psychiatry and Behavioral
Sciences, University of Texas, Mental Sciences Institute, Houston
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| Introduction: normally, generation of action and screening of action balanced by “fairly elegant system,” allowing individual
to decide what to do; failure of that balancing mechanism results in impulsivity; “truly impulsive behavior is not
poor judgment; it’s no judgment”; no behavior impulsive in and of itself, and impulsivity not related to risk (“eating an
ice cream cone can be impulsive”); impulsivity “is the short-circuiting of what normally relates behavior to its context”;
hallmark features of impulsivity include inability to regulate initiation of action and inability to inhibit behavior when its
context becomes inappropriate
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| Impulsivity and brain function: more than one system involved in protecting against impulsivity; each of those systems
involves >1 neurotransmitter and >1 brain region; in different contexts, rate-limiting step of impulsivity differs,
and therefore targets for treatment differ
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| Limbic arousal: probably major source of impulsivity; subject to balance between excitatory and amino acid functions;
anticonvulsants and possibly mood stabilizers effective in controlling limbic arousal
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| Serotonin and dopamine: balance between activation and inhibition of goal-directed, drive-related behavior strongly influenced
by balance between serotonin and dopamine; impulsivity may be reduced by treatments that enhance serotonergic
function
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| Attention deficit: impairs individual’s ability to scan environment efficiently to provide appropriate behavioral screening;
stimulants may improve ability to scan environment attentively
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| Impulsivity as personality characteristic: many impulsive characteristics and impulsivity-related psychiatric illnesses
strongly heritable; genes that might be involved include those related to catecholaminergic and serotonergic
systems, 5HT transporter, opioid systems, and second-messenger systems; early development and impulsivity overlap;
if parents have impulsivity-related disorder that impairs response inhibition, they may pass it on to their children
through both genetics and role modeling; clinical concern is to determine risk of patient’s doing something impulsive
in very near future
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| Likelihood of impulsive behavior: impulsive behavior related to normal survival; in high-risk situation, individual responds
without reflection and without thinking; in response to extreme stressors, locus ceruleus pours out norepinephrine,
one result of which is to impair function of cells normally involved in response inhibition; increase in
norepinephrine can be activated inappropriately due to unusually large stimulus, such as intoxication or mania, or due
to sensitization by past substance abuse or childhood trauma; in study, when yohimbine given to normal subjects,
which shut down locus ceruleus, increasing norepinephrine and resulting in more impulsivity on computer test of impulsivity,
subjects observed that in parallel with their impulsive responding, they “felt jazzed up inside; they felt different;
it was not pleasant; it was not necessarily high, but they felt different inside; they could recognize it”; this suggests
that people with impulsivity problems could be trained to recognize risky internal states and inhibit impulsive behavior
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| Impulsivity in psychiatric illness: impulsivity prominent in many psychiatric illnesses, including bipolar disorder; in
study of mixed states, as manic symptom scores increased, impulsivity scores also increased, possibly explaining why
people who have mixed states of bipolar disorder often have complications of illness (eg, substance use disorders, increased
suicidal behavior) that are related to impulsivity
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| Impulsivity and anxiety: “tantalizing relationship” exists between impulsivity and anxiety; shown to be orthogonal,
“which means that they’re not correlated,” but they combine in different ways; healthy people usually have low impulsivity
and low anxiety; those who have high impulsivity and low anxiety tend to be cold and antisocial; those with low impulsivity
and high anxiety usually have anxiety disorder in which avoidant behaviors are prominent; those with high
impulsivity and high anxiety may be in mixed state of bipolar disorder or have other severe affective disorder
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| Disorders in which impulsivity prominent: substance use disorders (impulsivity predisposes people to use drugs
of abuse, and most drugs of abuse increase impulsivity in short and long terms); impulsive aggression (in which individual
does not plan aggressive behavior); bipolar disorder (but not all behavior in manic stage is impulsive; some “wild
things” are done in response to, eg, delusions of grandeur)
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| Impulsivity and alcohol: alcohol has biphasic effect on behavior, usually having stimulatory effect first, followed by
sedative effect; sensitivity to activating and inhibiting effects of alcohol regulated independently of each other, and people
who are insensitive to sedating effects “usually have a very hard time with alcohol during their lives”
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| Impulsivity and suicide: depressed person may wish to die, but depression has protective elements (such as indecision,
disorganization, lack of initiative) that prevent his or her acting on that wish; suicide attempts that are mainly premeditated
and hopeless still require component of impulsivity, which is often provided by alcohol; with severe depression,
small increase in impulsivity can be decisive
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| Challenges in development of treatments for impulsivity: determining relationship of impulsivity to pathophysiology
of comorbid psychiatric disorders; time course; integrating pharmacologic and nonpharmacologic treatments
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| Conclusions: impulsivity represents failure of balance between initiation of action and screening of action; poorly regulated
norepinephrine function can lead to state-dependent increases in impulsivity; impulsivity cuts across pathophysiology
of many psychiatric disorders; combination of impulsivity and depression associated with increased risk for suicide;
pharmacologic treatment depends on rate-limiting step(s) for impulsivity in given disorders or patients
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Suggested Reading
Bjork JM et al: Incentive-elicited brain activation in adolescents: similarities and differences from young adults. J Neurosci
24:1793, 2004; Blumberg HP et al: Frontostriatal abnormalities in adolescents with bipolar disorder: preliminary
observations from functional MRI. Am J Psychiatry 160:1345, 2003; Dougherty DM et al: Laboratory measured behavioral
impulsivity relates to suicide attempt history. Suicide Life Threat Behav 34:374, 2004; Dougherty DM et al:
Suicidal behaviors and drug abuse: impulsivity and its assessment. Drug Alcohol Depend 76(Suppl):S93, 2004; Grant
JE, Potenza MN: Impulse control disorders: clinical characteristics and pharmacological management. Ann Clin Psychiatry
16:27, 2004; Hollander E et al: Clomipramine vs desipramine crossover trial in body dysmorphic disorder: selective
efficacy of a serotonin reuptake inhibitor in imagined ugliness. Arch Gen Psychiatry 56:1033, 1999; Hollander E
et al: Divalproex in the treatment of impulsive aggression: efficacy in cluster B personality disorders. Neuropsychopharmacology
28:1186, 2003; Hollander E et al: Does sustained-release lithium reduce impulsive gambling and affective
instability versus placebo in pathological gamblers with bipolar spectrum disorders? Am J Psychiatry 162:137, 2005; Hollander
E et al: Impact of trait impulsivity and state aggression on divalproex versus placebo response in borderline personality
disorder. Am J Psychiatry 162:621, 2005; Hollander E et al: Short-term single-blind fluvoxamine treatment of
pathological gambling. Am J Psychiatry 155:1781, 1998; Klin A et al: Visual fixation patterns during viewing of naturalistic
social situations as predictors of social competence in individuals with autism. Arch Gen Psychiatry 59:809, 2002;
Moeller FG et al: Psychiatric aspects of impulsivity. Am J Psychiatry 158:1783, 2001; Novotny S et al: Increased repetitive
behaviours and prolactin responsivity to oral m-chlorophenylpiperazine in adults with autism spectrum disorders.
Int J Neuropsychopharmacol 7:249, 2004; Potenza MN et al: An FMRI Stroop task study of ventromedial prefrontal
cortical function in pathological gamblers. Am J Psychiatry 160:1990,2003; Swann AC et al: Acute yohimbine increases
laboratory-measured impulsivity in normal subjects. Biol Psychiatry 57:1209, 2005; Swann AC et al: Impulsivity:
a link between bipolar disorder and substance abuse. Bipolar Disord 6:204, 2004; Swann AC et al: Impulsivity:
Differential relationship to depression and mania in bipolar disorder. J Affect Disord 2007, Epub ahead of print; Swann
AC et al: Increased impulsivity associated with severity of suicide attempt history in patients with bipolar disorder. Am J
Psychiatry 162:1680, 2005; Swann AC et al: Manic symptoms and impulsivity during bipolar depressive episodes. Bipolar
Disord 9:206, 2007; Swann AC et al: Two models of impulsivity: relationship to personality traits and psychopathology.
Biol Psychiatry 51:988, 2002.
Educational Objectives
| The goal of this program is to improve management of the spectrum of compulsive, impulsive, and autistic disorders.
After hearing and assimilating this program, the clinician will be better able to:
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| 1. Explain how psychiatric disorders that involve the dimension of compulsivity vs impulsivity will be
grouped together in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V).
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| 2. Discuss the selective efficacy of selective serotonin reuptake inhibitors in obsessive-compulsive disorder.
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| 3. Describe some of the new approaches to treatment of compulsive, impulsive, and autistic disorders.
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| 4. State the differences between impulsivity as a survival mechanism and as a pathologic trait.
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| 5. Discuss the role of impulsivity in psychiatric disorders.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee members
to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified
conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business
or commercial interest. For this program, the following has been disclosed: Dr. Hollander is a consultant/advisor to Nastech and
Neuropharm, Ltd. Dr. Swann and the planning committee reported nothing to disclose.
Acknowledgments
Drs. Hollander and Swann were recorded at Advances in Psychiatry 2007: Breakthrough Developments in Psychiatric Treatments,
held October 26-27, 2007, in New York, NY, and sponsored by Mount Sinai School of Medicine, Department of Psychiatry.
The Audio-Digest Foundation thanks the speakers and Mount Sinai School of Medicine for their cooperation in the production
of this program. Advances in Psychiatry 2008 will be held October 24-25, 2008, in New York, NY; for further information, contact
cme@mssm.edu or telephone 212-731-7950. This program is copyright 2008.
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