1. Impulse control disorders involve repetitive behaviors that are often pleasurable but interfere with daily life. They involve dysfunction of the striatum and overlap with substance addictions. 2. Serotonin and dopamine systems are implicated in impulse control through their roles in mood, reward, and impulsivity. Genetic studies also link these neurotransmitters to impulse control. 3. Additional neurotransmitter systems involved include norepinephrine, GABA, glutamate, opioids, and the hypothalamic-pituitary-adrenal stress response. Neuroimaging implicates the prefrontal cortex and striatum.

2. Biology of impulse Control
Disorders
Prof. Hani Hamed Dessoki, M.D.Psychiatry
Acting Dean, Faculty of Applied Mental Health sciences
Beni Suef University
Prof. Psychiatry
Chairman of Psychiatry Department
Beni Suef University
Supervisor of Psychiatry Department
El-Fayoum University
APA member

3. Definition
• Formal impulse control disorders (ICDs) for which there
are diagnostic criteria in the Diagnostic and Statistical
Manual (DSM-IV-TR) include pathological gambling
(PG), kleptomania, pyromania, intermittent explosive
disorder, trichotillomania and ICD not otherwise
specified
• Criteria for other ICDs (compulsive shopping,
problematic internet use, compulsive sexual behavior,
and compulsive skin picking) have been proposed and
are currently under consideration.

4. • ICDs have been hypothesized to lie along an
impulsive-compulsive spectrum, representing
obsessive-compulsive (OC) spectrum disorders.
• Although individuals with ICDs engage in
repetitive behaviors, often with strong associated
urges, beegosyntonichaviors are often related as
pleasurable or, whereas repetitive behaviors or
rituals in OC disorder (OCD) are generally
egodystonic .

5. • Individuals with ICDs typically score high on
measures of impulsivity and related constructs
like sensation-seeking whereas individuals
with OCD typically score high on measures of
harm avoidance.

6. biology
• Dysfunction of the striatum may prove to be
the link between OCD, ICD.
• According to research, the ‘impulsiveness’
that occurs in the later stages of OCD is
caused by progressive dysfunction of the
ventral striatal circuit.
• Whereas in case of ICD, the increased
dysfunction of dorsal striatal circuit increases
the "ICD behaviours that are driven by the
compulsive processes"

7. • Diagnostic criteria for ICDs like PG overlap with
those for substance dependence, with specific
criteria relating to tolerance, withdrawal,
repeated unsuccessful attempts to cut back or
quit, and interference in major areas of life
functioning .
• There are multiple neurobiological and genetic
similarities between ICDs and substance
addictions. Thus, ICDs may be considered
“behavioral addictions.

9. Serotonin
• 5-HT is one of the most widely-implicated
neurotransmitter systems in ICDs and, in
particular, in PG.
• 5-HT is involved in the regulation of mood states,
sleep, and appetitive behaviors.
• Reduced 5-HT neurotransmission has been
associated with increased impulsivity in humans
and animal models.

10. • A role for 5-HT in PG and ICDs is supported
from results of pharmacological challenge
studies that suggest decreased 5-HT synaptic
activity in PG, postsynaptic 5-HT receptor
hypersensitivity and reduced 5-HT availability,
and decreased platelet monoamine oxidase B
(MAO-B) activity in PG.

11. • Low levels of the 5-HT metabolite 5-
hydroxyindolacetic acid (5-HIAA) have been found
in individuals with impulsive characteristics and
early-onset alcoholism.
• Metachlorophenylpiperazine (m-CPP), a
metabolite of trazodone acts as a partial agonist
and has high affinity for 5-HT receptors
(especially 5-HT2c, which has been implicated in
the mediation of aspects of mood, anxiety
behavior and neuroendocrine function.

12. • In addition to pharmacological challenges, genetic
studies have implicated the 5-HT system in both
impulsivity and ICDs. A TPH1 (tryptophan hydroxylase
1, which encodes the enzyme for the rate-limiting step
in 5-HT production) gene.
• A polymorphism in the promoter region of the human
serotonin transporter gene (SLC6A4) encoding short
and long forms of the protein (with the short variant
producing functionally less protein) has been
associated with several dimensions of
psychopathology, including neuroticism, anxiety and
depression.

13. • In a randomized study of citalopram vs.
placebo in 28 homosexual men with
compulsive sexual behaviors, no differences
were seen in measures of compulsive sexual
behaviors between groups after 12 weeks of
therapy, although there was a significant
decrease in sexual drive related to active drug.

14. • A case report suggested efficacy of
escitalopram, and SSRI in the treatment of
problematic internet use, but further studies
need to be conducted regarding efficacy in
treatment (and diagnosis) of this disorder.

15. Dopamine, Impulsivity and ICDs
• Dopamine is relevant early in the addiction
process as well as in later aspects.
• Dopaminergic systems have been implicated in
impulsivity and ICDs.
• Psychostimulants such as amphetamine influence
dopamine and other biogenic systems and are
effective therapies for attention deficit
hyperactivity disorder (ADHD), a disorder that has
impulsivity as a central feature.

16. • DA may mediate rewarding or reinforcing
aspects of gambling, and DA has been
implicated in PG.
• Decreased levels of DA and increased levels of
it metabolites 3,4-dihydroxyphenylacetic acid
(DOPAC) and homovanillic acid (HVA) have
been found in the CSF of pathological
gamblers.

17. • Genetic studies have linked several genes to
impulsivity and addiction, including genes
encoding the DA D4 receptor (DRD4) and DA
transporter (SLC6A3).
• ADHD is highly heritable.

18. • A mechanism of addiction has been proposed
that is driven by diminished DA involving
multiple genes and environmental stimuli,
termed the "Reward Deficiency Syndrome",
and places vulnerable individuals at high risk
for addictive, impulsive, and compulsive
behaviors.

19. • A subset of dopaminergic neurons project
directly from the ventral tegmental area (VTA)
to the nucleus accumbens (NAc) via the
medial forebrain bundle.
• These neurons appear crucial for reward
reinforcement because interruptions in DA
impulse trafficking, along axonal routes or at
the receptor level, decrease the reward
valence of VTA DA-stimulation.

20. • It has been hypothesized that discrete areas of
frontal cortex (implicated in impulse control)
are divided into functionally "dissociable
areas"; for example, the ventral and dorsal
pre-frontal regions representing distinct
neuroanatomical substrates of impulsive
behavior with differentially regulated
monoamine neurotransmission.

21. Dopaminergic Regulation and ICDs: Roles for γ-
aminobutyric acid (GABA) and Glutamate
• γ-aminobutyric acid (GABA) is the main
inhibitory neurotransmitter in the brain.
• There is evidence of anatomic and functional
connectivity between GABA and dopaminergic
systems as well as increasing support for
effects of modulation of GABAergic systems
on substance use disorders.

22. • For example, tiagabine, a GABA reuptake
inhibitor used primarily to treat seizures, has
shown preliminary efficacy in cocaine
addiction.
• Glutamate, an excitatory neurotransmitter
and precursor of GABA has also been
implicated in addictions as well as ICDs.

23. Norepinephrine
• Norepinephrine (NE) is involved in cognitive
processes, particularly with regard to attention
and arousal, and has been implicated in PG.
• Central noradrenergic activity is increased in PG.
• Other findings suggest that the noradrenergic
system mediates selective attention in PG and is
related to heightened arousal, readiness for
gambling or risk-taking.

24. Monoamine oxidase activity
• The MAOs, subtypes MAO-A and MAO-B, are
enzymes that metabolize NE, 5-HT, and DA.
• Peripheral MAO derived from platelets is of the
MAO B subtype and has been suggested to be an
indicator of 5-HT function,1although MAO B also
binds with high affinity to and catabolizes DA.
• Decreased platelet MAO activity has been
reported in association with impulsive behaviors,
high levels of sensation-seeking, and other
disorders characterized by impaired impulse
control, including PG and eating disorders.

25. Opioidergic pathways
• Data suggest an important role for endogenous
opioids in mediating hedonia and for µ-opioid
receptors (mORs) in the mediation of reward and
reinforcement.
• Particularly relevant is opioidergic influence of
DA pathways via disinhibition of g-aminobutyric
acid (GABA) input to DA neurons in the VTA.
‫ا‬ ‫م‬ ‫العيان‬

26. • Opioidergic involvement in PG is supported by
clinical studies demonstrating the efficacy of
the opioid antagonists naltrexone and
nalmefene in the treatment of ICDs.

27. Stress response systems
• Cortisol, adrenergic, and heart rate measures
represent key components of stress
responses. Stress responsiveness has been
implicated in ICDs and other disorders
characterized by impaired impulse control.
• Urinary epinephrine and cortisol hormone
output was approximately two-fold higher in
individuals during gambling.

28. • Positive correlations were found between
gambling outcomes and NE plasma
concentrations.

29. Neuroimaging
• Relatively few brain imaging studies of ICDs
have been performed to date, and existing
studies have focused on PG. These studies
suggest similarities and differences between
PG and other psychiatric disorders.

30. • During the period of videotape viewing
corresponding to the most intense gambling
cues, individuals with PG showed relatively
diminished activation in the ventromedial
(VM)PFC, a brain region previously implicated
in disadvantageous decision-making and
disorders characterized by impaired impulse
control (for example, impulsive aggression).

31. • As compared with control subjects, those with PG
demonstrated greater deactivation of the VMPFC,
resulting in a between-group difference in left
VMPFC.
• A similar region of left VMPFC was found to
distinguish subjects with bipolar disorder from
those without during the performance of the
same fMRI task.
• These findings suggest a common neurocircuitry
underlying impaired impulse control across
diagnostic boundaries.

32. Conclusions and Future Directions
• Emerging data on the neurobiology of impulsivity
and ICDs suggest parallels with drug addictions.
• Although many fewer studies have investigated
ICDs than have drug addictions (and most existing
studies have investigated PG), genetic, behavioral
and treatment data implicate multiple
neurotransmitter systems and neuronal circuits in
the establishment and maintenance of behavioral
addictions.

33. • Despite these advances, controversy remains
regarding the nosology and underlying
pathophysiology of specific ICDs.
• For example, impulsivity, differential
endocrine responses to stress, or components
may represent important endophenotypes for
PG, other ICDs and substance addictions.

34. • Endophenotypes provide insight into the etiology
of disorders and such information can inform the
categorizations of disorders.
• Endophenotypic views of psychiatric disorders
like depression and schizophrenia are emerging.
• Endophenotypes are “measurable components
unseen by the unaided eye” and may be
neuropsychological, endocrinological, cognitive,
neuroanatomical or biochemical in nature.

35. • Multiple neurotransmitter systems have been
similarly implicated in ICDs and substance use
disorders.
• Further research is needed to understand the
molecular and biochemical factors underlying
the behavioral features seen in PG and other
ICDs.

37. Biology of Impulsivity and Addiction
• Emerging views of addiction involve a drug or behavior
acquiring saliency via reinforcement, with subsequent
transitions through reward-based learning processes
into habitual/compulsive levels of engagement.
• Appetitive conditioning is an important consideration
in the early stages of the addiction process.
• Appetitive conditioning, defined as “the process
through which new rewards are learned and acquire
their motivational salience,” includes conditioned
environmental stimuli that are closely associated in
time with addictive processes.

38. Several neuroanatomical structures important
in this conditioning process include the
amygdala, the anterior cingulate cortex (ACC)
and the orbitofrontal cortex (OFC).

39. Additional structures that are important in this
process include the hippocampus, which
provides contextual memory relevant to
motivational stimuli, and hypothalamic and
septal nuclei, which provide information
relevant to primitive motivational behaviors
such as sexual drives and nutrient ingestion.

40. • Also important in conditioning and addiction
is the nucleus accumbens (NAcc), which is
comprised of a shell and a core. The shell, via
reciprocal innervation with the ventral
tegmental area, is important in modulating
motivational salience, whereas the core is
more involved with expression of learned
behaviors in response to stimuli that predict
motivationally relevant events/conditioned
reinforcement.

41. • The ventral tegmental area (VTA), with its
dopaminergic projections to the amygdala,
NAcc and prefrontal cortex (PFC, which
includes the OFC and ACC), facilitates learned
associations with motivationally salient
events.

42. • Dopaminergic neurons are inhibited, likely via the
dorsal medial thalamus (habenula), when
expected rewards do not occur.
• It has been proposed that in the latter stages of
addiction, predominant influence over behavioral
drive transitions from corticostriatal circuits that
involve the ventral striatum to circuits that
involve the dorsal striatum, which has long been
implicated in habit formation.