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The Neuropathology and Treatment of Obsessive-Compulsive Disorder (OCD)
Anderson C, Forbes NC, Moy L, Reiter S, Rey de Castro NG & Verghese A.
Ruminations
 Patients argue and contradict
themselves, often struggling to make
simple decisions.
Neuropathology
Lay Abstract
OCD is a mental illness with a devastating
impact on the lives of sufferers and their
families. People with OCD often have
unwanted thoughts and try to control these
with ritualistic behaviour(s). The cause of
OCD is not completely clear. However,
researchers have discovered that some
parts of the brain work to control the way
we think and act, and in OCD these may
communicate differently with each other.
Some patients with OCD get better when
they are given anti-depressants or special
therapy to help them change their
unwanted thoughts and behaviours.
 Patients with OCD have deficits in cognitive flexibility and response inhibition, suggesting that OCD is caused by abnormal function of
the cortico-striatal-thalamic circuitry known to be involved in the inhibition of both motor and cognitive responses.
 In OCD there is disruption of communication between three regions: Orbitofrontal Cortex (OFC), Caudate nucleus and Anterior
Cingulate Cortex (ACC).
 PET scanning shows that glucose metabolism in the OCD circuit is hyperactive and symptoms are relieved by surgical disconnections of
the circuit.
Perfectionism
 Objects positioned in certain orders
 Strict daily schedules.
Obsessions
Hoarding
Patients feel that nothing can be thrown
away.
Compulsions
Caudate nucleus and basal ganglia
 The caudate nucleus is a component of the basal ganglia, whose main function is to regulate wanted and unwanted movements or
cognitive processes.
 The caudate nucleus inhibits the thalamus to prevent over-excitation of the cortex.
 Dysfunction of this area correlates to symptoms of repetitive obsessions and compulsions.
Evidence:
 The caudate nucleus has been show to have a smaller volume and a reduced function in patients with OCD 5. The thalamus is disinhibited,
leading to over-activity of the cortex.
Thought processes to correct an
obsession
 Prayer.
 Counting.
Avoidance
Perceived as ways to prevent bad things from
happening:
 Touching objects a number of times.
 Avoiding travel to certain places.
“
”
Introduction
 Part of the limbic system
controlling emotion, motivation
and modulation of behaviour 7.
Its involvement may explain the
motivation for the obsessive
behaviours of OCD.
The application of learned ritualistic and
superstitious rules in an inappropriate context
distinguishes OCD from normal rule-driven
behaviour acquired during infancy.
Neurotransmitters
 Compulsions:
Repetitive
and
behaviours driven by internal rules.
or
identifiable
Epidemiology
 Patients are typically diagnosed in early adulthood
but symptoms are thought to begin in childhood or
adolescence.
 3% of the general population and 0.25% of 5-15
year olds are affected2.
 OCD is a genetically heterogeneous disorder and
exhibits
concordance
rates
of
67.5%
(monozygotic) and 31% (dizygotic), respectively3.
5-HT re-uptake transporter
Orbitofrontal Cortex
Symptoms worsen under stress and behavioural
routines are used to relieve internal or external
stress.
 Obsessions: Unwanted images, thoughts
impulses that continually enter the mind.
Pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs)
SSRIs are the first choice of pharmacological treatment as they are safer in overdose and have less severe adverse effects than the tricyclic
antidepressant (TCA), Clomipramine.
 Patients under 18 years of age taking SSRIs should be closely monitored due to the associated suicidal impulses and self- harm.
 Termination of treatment with SSRIs frequently results in a relapse of the condition.
 SSRIs in use: Fluoxetine, Fluvoxamine, Paroxetine, Sertraline or Citalopram.
When SSRIs are ineffective:
Clomipramine can be used. Adverse effects include urinary retention and constipation, blurred vision and a dry mouth.
 Involved in higher functioning
processes, particularly the
reward circuits of facilitated
learning5.
 An overactive OFC results in
over-evaluation of the
consequences of a decision,
leading to uncontrolled thoughts
(obsessions) and behaviours
(compulsions) 5.
OCD is a serious, multifactoral mental illness with
two characteristic components:
Rituals
 Hand washing.
 Arranging objects.
 Checking body for
contamination.
Treatment
Anterior Cingulate Cortex
Life is painful. Life is not
enjoyable for me...it
frightens me1
Unpleasant thoughts
 Anxiety about
contamination or dirtiness.
 Doubts about causing
accidents or partners being
unfaithful.
 Worries about security such
as unlocked windows.
SSRI
Pre-synaptic knob
PostSynaptic
neuron
Psychological treatment
Cognitive Behavioural Therapy
(CBT) with Exposure and Response Prevention
(ERP) is the only psychological treatment
recommended by NICE11.
CBT:
The
patient
is
encouraged to analyse and then alter the way
they think about a problem in order to prevent
or change their resulting problematic behaviour.
ERP: Exposure to a trigger of
fear while monitoring anxiety levels. The
patient must not respond and should notice their
anxiety subside even though their usual ritual
has not been performed.
Fig 1: Key areas of the brain and serotinergic pathways involved in OCD9.
 In OCD there are changes in the levels of relevant neurotransmitters.
 Increased 5-Hydroxytryptamine and decreased dopamine and glutamate levels are found in patients with OCD.
Evidence:
 5-Hydroxytryptamine (Serotonin): SSRI treatment has a beneficial effect5.
 Dopamine: similarities of symptoms between OCD and other neuropathologies such as Parkinson's, Tourette's syndrome and Sydenhams
chorea6,7.
 Glutamate: treatment with just serotonin and dopamine is insufficient and cortical projections to basal ganglia are hyper-excitable8.
5-HT
Synaptic Cleft
5-HT receptor
Fig 2: SSRIs work by inhibiting 5-Hydroxytryptamine (5-HT) re-uptake into the presynaptic knob at
synapses, resulting in a higher 5-HT concentration in the synaptic cleft and stimulation of the postsynaptic
nerve cell.
Treatment time-line11
1. Initial treatment: 12 week course of an SSRI or 10 hours of CBT with ERP.
2. If unsuccessful: Combined CBT with ERP and a course of an SSRI.
3. If unsuccessful: Clomipramine or a course of a different SSRI.
4. If unsuccessful: Refer the patient to a multidisciplinary team.
Deep brain stimulation (DBS): a novel
treatment
 DBS is being researched as a possible
treatment for extreme cases of OCD.
 A recent study placed an electrode in the
ventral anterior limb of the internal capsule
next to the ventral striatum and found a 35%
improvement in the initial severity rating in
4 out of 6 patients receiving stimulation over
12 months12.
Psychological Models
Could you have OCD?
OCD has a social impact on sufferers and their families, leading to limits being placed on life choices. Sufferers may interpret social interaction with
others differently, with particular deficits in Theory of Mind. Fear of disclosure is a central factor in maintaining the problem, and prevents sufferers
seeking help. Help-seeking delay is estimated at 11 years on average10.
References
1. Olson T, Vera B & Perez O. From Primetime to Paradise: The Lived Experience of OCD in Hawaii. Fam Community Health 2007 30(2S): S59-S70.
1.
2.
3.
4.
5.
Do you wash or clean a lot?
Do you check things a lot?
Is there any thought that keeps
bothering you and that you'd like to
get rid of but can't?
Do your daily activities take a long
time to finish?
Are you concerned about symmetry
and orderliness?
Questions from the Zohar-Fineberg
Obsessive-Compulsive screen4
Individuals with OCD display:
Impulsivity
Inflexibility
Disinhibition
Sufferers may conceal their thoughts and behaviours:
Fear of arrest or imprisonment
Shame (at lack of control)
Belief that telling someone might make the dreaded event occur.
Low level of understanding and empathy in healthcare professionals
Sufferers and relatives feel misunderstood and alone.
Patients access support and treatment too late.
Restricted social functioning

Symptoms remain concealed

Relatives become complicit by
participating in disease-related
behaviours.

If symptoms are revealed,
family members are stigmatised
by virtue of courtesy stigma.

Family dependency maintains
and exacerbates disease.
2. Barton R & Heyman I. Obsessive-compulsive disorder in children and adolescents. Paediatr Child Health 2009 19(2) 67-72.
3. Mercadante MT, Rosario-Campos MC, Quarantini LC & Sato FP. The neurological bases of obsessive-compulsive disorder and Tourette syndrome. J
Pediatr (Rio J) 2004 80(Suppl No.2): S35-S44.
4. National Collaborating Centre for Mental Health (NCCMH). Obsessive-Compulsive disorder: Core interventions in the treatment of obsessive-compulsive
disorder
and
body
dysmorphic
disorder.
Royal
College
of
Psychiatrists
and
British
Psychological
society,
2006.
(www.rcpsych.ac.uk/files/samplechapter/ocdsc.pdf)
5. Simonds LM & Thorpe SJ. Attitudes toward obsessive-compulsive disorders. Soc Psychiatry Psychiatr Epidemiol 2003 38: 331-336.
6. Grisham JR, Henry JD, Williams AD & Bailey PB. Socioemotional deficits associated with obsessive-compulsive symptomatology. Psychiatry Res 2010
175(3): 256-259.
7. Britton JC, Rauch SL, Rosso IM, Killgore WD, Price LM, Ragan J, Chosak A, Hezel DM, Pine DS, Leibenluft E, Pauls DL, Jenike MA & Stewart SE.
Cognitive inflexibility and frontal-cortical activation in pediatric obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2010 49(9):944-53.
8. Insel TR. Toward a neuroanatomy of obsessive-compulsive disorder. Arch Gen Psychiatry 1992 49(9): 739-744.
9. Stein DJ. Obsessive-compulsive disorder. The Lancet 2002 360(9330):397-405.
10. Simonds LM & Thorpe SJ. Attitudes toward obsessive-compulsive disorders. Soc Psychiatry Psychiatr Epidemiol 2003 38: 331-336.
11. NICE. Obsessive-Compulsive Disorder: Core interventions in the treatment of Obsessive-Compulsive disorder and body dysmorphic disorder. Clinical
Guidelines 31, 2005. (http://www.nice.org.uk/nicemedia/live/10976/29945/29945.pdf)
12. Goodman WK, Foote KD, Greenberg BD, Ricciuti N, Bauer R, Ward H, Shapira NA, Wu SS, Hill CL, Rasmussen SA & Okun MS. Deep brain stimulation
for intractable obsessive compulsive disorder: pilot study using a blinded, staggered-onset design. Biol Psychiatry 2010 67(6):535-42.
Conclusion
OCD is a restrictive and complex condition. Sufferers exhibit
a myriad of symptoms, some of which can be commonly
grouped together. We have examined current theories of
pathology but the condition remains largely elusive.
Treatment techniques tackle the mind/body split by
encouraging patients to recognise the senselessness of their
obsessions and compulsions. Pharmacological management
highlights the important role of serotonin in correcting
dysfunctional circuitry of the brain. Treatment reduces
anxiety associated with the condition. It is possible for
patients to greatly improve their quality of life by engaging in
focussed cognitive behavioural therapy. The condition,
although described in general here, is a very personal
affliction and adherence to treatment is a key player in
predicting outcome.
Faculty of Life Sciences