Etiopathogenesis of obsessive compulsive disorder [autosaved]

By-Sadaf Siddiqui
Moderator-Prof.S.A.Azmi
Etiopathogenesis of Obsessive
Compulsive Disorder

Introduction
It is defined as occurring of unwanted and intrusive
thoughts or distressing images which
are accompanied by compulsive behaviors to
neutralize the obsessive thoughts.

 Up to 1980 considered a treatment resistant chronic
condition of psychological origin.
 The observation that CLOMIPRAMINE (a TCA with
serotogenic profile) is effective was a major breakthrough.

HISTORY
 Prehistoric times-possessed by devil and exorcism as
treatment.
 Obsessions and hand-washing rituals resulting from guilt
were immortalized in the 17th century in Shakespeare's
character, Lady Macbeth.
 With time, the explanation of obsessions and compulsions
moved from a religious view to a medical one.

 OCD was first described in the psychiatric literature by
Esquirol in 1838, and by the end of the 19th century, it was
generally regarded as a manifestation of melancholy or
depression.
 By the beginning of the 20th century, theories of
obsessive-compulsive neurosis shifted towards
psychological explanations.

 Pierre Janet reported successful treatment of rituals with
behavioral techniques; but with Sigmund Freud's writings
on psychoanalysis of the Rat Man, OCD came to be
conceptualized as resulting from unconscious conflicts and
from the isolation of thoughts and behaviors from their
emotional antecedents.
 With the rise of behavior therapy in the 1950s, learning
theories which had proved useful in dealing with phobias
were applied to OCD.

Different theories led to different treatment
 Phlebotomy.
 Laxative and purgatives.
 Henry Maudsley (1895) - opium and morphine, to be taken
three times a day,
 Adding low doses of arsenic along with these narcotics
could be helpful.

 As the twenty-first century begins, advances in
pharmacology, neuroanatomy, neurophysiology and
learning theory have allowed us to reach a more
therapeutically useful conceptualization of OCD.

EPIDEMIOLOGY
 Once believed to be rare, OCD was found to have a lifetime
prevalence of 2.5% in the Epidemiological Catchment Area
study.[1]
 Lifetime prevalence are generally in the range of 1.7-4%.
 The incidence of OCD is higher in dermatology patients
and cosmetic surgery patients
1.Karno M, Golding JM, Sorenson SB, Burnam MA. The epidemiology of obsessive-compulsive disorder in
five US communities. Arch Gen Psychiatry. Dec 1988;45(12):1094-9.

 Equal across sex and culture.
 Prevalence among adult and children same
 67% have MADD ,25% have social phobias.
 25% chronic schizophrenic have OCD symptoms.(poor
prognosis).
 British Epidemiology found a gender ratio of 1.4 to 1
(women to men).
Torres et al., 2006

 Other co-morbid- panic disorder ,eating disorder ,alcohol
use disorder.
 Relationship with OCPD is debatable.(OCPD) is not a
prominent risk factor for developing OCD

CLINICAL FEATURES
 Characterized by obsession, compulsion or both(75%)
 Obsessional thoughts are- ideas, images or impulses that
enter the individual's mind again & again in a stereotyped
form.
 Are invariably distressing ( they are violent or obscene, or
simply because they are perceived as senseless) .
 The sufferer often tries, unsuccessfully, to resist them.

 Are, recognized as the individual's own thoughts, even
though they are involuntary and often repugnant
 Compulsive acts are stereotyped behaviors that are
repeated again and again.
 Are not inherently enjoyable, nor do they result in the
completion of inherently useful tasks

 Individual often views them as preventing some
objectively unlikely event ,often involving harm to or
caused by himself or herself.
 Usually, this behaviour is recognized by the individual as
pointless or ineffectual and repeated attempts are made
to resist it;( in very long-standing cases, resistance may be
minimal).

 It was classified as anxiety disorder in DSM-4.
BUT
The DSM-5 chapter on anxiety disorder no longer includes
obsessive-compulsive disorder (which is included with the
obsessive-compulsive and related disorders).

 This is also reflected in the ICD 10 classification which lists
OCD as a separate entity from anxiety disorder .
Sims textbook of psychopathology states that:
“Certainly OCD is not an anxiety disorder. Isolated obsession
or obsessive compulsive disorder may occur with or
without anxiety, with or without depression and with or
without personality disorder .It is a distinct and separate
phenomenon”

ETIOLOGY
CAUSAL
FACTORS
Psychosocial
Causal
factors
Cognitive
Causal
factors
Biological
Causal
factors
Behavioral
factors

NEUROTRANSMITTERS
SEROTONIN
 Dysregulation of serotogenic system
 Measurng the level of 5HIAA( a measure of serotonic turn
over) in CSF
 Affinities of platelet serotonin binding sites to radiolabled
imipramine which binds to serotonin reuptake site and
reported variable finding of these measures in OCD.

 Some study - decreased level of 5HIAA after treatment
with clomipramine and normalization of platelet
transporter after treatment with clomipramine.
 Although research suggests that alteration of brain
serotonergic systems may be one mechanism through
which SSRIs have their therapeutic effects, there is no
evidence of baseline serotonergic dysfunction in OCD
patients.

DOPAMINE
 Some forms of OCD are etiologic related to TS. TS appears
to be predominantly dopaminergically mediated, as
evidenced by the well-documented clinical response to
haloperidol and other dopamine antagonists.
 OCD patients with comorbid tic disorder or TS are usually
resistant to conventional pharmacotherapy with
proserotonergic compounds, and may benefit from
adjuvant treatment with dopamine (DA) or DA/5-HT
blockers .

 This suggests that there is an involvement of DA in at least
some OCD patients.
 The serotonin and dopamine systems interact extensively,
particularly in the basal ganglia, an area that has been
implicated in the pathogenesis of obsessive-compulsive
phenomenology by several studies.

GLUTAMATE
 Attention has also been focused on glutamatergic
abnormalities and possible glutamatergic treatments for
OCD.[1,2]
 Although modulated by serotonin and other
neurotransmitters, the synapses in the cortico-striato-
thalamo-cortical circuits thought to be centrally involved in
the pathology of OCD principally employ the
neurotransmitters glutamate and gamma-aminobutyric
acid (GABA)
Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of
obsessive-compulsive disorder. NeuroRx.
Wu K, Hanna GL, Rosenberg DR, Arnold PD. The role of glutamate signaling in the pathogenesis and treatment of
obsessive-compulsive disorder. Pharmacol Biochem Behav.

 CSF glutamate concentration was significantly greater in
OCD patients as compared with control subjects
 Indeed, glutamate and serotonin interact on a number of
levels in the frontal striatal circuit.
 However, the persistence of symptoms despite targeting
serotonin and glutamate pharmacologically indicates
limits of the serotonin and glutamate hypothesis of OCD.

 Clearly, a solitary neurochemical hypothesis of a psychiatric
disorder is limited, as neurotransmitters do not operate in
a vacuum.

COPPER AND OCD
 Elevated copper and corresponding changes in dopamine
may result in increased number or sensitivity of post-
synaptic dopamine receptors in certain areas of the brain.
 Association between ceruloplasmin and OCD might be
examined through ceruloplasmin and copper relationship,
since there is now growing evidence that the dopamine
system may be involved also in the pathophysiology of
OCD

 However, association between ceruloplasmin and OCD
may be explained via copper and serotonin relationship,
too.
High ceruloplasmin levels are associated with obsessive compulsive disorder:
a case control study,Behav Brain Funct. 2008; 4: 52

THE AUTOIMMUNE HYPOTHESIS
 Allen, Leonard, and Swedo first proposed the intriguing
autoimmune hypothesis of OCD after a thoughtful review
of the literature.
 An association was drawn between infection with group A
-hemolytic Streptococcus (as well as other agents,
including viruses), and the onset or the exacerbation of
OCD in some children

 10 to 30% of patient of rheumatic fever develop
synderham’s chorea and show symptoms of ocd.
 Pediatric Autoimmune Neuropsychiatric Disorder
Associated with Streptococcus (PANDAS).
1. PANDAS form of OCD is rapid in onset.
2. Occurs in close association with a strep infection.
3. Usually have involuntary movements of the arms, legs
and face

 Fewer recent studies reports the herpes simplex virus as
the apparent precipitating infectious event.
 Increasing evidence linking streptococcal infection to OCD
in children suggests that microbiomics may prove an
important research area for understanding and treating
mental disorders.

 OCD has significant genetic component .
 Three to five times higher probability of OCD in relatives of
probands with OCD.
 Concordance for OCD in twins is significantly higher for
monozygotic twins than for dizygotic twins

 Twin studies have supported strong heritability for OCD,
with a genetic influence of 45-65% in studies in children
and 27-47% in adults.[1]
 Monozygotic twins may be strikingly concordant for OCD
(80-87%), compared with 47-50% concordance in dizygotic
twins.[2]

 Several genetic studies have supported linkages to a
variety of serotonergic, dopaminergic, and glutamatergic
genes
1.van Grootheest DS, Cath DC, Beekman AT, Boomsma DI. Twin studies on obsessive-compulsive
disorder: a review. Twin Res Hum Genet. Oct 2005;8(5):450-8.
2. Carey G, Gottesman I. Twin and family studies of anxiety, phobic, and obsessive disorders. In: Klein
DF, Rabkin JG. Anxiety: New Research and Changing Concepts. New York: Raven Press; 2000.

BRAIN IMAGING STUDIES
 Current research has gravitated toward structural and
functional neuroimaging
 These technological innovations have provided a better
understanding of the neuroanatomical risk factors of OCD

DAMAGE IN BASAL GANGLIA
 Scientists proposed that any damage to the basal ganglia
might result in the OCD symptoms.
 The significance of identifying the basal ganglia is that it
shows that physical damage to a brain structure results in a
neuropsychological (mental/emotional) condition.

CHANGES IN BRAIN ACTIVITY
 Modern brain imaging techniques have shown that people
with OCD have more than usual activity in three areas of
the brain. These are:
1. orbital frontal cortex,
2. cingulated cortex and
3. caudate nucleus of the basal ganglia

 The OFC and ACC are intricately connected to the basal
ganglia via the cortico—basal ganglia—
thalamocortical (CBGTC) loops.
 CT AND MRI have shown decreased size of caudate
nucleus bilaterally.
 PET scan has shown increased activity in the frontal lobe,
caudate nucleus, and the cingulum of patients

1.The caudate nucleus,specific brain cells in basal
ganglia
 This area of the brain acts as a filter for thoughts coming in
from other areas.
 The caudate nucleus is also considered to be important in
managing habitual and repetitive behaviors.

2.The prefrontal orbital cortex located in front area
of brain
 The level of activity in the prefrontal orbital cortex is
believed to affect appropriate social behavior.
 Lowered activity or damage in this region is linked to
feeling uninhibited, making bad judgments and feeling a
lack of guilt.
 More activity may therefore cause more worry about
social concerns

3.The cingulate gyrus in the centre of brain
 The cingulate gyrus is believed to contribute the emotional
response to obsessive thoughts. This area of the brain tells
you to perform compulsions to relieve anxiety.
 This region is highly interconnected to the prefrontal
orbital cortex and the basal ganglia via a number of brain
cell pathways

 Current theories suggests OCD the result of an imbalance
between “direct” & “indirect” pathways.
 Direct pathways run from the cortex to the striatum, then
to the GPi and SNr, then to the thalamus, and finally back
to the cortex.
 The indirect pathways are described as running from the
cortex to the striatum, then to the GPe, the STN, the GPi
and SNr, then thalamus, finally back TO cortex

 While the net effect of the direct pathway is excitatory,
the net effect of the indirect pathway is inhibitory
 OCD may result from excessive neural tone in the direct
pathway relative to the indirect pathway results in a
positive feedback loop whereby obsessive thoughts are
trapped.

 There is a broad consensus for widely distributed
abnormalities involving fronto-striatal circuits in OCD.[1]
 Moreover, reversal of orbitofrontal cortex (OFC)
dysfunction after treatment has also been reported.[2]
1. Jenike MA, Rauch SL, Cummings JL, Savage CR, Goodman WK. Recent developments in neurobiology of
obsessive-compulsive disorder. J Clin Psychiatry 1996;57:492-503.
2.Swedo SE, Pietrini P, Leonard HL, Schapiro MB, Rettew DC, Goldberger EL, et al. Cerebral glucose
metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy.
Arch Gen Psychiatry. 1992;49:690-4.

 Organic insult to these regions can produce obsessive and
compulsive symptoms.
 Results of neurosurgical treatment of OCD strongly
support this hypothesis.

 Cingulotomy- interrupts this loop at the anterior cingulate
cortex.
 Anterior capsulotomy -lesions within the anterior limb of
the internal capsules.
 subcaudate tractotomy (lesions in the substantia
innominata, just under the head of the caudate nucleus)

Ego marshalled certain defenses:
1. INTELLECTUALIZATION AND ISOLATION
2. UNDOING
3. REACTION FORMATION.
The imperfect success of these defenses gave rise to OCD
symptoms: (anxiety; preoccupation with dirt or germs or
moral questions; and, fears of acting on unacceptable
impulses.)

Psychoanalytic factor
 (Freud‘) patient's mind responded mal adaptively to
conflicts between unacceptable, unconscious sexual or
aggressive id and the demands of conscience and reality.
 It regressed to concerns with control and to modes of
thinking characteristic of the anal-sadistic stage of :
AMBIVALENCE- which produced doubting,
MAGICAL THINKING -superstitious compulsive acts

BEHAVIORAL FACTORS
 Mowrer’s two process theory of avoidance learning(1947) :
According to this theory, neutral stimuli become associated
with frightening thoughts or experience through classical
conditioning and come to elicit anxiety.
 EXAMPLE

 This model predicts, then, that exposure to feared objects
or situations should be useful in treating OCD if the
exposure is followed prevention of the rituals, enabling the
person to see that the anxiety will subside naturally in time
without the ritual.
 This indeed the cure of the most effective form of
Behavioral therapy for OCD

Classical experiment conducted by Rachman and
Hodgson
 They found that for most people with OCD, exposure to a
situation that provoked their obsession did indeed produce
distress, which would continue for a moderate amount of
time and then gradually dissipate.
Obsessive-Compulsive Disorder: Theory, Research, and Treatment edited by Richard P.
Swinson, Martin M. Antony, S. Rachman, Margaret A. Richte

Environmental factor
 A number of environmental factors may contribute to the
onset and maintenance of OCD.
 Although some research suggests no link between
negative life events and OCD, there are many reports in
which childhood OCD has been triggered by a specific,
often traumatic, event, including: the death of a loved one;
the loss of a pet; a divorce in the family; a change in school
etc.

 Furthermore, a recent study indicated that one to two
years prior to the onset of symptoms, both children and
adults who develop OCD experience more negative life
events than controls.
 Taken together, these results suggest that stress or trauma
can play a role in the development of OCD among certain
individuals.

 Injuries also have been associated with OCD.
 The results of one study, in which 80 children and
adolescents who suffered a traumatic brain injury were
examined, indicated that almost 30% of the young people
had new onset obsessive compulsive symptoms within one
year after the serious injury

 In a study, Berthier and colleagues (2001) assessed 10
referred patients who had developed OCD after TBI and
found peculiar symptoms of obsessive slowness in 3 cases
and compulsive exercise practice in 3 cases also (1 patient
had both symptoms).
 Grados states that obsessive-compulsive phenomena
following brain injury are probably more common than
generally expected,most symptoms have an early onset.(1)
1. Grados M. Obsessive-compulsive disorder after traumatic brain injury. Int Rev Psychiatry
2003;15:350-358

 Many cognitive theorists believe that individuals with OCD
have faulty or dysfunctional beliefs, and that it is their
misinterpretation of intrusive thoughts that leads to the
creation of obsessions and compulsions.
 According to the cognitive model of OCD, everyone
experiences intrusive thoughts. People with OCD,
however, misinterpret these thoughts as being very
important, personally significant, revealing about one’s
character, or having catastrophic consequences

 The Obsessive-Compulsive Cognitions Working Group, an
international group of researchers who have proposed that
the onset and maintenance of OCD are associated with
maladaptive interpretations of cognitive intrusions, has
identified six types of dysfunctional beliefs associated with
OCD:

1.Inflated sense of Responsibility
 A belief that one has the ability to cause and/or is
responsible for preventing negative outcomes;
 This sense of inflated responsibility for the harm they may
cause adds to the “perceived awe fullness of any harmful
consequences and may motivate compulsive behaviors
like washing and checking to reduce the likelihood of the
event.

2. Over importance of thoughts (also known as thought-
action fusion): the belief that having a bad thought can
influence the probability of the occurrence of a negative
event or that having a bad thought (e.g., about doing
something) is morally equivalent to actually doing it.
3. Control of thoughts: a belief that it is both essential and
possible to have total control over one’s own thoughts

4. Overestimation of threat: a belief that negative events
are very probable and that they will be particularly bad;
5. Perfectionism: a belief that one cannot make mistakes
and that imperfection is unacceptable; and
6. Intolerance for uncertainty: a belief that it is essential
and possible to know, without a doubt, that negative events
won’t happen.

 People with normal and abnormal obsessions differ
primarily in the degree to which the resist their own
thoughts.
 The factor contributing to the frequency of obsessive
thoughts and negative moods is the attempt to suppress
them.

CONCLUSION
 OCD is a chronic and delibitating condition.
 Understanding its aetiology and its pathophysiology will be
helpful in designing treatment which are directed towards
pathology.
 Brain scans of people with OCD have shown that they have
different patterns of brain activity than people without
OCD and that abnormal functioning of circuitry within a
certain part of the brain (striatum) may cause the disorder.

 Abnormalities in other parts of the brain and an imbalance
of brain chemicals, especially serotonin, may also
contribute to OCD.
 Some experts believe that a problem related to
streptococcal infections, such as streptococcal throat
infection and scarlet fever can suddenly bring on the
disorder or make its symptoms worse in some children.

 In sum, although the definitive cause or causes of OCD
have not yet been identified, research continually
produces new evidence that hopefully will lead to more
answers.
 It is likely, however, that a delicate interplay between
various risk factors over time is responsible for the onset
and maintenance of OCD.

REFERENCES
 Kaplan and saddocks synopsis of psychiatry-eleventh edition
 kaplan and sadock's comprehensive textbook of psychiatry
9th edition
 Karno M, Golding JM, Sorenson SB, Burnam MA. The epidemiology of obsessive-
compulsive disorder in five US communities. Arch Gen Psychiatry. Dec
1988;45(12):1094-9.
 Obsessive-Compulsive Disorder: Theory, Research, and Treatment edited by Richard P.
Swinson, Martin M. Antony, S. Rachman, Margaret A. Richte
 .van Grootheest DS, Cath DC, Beekman AT, Boomsma DI. Twin studies on obsessive-
compulsive disorder: a review. Twin Res Hum Genet. Oct 2005;8(5):450-8.
 Carey G, Gottesman I. Twin and family studies of anxiety, phobic, and obsessive
disorders. In: Klein DF, Rabkin JG. Anxiety: New Research and Changing Concepts. New
York: Raven Press; 2000

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