DOC e alterazioni immunitarie

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Donatella Marazziti, M. D.
Dipartimento di Psichiatria, Neurobiologia,
Farmacologia e Biotecnologie University of
Pisa, Italy
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Are normal and pathological OCD on a continuum?
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OCD-spectrum constructs

• 1. Dimensions
• 2. Symptom clusters
• 3. Neurobiology
• - Striatal topography model
• - Neuroanatomy
• - Neurogenetics
• - Neuroimmunology
• - Neurochemistry
• 4. Response to treatments

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Obsessive-Compulsive Disorder Spectrum
Preoccupations With Bodily Sensations Or
Appearance

• Body dysmorphic disorder
• Depersonalization
• Anorexia nervosa
• Hypochondrias

Neurologic Disorders

• Tourettes syndrome
• Sydenhams chorea
• Torticolis
• Autism

OCD
Impulsive Disorders

• Sexual compulsions
• Tricholillomania
• Pathological gambling
• Kleptomania
• Self-injurious behavior

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• 1. The cognitive-motoric dimension

Motoric
Cognitive
HYP
BorderlinePD
Trich
BDD
DEP
ChildhoodOCD
Pure obsessions
Hollander,
OCD-Related Disorders
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• 1. The certainty-uncertainty dimension

certainty
uncertainty
BDD delusion
OCD with delusion
SC with obsession
Overvalued ideas
BDD
OCD With uncertainty
Risk avoidance
Risk seeking
Hollander,
OCD-Related Disorders
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• 1. Dimensional aspects of the OCD Spectrum
  Disorders

Impulsive
Compulsive
BorderlinePD
SexualComp
PG
Trich
TS
DEP
AN
BDD
HYP
OCD
Hostile to risks Harm avoidance
Finding forRisks Risk Seeking
Hollander,
OCD-Related Disorders
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Obsessions

• - Contamination
• - Fear of harming
• - Doubting
• - Symmetry
• - Somatic

- Sexual - Hoarding - Religious
American Psychiatric Association. Diagnostic and
Statistical Manual of Mental Disorders, Fourth
Edition. 1994.
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Compulsions

• Checking
• Cleaning/washing
• Repeating
• Mental compulsions

Ordering Hoarding/collecting Touching Reassurance
seeking
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Obsessionality

• Obsessionality is a normal dimension with a
  profound adaptive significance which is
  represented by the maintainance of the focus on a
  specific task
• Without obsessionality, nobody could finish an
  activity, with no importance on how simple or
  complex it might be.

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Obsessionality/Compulsivity

• The border between adaptive and maladaptive
  can be set according to the classical criteria
  of
• . Persistence . Intrusivity
• . Egosynthonia . Sense of reality
• . Resistance . Appropriateness
• . Time spent . Awareness of
• . Recurrence provenience

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Dimensions
Certainty
Uncertainty
Insight
No Insight
Of the self
General Certainty/Uncertainty
Of the partner
Of the body
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General uncertainty/certainty
certainty
paranoia
overvalued idea
OCD
uncertainty
no insight
insight
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As a whole
of the body
Specific
Of parts of it
certainty
somatic delusion
dysmorphophobia (or hypocondriasis)
normal preoccupation for the body health
uncertainty
no insight
insight
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Specific uncertainty/certainty of the self
interpersonal/ rejection sensitivity
certainty
social phobia
shyness
uncertainty
no insight
insight
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Obsessionality

• In specific periods of the life, however, it
  seems to be quite adaptive to have a frankly
  pathological obsessionality which transversally
  might be judged maladaptive
• Romantic love
• Maternale love
• Infant attachment

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Obsessionality

• In all these conditions, the brain puts into
  questions its equilibrium, decides to cross the
  border and pass into the pathological side in
  order to
• - ensure the likehood of the relationship
• maintain the partners together
• oblige parents to take care of the children and
  viceversa

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Obsessionality

• Obviously, there is a cost to pay..
• a greater risk of developing the full-blown
  disorder

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Aim of the study

• Measurement of 3H-paroxetine binding in platelets
  of 20 patients with OCD-related disorders, as
  compared with 20 patients with OCD and 20 healthy
  subjects

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Characteristics of the patients with OCD-related
disorders

• 6 (4 M2 F, mean age 257) BDD
• 5 (4 M 1 F, mean age 254) ICD
• 5 (2 M3 F, mean age 243) KLEP
• 3 (M, mean age 156) TS
• 1 (M, 15) TRYC
• CBDS total score 234

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Characteristics of the OCD patients

• 20 (10 M, 10 F, mean age 296)
• Y-BOCS total score 193

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3H-paroxetine binding in patients with OCD and
OCD-related disorders

• Bmax Kd
• OCD 736257 0.160.0
• OCD-R 617214 0.130.07
• HC 1767601 0.110.04
• Significant F-test 16.54, p0.0001

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Aim of the study

• Measurement of 3H-paroxetine binding in platelets
  of 20 romantic lovers, 20 OCD patients and 20
  healthy subjects

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3H paroxetine binding parameters in romantic
lovers, OCD patients and controls

• Bmax Kd
• Lovers 625219 0.240.27
• OCD 736457 0.160.18
• Controls 1324486 0.170.28

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3H paroxetine binding parameters after 12/18
months from the beginning of the relationship (n.
6 subjects)

• Bmax Kd
• 1214367 0.210.19

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3H-Paroxetine binding parameters (meanSD) in
normal, jealous subjects and patients Bmax
Kd Normal subjects 1499 0.02 583 0
.01 Jealous Subjects 869 0.01 253 0.01
Patients 874 0.01 330 0.02
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• Romantic lovers and jealous subjects share a
  common dysfunction with OCD and OCDr patients at
  the level of the 5-HT transporter

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Altered Serotonin Transporter

• Mood disorders
• Anxiety disorders
• Eating disorders
• Schizophrenia
• Aggressive behaviors

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Neurocircuitry Of OCD
1 Block From SSRI Or BT
Cd
Neurosurgery
()
(-)
Gp
Orb
Relevant Output To Other Brain Regions
()
(-)
()
2 Block
()
Thalamus
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Activated regions
Romantic love (n17)
.
Maternal love (n19)
.
Bartels Zeki (2000 / 2004)
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Love A core network of regions involved

• Anterior cingulate cortex
• Cognitive interface to limbic system
• Insula
• Sensory interface to limbic system
• Striatum
• - reward

Bartels Zeki (2000 / 2004)
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Oxytocin and vasopressin receptor-rich
sites (Loup et al., 1991)
Romantic love (n17)
.
Maternal love (n19)
.
Bartels Zeki (2000 / 2004)
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Differences population comparison
Romantic - Maternal
Conclusion -Core set of regions activated with
both maternal and romantic love -these involve
nearly all regions rich in oxytocin/vasopressin
receptors -there are few but important
attachment-specific differences.
Maternal - Romantic
Visual face-processing regions (FFA)
Bartels Zeki (2000 / 2004)
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Love de-activated / suppressed regions

• A correlate to facets known from animal
  behaviour?
• Inhibition of aggression
• Inhibition of avoidance behaviour
• Inhibition of Theory of mind related regions!

Bartels Zeki (2000 / 2004)