Schizophrenia, ICD, DSM, Antipsychotics

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Dr.NidhiSharma

2. CONTENT
Dr. Nidhi Sharma
23-Jun-21
 Introduction
 Epidemiology
 Classification
 Signs and symptoms
 Pathophysiology
 Diagnosis
 Complications
 Management
 Prognosis
 Clinical Research
 Landmark Studies

3. Introduction
• Schizophrenia is a serious mental illness that interferes with a person’s ability to think
clearly, manage emotions, make decisions and relate to others.
• Schizophrenia literally means “Split Mind”. (Schizein means, "to split“ and phrēn means
"mind")
• Schizophrenia is among the most disabling and economically catastrophic medical
disorders
• Earliest case of schizophrenia - James Tilly Matthews (1809)
• The first, formal description of schizophrenia as a mental illness was made in 1887 by
Dr. Emile Kraepelin.
• He used the term "dementia praecox" to describe the symptoms now known as
schizophrenia.

4. Introduction
• The term “schizophrenia” was coined on April 24, 1908, by Professor Paul Eugene Bleuler.
• He suggested that dementia praecox was associated with neither dementia nor
precociousness, and emphasized that splitting of psychic functioning is an essential
feature of schizophrenia
• In 2002, new name was given to Schizophrenia - Integration Disorder
• It refers to a person’s inability to process information about their environment, which
may cause them to experience confusion about what is imagined and what is real.

5. James Tilly Matthews
• A former peace activist of the
Napoleonic Wars who was
confined to London's
notorious Bedlam asylum in
1797 for believing that his
mind was under the control of
the "Air Loom" - a terrifying
machine whose rays and
gases were brainwashing
politicians and plunging
Europe into revolution, terror,
and war.

6. Epidemiology
• Incidence - 1.5 per 10,000 people
• Prevalence – 1%
• Age of onset: Men: Between 18 and 25
Women: Between 25 and 35
• Schizophrenia is diagnosed 1.4 times more frequently in males than females
• Schizophrenia is associated with an average of 14.5 years of potential life lost.
• The loss was greater for men (15.9) than for women (13.6).
• Life expectancy was greatly reduced in patients with schizophrenia, at 64.7 years (59.9 for men
and 67.6 for women).

7. DSM Criteria/Symptoms
Two (or more) of the following, each present
for a significant portion of time during a 1-
month period (or less if successfully treated):
Positive Symptoms
a) Delusions: A belief or altered reality that is
persistently held despite evidence or
agreement to the contrary
• Erotomanic
• Grandiose
• Persecutory
• Jealous
• Somatic

8. DSM Criteria/Symptoms
b) Hallucinations: Sensory experiences that
appear real but are created by your mind
• Visual
• Olfactory
• Gustatory
• Auditory
• Tactile
c) Disorganized speech (e.g., frequent
derailment or incoherence)
d) Grossly disorganized or catatonic behavior

9. DSM Criteria/Symptoms
e) Negative Symptoms
Affective flattening: A loss or lack of
emotional expressiveness
Alogia: Lack of speech
Avolition: Lack of motivation that
makes it hard to get anything done

10. Classification
ICD-10 Description DSM-IV
Paranoid (F20.0)
Delusions and hallucinations are present but thought
disorder, disorganized behavior, and affective flattening are
not prominent.
Paranoid (295.3)
Hebephrenic (F20.1) Thought disorder and flat affect are present together.
Disorganized
(295.1)
Catatonic (F20.2)
Psychomotor disturbances are dominant features.
Symptoms can include catatonic stupor and waxy flexibility.
Catatonic (295.2)
Undifferentiated (F20.3)
Psychotic symptoms are present but the criteria for
paranoid, disorganized, or catatonic types have not been
met.
Undifferentiated
(295.9)
Post-schizophrenic
depression (F20.4)
A depressive episode arising in the aftermath of a
schizophrenic illness where some low-level schizophrenic
symptoms may still be present.
Not present
Residual (F20.5)
Positive symptoms are present at a low intensity and
negative symptoms are prominent.
Residual (295.6)
Simple (F20.6)
Delusions and hallucinations are not evident and negative
symptoms progress slowly.
Not present

11. Phases

12. Louis Wain’s Cat Illustrations

13. Pathophysiology
• Genetics
• Physical changes in brain
• Chemical changes in brain (Neurotransmitters)
• Pregnancy or birth complications
• Childhood trauma

14. Genetics
• Chromosome no. 1, 5, 6, 8, 11, 12 & 22
• Neuregulin – 1 Protein
• Deletion of a region on chromosome 22 (22q11.2-deletion syndrome) increases the risk of
developing schizophrenia approximately 30-fold in humans.

15. Genetics
57.7
4.4
8.5 8.2
2 2.2 2.8 3.2 2.9
8.2
13.8
36.6
0.86
0
10
20
30
40
50
60
70

16. Physical changes in brain
• Enlarged ventricles.
• Schizophrenia cases exhibited progressive brain reductions mainly in the prefrontal cortex and
temporal lobes.
• Localized gray matter volume reduction of the left temporal lobe.
• The size of the volume reduction in superior temporal gyrus is related to the degree of thought
disorder and hallucination.
• In schizophrenic patients with AVH (auditory verbal hallucinations), the left middle temporal
gyrus was found significantly thinner than in patients without AVHs.
• The temporal and the occipital lobe white matter shortfall can also exacerbate the chances of
acquiring schizophrenia.

17. Chemical changes in brain
• Dopamine Hypothesis
• Serotonin Hypothesis
• Glutamate Hypothesis
• GABA Hypothesis

18. Dopamine Hypothesis
Earlier Version:
• In Schizophrenic patients, neurons that uses Dopamine, fire too often and transmit too many
messages.
Revised Version:
• Hyperactivity of dopamine D2 receptor neurotransmission in subcortical and limbic brain regions
contributes to positive symptoms of schizophrenia
• Negative and cognitive symptoms of the disorder can be attributed to hypofunctionality of
dopamine D1 receptor neurotransmission in the prefrontal cortex
Evidence in support
• Increased density of the dopamine D2 receptor in postmortem brain tissue of schizophrenia
sufferers
• Dopamine-releasing drugs, such as amphetamine, possess psychotomimetic properties inducing
Schizophrenia like symptoms
• A group of drugs called the phenothiazines, including antipsychotics such as chlorpromazine,
has been found to antagonize dopamine binding (particularly at receptors known as D2
dopamine receptors) and reduce positive psychotic symptoms

19. Dopamine Hypothesis
Evidence against
• Some patients had over 90% of their D2 receptors blocked by antipsychotic drugs but showed
little reduction in their psychoses, primarily the patients who have had the psychosis for ten to
thirty years
• Although dopamine-inhibiting medications modify dopamine levels within minutes, the
associated improvement in patient symptoms is usually not visible for at least several days,
suggesting that dopamine may be indirectly responsible for the illness

20. Serotonin Hypothesis
• Increased level of Serotonin causes Schizophrenia
Evidence in support
• LSD , a 5-HT2 agonist causes hallucination
• 5HT2A regulates Dopamine release in Mesolimbic system.

21. Pregnancy and Birth Complications
Fetal Hypoxia
• Oxygen deficiency to the tissues of the fetus
• Risk for later schizophrenia related to fetal hypoxia is restricted to individuals with a family
history of psychosis
• In utero oxygen deprivation has been hypothesized as a mechanism contributing to the
anatomical changes in the brain
Maternal Infections during Pregnancy or Delivery
• Exposure to viruses and other infectious agents such as influenza, toxoplasmosis, and herpes
simplex virus type 2 during pregnancy and around the time of conception

22. Pregnancy and Birth Complications
Fetal malnutrition
• Shortage of nutrients influences neurodevelopment.
• Typically, these nutrients exist in the diet as folate (B vitamins), proteins, essential fatty acids,
and vitamins A and D.
• Deficiencies of B vitamins can lead to accumulated high levels of the potentially dangerous
amino acid, homocysteine and elevated levels of homocysteine have been found in patients with
schizophrenia
Hypoxia
Infection
Malnutrition

23. Childhood Trauma
• Childhood adversity (sexual abuse, physical abuse, emotional/psychological abuse, neglect,
parental death, and bullying) might be associated with increased risk for psychosis in adulthood
• Permanent separation from, or death of, one or both parents may lead to psychosis
• Childhood trauma is believed to be associated with the most severe forms of positive
symptomatology in adulthood, particularly hallucinations and affective symptoms

24. Diagnosis
• Rule out other mental health disorders and determine that symptoms are not due to substance
abuse, medication or a medical condition
• Physical exam to rule out other problems that could be causing symptoms and to check for any
related complications
• Tests to rule out conditions with similar symptoms, and screening for alcohol and drugs.
• Imaging studies, such as an MRI or CT scan
• Psychiatric evaluation
• DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria for schizophrenia,
published by the American Psychiatric Association

25. Complications
• Suicide, suicide attempts and thoughts of suicide
• Anxiety disorders and obsessive-compulsive disorder (OCD)
• Depression
• Abuse of alcohol or other drugs, including nicotine
• Inability to work or attend school
• Financial problems and homelessness
• Social isolation
• Aggressive behavior, although it's uncommon

26. Management
Medication
Psychosocial Therapy Electroconvulsive Therapy

27. Medication
• Antipsychotics
• Ease delusions and hallucinations
• Act on dopamine and serotonin
• Can be taken as an oral daily dose or a long-acting injectable antipsychotic medication
(LAI) given once or twice a month
• Work best on "positive" symptoms like hallucinations and delusions
• Less effective on "negative" symptoms like withdrawal and lack of emotion
Typical Antipsychotics
• Chlorpromazine (Thorazine)
• Fluphenazine (Prolixin)
• Haloperidol (Haldol)
• Perphenazine (Trilafon)
• Thioridazine (Mellaril)
• Thiothixene (Navane)
• Trifluoperazine (Stelazine)
Atypical Antipsychotics
• Aripiprazole (Abilify)
• Cariprazine (Vraylar)
• Clozapine (Clozaril)
• Iloperidone (Fanapt)
• Olanzapine (Zyprexa)
• Paliperidone palmitate (Invega Trinza)
• Risperidone(Risperdal)

28. Medication
• Mood stabilizers
• Lamotrigine (Lamictal)
• Carbamazepine (Tegretol)
• Valproic acid (Depakote)
• Antidepressants
• Citalopram (Celexa)
• Fluoxetine (Prozac)
• Paroxetine (Paxil, Pexeva)
• Sertraline (Zoloft)
• Escitalopram (Lexapro)

29. Psychosocial Therapy
Cognitive Enhancement
Therapy (CET)
• Assess the symptoms
and findings
• Improve their
attention, memory, and
ability to organize their
thoughts
Cognitive Behavioural Therapy
(CBT)
• Establish link between
thoughts, feelings, actions
& symptoms
• 5 – 20 sessions
• Trace the origin of
symptoms
• Challenge the belief and
test their validity
• Give the patient alternate
explanation and the coping
strategies for their false
beliefs
Assertive Community
Treatment
• Highly personalized
services to help
patients meet life’s
daily challenges, like
taking medications
Social Skills Training
• Improves
communication and
social interactions

30. Psychosocial Therapy
Rehabilitation
• Job counseling, problem-solving
support, and education in money
management
Family Education
Self-help Groups
• National Alliance on Mental
Illness (NAMI)
• Learn from people who have
experienced it themselves or
been through it with a loved one
Coordinated Specialty Care
• For first psychosis episode
• Combines medication and psychological therapies.
• The aim is to change the direction and prognosis for the
disease by catching it in its earliest stages

31. Electroconvulsive Therapy
• In Catatonic schizophrenia and Acute episode of Schizophrenia
• Seizures are electrically induced for the therapeutic effect
• Has proved to be successful when even medication is not effective
• 3 times a week (20 to 25 treatments)
• Side Effects: Confusion, Temporary Memory Loss, Heart Complications, Nausea, Vomiting,
Headache, Muscle Ache, Jaw Pain, Joint Dislocation, Fractures
• DEATH may also occur in rare cases

32. Chlorpromazine
• Classic or Typical Antipsychotic
• Blocks the postsynaptic dopamine receptors (D2) in cortical and limbic areas of the brain,
thereby prevents the excess of dopamine in the brain leading to reduction in positive
symptoms, such as hallucinations and delusions
• Oldest drug used in Schizophrenia
• Marketed under the brand name Thorazine
• Dosage: 30-75 mg/day initially; maintenance: usually 200 mg/day (up to 800 mg/day in some
patients; some patients may require 1-2 g/day

33. Clozapine
• 2nd Generation or Atypical Antipsychotic
• It is mainly a 5-HT2A antagonist improving depression, anxiety, and the negative cognitive
symptoms
• Indicated only in Treatment-Resistant Schizophrenia
• Reduces the Risk of Recurrent Suicidal Behavior
• Starting dose is 12.5 mg once daily or twice daily.
• The total daily dose can be increased in increments of 25 mg to 50 mg per day, if well-
tolerated, to achieve a target dose of 300 mg to 450 mg per day (administered in divided
doses) by the end of 2 weeks.

34. Typical Vs Atypical
Adverse effects ARI CPZ CLO HAL OLA PAL RIS
Anticholinergic effects 0 ++ +++ 0 ++ 0 0
Acute parkinsonism + + 0 +++ 0/+ ++ ++
Akathisia ++ + + +++ + + +
Tardive dyskinesia 0/+ ++ 0 ++ 0/+ 0/+ 0/+
Diabetes 0/+ +++ +++ 0/+ +++ + +
Weight gain 0/+ +++ +++ + +++ ++ ++
Increased lipids 0/+ +++ ++ 0/+ +++ + +
Neutropenia 0/+ 0/+ +++ 0/+ 0/+ 0/+ 0/+
Orthostatic
hypotension
0/+ ++ ++ 0 + + +
Hyperprolactinemia 0 + + ++ + +++ +++
Sedation 0/+ ++ +++ + +/++ 0/+ +
Seizures 0/+ 0/+ ++ 0/+ 0/+ 0/+ 0/+

35. Prognosis
• Developing countries have a larger proportion (50-60%) with a good outcome and lesser
percentage with a worst outcome as compared to developed countries
• Environmental factor plays an important role in prognosis of mild cases but not in severe
cases
• Family h/o schizophrenia indicates a poor prognosis
• If the schizophrenia onset was precipitating by some events/ factor, the prognosis is regarded
as good on the other hand absence of a precipitating factor indicates poor outcome
• Male gender, insidious onset, lesser social support, low level of employment predict a poor
outcome
• Being married, female gender, better premorbid adjustment, no drug use, acute onset, short
duration of illness and short duration of untreated illness – better outcome
• High level of Expressed Emotion (EE) is associated significantly with high rate of relapse and
poor outcome

36. Clinical Research
1960 1970 1980 1990 2000 2010
Etiology Epidemiology Epidemiology Epidemiology _ Epidemiology
_ Biological
Research
Biological
Research
Biological
Research
Biological
Research
Biological
Research
Clinical
aspects
Phenomenology Phenomenology Phenomenology Phenomenology Phenomenology
_ _ Psychological Psychological Psychological _
_ _ Psychosocial Psychosocial Psychosocial Psychosocial
Treatment Treatment Treatment Treatment Treatment Treatment
Course &
Outcome
Course &
Outcome
Course &
Outcome
Course &
Outcome
Course &
Outcome
_
_ _ Rehabilitation Rehabilitation Rehabilitation _

37. Landmark Studies
• International Pilot Study of Schizophrenia (IPSS) – Agra: Baseline, 2 Years and 5 Years of F/U
• Determinants of Outcome of Severe Mental Disorders (DOSMeD) – Agra, Chandigarh – 1 Year
and 2 Years of F/U
• International Study of Schizophrenia (ISoS) – 15 Years F/U of DOSMeD & RAPyD and 25 Years
F/U of IPSS
• ICMR Project (Vellore, Madras, Lucknow) – 2 Years F/U
• IPSS Agra Cohort – 13 to 14 Years of F/U of IPSS
• Madras longitudinal study – 10 Years F/U of ICMR
• Chandigarh Cohort – 15 Years F/U of DOSMeD

38. Landmark Studies
Name Acronym Indian Centers Follow-Up Period
International Pilot Study
of Schizophrenia
IPSS • Agra • Baseline
• 2 Years
• 5 Years
Determinants of
Outcome of Severe
Mental Disorders
DOSMeD • Agra
• Chandigarh
• 1 Year
• 2 Years
International Study of
Schizophrenia
ISoS • Agra
• Chandigarh
• IPSS – 15 Years
• DOSMeD – 25 Years
Study of Factors
Associated with Course
and Outcome of
Schizophrenia (ICMR)
SOFACOS • Madras
• Lucknow
• Vellore
• 2 Years
IPSS Agra Cohort _ • Agra • IPSS – 13 to 14 Years
Madras Longitudinal
Study
_ • Madras • SOFACOS – 10 Years
Chandigarh Cohort _ • Chandigarh • DOSMeD – 15 Years

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