The document discusses schizophrenia, including its symptoms, causes, diagnosis, treatment, and impact. Some key points: - Schizophrenia is a severe mental disorder characterized by distortions in thinking, perception, emotions, language, sense of self and behavior. It can be disabling and is often chronic or long-lasting. - It is caused by a complex combination of genetic and environmental factors. Research suggests abnormalities in certain neurotransmitter systems in the brain, including dopamine. - Treatment involves antipsychotic medications to reduce symptoms. Psychosocial interventions like family therapy and vocational rehabilitation also help support recovery. - The disorder places a significant burden on those affected and their families, as well as society.

1. Prof. Dr. Fareed A. Minhas
Head, Institute of Psychiatry
Rawalpindi General Hospital
Rawalpindi

2. "Schizophrenia is a cruel disease. The lives of those
affected are often chronicles of constricted
experiences, muted emotions, missed opportunities,
unfulfilled expectations. It leads to a twilight
existence, a twentieth-century underground man... It is
in fact the single biggest blemish on the face of
contemporary medicine and social services; when the
social history of our era is written, the plight of
persons with schizophrenia will be recorded as having
been a national scandal."
- E. Fuller Torrey, M.D., Surviving Schizophrenia

4.  Characterized in general by fundamental and
characteristic disorders in thinking and perception, and
by inappropriate or blunted affect
 Clear consciousness is usually maintained
 Intellectual capacity retained though cognitive
impairment may set in over time
 Disorder of thinking, emotion, volition and perception
along with disintegration of personality

6. Annual incidence between
0.1 and 0.5 per 1000
Onset characteristically
between ages 15 & 45
Equal among men and
women but mean age of onset is
5 years earlier in men
Lifetime risk between 7.0 and
9.0 per 1000
Prevalence equal in various
countries (WHO)
In America alone,
2.2 million people
are affected

8. WHERE DO PEOPLE SUFFERING FROM IT LIVE??

9. Stigmatization
• Knowledge of the illness lags behind facts ->”discrimination”
• “Fear of violence”
• “Fear of criminal intentions”
• “Fear of unknown and aversion to illness
Impact on the person’s life
• Work limitations such as difficulty performing multiple tasks,
interacting with co-workers, accepting criticism or supervision,
customer service/contact. Perform inconsistently and may need
work space with low stimulation(stress)
• Interpersonal relationships are difficult, mostly live alone or with
family

10. Impact on families
• Sorrow – “We feel like we have lost our child”
• Anxiety – “We are afraid to leave him alone or hurt his feelings”
• Fear – “Will he harm himself or others?”
• Shame and guilt – “Are we to blame? What will people think?”
• Feelings of isolation – “No one can understand”
• Bitterness – “Why did this happen to us?”
• Ambivalence towards the affected person
• Anger and jealousy of siblings
• Depression / Sleeplessness / Weight loss / Social withdrawal
• Total denial of the illness or its severity
• Blaming each other
• Marital discord / Divorce
• Concerns for the future

11. Community costs
• Schizophrenia costs Canadians more than $2.3 billion in direct
health care costs and an additional $2 billion in support costs such as
welfare, family benefits and community support services, for a total
of $4.3 billion annually. The cost in terms of human suffering is
immeasurable...
• People with this disease use nicotine and street drugs excessively
• Suicide rates are high (10 percent – mostly young males)
• Studies show increased prevalence
of various diseases in schizophrenics
such as female breast cancer, MI (s)
Infections, type II diabetes mellitus
• Homelessness
• Accidents

13. PARANOID SCHIZOPHRENIA
• Commonest type
• Predominant well-organized paranoid delusions
• Thought processes and mood relatively spared
• Disturbance of affect, volition, speech and catatonia mild / absent
SIMPLE SCHIZOPHRENIA
• Insidious development of odd behavior, social withdrawal and
declining performance at work
• Clear schizophrenic symptoms might be absent
CATATONIC SCHIZOPHRENIA
• Prominent psychomotor disturbances with alteration between
hyperkinesis and stupor, or automatic obedience and negativism
• Posturing / episodes of violent excitement

14. HEBEPHRENIC SCHIZOPHRENIA
• Affective changes are prominent; delusions and hallucinations
fleeting and fragmentary; behavior irresponsible and unpredictable
• Mannerisms are common
• Mood is shallow/inappropriate followed by giggling or selfsatisfied/self-absorbed smiling
• Hypochondriacal complaints common
• Thought is disorganized and speech rambling/incoherent
OTHER CATEGORIES
• Undifferentiated
• Residual
• Post-schizophrenia depression
• Schizophreniform disorder not otherwise specified

16. • POSITIVE SYMPTOMS (Delusions, Hallucinations)
• NEGATIVE SYMPTOMS (apathy, lack of drive, social withdrawal)
THE ACUTE SYNDROME
SYMPTOM
• Lack of insight into illness
FREQUENCY
(%)
• Auditory hallucinations
97
• Ideas of reference
74
• Suspiciousness
70
• Flatness of affect
66
• Voices speaking to the patient
66
• Delusional Mood
65
• Delusions of persecution
64
• Thought alienation
64
• Thoughts spoken aloud
52

17. THE CHRONIC SYNDROME
CHARACTERISTIC
FREQUENCY %
• Social withdrawal
74
• Under activity
56
• Lack of conversation
54
• Slowness
48
• Over activity
41
• Odd ideas / behavior
34
• Depression
34
• Neglect of appearance
30
• Odd postures and movements
25
• Threats or violence
23
• Socially embarrassing behavior
8
• Suicidal attempts
4

18. VARIATION OF THE CLINICAL PICTURE
• Different features may predominate within a syndrome eg.
In the acute syndrome one may have a predominant paranoid
delusion and another may have a thought disorder
• Some may have features of both syndromes
• Depressive symptoms / Water intoxication
FACTORS MODIFYING CLINICAL FEATURES
• Amount of social stimulation of the patient – under stimulated
ones have mostly negative symptoms and over stimulated ones
positive symptoms
• Social background – previously religious delusions were
common
• Intelligence – people of low intelligence exhibit simpler forms

20. Minimum of one very clear symptom(two or more if less clear)
belonging to any one of the groups (a)-(d) or from at least two
of the groups (e)-(h) during a period of one month or more
(a) Thought echo/ insertion or withdrawal and broadcasting
(b) Delusions of control,influence,passivity; delusional perception
(c) Hallucinatory voices as a running commentary, third-person or
somatic hallucinations
(d) Persistent delusions that are inappropriate and impossible
(e) Persistent hallucinations or over-valued ideas
(f) Breaks/interpolations in train of thought, neologisms
(g) Catatonic behavior such as waxy flexibility/negativism/stupor
(h) Negative symptoms eg. Marked apathy, paucity of speech
(i) Significant consistent change in personal behavior eg idleness

21. A.
CHARACTERISTIC SYMPTOMS OF ACTIVE PHASE
(delusions/hallucinations/disorganized
speech/catatonia/alogia)
B.
SOCIAL/OCCUPATIONAL DYSFUNCTION in at least one
major area of functioning such as work, interpersonal relations
or self-care
C.
DURATION persistent for at least 6 months…with at least
one month of symptoms of criterion A
D.
SCHIZOAFFECTIVE AND MOOD DISORDER EXCLUSION
E.
SUBSTANCE/GENERAL MEDICAL CONDITION
EXCLUSION
F.
RELATIONSHIP TO A PERVASIVE DEVELOPMENTAL
DISORDER

23. ORGANIC SYNDROMES (drug-induced states,
temporal lobe epilepsy, acute brain syndrome of the elderly,
dementia)
MOOD DISORDER
PERSONALITY DISORDER
CHILDHOOD AUTISM – ASPERGER’S SYNDROME

25. Study commenced in 1990 investigating about 20% genomes
in large families of history of schizophrenia in east Quebec
show association areas on chromosomes
• 11q / 3q / 18q / 6p
•STRONG EVIDENCE FOR SCHIZOPHRENIA
SUSCEPTIBILITY GENE 6P22-P24 AND 11Q21-22
Anticipation (increasing severity or early age of onset of
disease in successive generations) is found in Schizophrenia
A recent study by molecular biologists at UC Irvine
isolated a gene, hSKCa3 located on 22q, which leads to an
increased risk to schizophrenia. This isolated gene contains
a characteristic CAG repeat
American Journal of Genetics(Miziade M et al)

26. There is a strong genetic component however only 48%
concordance among identical twins says that is not all…

27. THE DOPAMINE HYPOTHESIS

28. SHOWS A
SIGNIFICANT
INCREASED
NUMBER OF
DOPAMINE
RECEPTORS IN A
SCHIZOPHRENIC
BRAIN
ROLE OF AMINO ACIDS IN SCHIZOPHRENIA
• Glutamate neurotransmitters might have a role – evidence of
increased presynaptic/postsynaptic uptake sites for glutamate in
orbito-frontal cortex and decreased density of glutamate receptors
in the left hippocampus (SEE NEXT SLIDE)

29. NORMAL
STRUCTURE

30.  People with schizophrenia have smaller and lighter brains
 Evidence of enlarged cerebral ventricles
 Cytoarchitectural disturbances have been noted
 There is evidence of regional cortical loss – volume changes in
gray matter
3D profile of gray matter loss
in brains of teenagers with
early-onset
disease.TEMPORAL and
FRONTAL areas most affected
(red shows maximum effect).
These areas are responsible for
memory, hearing, motor
functions and attention

31. Frontal composite variability
of normal and schizophrenic
brains by gender
Shows
Significant structural
variability suggestive of
changes
Normal vs. Schizophrenia –
Composite variability among
15 male subjects

32. VOLUME OF INTEREST
superimposed over three
orthogonal slices of the
schizophrenic brain – it is
simply a sphere of 60 mm
radius between midline
decussations of ant. And post.
commissures
Variability in the sulcal
anatomy of the brain between
normal and schizophrenic
brains is also noted

33. 3D average surface
representation and variability
maps of the lateral ventricles highest variability in the
posterior horns noted
: MRI imaging showing
differences in brain ventricle
size in twins - one schizophrenic,
one not. (image courtesy NIH Dr. Daniel Weinberger, Clinical
Brain Disorders Branch)

34. Coronal MR scans from a normal comparison
subject (left), and chronic schizophrenic (right).
Note increase in CSF in right amygdalahippocampal complex. (image courtesy of
Harvard University Schizophrenia Project

35. N
SCZ
HYPOFRONTALITY : At rest
DISARRAY of the
hippocampal
cytoarchitecture and
cingulate gyrus
During card sorting

36.  “Soft signs” have been reported in many studies – commonly
stereognosis, graphaesthesia, balance and proprioception
probably due to defects in integration of proprioceptive and
other sensory information (Rochford et al-1970/Sanders et al-1992)
 Movement disorders common such as dyskinesias and
extrapyramidal or parkinsonian signs. Initially the argument
was that these are side-effects of anti-psychotic drugs but now a
prevalence of 12% of spontaneous dyskinesias has been found
in 9 different recent studies of people who never received antipsychotics. Also 23% prevalence of parkinsonian signs is found
in the same category.
 Decreased pain perception exact mechanism not know..no
studies

37.  EEGs of schizophrenics show increased theta activity, fast
activity and paroxysmal activity with scalp electrodes. More
abnormal EEGs were seen in patients never treated. Using deep
implanted electrodes – spike abnormalities in septal region and
secondarily in the hippocampus and amygdala. Also there was
abnormality in ‘deep frontal’ and ‘subthalmic’ regions
 Evoked potential response (p300) makes use of the person’s
ability to identify a target stimulus among irrelevant stimuli
and this is lower in schizophrenics and their first-degree
relatives
 Eye-tracking studies – defective performance by
schizophrenics (Freidman et al-1992 and Muir et al-1992)

38.  Cognitive deficits proven by various studies. Studies using
subjects who never received anti-psychotics also show
significant results.
 Main areas of deficit are verbal learning and memory. Less
commonly, attention and vigilance as well as visuo-motor
processing.
 Latest study by Schuepbach et all in 2002 in which 20 patients
compared to 21 controls showed significant deficits on the
Stroop test for selective attention

39.  Use of comparatively new and technically complex methods –
POSITRON EMISSION TOMOGRAPHY (PET) ; SINGLE
PHOTON EMISSION COMPUTER TOMOGRAPHY (SPECT)
and FUNCTIONAL MAGNETIC RESONANCE IMAGING
(fMRI)
 10 studies conducted to date of patients without anti- psychotic
treatments. 8 show significant deficits in the dorsolateral
prefrontal cortex at the onset on disease
 Decreased blood flow in prefrontal and frontal areas

40.  PERINATAL FACTORS : Birth complications, season, influenza
 CHILDHOOD DEVELOPMENT/ ANTECEDENTS : Greater
hostility towards strangers, reading and speech difficulties
 PERSONALITY FACTORS : Asthenic built, schizoid traits
 SEX AND AGE OF ONSET : Myelination of frontal and
temporal cortex around puberty, sex hormone changes

41.  PSYCHODYNAMIC THEORIES
 FAMILY
• Deviant role relationships
• Disordered family communications
 CULTURE
 OCCUPATION AND SOCIAL CLASS
 PLACE OF RESIDENCE
 MIGRATION / SOCIAL ISOLATION
 PSYCHOSOCIAL STRESSES

43. According to the BIO-PSYCHO-SOCIAL MODEL
BIOLOGICAL TREATMENT
ANTI-PSYCHOTIC DRUGS
Conventional or Standard Antipsychotics are phenothiazines,
butyrophenones, diphenylbutyl pipiredines, thioxanthenes and
substituted benzamides. These include: chlorpromazine
(Thorazine); fluphenazine (Prolixin); haloperidol (Haldol);
thiothixene (Navane); trifluoperazine (Stelazine); perphenazine
(Trilafon) and thioridazine (Mellaril).
Atypical Antipsychotics are newer drugs with fewer side effects
and include risperidone (Risperdal); clozapine (Clozaril) and
olanzapine (Zyprexa).
Side-effects Commonly dry mouth, constipation, blurred vision and
drowsiness. Less commonly decreased libido, menstrual changes
Extrapyramidal effects : Parkinsonian tremors, Akathesias, Tardive
dyskinesias and dystonias.Watch for ‘Neuroleptic Malignant
Syndrome’

44. Anti-psychotic preparations available
• Oral drugs – Tablets and suspensions
• Injectables – Short acting( Haloperidol, zuclopenthixol acetate) or
depot preparations(zuclopenthixol decanoate, fluphenazine)

45. ECTs
Traditional indications are catatonic stupor and severe depressive
symptoms in schizophrenia.
ANTI-DEPRESSANTS AND MOOD STABILIZERS
Depression is a part of the syndrome of schizophrenia. Value of use
of anti-depressants is not proven, may be helpful in chronic
syndrome but might worsen active psychosis.
Value of lithium in treatment is uncertain. If a schizoaffective case,
some benefit might be present.
PSYCHOLOGICAL TREATMENT
INDIVIDUAL PSYCHOTHERAPY
FAMILY EDUCATION
SELF-HELP GROUPS
Good motivation and productivity from patient is essential

46. WORKING WITH RELATIVES working with emotional
expressions within family is most beneficial
BEHAVIORAL TREATMENT include ‘token economies’ and
‘cognitive behavior therapy’ (specially for positive symptoms as
they are amenable to structured reasoning)
SOCIAL TREATMENT
REHABILITATION include social and vocational training and
improvement of communication skills as the onset of the illness is
at a point where they are training for skilled work.
CASE MANAGEMENT (followed in US)
Most consumers with severe or chronic schizophrenia will have a
case manager. The role of the case manager is to assist in
coordinating all the services that the consumer may need. See
figure below as an example of how a case manager can work with
other professionals and agencies.

49. Two different approaches to preventing schizophrenia that are
currently being researched:
1. Preventative measures that are taken well prior to any measurable
signs of the early phase of schizophrenia (also called the prodromal
phase, in medical terms)
2. Preventative measures taken during the prodromal period of
schizophrenia. (People typically show some early signs of
schizophrenia well before the full development of schizophrenia).
REDUCING THE CHANCE OF GETTING SCHIZOPHRENIA
• Street Drugs increase risk of Schizophrenia particularly
cannabis and marijuana
• Enriched Educational, Nutrition and Social Environments
Lower Risk of Schizophrenia
• Essential fatty acid (EFA) deficiency and resulting lipid
membrane abnormalities may increase risk of schizophrenia
• Antioxidant Intake may reduce risks of schizophrenia and
decrease side effects of medications

50. • Country life (vs. city living) before age 15 is associated with
lower rates of schizophrenia
REDUCING THE CHANCE OF GETTING IT AT BIRTH
• Maternal infections during pregnancy are associated with
increased risk of schizophrenia mostly flu
• Pregnancy and baby delivery complications are associated
with increased risk of schizophrenia
• Season of Birth - Low Sunlight Exposure/Vitamin D is
associated with higher risk of schizophrenia
• Older Age of Father increases risk of Schizophrenia due to
high levels of DNA damage in sperms of father
• Lead and other Toxic Exposures to Pregnant Women Triples
Risk of Schizophrenia for Child
• X-Ray Radiation during Pregnancy may increase risk of
schizophrenia for child

52. Natural course of
Schizophrenia as
typically described
ICD 10 CLASSIFICATION
-Continuous
- Episodic+Progressive deficit
- Episodic+Stable deficit
- Episodic remittent
/
DSM IV CLASSIFICATION
- Episodic with interepisodic
residual symptoms
- Episodic with no interepisodic
residual symptoms
- Incomplete remission
- Continuous(+negative prominence)
- Complete remission
- Single episode+partial remission
- Other
- Single episode+full remission

53. Good prognostic factors :
• Sudden onset
• Married
• Short episode
• Good psychosexual adjustment
• No previous history
• Good previous personality
• Prominent affective symptoms
• Good work record
• Paranoid type of illness
• Good social relationships
• Older age of onset
• Good compliance
 Poor prognostic signs :
• Insidious onset
• Single/separated/widow/divorced
• Long episode
• Poor psychosexual adjustments
• Previous psychiatric history
• Abnormal previous personality
• Negative symptoms
• Poor work record
• Enlarged lateral ventricles/Male
• Social isolation
• Younger age at onset
• Poor compliance

55. EARLY DETECTION AND INTERVENTION may contribute to
lower incidence and prevalence of florid schizophrenia. These
programs combine (1) early detection of psychotic features by
family practitioners and other primary care providers and (2) close
liaison with mental health professionals well trained in psychiatric
assessment and treatment strategies effective in reducing the
prevalence of established cases of schizophrenia. Long-term
monitoring for signs of recurrence of these sub-threshold psychotic
episodes, with further intervention as needed, appears essential to
maintain these benefits.
Schizophrenia Bulletin, 22(2): 271-282, 1996
Linszen D, Lenoir M, de Haan L, Dingemans P, Gersons B (1998).
British Journal of Psychiatry 172 (Suppl 33): 84-89.
NEWER ANTI-PSYCHOTICS are comparatively safer
In 2001, Thompson's group produced the first time-lapse images
revealing a wave of tissue loss rolling across the brains of
schizophrenic children at the National Institute of Mental Health.
first flicker of the disease -small part of the parietal cortex

56. Loss of upto 5 percent gray matter per year has been recorded
compared to 1 percent per year in normal teenagers.
•In 2002, Desmond Smith of the University of California, Los
Angeles and his colleagues developed the technique called
"voxelation" to study Parkinson's disease in a mouse model. The
problem is that the trouble-making cells behind, schizophrenia,
for example, could be a small group of upstarts in the brain's
huge collection of specialised cells. And to make the matter
worse, only a few of our 30,000 or genes may be misfiring in these
cells. Smith is now dissecting brain slices for mapping. In five
years, he expects to have a complete genetic map of the healthy
human brain composed of 8000 voxels and a 300 voxel map of the
healthy mouse brain. At the same time, they will begin
developing genetic maps of abnormal brains.

58. • ADHERENCE TO TREATMENT is a special challenge for
both the doctor and the patient as paranoia and lack of
insight of the patient often interferes.
• SIDE EFFECTS OF THE DRUGS make a person refuse
treatment.
• Long-acting depot preparations are available only for the
older anti-psychotics. Future targets include development of
intramuscular newer anti-psychotics.
• Development of new drugs that act primarily on receptors
other than the dopamine system
• Development of community programmes that aid early
detection of psychosis and protection of the rights of the
mentally ill

60.  “The schizophrenic experience can be a terrifying journey
through a world of madness no one can understand, particularly
the person travelling through it. It is a journey through a world
that is deranged, empty, and devoid of anchors to reality. You
feel very much alone. You find it easier to withdraw than cope
with a reality that is incongruent with your fantasy world. You
feel tormented by distorted perceptions. You cannot distinguish
what is real from what is unreal. Schizophrenia affects all
aspects of your life. Your thoughts race and you feel fragmented
and so very alone with your “craziness...” (Janice Jordan – an
author)
 “The worst thing about having schizophrenia is the isolation
and the loneliness...”