• What is Psychosis?

• Caused by a variety of conditions that affect

the functioning of the brain.
• Includes hallucinations, delusions and thought
disorder

Schizophrenia
 Schizophrenia

• Major disturbances in thought, emotion, and behavior

– Disordered thinking
• Ideas not logically related
• Faulty perception and attention
– Lack of emotional expressiveness
• Inappropriate or flat emotions
– Disturbances in movement or behavior
– Can disrupt interpersonal relationships, diminish capacity to
work or live independently
• Significantly increased rates of suicide and death
• Lifetime prevalence ~1%
• Affects men slightly more often than women
• Onset typically late adolescence or early
adulthood
Proposed DSM-5 Criteria for Schizophrenia
• Two or more symptoms lasting for at least 1 month; one symptom
should be 1, 2, or 3:
– Delusions
– Hallucinations
– Disorganized speech
– Abnormal psychomotor behavior (catatonia)
– Negative symptoms (blunted affect, avolition, asociality)
• Functioning in work, relationships, or self-care have declined since
onset
• Signs of disorder for at least 6 months; at least 1 month of the
symptoms above; or, if during a prodromal or residual phase, negative
symptoms or two or more of symptoms 1-4 in less severe form
Positive Symptoms: Behavioral Excesses and Distortions

• Delusions • Hallucinations
– Firmly held beliefs
– Sensory experiences in
– Contrary to reality
the absence of sensory
– Resistant to disconfirming
evidence
stimulation
• Types of Content of thought : – Types of hallucinations:
– Persecutory delusions – Auditory
– Thought insertion • 74% have this symptom
– Thought broadcasting – Visual
– Outside control – Hearing voices
– Grandiose delusions • Increased levels of
– Ideas of reference activity in Broca’s area
during hallucinations
 Negative Symptoms: Disorganized Symptoms
Behavioral Deficits • Disorganized speech (Formal
thought disorder)
• Avolition: Lack of interest;
• Incoherence
apathy
• Asociality: Inability to form – Inability to organize ideas
close personal relationships • Loose associations
• Anhedonia: Inability to (derailment)
experience pleasure – Ramble, difficulty sticking
• Anticipatory pleasure to one topic
• Blunted affect: exhibits little • Disorganized behavior
or no affect in face or voice – Odd or peculiar behavior
• Alogia: Reduction in speech such as silliness, agitation,
• Difficulty in abstract unusual dress e.g., wearing
thinking. several heavy coats in hot
weather
Movement Symptoms
• Catatonia
– Motor abnormalities
– Repetitive, complex gestures
• Usually of the fingers or hands
– Excitable, wild flailing of limbs
• Catatonic immobility
– Maintain unusual posture for
long periods of time
• e.g., stand on one leg
• Waxy flexibility
– Limbs can be manipulated and
posed by another person
Other Psychotic Disorders
• Schizophreniform Disorder
– Same symptoms as schizophrenia
– Symptom duration greater than 1 month but less than
6 months
• Brief Psychotic Disorder
– Symptom duration of 1 day to 1 month
– Often triggered by extreme stress, such as
bereavement
• Schizoaffective Disorder
– Symptoms of both schizophrenia and mood disorder
• DSM-5 likely to require appearance of major
depressive or manic episode
• Delusional Disorder
– Delusions may include:
• Persecution
• Jealousy
• Being followed
• Erotomania (Loved by a famous person)
• Somatic delusions
– No other symptoms of schizophrenia
Etiology
a) Genetics
There is a strong tendency for schizophrenia to run in
families.
Twin studies show a higher concordance rate in monozygotic
(50%) than in dizygotic (10%).
Both parents with schizophrenia, the risk of developing
schizophrenia is 50%
One parent with schizophrenia, the risk of developing
schizophrenia is 13%
No relatives with schizophrenia the risk of developing
schizophrenia is 1% (for general population).
b) Season of birth appears to be correlated with the risk for
developing schizophrenia. In both the Northern and Southern
hemispheres, the risk for developing schizophrenia is greatest
.for individuals born in the late winter and early spring
Strong evidence now emerging that schizophrenia is associated
.with complication during pregnancy and birth
c) Brain abnormalities
Ventricular enlargement (appears associated with negative
symptoms)
d) Reduced brain size (frontal and temporal lobes, hippocampus,
amygdale, parahippocampus).
e) Life events
Stressful events occurs more frequently in the month before a
first psychotic episode or relapse, and may, therefore,
.precipitate the illness
f) Expressed emotion: When family or careers become over-
involved, over-critical, or hostile towards a schizophrenia
patient, he or she is more likely to relapse
g) Neurotransmitter hypothesis
The dopamine hypothesis: Disorder due to excess levels of
dopamine
• Drugs that alleviate symptoms reduce dopamine activity
• Amphetamines, which increase dopamine levels, can
induce a psychosis
• Serotonin hypothesis – Hyperactivity of serotonin
neurons in the limbic cortex may mediate the
symptoms of psychosis
• Norepinephrine hypothesis – Acutely paranoid
psychotic states may accompanied by increased
levels of norepinephrine
• GABA – Low levels of GABA are found early in the
course of schizophrenia and increase with the
duration of the illness.
Pathophysiology of Schizophrenia Nucleus
Accumbens
Mesolimbic Dopamine
Pathway

i o n
je ct
r o
g i cp
r
ine
pam
Do
Ventral Forebrain
tegmental
area
This part of the limbic system though to be
Midbrain involved in many behaviours, such as
pleasurable sensation,
the powerful of euphoria of drugs,
as well as delusions and hallucinations
Pathophysiology of Schizophrenia Cortex

Mesocortical Dopamine Limbic

Pathway Cortex

c tion
pr oje
Midbrain rg ic
in e
p a m
Do
Ventral
tegmental
area

This part of the limbic system may have a role in

mediating +ve and -ve psychotic symptoms or
cognitive side-effects of neuroleptic antipsychotic
medication
Pathophysiology of Schizophrenia Forebrain

Mesolimbic Dopamine Nucleus

Pathway Accumbens

tion
o jec
p r
ic
rg
ine
a m
p
Ventral Do
tegmental
area
Overactivity of dopamine in the mesolimbic
Midbrain pathway may mediate
the positive symptoms of psychosis.
Pathophysiology of Schizophrenia
Cortex

Mesocortical Dopamine Limbic

Pathway Cortex

t i o n
oj e c
Midbrain i c pr
g
am i ne r
Do p
Ventral
tegmental
area

Hypoactivity of dopamine in the mesocortical

pathway may mediate the cognitive symptoms and
negative symptoms of Schizophrenia
 Pathophysiology of Schizophrenia

Mesocortical Dopamine Pathway may mediate some

cognitive symptoms, especially the negative symptoms that
characterizes schizophrenia

Avolition: Lack of interest; apathy

Thought disturbance. Asociality: Inability to form close personal
Incoherence. relationships
Loss associations. Anhendonia: Inability to experience pleasure
Anticipatory pleasure
Impaired attention.
Blunted affect: exhibits little or no affect in
Impaired information process. face or voice
Alogia: Reduction in speech
Difficulty in abstract thinking.

Mesocortcal hypoactivity = Negative and Cognitive symptoms of

schizophrenia
 Pathophysiology of Schizophrenia
Alterations in Dopaminergic Neurotransmission
in Limbic and Mesocortical Dopamine Pathways
are critically involved in mediation of Cortex
schizophrenia symptoms
Limbic
Forebrain
Cortex
Midbrain tio n
Nucleusc projec
i ne rgi
Accumbens
m
Ventral Dopa
tegmental
area

Neg. & Cognitive

Positive Symptoms
Symptoms
Clinical course.
(1) Onset.
(a) Acute
(b) Prodromal phase: (negative symptoms)
– Social withdrawal
– Loss of interest in school and work
– Deterioration in hygiene and grooming
– Peculiar behaviour
– Apathy
– Blunted or inappropriate affect
– Vague, digressive and poverty of speech
– Unusual perceptual experiences such as recurrent illusions
“telepathy”
– Odd beliefs that are inconsistent with cultural group
(2) Active phase
Clinical features
Formal thought disorder (as experienced by the patient and displayed
through verbal communication):
• Loosening of associations
• Poverty of content and speech
• Thought blocking
• Content of thought (Delusions: are defined as fixed, false beliefs):
– Delusions of persecutory
– Delusions of reference
– Delusions of influence
– Thought broadcasting
– Grandiose delusions
– Somatic delusions
• Perceptual disorder (a variety of distortions of sensory experienced and
their interpretation include hallucinations and illusions):
– Hallucinations: are false sensory perceptions (auditory,
command, visual, tactile, gustatory, olfactory or somatic)
– Illusions: are misperceptions or misidentifications
(3) Affect (the observable manifestations of mood and
emotions: include blunted affect, flat affect and
inappropriate affect)
(4) Sense of self
– Loss of self-esteem
– Confusion about sexual identity
– An inability to separate oneself from events in the
environment
• Projection one’s own fear or suspicions onto others
• All good or all bad
(5) Volition symptoms (difficulties initiating and
maintain purposeful and goal-directed activity and
interest in the environment, include interest,
initiative, drive and ambition)
(6) Relationship to external world (i.e., patients to
become increasingly preoccupied with internal events
and decreasingly influenced by external events)
(6) Motor activity
– Catatonic stupor
– Catatonic excitement
– Catatonic posturing (catatonic rigidity and waxy flexibility)
– Echopraxia
– Automatic obedience
– Mannerisms and grimacing
– Stereotyped behaviours ( is purposeless repetitive movements or
verbalization)
– Perseveration (is involuntary repetitive of a task)
– Social behaviour
(7) Residual phase (those of prodromal phase, and may negative symptoms
be prominent)
(8) Duration (diagnosis of schizophrenia require that symptoms be present
for at least 6 months)
(9) Prognosis
(10) Complications
Small social network Impaired educational plans
Impaired worked performance Sexual relationship
Crime Premature death
Poverty, Homelessness Psychiatric comorbidity
 Active- Delusions, Hallucinations, Disorganized speech
phase Grossly disorganized behaviour or negative
symptoms symptoms

Prodromal phase: This phase may include

Duration at least 6 months • Social withdrawal
and must include at least 1 • Loss of interest in school and work
• Deterioration in hygiene and grooming
month of Active-phase • Peculiar behaviour
symptoms and may include • Blunted or inappropriate affect
periods of Prodromal or • Vague, digressive and poverty of
Residual symptoms speech
• Unusual perceptual experiences such
as recurrent illusions “telepathy
• Odd beliefs that are inconsistent with
cultural group of which is a member
Schizophrenia • Marked lack of initiative, drive,
ambition, interest or energy
 Delusions, Hallucinations, Disorganized Active-phase
speech, Grossly disorganized behaviour or symptoms
negative symptoms

Schizophrenia

Duration 0 1 2 3 4 5 6
in months
Prodromal Residual
symptoms symptoms

Prodromal symptoms
& Residual symptoms
Active-phase
symptoms
Negative symptoms
 Treatment of Schizophrenia: Medications

• First-generation antipsychotic medications

(neuroleptics; 1950s)
– Phenothiazines (Thorazine), butyrophenones
(Haldol), thioxanthenes (Navane)
• Reduce agitation, violent behavior
• Block dopamine receptors
• Little effect on negative symptoms
• Maintenance dosages to prevent relapse
Adverse effects of First-generation antipsychotic
medications
• Parkinsonian motor symptoms – Muscular rigidity,
bradykinesia (lack of, or slowing, of movement)
resting tremor. Generally occurs within a month of
starting antipsychotics.
• Acute dystonia – involuntary sustained muscular
contractions or spasm, e.g., neck (spasmodic
torticollis), clenched jaw (trismus), back
(opisthotonos) protruding tongue, eyes roll upwards
(oculogyric crisis). More common in young men, and
usually occurs within72 hours of treatment.
Treatment
1. Reduce dose of antipsychotics agent.
2. Anticholinergics e.g., procyclidine (10 mg I.V.),
benzotrpine (2-6 mg/day), trihexyphendyl (2-10
mg/day) or diphenhydramine (25-50 mg/day).
• Akathisia – Subjective feeling of inner restlessness and
agitation
Treatment
1. Reduce dose of antipsychotics agent or switching to
another antipsychotic
2. Propranolol, short-term benzodiazepine

• Tradive dyskinesia (TR)– Rhythmic, involuntary

movement of head, limbs, and trunk, especially chewing,
grimacing of mouth and protruding, darting movement of
tounge. It develops in up 20% of patients who receive
long-term treatment conventional antipsychotics.
Treatment
1. No effective treatment
2. Withdraw antipsychotic if possible
3. Clozapine may helpful
4. Consider benzodiazepine
5. Do not give anticholinergics (may worse TD)
Neuroleptic malignant syndrome is life-threatening condition
of Neuroleptic therapy.
Usually occurs within 4-11 days of initiation of treatment
or change of dose. This syndrome characterized by:
Motor signs: severe muscular rigidity
Mental signs: fluctuating consciousness
Autonomic disturbance: hyperthermia, unstable blood
pressur, rapid pulse, sweating
Blood tests: high creatinine kinase levels

Treatment
Stop antipsychotic
Dantrolene to reduce muscle spasm (up to 10
mg/kg/day I.V.)
Bromocriptine to reverse dopamine blockade
Cool patient, monitor vital signs, renal function, and
electrolytes
Muscarinic receptor blockade - Dry mouth, constipation urinary
retention, blurred vision

Histaminergic receptor blockade – Sedation, weight gain

Alpha-adrenergic receptor blockade – Postural hypotension
(dizziness, syncope)

Cardiac effects – Prolongation of QT-interval, arrythmias,

myocarditis, sudden death

Dermatological effects – Photosensitivity, skin rash, blue-grey skin

discoloration with carbamezapine

Others – Lowering of seizure threshold, hepatotoxicity, jaundice,

leukpenia
• Clinical Antipsychotic Trials of Intervention Effectiveness
(CATIE) study
– Second-generation drugs were not more effective than the older first-
generation drug
– Second-generation drugs did not produce fewer unpleasant side effects
– Nearly three-quarters stopped taking the medications before study ended
• Second-generation antipsychotics have serious side effects
– Weight gain, diabetes, pancreatitis
• Psychological Treatments
• Family therapy to reduce Expressed Emotion
– Educate family about causes, symptoms, and signs of relapse
– Stress importance of medication
– Help family to avoid blaming patient
– Improve family communication and problem-solving
– Encourage expanded support networks
– Instill hope
• Cognitive behavioral therapy
– Recognize and challenge delusional beliefs
– Recognize and challenge expectations associated with negative
symptoms
• e.g., “Nothing will make me feel better so why bother?”
• Cognitive remediation training or cognitive enhancement therapy
(CET)
– Improve attention, memory, problem solving and other cognitive-
based symptoms
• Case management
– Multidisciplinary team to provide comprehensive services
• Residential treatment
– Vocational rehabilitation