By

Pof. Dr. Adel El-Sheshai

Chairman of Neuropsychiatic Department Alexandria Faculty of Medicine

Schizophrenia

PSYCHOTIC DISORDER
This includes:

(1) Schizophrenia,
(2) Affective disorders (Manic-depressive

psychosis).
(3) Delusional psychosis (Paranoid reaction)

Schizophrenia

SCHIZOPHRENIA
Definition Schizophrenia is a disorder of unknown etiology, which is characterized by psychotic symptoms that significantly impair mental function and that involve disturbances in feeling~ thinking and behavior. The disorder occur in the adolesent stage, tends to be chronic and generally has a prodromal phase, active phase with delusions,

hallucinations or both and residual phase in which the

disorder may be in remission.

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Epidemiology Schizophrenia occurs in all cultures. Incidence is about 2-4 cases for 10000 population per year. Life time risk is about 1%. In industrialized countries, there are more schizophrenic patients in the lower socioeconomic classes. The peak incidence of onset is 15-26 in men and 25-35 years in women.

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Etiology
1. Genetic factor Genetic factors play a significant role but are not sufficient alone to account for the development of schizophrenia. Compelling data have come from family studies. In the general population, the lifetime risk of developing schiztophrema is approximately 1%. A child born with one schizophrenic parent has about a 14% chance of developing schizophrenia. This risk rises to approximately 50% if both parents are schizophrenic.

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Another approach has looked at siblings with varying degrees of genetic similarity. Nontwin siblings of a schizophrenic patient have about an 8% chance of developing schizophrenia. For nonindentical (dizygotic) twins, if one twin is schizophrenic, approximately 10% of the other twins develop schizophrenia. Concordance rate, rises to 40-50/o in identical (monozygotic) twins. Although such data support a strong role for genetics in the etiology of schizophrenia, they also clearly show that other factors play a significant role determining who does not develop schizophrenia.

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2. Structure Brain Changes:

Brain structural studies have failed to find a
pathogenomonic lesion in schizophrenia but have consistently found a number of abnormalities. CT, MRI, and poslmortem studies have shown decreased volume and density in limbic and frontal areas in schizophrenic patients. Some of these findings have been corroborated by changes in regional cerebral blood flow and positron emission

tomographic (PET) studies.

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3. Neurochemical Changes:
Multiple neurochemical changes also have been

implicated in schizophrenia. It has been long noted that

an excess in dopaminergic activity in the central nervous system is central to the development of

schizophrenic
the advent of

symptoms.
clozapine,

Compelling
the

data

also

implicate norepinephrine and serotinin systems. With prototypic atypical

antipsychotic,

it

has

been

hypothesized

that

interactions between these systems may be crucial in the pathogenesis of schizophrenia.

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4. Neurophysiological Changes:
Neurophysiological changes have been shown through
various neuropsychologic and physiologic measures. Schizophrenic patients have shown abnormal

informational processing on such measures as the Continuous Performance Test. They also have shown abnormal sensory processing on such measures as skin conductance habituation, backward masking, smooth pursuit eye movements, prepulse inhibition of acoustic

startle, and evoked potentials, such as P300.

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5. Endocrine factors:
Endocrine factors have long been suspected. Females tend to develop schizophrenia later and often have less severe symptoms than males. In males, the onset of schizophrenia is often during puberty. Changes in prolactin, melatonin, and thyroid functions have been found in schizophrenia.

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6. Viral and immune factors: Have also been implicated. Although the search for a causative virus in schizophrenia has thus far been unfruitful, various factors points to this possibility, for example, a number of immune changes have been found, including IgA, IgG and 1gM. Furthermore, a larger

than expected number of schizophrenic patients are

born in late winter and early spring, leading to the hypothesis that perinatal viral infections may be involved in causing schizophrenia.

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7. Psychosocial factors:
Are no longer left to be causative in schizophrenia but clearly play a role in

the course of the illness.

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Clinical picture:
The clinical presentation of schizophrenia

varies both between individuals, and

within the same individual at different stages of the illness, but the following are the most common features:

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1. Perceptual disturbance
Hallucinations are sensory perceptions in the absence of external stimuli. Auditory hallucinations (especially voices) are by far the most common in schizophernia. Their content varies, being sometimes threatening, insulting, commanding or helpful. According to their form they are classified as:

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Second person: Voices adress the patient directly. Third person: Voices discuss the patient in the third person. Running commentary: Voices comment on the patients actions, referring to him in the third person. Visual, tactile, oflactory and gustatory hallucinations may occur, but are less common. Ocasionally, schizophrenic patients report bizarre sensations in body organs such as burning in the brain or bursting of blood through the vessels.

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2.Thought disturbance
a. Disorders of thought process (formal thought disorders)

Loosening of associations: logical associations between

the ideas expressed are loose or incomprehensible; when severe speech becomes incoherent. Poverty of content of speech: Speech is sufficient in amount but conveys little information due to vagueness, stereotypy or repetition. Thought block: A sudden interruption in the train of thinking. Neologisms: Idiosyncratic words or phrases invented by the patient.

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b. Passivity phenomena:
These can take the form of:

Thought broadcasting: The experience of

ones thoughts becoming available to the outside world. Thought insertion: The experience of alien thoughts being inserted into ones mind.

Thought withdrowal: The experience of ones

own thoughts being removed from ones mind.

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C.Abnormal thoughts (Delusions):

Delusions are false beliefs that does not issue from reality, that are inconsistant with the patients educational and cultural background and are not amenable to reasoning or explanation. Persecutory delusions and delusions of reference (Paranoid delusions) are particularly common. Somatic, religious, nihilistic or grandiose delusions may also occur. Not unconunonly schizophrenic patients express complex delusions with

pseudoscientific or pseudo-philosaphical content.

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3. Cognitive defects:
Schizophrenic patients are usually oriented in time, place and person. However attention and concentration are often impaired, and memory and learning may be poor. For many years these cognitive deficits were

thought to be secondary to factors such as poor

motivation and distraction by psychotic symptoms. However in the past few years neuropsychological

deficits have come to be seen as an intrinsic part of

schizophrenia.

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4. Abnormal affect: The most characteristic affective abnormalities in schizophrenia are: Reduced motional expression (shallow emotion). Blunt of affect that is a quantitative abnormality with reduction in emotional intensity and variation. Inappropriate or incongruous affect: that is a quantitative abnormality where affective response is incompatible with the ideas or thoughts expressed.

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Anhedonia: Patients can not experience any pleasurable feeling. Ambivlance: Presence of contradictory emotion or idea towards the same stimulus at the same time. At the onset of the illness or during acute exacerbations patients may experience intence emotions such as terror, anxiety or exhilaration in response to the content of their delusions. Apathy: That is absence of emotional experience and expression.

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5. Motor abnormalities: Disturbances in motor behaviour were an essential part of the early descriptions of schizophrenia. Either quantitative or qualitative changes may occur: Posturing: Voluntary adoption of bizarre or inappropriate positions for prolonged periods, may have some symbolic meaning. Waxy flexibility: Sustaing imposed position for prolonged time. Negativism: Automatic resistance to instructions or attempts at movement. Ecopraxia: Pathological, automatic imitation of another persons movements.

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Sterotypy: Repeated, action.

purposeless

pattern

of

Catatonic stupor: There is no disturbance in the

state of consciousness, but the patients is not

responding to external or internal stimuli with sustaned immobility and apparent unawareness of the surroundings. Catatonic excitement: Intense, purposeless and

disorganized activity.

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6. Lack of volition and insight

Schizophrenic patients show lack of drive or initiation
and diminished interest to the outside world, this is especially apparent in the chronic stages of the illness. With regards to insight, the vast majority of patients either lack or have reduced awareness of their mental condition. Poor insight is associated with non-

compliance with medication, increased severity of

psychopathology and frequent hospital admissions.

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Clinical Phases:
I. Premorbid and Prodramal Phases: Social and cognitive deficits in schizophrenic patients can be traced back to childhood. The preschizophrenics showed increased deviance with age. The cognitive slippage become progressively more marked in early adolescence, prodromal phase starts by actual functional decline, accompanied by eccentric ideas and interests, changes in affect; unusual speech and bizarre perceptual experiences. The onset of the prodromal phase is often gradual, and as the symptoms are non specific, it is often difficult to draw a line between premorbid personality and prodromal phase.

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2. Acute Phase:
The most frequent symptoms in acute phase are
unreality state specially depersonalization,

suspiciousness delusional mood, lack of drive, thought alienation and lack of insight Patients may develop overwhelmed anxiety and depression and may commit suicide secondary to these changes.

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3. Chronic Phase:
That is the frank schizophrenic psychotic symptoms persist more than two years with either exacerbation of the symptoms or show no response to treatment.

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Clinical Types: According to the standard classification, schizophrenia is classified into:

Diagnostic criteria

Paranoid

Preoccupation with one or more delusions or frequent auditory hallucinations. None of the following should be prominent: Disorganized speech, disorganized or catatonic behavior, or flat or inappropriate affect.

Disorganized

Prominent disorganized speech and behavior, flat or

inappropriate affect. Should not meet any criteria for the catatonic type

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Catatonic

At least two of the following: motor immobility as evidenced by catalepsy or stupor; excessive motor activity apparently purposeless and not influenced by external stimuli; peculiarities of voluntary movement as evidenced by posturing, stereotyped movements, prominent mannerisms or prominent grimacing; echolalia or echopraxia. Does not fulfil the criteria for any of the above types. Absence of prominent delusions, hallucination, disorganized speech and grossly disorganized or catatonic behaviour; continuing evidence of the disturbance indicated by the presence of negative symptoms or two or more of the above symptoms in an attenuated form.

Undifferentiated Residual

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Course:
The course of schizophrenia was considered to
be one of continuous deterioration. Today, most clinicians would agree that this extremely pessimistic view is not justified and that there is a great degree of variability in the course:

In most cases, schizophrenia seems to follow

one of four broad patterns

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One episode only-no impairment

22%

Several episodes with no or Minimal impairment

Impairment after the first episode with subsequent exacerbation and no return to normally Impairment encrassing with eech of several eplsodes and no return to normally

35%

8%

35%

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Differential diagnosis From psychiatric conditions Mania: Though the symptoms often overlap, mania is characterized by prominent affective component (elation, grandiosity, disinhibition, ovberactivity, irriability and lability of mood), while acute schizophrenia is characterized most often by suspicion, paranoia or perplexity. Depression: Chronic schizophrenia may mimic or coexist with depression, patricularly in young people and those who retain insight into the nature of their illness.

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From organic conditions Includes very rare chorea, conditions Wilsons such as

Huntingtons

disease,

temporal lobe epilepsy, frontal or temporal lobe tumour.

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Management:
1. Hospitalization It is essential to hospitalize those with acute schizophrenic symptoms for investigation and treatment. Patients with chronic schizophrenia

should be admitted for relapse, but otherwise

often be maintained in the community or in sheltered carried out. accommodation. After discharge, regular follow-up schedule program should be

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2 Pharmacotherapy:
Antipsychotic drugs (major tranquilizers) ameliorate and reduce the signs and symptoms of schizophrenia. Consider

low potency antipsychotic drugs (e.g. chlorpromazine) if

patients is hyperactive or agitated and high potency drugs (e.g. trifluoperazine) if patients is withdrawn or lethargic.

Acute schizophrenic (positive) symptoms respond better than

chronic (negative) symptoms to typical anti psychotics while chronic symptoms respond better to atypical type. Depot antipsychotic preparations can be used for maintenance treatment and improve compliance. Extrapyramidal side effects can be treated with antimascarinic (anticholinergic) drugs e.g. benzhexol.

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3. ECT (electroconvulsive therapy)

ECT is given with regards to certain symptoms and signs in the psychotic patient

and to a certain diagnosis, hence ECT is given

to schizophrenic patient if there is: Catatonia or stupor - Severe depression Suicidal thoughts or act - Excitement It is given every second day for at least 12 settings in the chronic form of schizophrenia.

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4. Rehabilitation: Rehabilitation aims to allow the patient to lead as near normal life as possible and

incorporates in relapse prevention. Effective rehabilitation address all aspects of social,

psychological and emotional functioning.

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Psychopharmacology
Psychopharmacology deals with the drugs used in the

treatment of psychiatric patients through the following

group of drugs. 1. ntipsychotic medication (Neuroleptics or major transquilizers) 2. Antidepressent drugs.

3. Anxiolytic drugs.
4. Mood stabilizing drugs. 5. Cerebral stimulants.

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Antipsychotic Medications

Antipsychotic or neuroleptic drugs are used to

treat psychotic symptoms in patients with

schizophrenia and other conditions. They are

divided into two main groups the conventional or typical antipsychotics and the novel or atypical anti-psychotics.

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Conventional (typical) antipsychotics Phenothiazine derivatives 1. Aliphatic: Chlorpromazine (largctil). 100-1000 mg/day. 2. Piperidine: Thioridazine (melleril) 300 600 mg/day. 3. Piperazine: Trifluoperazine (stelezine) 5-30 mg/day. Non phenothazine: 1. Bytrophenones: Haloperidol (Safinase)

Oral tablets
Watery injection

5-30
5-20

mg/day
mg/day

Depot preparation Haldel decanoates

2. Sulpride (Dogmatil) tablets 50-400 mg/day.

3. Pimozide (orapforte) 4 mg/day.

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Mechanism of action: The typical antipsychotic drugs are believed to act via

central blockade of dopamine receptors in the

following areas: 1. In the limbic areas leads to wanted antipsychotic

effect.
2. In the basal ganglia leads to the unwanted extrapyramidal side effect.

3. In the hypothalamus (via blockade of dopamine

inhibition of anterior pituitary leads to increase prolactin level).

4. In the brain stem giving the antiemetic effects.

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Indications:
Acute and maintenance treatment of schizophrenia Psychosis associated with acute mania and major depression. Psychosis secondary to organic brain syndrome (delirium and dementia). Tics due to neurologic conditions e.g. tourettes syndrome and huntington chorea. In rheumatic chorea to get benefit from the extrapyramidal side effect so as to increase the muscle tone in a hypotonic patient, thus reach to the euotonia normal tone and disappearance of choriec movement. In flash back reaction, nightmares and agitation due to post-traumatic stress disorder. For medical uses (nausea and vomiting).

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Side effects:
1. Dopaminergic side effect:

Parkinsonian like disease: tremors, masked

face and cogwheel rigidity. Acute dystonia, such as opisthotonus,

torticollis and laiyngospasm. Akathisia in the form of subjective or

observable restlessness, the patient can not maintain set in one place.

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TARDIVE DYSKINESIA
It is a syndrome of abnormal involuntary movements such as buccoliingual masticatory movements, choreoathetoid movements of the limbs or even trunk and neck, and facial grimacing or tics. Its secondary to long administrations of antipsychotic drugs.

Neuroleptic malignant syndrome (N.M.S.): It is a

potentially fatal side effect. It is manifested by woody rigidity, autonomic dysfimction hyperpyrexia and

coma.
Oculogyric crisis that is upward movement of the eye globe inside the orbital cavity.

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2. Anticholinergic side effect Dry mouth Blurred vision

Constipation that may lead to a dynamic ileus

Urinary hesitancy or obstruction

Memory and concentration difficulties up to

frank delirium toxic confusional state.

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3. Alpha-adrenergic blockade. Hypotension.

Orthostatic hypotensmon.
4. Antihistaminergic side effects. Sedation.

Increase appetite and weight gain.

5. Others: Sexual dysfunction.

Pigmentary retinopathy.
Skin rashes. Agrnulocytosis.

Gynecomastia (due to increase prolactin level)

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Novel (Atypical) Antipsychotics

Atypical antipsychotics comprise a yarned group of compounds that share a number of characteristics: They reduce the spontaneous firing of the mesolimbic dopaniinergic neurons with minimal effect on the nigrostniatal neurons. They have higher 5-HT2 than D2 receptor affinities. They do not produce sustained elevation in prolactin, and have very low potency for inducing EPS.

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Preparation:
1. Clozapine (Leponex) given single dose at bed time, dose range between 100-300 mg/day, side effect: a. Agranulocytosis that is why patient should be monitored weekly for WBC. For 6 months then once/month for another 6 months. b. Less commonly are sialorrhia, excessive sleep and in rare cases nocturnal enuresis. 2. Rispridone (Risperdal) given in a dose of 4-6 mg/day. 3. Olanzapine zyprexa 4. Ziprazidene (zeldox) 5. Quitaban (Seoquel) 6. Sertendol (serdluct)