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Schizophrenia 1 WeiPing Wang Mental Health Institute WeiFang Medical University Contents • Overview • Epidemiology • Onset • Causes • Symptoms • Diagnosis • management

Learning objectives You should • Know the definition of schizophrenia • Know the positive and negative symptoms • Know about first rank symptoms • Know the dopamine hypothesis to explain the biological basis of schizophrenia • Know the management of schizophrenia Overview • Schizophrenia is a chronic, serious psychotic mental disorder characterized by symptoms of delusions and hallucinations, coupled with dysfunctional symptoms such as apathy and lack of volition.

Overview • It begins usually in late adolescence and early adulthood. Most people recover from the first episode but subsequently experience further episodes characterized by increasing levels of dysfunction.

Overview • One fifth remain symptom free. The illness has a strong genetic component and the concordance rate in identical twins is 40%. The condition is usually treated with antipsychotic medication.

• Education of the patient and family about the nature and management of schizophrenia is very important. Most patients require ongoing care from a community multidisciplinary team.

• Jane had a normal childhood and did well academically at school. In her second year at university, following the break up of a relationship, she developed over the course of a week auditory hallucinations of voices talking about her and commenting on what she was doing. She believed firmly that a university lecturer had implanted an electronic device in her head that could control her thoughts. After being seen by her GP, she was referred urgently to mental health services where she was assessed jointly by a nurse and psychiatrist.

• She was admitted to the day hospital. After routine investigations were normal, she was treated with haloperidol 5mg daily. After 3 weeks, her hallucinations had subsided and she recognized that her beliefs had been mistaken, she continued to improve over the next month and was able to return to her studies after a further month. • What positive symptoms did Jane have? • What is the differential diagnosis? • What good prognostic factors are present? History 1 answer • Passivity experiences, third person auditory hallucinations and running commentary. • Schizophrenia • Rapid onset of the condition, precipitated by a life event, the rather florid symptoms, normal childhood, without negative symptoms Definition • Schizophrenia was first recognized as a separate mental disorder in the 1890s. Often misunderstood as 'split personality', it is actually a serious mental illness with psychotic symptoms of delusions and hallucinations that comes on in early adult life.

• In most cases, it then runs a chronic, relapsing course. This is one reason why it is one of the top five most expensive disorders in all of medicine.

• Schizophrenia is defined as a psychotic mental illness, meaning it is a severe disorder with delusions and hallucinations (psychotic symptoms). Sufferers usually have episodes of acute psychotic symptoms, often with more persistent social impairment.

• Schizophrenia is a clinical syndrome with a profound influence on public health, schizophrenia has been called “arguably the worst disease affecting mankind, even AIDS not excepted” (Nature 1988)

• John Forbes Nash: A professor of Princeton University • A mathematical genius • He made an astonishing discovery early in his career and stood on the brink of international acclaim. • But Nash soon found himself on a painful journey of self-discovery once he was diagnosed with schizophrenia • After many years of struggle, he eventually triumphed over this tragedy, and finally, late in life, received the Nobel Prize. More information Emil Kraepelin • Modern history credits Kraepelin, a prominent nineteenth century German psychiatrist , with the identification of schizophrenia. He introduced the term dementia praecox indicated the early age of onset, usually in adolescence. Kraepelin also differentiated clients with dementia praecox from those with manic-depressive psychosis. He provided detailed descriptions of symptoms such as hallucination, delusions, and negativism.

Eugen Bleuler • Eugen Bleuler, a Swiss psychiatrist,renamed the illness schizophrenia(a term that meant “splitting of the mind”). • Bleuler’s theory reflected the belief that the cause of the illness was disharmony in the person’s psychic function versus a deteriorating course.

• He divided the symptoms into characteristics of thought disorders and affective emotional disturbances. Bleuler and Kraepelin both assumed that there was an underlying biological basis for this disorder (Campbell,1958).

4A symptoms • Association disorder • Affective blunting (apathy) • Ambivalence • Autism Kurt Schneider • In 1959,Kurt Schneider put forward the idea of first rank symptoms which are important in the making of today’s schizophrenia diagnostic criteria.

First rank symptoms • Some positive symptoms (delusion, hallucination) are called first rank symptoms because they occur in schizophrenia and rarely in other disorders.

a. Third person auditory hallucinations
b. Running commentary
c. Thought echo
d. Delusions thought insertion
e. Delusions thought withdrawal 

f. Delusions thought broadcasting g. Delusions passivity feelings h. Primary delusion (a delusion that arises suddenly, with no other prior symptoms. No any cause.)

• The second rank symptoms are considered less important for diagnosis of schizophrenia, like other forms of hallucinations, perplexity, and affect disturbances. Epidemiology • Incidence (rate of new cases): 2/10000 • Prevalence (number of existing cases): 1/200 • Social class: equal • Sex: equal • Peak age at onset: men/women18-25/20-28 • Family history: present in 1/3 of cases

Epidemiology the Tragedy of Schizophrenia • A catastrophic illness • Tends to persist chronically • 10% suicide rate • Very common -- 0.5-1% of population • The “cancer of mental illness”

• Prevalence ： • Point prevalence in China (1982): 4.75‰（rural area 3.42‰，urban 6.06 ‰ )。 • Total prevalence in China: (1982,5.69‰ )，(6.55 ‰,1999)。 • Lifetime prevalence in USA（1988）13‰。 Onset • The median age at onset is about 23 years in men and 28 years in women. Onset is very rare under 16, and uncommon over 40. Onset can be relatively acute, over the course of 2 or 3 weeks, or insidious (gradually evidence or severe).

• The typical history is for a period of several months increasingly poor functioning at home, work or school, with noticeable social withdrawal, non-specific anxiety and change in behavior (look into the mirror).

• Delusions and hallucinations then appear, sometimes after several days in which the person reports his or her surroundings to be changed in some strange way that is difficult to describe: so-called delusional mood. Course • Most people will recover from the first episode, usually within 3 months of taking treatment and 20% will then never have a further episode and return to full functioning. However, 70% will recover but relapse in the future, with increasing levels of negative symptoms between episodes.

• Even with treatment, 50% of patients will relapse in the first 2 years. Approximately 10% of patients will never recover from their first episode and will need high levels of health and social services input and support for many years. Over the first 5 years of the illness, 5% of patients will die by suicide. Causes • Predisposing factors • Precipitating factors • Maintaining factors • The biological basis • Structural brain changes Predisposing factors • The causes of schizophrenia are still largely unknown. Genetic and environmental factors are important. The risk of schizophrenia is increased 15-fold if a first-degree relative has schizophrenia.

• The concordance rate in identical twins is 40%, strongly suggesting a genetic effect as well as showing that environmental factors must be operating too. The genetic effect is likely to be several additive genes each of small individual effect: a polygenic model.

  Linkage studies and genetic association studies have provisionally identified some of these vulnerability genes. Also found in the families of schizophrenic probands are increased rates of a non-psychotic disorder of personality known as schizotypal disorder, with social isolation and eccentric thinking; this is genetically related to schizophrenia.

• About a third of people who develop schizophrenia have had lifelong abnormalities, with poor social skills and few friends, often with slightly delayed motor and cognitive milestones. These are sometimes called schizoid traits.

  Environmental risk factors include a range of early neurological insults that slightly increase the risk of schizophrenia many years later: obstetric complications, childhood head injury and childhood encephalitis.

• Schizophrenic patients often have minor non-progressive brain changes detectable by computed tomography (CT) or magnetic resonance imaging (MRI). The most common is minor enlargement of lateral cerebral ventricles, but not to a degree considered definitely abnormal by a radiologist. Genetics Studies Method: – Family studies – Twin studies – Adoption studies Family studies • The risk for developing schizophrenia in first-degree relatives of schizophrenic patients is elevated compared to the risk of general population. • Parents of schizophrenic patients have a lifetime prevalence of 5.9% and siblings have a prevalence of 10%. • Children of schizophrenic have a lifetime prevalence of 12.8%.

TWIN STUDY PHOTO Twin studies • Identical twins have identical DNA, while dizygotic twins share 50% of their DNA • If schizophrenia were completely genetic, concordance rates in MZ:DZ twins would be 100:50%, or 2:1 Twin studies • Concordance rates among MZ (monozygote) pairs is higher than that among control • concordance rates are about 50% for MZ and about 10% for DZ (dizygote) . It might be expected that some environmental factors relevant to etiology.

Adoption studies • The risk for schizophrenia is higher in biological relatives than in adoptive relatives of control. • The finding supports the genetic hypothesis

• PET (positron emission tomography )scans of a schizophrenia sufferer's brain (left) and normal brain (right). Genetic Risk Factors for Schizophrenic PHOTO

Precipitating factors • Although clear precipitating factors are usually absent, two important classes of factor can trigger the first onset of schizophrenia in predisposed people: stressful life events and street drug use, particularly of amphetamine-like drugs. Maintaining factors

  Stressful family environment was once thought to be a cause of schizophrenia. This is now known not to be the case. However, it can cause relapse in someone who has had schizophrenia. Ways of measuring how families interact have been developed. 

• Families who have high levels of criticism, hostility and overinvolvement are said to have high expressed emotion (EE) and studies have shown that people in remission from schizophrenia are more likely to have a relapse in such a family environment.

  Since families are often the principal caregivers for younger people with schizophrenia, techniques to support families and to reduce EE if necessary have been developed and shown to reduce relapse. 

  Family intervention involves education about the illness, then advice about dealing with problem behaviours and how to ask for help when needed. A family support worker may be available, often from the voluntary sector. Families find the negative symptoms the most stressful to deal with.

• Other maintaining factors are poor compliance with treatment and continued street drug use. The biological basis • The dopamine hypothesis: The so-called dopamine hypothesis states that the symptoms result from overactivity of dopamine, particularly in the mesocortical pathway projecting from temporal to frontal areas.

• First put forward in 1963, the hypothesis was based on two clinical observations: a. amphetamines, which released dopamine, could cause schizophrenia-like positive symptoms if overused; and b. antipsychotic drugs caused side effects resembling Parkinson's disease, which was known to be caused by dopamine deficiency.

• Further evidence was that the clinical potency (number of milligrams to have a clinical effect) of individual drugs could be shown to be closely correlated with their in vitro affinity to dopamine D2 receptors.

• Problems with the hypothesis were that it did not account well for negative symptoms and there was no direct evidence showing increased dopamine receptors in the brains of never-treated patients at postmortem or by scanning (positron emission tomography, PET).

  The hypothesis would not predict the effects of clozapine, the superior efficacy of which is achieved with a relatively low blockade of dopamine D2 receptors.

  The dopamine 1 (D1) receptor family, which includes Dl and D5 receptors, is present in high concentration in the cortex and striatum. The dopamine 2 (D2) receptor family consists of D2, D3, and D4 receptors and is concentrated in the limbic and striatal regions. 

• Serotonin hypothesis Serotonin (5-HT) neurons originate in the midbrain dorsal and median raphe nuclei, which project to the cortex, striatum, hippocampus , and other limbic regions. There are at least 15 types of 5-HT receptors; of these, the most relevant to schizophrenia are the 5-HTl, 5-HT1D, 5-HT2, 5-HT3, 5-HT6, and 5-HT7 receptors.

• Newer antipsychotic drugs such as clozapine, olanzapine, risperidone, quetiapine, and sertindole are potent antagonists of the 5-HT2A receptor. Some of the advantages of these drugs may result from their greater potency as 5-HT2A-receptor antagonists, relative to D2-receptor blockade.

• The most likely advantages of these drugs, related to their higher affinity to 5-HT2A versus DA receptors, are their low D2-induced EPS profile and their ability to improve negative symptoms.

• Glutamate hypothesis • Decreased levels of glutamate in the CSF(cerebrospinal fluid) of patients with schizophrenia • Some antagonists of NMDA receptors can produce a range of positive and negative symptoms and cognitive dysfunction in normal control subjects and in schizophrenic patients. • Neuroleptics can block some of the clinical effects of PCP. Structural brain changes • Structural brain imaging using CT and MRI consistently demonstrate mild non-progressive enlargement of cerebral spaces, such as the lateral cerebral ventricles, in patients with schizophrenia compared with normal individuals.

  These findings suggest that patients with schizophrenia have slightly less brain tissue, affecting, particularly, cortical grey matter and the limbic system; the latter is involved in the control of emotions and memory. 

  Other structures, such as the thalamus, which is involved in the regulation of the flow of information to the cerebral cortex, have also been implicated.

A Brain Disease:

CT scans showing ventricular enlargement in a patient with schizophrenia Hippocampal Atrophy in Schizophrenia MR Images of Brain, Ventricles, and Hippocampus

Schizophrenia 2 Symptoms • The symptoms of schizophrenia can be divided into positive symptoms and negative symptoms. Positive symptoms • a. delusions: in schizophrenia these are often bizarre. • b. hallucinations: these are usually auditory; about 20% of patients will have visual, olfactory or tactile hallucinations. • c. schizophrenic formal thought disorder.

Negative symptoms
a. poor self-care
b. little spontaneous speech
c. ‘blunted’ affect (mood)
d. loss of normal willpower

Prodromal syndrome • Changes in mood: depression, anxiety, mood swings, irritability • Changes in cognition: odd or unusual ideas, vagueness, deterioration in study or work • Changes in perception of self and the world • Changed behaviors, withdrawal and loss of interest in socializing, suspiciousness, deterioration in role function • Physical changes: in sleep and appetite, loss of energy, reduced drive and motivation, etc. Prodromal syndrome • Prodromal phase: a clear deterioration in functioning that occurs before the active phase. self care deficit academic, occupational and social function ,unusual behavior, thoughts, perceptual experiences

• You should be alert to the following signs and symptoms in the mental state examination of someone who might have schizophrenia. • Appearance and behaviour • Speech • Mood • Thoughts • Abnormal experiences • Cognitive state • Self-appraisal

A. Appearance and behaviour • Abnormal movements as a result of illness. The individual may be restless and agitated. They may be doing unusual things. Mannerisms are seemingly purposeful movements done for no reason, such as saluting.

A. Appearance and behaviour

 Stereotypies  are repetitive non-purposeful movements, such as rocking or grimacing. Rarely there may be catatonic signs, where the person is frozen like a statue, allowing their limbs to be moved to new positions like Plasticine. 

A. Appearance and behaviour

b. Abnormal movements as a result of drug treatment.  Antipsychotic drugs can themselves cause involuntary movements.
 c. Negative symptoms. These include poor personal hygiene and self-care. Is the person dishevelled or unwashed?

• Speech

    Speech is often normal. However, about half of patients with schizophrenia have a characteristic disorder of language called schizophrenic formal thought disorder. This is an abnormality in the way the person is speaking, which when mild is quite subtle, but when marked is striking. 

• Speech

    The person‘s speech loses the usual logical flow between one idea and the next, so that segments of speech become partly disjointed  from each other. This is known as loosening of associations or 'knight's move thinking', after the two-squares-forward-one-sideways move in chess.

Loosening of associations • Interviewer: How have you been feeling today? • Patient : Well, in myself I have been okay what with the prices in the shops being what they are and my flat is just round the corner. I keep a watch for the arbiters most of the time since it is just round the corner. There is not all that much to do otherwise.

Other formal thought disorder – poverty of thought – splitting of thought – incoherence of thought – blocking of thought – thought deprivation – thought insertion/forced thinking – thought hearing – diffusion of thought/thought broadcasting – neologism – paralogism thinking – obsessive idea

• Speech

    Concrete thinking describes an aspect of thought disorder that involves the impairment of the ability to think in abstract ways. This is often most obvious if you ask the person to solve an abstract verbal puzzle or explain a proverb. 

• Mood

      Mood in schizophrenia can be normal. Two particular abnormalities are important to look for on examination. 

• Mood

      a. Blunted affect  This is where mood in conversation can be seen to have lost its usual variability. Instead of the normal play of facial expressions and gestures in a social situation, a person with blunted affect appears to have an unresponsive, unchanging expression. This is one of the negative symptoms of schizophrenia. 

• Mood

      b. Incongruous affect  This is where, for no apparent reason, the person will giggle or smile secretively to themselves in a way that is inappropriate to the situation. Incongruous affect is found only in schizophrenia. It is called characteristic symptom of schizophrenia.

• Thoughts • Abnormal beliefs: Common in schizophrenia are ideas of reference, where the person has the impression that items on the television or radio, or in the newspapers, are referring specifically to them.

 This can also extend to everyday occurrences in the street, such as the impression that people in the street seem to be looking at the person, or the registration plates of passing cars have a special meaning for the person. These become delusions of reference if they become fixed and unshakeable.

• Thoughts • Other delusions in schizophrenia can be persecutory , grandiose, religious or hypochondriacal. They can be extremely bizarre. When a delusion becomes so extensive that it becomes a series of linked, fixed beliefs that govern much of what the person says or does, it is said to be a systematized delusion.

  Delusions in schizophrenia can be primary, where they arise out of the blue, often quite suddenly, or secondary to pre-existing hallucinations as an attempt to explain them, as the result of a radio receiver implanted in the brain, for instance. 

• Abnormal experiences

    Hallucinations are usually auditory, of speech, in schizophrenia. Visual, olfactory or tactile hallucinations can occur in schizophrenia but are unusual and should alert you to the possibility of organic illness. Most sufferers can describe their auditory hallucinations in some detail. 

• Cognitive state

    This will be essentially normal in schizophrenia, although deficits in concentration and abstract thought may be detected, particularly if the person is acutely psychotic or has chronic negative symptoms.

– Cognitive dysfunction Is a cardinal feature of schizophrenia – On average, first diagnosed schizophrenic patient’s IQ is 10 points lower than control. – Children at risk for schizophrenia have lower IQs than do control.

– The first episode patients exhibit impairments in attention, concentration, working memory, visual- spatial memory, semantic memory, recall memory, and executive function. – Cognitive impairment is often independent of positive and negative symptoms and even of the disorganization syndrome and the course of illness..

• G Self-appraisal

    Insight into the illness is usually lost in acute schizophrenia and sometimes is not regained fully after recovery. Insight is not a clear-cut issue. People can retain insight into the fact they have an illness but not agree they need treatment, for example. 

Subtypes of schizophrenia • Subtypes of schizophrenia can be based on the balance of symptoms and include paranoid, with prominent delusions, and hebephrenic, with prominent negative symptoms and poor outcome. Catatonic schizophrenia is rare and involves marked mannerisms and posturing. Paranoid schizophrenia • This type is the most common form of the illness. • Is characterized by prominent paranoid delusion, thought processes and mood are relatively spared. The patient may appear normal until his abnormal beliefs are uncovered

Hebephrenic schizophrenia • Is characterized by the absence of systematized delusions and the presence of incoherence and inappropriate affect. • Silly and childish in their behavior • With prominent negative symptoms and poor outcome

Catatonia schizophrenia • This type is much less frequently now than in previous years. • Motor disturbance is the dominant feature, consisting of either agitated hyperactivity or a decrease in gross motor activity with stupor, rigidity, or bizarre postures

Simple schizophrenia • Predominance of poverty of thought, apathy and abulia, lack of positive psychotic symptoms; • Severe impairment in social functioning with gradual decline; • The onset is insidious and progression is gradual with duration of at least 2 years. Undifferentiated schizophrenia • This type is also called mixed type or unclassified type. • absence of systematized delusions • the presence of incoherence and inappropriate affect. Residual schizophrenia • Schizophrenia without complete remission for at least 2 years; • Marked improvement in mental state with partial remission of symptoms and presence of at least one of the following: – specific positive symptom; – specific negative symptom, such as poverty of thought, apathy, abulia or social withdrawal; – personality change. – The impairment of social functioning. Symptoms are relatively stable and have minimal improvement or deterioration for at least one year Chronic schizophrenia

  Chronic schizophrenia  is characterized by long duration and 'negative' symptoms of underactivity, lack of drive, social withdrawal and emotional emptiness.

Post-schizophrenic depression • The patient exhibits features of schizophrenia in the past one year. The depressive symptoms occur when the schizophrenic symptoms are in partial remission • Prominent depressive symptoms have been present for at least two weeks, accompanied by residual psychotic symptoms • Depression and schizoaffective disorder are excluded.

Type I and type type II schizophrenia • Crow have described two syndromes in 1980 • The features of Type I: – acute onset – positive symptoms – good social function during remissions – good response to antipsychotic drug – DA over-activity.

Type I and type type II schizophrenia • The features of Type II: – negative symptoms – poor outcome – poor response to antipsychotic drugs – without evidence of DA over-activity – poor premorbid adjustment – an earlier age of onset – structure change in the brain. • Most of patients are a mixture of type I and type II

Diagnostic criteria  The Diagnostic and Statistical Manual of Mental Disorder, 4th edition (DSM-IV)  International Classification of Diseases (ICD-10)  Chinese Classificication and Diagnostic Criteria of Mental Disease, the third version (CCMD-3)

DSM-IV Diagnostic Criteria A. Characteristic symptoms: Two (or more) of the following, each present for a significant portion of time during a l-month period (or less if successfully treatment): (l) Delusions (2) Hallucinations (3) disorganized speech (e.g., frequent derailment or incoherence) (4) Grossly disorganized or catatonic behavior (5) Negative symptoms, i.e., affective flattening, alogia, or avolition

• B. Social/occupational dysfunction: For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations, or self-care are markedly below the level achieved prior to the onset (or when the onset is in childhood or adolescence, failure to achieve expected level of interpersonal, academic, or occupational achievement).

C. Duration: Continuous signs of the disturbance persist for at least 6months.This 6 month period must include at least 1month of symptoms (or less if successfully treated)that meet Criterion A (i.e., active-phase symptoms)and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or two or more symptoms listed in Criterion A present in an attenuated form ( eg , odd beliefs, unusual perceptual experience)

D. Schizoaffective and mood disorder exclusion: Schizoaffective disorder and mood disorder with psychotic features have been ruled out because either (1) no major depressive, manic, or mixed episodes have occurred concurrently with the active-phase symptoms, or (2)if mood episode have occurred during active-phase symptom, their total duration has been brief relative to the duration of the active and residual periods.

E. Substance/general medical condition exclusion: The disturbance is not due to the direct physiological effect of a substance (e.g., a drug of abuse, a medication)or a general medical condition.

F. Relationship to a pervasive developmental disorder: If there is a history of autistic disorder or another pervasive developmental disorder, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations are also present for at least a month (or less if successfully treated)

Clinical diagnosis considerations • Obtain as much information as possible: eg, medical and psychiatric history, family and social history, other pertinent information from family and friends. • In most cases , onset are insidious and uncommon over 40. • Prodromal symptoms. • Symptoms:first rank symptoms. • Increasingly poor functioning at home, work or school, social withdrawal. Differential diagnosis • a. schizoaffective disorder : Positive symptoms including first rank symptoms are combined with prominent mood disturbance, either manic or depressed; long-term outcome tends to be better than in schizophrenia

• b. delusional disorder Characterized by gradual onset of systematized persecutory delusions, without hallucinations or thought disorder.

• c. drug-induced psychosis Has a sudden onset and resolves over a few days after the drug is withdrawn; amphetamine-like drugs, including Ecstasy , are often responsible and the usual difficulty is distinguishing this from drug-induced relapse of schizophrenia.

• d. organic psychoses These can mimic schizophrenia and need to be excluded. • e. hallucination disorder Characterized by onset of systematized hallucination, without delusions or thought disorder. management

Management  Pharmacologic Treatments:  Electroconvulsive Treatment (ECT):  Psychosocial Treatment:

• Pharmacologic Treatments:  Typical antipsychotic drugs: chlorpromazine, haloperidol, sulpiride  Atypical antipsychotics: clozapine, risperidone, olanzapine, quetiapine

(antipsychotic drugs are not curative and do not eliminate the fundamental thinking disorder, but often do permit the psychotic patient to function in a supportive environment. )

– Antipsychotic drugs (also called neuroleptic drugs) are used primarily to treat schizophrenia but are also effective in other psychotic states, such as manic states and delirium. – Typical antipsychotic drugs are competitive inhibitors at a variety of dopamine receptors, but their antipsychotic effects reflect competitive blocking of dopamine receptors. In contrast, the newer atypical antipsychotic drugs appear to owe their unique activity to blockade of serotonin receptors.

Other drugs • Antidepressant drugs • Mood stabilizers • Anxiolytic drugs

The first episode • The longer the person has active psychotic symptoms, the worse the eventual outcome, so swift referral from primary to secondary care is important when psychotic symptoms are present.

  Some evidence indicates that prolonged delays in starting antipsychotic treatment may predict a poorer outcome, presumably because some aspects of the process of psychosis may be biologically toxic to brain structure（encephalatrophy） . 

Full history and assessment will lead to the diagnosis in most cases. Physical examination and investigations are essential; these include:

   a. neurological examination
   b. full blood count

c. erythrocyte sedimentation rate (ESR) d. electrolytes and urea e. thyroid function f. electroencephalograph (EEG) g. CT scan h. urine screen for street drugs.

   Care needs to be taken over how the diagnosis is discussed with the patient and family; skills in breaking bad news are important

Management of the first episode will usually involve admission as an inpatient or daypatient, although over a third of patients will be able to be managed at home throughout their first episode, with frequent visits from staff of the community mental health team (CMHT). Most people in their first episode will be young adults. Almost all patients will need antipsychotic drug treatment, although low doses of a conventional drug (e.g. haloperidol 1-2 mg twice daily) or new atypical drug are usually sufficient. Education of the patient and family about the nature and management of schizophrenia are very important.

Maintenance after the first episode • Maintenance management after the acute symptoms have resolved will include regular CPA (care programme approach) meetings organized by the keyworker. Maintenance antipsychotic drug treatment will be needed. • How long this should continue if the person has no symptoms depends partly on how severe the initial episode was. Drug treatment should be continued for a minimum of a year; if the first episode was severe, drugs should continue for at least 2 years.

Clear discussion of the 'pros and cons' of continued drug treatment will help compliance.

Electroconvulsive treatment • Patients who have not responded to recommended drugs should be considered for a trail of Electroconvulsive treatment (ECT). • ECT is used infrequently today because of the ease of administration of antipsychotics and the need for maintenance treatment, which is difficult to provide on an outpatient basis. • A short course of ECT (e.g. 6-12 treatments) may be useful as an adjunctive treatment to antipsychotic drugs of all classes, including clozapine, for patients with limited response to treatment and particularly when very rapid control of agitated behavior is necessary. • Excited catatonia and severe agitation will often respond to antipsychotics, benzodiazepines, reduced environmental stimulation, seclusion, and physical restraint. If these methods fail, ECT should be administered. There is inadequate data to recommend maintenance ECT for schizophrenia. • Acute relapse needs reinstatement, change or increase of antipsychotic drug treatment. Admission to daypatient or inpatient services may be needed. Attempts to clarify reasons for relapse are needed.

Common cause of relapse • Non-compliance with drug treatment • Discontinuation, or reduction, of drug treatment • Street drug use • Family stress; high expressed emotion • Life event • childbirth Summary • Hospitalization is required for acutely psychotic patients, especially those with violent commanding auditory hallucination. • Conventional antipsychotic drugs are effective against positive symptoms in 60% of patients but are often less useful for negative symptoms

Summary • The novel antipsychotic medications have become the mainstay of treatment as they are helpful in patients unresponsive to conventional neuroleptics and may also be useful for negative and cognitive symptoms • Long acting injectable forms of haloperidol and fluphenazine are ideal for noncompliant patients • Psychosocial intervention, rehabilitation, and family support are also essential. Management of chronic schizophrenia • Chronic schizophrenia is characterized by long duration and 'negative' symptoms of underactivity, lack of drive, social withdrawal and emotional emptiness. • Patients are often unable to live independently, needing sheltered housing or a residential placement with specialist staffing. （vagrant ）

• Persistent positive symptoms, which fail to respond well to other antipsychotic drugs, will improve with clozapine in about 50% of patients. • The starting dose is 25 mg per day with a maintenance dose of 150-300 mg daily. White cell counts should be monitored weekly for 18 weeks and then 2-weekly for the length of treatment.

• In addition to its antipsychotic actions, clozapine may also help reduce aggressive and hostile behaviour and the risk of suicide. It can cause considerable weight gain and sialorrhoea. There is an increased risk of diabetes mellitus.

  When the white blood cell count falls below 3000 cells per mm3, clozapine should be stopped and not restarted. If agranulocytosis has developed, granulocyte colony stimulating factor or some other growth factors can be used to hasten the recovery process. Recovery generally takes 7-14 days. 

Recent evidence supports the effectiveness of a modified form of cognitive-behaviour therapy for persistent delusions and hallucinations.

Persistent negative symptoms are more difficult to treat. Rehabilitation uses a set of graded techniques in order to reduce partially the negative symptoms that cause most disability.

• Rehabilitation includes occupational therapy, which starts with assessing the degree of functional disability in terms of doing everyday tasks.

• In chronically noncompliant patients who are unwilling to take oral medication, biweekly or monthly injections of fluphenazine decanoate or haloperidol decanoate (given at clinics or by visiting nurses) often decrease relapse rates significantly.

• Prognosis : The prognosis of schizophrenia is variable. A review of treatment studies suggests that 15-25% of people with schizophrenia recover completely, about 70% will have relapses and may develop mild to moderate negative symptoms, while about 10% will become seriously disabled. Prognosis factors • Good prognosis • Acute onset • Early treatment • Good response to treatment • female sex • Good educational and social adjustment previously • Poor prognosis • Early age at onset • Insidious onset • Poor previous adjustment • Negative symptoms • Street drug use

Intensive community treatments

   Assertive outreach involves the delivery of continuous and comprehensive community care and treatment to certain patients. It usually involves a multidisciplinary team, who provide 24 hour support and cover. 

There is a small patient-to-staff ratio of about 10:1, so that staff can provide close follow-up and contact with patients. Usually each member of the team is familiar with each of the patients, so any member of the team can respond to each patient in an appropriate fashion

It is most suitable for those patients with severe mental illness who are at high risk of self-harm or harm to others, and who will not attend clinic appointments or who are erratic in their pattern of attendance. These people often have multiple social problems and drug abuse in addition to psychosis. Assertive outreach, in the UK, is more effective at keeping patients in contact with services and in treatment than conventional care. It does not, however, result in a better clinical outcome. In the USA, it has been shown to reduce hospital admissions, but there is no evidence that it has such an effect in the UK. This may be because of differences in service delivery in the UK or because assertive outreach is not implemented as intensively in the UK as it has been in the USA.

   Case management is another form of intensive community care. It differs from assertive outreach in that one member of staff usually works with a small group of patients to provide intensive follow-up and care. 

The case manager will be part of a team but, usually, will work exclusively with his/her own patients. Twenty-four hour cover is not usually provided

Treatment recommendations 1. Antipsychotic medications, should be used as the first-line treatment to reduce psychotic symptoms for persons experiencing an acute symptom episode of schizophrenia. 2. The dosage of antipsychotic medication for an acute symptom episode should be in the range of 300-800 mg CPZ (chlorpromazine) equivalents per day for a minimum of 6 weeks. Outside this range should be justified. Treatment recommendations 3. Persons experiencing their first acute symptom episode should be treated with an antipsychotic drug. but the dosage should remain in the lower end of the range (300-500mg CPZ equivalents per day) 4. Rapid neuroleptization should not be used 5. No superior efficacy of any drugs over another in the treatment positive symptoms, choice of drugs should be made on the basis  patient acceptability  prior individual drug response  side-effect profile  long-term treatment planning

Treatment recommendations 6. Prophylactic use of anti-Parkinson agents to reduce the incidence of EPS (extrapyramidal side effect ) should be determined on a case-by- case basis.

• Steven had slightly slower milestones at walking and talking than his elder siblings. At primary school he was a timid child with few friends. At secondary school, he was bullied and for periods refused to attend. At 13, years of age, he was referred to child mental health service because of persistent nightmares. He told the assessment team that he knew his room was haunted and he could hear murmuring from under his bed. was referred urgently to mental health services where she was assessed jointly by a nurse and psychiatrist.

• He did not re-attend the clinic. His schoolteacher noticed that he seemed distracted and was whispering to himself. At age 15 he was reassessed and admitted to an adolescent mental health unit. He was noticed to be grimacing and smiling incongruously, His computed tomographic scan showed slight enlargement of his lateral ventricles, which was within normal limits. He complained that his movements were being controlled by ghosts.

• After taking risperidone, his delusions improved but he was still withdrawn and spoke little. He was frightened to return to his bedroom. He left home unannounced the next week. Three months later he was found sleeping rough in a nearby town, dishevelled, emaciated and muttering to himself. He was re-admitted to a psychiatric unit for further treatment. Diagnosis: schizophrenia • Symptoms: • Lack of selfcare • Poor motivation • Little spontaneous speech • Delusions • Hallucinations • Incongruous affect Characteristic • Soft neurological signs during childhood • Insidious onset • Early onset • Negative symptoms • Poor compliance with treatment • Little insight into his illness

Part 2 Other psychotic disorders Include: 1. Paranoid mental disorder 2. Acute and transient psychosis Schizophrenia-like psychosis Travelling psychosis Delusional episode 3. Induced psychosis 4. Schizoaffective psychosis

Paranoid mental disorders • Definition: This group includes a variety of disorders in which systemic delusions constitute the main clinical feature and in which etiology is unknown. Hallucinations may be transiently present but not prominent. Except the influence of delusions, the other psychological fields such as affect, speech, and behavior are not significantly abnormal. Usually, onset is after 30 years old. Acute and transient psychosis Definition: This group of disorders is characterized by psychotic symptoms, with an acute onset and transient course. Most patients can be remitted and almost remitted.

Travelling psychosis This disorder acutely occurs on the way of travelling (such as railway, highway, waterway, airway, etc.). There are obviously related with stress factors (such as mental stimulus, overly fatigue, excessive crowded, chronic anoxia, lack of sleep, lack of nutrition and water) just before the onset of disorder. The main manifestations are disturbance of consciousness, episodic delusions, episodic hallucinations, or behavioral disturbance. The course is transient. If the travelling is broken and the patients have adequate rest, they may be remitted in several hours or one week..

Delusional episodes Definition: the disorder often abruptly occurs (from a nonpsychotic state to a clearly psychotic state within one week or less) without obvious inducement. It is characterized by transient delusions. Mood and behavioral disorders may also be present. The disorder generally occurs in the young people, rarely occurs in the people over 50 years old, and never in children.

Schizoaffective psychosis Definition: This is a recurrent disorders in which both affective and schizophrenic symptoms are prominent within the same episode of illness. Schizophrenic symptoms are such positive psychotic symptoms as delusions, hallucinations, and disorder of thinking. Affective symptoms are depressive symptoms or manic symptoms.

Treatment • Just like the treatment of schizophrenia, the dosage should be lower and the period should be shorter. supplement • Prodromal phase:a clear deterioration in functioning that occurs before the active phase.self care deficit academic,occupational and social function ,unusual behavior,thoughts,perceptual experiences

• A 21-year-old man is brought to the emergency department by the police after he was found sitting in the middle of a busy street .By way of explanation, the patient states, “The voices told me to do it.” The patient says that for the past year he has felt that“ people are not who they say they are.” He began to isolate himself in his room and dropped out of school．He claims that he hears voices telling him to do “bad things．” There are often two or three voices talking，and they often comment to each other on his behavior．

• He denies that he currently uses drugs or alcohol，although he reports that he occasionally smoked marijuana in the past．He says that he has discontinued this practice over the past 6 months because“ it makes the voices louder．”He denies any medical problems and is taking no medication．

• On a mental status examination the patient is noted to be dirty and disheveled．with poor hygiene．He appears somewhat nervous in his surroundings and paces around the examination room．always with his back to a wall．He states that his mood is“OK”．His affect is congruent，although flat．His speech is of normal rate，rhythm，and tone．His thought processes are tangential．and loose associations are occasionally noted．His thought content is positive for delusionsand auditory hallucinations．He denies any suicidal or homicidal ideation． questions • What is the most likely diagnosis for this patient?

• What conditions are important to rule out before a diagnosis can be made?