Schizophrenia

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Epidemiology ��" Oxford Textbook of psychiatry", 2 nd edition

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(1)differences in diagnositic criteria
(2)differences in migration: more able to tolerate extreme isolation
(3)differences in methods of case-finding

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Acute syndrome ��" Oxford Textbook of psychiatry", 2 nd edition

1.Behavior: preoccupation, social withdraw, smile or laugh without obvious reason
2.Thought disorder: vagueness, concrete thought
3.Stream of thought disorder: pressure of thought, poverty, blocking
4.Loosening of association: illogical, talking past the point(Vorbeireden), verbigeration, paraphrases, neologism
5.Mood abnormalities:
(1)anxiety, depression, irritability, euphoria
(2)blunting of affect
(3)incongruity of affect
6.Auditory hallucinations: Gedankenlautwerden, écho de la pensée
7.Delusional halluscinations
8.Delusions(characteristic): "Wahnstimmung"
(1)of persecution
(2)of reference
(3)of control
(4)about possession of thought
9.Orientation: normal, Attention: impaired
10.Insight: impaired

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Chronic syndrome ��" Oxford Textbook of psychiatry", 2 nd edition

1.Schizophrenic defect state: negative features: diminished volition
2.Disorders of movement:
(1)Catatonia: stupor, excitement
(2)Waxy flexibility(Catalepsy): symbolic significance
(3)Stereotypy(not goal-directed), Mannerism(goal-directed)
(4)Ambitendence(Ambivalence, Mitgehen, forced grasping , automatic obedience)
3.Social behavior deterioration
4.Delusions with little emotion or "encapsulated"

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Depressive symtoms ��" Oxford Textbook of psychiatry", 2 nd edition

1.Side effect of antipsychotics: not the full, motor side-effects mistaken for depressive retardation
2.Response to recovery of insight
3.Intergral part of schizophrenia

Factors modifying the clinical features ��" Oxford Textbook of psychiatry", 2 nd edition

1.Social stimulation: Under-stimulation increases negative symptoms....Over-stimulation precipitates positive symptoms
2.Social background: religious ��
3.Age
4.Low intelligence

History ��" Oxford Textbook of psychiatry", 2 nd edition

19c     Einheitpsychose(Griesinger)����Classification(Morel)
1852   démence précoce(Morel): withdrawl, odd mannerism, self-neglect, intellectual deterioration
1863   catatonia(Kahlbaum)
1871   hebephrenia(Hecker)
1893   dementia praecox(Kraepelin)
��It is commonly held that Kraepelin regarded dementia precox as invariably progressing to chronic deterioration. However, he reported that , in his series of cases, 13 percent recovered completely, and 17 percent were ultimately able to live and work without difficulty.

1911   schizophrenia(Bleuler)
��concerned less with prognosis and more with the mechanisms of symptom formation
��Fundamental symptoms: associations, emotional reactions, autism
��Accessory symptoms: hallucinations, delusions, catatonia, abnormal behaviors

1959   first rank symptoms(Schneider)
��not supposed to have any central psychopathological role, but helping in diagnosis
��(1)auditory hallucinations:
hearing thoughts spoken aloud
hearing voices referring to himself / herself, made in the third person
auditory hallucinations in the form of a commentary
(2)thought withdrawal, insertion and interruption
(3)thought broadcasting
(4)somatic hallucinations
(5)delusional perception
(6)feelings or actions experienced as made or influenced by external agents

1960   Europe(Schneider's, narrower)����US(psychodynamic, wider)
����the former:
high reliability in diagnosis, no apparent heritability, meet criteria of mania
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��DSM-IV Diagnostic Criteria A. Characteristic symptoms: Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated):

Delusions
Hallucinations
Disorganized speech (e.g., frequent derailment, incoherence)
Grossly disorganized or catatonic behavior
Negative symptoms (e.g., affective flattening, alogia, avolition)

Note: Only one Criterion A symptom is required if delusions are bizarre or hallucinations consist of a voice keeping up a running commentary on the person�s behavior or thoughts, or two or more voices conversing with each other.

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 6 months. This 6-month period must include at least 1 month 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 (e.g., odd beliefs, unusual perceptual experiences).

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 episodes have occurred during active-phase symptoms, 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 effects 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).

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��ICD-10 Diagnostic Criteria The disturbance involves the most basic functions that give the normal person a feeling of individuality, uniqueness, and self-direction. The most intimate thoughts, feelings, and acts are often felt to be known to or shared by others, and explanatory delusions may develop, to the effect that natural or supernatural forces are at work to influence the afflicted individual's thoughts and actions in ways that are often bizarre.
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Although no strictly pathognomonic symptoms can be identified, for practical purposes it is useful to divide the above symptoms into groups that have special importance for the diagnosis and often occur together, such as:

(a) thought echo, thought insertion or withdrawal, and thought broadcasting;
(b) delusions of control, influence, or passivity, clearly referred to body or limb movements or specific thoughts, actions, or sensations; delusional perception;
(c) hallucinatory voices giving a running commentary on the patient's behaviour, or discussing the patient among themselves, or other types of hallucinatory voices coming from some part of the body;
(d) persistent delusions of other kinds that are culturally inappropriate and completely impossible, such as religious or political identity, or superhuman powers and abilities (e.g. being able to control the weather, or being in communication with aliens from another world);
(e) persistent hallucinations in any modality, when accompanied either by fleeting or half-formed delusions without clear affective content, or by persistent over-valued ideas, or when occurring every day for weeks or months on end;
(f) breaks or interpolations in the train of thought, resulting in incoherence or irrelevant speech, or neologisms;
(g) catatonic behaviour, such as excitement, posturing, or waxy flexibility, negativism, mutism, and stupor;
(h) "negative" symptoms such as marked apathy, paucity of speech, and blunting or incongruity of emotional responses, usually resulting in social withdrawal and lowering of social performance; it must be clear that these are not due to depression or to neuroleptic medication;
(i) a significant and consistent change in the overall quality of some aspects of personal behaviour, manifest as loss of interest, aimlessness, idleness, a self-absorbed attitude, and social withdrawal.

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Type I and Type II ��Crow, T.J. (1980). Molecular pathology of schizophrenia: More than one disease process? British Medical Journal, 280, 66-68.

1.Acute schizophrenia, also known as Type I syndrome, is characterized by the presence of positive symptoms (delusions, hallucinations, and thought disorder) that are associated with an increase in dopaminergic transmission. Type I symptoms tend to respond well to neuroleptic treatment because these drugs are dopamine antagonists, and therefore, may be reversible. Individuals with the Type I syndrome also have a better prognosis than individuals with the

2.Type II syndrome, which Crow argues is a more chronic form of schizophrenia that is characterized by the presence of negative symptoms.  Because these symptoms are apparently unrelated to dopaminergic transmission, and are instead thought to be associated with structural brain abnormalities, such as enlarged ventricles, neuroleptic treatment is often unsuccessful, and has actually been found to exacerbate the negative symptoms.

While episodes of Type I symptoms may be followed by the development of the Type II syndrome, explains Crow, Type II symptoms may occur in the absence of the Type I syndrome.

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Differential diagnosis Medical: Delirium
Neural: Dementia, Epilepsy(Temporal lobe)
Opioid: Medication, Alcohol, Drug
(����clouding of consciousness, disorientation)
Psychy:
1.Personality disorder
2.Mood disorder, esp. mania
(����degree and persistence, relation , previous episodes, family hx)
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Etiology ��" Oxford Textbook of psychiatry", 2 nd edition

1.Predisposing causes:
genetic
environmental
neurological
interpersonal and social
psychodynamic

2.Precipitating:
life eventts

3.Perpetuating:
social and family influences

"Neurodevelopmental hypothesis"

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1.Genetics 1.Family studiies: 5% lifetime risk
2.Twin studies
��Concordance rate: 50% in MZ, 10% in DZ
(1)environmental factors
(2)genetic susceptibility, the same, but not expressed
(3)differential gene expression

3.Adoption studies: supports the genetic hypothesis
4.Modes of inheritance
5.Molecular genetic studies (linkage analysis, candidate gene)

2.Neuroanatomy 1.enlargement of lateral ventricles, esp. anterior, temporal horns
2.reduction of medial temporal structures, esp. hippocampus, parahippocampal gyrus
3.more evident in left side of brain
4.cytoarchitectural disturbances in the hippocampus, frontal cortex, cingulate gyrus, entorhinal cortex, not associated with gliosis
����disturbances in late migration/differentiation of neurons, lateralization
5.reductions in the volume of temporal lobe(MRI)
3.Clinical Neurology 1.Soft signs: in stereognosis, graphaeshesia, balance, propioception
2.Movement disorder
3.Temporal lobe epilepsy, Huntington's chorea
4.Neurophysiology EEG:
����theta activity, fast activity, paroxymal activity
����P300 reponse

Functional imaging: Hypovascularity in PET& SPET
1.Hypofrontality, impaired WCST
2.Left dorsolateral prefrontal cortex, psychomotor poverty syndrome
3.MZ: all affected have decreased  prefontal flow and reduced hippocampal volume

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5.Neuropsychology 1.Attension deficit
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6.Biochemistry The dopamine hypothesis

1.Amphetamine releases dopamine at central synapses
2.Antipsychotic drugs share dopamine receptor blocking effects

7.Neurodevelopmental 1.Perinatal factors

(1)obsteric complications:
pre-existing brain dysfunction may predispose to the development of obsteric complications.
(2)season of birth:
8 % excess in winter birth, perhaps viral in origin

2.Childhood development and antecedents
��passive as a baby, short attention span as a child, fast recovery of galvanic skin reponses

3.Personality factors
��schizoid/schizotypal personality
��difficult to distinguish between premorbid/prodromal symptoms
��more common among schizo p't and 1 deg relatives

4.Sex and age of onset
��earlier in men than in women, determining prognosis

8.Psychoynamic factors 1.Freud: "On narcissism"

��libido was withdrawn from external objects and attached to the ego. The result was exaggerated self-importance.

2.Klein:

��only late did the child realize that the same person could be good at one time and bad at another.

9.Family factor 1.Deviant role relationships:

��"Schizophrenogenic mother"

��marital skew: complete yield to another
marital schism: contrary views

2.Disordered family communication

��"double blind": an instruction given overtly, but is contradicted by a second more cover instruction.

��amorphous/fragmented communications

��an association between abnormal social communication in parents and schizophrenic illness in children may, in fact, be a consequence of a shared genetic inheritance.

10.Social factors 1.Culture

2.Occupation and social class: over-represented in lower social class

3.Place of residence: over-represented in disadvantaged inner-city areas

4.Migration
(1)Social selection: those unsettled people are becoming mentally ill
(2)Social causation: the effects of new environment

5.Psychosocial stresses
Prognostic factors ��Overall, 1/3 of patients achieve significant and lasting improvement; 1/3 improve some but have intermittent relapses and residual disability; and 1/3 are severely and permanently incapacitated.

��Factors associated with a good prognosis include relatively good premorbid functioning, late and/or sudden onset of illness, a family history of mood disorders rather than schizophrenia, minimal cognitive impairment, and paranoid or nondeficit subtype.

��Factors associated with a poor prognosis include early age of onset, poor premorbid functioning, a family history of schizophrenia, and disorganized or deficit subtype with many negative symptoms. Men have poorer outcomes than women; women respond better to treatment with antipsychotic drugs.

Social environment and course 1.Cultural background

2.Life events

3.Social stimulation
��While an understimulating hospital environment is associated with worsening of the so-called poverty syndrome, and overstimulating environment can precipitate florid symptoms and lead to relapse.

4.Family life
��"high expressed emotion" (making critical comments, expressing hostility, showing signs of emotional over-involvement) & relapse

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��Neuroleptic Malignant Syndrome: 5 criteria: 1.Recent treatment with neuroleptics within past 1-4 weeks
2.Hyperthermia (above 38C)
3.Muscular rigidity
4.At least 5 of the following:
Change in mental status
Tachycardia
Hypertension or hypotension
Diaphoresis or sialorrhea
Tremor
Incontinence
Increased creatinine phosphokinase (CPK) or urinary myoglobin
Leukocytosis
Metabolic acidosis
5.Exclusion of other drug-induced, systemic, or neuropsychiatric illness
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��Neuroleptic Malignant Syndrome:Tx: ��aggressive supportive care (rhabdomyolysis ��vigorous hydration and alkalinize the urine with IV NaHCO3 to prevent renal failure)
��Dopamine agonists: Bromocriptine, Amantadine, Levodopa
��Skeletal muscle relaxant: Dantrolene
��The rabbit syndrome ��a neuroleptic induced extrapyramidal side effect with late onset, consists of rapid fine rhythmic movements of the lips that mimic the chewing movements of a rabbit.
��Unlike the buccolingual movements of the tardive dyskinesia, the rabbit syndrome improves with antiparkinsonian medication. The condition is reported to be rare.
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��restless legs syndrome (RLS) ��Centrally acting dopamine receptor antagonists reactivate symptoms when given to patients with the syndrome. Results of single-photon emission computed tomography (SPECT) have suggested deficiency of dopamine D2 receptors. Sympathetic hyperactivity also has been implicated on the basis of observations that sympathetic nerve blockade relieves periodic limb movements of sleep and that alpha-adrenergic blockers improve symptoms of RLS. Studies also have suggested possible underactivity of the serotonin and gamma-aminobutyric acid (GABA) neurotransmitter systems.


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��restless legs syndrome (RLS): criteria ��The criteria for diagnosis of RLS are based on those developed by the International Legs Syndrome Study Group in 1995; 4 basic elements must be present to make the diagnosis. They are as follows:
1. A compelling urge to move the limbs, usually associated with paresthesias/dysesthesias
2. Motor restlessness, as seen in activities such as floor pacing, tossing and turning in bed, and rubbing the legs
3. Symptoms worse or exclusively present at rest (ie, lying, sitting) with variable and temporary relief on activity
Circadian variation of symptoms, which are present in the evening and at night. Often, symptoms are relieved after 5:00 am. 4. In more severe cases, symptoms can be present throughout the day without circadian variation.
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