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Schizophrenia
Dr Alin Mascas
ST4 GAP
Definition
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“Schizo” (split) and “phrene” (mind) to describe a fragmented pattern of
thinking of people suffering from this disorder.
• Schizophrenia is a severe form of mental illness affecting about 7 per
thousand of the adult population, mostly in the age group 15-35
years.(WHO)
• Schizophrenia is one of the terms used to describe a major psychiatric
disorder(or cluster of disorders) that alters an individual’s perception,
thoughts, affect and behaviour (NICE).
Historical perspective
• Written documents describing symptoms of schizophrenia were traced
back to Ancient Egypt and around 2000 BC.
• Benedict Morel – “demence precoce”
• Emil Kraepelin (German)-described schizophrenia (1887) as “dementia
precox” and differentiated it from manic depression
• Eugen Bleuler (Swiss)-coined the term “Schizophrenia”(1911)+ 4 “A”S
(loosening of associations, apathy, autism(social withdrawal),
blunt/incongruous affect)
• Kahlbaum described catatonia (1868)
Demographics (WHO)
•Schizophrenia affects about 24 million people worldwide.
•More than 50% of persons with schizophrenia are not receiving
appropriate care.
•90% of people with untreated schizophrenia are in developing
countries.
Demographics
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Incidence variable up to 5X depending on site (between 7-14:100 000)
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Incidence 3-5 X higher in migrant population. AESOP study concluded that all psychoses are
more common in the black and minority ethnic group compared to white population.
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Incidence 2 X higher in urban vs rural born population. Marcelis et al. (1998) (Dutch National
Psychiatric Register study) found that the effect of urbanicity on all psychoses was greater for
men than for women.
Male: female difference in incidence of schizophrenia is estimated to be around 1.4:1.
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Prevalence: around 1%(variations depending on the study)
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Catatonia 10% (developing countries) vs 1% (developed countries)
Hebephrenia 13 % (developing countries) vs 4% (developing countries)
Demographics
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No evidence to support an overall change in the incidence of psychotic disorder over time,
though diagnostic shifts (away from schizophrenia) were reported.
Incidence of psychotic disorders varied markedly by age, sex, place and migration
status/ethnicity.
Raised rates of psychotic disorders across several ethnic minority groups. Effects were
strongest, and most consistent, amongst migrants and their descendants of black Caribbean
and black African origin. Although the evidence in England for raised rates amongst ethnic
minority groups descendant from the Indian subcontinent has been interpreted as equivocal,
our review suggested some elevation in rates for this group a phenomenon potentially
restricted to women
There was emerging evidence of raised rates amongst people of mixed ethnicity, a possible
marker of ‘third-generation’ descendants, and some suggestion of a smaller, though
significant elevation in rates amongst non-British white migrant groups.
Incidence of Schizophrenia and Other Psychoses in England, 1950–2009: A Systematic Review and Meta-Analyses James B.
Kirkbride mail,Antonia Errazuriz, Tim J. Croudace, Craig Morgan,Daniel Jackson,Jane Boydell, Robin M. Murray,Peter B. Jones
Incidence of schizophrenia by age and gender in England, 1950-2009, pooled and per
relevant citation
Incidence of Schizophrenia and Other Psychoses in England, 1950–2009: A Systematic Review and Meta-Analyses James B.
Kirkbride mail,Antonia Errazuriz, Tim J. Croudace, Craig Morgan,Daniel Jackson,Jane Boydell, Robin M. Murray,Peter B. Jones
Aetiology
• Genes (Neuregulin and Dysbindin)
• Environment(obstetric complications, maternal influenza, winter birth,
early cannabis use, paternal age)
• Social(migration, urban birth/living, recent life events)
• Structural (smaller brain size, reduced synaptic markers)
• Functional imaging (hypofrontality)
• Neurophysiological (abnormal eye tracking and sensory evoked
potentials)
• Neurochemical (Dopamine-”hyperdopaminaergia” and Glutamate-NMDA
receptor dysfunction)
Shorter Oxford Textbook of Psychiatry-5th edition, Michael Gelder, p281
Hypotheses
• Neurodevelopmental
• Aberrant connectivity (failure of integration of
mental functions)
• Stress vulnerability(interaction between early
factors and later life stresors)
Shorter Oxford Textbook of Psychiatry-5th edition, Michael Gelder, p281
Genetic risk in relatives
(Source: Gottesman, 1991)
Schizophrenia genetics
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In Down’s syndrome the risk of schizophrenia is same as or lower than general population
(probably less than 0.6%).
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A number of studies have shown higher familial risk to be associated with earlier age of
onset. Sham et al. (1994) showed that the morbid risk of schizophrenia is greater among the
relatives of those probands who had an onset before rather than after age 21 years.
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Severity of schizophrenia is not directly associated with family history or genetic loading.
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Broad heritability = 80%
Murray et al (ed). The epidemiology of Schizophrenia. Cambridge University Press, 2003. p212
Shared genes – BPAD and Schizophrenia
• DAO & BDNF – seen more in mood disorders than schizophrenia
• DISC 1 & NRG – shared with schizophrenia; seen in schizoaffective disorder
• Dysbindin – seen more in schizophrenia than mood disorders
• CREB1 (chr2) – unipolar depression
Craddock N, et al (2005) The genetics of schizophrenia and bipolar disorder: dissecting
psychosis. JMed Genet, 42, 193–204.
Dopamine pathways
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Nigrostriatal from sustantia nigra to striatum (movement-EPS , tardive dyskinesia),
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Mesocortical from ventral tegmental area( VTA) to frontal cortex (motivation and emotionsnegative symptoms of schizophrenia)
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Mesolimbic from the (VTA) to the limbic system via the nucleus
accumbens. (reward pathway-positive symptoms of schizophrenia).
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Tuberoinfundibular from hypothalamus to pituitary gland (prolactin inhibitinghyperprolactinaemia)
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Incertohypothalamic in hypothalamus (sexual behaviour)
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Amacrine cells in retina, olfactory system.
Dopamine pathways
Dopamine- mechanisms of action Ann D. Crocker, Associate Professor and Reader, Department of Clinical
Pharmacology, Flinders University of South Australia, Adelaide
Neuroanatomy of schizophrenia
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A decrease in brain weight, brain length and volume of the cerebral hemisphere
enlargement of the lateral ventricles
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Enlarged lateral ventricles and third ventricle
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Smaller medial temporal lobes
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Decreased cortical grey matter
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Reduced cerebral asymetry (Some evidence from postmortem examinations indicate
disturbed cerebral asymmetry (planum temporale). Planum temporale (the posterior
superior surface of the superior temporal gyrus) is a brain structure involved with language.
In schizophrenia there was noted a reversal of the normal left surface area.
Histological changes
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No evidence for astrogliosis
Reduced cell numbers or cell size especially affecting neurons in the hippocampus and
DLPFC.
Increase in neurone density, which may relate to the observed decrease in neurone size
(with decreased dendritic arborization and a decreased neuropil compartment)
Subtle cytoarchitectural anomalies were described in the hippocampal formation, frontal
cortex
Synaptic studies in the hippocampus and DLPFC in schizophrenia show decrements in
presynaptic markers. These changes may reflect a reduction in the number of synaptic
contacts formed and received in these areas which supports hypotheses of excessive synaptic
pruning.
Glutamatergic synapses may be especially vulnerable in the hippocampus and perhaps the
DLPFC, with predominantly GABAergic involvement in the cingulate gyrus.
Harrison PJ. “The neuropathology of schizophrenia. A critical review of the data and their
interpretation.” Brain 1999; 122:593-624
Relapse Duration, Treatment Intensity, and Brain Tissue Loss in Schizophrenia: A Prospective Longitudinal
MRI Study
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Nancy C. Andreasen, M.D., Ph.D.; Dawei Liu, Ph.D.; Steven Ziebell, B.A.; Anvi Vora, M.D.; Beng-Choon Ho, M.D.
J Psychiatry
2013;170:609-615.
The primary focus of the Andreasen et al. Am
study
was on clinical
associations of atrophic anatomic changes with duration of
persistent psychosis and intensity of antipsychotic treatment.
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Findings:
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Antipsychotic treatment intensity was related to brain volume reductions in the frontal and temporal cortex and in parietal
white matter.
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Antipsychotic-related effects on brain volume were notably smaller than those reported in rodent and nonhuman primate
models; this difference may reflect species differences, an interaction with disease, more variable dosing clinically, or
underreporting of treatment nonadherence. In any case, it is reassuring to see that progressive atrophic effects associated
with antipsychotic treatment are less than those seen in
animal models.
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Effects of relapse duration and antipsychotic treatment intensity on anatomic measures were of similar magnitude.
Diagnostic criteria-ICD 10
• ICD10-Schizophrenia, Schizotypal and
delusional disorders F20-F29
• Minimum 1symptom (a-d) or at least 2
symptoms(e-h) present most of the time
during a period of 1 month or more
Diagnostic criteria-ICD10
• a) Thought insertion, withdrawal, broadcasting, echo.
• b)Delusions of control, influence, pasivity, clearly referred to body or limb
movements or specific thoughts, actions or sensations, delusional
perception.
• c) Hallucinatory voices giving a running commentary on patient’s
behaviour, or discussing 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
Diagnostic criteria – ICD 10
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e) Persistent hallucinations in any modality when accompanied either by fleeting
or half formed delusions without clear affective content, or by persistent
overvalued 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. Should not be secondary to depression or to
neuroleptic medication.
i) significant and consistent change in overall quality of some aspects of personal
behaviour, manifest as loss of interest, aimlesness, idleness,a self absorbed
attitude and social withdrawal.
Sub-types
• Paranoid (the commonest type, persecutory delusions and hallucinations)
• Hebephrenic(thought disorder and affective sx are prominent. Negative Sx
occur early and mannerisms common)
• Catatonic
• Undiferentiated
• Residual (at least a year of persistent negative Sx)
• Simple(insidious onset with odd behaviour, social withdrawal and
functional decline)
• Postschizophrenic depression
• Other Schizophrenia
• Unspecified
• But…ICD11 will change Schizophrenia classification
The most significant recommendations that are being made on the basis of
evidence review and WGPD consensus
(Working Group on the Classification of Psychotic Disorders )
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The ICD-10 section “F2 Schizophrenia, schizotypal and delusional disorders” will be renamed
“Schizophrenia spectrum and other primary psychotic disorders.”
Accordingly, non-primary (ie, “secondary”) psychotic disorders such as psychotic disorders in general
medical conditions and psychotic disorders due to substance use or withdrawal will be placed in the
sections (or “blocks”) of the Mental and Behavioural Disorders chapter corresponding to “Substanceinduced disorders” and “Mental and behavioural disorders associated with disorders or diseases classified
elsewhere.”
The overall structure being proposed for the ICD-11 block on “Schizophrenia spectrum and other primary
psychotic disorders” is as follows:
– Schizophrenia
– Schizoaffective disorder
– Acute and transient psychotic disorder (ATPD)
– Schizotypal disorder
– Delusional disorder
– Other primary psychotic disorders
– Unspecified primary psychotic disorders
Status of Psychotic Disorders in ICD-11, Wolfgang Gaebel, Schizophr Bull (2012) 38 (5): 895-898.
The most significant recommendations that are being made on the basis of
evidence review and WGPD consensus
(Working Group on the Classification of Psychotic Disorders )
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Single disorders will continue to be categorized on the basis of their psychopathological
profile and duration.
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For ICD-11 schizophrenia, the WGPD recommends, in accordance with DSM-5, that the
9 ICD-10 subtypes—paranoid, hebephrenic, catatonic, etc.—be omitted because of
their longitudinal instability and prognostic invalidity.6 These would be replaced by a
system of coded qualifiers (see below). Although de-emphasizing the importance of
first-rank symptoms,7 a diagnosis of schizophrenia would require the presence of at
least 2 out of 8 symptoms, including at least one core symptom.
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The WGPD is recommending that in ICD-11 a diagnosis of “Schizoaffective disorder”
should be made only when the definitional requirements of schizophrenia and of a
mood disorder of moderate or severe degree are met simultaneously or within a few
days of each other. The total duration requirement would be 4 weeks, including both
mood and schizophrenic symptoms.
Schneider’s First Rank symptoms
• TI/TW/TB
• 3rd person auditory hallucinations + running
commentary +Thought eco
• Somatic hallucinations
• Delusional perception
• Feelings or actions experienced as made by an
external agency
Negative symptoms
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Alogia
Affective blunting
Asociality
Anhedonia
Avolition
These predict:
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Poor life quality
Poor social functioning
Poor interpersonal relationships
Poor work performance
Poor overall outcome
Definition of catatonic symptoms
• Excitement -Extreme hyperactivity, constant motor unrest that is
apparently nonpurposeful
• Immobility/stupor -Extreme hypoactivity, immobility. Minimally responsive
to stimuli
• Mutism - Verbally unresponsive or minimally responsive
• Staring-Fixed gaze, little or no visual scanning of environment, decreased
blinking
• Posturing/catalepsy - Maintains posture(s), including mundane (e.g.,
sitting or standing for hours without reacting)
• Grimacing-Maintenance of odd facial expressions
• Echopraxia/echolalia- Mimicking of examiner’s movements/speech
Definition of catatonic symptoms
• Ambitendency - The patient seems stuck in indecisive, hesitant motor
movements
• Grasp reflex - Strike open palm of patient with two extended fingers of
examiner’s hand. Automatic closure of patient’s hand
• Perseveration - Repeatedly returns to the same topic or persists with
same movements
• Combativeness - Usually in an undirected manner, without explanation
• Autonomic abnormality - Abnormality of temperature (fever), blood
pressure, pulse rate, respiratory rate, inappropriate
Definition of catatonic symptoms
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Stereotypy- Repetitive, nongoal-directed motor activity (e.g., finger play, repeatedly
touching, patting, or rubbing self)
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Mannerisms Odd, purposeful movements (hopping or walking tiptoe, saluting passersby, exaggerated caricatures of mundane movements)
Verbigeration Repetition of phrases or sentences
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Rigidity (Fig. 27.4 and 27.5) Maintenance of a rigid position despite efforts to be moved
Negativism Apparently motiveless resistance to instructions or to attempts to
move/examine the patient. Contrary behavior, does the opposite of the instruction
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Waxy flexibility (Fig. 27.6, 27.7 and 27.8) During reposturing, patients offers initial
resistance before allowing himself to be repositioned (similar to that of bending a warm
candle)
Definition of catatonic symptoms
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Withdrawal Refusal to eat, drink, and/or make eye contact
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Impulsivity Patient suddenly engages in inappropriate behavior (e.g., runs down
the hallway, starts screaming, or takes off clothes) without provocation. Afterward,
cannot explain
Automatic obedience Exaggerated cooperation with examiner’s request, or
repeated movements that are requested once
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Passive obedience (mitgehen) Raising arm in response to light pressure of finger,
despite instructions to the contrary
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Gegenhalten/counterpull Resistance to passive movement that is proportional to
strength of the stimulus; response seems automatic rather than willful
Schizophrenia and suicide
The estimate of lifetime suicide prevalence in those observed from first admission or
illness onset - 5.6%.
Factors with robust evidence of increased risk of suicide were
•previous depressive disorders
•previous suicide attempts
•drug misuse
•agitation or motor restlessness
•fear of mental disintegration
•poor adherence to treatment
•recent loss
“Schizophrenia and suicide: systematic review of risk factors” HAWTON Keith, et al , British Journal of Psychiatry, 187(1), July 2005, pp.9-20.
Schizophrenia and suicide
Prevention of suicide in schizophrenia is likely to result from treatment of affective
symptoms, improving adherence to treatment, and maintaining special vigilance in
patients with risk factors, especially after losses.
“Schizophrenia and suicide: systematic review of risk factors” HAWTON Keith, et al ,
British Journal of Psychiatry, 187(1), July 2005, pp.9-20.
Predictors of quality of life in schizophrenia
• This Canadian study aims to clarify the relationships between sociodemographics, clinical characteristics, stressors, coping strategies, social
support and quality of life (QOL) in 143 patients with a diagnosis of either
schizophrenia or schizoaffective disorders. The research design is crosssectional with repeated measures on the same subjects after a 6-month
interval. A regression analysis generated a model that accounts for 50% of
the variance in QOL at Time 1 and 43% at Time 2. The best predictors of
QOL were two components of social support: attachment and reassurance
of worth. Severity of daily hassles, the coping strategy of changing the
situation, level of education and life-time hospitalization length were also
related to QOL.
Management (NICE)
Indicators of good prognosis
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Sudden onset
Short episode
No past psychiatric Hx
Prominent affective Sx
Paranoid type
Older age
Married
Good psychosexual adjustment
Good premorbid personality
Good work record
Good social relationships
Compliance with treatment
Shorter Oxford Textbook of Psychiatry-5th edition, Michael Gelder, p295
Indicators of poor prognosis
• The opposite of above indicators +…..
• Negative Sx
• Enlarged lateral ventricles
• Male gender
Prognosis of EOS
“In contrast to the adult manifestation, the early manifestation of schizophrenia in
childhood and adolescence still carries a particularly poor prognosis. According to
these aggregated data analyses, longer follow-up periods, male sex, and patients
having been diagnosed before 1970 contribute predominantly to the rather poor
course of EOS. “
A systematic review of the long-term outcome of early onset schizophrenia
Lars Clemmensen1†, Ditte Lammers Vernal2† and Hans-Christoph Steinhausen234*† BMC Psychiatry
2012, 12:150 doi:10.1186/1471-244X-12-150 Published: 19 September 2012
Characteristics of individuals at high risk who fell ill, according to presence or absence of psychotic symptoms on
entry
Predicting schizophrenia: findings from the Edinburgh High-Risk Study, Eve C. Johnstone, FRCPsych, Klaus P. Ebmeier, MD, Patrick
Miller, PhD, David G. C. Owens, FRCPsych and Stephen M. Lawrie, MRCPsych The British Journal of Psychiatry (2005)186: 18-25
Without psychotic
With psychotic
symptoms on entry symptoms on entry
Overall
Statistic
P
0.005
Gender, n
Male
2
10
12
Fisher’s exact
Female
7
1
8
probability
Manual
6
9
15
Fisher’s exact
Non-manual
3
2
5
probability
Parent or
sibling, n
Other relative, n
7
4
11
Fisher’s exact
2
7
9
probability
Age on entry,
years: mean
Time between entry
and illness onset,
years: mean
18.38
21.01
19.95
t=2.94
0.009
2.87
2.21
2.58
t=0.867
0.398
Social class, n
0.617
Illness present in
0.092
CLINICAL IMPLICATIONS of Edinburgh High-Risk study
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Among individuals at enhanced genetic risk of schizophrenia, a state of
vulnerability, including transient and partial symptoms, will occur in many more
individuals than will develop florid schizophrenia.
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It is possible, using simple behavioural assessments of schizotypal and anxiety
cognitions, to predict with some accuracy those of a high-risk group who will (and
with considerable accuracy those who will not) develop schizophrenia, some years
before the development of the psychosis.
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Neuropsychological and neurodevelopmental measures are more successful in
distinguishing individuals at high risk from healthy controls than they are in
distinguishing high-risk individuals who will develop schizophrenia from those who
will not.