2Definition“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 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).
3Historical 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 depressionEugen Bleuler (Swiss)-coined the term “Schizophrenia”(1911)+ 4 “A”S (loosening of associations, apathy, autism(social withdrawal), blunt/incongruous affect)Kahlbaum described catatonia (1868)
4Demographics (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.
5DemographicsIncidence variable up to 5X depending on site (between 7-14: )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.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.Prevalence: around 1%(variations depending on the study)Catatonia 10% (developing countries) vs 1% (developed countries)Hebephrenia 13 % (developing countries) vs 4% (developing countries)
6DemographicsNo 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
7Incidence of schizophrenia by age and gender in England, , 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
8Aetiology 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
9Hypotheses 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
10Genetic risk in relatives (Source: Gottesman, 1991)
11Schizophrenia genetics In Down’s syndrome the risk of schizophrenia is same as or lower than general population (probably less than 0.6%).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.Severity of schizophrenia is not directly associated with family history or genetic loading.Broad heritability = 80%Murray et al (ed). The epidemiology of Schizophrenia. Cambridge University Press, p212
12Shared genes – BPAD and Schizophrenia DAO & BDNF – seen more in mood disorders than schizophreniaDISC 1 & NRG – shared with schizophrenia; seen in schizoaffective disorderDysbindin – seen more in schizophrenia than mood disordersCREB1 (chr2) – unipolar depressionCraddock N, et al (2005) The genetics of schizophrenia and bipolar disorder: dissecting psychosis. JMed Genet, 42, 193–204.
13Dopamine pathwaysNigrostriatal from sustantia nigra to striatum (movement-EPS , tardive dyskinesia),Mesocortical from ventral tegmental area( VTA) to frontal cortex (motivation and emotions-negative symptoms of schizophrenia)Mesolimbic from the (VTA) to the limbic system via the nucleusaccumbens. (reward pathway-positive symptoms of schizophrenia).Tuberoinfundibular from hypothalamus to pituitary gland (prolactin inhibiting-hyperprolactinaemia)Incertohypothalamic in hypothalamus (sexual behaviour)Amacrine cells in retina, olfactory system.
14Dopamine pathways Dopamine- mechanisms of action Ann D Dopamine pathways Dopamine- mechanisms of action Ann D. Crocker, Associate Professor and Reader, Department of Clinical Pharmacology, Flinders University of South Australia, Adelaide
15Neuroanatomy of schizophrenia A decrease in brain weight, brain length and volume of the cerebral hemisphere enlargement of the lateral ventriclesEnlarged lateral ventricles and third ventricleSmaller medial temporal lobesDecreased cortical grey matterReduced 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.
16Histological changes 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, frontalcortexSynaptic 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 theDLPFC, 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:
17Relapse Duration, Treatment Intensity, and Brain Tissue Loss in Schizophrenia: A Prospective Longitudinal MRI Study Nancy C. Andreasen, M.D., Ph.D.; Dawei Liu, Ph.D.; Steven Ziebell, B.A.; Anvi Vora, M.D.; Beng-Choon Ho, M.D. Am J Psychiatry 2013;170: The primary focus of the Andreasen et al. study was on clinical associations of atrophic anatomic changes with duration of persistent psychosis and intensity of antipsychotic treatment.Findings:Antipsychotic treatment intensity was related to brain volume reductions in the frontal and temporal cortex and in parietal white matter.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 inanimal models.Effects of relapse duration and antipsychotic treatment intensity on anatomic measures were of similar magnitude.
18Diagnostic criteria-ICD 10 ICD10-Schizophrenia, Schizotypal and delusional disorders F20-F29Minimum 1symptom (a-d) or at least 2 symptoms(e-h) present most of the time during a period of 1 month or more
19Diagnostic 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
20Diagnostic criteria – ICD 10 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.
21Sub-types But…ICD11 will change Schizophrenia classification Paranoid (the commonest type, persecutory delusions and hallucinations)Hebephrenic(thought disorder and affective sx are prominent. Negative Sx occur early and mannerisms common)CatatonicUndiferentiatedResidual (at least a year of persistent negative Sx)Simple(insidious onset with odd behaviour, social withdrawal and functional decline)Postschizophrenic depressionOther SchizophreniaUnspecifiedBut…ICD11 will change Schizophrenia classification
22The most significant recommendations that are being made on the basis of evidence review and WGPD consensus (Working Group on the Classification of Psychotic Disorders )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 “Substance-induced 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:SchizophreniaSchizoaffective disorderAcute and transient psychotic disorder (ATPD)Schizotypal disorderDelusional disorderOther primary psychotic disordersUnspecified primary psychotic disordersStatus of Psychotic Disorders in ICD-11, Wolfgang Gaebel, Schizophr Bull (2012) 38 (5):
23The most significant recommendations that are being made on the basis of evidence review and WGPD consensus (Working Group on the Classification of Psychotic Disorders )Single disorders will continue to be categorized on the basis of their psychopathological profile and duration.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.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.
24Schneider’s First Rank symptoms TI/TW/TB3rd person auditory hallucinations + running commentary +Thought ecoSomatic hallucinationsDelusional perceptionFeelings or actions experienced as made by an external agency
25Negative symptoms Alogia Affective blunting Asociality Anhedonia AvolitionThese predict:Poor life qualityPoor social functioningPoor interpersonal relationshipsPoor work performancePoor overall outcome
26Definition of catatonic symptoms Excitement -Extreme hyperactivity, constant motor unrest that is apparently nonpurposefulImmobility/stupor -Extreme hypoactivity, immobility. Minimally responsive to stimuliMutism - Verbally unresponsive or minimally responsiveStaring-Fixed gaze, little or no visual scanning of environment, decreased blinkingPosturing/catalepsy - Maintains posture(s), including mundane (e.g., sitting or standing for hours without reacting)Grimacing-Maintenance of odd facial expressionsEchopraxia/echolalia- Mimicking of examiner’s movements/speech
27Definition of catatonic symptoms Ambitendency - The patient seems stuck in indecisive, hesitant motor movementsGrasp reflex - Strike open palm of patient with two extended fingers of examiner’s hand. Automatic closure of patient’s handPerseveration - Repeatedly returns to the same topic or persists with same movementsCombativeness - Usually in an undirected manner, without explanationAutonomic abnormality - Abnormality of temperature (fever), blood pressure, pulse rate, respiratory rate, inappropriate
28Definition of catatonic symptoms Stereotypy- Repetitive, nongoal-directed motor activity (e.g., finger play, repeatedly touching, patting, or rubbing self)Mannerisms Odd, purposeful movements (hopping or walking tiptoe, saluting passers-by, exaggerated caricatures of mundane movements)Verbigeration Repetition of phrases or sentencesRigidity (Fig and 27.5) Maintenance of a rigid position despite efforts to be movedNegativism Apparently motiveless resistance to instructions or to attempts to move/examine the patient. Contrary behavior, does the opposite of the instructionWaxy 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)
29Definition of catatonic symptoms Withdrawal Refusal to eat, drink, and/or make eye contactImpulsivity Patient suddenly engages in inappropriate behavior (e.g., runs down the hallway, starts screaming, or takes off clothes) without provocation. Afterward, cannot explainAutomatic obedience Exaggerated cooperation with examiner’s request, or repeated movements that are requested oncePassive obedience (mitgehen) Raising arm in response to light pressure of finger, despite instructions to the contraryGegenhalten/counterpull Resistance to passive movement that is proportional to strength of the stimulus; response seems automatic rather than willful
30Schizophrenia and suicide The estimate of lifetime suicide prevalence in those observed from first admission or illness onset %.Factors with robust evidence of increased risk of suicide wereprevious depressive disordersprevious suicide attemptsdrug misuseagitation or motor restlessnessfear of mental disintegrationpoor adherence to treatmentrecent loss“Schizophrenia and suicide: systematic review of risk factors” HAWTON Keith, et al , British Journal of Psychiatry, 187(1), July 2005, pp.9-20.
31Schizophrenia and suicide Prevention of suicide in schizophrenia is likely to result from treatment of affectivesymptoms, improving adherence to treatment, and maintaining special vigilance inpatients 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.
32Predictors of quality of life in schizophrenia This Canadian study aims to clarify the relationships between socio-demographics, 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 cross-sectional 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.
34Indicators of good prognosis Sudden onsetShort episodeNo past psychiatric HxProminent affective SxParanoid typeOlder ageMarriedGood psychosexual adjustmentGood premorbid personalityGood work recordGood social relationshipsCompliance with treatmentShorter Oxford Textbook of Psychiatry-5th edition, Michael Gelder, p295
35Indicators of poor prognosis The opposite of above indicators +…..Negative SxEnlarged lateral ventriclesMale gender
36Prognosis 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 schizophreniaLars Clemmensen1†, Ditte Lammers Vernal2† and Hans-Christoph Steinhausen234*† BMC Psychiatry2012, 12:150 doi: / X Published: 19 September 2012
37Without psychotic symptoms on entry With psychotic symptoms on entry 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: 18-25Without psychotic symptoms on entryWith psychotic symptoms on entryOverallStatisticPGender, n Male21012Fisher’s exact0.005 Female718probabilitySocial class, n Manual69150.617 Non-manual35Illness present in Parent or sibling, n4110.092 Other relative, nAge on entry, years: mean18.3821.0119.95t=2.940.009Time between entry and illness onset, years: mean2.872.212.58t=0.8670.398
38CLINICAL IMPLICATIONS of Edinburgh High-Risk study 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.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.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.