2Historical background First descriptions of symptoms appear in ancient Greek textsChanging attitudes in the 18th century led to an increase interest in studying mental illness; previously there behaviour was regarded as reprehensibleThe discovery of the pathology and treatment of general paresis of the insane led Emil Kraepelin to identify another unique syndrome which he named Dementia Praecox
3“On the one hand we observe a weakening of those emotional activities which permanently form the mainsprings of volition. In connection with this , mental activity and instinct for occupation become mute. The result of this part of the process is emotional dullness, failure of mental activities, loss of mastery of volition, of endeavour and of ability for independent action. The essence of personality is thereby destroyed, the best and most precious part of being; torn from her….”Kraepelin Dementia Praecox 1919
4EpidemiologySchizophrenia is a world wide public health concern being present in all countries and culturesInterestingly its incidence is almost uniform across geographical, cultural and religious bordersJust less than 1% of people suffer from schizophrenia, if the schizophrenia spectrum disorders are included this rises to 5%
5Almost equal sex distribution with a slight excess of male patients. Females tend to develop the disease on average 4 years later than malesFemale distribution of the disease also shows a second “spike” at menopauseAlso a third spike occurs for both sexes at around years, these patients are termed late onset schizophrenia. Many clinicians view this as a distinct clinical entity to schizophrenia.
7Aetiology Several models which can be grouped into…. Biological Social Psychological
8Biological theoriesAgain the precise aetiology remains unknown but there is good evidence to support a biological cause for Schizophrenia and several promising lines of enquiryMany people would regard schizophrenia as a syndrome. A collection of disease entities producing similar clinical picture but with distinct aetiologies. Much like Learning disability being classified a s a single disease entity before a plethora of causes were identified
9GeneticsFamily twin and adoptive studies have shown beyond doubt that a large degree of risk of Schizophrenia is genetically determinedRisk as high as 55% for identical twins. Around 15 5 if one parent is affected rising to almost 40% if both parents affected
11Eight linkage sites have thus far been identified on the 1st 6th 8th 10th thirteenth and 15th chromosomes.Several specific genes have also been identified each of which confers a degree of vulnerability to the diseaseAlthough genetic studies do support a biological causation they also demonstrate that other factors must be involved as many genetically risky individuals never develop schizophrenia.
12Pathology contribution Post mortem studies of schizophrenic brains first identified morphological features of the conditionBrains show enlarged lateral ventricles at PM and reduced volume of hypocampusThere brains are lighter than controlsNewer imaging techniques have shown a more rapid reduction of cortical volume during first illness episode
13Identified risksA number of interesting possibilities supported by studies…An excess of birth and gestational complications leading some to postulate anoxic brain injury as a risk factorAn excess of winter births of individuals with the disease has led to speculation of a viral or post-viral autoimmune process
14Studies of incidence rates have also shown an increased incidence of children who were in utero during influenza epidemicsThe same has also been demonstrated for children born during times of famine.Another risk factor which has shown statistical significant association is that children with rhesus incompatibility also show an increased risk
15The Dopamine hypothesis “normal” individuals exposed to dopamine releasing drugs such as amphetamines over a period of days will develop a psychosis clinically indistinguishable from schizophrenia which generally disappears with abstinence from the drugsAll effective antipsychotic drugs have dopamine blocking properties
16Overactivity in dopaminergic meso-frontal and mesocortical neurones and their associated dopamine-D2 receptors has been suggested as the basis of “positive” features of schizophrenia such as acute hallucinations and delusions.When psychotic scizophrenic patients are given amphetamine they release substantially more dopamine than healthy controls.
17Beyond the dopamine hypothesis The improvement in “negative” features (such as lack of volition or planning ability) achieved by the newer atypical antipsychotic drugs suggests that neuronal pathways other than just dopaminergic ones are important in some of the symptoms schizophrenia.
18Neuro-cognitive testing Schizophrenic patients perform worse as a group on all neuropsychological tests compared to IQ matched controls.First degree relatives also perform worse on average than controls
19SocialStudies have shown an excess of schizophrenic patients in lower socioeconomic groups and in urbanised areas. This used to be attributed to “social drift”Newer studies following children from various backgrounds suggest this is not the case and living in a highly urbanised area is indeed a risk factor for schizophrenia
20Psychosocialabnormalities in processing sensory information, in separating “signal from background noise”, or in manipulating abstract informationConsistently demonstrate “Jump to conclusion” reasoning or JTCExcess life traumas against controls at first presentation
21Clinical featuresThe prodrome- Increasingly recognised is a prodromal state of 1-2 years duration preceding the onset of psychosisTypical features of the prodrome are: anxiety, depression, reduced concentration, difficulty communicating ,reduced motivation and suspiciousnessBrief and transitory psychotic ideas lasting minutes or hours may also feature
22These problems often lead to a reduced level of functioning and may lead to unemployment or below expected educational achievementWhen taking a history from a patient with new onset psychosis establishing a prodromal phase raises suspicion of a diagnosis of ScizophreniaCollateral history is often of value in screening for prodromal symptom's
23ICD-10 criteria-1Based on First Rank symptoms described by Kurt Schneider, German PsychiatristThere are two groups of symptoms:Major: at least one of these must be present to make a diagnosis of schizophreniaMinor: at least two of these must be present to make a diagnosis.These symptoms must be present most of the time for at least one month
24Schneider’s 1st Rank Symptoms Auditory Hallucinations: runningcommentary, discussing him amongthemselves, thought echoThought insertion, withdrawal, broadcastPassivity phenomena: actions, feelingsDelusional perception: a normal perceptionhappens, and a delusional interpretation isattached to it.
25Major symptoms/signs1-Thought echo, thought insertion, withdrawal or broadcasting2-Delusional perception OR delusions of control (passivity phenomena)3-Hallucinatory voices: Running commentary, discussing him among themselves or coming from some part of the body.4-Delusions that are culturally inappropriate & completely impossible, e.g.: controlling weather
26Minor SymptomsPersistent hallucinations in any modality, everyday for at least 1 month, when accompanied by delusions without affective contentNeologisms, incoherent/irrelevant speechCatatonic behaviour (excitement, mutism….)Negative symptoms (apathy, paucity ofspeech, etc) which are not due todepression or medication side effect.
27Symptom development and Dopamine Understanding the normal function of Dopamine in the brain is key to understanding the psychopathology of schizophreniaDopamine is released in the healthy subject in response to innately rewarding or adverse events.An example would be playing a difficult level on a computer game and unexpectedly succeeding.Another would be in response to seeing on hearing footsteps behind you in a dark alley.
28In the schizophrenic patients brain, during a psychotic episode, dopamine can be released at any time and can lead to the individual falsely attributing significance or fear to objects, sensory information or thoughts.They may for instance get a feeling of intense significance, such as one might get when the killer is unmasked in a murder mystery, whilst looking at a car number plate.
29Alternatively they might get a surge of dopamine whilst concentrating on their own thoughts and interpret their thoughts as alien, (thought insertion)They could get a surge of dopamine whilst watching television and suddenly feel they are somehow related to or responsible for the death of Michael Jackson or the Credit Crunch
30Using this model it is easy to see how anyone could quickly build up a complex delusionary system. We all want to make sense of what is happening around us and we all trust our own senses.Patients delusions are often built up from a single or several unusual experiences which they then try and rationalise.If you heard voices that no one else could hear would it not be preferable to think it was a microchip implanted in your skull rather than face up to the fact you might be mentally ill?
31Prognosis/ course1/3 recover; 1/3 relapse and remit; 1/3 become chronic 6-10% suicideIncreased rates violence about 5x to carers and staff, least often strangersSimilar number to suicide dies prematurely from physical illnessIncreased rates dependent living, homelessness, unemploymentAs become older negative symptoms increase whilst positive symptoms diminish
32InvestigationAs always in psychiatry your first objective should be to exclude an organic problemIn the case of patient presenting with symptoms suggestive of schizophrenia there are two important organic differential diagnosisA Drug induced psychosis can closely resemble a schizophrenia presentation
33Undiagnosed temporal lobe epilepsy can present in a similar way to an acutely psychotic patient Always complete a urine drug screen on admission, Amphetamines can be clear from the urine in 48 hoursPatients should routinely have an ECG at first presentationALWAYS complete a thorough neurological exam rarely malignancy can masquerade as psychosis
36Sub types Classically divided into four sub types Paranoid Hebephrenic Simple or undifferentiatedCatatonic
37Paranoid type Relatively stable, often persecutory delusions Usually hallucinations, particularly of theauditory variety, and other perceptualdisturbancesAffect, volition and speech disturbances,and catatonic symptoms are either absentor inconspicuous.
38Hebephrenic Schizophrenia Prominent affective changesdelusions and hallucinations: fleeting/rudimentaryIrresponsible and unpredictable behaviourMannerismsShallow and inappropriate moodDisorganised thoughtIncoherent speechSocial isolationUsually poor prognosis (because of the rapiddevelopment of "negative" symptoms, particularlyflattening of affect and loss of volition
39Catatonic Schizophrenia Prominent psychomotor disturbances thatmay alternate between extremes such asviolent excitement & stupor, or automaticobedience & negativism. Constrainedattitudes and postures may be maintainedfor long periods.Uncommon in industrialised countries
40Undifferentiated Schizophrenia Psychotic conditions meeting the generaldiagnostic criteria for schizophrenia but notconforming to any of the other subtypes, orexhibiting the features of more than one ofthem, without a clear predominance of aparticular set of diagnostic characteristics.
41Treatment Treatment & Management This should be again 3-fold: Bio-psychosocialMedicationRisk reduction (to himself & others)ObservationPsychology (CBT for delusions)Occupational therapyFamily therapySocial integration
42Medication-1 ►Older anti-psychotics (conventional) vs newer anti-psychotics►Older ones had more side effects (ExtrapyramidalSide Effects [EPSEs])►Anti-muscarinic meds are used to counterEPSEs (eg: procyclidine, orphenadrine, etc)►Newer ones are much more expensive►Depot vs Oral
43Clozapine Targets Serotonin 2 receptors and D4 receptors; the ordinary old and newantipsychotics target D2 receptors.►NICE advises to use Clozapine, once 2different anti-psychotics (of 2 differentgroups) have been tried for appropriateperiods (each 6-12 weeks) and thepsychosis continues termed treatment resistant scizophrenia.
44Medication-ECG Possibly serious ECG abnormalities At least once yearly ECGs requiresdQTc prolongation: the normal range is from 370ms to 450 in men & 470 in women.If pre-existing abnormalities, more prone forSudden Cardiac Death.Consider referral or senior review if not sure
45Neuroleptic Malignant syndrome Potentially fatal complication of antipsychotic useMore common in neuroleptically naïve patientsPresents with- Severe muscle rigidity, High fever, mutism, delirium.Caused by muscle break down leading to Rhabdomyalysis
46Patient will often appear confused and may be agitated The clinical picture may be mistaken for catatonia or acute psychosisBloods will show a marked elevation in Ck in the 1000sIt is a medical emergency and patient’s will require fluids and may need dialysis, urgent transfer to medical unit is indicated
47Tarditive dyskinesiaDistressing condition in which involuntary movements (chewing, sucking grimacing) occur persistentlyThis occurs more commonly with typical antipsychotic drugs and is usually first noticed when stopping or changing medicationBelieved to be caused by dopamine hypersensitisation no universally effective treatment exists.