Introducing SchizophreniaIntroducing Schizophrenia

Dr Eddy MellorDr Eddy Mellor

Historical backgroundHistorical background

• First descriptions of symptoms appear in First descriptions of symptoms appear in ancient Greek textsancient Greek texts

• Changing attitudes in the 18Changing attitudes in the 18thth century led to century led to an increase interest in studying mental an increase interest in studying mental illness; previously there behaviour was illness; previously there behaviour was regarded as reprehensibleregarded as reprehensible

• The discovery of the pathology and The discovery of the pathology and treatment of general paresis of the insane led treatment of general paresis of the insane led Emil Kraepelin to identify another unique Emil Kraepelin to identify another unique syndrome which he named Dementia syndrome which he named Dementia PraecoxPraecox

• ““On the one hand we observe a weakening On the one hand we observe a weakening of those emotional activities which of those emotional activities which permanently form the mainsprings of permanently form the mainsprings of volition. In connection with this , mental volition. In connection with this , mental activity and instinct for occupation become activity and instinct for occupation become mute. The result of this part of the process mute. The result of this part of the process is emotional dullness, failure of mental is emotional dullness, failure of mental activities, loss of mastery of volition, of activities, loss of mastery of volition, of endeavour and of ability for independent endeavour and of ability for independent action. The essence of personality is action. The essence of personality is thereby destroyed, the best and most thereby destroyed, the best and most precious part of being; torn from her….”precious part of being; torn from her….”

• Kraepelin Dementia Praecox 1919Kraepelin Dementia Praecox 1919

EpidemiologyEpidemiology

• Schizophrenia is a world wide public health Schizophrenia is a world wide public health concern being present in all countries and concern being present in all countries and culturescultures

• Interestingly its incidence is almost uniform Interestingly its incidence is almost uniform across geographical, cultural and religious across geographical, cultural and religious bordersborders

• Just less than 1% of people suffer from Just less than 1% of people suffer from schizophrenia, if the schizophrenia spectrum schizophrenia, if the schizophrenia spectrum disorders are included this rises to 5%disorders are included this rises to 5%

• Almost equal sex distribution with a Almost equal sex distribution with a slight excess of male patients. slight excess of male patients.

• Females tend to develop the disease Females tend to develop the disease on average 4 years later than maleson average 4 years later than males

• Female distribution of the disease also Female distribution of the disease also shows a second “spike” at menopauseshows a second “spike” at menopause

• Also a third spike occurs for both Also a third spike occurs for both sexes at around 60-65 years, these sexes at around 60-65 years, these patients are termed late onset patients are termed late onset schizophrenia. Many clinicians view schizophrenia. Many clinicians view this as a distinct clinical entity to this as a distinct clinical entity to schizophrenia.schizophrenia.

AetiologyAetiology

• Several models which can be Several models which can be groupedgrouped

into….into….

• BiologicalBiological

• SocialSocial

• PsychologicalPsychological

Biological theoriesBiological theories

• Again the precise aetiology remains unknown Again the precise aetiology remains unknown but there is good evidence to support a but there is good evidence to support a biological cause for Schizophrenia and several biological cause for Schizophrenia and several promising lines of enquirypromising lines of enquiry

• Many people would regard schizophrenia as a Many people would regard schizophrenia as a syndrome. A collection of disease entities syndrome. A collection of disease entities producing similar clinical picture but with distinct producing similar clinical picture but with distinct aetiologies. Much like Learning disability being aetiologies. Much like Learning disability being classified a s a single disease entity before a classified a s a single disease entity before a plethora of causes were identifiedplethora of causes were identified

GeneticsGenetics

• Family twin and adoptive studies Family twin and adoptive studies have shown beyond doubt that a have shown beyond doubt that a large degree of risk of Schizophrenia large degree of risk of Schizophrenia is genetically determinedis genetically determined

• Risk as high as 55% for identical Risk as high as 55% for identical twins. Around 15 5 if one parent is twins. Around 15 5 if one parent is affected rising to almost 40% if both affected rising to almost 40% if both parents affected parents affected

• Eight linkage sites have thus far been Eight linkage sites have thus far been identified on the 1identified on the 1stst 6 6thth 8 8thth 10 10thth thirteenth and 15thirteenth and 15thth chromosomes. chromosomes.

• Several specific genes have also been Several specific genes have also been identified each of which confers a identified each of which confers a degree of vulnerability to the diseasedegree of vulnerability to the disease

• Although genetic studies do support a Although genetic studies do support a biological causation they also biological causation they also demonstrate that other factors must be demonstrate that other factors must be involved as many genetically risky involved as many genetically risky individuals never develop individuals never develop schizophrenia.schizophrenia.

Pathology contributionPathology contribution

• Post mortem studies of schizophrenic Post mortem studies of schizophrenic brains first identified morphological brains first identified morphological features of the conditionfeatures of the condition

• Brains show enlarged lateral ventricles at Brains show enlarged lateral ventricles at PM and reduced volume of hypocampus PM and reduced volume of hypocampus

• There brains are lighter than controlsThere brains are lighter than controls• Newer imaging techniques have shown a Newer imaging techniques have shown a

more rapid reduction of cortical volume more rapid reduction of cortical volume during first illness episode during first illness episode

Identified risksIdentified risks

• A number of interesting possibilities A number of interesting possibilities supported by studies…supported by studies…

• An excess of birth and gestational An excess of birth and gestational complications leading some to postulate complications leading some to postulate anoxic brain injury as a risk factoranoxic brain injury as a risk factor

• An excess of winter births of individuals An excess of winter births of individuals with the disease has led to speculation of with the disease has led to speculation of a viral or post-viral autoimmune processa viral or post-viral autoimmune process

• Studies of incidence rates have also Studies of incidence rates have also shown an increased incidence of shown an increased incidence of children who were in utero during children who were in utero during influenza epidemicsinfluenza epidemics

• The same has also been demonstrated The same has also been demonstrated for children born during times of for children born during times of famine.famine.

• Another risk factor which has shown Another risk factor which has shown statistical significant association is statistical significant association is that children with rhesus that children with rhesus incompatibility also show an increased incompatibility also show an increased riskrisk

The Dopamine hypothesis The Dopamine hypothesis

• ““normal” individuals exposed to normal” individuals exposed to dopamine releasing drugs such as dopamine releasing drugs such as amphetamines over a period of days will amphetamines over a period of days will develop a psychosis clinically develop a psychosis clinically indistinguishable from schizophrenia indistinguishable from schizophrenia which generally disappears with which generally disappears with abstinence from the drugsabstinence from the drugs

• All effective antipsychotic drugs have All effective antipsychotic drugs have dopamine blocking propertiesdopamine blocking properties

• Overactivity in dopaminergic meso-Overactivity in dopaminergic meso-frontal and mesocortical neurones frontal and mesocortical neurones and their associated dopamine-D2 and their associated dopamine-D2 receptors has been suggested as the receptors has been suggested as the basis of “positive” features of basis of “positive” features of schizophrenia such as acute schizophrenia such as acute hallucinations and delusions.hallucinations and delusions.

• When psychotic scizophrenic patients When psychotic scizophrenic patients are given amphetamine they release are given amphetamine they release substantially more dopamine than substantially more dopamine than healthy controls.healthy controls.

Beyond the dopamine Beyond the dopamine hypothesishypothesis

• The improvement in “negative” The improvement in “negative” features (such as lack of volition or features (such as lack of volition or planning ability) achieved by the planning ability) achieved by the newer atypical antipsychotic drugs newer atypical antipsychotic drugs suggests that neuronal pathways suggests that neuronal pathways other than just dopaminergic ones other than just dopaminergic ones are important in some of the are important in some of the symptoms schizophrenia.symptoms schizophrenia.

Neuro-cognitive testingNeuro-cognitive testing

• Schizophrenic patients perform Schizophrenic patients perform worse as a group on all worse as a group on all neuropsychological tests compared neuropsychological tests compared to IQ matched controls.to IQ matched controls.

• First degree relatives also perform First degree relatives also perform worse on average than controlsworse on average than controls

SocialSocial

• Studies have shown an excess of Studies have shown an excess of schizophrenic patients in lower socioeconomic schizophrenic patients in lower socioeconomic groups and in urbanised areas. This used to be groups and in urbanised areas. This used to be attributed to “social drift”attributed to “social drift”

• Newer studies following children from various Newer studies following children from various backgrounds suggest this is not the case and backgrounds suggest this is not the case and living in a highly urbanised area is indeed a living in a highly urbanised area is indeed a risk factor for schizophreniarisk factor for schizophrenia

PsychosocialPsychosocial

• abnormalities in processing sensory abnormalities in processing sensory information, in separating “signal information, in separating “signal from background noise”, or in from background noise”, or in manipulating abstract informationmanipulating abstract information

• Consistently demonstrate “Jump to Consistently demonstrate “Jump to conclusion” reasoning or JTCconclusion” reasoning or JTC

• Excess life traumas against controls Excess life traumas against controls at first presentationat first presentation

Clinical featuresClinical features

• The prodrome- Increasingly recognised is a The prodrome- Increasingly recognised is a prodromal state of 1-2 years duration prodromal state of 1-2 years duration preceding the onset of psychosispreceding the onset of psychosis

• Typical features of the prodrome are: Typical features of the prodrome are: anxiety, depression, reduced concentration, anxiety, depression, reduced concentration, difficulty communicating ,reduced difficulty communicating ,reduced motivation and suspiciousnessmotivation and suspiciousness

• Brief and transitory psychotic ideas lasting Brief and transitory psychotic ideas lasting minutes or hours may also feature minutes or hours may also feature

• These problems often lead to a These problems often lead to a reduced level of functioning and may reduced level of functioning and may lead to unemployment or below lead to unemployment or below expected educational achievementexpected educational achievement

• When taking a history from a patient When taking a history from a patient with new onset psychosis with new onset psychosis establishing a prodromal phase establishing a prodromal phase raises suspicion of a diagnosis of raises suspicion of a diagnosis of ScizophreniaScizophrenia

• Collateral history is often of value in Collateral history is often of value in screening for prodromal symptom's screening for prodromal symptom's

ICD-10 criteria-1ICD-10 criteria-1

• Based on First Rank symptoms described by Based on First Rank symptoms described by Kurt Schneider, German PsychiatristKurt Schneider, German Psychiatrist

• There are two groups of symptoms:There are two groups of symptoms:

• Major: at least one of these must be present Major: at least one of these must be present to make a diagnosis of schizophreniato make a diagnosis of schizophrenia

• Minor: at least two of these must be present Minor: at least two of these must be present to make a diagnosis.to make a diagnosis.

• These symptoms must be present most of These symptoms must be present most of the time for at least one monththe time for at least one month

Schneider’s 1st Rank Schneider’s 1st Rank SymptomsSymptoms

• Schneider’s 1st Rank SymptomsSchneider’s 1st Rank Symptoms• Auditory Hallucinations: runningAuditory Hallucinations: running• commentary, discussing him amongcommentary, discussing him among• themselves, thought echothemselves, thought echo• Thought insertion, withdrawal, broadcastThought insertion, withdrawal, broadcast• Passivity phenomena: actions, feelingsPassivity phenomena: actions, feelings• Delusional perception: a normal perceptionDelusional perception: a normal perception• happens, and a delusional interpretation ishappens, and a delusional interpretation is• attached to it.attached to it.

Major symptoms/signsMajor symptoms/signs

• 1-Thought echo, thought insertion, withdrawal 1-Thought echo, thought insertion, withdrawal or broadcastingor broadcasting

• 2-Delusional perception OR delusions of 2-Delusional perception OR delusions of control (passivity phenomena)control (passivity phenomena)

• 3-Hallucinatory voices: Running commentary, 3-Hallucinatory voices: Running commentary, discussing him among themselves or coming discussing him among themselves or coming from some part of the body.from some part of the body.

• 4-Delusions that are culturally inappropriate & 4-Delusions that are culturally inappropriate & completely impossible, e.g.: controlling completely impossible, e.g.: controlling weatherweather

Minor SymptomsMinor Symptoms

• Persistent hallucinations in any modality, Persistent hallucinations in any modality, everyday for at least 1 month, when everyday for at least 1 month, when accompanied by delusions without affective accompanied by delusions without affective contentcontent

• Neologisms, incoherent/irrelevant speechNeologisms, incoherent/irrelevant speech• Catatonic behaviour (excitement, mutism….)Catatonic behaviour (excitement, mutism….)• Negative symptoms (apathy, paucity ofNegative symptoms (apathy, paucity of• speech, etc) which are not due tospeech, etc) which are not due to• depression or medication side effect.depression or medication side effect.

Symptom development and Symptom development and DopamineDopamine

• Understanding the normal function of Understanding the normal function of Dopamine in the brain is key to understanding Dopamine in the brain is key to understanding the psychopathology of schizophreniathe psychopathology of schizophrenia

• Dopamine is released in the healthy subject in Dopamine is released in the healthy subject in response to innately rewarding or adverse response to innately rewarding or adverse events.events.

• An example would be playing a difficult level An example would be playing a difficult level on a computer game and unexpectedly on a computer game and unexpectedly succeeding.succeeding.

• Another would be in response to seeing on Another would be in response to seeing on hearing footsteps behind you in a dark alley.hearing footsteps behind you in a dark alley.

• In the schizophrenic patients brain, In the schizophrenic patients brain, during a psychotic episode, dopamine during a psychotic episode, dopamine can be released at any time and can can be released at any time and can lead to the individual falsely lead to the individual falsely attributing significance or fear to attributing significance or fear to objects, sensory information or objects, sensory information or thoughts.thoughts.

• They may for instance get a feeling of They may for instance get a feeling of intense significance, such as one intense significance, such as one might get when the killer is unmasked might get when the killer is unmasked in a murder mystery, whilst looking at in a murder mystery, whilst looking at a car number plate.a car number plate.

• Alternatively they might get a surge Alternatively they might get a surge of dopamine whilst concentrating on of dopamine whilst concentrating on their own thoughts and interpret their own thoughts and interpret their thoughts as alien, (thought their thoughts as alien, (thought insertion)insertion)

• They could get a surge of dopamine They could get a surge of dopamine whilst watching television and whilst watching television and suddenly feel they are somehow suddenly feel they are somehow related to or responsible for the related to or responsible for the death of Michael Jackson or the death of Michael Jackson or the Credit CrunchCredit Crunch

• Using this model it is easy to see how Using this model it is easy to see how anyone could quickly build up a complex anyone could quickly build up a complex delusionary system. We all want to make delusionary system. We all want to make sense of what is happening around us and sense of what is happening around us and we all trust our own senses. we all trust our own senses.

• Patients delusions are often built up from Patients delusions are often built up from a single or several unusual experiences a single or several unusual experiences which they then try and rationalise.which they then try and rationalise.

• If you heard voices that no one else could If you heard voices that no one else could hear would it not be preferable to think it hear would it not be preferable to think it was a microchip implanted in your skull was a microchip implanted in your skull rather than face up to the fact you might rather than face up to the fact you might be mentally ill?be mentally ill?

Prognosis/ coursePrognosis/ course

• 1/3 recover; 1/3 relapse and remit; 1/3 1/3 recover; 1/3 relapse and remit; 1/3 become chronic 6-10% suicidebecome chronic 6-10% suicide

• Increased rates violence about 5x to carers Increased rates violence about 5x to carers and staff, least often strangersand staff, least often strangers

• Similar number to suicide dies prematurely Similar number to suicide dies prematurely from physical illnessfrom physical illness

• Increased rates dependent living, Increased rates dependent living, homelessness, unemploymenthomelessness, unemployment

• As become older negative symptoms As become older negative symptoms increase whilst positive symptoms diminishincrease whilst positive symptoms diminish

InvestigationInvestigation

• As always in psychiatry your first As always in psychiatry your first objective should be to exclude an organic objective should be to exclude an organic problemproblem

• In the case of patient presenting with In the case of patient presenting with symptoms suggestive of schizophrenia symptoms suggestive of schizophrenia there are two important organic there are two important organic differential diagnosisdifferential diagnosis

• A Drug induced psychosis can closely A Drug induced psychosis can closely resemble a schizophrenia presentationresemble a schizophrenia presentation

• Undiagnosed temporal lobe epilepsy Undiagnosed temporal lobe epilepsy can present in a similar way to an can present in a similar way to an acutely psychotic patient acutely psychotic patient

• Always complete a urine drug screen Always complete a urine drug screen on admission, Amphetamines can be on admission, Amphetamines can be clear from the urine in 48 hoursclear from the urine in 48 hours

• Patients should routinely have an Patients should routinely have an ECG at first presentationECG at first presentation

• ALWAYS complete a thorough ALWAYS complete a thorough neurological exam rarely malignancy neurological exam rarely malignancy can masquerade as psychosiscan masquerade as psychosis

Differential diagnosisDifferential diagnosis

• Acute & Transient Psychotic DisordersAcute & Transient Psychotic Disorders• Persistent Delusional DisorderPersistent Delusional Disorder• Bipolar Disorder (manic or mixed episode withBipolar Disorder (manic or mixed episode with• psychosis)psychosis)• Severe Depressive Episode (with psychosis)Severe Depressive Episode (with psychosis)• Schizo-affective DisorderSchizo-affective Disorder• Drug Induced PsychosisDrug Induced Psychosis• Organic Delusional Disorder: epilepsy; brainOrganic Delusional Disorder: epilepsy; brain• tumours, etctumours, etc• DeliriumDelirium• DementiaDementia

Differential Diagnosis 2Differential Diagnosis 2

• Schizotypal DisorderSchizotypal Disorder

• Personality DisordersPersonality Disorders

• ParanoidParanoid

• SchizoidSchizoid

• Emotionally unstable, borderline typeEmotionally unstable, borderline type

• Dissociative DisordersDissociative Disorders

• MalingeringMalingering

Sub typesSub types

• Classically divided into four sub typesClassically divided into four sub types

• ParanoidParanoid

• HebephrenicHebephrenic

• Simple or undifferentiatedSimple or undifferentiated

• CatatonicCatatonic

Paranoid typeParanoid type

• Relatively stable, often persecutoryRelatively stable, often persecutory

delusionsdelusions

• Usually hallucinations, particularly of theUsually hallucinations, particularly of the

auditory variety, and other perceptualauditory variety, and other perceptual

disturbancesdisturbances

• Affect, volition and speech disturbances,Affect, volition and speech disturbances,

and catatonic symptoms are either absentand catatonic symptoms are either absent

or inconspicuous.or inconspicuous.

Hebephrenic SchizophreniaHebephrenic Schizophrenia

• Prominent affective changesProminent affective changes• delusions and hallucinations: fleeting/rudimentarydelusions and hallucinations: fleeting/rudimentary• Irresponsible and unpredictable behaviourIrresponsible and unpredictable behaviour• MannerismsMannerisms• Shallow and inappropriate moodShallow and inappropriate mood• Disorganised thoughtDisorganised thought• Incoherent speechIncoherent speech• Social isolationSocial isolation• Usually poor prognosis (because of the rapidUsually poor prognosis (because of the rapid• development of "negative" symptoms, particularlydevelopment of "negative" symptoms, particularly• flattening of affect and loss of volitionflattening of affect and loss of volition

Catatonic SchizophreniaCatatonic Schizophrenia

Prominent psychomotor disturbances thatProminent psychomotor disturbances that

may alternate between extremes such asmay alternate between extremes such as

violent excitement & stupor, or automaticviolent excitement & stupor, or automatic

obedience & negativism. Constrainedobedience & negativism. Constrained

attitudes and postures may be maintainedattitudes and postures may be maintained

for long periods.for long periods.

Uncommon in industrialised countriesUncommon in industrialised countries

Undifferentiated SchizophreniaUndifferentiated Schizophrenia

• Psychotic conditions meeting the generalPsychotic conditions meeting the general

• diagnostic criteria for schizophrenia but notdiagnostic criteria for schizophrenia but not

• conforming to any of the other subtypes, orconforming to any of the other subtypes, or

• exhibiting the features of more than one ofexhibiting the features of more than one of

• them, without a clear predominance of athem, without a clear predominance of a

• particular set of diagnostic characteristics.particular set of diagnostic characteristics.

TreatmentTreatment

• Treatment & ManagementTreatment & Management• This should be again 3-fold: Bio-This should be again 3-fold: Bio-

psychosocialpsychosocial• MedicationMedication• Risk reduction (to himself & others)Risk reduction (to himself & others)• ObservationObservation• Psychology (CBT for delusions)Psychology (CBT for delusions)• Occupational therapyOccupational therapy• Family therapyFamily therapy• Social integrationSocial integration

Medication-1Medication-1

• ►►Older anti-psychotics (conventional) vsOlder anti-psychotics (conventional) vs• newer anti-psychoticsnewer anti-psychotics• ►►Older ones had more side effects Older ones had more side effects

(Extrapyramidal(Extrapyramidal• Side Effects [EPSEs])Side Effects [EPSEs])• ►►Anti-muscarinic meds are used to Anti-muscarinic meds are used to

countercounter• EPSEs (eg: procyclidine, orphenadrine, etc)EPSEs (eg: procyclidine, orphenadrine, etc)• ►►Newer ones are much more expensiveNewer ones are much more expensive• ►►Depot vs OralDepot vs Oral

ClozapineClozapine

• Targets Serotonin 2 receptors and D4Targets Serotonin 2 receptors and D4• receptors; the ordinary old and newreceptors; the ordinary old and new• antipsychotics target D2 receptors.antipsychotics target D2 receptors.►►NICE advises to use Clozapine, once 2NICE advises to use Clozapine, once 2• different anti-psychotics (of 2 differentdifferent anti-psychotics (of 2 different• groups) have been tried for appropriategroups) have been tried for appropriate• periods (each 6-12 weeks) and theperiods (each 6-12 weeks) and the• psychosis continues termed treatment psychosis continues termed treatment

resistant scizophrenia.resistant scizophrenia.

Medication-ECGMedication-ECG

• Possibly serious ECG abnormalitiesPossibly serious ECG abnormalities

• At least once yearly ECGs requiresdAt least once yearly ECGs requiresd

• QTc prolongation: the normal range is from QTc prolongation: the normal range is from 370370

• ms to 450 in men & 470 in women.ms to 450 in men & 470 in women.

• If pre-existing abnormalities, more prone forIf pre-existing abnormalities, more prone for

• Sudden Cardiac Death.Sudden Cardiac Death.

• Consider referral or senior review if not sureConsider referral or senior review if not sure

Neuroleptic Malignant Neuroleptic Malignant syndromesyndrome• Potentially fatal complication of Potentially fatal complication of

antipsychotic useantipsychotic use

• More common in neuroleptically naïve More common in neuroleptically naïve patientspatients

• Presents with- Severe muscle rigidity, Presents with- Severe muscle rigidity, High fever, mutism, delirium.High fever, mutism, delirium.

• Caused by muscle break down leading Caused by muscle break down leading to Rhabdomyalysis to Rhabdomyalysis

• Patient will often appear confused Patient will often appear confused and may be agitatedand may be agitated

• The clinical picture may be mistaken The clinical picture may be mistaken for catatonia or acute psychosisfor catatonia or acute psychosis

• Bloods will show a marked elevation Bloods will show a marked elevation in Ck in the 1000sin Ck in the 1000s

• It is a medical emergency and It is a medical emergency and patient’s will require fluids and may patient’s will require fluids and may need dialysis, urgent transfer to need dialysis, urgent transfer to medical unit is indicatedmedical unit is indicated

Tarditive dyskinesiaTarditive dyskinesia

• Distressing condition in which involuntary Distressing condition in which involuntary movements (chewing, sucking grimacing) movements (chewing, sucking grimacing) occur persistentlyoccur persistently

• This occurs more commonly with typical This occurs more commonly with typical antipsychotic drugs and is usually first antipsychotic drugs and is usually first noticed when stopping or changing noticed when stopping or changing medicationmedication

• Believed to be caused by dopamine Believed to be caused by dopamine hypersensitisation no universally effective hypersensitisation no universally effective treatment exists.treatment exists.