 \200 opportunistic infections 05_Semple_Chap05.indd 160 12/7/2012 3:28:35 PM HIV/AIDS AND PSYCHIATRY 1 161 Counseling HIV/AIDS patients \200 Pre-test counseling Consider: meaning of a +ve result; what actions the individual will tak e; con \201 dentiality issues; fears of individual; high- risk behaviors; reactions to str ess; social and other implications of +ve result. Post-test counseling to tell; discuss pre vention of transmission; offer support to individual and family. Clarify distortions; assess emotions; decide who Ethical issues \200 HIV testing test result will signi \201 cantly alter clinical manage ment. : encourage individual to tell sexual partner and other Con \201 dentiality medical personnel; if individual refuses, one may be obliged to inform without consent. Resource al location : issues of informed consent; only test without consent if a : e.g. availability of anti-retroviral drugs. 05_Semple_Chap05.indd 161 12/7/2012 3:28:36 PM CHAPTER 5 Organic illness 162 HIV/AIDS and psychiatry 2: clinical presentations Depression At least 30 \200\22350% of ind ividuals suffer a major depressive episode at some time following diagnosis. Clearly depres sion in this context has multiple causes and the challenge is to identify all the contribut ory fac- tors. Depressive illness should be differentiated from physical effects of HIV (we ight loss, loss of energy, etc.) as well as from HIV-associated dementia. Treatment: SSRIs, but problems of weight loss and headache; newer com- pounds such as nefaz odone and venlafaxine may be indicated. Suicide There is a 30x increased risk of suicide in individuals who are HIV +ve. High-risk times include: at diagnosis; at the death of an HIV +ve friend; as the individual experienc es deterioration in physical health. Mania Manic symptoms may develop in the context of HIV psychosis or as a result of treatmen t with anti-retroviral agents such as zidovudine (AZT). Treatment: Lithium is preferable (b eware risk of toxicity) since there is some evidence suggesting that sodium valproate may i ncrease viral repli- cation and reduce white cell count (WCC). Anxiety Infection with the virus is associated with increased risk of generalized anxiety d isorder (GAD), panic disorder, PTSD, and OCD. Chronic pain Up to 80% of patients experience chronic pain at some point, in particular chr onic headache. This may lead some individuals to self-medicate, putting them at risk of sub stance dependence. Delirium Delirium occurs in up to 30% of infected patients and is sometimes irre- versible. It is caused either by direct infection of the brain by the virus or by 2 infections and /or tumors. Delirium may be the initial manifestation of HIV-associated dementia. Psychosis A psychotic illness characterized by \202 uctuating symptoms that may alter ove r hours to days may occur in the context of HIV infection. Atypical bizarre psychotic sympt oms may give way to prominent mixed affective symptoms, which in turn may change to a withd rawn apathetic state. Aetiological factors include the effects of stress, medications, and 2 infections/tumors superimposed on the effects of direct infection of the brain by the virus. Thus psychosis i s a common early manifestation of 05_Semple_Chap05.indd 162 12/7/2012 3:28:36 PM HIV/AIDS AND PSYCHIATRY 2: CLINICAL PRESENTATIONS 163 subsequent HIV-associated dementia and it is likely that mild cognitive de \201 cits co-ex ist with the psychotic illness. Preferred treatment includes low-dose haloperidol or an atypical antipsychotic (e.g. olanza pine, quetiapine) \200\224due to increased sensitivity to extra-pyramidal side-effects. Ant i-retroviral agents such as zidovudine (AZT) may also reduce psychotic symptoms. HIV-associated dementia (HAD) Previously termed AIDS dementia, HAD is a relatively common o utcome in full-blown AIDS. Epidemiology 90% of AIDS patients have CNS changes post-mortem. 70 \200\22380% develop a co gnitive disorder. 30% develop HAD. Mean survival after diagnosis with HAD is 6 months. Pathology (a) Direct CNS infection: HIV is neurotropic, entering the brain through endothel ial gaps; the virus attaches to group 120 on CD4 +ve sites of microglial cells; a cascade o pens calcium channels leading to glutamate and nitrous oxide excitotoxicity; this results i n neuronal death and increased apoptosis. Sites include basal ganglia and subcortical and l imbic white matter. (b) Opportunistic infections/tumors: toxoplasmosis, papovavirus, cytome ga- lovirus (CMV), HSV, non-Hodgkin \200\231s lymphoma, and Kaposi sarcoma give rise to var iable neuropathology including encephalitis and focal necrosis. Clinical presentation \200 Early \200\230minor \200\231 cognitive disorder have very early CNS infection that is ofte n discounted as stress. Symptoms include cognitive slowing and memory de \201 cits as well as motor slowing and subtle incoordination. : with worsening of symptoms, HIV-associated d ementia (HAD) the clinical picture constitutes a dementia syndrome and is an AIDS-de \201 ning disorder. Clinical features are classi \201 ed as cognitive (subcortical dementia, fo cal cognitive de \201 cits, amnesia, mutism), motor (movement disorders, e.g. tremor, atax ia, choreo-athetosis, spasticity, myoclonus), and affective (depression, apathy, agitation, disinhibition, mania). Cognitive decline can be assessed using the HIV Dementia Scale and the Global Deterioration Scale of Reisberg (functional measure). : asymptomatic HIV +ve patients may Investigations CT/MRI: atrophy, iT2 signal. CSF: opportunistic infection, cytology, enzyme- linked immunosorbent assay (ELISA) +ve. EEG: general- ized slowing. Treatment Reverse transcriptase inhibitors (zidovudine [AZT]) delay HAD progression, while protease inhibitors reduce HIV load. 05_Semple_Chap05.indd 163 12/7/2012 3:28:36 PM CHAPTER 5 Organic illness 164 Neuropsychiatric aspects of CNS infections Viral encephalitis \200 Mumps , varicella-zoster, arbovirus, rubella \200\224may result in behavioral problems, lea rning dif \201 culties, and ADHD-like symptoms in children. HSV 1 \200\224involves inferi or frontal and anterior temporal lobes, resulting \200\224in the acute phase \200\224in del irium, hallucinations, and TLE. Chronic outcomes include Korsakoff psychosis, dementia, and Kluwer \200\223Bucy syndrome. EEG: slowing with bursts of increased slow- wave in the temp oral region. In \202 uenza (see b p. 167), characterized by Parkinsonism, oculogyric crise s, and psychosis. Epstein \200\223Barr virus/infectious mononucleosis encephalitis or chron ic fatigue syndrome. Measles slow virus infection. Features: behavioral problems, deteriora ting intellectual function, movement disorders (ataxia, myoclonus), seizures, and, \201 n ally, dementia in a child. Pathology: white and gray matter changes to occiput, cerebellum and basal ganglia. EEG: periodic complexes. \200\224a rare chronic outcome is encephalitis lethargica \200\224may result in myalgic \200\224rarely gives rise to subacute sclerosing panencephalitis, a Tuberculosis \200 TB meningitis exudate covers the base of the skull leading to vascular infarcts and hydrocephalus; cranial nerves may become involved. Psychiatric symptoms: apath y; withdrawal; insidious personality changes; delirium; hallucinations; chronic behavioral problems. Tuberculoma pressure (ICP). \200\224especially in children and young adults; caseating \200\224presents with focal signs, seizures, raised intracranial Neurosyphilis Historically known as general paresis of the insane or Cupid \200\231s diseas e, neurosyphilis is a chronic outcome of direct spirochaetal infection of the brain parench yma. It manifests more commonly in men in their 40s \200\22350s, roughly 15 \200\22320yrs a fter infection. The spirochaetes have a predilection for frontal and parietal lobes and the disease typically presents as a progres- sive frontal dementia. Classic symptoms Grandiosity, euphoria, and mania with mood-congru- ent delusions. Disinhib ition, personality change, and memory impairment are also common. Neurological features Argyll \200\223Robertson pupils; \200\230trombone tongue \200\231; t remor; ataxia; dysarthria; myoclonus; hyperre \202 exia; spasticity; and extra- pyramidal signs. 05_Semple_Chap05.indd 164 12/7/2012 3:28:36 PM NEUROPSYCHIATRIC ASPECTS OF CNS INFECTIONS 165 Megalomania in general paralysis Gentlemen, \200\224You have before you today a merchant, aged forty-three, who sits down wi th a polite greeting, and answers questions \202 uently and easily His illness bega n about two years ago. He became absent- minded and forgetful, to such an extent at last th at he was dismissed by the \201 rm for whom he had worked. Then, a year ago, he became ex cited, made extensive purchases and plans, weeping now and then in the deep- est despair, s o that he had to be taken into the hospital. On admission, he felt full of energy and intended to write verses here, where he was particularly comfortable. He could write bette r than Goethe, Schiller, and Heine. The most fabulous megalomania quickly developed. He pro - posed to invent an enormous number of new machines, rebuild the hos- pital, build a cathe dral higher than that at Cologne, and put a glass case over the asylum. He was a genius, sp oke all the languages in the world, would cast a church of cast-steel, get us the highest o rder of merit from the Emperor, \201 nd a means of taming the madmen, and present the asy - lum library with 1000 volumes, principally philosophical works. He had quite godly though ts When at its height, the disease may present a great resemblance to maniacal states , but the physical examination and proof of the defective memory will save us from confusin g it with them. So also will the senseless nature of the plans and the possibility of in \202 u- encing them, and the feebleness and yielding character of the manifesta- tions of t he will, which are all greater in general paralysis. Kraepelin E (1913) Lectures on Clinical Psychiatry, 3rd English edn. London: Bailli re, Ti ndall and Cox. 05_Semple_Chap05.indd 165 12/7/2012 3:28:36 PM CHAPTER 5 Organic illness 166 Autoimmune disorders and psychiatry Systemic lupus erythematosus (SLE) This multi-system au toimmune vasculitis is most common in women in their 30s and neuropsychiatric symptoms occu r in 75% of individuals with the disease. CNS changes include microvasculitis with infarcti on, in \202 am- mation, and coagulopathy. Seizures, cranial nerve palsies, peripheral neur opathy, \200\230spinal stroke \200\231, and other focal signs may occur in addition to der matological, rheumatological, hematological, and cardiovascular complications of the disord er. Importantly, drugs used to treat the condi- tion may have psychiatric side-effects (e.g . steroids; isoniazid; hydralazine). Psychiatric symptoms occur in 60% of cases and syndrom es include: \200 Lupus psychosis \200\224transient psychotic episodes with a recurrent and \202 uctuating course. Relapses are frequent and symptoms are variable with auditory and visual hallucina tions as well as paranoia, affective instability, and disturbed sensorium characteristic of the illness. Severe and prolonged psychosis due to SLE may result in vascular dementia. De pression depressive illness. Schizophrenia-like psychosis \200\224up to 30% of SLE patients experience clinically signi \201 cant \200\224a rare \201 nding in SLE. Polyarteritis nodosa (PAN) Most common in young men, PAN is an immune-mediated necrotizing vas- culitis characterized by saccular aneurysms and infarction. Neuropsychiatric \201 nd ings include: stroke; focal signs; seizures; \200\230spinal stroke \200\231; delirium; aud i- tory and visual hallucinations. 05_Semple_Chap05.indd 166 12/7/2012 3:28:36 PM MOVEMENT DISORDERS IN PSYCHIATRY 167 Movement disorders in psychiatry Movement disorders occur in three contexts within psychiat ry: \200 Extra-pyramidal diseases with psychiatric symptoms disease) Psychiatric disorders with abno rmal movements tics) Medication-induced movement disorders (e.g. Parkinson \200\231s (e.g. stereotypies; (e.g. EPSEs) Pathophysiology Movement disorders commonly involve a disequilib- rium of neurotransmitters such as dopamine (DA), acetylcholine (ACh), and gamma-aminobutyric acid (GABA) within the circuits of the basal gan- glia. Levels of DA and ACh tend to be inversely related. For exa mple, in Parkinsonism, there is dDA with iACh; conversely, chorea is character- ized by iDA and dACh. Core symptoms in extra-pyramidal disease: \200 \200 Negative symptoms Positive symptoms tremor, chorea, athetosis, hemiballismus, dystonia) \200\224bradykinesia, postural abnormalities, etc. \200\224rigidity and involuntary movem ents (resting Parkinsonism This is a syndrome characterized by 4 core symp- toms: slow \200\230pill-roll ing \200\231 tremor (4Hz); rigidity; bradykinesia; postural abnormalities. Etiology: \200 Degenerative diseases \200\224idiopathic Parkinson \200\231s disease (PD) (85% cases); prog ressive supranuclear palsy (PSNP); multiple system atrophy (MSA); corticobasal degeneration (CBD); ALS \200\223dementia \200\223Parkinson complex of Guam (ADPG) Medication \200\224ne uroleptics; antidepressants Toxins \200\224cobalt; manganese; magnesium; organophosphates I nfections \200\224encephalitis lethargica (post-in \202 uenza); CJD Miscellaneous \200\224 CVA of the basal ganglia; trauma of the basal ganglia; NPH; neoplasia of the basal ganglia; dementia pugilistica (punch-drunk syndrome); Lewy body dementia \200 \200 \200 Multiple system atrophy (MSA) 3 syndromes: striatonigral degen- eration; Shy \200\223Drager syndrome; olivopontocerebellar degeneration. Characterized by: Parkinsonism; ataxia; verti cal gaze palsies; pyramidal signs; autonomic abnormalities. Progressive supranuclear palsy (PSNP) Also known as Steele \200\223 Richardson \200\223Olszewski syndrome, PSNP has its on set in the 50s and 60s and is characterized by a tetrad of clinical \201 ndings: subcorti cal dementia; pseudobulbar palsy; supranuclear palsy; dystonia (of the head and neck). Ence phalitis lethargica Roughly 20yrs after the great in \202 uenza epi- demic of the 1920s, l arge numbers of patients who had suffered in \202 uenza encephalitis during the epidemic d eveloped this disorder (also called post- encephalitic Parkinsonism). Clinical \201 nding s: Parkinsonism; oculogyric cri- ses; pupillary abnormalities; psychosis). The disorder was the subject of the book (and \201 lm) by Oliver Sacks entitled Awakenings. 05_Semple_Chap05.indd 167 12/7/2012 3:28:36 PM CHAPTER 5 Organic illness 168 Parkinson \200\231s disease (PD) and psychiatry Parkinson \200\231s disease results in prog ressive impairment of voluntary initia- tion of movement, associated with a dementia of var iable severity, as well as psychiatric morbidity. It is caused by gradual loss of dopaminer gic neu- rons in the substantia nigra (pars compacta). This results in reduced DA and incre ased ACh in the basal ganglia. The remaining cells of the substan- tia nigra contain Lewy b odies. Epidemiology Occurs in 20:100 000 people; typically has its onset in the 50s and pea ks during the 70s; 4:5 = 3:2; 5% of cases are familial; 25% patients are disabled or die wi thin 5yrs and 60% within 10yrs; rare survival 20yrs. Symptoms and signs of PD \200 Tremor may start unilaterally and may be asymmetrical in intensity; tremor increases with e xcitement or fatigue and diminishes during sleep. Rigidity muscles. Bradykinesia \200\224s lowness; dif \201 culty initiating movement; reduced facial expression and blinking; \200 \230mask facies \200\231; reduced arm swing; \200\230festinating gait \200\231; reduced vo luntary speech; micrographia; \200\230freezing \200\231 episodes. Postural abnormalities \200\224 \202 exed posture; postural instability with frequent falls. Autonomic instabilit y retention; sweaty, greasy, seborrhoeic skin; hypersalivation with drooling. Fatiguability +ve glabellar tap . \200\230Air pillow sign \200\231 \200\224resting, \200\230pill-rolling \200\231 tremor of 4Hz; this is an early sign that \200\224 \200\230lead-pipe \200\231 or \200\230cog-wheel \200\231 rigidity, especially in \202 exor \200\224postural hypotension; constipation; urinary \200 \200 . . Dementia in PD 20 \200\22330% of patients develop some cognitive deterioration. Risk of dem en- tia in patients with PD is increased 2 \200\2233-fold. Risk of dementia increases with increasing age, increasing severity of symptoms, and coexistent car- diovascular disease. Clinically Usually a subcortical dementia with slowing, impaired execu- tive function, pers onality change, and memory impairment. Some patients merely develop subtle cognitive de \201 cits (dif \201 culties with shifting and sequence). Pathology Due to reduced DA in the frontal lobes; there is some evi- dence of overlap with DLB (b p. 140), while some patients have coexisting DAT. Depression in PD Very common \201 nding with 40 \200\22370% patients affected. While depr ession may be partly reactive to receiving the diagnosis or experiencing a worsening of PD symptoms, the depressive illness may be due to the actual disease process itself. Speci \201 cally, reduced levels of monoamines (DA, NE, 5HT) may lead to depression. Mood \202 uctuations are often noted in association 05_Semple_Chap05.indd 168 12/7/2012 3:28:36 PM PARKINSON \200\231S DISEASE AND PSYCHIATRY 169 with changes in plasma DA levels. Depression in PD is more common in women and in left-side d disease and is often atypical in nature. Treatment SSRIs; ECT (improves the depressive illness but can precipi- tate delirium). Psychosis/delirium in PD Psychotic depression is most common. Psychosis is commonly due to medications used in PD such as: \200 \200 Anticholinergics \200\224delirium; agitation; hallucinations; etc. Levodopa (L-dopa) and DA agonists \200\22410 \200\22350% have psychiatric complications including delirium, psychos is, and mania. Treatment Use atypical antipsychotics with a lower risk of EPSEs. 05_Semple_Chap05.indd 169 12/7/2012 3:28:36 PM CHAPTER 5 Organic illness 170 Huntington \200\231s disease (HD) A genetic disease characterized by a combination of progr essive demen- tia and worsening chorea. There is autosomal dominant inheritance with 100% p enetrance; thus 50% of a patient \200\231s offspring will be affected. Onset of symptoms an d diagnosis is usually after the patient has reproduced. A diagnostic test has become avail able which allows presymptomatic diag- nosis, but as no treatment is available, there are m ajor ethical issues sur- rounding screening. Pathology The genetic defect is a trinucleotid e repeat of CAG \200\224 between 37 and 120 repeats on chromosome 4. ddGABA neurons in the basal ganglia; this leads to increased stimulation of the thalamus and cortex by the globus pallidus. Also increase in DA transmission. Clinical features Classic triad of chorea, dem entia, and a family history of HD. Chorea is a movement disorder characterized by initial j erks, tics, gross involuntary movements of all parts of the body, grimacing, and dys- arthr ia. There is increased tone with rigidity and stiffness, positive primitive re \202 exes, and abnormal eye movements. Clinical course Onset usually during 30s and 40s; a small numbe r of juvenile onset cases; deteriorating course to death within 10 \200\22312yrs. Psychiatr ic syndromes Occur in 60 \200\22375% of patients with HD. \200 \200 \200 \200 Anxiety and depression are common Psychosis occurs early and paranoia is common \200\224 \200\230schizophrenia-like \200\231 Aggression and violence Subcortical dementia \200\224sl owing, apathy, and amnesia Investigations EEG: slowing. CT/MRI: atrophy of basal ganglia with \200\230boxing \200\231 of the caudate and dilation of ventricles. PET: dmetabolism in the basal ganglia. Treatmen t No treatment arrests the course of the disease. However, haloperidol (or other antipsycho tics) may help reduce abnormal movements. 05_Semple_Chap05.indd 170 12/7/2012 3:28:36 PM WILSON \200\231S DISEASE 171 Wilson \200\231s disease (WD) A rare genetic disease mapped to the long arm of chromosome 1 3 that involves an abnormality of copper metabolism. Copper deposits in the liver cause cir rhosis and in the basal ganglia, resulting in degeneration of the lentiform nucleus (hepato -lenticular degeneration). Clinical features Onset in childhood/adolescence or early adulth ood. Liver cirrhosis. Extra-pyramidal (E/P) signs include: tremor; dystonia; increased tone ; \202 apping tremor of wrists; wing-beating tremor of shoul- ders; risus sardonicus of f ace; bulbar signs (dysphagia, dysarthria); Kayser \200\223 Fleisher rings (green-brown corn eal deposits). Psychiatric syndromes \200 \200 \200 Investigations iserum/urine copper; dcaeruloplas min. Treatment Penicillamine. Mood disturbances \200\224common Subcortical dementia \200\22425% Psychosis \200\224rare 05_Semple_Chap05.indd 171 12/7/2012 3:28:36 PM CHAPTER 5 Organic illness 172 Other movement disorders Tics Tics are spontaneous, stereotyped movements that can be motor or vocal and usually involve iDA in the basal ganglia. Tics are classi \201 ed as p or s. p tics A spectrum with genetic overlap with each other and with ADHD and OCD (b p. 376): \200 \200 \200 s tics \200 \200 \200 Tourette \200\231s syndrome Transient tic disorder Chronic motor or vocal tic disorder Infection \200\224CJD; Sydenham \200\231s chorea; encephalitis Drugs \200\224levodopa (L-do pa); methylphenidate; cocaine; amfetamines Other \200\224toxic carbon monoxide (CO); CVA; t rauma Tremor \200 Exaggerated physiological tremor action; causes: stress; anxiety; caffeine; medications. Es sential tremor noticeable symmetrically in upper limbs. Extrapyramidal tremor Cerebellar, m idbrain, or red nucleus causes: trauma; vascular; MS; neoplasia; etc. \200\224(8 \200\22312Hz); occurs at rest and with \200\224(6 \200\22312Hz); at rest, with action and postural; most \200 \200\224(4Hz); resting tremor; e.g. Parkinsonism. \200\224(4 \200\2236Hz); intention trem or; Catatonia (b p. 992) A motor syndrome that has several causes and is diagnosed (DSM-IV) by the presence of 2 or more of the following: \200 \200 \200 \200 \200 Motor immobility \200\224catalepsy ( \200\230waxy \202 exibility \200\231); stupor Motor excitement Negativism or mutism Posturing, stereotypies, or mannerisms Echolalia or echopra xia 05_Semple_Chap05.indd 172 12/7/2012 3:28:37 PM 173 Chapter 6 Schizophrenia and related psychoses Introduction 174 Historical views of schizophrenia 176 The diagnosis of schizophrenia 178 D ifferential diagnosis of schizophrenia 180 Aetiological theories 182 Epidemiology of schizo phrenia 184 Examination of the patient with psychotic symptoms 186 Presentations of psychot ic illness 188 Initial assessment of acute psychosis 190 Initial treatment of acute psychos is 192 Maintenance phase 194 Discharge planning 196 Outpatient treatment and follow-up 198 First generation antipsychotics (FGAs) 200 Second generation antipsychotics (SGAs) 202 Anti psychotic side-effects 206 An approach to treatment-resistant schizophrenia (TRS) 208 Cloza pine 1: general guidelines 210 Clozapine 2: stopping and starting 212 Clozapine 3: side-eff ects 214 Antipsychotic depot injections 216 Disorders related to schizophrenia 218 Delusion al disorder 1: clinical features 220 Delusional disorder 2: differential diagnosis and etio logy 222 Delusional disorder 3: assessment and management 224 Acute and transient psychotic disorders 226 Induced delusional disorder 228 Delusional misidenti \201 cation syndromes 230 06_Semple_Chap06.indd 173 12/7/2012 3:30:27 PM CHAPTER 6 Schizophrenia and related psychoses 174 Introduction Schizophrenia and the related psychotic illnesses belong to a group of disorde rs traditionally called the \200\230functional psychoses \200\231. \200\230Functional \200\231 in this context means a disorder of brain function with no corresponding structura l abnormality. Despite improvements in our understanding of the pathology of these disorder s, their etiology is currently unknown and there is no de \201 nitive diagnostic test avai lable. For this reason, diagnosis is made clinically, using operationally de \201 ned crit eria (characteristic symp- toms and signs) and speci \201 c exclusion criteria (e.g. absen ce of primary organic disorder). The cardinal feature of schizophrenia and the related psychotic illnesses is the presence o f psychotic symptoms \200\224hallucinations and/or delusions. These symptoms are qualitativ ely different from normal experiences rather than the quantitatively abnormal responses of the neurotic and affective disorders and because of this they are regarded \200\224by patie nts and other health professionals \200\224as more serious and needing immediate psychiatri c attention. However, when an individual experiences hallucina- tions or becomes paranoid t hat people are talking about them, for exam- ple, it does not mean they necessarily have a severe and enduring mental disorder. They could be experiencing a reaction to drugs (prescr ibed or recreational), be experiencing severe anxiety, be acutely confused, or have early s igns of dementia. The differential diagnosis encompasses almost all psychiatric diagnoses ( see b p. 180) as well as some \200\230normal experiences \200\231. Careful history-taking and appropriate investigations (see b p. 187) are essential. Of the psychoses, schizophrenia has received the greatest attention in terms of research. T his is almost certainly because of the dramatic and devastating effects the disorder can ha ve on an individual \200\231s quality of life and their prospects for employment, marriage, and parenthood. Schizophrenia affects about 1 in 100 individuals, usually beginning in lat e adolescence or early adulthood. Untreated, it runs a chronic, deteriorat- ing course. In addition to the personal tragedy, schizophrenia creates a substantial public health burden due to the cost of lifelong health care needs and lost productivity. The symptoms of schizophrenia are conventionally divided into positive symptoms (an excess or a distortion of normal functioning) and negative symptoms (a decrease or loss of functio ning): \200 Positive symptoms interference, or passivity delusions). Hallucinations (usually auditory h allucinations commenting on the subject or referring to them in the third person e.g. \200 \230he looks like a fool \200\231). Formal thought disorder (a loss of the normal \202 ow of thinking usually shown in the subject \200\231s speech or writing). Negative symptoms s pontaneous behavior. Loss of awareness of socially appropriate behavior and social withdraw al. Flattening of mood, blunting of affect and anhedonia. Poverty of thought and speech. Delusions (commonly persecutory, thought Impairment or loss of volition, motivation, and 06_Semple_Chap06.indd 174 12/7/2012 3:30:27 PM INTRODUCTION 175 Fortunately, there are effective interventions that can bene \201 t individuals and help t hem to lead more normal lives. Current research is directed towards establishing the cause( s) of schizophrenia and investigating the possibility of early interventions in those ident i \201 ed at high risk for the dis- order or with prodromal symptoms (possible early signs of the disorder). Other psychoses with more speci \201 c symptoms, e.g. delusional miside nti \201 - cation syndromes (see b p. 230), may even help us understand how we normally pe rceive the world and help solve the mystery of the true nature of conscious experience. Why are there so few famous people with schizophrenia? Often there is a history of declining social and educational function which precludes signi \201 cant achievements (sometimes in spite of early promise). The chronic course of the c ondition and the major disruptions caused by periods of more severe symptoms also make it l ess likely that a person with schizophrenia will achieve as much as their peers. Until rela tively recently there have been few speci \201 c treatments for the disor- der, and even t oday prognosis is at best guarded. Nonetheless, there are notable exceptions to the rule: people who have battled with the dis order and achieved greatness in their chosen \201 elds \200\224in the arts, Vaslov Fomich Nijinski (1891 \200\2231950), the God of the Dance, whose personal account is to be found in his autobiography The Diary of Vaslov Nijinksy (1999); in sport, Lionel Aldridge (1941 \200\2231998), a member of Vince Lombardi \200\231s legendary Green Bay Packers of the 1960 s, who played in two Super Bowls, and, until his death, gave inspirational talks on his bat tle against paranoid schizophrenia; and, in popular music, Roger (Syd) Barrett (1946 \200 \2232006) of Pink Floyd and Peter Green (1946 \200\223) of Fleetwood Mac. Perhaps the most famous, due to a recent academy award-winning dramatization of his life, is the mathematici an John Forbes Nash Jr (1928 \200\223), who was awarded (jointly with Harsanyi and Selten) the 1994 Nobel Prize in Economic Science for his work on game theory. His life story (upon which the \201 lm was based) is recorded by Sylvia Nasar in the book A Beautiful Mind (19 98). 06_Semple_Chap06.indd 175 12/7/2012 3:30:27 PM CHAPTER 6 Schizophrenia and related psychoses 176 Historical views of schizophrenia In 1856, Morel coined the term D mence Pr coce to descr ibe a once bright and active adolescent patient who had gradually become silent and with- d rawn. Other clinical descriptions included Kahlbaum \200\231s Katatonie (1868), Griesinger \200\231s primare Verr cktheit (1868), Hecker \200\231s Hebephrenie (1869), and Sommer \200\231s inclusion of deteriorating paranoid syndromes in the concept of dementia (1894). In 1896 Emil Kraepelin described and separated the two major forms of insanity on the basis of different symptoms, course, and outcome. The \201 rst, manic-depressive insanity, had a relapsing and remitting course, with full recovery after each episode. The second groupe d together catatonia, hebephrenia, and the paranoid psychoses under the term dementia prae- cox, which had a progressive deteriorating course, where any improve- ment was only partia l. Over the next two decades (and further revisions of his textbook), Kraepelin \200\231s idea s were gradually accepted. Later the in \202 uence of Freud \200\231s psychoanalytical ide as shifted the focus from Kraepelin \200\231s \200\230disease of the brain \200\231 to a \200\230splitting of the mind \200\231 (schizophrenia), as proposed by Eugen Bleuler in his book Dementia praecox or the group of schizophrenias (1911). He believed the disorder to b e due to a \200\230loosening of associations \200\231 between psychic functions, with fund amental symptoms being thought dis- order, blunting/incongruity of affect, autism, and ambi valence. He added \200\230simple schizophrenia \200\231 to Kraepelin \200\231s subtypes an d did not consider hal- lucinations, delusions, and catatonic symptoms to be necessary for the diagnosis. This view of schizophrenia was to have a profound in \202 uence on clinical practice, particularly in the USA. European psychiatrists, particularly in Germany, continued to regard schizophrenia as a dis ease of the brain. Detailed classi \201 cation systems were developed based on symptomatol ogy, culminating in the teachings of Kurt Schneider, who described \200\230symptoms of \201 rst rank \200\231 in the acute phase of the illness (see b p. 95) and \200\230second- rank symptoms \200\231 which, although highly suggestive of schizophrenia, could also occur in other psy- choses (e.g. emotional blunting, perplexity, and other kinds of delusions an d hallucinations). The differences in diagnostic practices were highlighted in the 1970s. In 1972, Cooper foun d identical symptomatology in psychiatric admissions in New York and London, but higher rat es of schizophrenia diagnosed in New York. Similarly, in 1973, the WHO \200\231s Internatio nal pilot study of schizo- phrenia found the incidence of schizophrenia, using agreed diagn ostic cri- teria, to be 0.7 \200\2231.4 per 10 000 aged 15 \200\22354 across all countries studied, but with much higher rates of diagnosis evident in the USA and the USSR. This was explained by broader syndrome de \201 nition, related in the USA to con- sidering many mil der abnormalities as part of the schizophrenia spectrum, and in the USSR to the political p ressure to declare dissidents insane. This led to an international push towards operationally de \201 ned criteria (based on sym ptoms and course), with various systems proposed. The St Louis Criteria (Feighner et al. 19 72) require the patient to have been con- tinuously ill for 6mths, with no prominent affect ive symptoms, the pres- ence of delusions, hallucinations, or thought disorder, and for per sonal 06_Semple_Chap06.indd 176 12/7/2012 3:30:27 PM HISTORICAL VIEWS OF SCHIZOPHRENIA 177 and family history to be taken into account (marital status, age under 40, premorbid social adjustment). Other systems adopt the Schneiderian con- cept of schizophrenia, including Ca tego (Wing et al. 1974) \200\224a computer program that uses the Present State Examination (PSE) to generate diag- noses; Spitzer et al. \200\231s (1975) research diagnostic criteria (RDC) \200\224requiring at least 2wks duration, lack of affective symptoms, presence of th ought disorder, and hallucinations and delusions similar to Schneiderian \201 rst- rank s ymptoms; as well as our current versions of the ICD-10 (WHO 1992) and the American Psychiat ric Association \200\231s DSM-IV (1994) (see b p. 178). With the advent of neuroimaging, the biological substrate of schizophre- nia could be inves tigated in the living brain. In 1974 Ingvar and Franz n showed, with the aid of radiolabel led xenon gas, that blood \202 ow was reduced in the frontal lobes. In 1976 Johnstone et al. published the \201 rst controlled CT brain study which found enlarged ventricles asso ciated with poorer cognitive performance. In the absence of an aetiological model of schizo phrenia, pathophysiological models were developed to describe and explain the varieties of presentations found within the disease. In 1980 Crow described his \200\230Two syndrome hy pothesis \200\231, dividing schizophrenia into type 1 (predominant positive symptoms, acute onset, good premorbid adjust- ment, good treatment response, normal cognition and brain st ructure, reversible neurochemical disturbance) and type 2 (predominant negative symptoms, i nsidious onset, poor premorbid adjustment, poor treatment response, impaired cognition, str uctural brain abnormalities \200\224ventricular enlargement \200\224underlying irreversible neuronal loss). The \201 rst quantitative MRI study by Andreasen et al. in 1986 also dem onstrated smaller frontal lobes, and reduced intracranial and cerebral volume, providing fu rther evi- dence for schizophrenia as a neurodevelopmental disorder. Based upon examination of symptomatology and functional brain imaging Liddle (1992) identi \201 ed three syndromes in schizophrenia disease proc- esses with associated perfusion pat terns. This \200\230Three syndrome hypothesis of schizophrenia \200\231 consists of: (1) P sychomotor poverty syndrome \200\224poverty of speech, \202 attened affect, and decreased spontaneous movement; hypoperfusion of left dorsal prefrontal cortex, extending to the med ial pre- frontal cortex and the cingulate cortex and hypoperfusion in the head of caudate; reduced ability to generate action; (2) Disorganization syndrome \200\224 disorders of form of thought and inappropriate affect; hypoperfusion of right ventral prefrontal cortex and increased activity in anterior cingulate and dorsomedial thalamic nuclei projecting to the prefrontal cortex; rela- tive hypoperfusion of Broca \200\231s area and bilateral hypoperfu sion of parietal association cortex; reduced ability to inhibit inappropriate mental activi ty; and (3) Reality distortion syndrome \200\224delusions and hallucinations; increased act ivity in left parahippocampal region and left striatum; disorder of inter- nal monitoring. Schizophrenia research in the last two decades has focused more on \201 nding fundamental neuronal, neurochemical, or cognitive mechanisms than on localizing speci \201 c symptoms (see b p. 182). It is hoped that this approach may provide workable hypotheses that can fa cilitate the search for molecular mechanisms and lead to new treatment approaches. 06_Semple_Chap06.indd 177 12/7/2012 3:30:27 PM CHAPTER 6 Schizophrenia and related psychoses 178 The diagnosis of schizophrenia The diagnosis of schizophrenia is made on the basis of the p atient \200\231s symp- toms, and currently no con \201 rmatory test is available. DSM-IIIR (and its successor DSM-IV) and ICD-10 set out operational criteria against which a clinica l diagnosis can be con \201 rmed (see Table 6.1). Both give greater weight to certain type s of delusions or hallucinations formerly referred to as \201 rst-rank (see b p. 95). ICD-10 schizophrenia 1. At least one of the following: \200 \200 Thought echo, insertion, withdrawal, or broadcasting. Delusions of control, in \202 uence, or passivity; clearly referred to body or limb movements or speci \201 c thoughts, action s, or sensations; and delusional perception. Hallucinatory voices giving a running commenta ry on the patient \200\231s behavior or discussing him/her between themselves, or other typ es of hallucinatory voices coming from some part of the body. Persistent delusions of other kinds that are culturally inappropriate or implausible (e.g. religious/political identity, superhuman powers and ability). 2. Or, at least two of the following: \200 Persistent hallucinations in any modality, when accompanied by \202 eeting or half-formed delusions without clear affective content, persistent over-valued ideas, or occurring ever y day for weeks or months on end. Breaks of interpolations in the train of thought, resulti ng in incoherence or irrelevant speech or neologisms. Catatonic behavior such as excitement , posturing, or waxy \202 exibility, negativism, mutism, and stupor. Negative symptoms su ch as marked apathy, paucity of speech, and blunting or incongruity of emotional responses. A signi \201 cant and consistent change in the overall quality of some aspects of persona l behavior, manifest as loss of interest, aimlessness, idleness, a self-absorbed attitude, and social withdrawal. 3. Duration of \211 1mth. DSM-IV schizophrenia A. Characteristics of symptoms: two or more of the following, each pre sent for a signi \201 cant portion of time during a 1-mth period (or less if successfully treated): \200 \200 \200 \200 \200 Note: Only one \200\230A \200\231 symptom is required if delusions are bizarre or hal- lucinations consist of a voice keeping up a runni ng commentary on the person \200\231s behavior or thoughts, or two or more voices conversin g with each other. Delusions Hallucinations Disorganized speech Grossly disorganized or catatonic behavior Neg ative symptoms (i.e. affective \202 attening, alogia, or avolition) 06_Semple_Chap06.indd 178 12/7/2012 3:30:27 PM THE DIAGNOSIS OF SCHIZOPHRENIA 179