\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 B. Social/occupational dysfunction C. Duration: continuous signs of the disturbance persist for at least 6mths. This 6-mth period must include at least 1mth of symptoms that meet cri terion A. Note: DSM-IV also allows for course speci \201 ers: episodic \200\224with (no) i nter- episode residual symptoms (with negative symptoms); continuous (with prominent negati ve symptoms); single episode in partial remission (with prominent negative symptoms); singl e episode in full remission; other or unspeci \201 ed pattern. Table 6.1 Categories ICD-10 DSM-IV Key symptoms Paranoid schizophrenia Paranoid type Delusions and hallucinations Hebephrenic schizophrenia Disorganized type Disorganized speech behavior (often silly/ shallow) and \202 at or inappropriate affect Catatonic schizophrenia Catatonic type Psychomotor disturbance (see p. 992) Undifferentiated schizophrenia Undifferentiated type Meeting general criteria, but no speci \201 c symptom subtype predominates Post-schizophrenic depression Some residual symptoms, but depressive picture predominates Residual schizophrenia Residual type Previous \200\230positive symptoms \200\231 less marked; prominent \200\230negative \200 \231 symptoms Simple schizophrenia No delusions or hallucinations \200\224a \200\230defect state \200\231 (negative symptoms) gradually arises without an acute episode 06_Semple_Chap06.indd 179 12/7/2012 3:30:27 PM CHAPTER 6 Schizophrenia and related psychoses 180 Differential diagnosis of schizophrenia The differential diagnosis of schizophrenia is wide . Early in the course of the illness there may be signi \201 cant uncertainty as to the tr ue diagnosis. In general, compared to other disorders with psychotic symptoms, in schizo- p hrenia there is a broader range of psychotic symptoms (e.g. other than relatively circumscr ibed delusions) and greater functional impairment. Substance-induced psychotic disorder (e.g., alcohol, stimulants, hallucinogens, steroids, a ntihistamines, sympatho- mimetics). Careful history-taking may reveal onset, persistence, a nd cessa- tion of symptoms to be related to drug use or withdrawal. Psychotic disorder due to a general medical condition Focused history, examination, and inv estigations should help exclude other disorders including brain disease (e.g. head injury, CNS infection, CNS tumor, TLE, post-epileptic states, vCJD), metabolic (hypernatraemia, hyp ocalcaemia) or endocrine disturbance (hyperthyroidism, Cushing \200\231s syndrome). Mood disorders with psychotic features Mood and related biological symptoms are usually mor e severe and pre- cede psychosis. The psychotic features will usually be mood congruent (b p. 236). There may be a personal or family history of affective disorder. Acute/transient ( brief) psychotic disorder and schizophreniform disorder Diagnosed only after the psychotic symptoms have resolved based on the time course (see b p. 226). Sleep-related disorders Whe n symptoms characteristically only occur whilst falling asleep or on waking up (hypnagogic/ hypnopompic hallucinations \200\224see b p. 57). If there is excessive daytime tiredness du e to lack of sleep or side-effects of medication symptoms may occur at any time of the day. Delusional disorder Presence of at least one non-bizarre delusion with a lack of thought di s- order, prominent hallucinations, mood disorder, and \202 attening of affect (see b p. 220). Dementia and delirium Evidence of cognitive impairment or altered/ \202 uctuating le vel of conscious- ness, respectively. Delirium characteristically has a waxing and waning c ourse. Note: also consider \200\230late paraphrenia \200\231 which has an extensive litera - ture and is thought to be distinct from delusional disorder and schizophre- nia, associat ed with social isolation, ageing, medical problems/treatments, and sensory loss (see b p. 5 22). Body dysmorphic disorder Signi \201 cant overlap with delusional disorder, few signi \201 cant differentiating factors exist (see b p. 810). Post-traumatic stress disorder Evi dence of a past, life-threatening trauma (see b p. 390). 06_Semple_Chap06.indd 180 12/7/2012 3:30:27 PM DIFFERENTIAL DIAGNOSIS OF SCHIZOPHRENIA 181 Pervasive developmental disorder Evidence of impairment in functioning from the pre-school years. Obsessive \200\223compulsive disorder Signi \201 cant overlap with delusional disorder and , if reality testing regarding obsessions or compulsions is lost, delusional disorder is of ten diagnosed (see b p. 376). Hypochondriasis Health concerns generally are more amenable t o reality testing and are less \201 xed than in delusional disorder. Paranoid personality disorder Absence of clearly circumscribed delusions, presence of a per vasive, stable pattern of suspiciousness or distrust (see b p. 495). Schizotypal personalit y disorder Odd or eccentric behavior, absence of clearly circumscribed delusions (see b p. 495). Misidenti \201 cation syndromes Easily confused with delusional disorder, may be ass ociated with other CNS abnormalities (see b p. 230). Induced/shared psychotic disorder Evid ence that relatives or close friends share similar delusional beliefs (see b p. 228). Anxie ty disorder Sometimes patients use \200\230paranoia \200\231 or \200\230feeling paranoid \200\231 to describe over-concern, hypersensitivity, anxiety, agoraphobia, or social phobia \200\224 clari \201 cation is all that is required when terminology has acquired common p arlance. Factitious disorder Rarely psychotic symptoms may be feigned, usually to avoid responsibili - ties and/or to maintain a sick role (see b p. 814). 06_Semple_Chap06.indd 181 12/7/2012 3:30:27 PM CHAPTER 6 Schizophrenia and related psychoses 182 Aetiological theories Neurochemical abnormality hypotheses It seems unlikely that the etiol ogy of schizophrenia can be fully attributed to a single neurotransmitter abnormality (alth ough there are precedents, notably Parkinson \200\231s disease). In the study of models for psychosis, par- ticularly with the psychotomimetic (psychosis-mimicking) effects of certai n drugs, there is evidence for the involvement of multiple neurotransmitters in the genesis of psychotic symptoms. Some of the evidence implicating different neurotransmitters is out lined here (b p. 182).: Dopaminergic overactivity \200 \200 The fact that all known effective antipsychotics are DA antagonists. Positive correlation b etween the antipsychotic ef \201 cacy of a drug and its potency as a DA receptor antagonis t. Induction of psychotic symptoms by dopaminergic agents (e.g. amfetamine, cocaine, phency clidine [PCP], levodopa [L-dopa], bromocriptine). Imaging studies showing that amfetamine i nduces a greater displacement of radiolabelled-ligand bound to D2 receptors in the striatum in never-treated schizophrenia patients (suggesting a predisposition to increased DA relea se). Evidence of a correlation between the DA metabolite homovanillic acid (HVA) plasma lev els and both severity of psychotic symptoms and treatment response to antipsychotics. Glutaminergic hypoactivity \200 NMDA receptor antagonists, (e.g. ketamine, PCP) have been shown to induce both positive and negative symptoms of schizophrenia in healthy volunteers (possibly via modulation of the D A system) and exacerbate symptoms of patients with schizophrenia. The effects of ketamine ( in both animals and humans) are attenuated by antipsychotic medication (notably clozapine). Facilitation of NMDA receptor function by glycine (which binds to a modulatory site on NMD A receptors) and D-cycloserine (a selective partial agonist at the glycine modulatory site) may lead to symptomatic improvement. Serotonergic (5-HT) overactivity \200 The primary mode of action of LSD is through partial 5-HT agonism, associated with sensory distortions and hallucinations. The ef \201 cacy of clozapine in treatment-resistant schiz ophrenia is thought to be due to its combined dopaminergic and serotonergic antagonism. A-adrenergic overactivity \200 \200 Some antipsychotics also have clear adrenergic antagonism. Increased levels of noradrenalin e (NE) have been found in the CSF of patients with acute psychotic symptoms. Chronic treatm ent with antipsychotic drugs leads to decreased \201 ring rates in the locus coeruleus (t he origin of the noradrenergic system). 06_Semple_Chap06.indd 182 12/7/2012 3:30:27 PM AETIOLOGICAL THEORIES 183 -aminobutyric acid (GABA) hypoactivity \200 Loss of GABA inhibition has been shown to lead to overactivity in other neurotransmitter sy stems (e.g. DA, 5-HT, NE). There is some evidence to support loss of GABAergic neurons in t he hippocampus of patients with schizophrenia. Use of benzodiazepines may augment the thera peutic effects of antipsychotics by their GABA facilitation. The neurodevelopmental hypothesis Some authors hypothesize that schizophrenia may be a diso rder of neu- rodevelopment based on the following: \200 There is an excess of obstetric complications in those who develop the disorder. Affected s ubjects have motor and cognitive problems which precede the onset of illness. Schizophrenic subjects have abnormalities of cerebral structure at \201 rst presentation. Schizophreni c subjects have dermatoglyphic and dysmorphic features. Although the brain is abnormal, gli osis is absent \200\224suggesting that differences are possibly acquired in utero. \200 The disconnection hypothesis Neuropsychological, neuroanatomical, and functional investigat ions (SPET, PET, fMRI) have revealed: \200 Widespread reductions in gray matter in schizophrenia (particularly temporal lobe). Disorde rs of memory and frontal lobe function occurring in a background of widespread cognitive ab normalities. Reduced correlation between frontal and temporal blood \202 ow on speci \201 c cognitive tasks. A reduction in white matter integrity in tracts connecting the fron tal and temporal lobes. These \201 ndings have led to speculation that frontal \200\223temporal/parietal connecti vity may be the \201 nal common pathway for the development of schizophrenia. Other theories In the 1960s social theories of schizophrenia (e.g. schizophrenogenic mother , marital skew and schism) were common. They are now of his- torical interest only, not hav ing withstood scienti \201 c scrutiny. A number of other theories exist, including those w hich postulate that schizophrenia is an abnormality of information processing (Braff, 1993) , a problem of working memory (Goldman-Rakic, 1994), caused by cognitive dysmetria (Andreas en et al., 1999), an inability to think in \200\230meta-representations \200\231 or grasp \200\230theory of mind \200\231 (Pickup & Frith, 2001), a neurodegenerative dis- order (We iberger & McClure, 2002), a disorder of language (Berlim & Crow, 2003), or due to abnormal neuronal migration and the DISC1 gene (Johnstone et al., 2011). 06_Semple_Chap06.indd 183 12/7/2012 3:30:28 PM CHAPTER 6 Schizophrenia and related psychoses 184 Epidemiology of schizophrenia Incidence The incidence of schizophrenia worldwide is relatively similar when restricted, o perational diagnostic criteria are used to establish the diagnosis. The incidence in the UK and US is around 15 new cases per 100 000 population. 4 = 5, although males tend to have a n earlier onset than females (23 vs. 26yrs) and develop more severe illnesses. A few stud- ies have reported a falling incidence over time, although this may be due to changing diagn ostic practices/criteria. Prevalence The lifetime risk of schizophrenia is between 15 and 19 per 1000 popula- tion. T he point prevalence is between 2 and 7 per 1000. There are some differences between countri es, although these differences are minimized when a restrictive de \201 nition of schizoph renia based on \201 rst-rank symp- toms is used. Fertility Early studies reported low fertility in both men and women with schizo- phrenia. More recent studies suggest that although men are reproductively disadvantaged, the fertili ty of women with schizophrenia has increased probably due to deinstitutionalization. Mortality The diagnosis of schizophrenia carries around a 20% reduction in life expectancy. Suicide is the most common cause of premature death in schizophrenia. It accounts for 10 \200\22338% of all deaths in schizophrenia. Risk is probably highest in the year after \201 rst presentation and is greater in men. Morbidity There is signi \201 cant comorbidity in patients with schizophrenia: \200 Comm on medical problems that occur more frequently, e.g. communicable diseases (HIV, HepC, TB), epilepsy, diabetes, arteriosclerosis, IHD. Rare conditions that co-occur with schizophreni a, e.g. metachromic leukodystrophy, acute intermittent porphyria, coeliac disease, dysmorph ic features (high-arched palate, low-set ears, minor physical abnormalities). Substance mis use \200\224cannabis, stimulants, and nicotine in particular. Inheritance Genetic factors account for the majority of liability to schizophrenia. Heritab ility estimates range from 60 \200\22380%. The risk of developing schizo- phrenia when one has an affected relative is shown in Table 6.2. Molecular genetic studies have implicated c ertain genes \200\224most evidence is for: \200 Neuregulin brain development, synaptic plasticity and glutamate signaling. Dysbindin: relea se. : NRG1 on chromosome 8p21-22 \200\224has multiple roles in DTNBP1 on chromosome 6p22.3 \200\224helps regulate glutamate 06_Semple_Chap06.indd 184 12/7/2012 3:30:28 PM EPIDEMIOLOGY OF SCHIZOPHRENIA 185 DISC1 translocation (1,11)(q42;q14.3) \200\224has multiple roles in synaptic signaling and cell functioning. Catecholamine O-methyl transferase (COMT) polymorphism (e.g. valine to me thionine substitution at codon 158 \200\224Val158Met): helps regulate dopamine function in the frontal cortex. (Disrupted In SChizophrenia): a balanced chromosomal It is likely that an individual needs to have several genes \200\230of small effect \200 \231 that interact with each other and with time-speci \201 c exposure to other environmen tal risk factors. Environmental factors The schizophrenia: \200 \200 \200 \200 \200 \200 \200 following have been associated with an increased risk of Complications of pregnancy, delivery, and the neonatal period. Delayed walking and neurodev elopmental dif \201 culties. Early social services contact and disturbed childhood behavio r. Severe maternal malnutrition. Maternal in \202 uenza in pregnancy and winter births. De gree of urbanization at birth. Use of cannabis, especially during adolescence. Table 6.2 Schizophrenia liability based on affected relatives Family member(s) affected Risk (approximate) Identical twin 46% One sibling/fraternal twin 12 \200\22315% Both parents 40% One parent 12 \200\22315% One grandparent 6% No relatives affected 0.5 \200\2231% 06_Semple_Chap06.indd 185 12/7/2012 3:30:28 PM CHAPTER 6 Schizophrenia and related psychoses 186 Examination of the patient with psychotic symptoms A thorough medical history, including a systematic review and thorough physical examination, is important is the assessment of all patients present- ing with psychotic symptoms. It is all too easy to focus on the psychiatr ic aspects of the assessment to the exclusion of medical aspects which may inform the diagn osis and aid treatment planning. Key features in systematic review \200 Neurological \200\224headache, head injury, abnormal movements of the mouth or tongue, dipl opia, hearing or visual impairment (delusional disorder is more common when there is sensor y impairment), \201 ts/ faints/blackouts/dizzy spells, altered consciousness or memory pr oblems, stroke, coordination problems, marked tremor or muscle stiffness. Respiratory \200 \224dyspnoea, orthopnea. Cardiovascular \200\224chest pain, palpitations. Gastrointestinal \200\224constipation (can be side-effect of anticholinergic psychotropic drugs), nausea, vo miting. Genitourinary \200\224urinary hesitancy (retention related to anticholinergic drugs ); in women, a menstrual history; for both: sexual problems (which may be secondary to medi cation). \200 \200 Mental state examination \200 Aside from the more obvious psychotic features, a comprehensive assessment includes asking about mood, sleep, symptoms of anxiety, and cognitive function. Be sure to check orientatio n, attention, concentration, and anterograde/retrograde memory at a minimum \200\224always consider underlying neurological condition when disorientation is present or if memory prob lems are severe or persistent in spite of adequate treatment. Diagnostic formulation Even in the absence of a speci \201 c cause, the etiology of schizo phrenia is predominantly in \202 uenced by factors affecting the brain. However, the follo wing areas might be considered as a guide to the assessment of pre- disposing, precipitatin g, and perpetuating factors: \200 Biological substance misuse, drug non-compliance, history of obstetric complications, brain injury, and comorbid medical illness. Psychosocial friction, living conditions, attitude a nd knowledge of illness. Consider family history of psychiatric illness, recent Consider recent stressful life events, family cohesion/ Physical examination \200 \200 Full physical examination is essential for all inpatients. The need for a complete physical examination in an outpatient setting tends to be based on presenting complaints and/or the availability of adequate facilities/time constraints. 06_Semple_Chap06.indd 186 12/7/2012 3:30:28 PM EXAMINATION OF THE PATIENT WITH PSYCHOTIC SYMPTOMS 187 There really can be no excuse for overlooking systemic comorbidities \200\224at the very le ast arrange for the primary care physician to review the patient or reschedule a longer app ointment somewhere where facilities are available. A full neurological examination may be t he most important investigation, and should focus on gait inspection; examination of the ex tremities for weakness and/or altered sensation; examination of hand \200\223eye coordinati on; examination of smooth ocular pursuit; and examination of the cranial nerves. Scales, su ch as the Abnormal Involuntary Movement Scale (AIMS), may be useful to record and monitor p otential movement side-effects of medication. Investigations Blood tests \200 Routine \200 When suggested by history/examination horm one (PTH), cortisol, tumor markers. : U&Es, LFT, calcium, FBC, glucose. : VDRLs, TFTs, parathyroid Radiological \200 CT or MRI in the presence of suggested neurological abnormality or persistent cognitive imp airment. CXR only where examination/history suggests comorbid respiratory/ cardiovascular c ondition. Urine \200 \200 Urinary drugs screen (particularly stimulants and cannabis). Microscopy and culture (where history suggestive). Other \200 EEG rarely necessary unless history of seizure or symptoms suggest TLE. Special investigations \200 24-hr collection for cortisol (if Cushing \200\231s disease suggested from history/examinat ion). 24-hr catecholamine/5-HIAA collection for suspected phaeochromocytoma/carcinoid syndr ome respectively. 06_Semple_Chap06.indd 187 12/7/2012 3:30:28 PM CHAPTER 6 Schizophrenia and related psychoses 188 Presentations of psychotic illness When discussing the management of schizophrenia in parti cular, and the psychotic illnesses more generally, it is helpful to consider two distinct b ut related phases: the acute psychotic episode and the maintenance phase. An acute psychoti c episode may represent a \201 rst episode or a relapse of schizophrenia or may represent another illness within the differential diag- nosis (b p. 180). The aim of treatment in an acute episode is to abolish psychotic symptoms while minimizing distress and ensuring pati ent safety. Treatment of acute episodes is similar whatever the underlying diagnosis. Once psychotic symptoms have been abolished (or improved as far as possible), one enters the mai ntenance phase. Here the concern shifts to prophylaxis (which often includes maintenance me dication), rehabilitation, and maximization of function. Unfortunately acute psychotic rela pse is possible in schizophrenia despite optimum maintenance treatment. Prodromal schizophrenia \200\230Prodrome \200\231 is a retrospective concept relating to e vidence of premorbid change in an individual who later develops a condition. In schizophren ia, there is evidence of prodromal symptoms in 80 \200\22390% of cases (10 \200\22320% have acute onset). The typical presentation is of non-speci \201 c or negative symptoms (early prodrome) followed by attenuated, mild, positive symp- toms (late prodrome).1 The main pro blem in detecting attenuated or sub- threshold symptoms is that the rate of conversion to s chizophrenia is low. Use of speci \201 c screening tools such as the PACE (Personal Assess ment and Crisis Evaluation Clinic), COPS (Criteria of Prodromal Syndromes), or SIPS (Struct ured Interview for Prodromal Syndromes), raises detection rates to 20 \200\22340%.2 These p opulations are perhaps better termed as having an \200\230at-risk \200\231 mental state (A RMS) for psychosis, or being at \200\230ultra high risk \200\231 (UHR) of psychosis. Wheth er treatment is indicated at this stage remains controversial (see b p. 195). The \201 rst schizophrenic episode The \201 rst episode of schizophrenia in an individu al generally occurs in late adolescence or early adult life. Many people experiencing their \201 rst epi- sode will have no personal or family experience of mental ill-health and s ome will lack insight that their symptoms are a result of mental illness. As a result many patients will present in crisis and not directly complain- ing of psychotic symptoms. The r ange of possible presentations is very wide, however the following presentations (or their variants) are com- monly seen: \200 \200 A spouse or relative noticing withdrawn or bizarre behavior. Failure to achieve educational potential with referral by school or student health services. Onset of personality change, social withdrawal and \200\230odd \200\231 behavior. Presentation via criminal justice sy stem (see section on schizophrenia and offending, b p. 690). Presentation following deliber ate self-harm or suicide attempt. Complaining to council/police etc. on basis of delusional symptoms (e.g. hearing voices of neighbors throughout the night). \200 \200 06_Semple_Chap06.indd 188 12/7/2012 3:30:28 PM PRESENTATIONS OF PSYCHOTIC ILLNESS 189 Occasionally the \201 rst sign may be symptoms more typically characteristic of another d isorder (e.g. depression, mania, OCD, panic disorder). The \201 rst episode of schizophrenia is often a time of diagnostic uncer- tainty (and oc casionally the diagnosis may take months/years to become clear). Frequently, the clinical p icture includes comorbid substance misuse, personality dif \201 culties, recent stressful life events, or a combination of all three. It is usually necessary to admit people suspect ed of \201 rst schizo- phrenic episodes in order to assess the extent of their psychopath ology, to provide a time for education of both the patient and their family, and to provide pharmacological and psychological treatments in an environment where compliance can be car efully assessed. Inpatient admission is always necessary where the patient poses a signi \201 cant danger to themselves or others. Subsequent episodes Subsequent presentations may be due to relapse of psychotic symptoms af ter remission, a deterioration in or a change in the quality of partially treated psychotic symptoms, or a crisis relating to life events in a patient who, as a result of their illne ss, has an impaired ability to manage stress. Relapses can occur spontaneously in the absence of causative factors and in spite of good c ompliance with anti-psychotic treatment. However, very often relapses relate to medication non-compliance, drug or alcohol misuse or life stresses (or a combination of these). Often in an individual patient the time course, prodromal features and symptomatology of a relapse are characteristic \200\224the so-called \200\230relapse signature \200\231. Educa ting patient and carers about these warning signs, and awareness of and documentation of th ese features within the treating team, are important parts of relapse prevention. 1 Yung AR, Phillips LJ, McGorry PD, et al. (1998) Prediction of psychosis: a step towards i ndicated prevention of schizophrenia. Br J Psychiat Suppl 172: 14 \200\22320. 2 Miller TJ, McGlashan TH, Rosen JL, et al. (2002) Prospective diagnosis of the initial prodrome for sch izophrenia based on the Structured Interview for Prodromal Syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiat 159: 863 \200\2235. 06_Semple_Chap06.indd 189 12/7/2012 3:30:28 PM CHAPTER 6 Schizophrenia and related psychoses 190 Initial assessment of acute psychosis Issues affecting initial management decisions In view of the range and variety of presentations and the broad differential (b p. 180), it is dif \201 cult to be prescriptive in dealing with a patient who presents with psychotic sympto ms. Symptoms may range from mild para- noid ideas to elaborate and \201 rmly held delusio ns with associated auditory hallucinations urging the patient to violence. Often it is dif \201 cult to estab- lish a clear history initially, and assessment is focused on the immed iate concerns: \200 The risk they currently pose to themselves \200\224not just the possibility of acts of self -harm or suicide, but also because of other aspects of their behavior (e.g. police becoming involved, family relationships, work, continued driving, etc.). Risk of violence \200\224t he nature of risk ( with current symptoms (e.g. delusions about a speci \201 c person or g roup of individuals; what the \200\230voices \200\231 are telling them to do). The degree of insight retained by the patient and the likelihood of them cooperating with medical mana gement. Whether hospital admission or transfer to a psychiatric ward is warranted to assess and manage the acute symptoms (with or without the use of the Mental Health Act). Whether their current behavior is so disturbed as to require urgent treatment (b p. 990) to allow f urther assessment, including physical examination and other routine investigations (b p. 18 7). The person \200\231s current social circumstances and the level of support available to them (partner, relatives, friends, community psychiatric nurse [CPN], etc.) that may allow some \202 exibility in management (as well as being a source of third-party information) . b p. 692) and any association The greatest in \202 uence on your course of action will often be the reason why the perso n has been referred in the \201 rst place (e.g. brought up by a concerned relative, no lo nger able to be managed at home, breach of the peace, self-referral because of own concerns , attempted suicide). When there is a good account of the history of the presenting complaint(s), it may be possi ble to establish the most likely diagnosis and proceed accordingly, e.g. a drug- or alcohol -related disorder, acute confu- sional state (b p. 790), \201 rst episode of schizophreni a (b p. 188), relapse of known schizophrenia (b p. 189), delusional disorder (b p. 220), ac ute psychotic disorder (b p. 226). During initial assessment, particularly with unmedicated patients, record (verbatim if poss ible) speci \201 c aspects of the patient \200\231s psychopathology (nature and content of delusions and hallucinations), before they become modi \201 ed by the necessary use of me dication. This information is important as it will in \202 uence later decisions regarding , for example, assessment of treatment response and need for continued use of the Mental He alth Act (MHA). Many patients with a psychotic presentation will have comorbid drug and/or alcohol problems . The fact that the psychotic episode is suspected to be wholly or partially attributable t o comorbid substance use should 06_Semple_Chap06.indd 190 12/7/2012 3:30:28 PM INITIAL ASSESSMENT OF ACUTE PSYCHOSIS 191 not be allowed to affect the treatment offered acutely, which should be planned on the basi s of the nature and severity of the psychotic symptoms and the associated risk. On recovery from the acute episode the comorbid substance use should become a focus for clinical atten tion. The need for hospital admission As noted in Issues affecting initial management decidions, b p. 190, cer- tain clinical features and situations will determine whether hospital admis- sion (or transfer to psychiatric ward) is necessary: \200 \200 High risk of suicide or homicide. Other illness-related behavior that endangers relationshi ps, reputation, or assets. Severe psychotic, depressive, or catatonic symptoms. Lack of cap acity to cooperate with treatment. Lack or loss of appropriate psychosocial supports. Failu re of outpatient treatment. Non-compliance with treatment plan (e.g. depot medication) for patients detained under the MHA. Signi \201 cant changes in medication for patient at high risk of relapse (including clozapine \200\230red \200\231 result \200\224b p. 213). Need to address comorbid conditions (e.g. inpatient detoxication, physical problems, serious med ication side-effects). \200 \200 \200 \200 Suitability of the ward environment A busy psychiatric ward may not be an ideal environment for a patient experiencing acute psychotic symptoms. As far as possible the person should be nursed in calm surroundings (a single room, if possible), with minimal stimulation (e.g. unfamiliar people, TV, radio). A balance should be struck between the need for regular obs ervation and the likelihood that this may reinforce persecutory delusions. If behavior beco mes unmanageable, despite regular medication, it may be necessary to consider referral of t he patient to a more secure environment, e.g. an intensive psychiatric care unit (IPCU). Early review Regular review is critical in the \201 rst 72hrs to assess any improvement i n mental state, response to medication, level of observation needed, and carry out statutor y duties under the MHA (including the need for contin- ued detention, if emergency powers h ave been used). This is also a time for information-gathering from friends, family, GP, oth er agencies, etc. and organizing any investigations, including physical examination and rou tine blood tests that may not have been possible initially. 06_Semple_Chap06.indd 191 12/7/2012 3:30:28 PM CHAPTER 6 Schizophrenia and related psychoses 192 Initial treatment of acute psychosis The management of psychotic patients should include, w herever possible, the usual features of good medical practice: undertaking a comprehensive assessment of medical, social, and psychological needs; involving patients and their relati ves in decisions about medical care; and providing patients and carers with clear verbal an d, if necessary, written information (see NICE guidelines, Box 6.1). Emergency treatment of behavioral disturbance Follow guidance as detailed for the managemen t of acute behavioral dis- turbance (b p. 990). Points to note \200 