Schizophrenia for postgraduates


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Schizophrenia for postgraduates

  1. 1. By Mohamed Abdelghani Schizophrenia Schizophrenia is a clinical syndrome that involves cognition, emotion, perception, and other aspects of behavior. The expression of these manifestations varies across patients and over time, but the effect of the illness is always severe and is usually long lasting. The disorder usually begins before age 25, persists throughout life, and affects persons of all social classes. Both patients and their families often suffer from poor care and social ostracism because of widespread ignorance about the disorder. Clinicians should appreciate that the diagnosis of schizophrenia is based entirely on the psychiatric history and mental status examination. There is no laboratory test for schizophrenia. History Early Greek physicians described delusions of grandeur, paranoia, and deterioration in cognitive functions and personality. However, in the 19th century, schizophrenia emerged as a medical condition for study and treatment. i. Benedict Morel (1809-1873) A French psychiatrist, used the term demence precoce to describe deteriorated patients whose illness began in adolescence.ii. Emil Kraepelin (1856-1926) Kraepelin translated Morels demence precoce into dementia precox, a term that emphasized the change in cognition (dementia) and early onset of the disorder (precox). Patients with dementia precox were described as having a long-term deteriorating course and the clinical symptoms of hallucinations and delusions. Kraepelin distinguished these patients from those who underwent distinct episodes of illness alternating with periods of normal functioning which he classified as having manic-depressive psychosis. Another separate condition called paranoia was characterized by persistent persecutory delusions. These patients lacked the deteriorating course of dementia precox and the intermittent symptoms of manic-depressive psychosis. i
  2. 2. By Mohamed Abdelghaniiii. Eugene Bleuler (1857-1939) Bleuler coined the term schizophrenia, which replaced dementia precox. He chose the term to express the presence of schisms between thought, emotion, and behavior in patients with the disorder. Bleuler stressed that, unlike Kraepelins concept of dementia precox, schizophrenia need not have a deteriorating course. This term is often misconstrued, especially by lay people, to mean split personality. Split personality, called dissociative identity disorder, in DSM-IV- TR differs completely from schizophrenia . The Four As (Associations, Affect, Autism, and Ambivalence). According to Bleuler: Fundamental (or primary) symptoms of schizophrenia: associational disturbances of thought, especially looseness, affective disturbances, autism, and ambivalence. Accessory (secondary) symptoms: hallucinations and delusions; these symptoms are seen by Kraepelin as major indicators of dementia precox.iv. Ernst Kretschmer (1888-1926): Kretschmer collected data to support the idea that schizophrenia occurred more often among persons with asthenic (i.e., slender, lightly muscled physiques), athletic, or dysplastic body types rather than among persons with pyknic (i.e., short, stocky physiques) body types which were more likely to incur bipolar disorders. His observations may seem strange, but they are not inconsistent with a superficial impression of the body types in many persons with schizophrenia. v. Kurt Schneider (1887-1967): "First-rank symptoms" First-rank symptoms were not specific for schizophrenia and were not to be rigidly applied but were useful for making diagnoses. In patients who showed no first-rank symptoms, the disorder could be diagnosed exclusively on the basis of second-rank symptoms and an otherwise typical clinical appearance. ii
  3. 3. By Mohamed Abdelghani Clinicians frequently ignore this warnings and sometimes see the absence offirst-rank symptoms during a single interview as evidence that a person does nothave schizophrenia.Kurt Schneider Criteria for Schizophrenia 1. First-rank symptoms a. Audible thoughts b. Voices arguing or discussing or both c. Voices commenting d. Somatic passivity experiences e. Thought withdrawal and other experiences of influenced thought f. Thought broadcasting g. Delusional perceptions h. All other experiences involving volition made affects, and made impulses 2. Second-rank symptoms a. Other disorders of perception b. Sudden delusional ideas c. Perplexity d. Depressive and euphoric mood changes e. Feelings of emotional impoverishment f. "…..and several others as well"N.B.: ‫ ﻟﻠﺘﺴﮭﯿﻞ‬First-rank symptoms --- "11 symptoms in 4 categories: i. Auditory hallucinations:  Voices arguing  Voices commenting  Audible thoughts ii. Delusion of thought interference:  Thought insertion  Thought withdrawal  Thought broadcasting iii. Delusion of control:  Passivity of affect  Passivity of impulse  Passivity of volition  Somatic passivity iv. Delusional perception: iii
  4. 4. By Mohamed Abdelghani  1ry delusion following normal perceptionvi. Karl Jaspers (1883-1969): Jaspers paved the way to understand the psychological meaning of schizophrenic signs and symptoms such as delusions and hallucinations.vii. Adolf Meyer (1866-1950): Meyer, the founder of psychobiology, saw schizophrenia as a reaction to life stresses and called it "the schizophrenic reaction". In later editions of DSM, the term reaction was dropped. Epidemiology In U.S.A., the lifetime prevalence of schizophrenia is about 1%. According to DSM-IV-TR, the annual incidence of schizophrenia ranges from 0.5 to 5.0 per 10,000, with some geographic variation (e.g., the incidence is higher for persons born in u rban areas of industrialized nations). Schizophrenia is found in all societies and geographical areas, and incidence and prevalence rates are equal worldwide. In U.S.A., about 0.05% of the total population is treated for schizophrenia in any single year, and only about half of all patients with schizophrenia obtain treatment, despite the severity of the disorder. 1. Gender Schizophrenia is equally prevalent in men and women. However, the two genders differ in the onset and course of illness. Onset is earlier in men than in women. The peak ages of onset are 10 to 25 years for men and 25 to 35 years for women. Unlike men, women display a bimodal age distribution, with a second peak occurring in middle age. Approximately 3 to 10% of women with schizophrenia present with disease onset after age 40. Some studies indicated that men are more likely to be impaired by negative symptoms than are women and that women are more likely to have better social functioning than are men prior to disease onset. iv
  5. 5. By Mohamed Abdelghani In general, the outcome for female schizophrenia patients is better than thatfor male schizophrenia patients. 2. Age About 90% of patients are between 15 and 55 years old. Onset before age 10or after age 60 is extremely rare. When onset occurs after age 45, the disorder is characterized as late-onsetschizophrenia. 3. Reproductive Factors The use of psychopharmacological drugs, the open-door policies and thedeinstitutionalization in state hospitals, and the emphasis on rehabilitation andcommunity-based care for patients have all led to an increase in the marriageand fertility rates among persons with schizophrenia. So, the number of children born to parents with schizophrenia is continuallyincreasing. The fertility rate for persons with schizophrenia is close to that forthe general population. First-degree biological relatives of persons with schizophrenia have a tentimes greater risk for developing the disease than the general population. 4. Medical Illness Persons with schizophrenia have a higher mortality rate from accidents andnatural causes than the general population. The higher rate may be related to the fact that the diagnosis and treatment ofmedical and surgical conditions in schizophrenia patients can be clinicalchallenges. Several studies have shown that up to 80% of all patients havesignificant concurrent medical illnesses and that up to 50% of these conditionsmay be undiagnosed. 5. Infection and Birth Season Schizophrenics are more likely to have been born in the winter and earlyspring and less likely to have been born in late spring and summer. In the Northern Hemisphere, Schizophrenics are more often born in themonths from January to April. In the Southern Hemisphere, persons withschizophrenia are more often born in the months from July to September. v
  6. 6. By Mohamed AbdelghaniThis may be due to:  Season-specific risk factors, such as a virus or a seasonal change in diet.  Another hypothesis is that persons with a genetic predisposition for schizophrenia have a decreased biological advantage to survive season- specific insults.Other factors include: o Gestational and birth complications o Exposure to influenza epidemics o Maternal starvation during pregnancy o Rhesus factor incompatibility o Excess of winter births The nature of these factors suggests a neurodevelopmental pathologicalprocess in schizophrenia, but the exact pathophysiological mechanism is notknown. Evidence that prenatal malnutrition may play a role in schizophrenia wasderived from the studies of the Dutch Hunger Winter of 1944 to 1945. Exposureto the peak of the famine during the periconceptional period was associated witha significant, twofold increased risk of schizophrenia. In a subsequent study, thiscohort exposed to famine in early gestation also showed an increase in risk ofschizoid personality disorders. Epidemiological data show a high incidence of schizophrenia after prenatalexposure to influenza during several epidemics of the disease. Some studies show that the frequency of schizophrenia is increasedfollowing exposure to influenza "which occurs in the winter" during the secondtrimester of pregnancy. Other data supporting a viral hypothesis are an increased number of physicalanomalies at birth, an increased rate of pregnancy and birth complications,seasonality of birth consistent with viral infection, geographical clusters of adultcases, and seasonality of hospitalizations. Viral theories stem from the fact that several specific viral theories have thepower to explain the particular localization of pathology necessary to accountfor a range of manifestations in schizophrenia without overt febrile encephalitis. vi
  7. 7. By Mohamed Abdelghani There are six hypothetical models of viral and immune pathophysiology relevant to schizophrenia: Models of Viral and Immune Causes of Schizophrenia Retroviral Altered expression of the hosts own genes and the genes of the hosts offspring toward the development of infection schizophrenia (the virogene hypothesis). Viruses with an affinity for CNS can cause sustained alterations in the functioning and can infect the brain, with substantive disease manifestations only showing up Current or active many years later. The past viral infection hypothesis viral infection posits a virus infecting certain brain tissues early in life to create a vulnerability to schizophrenia or as a causal mechanism for the initial illness processes that later lead to the picture of classical schizophrenia. In theory, viral reactivation might result in an induction Virus-activated of schizophrenic psychopathology. Alternatively, a virusimmunopathology may induce the host to fail to recognize its own tissues as "self" and, to mount a destructive immune response. Schizophrenia has been hypothesized to be an idiopathic autoimmune disease, such as rheumatoid arthritis or Autoimmune systemic lupus erythematosus, where, for reasons pathology probably genetics, some tissues are not recognized as self and become the target of immune response. Exposure to influenza epidemics during the 2nd trimester Maternal of pregnancy are more likely to give birth to offspring at increased risk for schizophrenia. Prenatal rubella infection infection may increase the risk for development of schizophrenia and other nonaffective psychotic disorders. 6. Substance Abuse Substance abuse is common in schizophrenia. The lifetime prevalence of any drug abuse (other than tobacco) is often greater than 50%, Abuse is associated with poorer function. In one population-based study, the lifetime prevalence of alcohol within schizophrenia was 40%. Alcohol abuse increases risk of hospitalization and may increase psychotic symptoms. People with schizophrenia have an increased prevalence of abuse of common street drugs. There is a strong association between cannabis and vii
  8. 8. By Mohamed Abdelghanischizophrenia. Those reporting high levels of cannabis use were at sixfoldincreased risk of schizophrenia compared to nonusers. The use of amphetamines, cocaine, and similar drugs should raiseparticular concern due to their marked ability to increase psychotic symptoms. Nicotine: Up to 90% of schizophrenics may be dependent on nicotine. Apart from smoking-associated mortality, nicotine decreases the bloodconcentrations of some antipsychotics. The increased prevalence in smoking is due, at least in part, to brainabnormalities in nicotinic receptors. A specific polymorphism in a nicotinicreceptor has been linked to genetic risk for schizophrenia So, o Nicotine administration appears to improve some cognitive impairments and Parkinsonism in schizophrenia, possibly because of nicotine- dependent activation of dopamine neurons. o Recent studies demonstrated that nicotine may decrease positive symptoms such as hallucinations in schizophrenics by its effect on nicotine receptors in the brain that reduce the perception of outside stimuli, especially noise. In that sense, smoking is a form of self-medication. 7. Population Density The prevalence of schizophrenia is correlated with local population densityin cities of more than 1 million people. The correlation is weaker in cities of100,000 to 500,000 people and is absent in cities with fewer than 10,000 people. The effect of population density is consistent with the observation that theincidence of schizophrenia in children of either one or two parents withschizophrenia is twice as high in cities as in rural communities. Theseobservations suggest that social stressors in urban settings may affect thedevelopment of schizophrenia in persons at risk. 8. Socioeconomic and Cultural Factors a. Economics The financial cost of the illness in the United States is estimated to exceedthat of all cancers combined because schizophrenia: o Begins early in life and causes significant and long-lasting impairments viii
  9. 9. By Mohamed Abdelghani o Makes heavy demands for hospital care, and requires ongoing clinical care, rehabilitation, and support services. Deinstitutionalization has dramatically reduced the number of beds incustodial facilities. Many patients are transferred to alternative forms ofcustodial care (in contrast to treatment or rehabilitative services), includingnursing home care and poorly supervised shelter arrangements. Patients with a diagnosis of schizophrenia are reported to account for 15 to45 percent of homeless Americans. b. Hospitalization The development of effective antipsychotic drugs and changes in politicaland popular attitudes toward the treatment and the rights of persons who arementally ill have dramatically changed the patterns of hospitalization forschizophrenia patients since the mid-1950s. However, even with antipsychotic medication, the probability ofreadmission within 2 years after discharge from the first hospitalization is about40 to 60%. Patients with schizophrenia occupy about 50% of all mentalhospital beds and account for about 16% of all psychiatric patients who receiveany treatment.Etiologyi. Genetic Factors There is a genetic contribution to some, perhaps all, forms of schizophrenia,and a high proportion of the variance in liability to schizophrenia is due toadditive genetic effects. For example, schizophrenia and schizophrenia-related disorders (e.g.,schizotypal, schizoid, and paranoid personality disorders) occur at an increasedrate among the biological relatives of patients with schizophrenia. The likelihood of schizophrenia is correlated with the closeness of therelationship to an affected relative (e.g., 1st or 2nd degree relative). In the case of monozygotic twins, there is an approximately 50%concordance rate for schizophrenia. This rate is four to five times theconcordance rate in dizygotic twins or the rate of occurrence found in other 1stdegree relatives (i.e., siblings, parents, or offspring). ix
  10. 10. By Mohamed Abdelghani The role of genetic factors is further reflected in the drop-off in theoccurrence of schizophrenia among 2nd and 3rd degree relatives, in whom onewould hypothesize a decreased genetic loading. The finding of a higher rate of schizophrenia among the biological relativesof an adopted-away person who develops schizophrenia, as compared to theadoptive, nonbiological relatives who rear the patient, provides further supportto the genetic contribution in the etiology of schizophrenia. Nevertheless, the monozygotic twin data clearly demonstrate the fact thatindividuals who are genetically vulnerable to schizophrenia do not inevitablydevelop schizophrenia; other factors (e.g., environment) must be involved indetermining a schizophrenia outcome. If a vulnerability-liability model of schizophrenia is correct in its postulationof an environmental influence, then other biological or psychosocialenvironment factors may prevent or cause schizophrenia in the geneticallyvulnerable individual. Prevalence of Schizophrenia in Specific Populations Population Prevalence (%)General population 1Non-twin sibling of a schizophrenia patient 8Child with one parent with schizophrenia 12Dizygotic twin of a schizophrenia patient 12Child of two parents with schizophrenia 40Monozygotic twin of a schizophrenia patient 47 There is robust data indicating that the age of the father has a directcorrelation with the development of schizophrenia. It was found that those bornfrom fathers older than the age of 60 were vulnerable to developing the disorder.Presumably, spermatogenesis in older men is subject to greater epigeneticdamage than in younger men. The modes of genetic transmission in schizophrenia are unknown, butseveral genes are associated with schizophrenia vulnerability. Genetic studies determine nine linkage sites: 1q, 5q, 6q, 13q, 15q, 22q, 6p,8p and 10p. Further analyses of these chromosomal sites identify specific candidategenes: e.g. α-7 nicotinic receptor, DISC 1, GRM 3, COMT, NRG 1, RGS 4, andG 72. x
  11. 11. By Mohamed Abdelghani Recently, mutations of the genes dystrobrevin (DTNBP1) and neureglin 1are associated with negative features of schizophrenia.ii. Neurobiological Factors: 1. Biochemical Factors a) Dopamine Hypothesis It states that schizophrenia results from too much dopaminergic activity. The theory evolved from two observations: i. First, the efficacy and the potency of many antipsychotic drugs (i.e., the dopamine receptor antagonists) are correlated with their ability to act as antagonists of (D2) receptor. ii. Second, drugs that increase dopaminergic activity, notably cocaine and amphetamine, are psychotomimetic. The basic theory does not determine whether the dopaminergic hyperactivityis due to too much release of dopamine, too many dopamine receptors,hypersensitivity of the dopamine receptors to dopamine, or a combination ofthese mechanisms. Which dopamine tracts in the brain are involved is also not specified in thetheory, although the mesocortical and mesolimbic tracts are most oftenimplicated. The dopaminergic neurons in these tracts project from their cellbodies in the midbrain to dopaminoceptive neurons in the limbic system andthe cerebral cortex. Excessive dopamine release in schizophrenics is linked to the severity ofpositive psychotic symptoms. PET studies show an increase in D2 receptors inthe caudate nucleus of drug-free patients with schizophrenia. There are alsoreports of increased dopamine concentration in the amygdala, decreased densityof the dopamine transporter, and increased numbers of D4 receptors in theentorhinal cortex. b) Serotonin Current hypotheses posit serotonin excess as a cause of both positive andnegative symptoms in schizophrenia. The robust serotonin antagonist activity of clozapine and other second-generation antipsychotics, coupled with the effectiveness of clozapine to xi
  12. 12. By Mohamed Abdelghanidecrease positive symptoms in chronic patients contributes to the validity of thisproposition. c) Norepinephrine Anhedonia "the impaired capacity for emotional gratification and thedecreased ability to experience pleasure" is noted to be a prominent feature ofschizophrenia. A selective neuronal degeneration within the norepinephrinereward neural system could account for this aspect of schizophrenia. However,biochemical and pharmacological data bearing on this proposal are inconclusive. d) GABA The inhibitory amino acid neurotransmitter GABA was implicated in thepathophysiology of schizophrenia based on the finding that some patients withschizophrenia have a loss of GABAergic neurons in the hippocampus. GABA has a regulatory effect on dopamine activity, and loss of inhibitoryGABAergic neurons could lead to the hyperactivity of dopaminergic neurons. e) Neuropeptides Neuropeptides, such as substance P and neurotensin, are localized with thecatecholamine and indolamine neurotransmitters and influence the action ofthese neurotransmitters. Alteration in neuropeptide mechanisms could facilitate, inhibit, or otherwisealter the pattern of firing these neuronal systems. f) Glutamate Glutamate was implicated because ingestion of phencyclidine, a glutamateantagonist, produces an acute syndrome similar to schizophrenia. The hypotheses about glutamate include those of hyperactivity, hypoactivity,and glutamate-induced neuro- toxicity. g) Acetylcholine and Nicotine Postmortem studies in schizophrenia have demonstrated decreasedmuscarinic and nicotinic receptors in the caudate-putamen, hippocampus, andselected regions of the prefrontal cortex. These receptors play a role in theregulation of neurotransmitter systems involved in cognition, which is impairedin schizophrenia. xii
  13. 13. By Mohamed Abdelghani 2. Neuropathology In the 19th century, neuropathologists classified schizophrenia as a functionaldisorder. However, by the end of the 20th century, researchers revealed apotential neuropathological basis for schizophrenia, primarily in the limbicsystem and the basal ganglia, including neuropathological or neurochemicalabnormalities in the cerebral cortex, the thalamus, and the brainstem. The loss of brain volume widely reported in schizophrenic brains appearsto result from reduced density of the axons, dendrites, and synapses that mediateassociative functions of the brain. Synaptic density is highest at age 1, then ispared down to adult values in early adolescence. One theory, based on the observation that patients often developschizophrenic symptoms during adolescence, holds that schizophrenia resultsfrom excessive pruning of synapses during this phase of development.a) Cerebral Ventricles CT scans of patients with schizophrenia showed lateral and third ventricularenlargement and some reduction in cortical volume. Reduced volumes of cortical gray matter are demonstrated during theearliest stages of the disease. Some studies have concluded that the lesions observed on CT scan arepresent at the onset of the illness and do not progress. However, other studieshave concluded that the pathological process visualized on CT scan continues toprogress during the illness. Thus, whether an active pathological process iscontinuing to evolve in schizophrenia patients is still uncertain.b) Reduced Symmetry There is a reduced symmetry in several brain areas in schizophrenia,including the temporal, frontal, and occipital lobes. This reduced symmetry isbelieved to originate during fetal life and to be indicative of a disruption in brainlateralization during neurodevelopment.c) Limbic System The limbic system is involved in the pathophysiology of schizophrenia dueto its role in controlling emotions. Studies of postmortem brain samples from schizophrenics show a decreasein the size of the region including the amygdala, the hippocampus, and the xiii
  14. 14. By Mohamed Abdelghaniparahippocampal gyrus. These findings agree with the observations made byMRI studies of patients with schizophrenia. The hippocampus is not only smaller in size in schizophrenia, but is alsofunctionally abnormal as indicated by disturbances in glutamate transmission.Disorganization of the neurons within the hippocampus of schizophreniapatients are also reported.d) Prefrontal Cortex Postmortem brain studies support anatomical abnormalities in the prefrontalcortex in schizophrenia. Functional deficits in the prefrontal brain imagingregion are also demonstrated. It was noted that several symptoms of schizophrenia mimic those found inpersons with prefrontal lobotomies or frontal lobe syndromes.e) Thalamus Some studies show evidence of volume shrinkage or neuronal loss, inparticular subnuclei. The medial dorsal nucleus of the thalamus, which has reciprocalconnections with the prefrontal cortex, contains a reduced number of neurons.The total number of neurons, oligodendrocytes, and astrocytes is reduced by 30to 45% in schizophrenic patients. This finding is not due to the effects of antipsychotic drugs because thevolume of the thalamus is similar in size between schizophrenics treatedchronically with medication and neuroleptic-naive subjects.f) Basal Ganglia and Cerebellum The basal ganglia and cerebellum have interest in schizophrenia for at leasttwo reasons:  First, many patients with schizophrenia show odd movements, even in the absence of medication-induced movement disorders (e.g., tardive dyskinesia) including an awkward gait, facial grimacing, and stereotypies. Because the basal ganglia and cerebellum are involved in the control of movement, disease in these areas is implicated in the pathophysiology of schizophrenia.  Second, the movement disorders involving the basal ganglia (e.g., Huntingtons disease, Parkinsons disease) are the most common associated disorders with psychosis. xiv
  15. 15. By Mohamed Abdelghani Neuropathological studies of the basal ganglia may show cell loss or thereduction of volume of the globus pallidus and the substantia nigra. Studieshave also shown an increase in the number of D2 receptors in the caudate, theputamen, and the nucleus accumbens. However, the question is, whether theincrease is secondary to the patient having received antipsychotic medications. Some investigators began to study the serotonergic system in the basalganglia; which is suggested by the clinical usefulness of antipsychotic drugs thatare serotonin antagonists (e.g., clozapine, risperidone). 3. Neural Circuits Some authers views schizophrenia as a disorder of brain neural circuits. Forexample, as mentioned previously, the basal ganglia and cerebellum arereciprocally connected to the frontal lobes, and the abnormalities in frontal lobefunction may be due to disease in either area rather than in the frontal lobesthemselves. It is also hypothesized that an early developmental lesion of thedopaminergic tracts to the prefrontal cortex results in the disturbance ofprefrontal and limbic system function leading to the positive and negativesymptoms and cognitive impairments observed in patients with schizophrenia. Also the link between the prefrontal cortex and limbic system aredemonstrated by a relationship between hippocampal morphologicalabnormalities and disturbances in prefrontal cortex metabolism or function, orboth. Imaging studies in humans suggest that dysfunction of the anteriorcingulate basal ganglia thalamocortical circuit underlies the production ofpositive psychotic symptoms, whereas dysfunction of the dorsolateralprefrontal circuit underlies the production of negative or deficit symptoms. There is a neural basis for cognitive functions impaired in patients withschizophrenia. The observation of the relationship among impaired workingmemory performance, disrupted prefrontal neuronal integrity, alteredprefrontal, cingulate, and inferior parietal cortex, and altered hippocampalblood flow provides strong support for disruption of the normal workingmemory neural circuit in patients with schizophrenia. The involvement of thiscircuit, at least for auditory hallucinations, has been documented in a number offunctional imaging studies that contrast hallucinating and nonhallucinatingpatients. 4. Brain Metabolism MR spectroscopy of patients with schizophrenia shows: xv
  16. 16. By Mohamed Abdelghani i. lower levels of phosphomonoester and inorganic phosphate ii. higher levels of phosphodiester than a control group.iii. lower concentrations of N-acetyl aspartate, a marker of neurons, in the hippocampus and frontal lobes. 5. Applied Electrophysiology EEG studies of many schizophrenia patients may show: o abnormal records o increased sensitivity to activation procedures (e.g., frequent spike activity after sleep deprivation) o decreased alpha activity o increased theta and delta activity o possibly more epileptiform activity than usual o possibly more left-sided abnormalities than usual. Sound Sensitivity: Schizophrenia patients also cant filter out irrelevantsounds and are extremely sensitive to background noise. This makesconcentration difficult and may be a factor in the production of auditoryhallucinations. This sensitivity may be associated with a genetic defect. a) Complex Partial Epilepsy Schizophrenia-like psychoses occur more frequently than expected inpatients with complex partial seizures, especially seizures involving thetemporal lobes. Associated Factors include: a left-sided seizure focus, medial temporallocation of the lesion, and early onset of seizures. The first-rank symptoms described by Schneider may be similar tosymptoms of patients with complex partial epilepsy and may reflect the presenceof a temporal lobe disorder when seen in patients with schizophrenia. b) Evoked Potentials The P300 is defined as a large, positive evoked-potential wave that occursabout 300 milliseconds after a sensory stimulus is detected. The major source ofthe P300 wave may be located in the limbic system structures of the medialtemporal lobes. In schizophrenics, the P300 is statistically smaller than that in comparisongroups. Abnormalities in the P300 wave are more common in children who,because they have affected parents, are at high risk for schizophrenia. xvi
  17. 17. By Mohamed Abdelghani Other abnormal evoked potentials in schizophrenics are the N100 and thecontingent negative variation. The N100 is a negative wave that occurs about 100 milliseconds after astimulus. The contingent negative variation is a slowly developing, negative-voltageshift following the presentation of a sensory stimulus that is a warning for anupcoming stimulus. The evoked-potential data indicates that although schizophrenics areunusually sensitive to a sensory stimulus (larger early evoked potentials), theycompensate by blunting the processing of information at higher cortical levels(smaller late evoked potentials). 6. Eye Movement Dysfunction The inability to follow a moving visual target accurately is the defining basisfor the disorders of smooth visual pursuit and disinhibition of saccadic eyemovements seen schizophrenics. Eye movement dysfunction may be a trait marker for schizophrenia; it isindependent of drug treatment and clinical state and is also seen in first-degreerelatives of probands with schizophrenia. Various studies reported abnormal eye movements in 50 to 85% ofschizophrenics, compared with about 25% in psychiatric patients withoutschizophrenia and less than 10% in nonpsychiatrically ill control subjects. 7. Psychoneuroimmunology Immunological abnormalities include: 1) decreased T-cell interleukin-2 production 2) reduced number and responsiveness of peripheral lymphocytes 3) abnormal cellular and humoral reactivity to neurons 4) the presence of brain-directed (antibrain) antibodies Most investigations searched for evidence of neurotoxic viral infections inschizophrenia had negative results, although epidemiological data show a highincidence of schizophrenia after prenatal exposure to influenza during severalepidemics of the disease. Other data supporting a viral hypothesis are an increased number of physicalanomalies at birth, an increased rate of pregnancy and birth complications, xvii
  18. 18. By Mohamed Abdelghani seasonality of birth consistent with viral infection, geographical clusters of adult cases, and seasonality of hospitalizations. Nonetheless, the inability to detect genetic evidence of viral infection reduces the significance of all circumstantial data. The possibility of autoimmune brain antibodies has some data to support it. 8. Psychoneuroendocrinology Neuroendocrine abnormalities include: o Dexamethasone-suppression test is abnormal in various subgroups of schizophrenics. However, persistent nonsuppression may be correlated with a poor long-term outcome. o Decreased concentrations of LH&FSH, perhaps correlated with age of onset and length of illness. o A blunted release of prolactin and GH on GnRH or TRH stimulation, and a blunted release of GH on apomorphine stimulation may be correlated with the presence of negative symptoms.iii. Psychosocial and Psychoanalytic Theories If schizophrenia is a disease of the brain, it is likely to parallel diseases of other organs (e.g., myocardial infarctions, diabetes) whose courses are affected by psychosocial stress. Thus, clinicians should consider both psychosocial and biological factors affecting schizophrenia. a) Psychoanalytic Theories 1. Sigmund Freud postulated that schizophrenia resulted from developmental fixations that occurred earlier than those of neuroses. These fixations produce defects in ego development and such defects contributed to the symptoms of schizophrenia. Ego disintegration in schizophrenia represents a return to the time when the ego had just begun, to be established. Because the ego affects the interpretation of reality and the control of inner drives, such as sex and aggression, these ego functions are impaired. Thus, intrapsychic conflict arising from the early fixations and the ego defect fuel the psychotic symptoms. 2. Margaret Mahler postulated that there are distortions in the reciprocal relationship between the infant and the mother. The child is unable to separate from the closeness and complete dependence that characterize the mother- child relationship in the oral phase of development. As a result, the persons identity never becomes secure. xviii
  19. 19. By Mohamed Abdelghani 3. Paul Federn hypothesized that the defect in ego functions permits intense hostility and aggression to distort the mother-infant relationship, which leads to eventual personality disorganization and vulnerability to stress. The onset of symptoms during adolescence occurs when teenagers need astrong ego to function independently, to separate from the parents, to identifytasks, to control increased internal drives, and to cope with intense externalstimulation. 4. Harry Stack Sullivan viewed schizophrenia as a disturbance in interpersonal relatedness. The patients massive anxiety creates a sense of unrelatedness that istransformed into parataxic distortions, which are usually, but not always,persecutory. To Sullivan, schizophrenia is an adaptive method used to avoid panic, terror,and disintegration of the sense of self. The source of pathological anxiety resultsfrom cumulative experiential traumas during development. 5. Symbolic Meaning: Psychoanalytic theory also postulates that the various symptoms of schizophrenia have symbolic meaning for individual patients. For example: o Fantasies of the world coming to an end may indicate a perception that a persons internal world has broken down. o Feelings of inferiority are replaced by delusions of grandeur and omnipotence. o Hallucinations may be substitutes for a patients inability to deal with objective reality and may represent inner wishes or fears. o Delusions, like hallucinations, are regressive, restitutive attempts to create a new reality or to express hidden fears or impulses. N.B.: All psychodynamic approaches are founded on the premise thatpsychotic symptoms have meaning in schizophrenia. E.g., Patients may becomegrandiose after an injury to their self-esteem. Similarly, all theories recognizethat human relatedness may be terrifying for persons with schizophrenia. N.B.: Although research on the efficacy of psychotherapy withschizophrenia shows mixed results, concerned persons who offer compassionand a sanctuary in the confusing world of the schizophrenic must be acornerstone of any overall treatment plan. xix
  20. 20. By Mohamed Abdelghani N.B.: Long-term follow-up studies show that some patients who bury psychotic episodes probably do not benefit from exploratory psychotherapy, but those who are able to integrate the psychotic experience into their lives may benefit from some insight-oriented approaches. There is renewed interest in the use of long-term individual psychotherapy in the treatment of schizophrenia, especially when combined with medication. b) Learning Theories Children who later have schizophrenia learn irrational ways of thinking by imitating parents who have their own significant emotional problems. In learning theory, the poor interpersonal relationships of persons with schizophrenia develop because of poor models for learning during childhood.iv. Family Dynamics In a study of 4-year-old children: Those who had a poor mother-child relationship had a sixfold increase in the risk of developing schizophrenia. Offspring from schizophrenic mothers who were adopted away at birth were more likely to develop the illness if they were reared in adverse circumstances compared to those raised in loving homes by stable adoptive parents. Nevertheless, no evidence indicates that a specific family pattern plays a causative role in the development of schizophrenia. However, it is important not to overlook pathological family behavior that can significantly increase the emotional stress with which a vulnerable patient with schizophrenia must cope. 1) Double Bind: The double-bind concept was formulated by Gregory Bateson and Donald Jackson to describe a hypothetical family in which children receive conflicting parental messages about their behavior, attitudes, and feelings. In Batesons hypothesis, children withdraw into a psychotic state to escape the unsolvable confusion of the double bind. The theory has value only as a descriptive pattern, not as a causal explanation of schizophrenia. An example of a double bind is the parent who tells the child to provide cookies for his or her friends and then chastises the child for giving away too many cookies to playmates. xx
  21. 21. By Mohamed Abdelghani 2) Schisms and Skewed Families: Theodore Lidz described two abnormal patterns of family behavior:  In one family type, with a prominent schism between the parents, one parent is overly close to a child of the opposite gender.  In the other family type, a skewed relationship between a child and one parent involves a power struggle between the parents and the resulting dominance of one parent. These dynamics stress the tenuous adaptive capacity of the schizophrenicperson. 3) Pseudomutual and Pseudohostile Families: "described by Lyman Wynne" Some families suppress emotional expression by consistently usingpseudomutual or pseudohostile verbal communication. In such families, a unique verbal communication develops, and when a childleaves home and must relate to other persons, problems may arise. The childsverbal communication may be incomprehensible to outsiders. 4) Expressed Emotion: Parents or other caregivers may behave with overt criticism and hostilitytoward a person with schizophrenia. Many studies indicated that in families with high levels of expressedemotion, the relapse rate for schizophrenia is high. The assessment of expressed emotion involves analyzing both what is saidand the manner in which it is said.Diagnosis The presence of hallucinations or delusions is not necessary for a diagnosisof schizophrenia. Patients disorder is diagnosed as schizophrenia when the patient exhibitstwo of the symptoms listed as symptoms 1 through 5 in Criterion A (e.g.,disorganized speech). Criterion B requires that impaired functioning be present during the activephase of the illness. xxi
  22. 22. By Mohamed Abdelghani Symptoms must persist for at least 6 months, and a diagnosis ofschizoaffective disorder or mood disorder must be absent. DSM-IV-TR Diagnostic Criteria for Schizophrenia A. Characteristic symptoms: Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated): 1. delusions 2. hallucinations 3. disorganized speech (e.g., frequent derailment or incoherence) 4. grossly disorganized or catatonic behavior 5. negative symptoms, i.e., affective flattening, alogia, or avolition Note: Only one Criterion A symptom is required if delusions are bizarre or hallucinations consist of a voice keeping up a running commentary on the persons behavior or thoughts, or two or more voices conversing with each other. B. Social/occupational dysfunction: For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations, or self-care are markedly below the level achieved prior to the onset (or when the onset is in childhood or adolescence, failure to achieve expected level of interpersonal, academic, or occupational achievement). C. Duration: Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms (or less if successfully treated) that meet Criterion A (i.e., active-phase symptoms) and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or two or more symptoms listed in Criterion A present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences). D. Schizoaffective and mood disorder exclusion: Schizoaffective disorder and mood disorder with psychotic features have been ruled out because either: (1) no major depressive, manic, or mixed episodes have occurred concurrently with the active-phase symptoms; or (2) if mood episodes have occurred during active-phase symptoms, their total duration has been brief relative to the duration of the active and residual periods. xxii
  23. 23. By Mohamed Abdelghani E. Substance/general medical condition exclusion: The disturbance is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition. F. Relationship to a pervasive developmental disorder: If there is a history of autistic disorder or another pervasive developmental disorder, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations are also present for at least a month (or less if successfully treated). Classification of longitudinal course: (applied only after at least 1 year haselapsed since the initial onset of active-phase symptoms): i. Episodic with interepisode residual symptoms: (episodes are defined by the reemergence of prominent psychotic symptoms); also specify if: with prominent negative symptoms ii. Episodic with no interepisode residual symptoms:  Continuous (prominent psychotic symptoms are present throughout the period of observation); also specify if: with prominent negative symptoms.  Single episode in partial remission: also specify if: with prominent negative symptoms  Single episode in full remission  Other or unspecified patternSubtypes According to DSM-IV-TR: (paranoid, disorganized, catatonic,undifferentiated, and residual). 1. Paranoid type: A type of schizophrenia in which the following criteria are met: A. Preoccupation with one or more delusions or frequent auditory hallucinations. B. None of the following is prominent: disorganized speech, disorganized or catatonic behavior, or flat or inappropriate affect. 2. Disorganized type: A type of schizophrenia in which the following criteria are met: xxiii
  24. 24. By Mohamed Abdelghani A. All of the following are prominent: 1. disorganized speech 2. disorganized behavior 3. flat or inappropriate affect B. The criteria are not met for catatonic type. 3. Catatonic type: A type of schizophrenia in which the clinical picture is dominated by at leasttwo of the following: 1. Motoric immobility as evidenced by catalepsy (including waxy flexibility) or stupor 2. Excessive motor activity (that is apparently purposeless and not influenced by external stimuli) 3. Extreme negativism (an apparently motiveless resistance to all instructions or maintenance of a rigid posture against attempts to be moved) or mutism 4. Peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of inappropriate or bizarre postures), stereotyped movements, prominent mannerisms, or prominent grimacing 5. Echolalia or echopraxia 4. Undifferentiated type: A type of schizophrenia in which symptoms that meet Criterion A arepresent, but the criteria are not met for the paranoid, disorganized, or catatonictype. 5. Residual type: A type of schizophrenia in which the following criteria are met: A. Absence of prominent delusions, hallucinations, disorganized speech, and grossly disorganized or catatonic behavior. B. There is continuing evidence of the disturbance, as indicated by the presence of negative symptoms or two or more symptoms listed in Criterion A for schizophrenia, present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences).According to ICD-10: in contrast, uses nine subtypes:  Paranoid schizophrenia  Hebephrenia  Catatonic schizophrenia xxiv
  25. 25. By Mohamed Abdelghani  Undifferentiated schizophrenia  Postschizophrenic depression  Residual schizophrenia  Simple schizophrenia  Other schizophrenia  Schizophrenia, unspecifiedN.B.1: Paranoid Type: Characterized by preoccupation with one or more delusions or frequentauditory hallucinations. Classically, characterized mainly by the presence of delusions of persecutionor grandeur. Patients with paranoid schizophrenia usually have their first episode ofillness at an older age than do patients with catatonic or disorganizedschizophrenia. Patients in whom schizophrenia occurs in the late 20s or 30s have usuallyestablished a social life that may help them through their illness, and the egoresources of paranoid patients tend to be greater than those of patients withcatatonic and disorganized schizophrenia. Patients with the paranoid type of schizophrenia show less regression oftheir mental faculties, emotional responses, and behavior than do patients withother types of schizophrenia. Patients with paranoid schizophrenia are typically tense, suspicious,guarded, reserved, and sometimes hostile or aggressive, but they canoccasionally conduct themselves adequately in social situations. Theirintelligence in areas not invaded by their psychosis tends to remain intact.N.B.2:Disorganized Type The disorganized (formerly called hebephrenic) type of schizophrenia ischaracterized by a marked regression to primitive, disinhibited, and unorganizedbehavior. Also there is absence of symptoms that meet the criteria for the catatonictype. The onset of this subtype is generally early, occurring before age 25. xxv
  26. 26. By Mohamed Abdelghani Disorganized patients are usually active but in an aimless, nonconstructivemanner. Their thought disorder is pronounced, and their contact with reality ispoor. Their personal appearance is disheveled, and their social behavior andtheir emotional responses are inappropriate. They often burst into laughter without any apparent reason. Incongruousgrinning and grimacing are common in these patients, whose behavior is bestdescribed as silly or fatuous.N.B.3:Catatonic Type The classic feature of the catatonic type is a marked disturbance in motorfunction; which may involve stupor, negativism, rigidity, excitement, orposturing. Sometimes, the patient shows rapid alteration between extremes ofexcitement and stupor. Associated features include stereotypies, mannerisms, and waxy flexibility.Mutism is particularly common. During catatonic excitement, patients need careful supervision to preventthem from hurting themselves or others. Medical care may be needed because of malnutrition, exhaustion,hyperpyrexia, or self-inflicted injury.N.B.4:Undifferentiated Type They are the patients who are clearly schizophrenic but cannot be easily fitinto one type or another.N.B.5:Residual Type Characterized by continuing evidence of the schizophrenic disturbance in theabsence of a complete set of active symptoms or of sufficient symptoms to meetthe diagnosis of another type of schizophrenia. Emotional blunting, social withdrawal, eccentric behavior, illogical thinking,and mild loosening of associations commonly appear in the residual type. When delusions or hallucinations occur, they are neither prominent noraccompanied by strong affect. xxvi
  27. 27. By Mohamed AbdelghaniOther Subtypes Other subtyping schemes appear in the literature, especially literature fromcountries other than the United States.  Bouffee Delirante (Acute Delusional Psychosis) The symptom duration is less than 3 months. The diagnosis is similar to theDSM-IV-TR diagnosis of schizophreniform disorder. French clinicians report that about 40 percent of patients with a diagnosis ofbouffee delirante progress to schizophrenia.  Latent Latent schizophrenia was often the diagnosis used for what are now calledborderline, schizoid, and schizotypal personality disorders. These patients may occasionally show peculiar behaviors or thoughtdisorders but without manifest psychotic symptoms. In the past, the syndrome was also termed borderline schizophrenia.  Oneiroid The oneiroid state refers to a dream-like state in which patients may bedeeply perplexed and not fully oriented in time and place. The term oneiroid schizophrenic has been used for patients who are engagedin their hallucinatory experiences to the exclusion of involvement in the realworld. When an oneiroid state is present, clinicians should be particularly careful toexamine patients for medical or neurological causes of the symptoms.  Paraphrenia The term paraphrenia is sometimes used as a synonym for paranoidschizophrenia, or for either a progressively deteriorating course of illness or thepresence of a well-systemized delusional system. The multiple meanings of the term render it ineffectual in communicatinginformation. xxvii
  28. 28. By Mohamed Abdelghani  Pseudoneurotic Schizophrenia Occasionally, patients who initially have such symptoms as anxiety,phobias, obsessions, and compulsions later reveal symptoms of thought disorderand psychosis. These patients are characterized by symptoms of pananxiety, panphobia,panambivalence, and sometimes chaotic sexuality. Unlike persons with anxiety disorders, pseudoneurotic patients have free-floating anxiety that rarely subsides. In clinical descriptions, the patients seldom become overtly and severelypsychotic. This condition is currently diagnosed in DSM-IV-TR as borderlinepersonality disorder.  Simple Deteriorative Disorder (Simple Schizophrenia) Characterized by a gradual, insidious loss of drive and ambition. Patients with the disorder are usually not overtly psychotic and do notexperience persistent hallucinations or delusions. Their primary symptom is withdrawal from social and work-relatedsituations. The syndrome must be differentiated from depression, a phobia, a dementia,or an exacerbation of personality traits. Clinicians should be sure that patients truly meet the diagnostic criteria forschizophrenia before making the diagnosis.DSM-IV-TR Research Criteria for Simple Deteriorative Disorder (SimpleSchizophrenia) A. Progressive development over a period of at least a year of all of the following: 1. marked decline in occupational or academic functioning 2. gradual appearance and deepening of negative symptoms such as affective flattening, alogia, and avolition 3. poor interpersonal rapport, social isolation or withdrawal B. Criterion A for schizophrenia has never been met. C. The symptoms are not better accounted for by schizotypal or schizoid personality disorder, a psychotic disorder, a mood disorder, an anxiety disorder, a dementia, or mental retardation and are not due to the direct physiological effects of a substance or a general medical condition. xxviii
  29. 29. By Mohamed Abdelghani  Postpsychotic Depressive Disorder of Schizophrenia Following an acute schizophrenia episode, some patients become depressed. The symptoms of postpsychotic depressive disorder of schizophrenia canclosely resemble the symptoms of the residual phase of schizophrenia and theadverse effects of antipsychotic medications. The diagnosis should not be made if they are substance induced or part of amood disorder due to a general medical condition. ICD-10 describes a category called postschizophrenia depression arising inthe aftermath of a schizophrenic illness. These depressive states occur in up to 25% of patients with schizophreniaand are associated with an increased risk of suicide.  Early-Onset Schizophrenia A small minority of patients manifest schizophrenia in childhood. Suchchildren may at first present diagnostic problems, particularly withdifferentiation from mental retardation and autistic disorder. Recent studies have established that the diagnosis of childhoodschizophrenia may be based on the same symptoms used for adultschizophrenia. Its onset is usually insidious, its course tends to be chronic, and theprognosis is mostly unfavorable.  Late-Onset Schizophrenia Late-onset schizophrenia has an onset after age 45. This condition tends toappear more frequently in women and also tends to be characterized by apredominance of paranoid symptoms. The prognosis is favorable, and these patients usually do well onantipsychotic medication.  Deficit Schizophrenia In the 1980s, criteria were promulgated for a subtype of schizophreniacharacterized by enduring, idiopathic negative symptoms. This group of patientsis now said to have deficit schizophrenia. xxix
  30. 30. By Mohamed Abdelghani Patients with schizophrenia with positive symptoms are said to havenondeficit schizophrenia. The symptoms of deficit schizophrenia are stronglyinterrelated, although various combinations of the six negative symptoms in thecriteria can be found. Diagnostic Criteria for Deficit Schizophrenia At least two of the following six features must be present and of clinically significant severity:  Restricted affect  Diminished emotional range  Poverty of speech  Curbing of interests  Diminished sense of purpose  Diminished social drive Two or more of these features have been present for the preceding 12 months and were always present during periods of clinical stability (including chronic psychotic states). These symptoms may or may not be detectable during transient episodes of acute psychotic disorganization or decompensation. Two or more of these enduring features are also idiopathic (not secondary to factors other than the disease process). Such factors include:  Anxiety  Drug effect  Suspiciousness  Formal thought disorder  Hallucinations or delusions  Mental retardation  Depression The patient meets DSM-IV-TR criteria for schizophrenia. The onset of the first psychotic episode is more often insidious, and thesepatients show less long-term recovery of function than do nondeficit patients. Deficit patients have a more severe course of illness than nondeficit patients,with a higher prevalence of abnormal involuntary movements beforeadministration of antipsychotic drugs and poorer social function before the onsetof psychotic symptoms. Deficit patients are also less likely to marry than are other patients withschizophrenia. However, despite their poorer level of function and greater social xxx
  31. 31. By Mohamed Abdelghaniisolation, both of which should increase a patients stress and, therefore, the riskof serious depression, deficit patients appear to have a decreased risk of majordepression and probably have a decreased risk of suicide as well. The risk factors of deficit patients differ from those of nondeficit patients;  Deficit schizophrenia is associated with an excess of summer births, whereas nondeficit patients have an excess of winter births.  Deficit schizophrenia may also be associated with a greater familial risk of schizophrenia and of mild, deficit-like features in the nonpsychotic relatives of deficit probands.  Within a family with multiply affected siblings, the deficit-nondeficit categorization tends to be uniform.  The deficit group also has a higher prevalence of men. The psychopathology of deficit patients impacts treatment; o Their lack of motivation, lack of distress, greater cognitive impairment, and asocial nature undermine the efficacy of psychosocial interventions, as well as their adherence to medication regimens. o Their cognitive impairment, which is greater than that of nondeficit subjects, also contributes to this lack of efficacy.Psychological Testing Patients with schizophrenia perform poorly on a wide range ofneuropsychological tests. Vigilance, memory, and concept formation are most affected and consistentwith pathological involvement in the frontotemporal cortex. Objective measures of neuropsychological performance: Halstead-Reitan battery and Luria-Nebraska battery, often give abnormalfindings, such as: o Bilateral frontal and temporal lobe dysfunction, including impairments in attention, retention time, and problem-solving ability. o Motor ability is also impaired, possibly related to brain asymmetry.Intelligence TestsThe schizophrenia patients tend to score lower on intelligence tests comparedwith other groups. Statistically, low intelligence is often present at the onset, andintelligence may continue to deteriorate with the progression of the disorder. xxxi
  32. 32. By Mohamed AbdelghaniProjective and Personality TestsProjective tests: "Rorschach test and the Thematic Apperception Test" mayindicate bizarre ideation.Personality inventories: "e.g. Minnesota Multiphasic Personality Inventory" giveabnormal results in schizophrenia, but the contribution to diagnosis andtreatment planning is minimal.Clinical Features Three key issues must be taken into account: First, no clinical sign or symptom is pathognomonic for schizophrenia; Every sign or symptom seen in schizophrenia occurs in other psychiatric andneurological disorders. This is contrary to the often-heard clinical opinion thatcertain signs and symptoms are diagnostic of schizophrenia. So, a patients history is essential for the diagnosis of schizophrenia;clinicians cannot diagnose schizophrenia simply by results of a mental statusexamination, which may vary. Second, a patients symptoms change with time. For example, a patient mayhave intermittent hallucinations and a varying ability to perform adequately insocial situations, or significant symptoms of a mood disorder may come and goduring the course of schizophrenia. Third, clinicians must take into account the patients educational level,intellectual ability, and cultural and subcultural membership. For example, animpaired ability to understand abstract concepts may reflect either the patientseducation or his or her intelligence. Religious organizations and cults may havecustoms that seem strange to outsiders but are normal to those within thecultural setting.i. Premorbid Signs and Symptoms Premorbid signs and symptoms appear before the prodromal phase of theillness. Patients had schizoid or schizotypal personalities characterized as:o Quiet, passive, and introvertedo As children, they had few friends.o Preschizophrenic adolescents: xxxii
  33. 33. By Mohamed Abdelghani  Have no close friends and no dates and may avoid team sports.  They may enjoy watching movies and television, listening to music, or playing computer games to exclude social activities.  Some adolescent patients may show a sudden onset of obsessive- compulsive behavior as part of the prodromal picture. The validity of the prodromal signs and symptoms is uncertain; onceschizophrenia is diagnosed, the retrospective remembrance of early signs andsymptoms is affected. Nevertheless, although the first hospitalization is often believed to mark thebeginning of the disorder, signs and symptoms have often been present formonths or even years. The signs may have started with complaints about somatic symptoms, suchas headache, back and muscle pain, weakness, and digestive problems. Theinitial diagnosis may be malingering, chronic fatigue syndrome, or somatizationdisorder. Family and friends may eventually notice that the person has changed and isno longer functioning well in occupational, social, and personal activities.During this stage, a patient may begin to develop an interest in abstract ideas,philosophy, and the occult or religious questions. Additional prodromal signs and symptoms can include markedly peculiarbehavior, abnormal affect, unusual speech, bizarre ideas, and strange perceptualexperiences.ii. Mental Status Examination a. General DescriptionAppearance: Range from a completely disheveled, screaming, agitated person to anobsessively groomed, completely silent, and immobile person. Between these two poles, patients may be talkative and may exhibit bizarrepostures.Behavior: May become agitated or violent, apparently in an unprovoked manner, butusually in response to hallucinations. xxxiii
  34. 34. By Mohamed Abdelghani In contrast, in catatonic stupor, often referred to as catatonia, patients seemcompletely lifeless and may exhibit such signs as muteness, negativism, andautomatic obedience. Waxy flexibility, once a common sign in catatonia, hasbecome rare, as has manneristic behavior. A person with a less extreme subtype of catatonia may show marked socialwithdrawal and egocentricity, lack of spontaneous speech or movement, and anabsence of goal-directed behavior. Patients with catatonia may sit immobile and speechless in their chairs,respond to questions with only short answers, and move only when directed tomove. Other obvious behavior may include odd clumsiness or stiffness in bodymovements, signs now seen as possibly indicating a disease process in the basalganglia. Patients with schizophrenia are often poorly groomed, fail to bathe, anddress much too warmly for the prevailing temperatures. Other odd behaviors include tics, stereotypies, mannerisms, and,occasionally, echopraxia, in which patients imitate the posture or the behaviorof the examiner.N.B.: Precox Feeling: Some experienced clinicians report a precox feeling, an intuitive experienceof their inability to establish an emotional rapport with a patient. Although the experience is common, no data indicate that it is a valid orreliable criterion in the diagnosis of schizophrenia. b. Mood, Feelings, and Affect Two common affective symptoms in schizophrenia are:  Reduced emotional responsiveness, sometimes severe enough to warrant the label of anhedonia.  Overly active and inappropriate emotions such as extremes of rage, happiness, and anxiety. A flat or blunted affect can be a symptom of the illness itself, of theparkinsonian adverse effects of antipsychotic medications, or of depression, anddifferentiating these symptoms can be a clinical challenge. xxxiv
  35. 35. By Mohamed Abdelghani Overly emotional patients may describe exultant feelings of omnipotence,religious ecstasy, terror at the disintegration of their souls, or paralyzing anxietyabout the destruction of the universe. Other feeling tones include perplexity, a sense of isolation, overwhelmingambivalence, and depression. c. Perceptual DisturbancesHallucinations Any of the five senses may be affected by hallucinatory experiences inpatients with schizophrenia. However, the most common hallucinations are auditory, with voices that areoften threatening, obscene, accusatory, or insulting. Two or more voices may converse among themselves, or a voice maycomment on the patients life or behavior. Visual hallucinations are common. Tactile, olfactory, and gustatory hallucinations are unusual; their presenceshould prompt the clinician to consider the possibility of an underlying medicalor neurological disorder that is causing the entire syndrome. Cenesthetic Hallucinations: They are unfounded sensations of altered states in bodily organs, e.g. aburning sensation in the brain, a pushing sensation in the blood vessels, and acutting sensation in the bone marrow. Bodily distortions may also occur.Illusions Illusions are distortions of real images or sensations, whereas hallucinationsare not based on real images or sensations. Illusions can occur in schizophrenics during active phases, but they can alsooccur during the prodromal phases and during periods of remission. Whenever illusions or hallucinations occur, clinicians should consider thepossibility of a substance-related cause for the symptoms, even when patientshave already received a diagnosis of schizophrenia. xxxv
  36. 36. By Mohamed Abdelghani d. Thought Disorders of thought are the core symptoms of schizophrenia. Dividing thedisorders of thought into disorders of thought content, form of thought, andthought process is one way to clarify them. i. Thought Content Disorders of thought content reflect the patients ideas, beliefs, andinterpretations of stimuli. The most obvious example of a disorder of thought content is Delusions,which are varied in schizophrenia and may assume persecutory, grandiose,religious, or somatic forms. Patients may believe that an outside entity controls their thoughts orbehavior or, conversely, that they control outside events in an extraordinaryfashion (such as causing the sun to rise and set or by preventing earthquakes). Patients may have an intense preoccupation with esoteric, abstract,symbolic, psychological, or philosophical ideas. Patients may also worry about allegedly life-threatening but bizarre andimplausible somatic conditions, such as the presence of aliens inside thepatients testicles affecting his ability to father children. Loss of ego boundaries: Its the lack of a clear sense of where the patients own body, mind, andinfluence end and where those of other animate and inanimate objects begin,e.g., patients may think that other persons, the television, or the newspapers arereferring to them (ideas of reference). Other symptoms of the loss of ego boundaries include:  The sense that the patient has physically fused with an outside object (e.g., a tree or another person) or  The patient has disintegrated and fused with the entire universe (cosmic identity). With such a state of mind, some patients with schizophrenia doubt theirgender or their sexual orientation. These symptoms should not be confused withtransvestism, transsexuality, or other gender identity problems. xxxvi
  37. 37. By Mohamed Abdelghani ii. Form of Thought Disorders of the form of thought are observed in patients spoken and writtenlanguage. The disorders include looseness of associations, derailment, incoherence,tangentiality, circumstantiality, neologisms, echolalia, verbigeration, word salad,and mutism. Although looseness of associations was once described as pathognomonicfor schizophrenia, the symptom is frequently seen in mania. Distinguishing between looseness of associations and tangentiality can bedifficult for even the most experienced clinicians. iii. Thought Process Disorders in thought process concern the way ideas and languages areformulated. They are inferred from what and how the patient speaks, writes, ordraws and also assessed by observing his or her behavior, especially in carryingout discrete tasks (e.g., in occupational therapy). Disorders of thought process include flight of ideas, thought blocking,impaired attention, poverty of thought content, poor abstraction abilities,perseveration, idiosyncratic associations (e.g., identical predicates, clangassociations), over inclusion, and circumstantiality. Thought control, in which outside forces are controlling what the patientthinks or feels, is common, as is thought broadcasting, in which patients thinkothers can read their minds or that their thoughts are broadcast throughtelevision sets or radios. e. Impulsiveness, Violence, Suicide, and HomicidePatients with schizophrenia may be agitated and have little impulse control ordecreased social sensitivity when ill.For example, when they grab another patients cigarettes, change televisionchannels abruptly, or throw food on the floor.Some apparently impulsive behavior, including suicide and homicide attempts,may be in response to hallucinations commanding the patient to act. xxxvii
  38. 38. By Mohamed Abdelghani 1. Violence Violent behavior (excluding homicide) is common among untreatedschizophrenia patients. Risk factors for violent or impulsive behavior are delusions of a persecutorynature, previous episodes of violence, and neurological deficits. Management includes appropriate antipsychotic medication. Emergency treatment consists of:  Restraints and seclusion.  Acute sedation with lorazepam (Ativan), 1-2 mg I.M., repeated every hour as needed, to prevent the patient from harming others. If a clinician feels fearful in the presence of a schizophrenia patient, it is aninternal clue that the patient may be on the verge of acting out violently and theinterview should be terminated or be conducted with an attendant at the ready. 2. Suicide Suicide is the single leading cause of premature death among people withschizophrenia. Suicide attempts are made by 20 to 50% of the patients, with long-term ratesof suicide estimated to be 10 to 13%. These numbers are 20-fold increase over the suicide rate in the generalpopulation. Often, suicide in schizophrenia occurs "out of the blue" without priorwarnings or expressions of verbal intent. The most important factor is the presence of a major depressive episode: o 80% of schizophrenia patients may have a major depressive episode at some time in their lives. o Some data suggest that those with the best prognosis (few negative symptoms, preservation of capacity to experience affects, better abstract thinking) can paradoxically also be at highest risk for suicide. o The profile of the patient at greatest risk is a young man who once had high expectations, declined from a higher level of functioning, realizes that his dreams are not likely to come true, and has lost faith in the effectiveness of treatment. xxxviii
  39. 39. By Mohamed Abdelghani Other possible contributors to the high rate of suicide include commandhallucinations and drug abuse. A large pharmacological study suggests that clozapine (Clozaril) may haveparticular efficacy in reducing suicidal ideation in schizophrenia patients withprior hospitalizations for suicidality. Adjunctive antidepressant medications were shown to be effective inalleviating co-occurring major depression in schizophrenia. 3. Homicide The available data indicate that patients are no more likely to commithomicide than is a member of the general population. When a patient with schizophrenia does commit homicide, it may be forunpredictable or bizarre reasons based on hallucinations or delusions. Predictors of homicidal activity are a history of previous violence,dangerous behavior while hospitalized, and hallucinations or delusionsinvolving such violence. f. Sensorium and Cognition o Orientation Patients with schizophrenia are usually oriented to person, time, and place. The lack of orientation should prompt clinicians to investigate the possibilityof a medical or neurological brain disorder. Some patients with schizophrenia may give incorrect or bizarre answers toquestions about orientation, e.g., "I am Christ; this is heaven". o Memory Memory, as tested in MSE, is usually intact, but there can be minorcognitive deficiencies. However, it may not be possible to get the patient to attend closely enoughto the memory tests for the ability to be assessed adequately. o Cognitive Impairment In outpatients, cognitive impairment is a better predictor of level of functionthan is the severity of psychotic symptoms. xxxix
  40. 40. By Mohamed Abdelghani Patients with schizophrenia typically exhibit subtle cognitive dysfunction inthe domains of attention, executive function, working memory, and episodicmemory. Although a substantial percentage of patients have normal I.Q., it is possiblethat every person who has schizophrenia has cognitive dysfunction compared towhat he or she would be able to do without the disorder. Although these impairments are not diagnostic tools, they are stronglyrelated to the functional outcome of the illness and, for that reason, have clinicalvalue as prognostic variables, as well as for treatment planning. The cognitive impairment are present when patients have their first episodeand appears largely to remain stable over the course of early illness. There may be a small subgroup of patients who have a true dementia in latelife that is not due to other cognitive disorders, such as Alzheimers disease. Cognitive impairments are also present in attenuated forms in nonpsychoticrelatives of schizophrenia patients. It is likely that effective treatments will become widely available within afew years, and these are likely to lead to an improvement in the quality of lifeand level of functioning of people with schizophrenia. o Judgment and Insight Classically, patients with schizophrenia have poor insight into the nature andthe severity of their disorder. Lack of insight is associated with poor compliance with treatment. When examining schizophrenia patients, clinicians should carefully definevarious aspects of insight, such as awareness of symptoms, trouble getting alongwith people, and the reasons for these problems. Such information can beclinically useful in tailoring a treatment strategy and theoretically useful inpostulating what areas of the brain contribute to the observed lack of insight(e.g., the parietal lobes). o Reliability A patient with schizophrenia is not less reliable than any other psychiatricpatient. However, the nature of the disorder requires the examiner to verifyimportant information through additional sources. xl
  41. 41. By Mohamed Abdelghaniiii. Somatic Comorbidity A. Neurological Findings Localizing (hard signs) and nonlocalizing neurological signs (soft signs) aremore common in patients with schizophrenia than in other psychiatric patients. Nonlocalizing signs include dysdiadochokinesia, astereognosis, primitivereflexes, and diminished dexterity. The presence of neurological signs and symptoms correlates with increasedseverity of illness, affective blunting, and a poor prognosis. Other abnormal neurological signs include tics, stereotypies, grimacing,impaired fine motor skills, abnormal motor tone, and abnormal movements. One study found that only about 25% of patients with schizophrenia areaware of their own abnormal involuntary movements and that the lack ofawareness is correlated with lack of insight about the primary psychiatricdisorder and the duration of illness. B. Eye Examination In addition to the disorder of smooth ocular pursuit (saccadic movement),patients with schizophrenia have an elevated blink rate. The elevated blink rate is due to hyperdopaminergic activity. In primates,blinking can be increased by dopamine agonists and reduced by dopamineantagonists. C. Speech Although the disorders of speech in schizophrenia (e.g., looseness ofassociations) are classically considered to indicate a thought disorder, they mayalso indicate a forme fruste of aphasia, perhaps implicating the dominant parietallobe. The inability of schizophrenia patients to perceive the prosody of speech orto inflect their own speech can be seen as a neurological symptom of a disorderin the nondominant parietal lobe. Other parietal lobe-like symptoms in schizophrenia include the inability tocarry out tasks (i.e., apraxia), right-left disorientation, and lack of concern aboutthe disorder. xli
  42. 42. By Mohamed Abdelghaniiv. Other Comorbidity 1. Obesity Patients with schizophrenia appear to be more obese, with higher bodymass indexes (BMIs) than in the general population. This is due, at least in part, to the effect of many antipsychoticmedications, as well as poor nutritional balance and decreased motor activity. This weight gain leads to an increased risk of cardiovascular morbidityand mortality, an increased risk of diabetes, and other obesity-related conditionssuch as hyperlipidemia and obstructive sleep apnea. 2. Diabetes Mellitus Schizophrenia is associated with an increased risk of type II diabetesmellitus. This is due, in part, to the association with obesity noted previously, butthere is also evidence that some antipsychotic medications cause diabetesthrough a direct mechanism. 3. Cardiovascular Disease Many antipsychotics have direct effects on cardiac electrophysiology. In addition, obesity, increased rates of smoking, diabetes, hyperlipidemia,and a sedentary lifestyle all increase the risk of cardiovascular morbidity andmortality. 4. HIV Patients with schizophrenia appear to have a risk of HIV infection that is 1.5to 2 times that of the general population. This association is due to increased risk behaviors, such as unprotected sex,multiple partners, and increased drug use. 5. Chronic Obstructive Pulmonary Disease Rates of COPD are reportedly increased in schizophrenia compared to thegeneral population due to increased prevalence of smoking. xlii
  43. 43. By Mohamed Abdelghani 6. Rheumatoid Arthritis Patients with schizophrenia have approximately one-third the risk ofrheumatoid arthritis that is found in the general population. This inverseassociation has been replicated several times, the significance of which isunknown.Differential Diagnosis i. Secondary Psychotic Disorders A wide range of nonpsychiatric medical conditions and a variety ofsubstances can induce symptoms of psychosis and catatonia ( see the table). The diagnosis for such psychosis or catatonia is psychotic disorder due to ageneral medical condition, catatonic disorder due to a general medicalcondition, or substance-induced psychotic disorder. When evaluating a patient with psychotic symptoms, clinicians should followthe general guidelines for assessing nonpsychiatric conditions:  First, clinicians should aggressively pursue an undiagnosed nonpsychiatric medical condition when a patient exhibits any unusual symptoms or any variation in the level of consciousness.  Second, clinicians should obtain a complete family history, including a history of medical, neurological, and psychiatric disorders.  Third, clinicians should consider the possibility of a nonpsychiatric medical condition, even in patients with previous diagnoses of schizophrenia. A patient with schizophrenia is just as likely to have a brain tumor that produces psychotic symptoms as is a patient without schizophrenia. ii. Other Psychotic Disorders The psychotic symptoms of schizophrenia can be identical with those ofschizophreniform disorder, brief psychotic disorder, schizoaffective disorder,and delusional disorders. Schizophreniform disorder differs from schizophrenia in that thesymptoms have a duration of at least 1 month but less than 6 months. Brief psychotic disorder is the appropriate diagnosis when the symptomshave lasted at least 1 day but less than 1 month and when the patient has notreturned to the premorbid state of functioning within that time. There may alsobe a precipitating traumatic event. xliii
  44. 44. By Mohamed Abdelghani Schizoaffective disorder is the appropriate diagnosis when a manic ordepressive syndrome develops concurrently with the major symptoms ofschizophrenia,. Delusional disorder is the appropriate diagnosis when nonbizarre delusionspresent for at least 1 month without other symptoms of schizophrenia or a mooddisorder. iii. Mood Disorders A patient with a major depressive episode may present with delusions andhallucinations, whether the patient has unipolar or bipolar mood disorder. Delusions are typically mood congruent and involve themes such as guilt,self-depreciation, deserved punishment, and incurable illnesses. In mood disorders, psychotic symptoms resolve completely with theresolution of depression. A severe depressive episode may also result in loss of functioning, decline inself-care, and social isolation, but these are secondary to the depressivesymptoms and should not be confused with the negative symptoms ofschizophrenia. A full-blown manic episode often presents with delusions and sometimeshallucinations. Delusions in mania are most often mood congruent and typically involvegrandiose themes. The flight of ideas seen in mania may be confused with the thought disorderof schizophrenia. Special attention during MSE of a patient with a flight of ideasis required to note whether the associative links between topics are conserved,although the conversation is difficult for the observer to follow because of thepatients accelerated rate of thinking. iv. Personality Disorders Various personality disorders may have some features of schizophrenia. Schizotypal, schizoid, and borderline personality disorders are thepersonality disorders with the most similar symptoms. Severe obsessive-compulsive personality disorder may mask an underlyingschizophrenic process. xliv
  45. 45. By Mohamed Abdelghani Personality disorders, unlike schizophrenia, have mild symptoms and ahistory of occurring throughout a patients life; they also lack an identifiabledate of onset. v. Malingering and Factitious Disorders For a patient who imitates the symptoms of schizophrenia but does notactually have the disorder, either malingering or factitious disorder may be anappropriate diagnosis. Malingering is the appropriate diagnosis when the patients are completely incontrol of their symptom production; such patients usually have obviousfinancial or legal reason to want to be considered mentally ill. Factitious Disorders is the appropriate diagnosis when the patients are lessin control of their falsification of psychotic symptoms. Some patients with schizophrenia, however, may falsely complain of anexacerbation of psychotic symptoms to obtain increased assistance benefits or togain admission to a hospital. Differential Diagnosis of Schizophrenia-Like Symptoms i. Medical and Neurological o Substance induced: amphetamine, hallucinogens, belladonna alkaloids, alcohol hallucinosis, barbiturate withdrawal, cocaine, phencyclidine. o Epilepsy: especially temporal lobe epilepsy o Neoplasm, cerebrovascular disease, or trauma"especially frontal or limbic". o Other conditions:  Acute intermittent porphyria  AIDS  B12 deficiency  Carbon monoxide poisoning  Cerebral lipoidosis  Creutzfeldt-Jakob disease  Fabrys disease  Fahrs disease  Hallervorden-Spatz disease  Heavy metal poisoning  Herpes encephalitis  Homocystinuria  Huntingtons disease  Metachromatic leukodystrophy  Neurosyphilis xlv
  46. 46. By Mohamed Abdelghani  Normal pressure hydrocephalus  Pellagra  Systemic lupus erythematosus  Wernicke-Korsakoff syndrome  Wilsons disease ii. Psychiatric  Atypical psychosis  Autistic disorder  Brief psychotic disorder  Delusional disorder  Factitious disorder with predominantly psychological signs and symptoms  Malingering  Mood disorders  Normal adolescence  Obsessive-compulsive disorder  Personality disorders"schizotypal, schizoid, borderline, paranoid"  Schizoaffective disorder  Schizophrenia  Schizophreniform disorderCourse and PrognosisCourse A premorbid pattern of symptoms may be the first evidence of illness,although the importance of the symptoms is usually recognized onlyretrospectively. Characteristically, the symptoms begin in adolescence and are followed bythe development of prodromal symptoms in days to a few months. Social or environmental changes, such as going away to college, using asubstance, or a relatives death, may precipitate the disturbing symptoms, andthe prodromal syndrome may last a year or more before the onset of overtpsychotic symptoms. The classic course of schizophrenia is one of exacerbations and remissions:  After the first psychotic episode, a patient gradually recovers and may then function relatively normally for a long time. xlvi
  47. 47. By Mohamed Abdelghani  However, patients usually relapse, and the pattern of illness during the first 5 years after the diagnosis generally indicates the patients course.  Further deterioration in the patients baseline functioning follows each relapse. This failure to return to baseline functioning after each relapse is the major distinction between schizophrenia and the mood disorders. Sometimes, a clinically observable postpsychotic depression follows apsychotic episode, and the schizophrenia patients vulnerability to stress isusually lifelong. Positive symptoms tend to become less severe with time, but the sociallydebilitating negative or deficit symptoms may increase in severity. Although about one-third of all schizophrenics have some marginal orintegrated social existence, most have lives characterized by aimlessness,inactivity, frequent hospitalizations, homelessness and poverty.Prognosis Only about 10 to 20% of patients have a good outcome within 5-10 yearsafter the first psychiatric hospitalization for schizophrenia. More than 50% of patients have a poor outcome, with repeatedhospitalizations, exacerbations of symptoms, episodes of major mood disorders,and suicide attempts. However, schizophrenia does not always run a deteriorating course, andseveral factors have been associated with a good prognosis (see before). Reported remission rates range from 10 to 60%, and a reasonable estimate isthat 20 to 30% of all schizophrenia patients are able to lead somewhat normallives. About 20 to 30% of patients continue to experience moderate symptoms, and40 to 60% of patients remain significantly impaired for their entire lives. Patients with schizophrenia do much poorer than patients with mooddisorders, although 20 to 25% of mood disorder patients are also severelydisturbed at long-term follow-up. Features Weighting Toward Good to Poor Prognosis in Schizophrenia Good Prognosis Poor Prognosis Late onset Young onset Obvious precipitating factors No precipitating factors xlvii