SCHIZOPHRENIA A severe & prolonged mental disturbance manifested as a wide range of disturbed behavior Considered as a group of disorders rather

er than a single disease entity, the cause of which is uncertain but with similar clinical pictures which include disturbances in thought, feelings & mood (without sensory disturbances) &with such characteristic symptom as hallucinations delusions, bizarre behavior & deterioration in the general level of functioning. History of the concept of schizophrenia Emil Kraeplin: a German psychiatrist who was the first to classify all previously described psychoses, in 1896. He introduced the term Dementia Praecox for a group of disorder which featured psychoses with severe disturbances in functioning that began in adolescence & progressively worsened. Bleuler: a Swiss Psychiatrist who introduced the term schizophrenia (meaning splitting of the mind). He believed that 4 processes were primary to the illness, which is ambivalence & disturbances in affect & association. Meyer: a Swiss psychiatry who emphasized importance of life; Stress as a modifier of normal development in the genesis of all mental health. Harry Stack Sullivan: an American who contributed an original explanation how an interpersonal relationship are influenced by & causally related to both the development & the treatment of schizophrenia. Onset of Schizophrenia This usually begin s 2nd or 3rd decade of 1st onset after age 45 is often related to identifiable organic factor & is not schizophrenia. Patients may experience the following feeling as they lose their grip on reality: 1) Perplexity: a sense of strangeness about the experience as well as confusion about where the symptoms are coming from. 2) Isolation: the schizophrenic person experiences an overwhelming sense of being different & separated from other people. 3) Anxiety & Terror: a general sense of discomfort & anxiety often pervades the experience Symptoms & Sign The following disorders may also be observed in other forms of psychiatric disorders. It is the number of psychological processes involved & the degree of impairment that characterize schizophrenia. A. Disturbances in language & communication

1) Formal though disorder 2) Derailment or looseness of association: the individual cannot maintain a consistent train of thought & communication is severely impaired 3) Circumstantiality: irrelevant Detours in speech 4) Tangentially; continuing depression in speech so that the conversation fails to reach the anticipated goal. 5) Poverty of speech: little information is communicated because many words are vague, abstract, concrete, repetitive or stereotyped. 6) Neologisms: New words formed by condensing & combining several known words in a manner unique to the individual 7) Word salad: mixture of words lacking meaning & logical coherence B. Disturbances in Content of thought 1) Delusion: a false belief that may fixed or temporary a. Thought broadcasting: the notion that ones thought are being broadcast into external world so that other can hear them. b. Delusion of influence: an individual or machine is dominating controlling ones life c. Thought insertion: thought are inserted into ones mind by another individual or superior force d. Ideas of reference: events that are in reality not related to the patient (like TV show or newspaper articles ) are perceived by the patient as containing a message only for him e. Paranoid delusion: persecutory themes that one is being watched followed or plotted against f. Grandiosity: Belief that one has a special power, influence or wealth g. Somatic Delusion: belief that something is rooting inside ones body C. Disturbances in Perception Hallucinations: false perception in the absence of external reality in schizophrenia, they are usually auditory, where voices seem to speak directly to the patient or make comments (frequently negative ones) about the patients behavior. D. Disturbance in affect Affect is the outward manifestation or expression of emotions as opposed to mood which can be inferred or from the patients own statements. In schizophrenia, affect may be inappropriate (inconsistent with the topic or context of communication). Affect may also be labile, showing rapid shifts form tears to joy for no obvious reason or flat, with virtually no signs of emotional expression.

F. Disturbances in Volition In schizophrenia, disturbances in self-initiated, goal-directed; activity is invariable and may grossly impair work performance or functioning in other roles. The disruption takes the form if inadequate interest, drive, or ability to complete a course of action successfully. G. Disturbances in relationship to the external world The individual tends to withdraw from involvement with other people and to direct attention inward toward egocentric and illogical ideas and fantasies. The word autistic (from Greek word autos, self) has been used to describe the overwhelming self-centered concerns of the patient with a Schizophrenic disorder. H. Disturbances in motor behavior This may range from catatonic stupor in which there is total reduction of spontaneous movements and activity, or bizarre motions which are wildly aggressive continuing until exhaustion, treatment or death intervenes Types of Schizophrenia A. Disorganized type (hebephrenic) - Features include incoherence, lack of systematized delusions and blunted inappropriate or silly affect. The clinical picture is usually associated with a history of poor functioning and poor adaptation even before the illness and early insidious onset and a chronic course without significant remissions; social impairment is usually extreme. B. Catatonic type - Features include excitement or stupor and mutism, negativism, rigidity and posturing. The features of catatonic symptoms alone without other features of schizophrenic development, suggest a psychotic mood disorder or an organic mental disorder. C. Paranoid type -Features include delusions or hallucinations which may not be restricted to persecutory themes and specifically include somatic themes as well as absence of the more regressive symptoms. This subtype identifies a patient as having a better prognosis and less family connectedness than the other subtypes. Onset occurs later in life than in other types and symptoms are more stable. Functioning also remains at a more or less constant level without episodes of marked deterioration followed by recovery. Patients in this subgroup may be quite intelligent and well-informed. D. Undifferentiated type - Features include grossly disorganized behavior, hallucinations, incoherence or prominent delusions E. Residual type - Features include current lack of schizophrenic episode in the past. These

Patients often function as long term out-patients but are usually incapable of maintaining employment Type I & Type II Symptoms a) Type I symptoms: these are the positive symptoms of hallucinations or delusions, bizarre, agitated behavior & disorganized speech. These symptoms are more frequently seen in the earlier years of psychoses & are usually suppressed by neuroleptic drugs b) Type II symptoms: these are negative or deficit symptom of emotional bluntingsocial withdrawal, cognitive deficits & poverty of speech & motor activity. These symptoms imply a poor prognosis even in acute episode & they become more common in chronic illness. Type II symptoms are usually associated with a family history of schizophrenia, deficits in premorbid development & less favorable response to conventional neuroleptic drugs. Differential diagnosis a) Organic Mental Disorder Psychoses where disorientation & amnesia are usually present may be due to amphetamine, LSD, PCP, alcohol where symptoms usually clears up dramatically after only a few days of close supervision: may also be due to metabolic or cardiovascular disease b) Mood Disorders Intermittent course, with symptom-free intervals in between episodes of the illnesses (unlike in schizophrenia where the course is usually marked by persistent impairment); family history of mood disorder is also fairly common c) Schizophreniform (Atypical) Psychoses May resemble schizophrenia at any given point but the psychoses are short-lived & have a different course. d) Personality Disorders Patients may have transient psychotic symptoms similar to those of schizophrenia but in contrast to schizophrenia , these are very brief (hours) & there are periods of much better functioning e) Severe Neuroses Such as obsessive-compulsive disorder or phobic disorder f) Mental Retardation

The low-level of functioning & odd-behavior with impoverished effect may suggest longstanding chronic schizophrenia g) Members of Sub Cultural or Religious Groups These persons may have beliefs or experiences that are difficult to distinguish from pathological delusions or hallucinations. h) Normal Adolescence Projective psychological test like the Rorschach (inkblots) & TAT (Thematic Apperception Test) may assist in the diagnosis. Although no thought pattern is pathognomonic , the probability of correct diagnosis becomes much more certain when these systems are used. Natural History Onset: usually 2nd or 3rd decades; may sudden or with prodromal symptoms; trigger factor or event is common. Characteristic Presentation: gradual withdrawal from people, acute psychotic period, postpsychotic depression, recovery, remission; Each recurrence leads to increasing impairment; most patients are not dangerous to others. Prognosis Measurements of: 1) Residual Thought Disorder 2) Social Function 3) Work Function Consider the total picture of the individual 2. Precipitating stress is identifiable 3. Social function of the patient is adequate before the illness 4. Successful performance of work situation outside family environment Prognosis is poor if: 1. Onset is insidious 2. No identifiable precipitating stress 3. No adequate social function Epidemiology

Non between 15-24 y/o illness onset & women between 25-34 y/o first treatment Average prodrome: for women Better outcome for women 35-44 y/o; peak of treatment 15-54 y/o; 90% of schizophrenic in treatment Less than 40% of hospitalized psychiatric patient are schizo.

Etiology & Pathogenesis No single causative factor Studies of: genetics, development of the individual before the illness becomes apparent; biopsychosocial states a. Genetics Genetic relationship correlated with incidence of schizophrenia Relationship General population Sibling schizophrenic 1 parent schizophrenia Dizygotic twin schizophrenic (B) parents schizophrenic Monozygotic twin schizophrenic Incidence 1% 8% 12% 14% 39% 47%

Risk factors: 1. Identifiable perinatal & development stressors 2. Consanguinity-the closer the relationship, the greater will be the risk of developing the illness 3. Premorbid personality disorders of schizoid, avoidant or schizotypical disorder 4. Specific abnormalities in brain anatomy, biochem, physiology b. Development 1. Development of the individual: according to this theory, the normal child goes through a stage of separation from the mother between 1 & 3 years of age & begins to function independently. This process is thought to be essential for the formation of stable sense of self as separate from the parents & all the others. One theory is that the psychological abnormalities noted after the onset of schizophrenia in adolescent result from the young childs failure to develop a mature ego capable interpreting reality & coping with inner drives & the effects of the resulting deficits & further development. 2. Development within family: patient as reflection of disturbed communication among family members Communicable Deviance

3. Development within Society & the larger environment: a. Population density: urban settings (more than 1 million) B . Socioeconomic class : lower SEC because of social handicap which lead to social stresses C . Date of birth : in the winter months, because of the prevalence of viral infection among pregnant women. D . Other factors : cultural dislocation, industrialization Specific abnormalities in patient A. Anatomic: enlarged lateral and 3rd ventricles: smaller frontal and temporal lobes B. Biochemical : schizophrenia may be related to an increased number of receptors Drugs which may cause a transient psychosis by increasing dopamine level or activity in neuronal synapses : a. Levodopa b. Disulfiram c. Amphetamine d. Phencyclidine e. LSD C . Physiological : abnormalities in saccadic eye movements information processing Treatment : Historical Method 1. Coma; earliest chemical treatment, include by insulin or barbiturates 2. Electroconvulsive therapy (ECT); current used is limited to occasional patient who fail to respond anti psychotic edication 3. Psychosurgery: transaction of tracts between the frontal lobe and midbrain Contemporary treatment 1. Psychosocial treatment; therapeutic alliance between the doctor and the patients family support the basic personality structure of the patient 2. Drug treatment : Phenothiazines; remission in weeks in 90 % of patients a. Choice of Neuroleptics :

 Should be effective in 2-4 weeks Low potency drugs : greater sedative and hypotensive properties; malignant hyperthermia; obesity; anti-cholinergic High potency : extrapyramidal symptoms (dystonia); neuroleptic malignant syndrome b. Fluphenazine , Haloperidol , Clozapine c. Dosage of neuroleptic Moderate doses (600-1200mg); acute psychotic symptoms Tardive dyskinea; low dose approach to prevent relapse; 5 mg Fluphenazine I.M every 2 weeks; 5 mg Haloperidol aral every day c . Duaration of drug treatment Agitation is calmed within 1-2 days Psychosis resolves only after 2-6 weeks of moderate regimen Reduction of dosage about 3-6 months after discharge (gradual) d. Adjunctive drugs To treat resistant symptoms Stabilize mood ; lithium or carbamazepines Treat depression ; non anti-cholinergic antidepressants e . Combined treatment : to enhance a patients quality of life Causes A combination of genetic and environmental factors play a role in the development of schizophrenia. People with a family history of schizophrenia who suffer a transient or selflimiting psychosis have a 2040% chance of being diagnosed one year later. Genetic Estimates of heritability vary because of the difficulty in separating the effects of genetics and the environment. The greatest risk for developing schizophrenia is having a first-degree relative with the disease (risk is 6.5%); more than 40% of monozygotic twins of those with schizophrenia are also affected It is likely that many genes are involved, each of small effect. Many possible candidates have been proposed, including specific copy number variations, NOTCH4 and histone protein loci.] A number of genome-wide associations such as zinc finger protein 804A

have also been linked There appears to be significant overlap in the genetics of schizophrenia and bipolar disorder. Assuming a hereditary basis, one question from evolutionary psychology is why genes that increase the likelihood of psychosis evolved, assuming the condition would have been maladaptive from an evolutionary point of view. One theory implicates genes involved in the evolution of language and human nature, but so far all theories have been disproved or remain unsubstantiated. Environment Environmental factors associated with the development of schizophrenia include the living environment, drug use and prenatal stressors. Parenting style seems to have no effect, although people with supportive parents do better than those with critical parents. Living in an urban environment during childhood or as an adult has consistently been found to increase the risk of schizophrenia by a factor of two even after taking into account drug use, ethnic group, and size of social group. Other factors that play an important role include social isolation and immigration related to social adversity, racial discrimination, family dysfunction, unemployment, and poor housing conditions. Childhood experiences of abuse or trauma are risk factors for a diagnosis of schizophrenia later in life. Substance abuse A number of drugs have been associated with the development of schizophrenia, including cannabis, cocaine, and amphetamines. About half of those with schizophrenia use drugs and/or alcohol excessively. The role of cannabis could be causal, but other drugs may be used only as coping mechanisms to deal with depression, anxiety, boredom, and loneliness. Cannabis is associated with a dose-dependent increase in the risk of developing a psychotic disorder. Frequent use has been found to double the risk of psychosis and schizophrenia; however the causality of this link has been questioned, and it remains controversial. Amphetamine, cocaine, and to a lesser extent alcohol, can result in psychosis that presents very similarly to schizophrenia.[3][40] Although not generally believed to be a cause of schizophrenia, schizophrenics as a group use nicotine at much greater rates than the general population. Prenatal Factors such as hypoxia and infection, or stress and malnutrition in the mother during fetal development, may result in a slight increase in the risk of schizophrenia later in life.] People diagnosed with schizophrenia are more likely to have been born in winter or spring (at least in the northern hemisphere), which may be a result of increased rates of viral exposures in utero. This difference is about 5 to 8%. Mechanisms A number of attempts have been made to explain the link between altered brain function and schizophrenia.[2] One of the most common is the dopamine hypothesis, which attributes psychosis to the mind's faulty interpretation of the misfiring of dopaminergic neurons.

Psychological Many psychological mechanisms have been implicated in the development and maintenance of schizophrenia. Cognitive biases have been identified in those with the diagnosis or those at risk, especially when under stress or in confusing situations.[Some cognitive features may reflect global neurocognitive deficits such as memory loss, while others may be related to particular issues and experiences. Despite a demonstrated appearance of "blunted affect", recent findings indicate that many individuals diagnosed with schizophrenia are emotionally responsive, particularly to stressful or negative stimuli, and that such sensitivity may cause vulnerability to symptoms or to the disorder. Some evidence suggests that the content of delusional beliefs and psychotic experiences can reflect emotional causes of the disorder, and that how a person interprets such experiences can influence symptomatology. The use of "safety behaviors" to avoid imagined threats may contribute to the chronicity of delusions.] Further evidence for the role of psychological mechanisms comes from the effects of psychotherapies on symptoms of schizophrenia. Neurologica

Functional magnetic resonance imaging (fMRI), and other brain imaging technologies, allow for the study of differences in brain activity in people diagnosed with schizophrenia. The image shows two levels of the brain, with areas that were more active in healthy controls than in schizophrenia patients shown in red, during an fMRI study of working memory. Those with a diagnosis of schizophrenia have changes in both brain structure and chemistry. Studies using neuropsychological tests and brain imaging technologies such as fMRI and PET to examine functional differences in brain activity have shown that differences seem to most commonly occur in the frontal lobes, hippocampus and temporal lobes. Reductions in brain volume, smaller than those found in Alzheimer's disease, have been reported in areas of the frontal cortex and temporal lobes. It is uncertain whether these volumetric changes are progressive or preexist prior to the onset of the disease. These differences have been linked to the neurocognitive deficits often associated with schizophrenia. Because neural circuits are altered, it has alternatively been suggested that schizophrenia should be thought of as a collection of neurodevelopmental disorders. Particular attention has been paid to the function of dopamine in the mesolimbic pathway of the brain. This focus largely resulted from the accidental finding that phenothiazine drugs, which block dopamine function, could reduce psychotic symptoms. It is also supported by the fact that amphetamines, which trigger the release of dopamine, may exacerbate the psychotic symptoms in schizophrenia. The influential dopamine hypothesis of schizophrenia proposed that excessive activation of D2 receptors was the cause of (the positive symptoms of) schizophrenia. Although postulated for about 20 years based on the D2 blockade effect common to all antipsychotics, it was not until the mid-1990s that PET and SPET imaging studies provided supporting evidence. The dopamine hypothesis is now thought to be simplistic, partly because newer antipsychotic medication (atypical antipsychotic medication) can be just as effective as older medication

(typical antipsychotic medication), but also affects serotonin function and may have slightly less of a dopamine blocking effect. Interest has also focused on the neurotransmitter glutamate and the reduced function of the NMDA glutamate receptor in schizophrenia, largely because of the abnormally low levels of glutamate receptors found in the postmortem brains of those diagnosed with schizophrenia, and the discovery that glutamate-blocking drugs such as phencyclidine and ketamine can mimic the symptoms and cognitive problems associated with the condition. Reduced glutamate function is linked to poor performance on tests requiring frontal lobe and hippocampal function, and glutamate can affect dopamine function, both of which have been implicated in schizophrenia, have suggested an important mediating (and possibly causal) role of glutamate pathways in the condition. But positive symptoms fail to respond to glutamatergic medication.