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2012

Schizophrenia
A clinical syndrome of variable but profoundly disruptive, psychopathology that involves cognition, emotion, perception and other aspects of behavior Manifestation varies with patients and its effects are always severe and long lasting Begins before age 25 and persists throughout life Diagnosis is based entirely on psychiatric history and mental status examination There is no laboratory test for schizophrenia

diagnosed exclusively on the basis of second-rank symptoms and an otherwise typical clinical appearance Karl Jaspers o Major role in developing existential psychoanalysis Adolf Meyer o Founder of psychobiology o Saw schizophrenia as a maladaptive reaction to life stresses

History
Emil Kraeplin Dementia Precox - patients having a long term deteriorating course of clinical symptoms of hallucinations and delusions. He emphasized the difference of dementia precox from manic-depressive psychosis and paranoia o Manic depressive psychosis alternate episodes of illness and normal functioning o Paranoia persistent persecutory delusions which lacked a deteriorating course of dementia precox and the intermittent symptoms of manic-depressive psychosis

Epidemiology
Gender and Age M=F Onset earlier in men (10-25 years) than in women (25-35 years) Females exhibit a bimodal age distribution Outcome for female patients is better Late onset schizophrenia (>45 years old)

Reproductive Factors Use of psychopharmacological drugs, the open door policies in hospitals, the deinstitutionalization in state hospitals, and the emphasis of rehab and community-based care for patients have led to an increase in the marriage and fertility rates among persons with schizophrenia First degree relatives/children of schizophrenic patients have a 10x risk for developing the disease

Eugine Pleuler Coined the term schizophrenia which replaced dementia precox Chose the term schizophrenia to express the presence of schisms between thought, emotion and behavior in patients with the disorder Emphasized that unlike dementia precox, schizophrenia need not have a deteriorating course The Four As o Associations o Affect o Autism o Ambivalence Secondary symptoms o Hallucinations o Delusions

Medical Illness Persons with schizophrenia have a higher mortality rate from accidents and natural causes than the general population 80% of all schizophrenia patients have concurrent medical illness with 50% of such conditions left undiagnosed

Infection and Birth Season Other Theorists Ernst Kretschmer o Schizophrenia occurred more often among patients with asthenic, athletic, or dysplastic body types rather than those with pyknic body types Kurt Schneider o Emphasized that in patients who showed no first-rank symptoms, the disorder could be Prenatal exposure to influenza which occurs during winter on the 2nd trimester of pregnancy Malnutrition and times of famine increase the incidence

Substance Abuse

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Patients with schizophrenia have an increased prevalence of abuse of common street drugs and alcohol The use of drugs such as cannabis increases the risk of schizophrenia and increases the psychotic symptoms associated with the disease 90% of schizophrenic patients are dependent on nicotine because it serves to alleviate the symptoms of schizophrenia. It appears to improve cognitive impairments and parkinsonism therefore serving as a form of self medication for patients

Biochemical Factors Dopamine Hypothesis Dopamine - Schizophrenia results from too much dopaminergic activity Evolved from two observations; the first being that the efficacy and the potency of many antipsychotic drugs are correlated with their ability to act as antagonists of the dopamine type 2 receptor. Second, drugs that increase dopaminergic activity such as cocaine and amphetamine are psycotomimetic Serotonin current hypothesis points that serotonin excess is a cause of both positive and negative symptoms of schizophrenia Norepinephrine Anhedonia, the impaired ability for emotional gratification and experience pleasure has long been noted to be a prominent feature of schizophrenia. A selective neuronal degeneration with NE reward neural system could be the cause but data are inconclusive GABA some patients with schizophrenia have a loss of GABAergic neurons in the hippocampus leading to the disinhibition in dopamine activity which leads to dopamine hyperactivity Neuropeptides localized with catecholamine and indolamine neurotransmitters and could influence its action Glutamate - glutamate antagonists produce acute symptoms similar to schizophrenia Acetylcholine and Nicotine studies show that there is a decrease muscarinic and nicotinic receptors in the caudate-putamen, hippocampus and selected regions of the prefrontal cortex in schizophrenics

Population Density Prevalence of schizophrenia has been correlated with local population density in cities with more than 1 million people Related to the fact that there is a higher chance of genetic and reproductive transfer of the disease

Socioeconomic and Cultural Factors Antispsychotic drugs and the shift from a costly primary hospital based care to an acute hospital and a community based care has increased the number of ill patients in the community. Patients with a diagnosis of schizophrenia are reported to account for 15-45% of homeless Americans

Etiology
Genetic Factors Schizophrenia and schizophrenia-related disorders occur at an increased rate among the biological relatives of patients with schizophrenia Individuals who are genetically vulnerable to schizophrenia do not inevitably develop schizophrenia; other factors (e.g., environment) must be involved in determining a schizophrenia outcome Spermatogenesis in older man is subject to greater epigenetic damage than in younger men

Neuropathology Cerebral Ventricles o Lateral and third ventricular enlargement o Reduction in cortical volume Reduced Symmetry o Frontal, temporal and occipital lobes Limbic System o Controls emotions o Decrease in size of the amygdale, hippocampus and parahippocampal gyrus o Hippocampus is also functionally abnormal as indicated by the disturbances in glutamate transmission Prefrontal Cortex o Symptoms of schizophrenia mimic those found in persons with prefrontal lobotomies

Prevalence of Schizophrenia is Specific Populations Population General population Non twin sibling of a schizophrenia patient Child with one parent with schizophrenia Dizygotic twin of a schizophrenia patient Child of two parents with schizophrenia Monozygotic twin of a schizophrenia patient Prevalence 1% 8% 12% 12% 40% 47%

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Thalamus o Volume shrinkage or neuronal loss in particular subnuclei Basal Ganglia and Cerebellum o Basal ganglia and cerebellum control movements and patients with schizophrenia have odd movements, also, movement disorders involving the basal ganglia are the ones most commonly associated with psychosis

Independent of drug treatment and clinical states and seen in first degree relatives of probands with schizophrenia

Psychoneuroimmunology Decreased T-cell IL-2 production Reduced number and responsiveness of peripheral lymphocytes Abnormal cellular and humoral reactivity to neurons Presence of brain-directed or antibrain antibodies

Neural Circuits Dysfunction of the anterior cingulated basal ganglia thalamocortical circuit positive psychotic symptoms Dysfunction of the dorsolateral prefrontal circuit primary, enduring, negative or deficit symptoms

Psychoneuroendocrinology Decreased concentrations of LH and FSH Blunted release of prolactin and GH on GRH or TRH Blunted release of GH on apomorphine stimulation

Brain Metabolism Patients with schizophrenia had lower levels of phosphomonoester and inorganic phosphate and higher levels of phosphodiester N-acetyl aspartate, a marker of neurons, were lower in the hippocampus and frontal lobes of patients with schizophrenia

Family Dynamics Double Bind family in which children receive conflicting parental messages about their behavior, attitudes and feelings. Children withdraw into a psychotic state to escape the unsolvable confusion of the double bind Schisms and Skewed Families a prominent schism between parents is when one parent is overly close to a child of the opposite gender while a skewed relationship between a child and one parent involves a power struggle between the parents and the resulting dominance of one parent Pseudomutual and Pseudohostile Families some families suppress emotional expression by pseudomutal/hostile verbal communication. The child adapts such communication and has difficulty relating to other persons Expressed Emotion parents or caregivers who behave with overt criticism, hostility and over involvement towards a person with schizophrenia worsens the disease causing a higher relapse rate

Applied Electrophysiology Patients have abnormal records, increased sensitivity to activation procedures, decreased alpha activity, increased theta and delta activity Inability to filter out irrelevant sounds and extremely sensitive to background noise Complex Partial Epilepsy Schizophrenia-like psychoses have been reported to occur more frequently than expected in patients with complex partial seizures, especially seizures involving the temporal lobes Evoked Potentials p300 potential has been the most studied as is defined as a large, positive evokedpotential wave that occurs about 300 milliseconds after a sensory stimulus is detected. P300 is located in the limbic system structures of the medial temporal lobes o P300 wave smaller in schizophrenia o N100 wave and contingent negative variation (warning for upcoming stimulus) is also abnormal

Diagnosis
Diagnostic Criteria for Schizophrenia DSM-IV-TR 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,

Eye Movement Dysfunction The inability to follow a moving visual target accurately is the defining basis for the disorders of smooth visual pursuit and disinhibition of saccadic eye movements seen in patients with schizophrenia Trait marker for schizophrenia

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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 person's 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). 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., activephase 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). 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 activephase symptoms, their total duration has been brief relative to the duration of the active and residual periods. 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. 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).

Single episode in partial remission: also specify if: with prominent negative symptoms Single episode in full remission Other unspecified pattern

Subtypes
Diagnostic Criteria for Schizophrenia Subtypes DSM-IV-TR

Paranoid type A type of schizophrenia in which the following criteria are met: A. B. Preoccupation with one or more delusions or frequent auditory hallucinations. None of the following is prominent: disorganized speech, disorganized or catatonic behavior, or flat or inappropriate affect.

C.

Disorganized type A type of schizophrenia in which the following criteria are met: A. All of the following are prominent: 1. disorganized speech 2. disorganized behavior 3. flat or inappropriate affect The criteria are not met for catatonic type.

D.

B.

E.

Catatonic type A type of schizophrenia in which the clinical picture is dominated by at least two of the following: 1. 2. 3. motor immobility as evidenced by catalepsy (including waxy flexibility) or stupor excessive motor activity (that is apparently purposeless and not influenced by external stimuli) extreme negativism (an apparently motiveless resistance to all instructions or maintenance of a rigid posture against attempts to be moved) or mutism peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of inappropriate or bizarre postures), stereotyped movements, prominent mannerisms, or prominent grimacing echolalia or echopraxia

F.

4.

Classification of longitudinal course (can be applied only after at least 1 year has elapsed since the initial onset of active phase symptoms): Episodic with interepisode residual symptoms (episodes are defined by the reemergence of prominent psychotic symptoms); also specify if: with prominent negative symptoms Episodic with no interepisode residual symptoms Continuous (prominent psychotic symptoms are present throughout the observation period); also specify if: with prominent negative symptoms

5.

Undifferentiated type A type of schizophrenia in which symptoms that meet Criterion A are present, but the criteria are not met for the paranoid, disorganized, or catatonic type. Residual type A type of schizophrenia in which the following criteria are met:

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A.

B.

Absence of prominent delusions, hallucinations, disorganized speech, and grossly disorganized or catatonic behavior. 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).

---------------------------------------------------------------------------------------Latent Past diagnosis for what we now call borderline, schizoid and schizotypal personality disorders

Oneiroid Paranoid Type Preoccupation with one or more delusions or frequent auditory hallucinations Late onset Less regression of their mental faculties, emotional responses and behavior than the other types Typically tense, suspicious, guarded and reserved Can occasionally conduct themselves adequately in social situations Intelligence remains intact Dream-like state wherein patients are not fully oriented to time and place Patients who are engaged in their hallucinatory experiences to the exclusion of involvement of the real world

Paraphrenia Synonym for paranoid schizophrenia The multiple meanings of the word made it ineffectual in communicating information

Pseudoneurotic Schizophrenia Patients express symptoms of pananxiety, panphobia, panambivalence and sometimes chaotic sexuality Free floating anxiety that rarely subsides Currently diagnosed in DSM-IV-TR as borderline personality disorder

Disorganized Type Marked regression to primitive, disinhibited, and unorganized behavior not related to the catatonic type Early onset Active but in aimless non constructive manner Thought disorder is pronounced, contact with reality is poor Personal appearance is disheveled, and their social behavior and emotional responses are inappropriate Bursts into laughter, grimacing and grinning inappropriately

Simple Deteriorative Disorder | Simple Schizophrenia Gradual, insidious loss of drive or ambition Primary symptom is withdrawal from social and work related situations Research Criteria for Simple Deteriorative Disorder DSM-IV-TR 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 social withdrawal Criterion A for schizophrenia has never been met. 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.

Catantonic Type Marked disturbance in motor function; hyperreflexia, stupor, etc Mutism is common Associated symptoms include waxy flexibility, mannerisms and stereotypies

Undifferentiated Type Patients who are clearly schizophrenic and can easily fit into any other category due to the vast symptoms exhibited B. C.

Residual Type Continuing evidence of schizophrenic disturbance in the absence of complete set of active symptoms to meet the diagnosis of another type of schizophrenia

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Postpsychotic Depressive Disorder of Schizophrenia Onset of depression after an acute schizophrenic episode Diagnosis should not be made if substance induced, part of a mood disorder or due to a general medical condition

o Cannot be diagnosed solely on MSE Clinicians must understand patients educational level

Premorbid Signs and Symptoms Premorbid signs and symptoms exist before the disease process evidences itself and that the prodromal signs and symptoms are parts of the evolving disorder Patients had schizoid or schizotypal personalities characterized as quiet, passive, and introverted; as children, they had few friends. Preschizophrenic adolescents may have no close friends and no dates and may avoid team sports Signs may have started with complaints about somatic symptoms, such as headache, back and muscle pain, weakness, and digestive problems. The initial diagnosis may be malingering, chronic fatigue syndrome, or somatization disorder Family and friends may eventually notice that the person has changed and is no longer functioning well in occupational, social, and personal activities

Early Onset Schizophrenia Manifest in childhood Insidious, chronic and poor prognosis

Late Onset Schizophrenia Onset >45 years old Appear more frequently in women with a predominance of paranoid symptoms

Deficit Schizophrenia Enduring, idiopathic negative symptoms More severe outcome than non deficit or positive schizophrenia Decreased risk of major depression and suicide Deficit patients 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. Their cognitive impairment, which is greater than that of nondeficit subjects, also contributes to this lack of efficacy

Mental Status Examination

General Description Patients can present as a completely disheveled, screaming, agitated person to an obsessively groomed, completely silent immobile person Precox feeling intuitive feeling that clinicians feel that they are not able to establish an emotional rapport with a patient Two most common affective symptoms o Reduced emotional responsiveness o Overly active and inappropriate emotions

Psychological Testing Schizophrenics perform poorly on a wide range of neuropsychological tests Vigilance, memory and concept formation are most commonly affected

Perceptual Disturbances Hallucinations o Not based on any real images or sensations o Can affect any of the 5 senses o Most common is auditory followed by visual o Tactile, olfactory and gustatory are unusual and possibly associated with an underlying medical or neurological disorder o Cenesthetic Hallucinations Unfounded sensations of altered states in bodily organs Illusions o Distortions of real images or sensations Thought o Thought Content

Intelligence Testing Poor results suggesting that low intelligence is present at onset and continues to deteriorate

Projective and Personality Tests Abnormal results Minimal contribution to diagnosis

Clinical Features
No signs or symptoms are pathognomonic of schizophrenia o Symptoms change over time o History is essential in diagnosis

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Reflect the patients ideas, beliefs and interpretation of stimuli Examples include delusions and loss of ego boundaries Form of Thought Observed in a patients spoken or written language Thought Process The way ideas and languages are formulated

inability of schizophrenia patients to perceive the prosody of speech or to inflect their own speech can be seen as a neurological symptom of a disorder in the nondominant parietal lobe Obesity DM CVD HIV COPD RA

Others o o o o o o

Impulsiveness, Violence, Suicide and Homicide o Violence o Suicide Leading cause of premature death in schizophrenia Major depression is a strong factor o Homicide Schizophrenics are not likely to commit homicide

Course
Premorbid pattern is the first evidence of illness Classic course of schizophrenia is one of exacerbations and remissions Deterioration of patients functioning occurs after every relapse causing a failure of the patient to return to baseline functioning = characteristic of schizophrenia from mood disorders 10-20% good outcome 50% poor outcome with repeated hospitalizations, exacerbations of symptoms, episodes of major mood disorders, and suicide attempts

Prognosis

Sensorium and Cognition Orientation o Patients are usually oriented to person, time and place Memory o Usually intact but there can be minor cognitive deficiencies Cognitive Impairment o Patients with schizophrenia typically exhibit subtle cognitive dysfunction in the domains of attention, executive function, working memory, and episodic memory o Seems to be present when patients have their first episode and appears to remain Judgement and Insight o Poor insight to their disorder o Associated with poor compliance of treatment Reliability o Poor reliability

Treatment
Pharmacotherapy There are two types of drugs, the first generation antipsychotics or dopamine receptor antagonists and the second generation antipsychotics or serotonin dopamine agonists R o Acute Psychosis Benzodiazepines fast acting; marked sedation Fluphenazine | Haloperidol fast acting; calming without an excess of sedation; causes EPS Ziprasidone | Olanzapine less EPS o Non compliance Fluphenazine | Haloperidol Long acting o Poor responders Clozapine Psychotherapy Social skills training Family-oriented therapy Group therapy Cognitive-behavioral therapy Individual psychotherapy Personal therapy Dialectical-behavior therapy Vocational therapy Art therapy

Somatic Comorbidity Neurological Findings o Localizing and non localizing signs are more common Eye Exam o Saccadic movement / smooth ocular pursuit o Elevated blink rate due to hyperdopaminergic activity Speech

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