Schizophrenia and Other Psychotic Disorders

5 Subtypes of schizophrenia:

    • 1) Paranoid (best outcome)

      • a) Presence of delusions (often persecutory)

      • b) Frequent auditory hallucinations

      • c) Onset of illness (late 20s or 30s) later than for other subtypes

      • d) More likely to marry and have children

    • 2) Disorganized (formally called hebephrenic)

      • a) Display disorganized, nonproductive behaviors and demonstrate disorganized speech patterns

      • b) Exhibit flat or inappropriate affect; grimacing is common

      • c) Can act silly or childlike and burst out laughing for no reason

      • d) Delusions and hallucinations are less organized and fragmentary

      • e) Earlier onset

    • 3) Catatonic (less commonly seen now than in previous years)

      • a) According to DSM-IV-TR, must have at least two of the following:

        • i) Motoric immobility (catalepsy, stupor)

        • ii) Excessive motor activity

        • iii) Extreme negativism

        • iv) Stereotypies, mannerisms, grimacing

        • v) Echolalia, echopraxia

    • 4) Undifferentiated: these patients do not satisfy criteria for any other schizophrenia subtype

    • 5) Residual: according to DSM-IV-TR, these patients no longer have any major psychotic symptoms but still exhibit evidence of the illness, with negative symptoms or at least 2 other odd or eccentric behaviors or perceptual experiences.

Symptoms of disorganization:

    • 1) Disorganized speech or thought

    • 2) Blocking of thought, clanging, distractibility, derailment, neologisms, poverty of speech and content of speech, preservation of thought, tangential speech

    • 3) Disorganized or bizarre behavior, catatonic stupor or excitement, stereotypy (repeated purposeless movements), odd mannerisms, echopraxia

    • 4) Negativism, incongruous affect, inappropriate smiling

    • 5) Deterioration of social functioning, inappropriate social behaviors, unkempt in appearance, messy or has much clutter in surroundings

Typical course involves psychotic episodes with periods of remissions; however, the Pt's baseline functioning deteriorates over time. Clinically, patients often exhibit both negative and positive sx at the same time.

Other symptoms and associations:

    • 1) Poor insight into illness

    • 2) Abnormalities of eye movements (increased frequency of blinking and abnormal saccades during test of smooth pursuits)

    • 3) Decreased stage IV sleep

    • 4) Loss of normal gracefulness of body movements

    • 5) Up to 25% may have shown schizoid traits before schizophrenia developed

    • 6) Tend to be less interested in sexual activity

    • 7) Up to 10% of schizophrenics commit suicide within first 10 years of their illness

    • 8) Up to 20% of schizophrenics drink excessive amounts of water, which may lead to chronic hyponatremia and possible water intoxication.

    • 9) Alcohol and drug abuse is common, and schizophrenics smoke cigarettes three times more than the general population.

Dx: Symptoms must be present for at least 6 months. Medical conditions and substance use explaining the sx must be ruled out to make the psychiatric dx.

UDS, SDS. EEG.

Schizophrenia: Associated Neurologic Manifestations

    • Ventricular enlargement

    • Frontal lobe abnormality

    • Cerebellar vermis atrophy

    • Decreased volume: basal ganglia, limbic areas, hippocampus, thalamus, temporal regions, parahippocampal gyrus

    • Hypofrontalility: frontal lobe dysfunction

    • Increased D2 receptor density in striatum & nucleus accumbens

    • Abnormal saccadic eye movements

    • Primitive reflexes

Tx: Always hospitalize, if there is a risk of suicide. Give benzodiazepines for agitation and start atypical antipsychotics.

There is strong evidence to suggest without continuous treatment, virtually all schizophrenic patients relapse within 12-24 months. Injectable depot medications such a haloperidol decanoate and fluphenazine decanoate are effective in decreasing the rate of relapse in patients who are not compliant with oral medication. Pt. must take oral medication after receiving depot shots.

Antipsychotics (also called neuroleptics or major tranquilizers) are used, including dopamine-receptor antagonists (chlorpromazine, haloperidol) and serotonin-dopamine antagonists (clozapine, risperidone, olanzapine, and quetiapine). Atypical psychotics are the most effective treatment for negative symptoms. All medications need a trial period of at least 4-6 weeks. Hospitalization may be needed to stabilize severe disease or for patient's safety. Psychosocial therapy should be integrated into a comprehensive treatment plan.

Continuing antipsychotic medication for at least 6 months after an acute episode reduces relapse rates.

Side effects of dopamine receptor antagonists are numerous, including orthostatic hypotension, peripheral anticholinergic effects (dry mouth, blurry vision, constipation, urinary retention, mydriasis), and increased prolactin secretion (causing breast enlargement, galactorrhea, and impotence in men and amenorrhea and anorgasmia in women). Parkinson symptoms (cogwheel rigidity, pill-rolling tremor, and shuffling gait) may begin in 3 months, and tardive dyskinesia (often irreversible stereotypic movements, such as chewing) may develop after at least 6 months of use. Clozapine is usually used as a second-line treatment because of its side effects (seizures and agranulocytosis). Nonclozapine serotonin-dopamine antagonists have fewer side effects and are becoming the first-line treatment.

Cocaine and amphetamines that stimulate dopaminergic activity induces psychosis.

Schizophrenia is a devastating psychotic disorder with a poor prognosis.

Onset from late teens to the early 20s in men. Women usually get it later around the 30s. It has a chronic course. Average age of onset: 25 years.

1:100 people can get it in their lifetime.

A prototype psychotic illness characterized by chronic course, deterioration in social and occupational functions, and positive (delusion, hallucination) and negative (flat affect, alogia, avolition) symptoms

Etiology is unknown, although dopaminergic hyperactivity is implicated. The rate of schizophrenia in the general population is ~1%. However, a genetic predisposition seems to exists as well. When one member of a monozygotic twin pair is dx with schizophrenia, the other twin, who is genetically identical, has nearly 50% chance of also developing the disease and first-degree relatives of schizophrenic Pts have 10 times the rate of disease as the general population.

Schizophrenia: Neurotransmitters Implicated in Pathogenesis

    • Dopamine: excessive dopaminergic activity in mesolimbic areas

    • Serotonin: hyperactivity

    • Norepinephrine: hyperactivity

    • γ-Aminobutyric acid (GABA): loss of GABAergic neurons in hippocampus (decreased GABA, increased dopamine)

Risk genes

Disrupted in schizophrenia (DISC1), a gene disrupted by a balanced chromosomal translocation, distrobrevin-binding protein 1 (DTNBP1); and neuroregulin 1 (NRG1), which encodes a protein involved in neuronal migration and is expression of NMDA glutmate rcp. Other potential candidates include DAOA, RGS4, and AKT1 but evidence supporting them is weaker.

Genes by themselves are not causative, other factors, a "second-hit" must contribute. It is difficult to identify these. Maternal famine during gestation is correlated with increased incidence of schizophrenia. Other factors include urban birth, migration, increasing paternal age, and intrauterine exposure to viral infection, stressors.

Siblings of schizophrenics: 10% develop schizophrenia

Children of parent with schizophrenia: 6% chance

Children of both parents with schizophrenia: 46% chance

Twins: nearly 50% chance for monozygotic and 17% chance for dizygotic twins

Chromosomes implicated: 3p, 5q, 6p, 6q, 8p, 10p, 13q, 15q, 18p, 22q.

Trinucleotide repeat (CAG/CTG) on chromosomes 17 & 18

Schizophrenia affects all socioeconomic and ethnic groups. The disproportionate number of poor and homeless people with schizophrenia is probably due to "downward drift," as these patients function poorly in society. Schizophrenic patients have an overall high mortality rate, and 50% attempt suicide. 10% of these attempts are successful.

Prognosis is best when the disease has early onset in a patient with good premorbid functioning, especially when an obvious event precipitates the onset of symptoms. Men have worse prognosis than women. Pts with a family history of mood d/o and those who have primarily affective or positive symptoms tend to do better. Married patients with good support systems also have a better prognosis.

History of perinatal trauma, family history of schizophrenia, personal history of aggressive behavior, presence of negative symptoms, and neurologic signs and symptoms are considered poor prognostic features.

Patients with schizophrenia generally have a history of abnormal premorbid functioning. The prodrome includes poor social skill, social withdrawal, and unusual thinking. Inquiring about the premorbid history may help to distinguish schizophrenia from a psychotic illness secondary to mania or drug ingestion.

Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSMIV-TR) diagnostic criteria

    • a. The presence of at least two of five characteristic positive or negative symptoms for at least 1 month: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, or negative symptoms—only need one of five if the delusions are bizarre or a voice or voices are keeping running commentary on the person’s behavior or two or more voices are conversing

    • b. Deterioration in social, occupational, and interpersonal relationships

    • c. Continuous signs of the disturbance for at least 6 months (can include prodromal or residual symptoms like amotivation)

    • d. Schizoaffective disorder and mood disorder with psychotic features have been ruled out

    • e. Not due to effects of substances or general medical condition

Positive symptoms: Associated with dopamine receptors. Comprise of hallucinations and delusions.

    • Hallucinations: Perceptual experiences that have no external stimulus (e.g., hearing voices but no one is speaking). Auditory (e.g., voices commenting, arguing,repeating patient’s thoughts), visual, tactile, gustatory, or olfactory—auditory hallucinations are the most common.

    • Delusions: disturbance of thought. Firmly held false beliefs that can be bizarre or nonbizarre.

Negative symptoms: Associated with dopamine and muscarinic receptors.

Lack of motivation, flat affect (decreased expression of emotion, lack of gestures), alogia (lack of words poverty of speech and thought content), apathy, anhedonia, inattentiveness.

Psychotic d/o are a group of psychiatric conditions in which the chief symptom is psychosis. Psychosis is defined as gross impairment in reality testing. Specific sx of psychosis include delusions, hallucinations, ideas of reference, and disorder of thought.

Psychotic d/o are different from mood d/o with psychotic features. Some Pts with severe depression have delusions. Some Pts with a manic episode may have hallucinations. These two group of patients do not have a primary psychotic d/o; rather, their psychosis is secondary to a mood d/o.

Disability due to psychotic d/o is due to extreme degree of social and occupational dysfunction associated with these d/o.

Schizophreniform Disorder

Sx of schizophrenia have lasted > 1 mo, but <6 mo. If pt has active sx for < 6 mo, schizophreniform d/o is applied as a provisional dx b/c the criteria for schizophrenia may be met in the future. Pt's typically do not have social withdrawal. However, most Pts go on to develop full blown schizophrenia, and some others appear to develop a mood d/o.

Pts have delusions, hallucinations, disorganized speech, or negative symptoms, but the duration of the illness last 1 - 6 mo.

Patient are at greater risk of depression and suicide after the episode of psychosis resolves. Hospitalize if there is risk of suicide.

Antipsychotic med or ECT are used, and hosp. may be needed for effective monitoring and treatment.

Schizoaffective d/o

When there in an uninterrupted period of illness during which, at some time, there is a Major depressive episode, a Manic episode, or a Mixed Episode. Pt has a mood d/o and separate psychotic sx, the term schizoaffective d/o applies. Pt must experience delusions or hallucinations for at least 2 wks w/o concurrent mood sx to establish the presence of separate psychotic features. Mood d/o need to be present for a substantial portion of the illness. The disturbance is not due to substance abuse or general medical condition.

Age of onset similar to schizophrenia.

Two types:

    • Depressive: If the disturbance only includes Major Depressive episode only.

    • Bipolar: If the disturbance includes manic or a mixed episode

Mania or depression may be present, and antimanic or antidepressant meds are the first line of Tx. Antipsychotics are used only when needed for acute management. Hosp. and psychosocial approaches are appropriate as well. ECT may be needed for an acute depressive episode.

Suicide risk: 10%

Schizophrenia is differentiated from schizoaffective /o by the absence of a prominent mood d/o in the course of the illness.

Delusional d/o

Delusional d/o is a d/o of though content. It involves the presence of one or more non-bizarre delusions in a patient w/o markedly impaired functioning. Non-bizarre delusions have a shred of plausibility (things that could happen in real life such as being followed, poisoned, shot, deceived by friends or lover, loved at a distance), whereas bizarre delusions are outside accepted cultural possibilities. Delusions are unshakable. Delusions must be present for at least 1 month. The patient's social adjustment appears normal.

Tactile and olfactory hallucinations may be present in delusional d/o, if they are related to the delusional theme.

Delusions is defined as a firmly held false beliefs, not shared by other people in the same social and cultural group, and firmly held against evidence that disproves the belief. False beliefs that change in the face of strong evidence are called overvalued ideas. It is rare d/o. Onset in middle to late life; it affects women more often than men. It has a chronic and unremitting course.

Psychosocial stressors appear to play a role, for example, following migration. In migration psychosis, the recently immigrated person develops persecutory delusions. Many patients with delusional d/o have a paranoid character premorbidly.

Delusional d/o subtypes:

    • Erotomanic: A person becomes falsely convinced that another person usually of higher status, is in love with him or her.

    • Grandiose: A person becomes falsely convinced that he or she has special abilities or is in other ways much more important than reality indicates. Delusions of inflated worth, power, knowledge, identity, or special relationship to a deity or a famous person.

    • Jealous: A person becomes falsely convinced that his or her lover is unfaithful.

    • Persecutory: A person becomes falsely convinced that other are out to do harm him or her and that he or she is being conspired against in general.

    • Somatic: A person becomes falsely convinced that he or she has a bodily function disorder, for example organ dysfunction, body odor, or parasite infection.

    • Mixed: Diagnosed when no single delusional theme predominates.

    • Unspecified: Diagnosed when a single delusional theme cannot be determined or when the predominant delusional theme does not match subtype criteria.

    • Capgras’ Belief that a person closely related to him or her has been replaced by a double.

    • Fregoli Identifies a familiar person in various other people he or she encounters; even if no physical resemblance

    • Koro Belief that penis is getting smaller and will disappear.

    • van Gogh’s Self-mutilation driven by delusions.

    • Thought insertion: Belief that thoughts can be implanted into the brain

    • Thought withdrawal: Belief that thoughts can be withdrawn from the brain

    • Thought control: Belief that someone can control one’s thoughts.

    • Thought broadcasting: Belief that one’s thoughts can be heard by others

Si & Sx: delusions may be grandiose, jealous, erotomanic (when the patient believes that a certain individual, who may be entirely unconnected with the patient, is in love with him or her), or persecutory and have malevolent intentions to harm the individual. Ideas of reference, in which random events are interpreted as having personal significance, are common. Auditory or visual hallucinations are not common. Tactile or olfactory hallucinations, on the other hand, may be prominent and may be related to the delusion. Otherwise, psychosocial functioning and behavior are not severely impaired.

Dx: Sx last at least 1 mo. If delusions are bizarre, the dx of schizophrenia or schizophreniform d/o applies.

Tx: Antipsychotic medications with hospitalizations and psychotherapy. Do not refute or support the delusion. Maintain a therapeutic alliance with the patient. Half of patients recover completely.

Brief Psychotic d/o

Formerly called brief reactive psychosis, these pts have an abrupt onset of psychotic features, followed by complete recovery and they are back to baseline mental status within a period of 1 month. Sx are usually abrupt, dramatic, and thematically directed towards the precipitating circumstances. Delusion, hallucinations, loose associations, and disorganized behaviors are common. Severe stress may trigger the d/o. Associated with borderline personality d/o and schizotypal personality d/o.

Postpartum psychosis is a rare event (1-2:1000 postpartum women). Within the first two to four weeks of delivery, restlessness, disorganized behavior, derealization, hallucinations, and delusions develop rapidly. Delusional beliefs and hallucinations often center on the infant. Although infanticide is uncommon, risk of suicide is high.

Si & Sx: Sx of delusions, hallucination, and disorganized speech or behavior are present. Functional impairment may be extreme. However, the individual eventually returns to premorbid functioning.

Dx: Sx are present for more than 1 day and less than 1 month. Dx is specified as "with marked stressor," "without marked stressor," or "with postpartum onset." Pts with the postpartum subtype typically develop sx within 1-2 weeks after delivery that resolve within 2-3 months.

Tx: Hospitalization, low-dose antipsychotics, and psychotherapy.

Shared Psychotic d/o (Folie a Deux)

Shared psychotic d/o refers to a delusional d/o and occurs when a patient becomes involved in the delusions of a psychotic person. The inducer, or primary case, is typically the dominant person in a close relationship. The inducer or primary case often has schizophrenia, and the delusions may be bizarre. The primary case, gradually imposes his or her delusional system on the more passive and, at least initially, healthier individual. If the relationship between the two is interrupted, the Pt's delusional belief will diminish. Significant support is needed for this separation. Antipsychotics may be used, and family therapy is critical.

Psychotic d/o due to a General Medical Condition

Prominent delusions or hallucinations are directly caused by another medical d/o. Common conditions include neurologic disease (neoplasms, epilepsy, CVA, and dementias), endocrine or metabolic diseases, electrolyte imbalance, and renal disease. This diagnosis is supported by an appropriate temporal relation between the medical condition and the psychotic d/o, or by atypical features such as olfactory hallucinations.

Work-up for medical and neurologic causes, most commonly for the following:

    • Temporal lobe epilepsy

    • Structural brain changes (trauma, neoplasm, cerebrovascular accident, normal-pressure hydrocephalus)

    • Thyroid disorders

    • Multiple sclerosis

    • Dementias

    • Deficiencies (vitamin B12, pellagra)

    • Central nervous system (CNS) infections (human immunodeficiency virus [HIV], neurosyphilis, Creutzfeldt-Jakob disease, encephalitis)

    • Parkinson’s disease, Huntington’s disease, Wilson’s disease

    • Systemic lupus erythematosus

Endocrine psychoses: Apparently healthy individuals become psychotic

    • Hyperthyroidsim

    • Hypothyroidism

    • Cushing syndrome

    • Adrenal insufficiency

    • Steroid induced (corticosteroids).

Corticosteroid and Adrenocorticotropic Hormone Psychosis:

    • Psychoses usually develops over a period of a few days after the patient has received the hormone for a week or more.

    • Variable features.

    • Depression and insomnia are early and most frequent features, but some patients may develops elation, agitated, excited, and talkative, as though under pressure to speak. Others may be mute; or have anxiety or panic.

    • Thinking is illogical, tangential, or incoherent.

    • Hallucinations

    • Delirium is not prominent - no clouding of sensorium and disorientation

    • Discontinuation of the steroid or hormone as soon as symptoms appear, the psychosis subsides gradually over several days to week, with complete recovery.

Substance-Induced Psychotic Disorder 1. Overview of DSM-IV-TR criteria

    • Presence of prominent hallucinations or delusions

    • Evidence points to substance or medication as a cause of symptoms

    • Not better accounted for by other psychotic disorder or as part of a delirium

    • Clinical findings and issues

  • Work-up for substance-induced psychosis:

    • 1) Cocaine, amphetamines, ephedrine, other stimulants

    • 2) Alcohol, benzodiazepines, barbiturates

    • 3) Hallucinogens (lysergic acid diethylamide [LSD], phencyclidine [PCP], marijuana, mushrooms)

    • 4) Anticholinergic agents (jimson weed, trihexyphenidyl)

    • 5) Medications (glucocorticoids, belladonna alkaloids)