Schizophrenia

History of Concept of Schizophrenia

1400 B.C. - written records of a syndrome resembling schizophrenia in Sanskrit writings; Treated with plant extracts (R. serpentina; active ingredient was reserpine)

500 B.C. - Greeks termed this syndrome "dementia"

200 A.D.-1200’s - Western cultures considered this syndrome a "possession by demons"

1900’s - Kraepelin and Bleuler

Kraepelin’s Dementia praecox: noted 2 types of psychosis - one waxed and waned, the other declined (13% recovered) Þ the inevitable decline is schizophrenia

Bleuler’s 4 A’s: autism, association (thinking disorder), affect (inappropriate in schizophrenia), ambivalence

1950’s-60’s - Schneiderian 1^st rank symptoms: delusions, audible thoughts, running commentary hallucinations, somatic hallucinations, thought control, thought withdrawal, thought insertion

Schneider thought diagnosis could be made if any of these symptoms were present; now we know these are just symptoms of psychosis (i.e. mania with psychotic features) that are not specific for schizophrenia

1950’s-1970’s - two extreme viewpoints emerged:

(1) RD Laing - believed that schizophrenics should not be treated at all Þ "sane way of dealing with an insane society"

(2) Psychoanalytic/psychological theories (i.e. Freud) - schizophrenia is due to problems in upbringing (primarily due to mother) or due to having "schizophrenogenic" parents; double-bind theories

1980-present - genetic and viral etiologies predominate: schizophrenia is an organic mental disorder

Diagnostic Criteria for Schizophrenia (DSM-IV)

(1) two of the following: delusions, prominent hallucinations, incoherence or marked loosening of associations, catatonic behavior, flat or grossly inappropriate affect (list influenced by Schneider’s list and Bleuler’s 4 A’s)

(2) bizarre delusions: space aliens are in direct contact with you and communicating to you in some way (impossible), whereas a "regular" delusion would be the CIA spying on you (possible though unlikely)

(3) prominent hallucinations of a voice with content having no apparent relation to depression or elation, or a voice keeping a running commentary on the person’s behavior or thoughts, or two or more voices conversing with each other

recognizes Schneider’s observation of running commentary hallucinations (voice has a continuous running commentary with the individual about their daily life)

(4) Schizoaffective disorder and mood disorder with psychotic features have been ruled out

(5) Continuous signs of the disturbance for at least 6 months

must have (4) and (5) and at least one of the 1^st three in order to make the diagnosis of schizophrenia

Diagnostic Criteria for Prodromal or Residual Symptoms

Need to have at least 3 of the following symptoms:

marked social isolation or withdrawal
marked impairment in role functioning
markedly peculiar behavior
marked impairment in personal hygiene and grooming (negative symptom)
blunted or inappropriate affect
digressive, vague, over elaborate, or circumstantial speech
odd beliefs or magical thinking
unusual perceptual experience
marked lack of initiative, interests, or energy (negative symptom)

Types of Schizophrenia

Paranoid: delusions of a systematic nature are prominent; has the most longitudinal validity (i.e. not common to switch between the different types, whereas it is common for the other types to go back and forth between the different types of schizophrenia), thus is a more stable diagnosis

Disorganized: disorganized speech and thought are prominent

Catatonic: catatonia prominent - waxy flexibility (stays in position like a mannequin) or catatonic excitement (tight energy movement; can lead to exhaustion and death if extreme; presence of stupor (i.e. are mute, won’t respond to a question)); catatonia is actually more frequently seen in mood disorders

Undifferentiated: no clear predominant type

Risks for family members with schizophrenia

Population = 1% risk; single parent with schizophrenia = 10% risk; both parents = 25%; sibling = 10%

Identical twin = 50%, thus, it’s autosomal dominant with incomplete penetrance; 50% even if adopted away!

Not 100% genetic since risk with identical twins is only 50%

Multifactorial with multiple genes and environmental factors (viral, toxins, drugs, alcohol, psychological stressors)

viral intrauterine factors (i.e. influenza virus in 1^st trimester of pregnancy Ý risk from 1 to 3%) are now the hot topic

How theory underlies treatment options

Early India treated with plant extracts (R. serpentinia) with good success

In middle ages, were "burned at the stake"

In 1900’s through 1950’s were treated with a variety of approaches (none too successful): ECT (electroconvulsive therapy), Prefrontal lobotomy (Nobel prize), Psychoanalytic approaches, Institutionalization

Current - Biopsychosocial model, (assumes a multifactorial illness that can include psychological stressors) - 3 parts:

Medications: antipsychotic, not specifically antischizophrenic; treat mainly florid, psychotic symptoms. Do not treat deficit symptoms well

Psychological treatments: supportive psychotherapy, reality oriented; family therapies

Social interventions aimed at reducing relapses and facilitating reintegration

Evidence for Biological Basis of Schizophrenia

Strong genetic loading - 50% risk of twins even when separated at birth

Structural brain changes in schizophrenia: prefrontal cortical atrophy, enlarged lateral ventricles, hippocampal/thalamic atrophy

Neurochemical abnormalities - a large number of neurochemical abnormalities discovered of which none have been uniformly replicated

Dopamine Hypothesis of Schizophrenia

Dopamine-mimetic drugs can worsen or even induce symptoms of schizophrenia (amphetamines, cocaine); specifically, these drugs may have effects which may be indistinguishable from paranoid schizophrenia
Dopamine receptor antagonists improve symptoms of schizophrenia
? Alterations in dopamine receptors/dopamine levels in schizophrenia - less routinely replicated

Multiple Neurotransmitters Most Likely Involved in Schizophrenia

Abnormalities in glutamatergic neurotransmission described; PCP may induce symptoms similar to schizophrenia (produces more delerium than schizophrenia)
Abnormalities in serotonergic neurotransmission described; 5-HT_2A antagonists are therapeutic in schizophrenia; Most antipsychotic drugs have high affinity for the 5-HT2A receptor
Many other neurotransmitter systems involved - ? Generalized ‘wiring’ deficit? Prenatal insult?

Differential Diagnosis

Organic mental disorder: LSD, PCP, amphetamines, toxins

Mood disorder with psychotic/catatonic features

Schizoaffective disorder

Rare metabolic disorders: porphyria (alteration in hemoglobin metabolism), Cushing’s syndrome, alterations in Ca⁺⁺ metabolism, metachromatic leukodystrophy, Huntington’s disease

Most treatable/curable causes of schizophrenic-like symptoms can be ruled out with thorough physical/mental status exam, CT/MRI scan, and routine lab tests

Clinical Features associated with Schizophrenia Diagnosis

flat affect, gradual onset, progressive decline in function, onset at late adolescence/early adulthood, family history of schizophrenia, catatonia more typically due to mood disorders, deficit symptoms predominate

Schizophrenia does improve, but not without medication

~10% of patients initially diagnosed with schizophrenia spontaneously improve (probably did not have schizophrenia)
delay of treatment is correlated with worsening outcome
the earlier antipsychotic medication is started, the better the ultimate outcome