ABSTRACT
Hallmark: Positive symptoms: delusions, hallucinations, bizarre behavior
Negative symptoms: blunting of affect, autism, ambivalence, social withdrawal, poverty of speech
Subtypes: Paranoid (best prognosis), disorganized, catatonic, undifferentiated, residual
At least 6 months of symptoms
d) Delusions with special reference (Capgras’ syndrome, koro, prison psychosis, van Gogh’s syndrome)
c. Symptoms of disorganization 1) Disorganized speech or thought 2) Blocking of thought, clanging, distractibility, derail-
ment, neologisms, poverty of speech and content of speech, preservation of thought, tangential speech
3) Disorganized or bizarre behavior, catatonic supor 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
d. Negative symptoms (3 per DMS-IV-TR) 1) Alogia: speech that is empty or with decreased
spontaneity 2) Affective blunting: sparsity of emotional reactivity 3) Avolition: unable to initiate or complete goals 4) Other common negative symptoms: anhedonia
(unable to experience pleasure), inability to concentrate or “attend,” inappropriate affect, poor hygiene
e. 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
f. Subtypes of schizophrenia (paranoid, disorganized, catatonic, undifferentiated, residual) 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
Table 6-1. Delusions
Delusion Definition
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
6) Psychiatric terms and definitions are listed in Table 6-2
4. Course a. Chronic, usually early onset, poor long-term outcome,
devastating illness 1) Prodromal phase: often prolonged period of social
withdrawal, delayed developmental milestones, awkward in motor skills, loss of interest in self-care
2) Active phase: psychotic symptoms appear, diagnosis is made more clear
3) Residual phase: similar to prodomal phase b. Prognostic features and indicators
1) Good outcome a) Acute onset, short duration, no previous psychi-
atric history, no family history of schizophrenia b) Mood symptoms present, sensorium clouded c) No obsessive-compulsive disorder, no
assaultiveness d) Premorbid functioning good, high socioeconomic
class e) Married, good psychosexual functioning f) Normal findings on neuroimaging
2) Poor outcome a) Insidious onset, chronic duration, psychiatric his-
tory present, positive family history of schizophrenia
b) Mood symptoms absent, sensorium clear c) Obsessive-compulsive disorder is present,
assaultiveness is present d) Poor premorbid functioning, low socioeconomic
class
e) Never married, poor psychosexual functioning f) Structural abnormalities present on neuroimaging
5. Epidemiology a. Prevalence over lifetime is about 1.0% (no differences
worldwide) b. Average age at onset: men, 21 years (17-27 years);
women, 27 years (17-37 years) c. Male (M):Female (F) equal frequency d. M>F in severity of illness, negative symptoms, suicide
risk e. F>M in mood comorbidity, better prognosis, better
social functioning f. Onset before age 10 and after age 45 are uncommon
6. Etiology a. “Two-hit” or “multiple-hit” idea has strong support: the
subject may have genetic predisposition to develop schizophrenia but does not manifest it unless other factors are encountered (e.g., environmental stressors)
b. Genetics
Table 6-2. Psychiatric Terms and Definitions
Schizophrenia Prognostic Factors Better prognosis: female, older onset, married, good premorbid functioning, acute onset, mood symptoms present, clouded sensorium, short duration
1) Siblings of schizophrenics: 10% develop schizophrenia 2) Children of parent with schizophrenia: 6% chance 3) Children of both parents with schizophrenia: 46%
chance 4) Twins: nearly 50% chance for monozygotic and 17%
chance for dizygotic twins 5) Multiple linkages (chromosomes 3p, 5q, 6p, 6q, 8p,
10p, 13q, 15q, 18p, 22q) 6) Large trinucleotide repeats: CAG/CTG on chromo-
somes 17 and 18 7. Neuroanatomical findings on imaging
a. Most consistent finding is ventricular enlargement, especially third and lateral ventricles
b. Selective reduction in size of frontal lobe, basal ganglia, thalamus, and limbic regions, including the hippocampus and medial temporal lobe
c. Possible decrease in volume of neocortical and deep gray matter
d. Sulcal widening, especially frontal and temporal areas e. Some studies indicate small but significant difference in
brain and intracranial volume f. Increased incidence of
1) Cavum septum pellucidum 2) Partial callosal agenesis
8. Functional neuroimaging a. Hypofrontality (frontal and prefrontal cortex): negative
symptoms and neurocognitive deficits b. Positron emission tomographic (PET) studies implicate
frontal cortex (orbital, dorsolateral, medial), anterior cingulate gyrus, thalamus, several temporal lobe subregions, and cerebellum
c. PET studies: anatomic substrate for visual hallucinations in schizophrenia 1) Inferotemporal cortex is responsible for visual recogni-
tion of objects and faces 2) Basal ganglia output (primarily substantia nigra pars
reticulata) to inferotemporal cortex with relay in ventral anterior thalamic nucleus-influences visual
processing and causes altered visual perception (hallucinations) as a result of increased dopaminergic activity in basal ganglia (may also be the mechanism of hallucinations in parkinsonian syndromes sensitive to dopaminergic agents [diffuse Lewy body disease more so than idiopathic Parkinson disease])
9. Neuropathology a. Decreased cell density in the dorsomedial nucleus of
thalamus b. Displacement of interneurons in frontal lobe cortex c. Developmental issues
1) History of injury at birth may contribute to development of schizophrenia
2) Season of birth: more schizophrenics are born in early spring or winter
10. Neurochemical considerations a. Dopamine hypothesis: excess of dopamine linked to
psychotic symptoms 1) Dopamine-blocking drugs seemed to lessen psychotic
symptoms (antipsychotics) 2) Drugs stimulating dopamine release caused psychotic
symptoms (amphetamine, cocaine) 3) Five types of dopamine receptors: D1, D2, D3, D4,
D5 a) D1: located in cerebral cortex and basal ganglia b) D2: located in striatum c) D3 and D4: high concentration in the limbic
system d) D5: located in thalamus, hippocampus, and
hypothalamus 4) Hyperactivity of dopamine system (especially D2
receptor): thought important to positive symptoms of schizophrenia
b. Postmortem findings in schizophrenics 1) Increased dopamine or homovanillic acid in limbic
areas and left amygdala (may be consequence of treatment with antipsychotics)
c. PET used to measure receptor occupancy of antipsychotic medications 1) Typicals: D2 receptors (78% receptor occupancy), no
obvious D1 receptors 2) Atypicals: D2 receptors (48%), D1 receptors (38%-
52%), D1 receptors are associated with fewer extrapyramidal symptoms
11. Clinical management (see PSYCHOPHARMACOLOGY AND OTHER TREATMENTS) a. Mainstay treatments: antipsychotics (D2 receptor block-
ers [postsynaptic]) b. Treatment
1) First line, atypicals (may improve neurocognitive
Schizophrenia Genetics Twin studies: nearly 50% monozygotic, 17% dizygotic
Chromosomes implicated: 3p, 5q, 6p, 6q, 8p, 10p, 13q, 15q, 18p, 22q
Trinucleotide repeat (CAG/CTG) on chromosomes 17 & 18
impairment in schizophrenia): risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), aripiprasole (Abilify)
2) Second line: clozapine (Clozaril), is atypical, expensive, and needs monitoring because of the potential for severe agranulocytosis
3) Typicals (may worsen neurocognitive functioning): chlorpromazine (Thorazine), thioridazine (Mellaril), perphenazine (Trilafron), loxapine (Loxitane), trifluoperazine (Stelazine), thiothixene (Navane), haloperidol (Haldol), fluphenazine (Prolixin)
c. Maintenance therapy, for at least 1 to 2 years after the initial psychotic episode
d. Alternative treatments 1) Electroconvulsive therapy (ECT): schizophrenia does
not typically respond to ECT, but it could be considered for catatonic schizophrenia
2) Many benefit from benzodiazepines, mood stabilizers, antidepressants
12. Psychosocial intervention strategies a. Emphasis on outpatient treatment b. Partial hospitalization, day treatments, outpatient care c. Family therapy reduces relapse rate d. Self-help organizations e. Cognitive therapy techniques: the goal is to remediate
the abnormal thought processes f. Social skills training: little effect on risk of relapse g. Psychosocial rehabilitation
1) Restore the patient’s ability to function in the community
2) Appropriate/affordable housing, group homes 3) Vocational training 4) Assertive community treatment
B. Schizophreniform Disorder 1. Duration of clinical signs and symptoms is less than 6
months 2. Overview of DSM-IV-TR criteria
a. At least two of the following: delusions, hallucinations, disorganized speech, disorganized behavior or catatonia, or negative symptoms
b. Symptoms not caused by schizoaffective disorder, mood disorder with psychotic features, substance-induced disorders, or general medical condition
c. Symptoms last at least 1 month, but less than 6 months 3. Clinical findings and issues
a. Similar to schizophrenia except for duration b. 33% fully recover within 6 months c. 66% usually progress to schizophrenia or schizoaffective
disorder 4. Course
a. Good prognostic factors: onset of psychosis within 4 weeks after change of behavior/functioning, good premorbid functioning, positive symptoms, confusion and
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
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)
Schizophreniform Disorder Like schizophrenia but duation <6 months
66% progress to schizophrenia/schizoaffective disorder
Prevalence: 0.2%
M=F
disorganization at peak of psychotic symptoms b. Depression is often comorbid: increases risk of suicide
5. Epidemiology: prevalence, 0.2%; M=F 6. Clinical management and psychosocial interventions:
same as for schizophrenia
C. Schizoaffective Disorder 1. Prominent mood symptoms and at least 2 weeks of
psychotic symptoms in the absence of mood symptoms 2. Overview of DSM-IV-TR criteria
a. Uninterrupted period during which a mood disorder (major depression, mania, or mixed episode) coexists with symptoms of the active phase of schizophrenia.
