Teaching Presentation/Review | Schizophrenia

Date: 12/12/2017

Schizophrenia (Review)
Introduction: Schizophrenia is a psychiatric disorder involving chronic or
recurrent psychosis characterized by a constellation of abnormalities in thinking,
emotion, and behavior.
 There is no single symptom that is pathognomonic, and it has a heterogeneous
clinical presentation.
 It is commonly associated with impairments in social and occupational
functioning.

 It is among the most disabling and economically catastrophic medical disorders,

ranked by the World Health Organization as one of the top ten illnesses
contributing to the global burden of disease.

Symptomatology:
 Types: Generally, the symptoms of schizophrenia are broken up into 3 main
categories:
o Positive – Hallucinations, delusions, bizarre behavior, disorganized
speech.
 These tend to respond better to antipsychotic medications.
o Negative – Flat or blunted affect, anhedonia, apathy, alogia, and lack of
interest in socialization.
 These symptoms are comparatively more often treatment resistant
and contribute significantly to the social isolation of schizophrenic
patients.
o Cognitive – Impairments in attention, executive function, and working
memory.
 These symptoms usually result in poor work and school
performance.
 Phases: Symptoms of schizophrenia tend to present in 3 different phases:
o (1) Prodromal – Involves a decline in functioning that precedes the first
psychotic episode.
 The patient may become socially withdrawn and irritable.
 He or she may have physical complaints, declining school/work
performance, and/or newfound interest in religion or the occult.
o (2) Psychotic – Perceptual disturbances, delusions, and disordered
thought process/content.
o (3) Residual – Occurs following an episode of active psychosis.
 It is marked by mild hallucinations or delusions, social withdrawal,
and negative symptoms.

Diagnosis (DSM-5 Criteria):

 Two or more of the following must be present for at least a 1-month “active”
period within the diagnostic 6-month timeframe:
o (1) Delusions
o (2) Hallucinations
o (3) Disorganized speech
Teaching Presentation/Review | Schizophrenia
Date: 12/12/2017

o (4) Grossly disorganized or catatonic behavior

o (5) Negative symptoms
o Note: At least one must be 1, 2, or 3.
 Must cause significant social, occupational, or self-care functional deterioration.
 Duration of illness for at least 6 months (including prodromal or residual
periods in which the above full criteria may not be met).
 Symptoms not due to effects of a substance or another medical condition.

Timeline & Related-Disorders:

 Schizophreniform Disorder:
o Meet schizophrenia criteria, but symptoms have lasted between 1 and 6
months
 Brief Psychotic Disorder:
o Same psychotic symptoms as in schizophrenia, but symptoms last
between 1 day to 1 month, and there must be eventual full return to
premorbid level of functioning.
 Schizoaffective Disorder:
o Meet criteria for either a major depressive or manic episode during
which psychotic symptoms consistent with schizophrenia are also met.
 Delusions or hallucinations for at least 2 weeks in the absence of
mood disorder symptoms – this is the key detail for differentiating
schizoaffective disorder from mood disorder with psychotic
features!
o Mood symptoms present for a majority of the psychotic illness.

Psychiatric Exam – Typical Findings in Schizophrenia Patients:

 Disheveled appearance
 Flat affect
 Disorganized thought process
 Intact procedural memory and orientation
 Auditory hallucinations
 Paranoid delusions
 Ideas of reference
Teaching Presentation/Review | Schizophrenia
Date: 12/12/2017

 Lack of insight into their disease

Epidemiology:
 Schizophrenia affects approximately 0.3-0.7% of people over their lifetime.
 Men and women are equally affected but have different presentations and
outcomes:
o Men tend to present in early to mid-20s
o Women present in late 20s
o Men tend to have more negative symptoms and poorer outcome
compared to women.
 Schizophrenia rarely presents before age 15 or after age 55.
 There is a strong genetic predisposition:
o 50% concordance rate among monozygotic twins
o 40% risk of inheritance if both parents have schizophrenia
o 12% risk if one first-degree relative is affected
 Substance use is comorbid in many patients with schizophrenia.
o The most commonly abused substance is nicotine (> 50% of patients),
followed by alcohol, cannabis, and cocaine.
 Lower socioeconomic groups have higher rates of schizophrenia.
o This may be due to the downward drift hypothesis, which suggests that
people suffering from schizophrenia are unable to function well in society
and hence end up in lower socioeconomic groups.
o Many homeless people in urban areas suffer from schizophrenia.

Pathophysiology:
 The exact cause of schizophrenia is not known, but it appears to be partly
related to increased dopamine activity in certain neuronal tracts.
o The main supporting evidence for this hypothesis is that most
antipsychotics successful in treating schizophrenia are dopamine
receptor antagonists.
Teaching Presentation/Review | Schizophrenia
Date: 12/12/2017

o Additionally, cocaine and amphetamines which increase dopamine

activity (and dopamine agonists such as pramipexole and amantadine)
can cause schizophrenic-like symptoms.
 Dopamine Pathways Affected in Schizophrenia include:
o Mesolimbic – Excessive dopaminergic activity here is responsible for
positive symptoms
o Prefrontal Cortical – Inadequate dopaminergic activity here is
responsible for negative symptoms
 Dopamine Pathways Affected by Antipsychotic Drugs include:
o Tuberoinfundibular – Dopaminergic activity here is blocked by
antipsychotics, causing hyperprolactinemia (note that dopamine is AKA
prolactin-inhibiting factor) which results in gynecomastia, galactorrhea,
sexual dysfunction, and menstrual irregularities.
o Nigrostriatal – Dopaminergic activity here is blocked by antipsychotics,
causing Parkinsonism/extrapyramidal side effects such as tremor, rigidity,
slurred speech, akathisia, dystonia, and other abnormal movements.
 Other Neurotransmitter Abnormalities seen in Schizophrenia:

Neurotransmitter Explanation
Change
Elevated Serotonin Some 2nd generation antipsychotics (such as
risperidone and clozapine) antagonize serotonin
and weakly antagonize dopamine
Elevated Long-term use of antipsychotics has been shown
Norepinephrine to decrease activity of noradrenergic neurons
Decreased GABA There is decreased expression of the enzyme
necessary to create GABA in the hippocampus of
schizophrenic patients
Decreased Levels of Schizophrenic patients have fewer NMDA
Glutamate Receptors receptors – this is consistent with the psychotic
symptoms observed with NMDA antagonists like
ketamine

Prognostic Factors:
 Even with medication, 40–60% of patients remain significantly impaired after
their diagnosis, while only 20–30% function fairly well in society.
 About 20% of patients with schizophrenia attempt suicide and many more
experience suicidal ideation.
 The various factors associated with a better or worse prognosis are as follows:

Associated with Better Associated with Worse Prognosis

Prognosis
Later Onset Early Onset
Good Social Support Poor Social Support
Positive Symptoms Negative Symptoms
Mood Symptoms Family History of Schizophrenia
Acute Onset Gradual Onset
Female Gender Male Gender
Teaching Presentation/Review | Schizophrenia
Date: 12/12/2017

Few Relapses Many Relapses

Good Premorbid Poor Premorbid Functioning (e.g.
Functioning Social Isolation)
Comorbid Substance Use

Treatment/Management:
 Pharmacologic Therapy: Antipsychotic medications (AKA neuroleptics) are
first-line treatment for schizophrenia.
o They have been shown in clinical trials to be effective in reducing
symptoms and behaviors associated with the disorder.
o (1) First-generation (typical) antipsychotic medications (include
chlorpromazine, fluphenazine, haloperidol, perphenazine and
trifluoperazine):
 These are primarily dopamine (mostly D2) antagonists.
 Treat positive symptoms and have minimal impact on negative
symptoms.
 Side effects include extrapyramidal symptoms, neuroleptic
malignant syndrome, and tardive dyskinesia.
o (2) Second-generation (or atypical) antipsychotic medications (include
aripiprazole, asenapine, clozapine, iloperidone, lurasidone, olanzapine,
quetiapine, risperidone, ziprasidone):
 These antagonize serotonin receptors (5-HT2) as well as dopamine
(D4 > D2) receptors.
 Research has shown no significant difference between first- and
second-generation antipsychotics in efficacy.
 The selection requires the weighing of benefits and risks in
individual clinical cases.
 Lower incidence of extrapyramidal side effects, but higher risk for
metabolic syndrome.
 Medications should be taken for at least 4 weeks before efficacy is
determined.
 Clozapine is reserved for patients who have failed multiple
antipsychotic trials due to its high risk of agranulocytosis.

 Non-Pharmacologic Therapy: Following treatment with antipsychotic

medication, which is often only partially effective, most individuals with
schizophrenia would benefit from systematic rehabilitation – this may include
the following:
o Cognitive Behavioral Therapy/ Social Skills Training
 Aimed at improving patients’ ability to function in society.
 Patients are helped through a variety of methods to improve their
social skills, become self-sufficient, and minimize disruptive
behaviors.
 Good for individuals who experience persistent delusions or
hallucinations despite adequate trials of antipsychotic medication.
Teaching Presentation/Review | Schizophrenia
Date: 12/12/2017

o Family psychoeducational intervention

 Aimed at reducing the level of stress between the patient and their
environment (i.e. family members), thereby reducing the frequency
of psychotic relapse.

References:
 Bustillo, Juan and Elizabeth Weil. Psychosocial interventions for schizophrenia.
In: UpToDate, Ed. Ted. W. Post and Stephen Marder. UpToDate, Waltham, MA,
2017. Web. 10 December 2017.
<https://www.uptodate.com/contents/psychosocial-interventions-for-
schizophrenia>.
 Fischer, Bernard A. and Robert W. Buchanan. Schizophrenia in adults: Clinical
manifestations, course, assessment, and diagnosis. In: UpToDate, Ed. Ted. W.
Post and Stephen Marder. UpToDate, Waltham, MA, 2017. Web. 9 December
2017. <https://www.uptodate.com/contents/schizophrenia-in-adults-clinical-
manifestations-course-assessment-and-diagnosis>.
 Ganti, Latha, Matthew S. Kaufman, and Sean M. Blitzstein. “Chapter 3:
Psychotic Disorders.” First Aid for the Psychiatry Clerkship, 4th ed. New York:
McGraw-Hill Education, 2016. 23–30. Print.
 Le, Tao, et al. “Section 3: Psychiatry - Pathology.” First Aid for the USMLE Step
1 2017. New York: McGraw-Hill Education, 2017. 530. Print.
 Stroup, T. Scott and Stephen Marder. Pharmacotherapy for schizophrenia:
Acute and maintenance phase treatment. In: UpToDate, Ed. Ted. W. Post and
Murray B. Stein. UpToDate, Waltham, MA, 2017. Web. 10 December 2017.
<https://www.uptodate.com/contents/pharmacotherapy-for-schizophrenia-acute-
and-maintenance-phase-treatment>.