Psychosis and Schizophrenia Spectrum 

 Historical perspective
o Schizophrenia coined 1910 by swiss psychiatrist Paul Eugen Bleuler 
 Believed caused sharpening of senses 
 Suggested symptoms known as 4 As: blunted Affect – a reduction in emotional
response to stimuli, loosening of Associations and disordered pattern of
thought, Ambivalence, or difficulty making decisions, and Autism, by which he
meant a loss of awareness of external events and preoccupation with one’s own
thoughts.
o German psychiatrist Emil Kraepelin previously called collection of symptoms dementia
praecox in 1887
 Believed only affected young people and inevitably led to mental deterioration
 Kraepelin wrote the Compendium der psychiatrie 
o Ebers Papyrus, Egypt ~1500-1550 BC
 One of the oldest preserved medical documents
o 1400 BC Hindu Arthava Veda
 Describes illnesses marked by bizarre behavior and lack of self control
o 1000 BC Chinese text The Yellow Emperor’s Classic of Internal Medicine 
 Attributes insanity and seizures to supernatural and demonic forces 
o Medieval era
 Formal institutionalization 
 “fool’s tower”- housed madmen
 England 1247- The Priory of Saint Mary of Bethlehem founded, later known as
Bedlam 
o First published in 1563, De præstigiis dæmonum [The  Deception  of Demons] argued that
the madness of ‘heretics’ resulted not from divine punishment or demonic possession,
but from natural causes. 
 The Church proscribed the book and accused its author, Johann Weyer, of being
a sorcerer.
o Philippe Pinel (d. 1826) began regarding mental disorder as the result of exposure to
psychological and social stressors, and, to a lesser extent, of heredity and physiological
damage. A landmark in the history of psychiatry, Pinel’s Traité Médico -philosophique
sur l’aliénation mentale ou la manie [A Treatise on Insanity] called for a more humane
approach to the treatment of mental disorder. 
 This ‘moral treatment’ included respect for the person, a trusting and confiding
doctor-patient relationship, decreased stimuli, routine activity, and the
abandonment of old-fashioned Hippocratic treatments. 
 Definition
o Psychosis is a condition of the mind broadly defined as a loss of contact with reality. It is
estimated that 13 to 23 percent of people experience psychotic symptoms at some
point in their lifetime, and 1 to 4 percent will meet criteria for a psychotic disorders
 Timelines
 Brief psychotic disorder 1 day to 1 month
 Delusions/hallucinations/disorganized speech/disorganized behavior
 Need 1 or more
 More common in females versus males
 Average age onset mid 30s
  Schizophreniform <6 months
 Delusions/hallucinations/disorganized speech/disorganized
behavior/negative symptoms
 2 or more
 Good prognostic features (2 or more)
 Onset of prominent psychotic symptoms within 4 weeks of the
first noticeable change in usual behavior or functioning
 Confusion or perplexity
 Good premorbid social and occupational functioning
 Absence of blunted or flat affect
 No criteria for impaired occupational or social functioning (opposed to
schizophrenia)
 1/3 recover
 2/3 progress to schizophrenia or schizoaffective
 Schizophrenia >6 months and >=1 month active symptoms
 2 or more criterion A symptoms prominent for 1 month PLUS level of
functioning in 1 or more areas is markedly below the level achieved
prior to onset
 If there is a history of autism or a communication disorder, the
additional diagnosis of schizophrenia is made only if prominent
delusions or hallucinations, in addition to the other required symptoms
of schizophrenia, are also present for at least 1 month (or less if
successfully treated).
 Onset 10-25 in males, 25-35 in females
 Insidious
 High rates comorbidity
 50% depression
 65% OCD
 Schizoaffective disorder
 An uninterrupted period of illness during which there is a major mood
episode (major depressive or manic) concurrent with Criterion A of
schizophrenia.
 Delusions or hallucinations for 2 or more weeks in the absence of a
major mood episode (depressive or manic) during the lifetime duration
of the illness.
 Functioning is frequently impaired, but not required for diagnosis (as
opposed to schizophrenia)
 Negative symptoms are not usually as pervasive as with schizophrenia
 Better prognosis than schizophrenia due to mood symptoms (the more
mood symptoms, the better)
 Only 1/3 as common as schizophrenia (0.3%)
 Higher in females
 Lifetime risk of suicide is 5%-10%


 DSM-5 criteria
o Domains
 Delusions- positive symptom
 Fixed beliefs not amenable to change in light of conflicting evidence
 Persecutory- person will be harmed/harassed
 Referential- certain gestures, comments, environmental cues
are directed at oneself
 Grandiose- individual believes they have exceptional
abilities/wealth/fame
 Erotomanic- falsely believes another person is in love with them
 Nihilistic- conviction that major catastrophe will occur
 Somatic- preoccupations with health and organ function
 Control- something other than person is controlling thoughts or
body
 Bizarre versus non-bizarre
 Bizarre- clearly implausible, no way could be true
 Aliens have cloned a perfect body for the patient but
they must find a way to take their head off so that their
spirit can flow into the new body
 Non-bizarre- not true but understandable and has the
possibility of being true
 Hallucinations- positive symptoms
 Perception like experiences that occur without an external stimulus,
vivid and clear, not under voluntary control
 Auditory most common in schizophrenia- estimate between 40-80
percent
 Voices distinct from one’s own thoughts, may be familiar or
unfamiliar
 Can also be music, body noises or machinery
 Auditory hallucinations are often most responsive to
antipsychotic medications, “turn down the volume”
 Visual- often unformed, glowing orbs, flashes of color
 Somatic- feelings of being touched, of sexual intercourse or pain
 Disorganized thinking and speech- thought process inferred from speech-
positive symptoms
 Symptoms severe enough to impair effective communication
 May be less severe in prodromal and residual periods 
 Tangential- increasingly further off topic without answering question
 Circumstantial- person answers question in roundabout manner
 Derailment- suddenly switching topics without logic or segue
 Neologisms- creation of new, idiosyncratic words
 Word salad- words are thrown together without any sensible meaning
 Grossly disorganized or abnormal motor behavior including catatonia
 Childlike silliness to unpredictable agitation
 Problems in goal directed behavior
 Negativism= resistance to instructions
 Mutism/stupor/repeated stereotyped movements
 Negative symptoms/deficit symptoms
 Represent core feature of schizophrenia
  Diminished emotional expression in face, eye contact,
intonation of speech, movement of hand, head and face 
 Avolition- decrease in purposeful activities
 Alogia- diminished speech output
 Anhedonia- decreased ability to experience pleasure
 Asociality- lack of interest in social interactions
 Primary negative symptoms very resistant to treatment and closely
related to functional outcome
 Severity of negative symptoms is independent of positive symptoms
o Clinicians should first consider conditions that do not reach full criteria for a psychotic
disorder
o For diagnosis of schizophrenia, must exclude other conditions that could give rise to
psychosis 
 Important clinical pearls
o Schizophrenia prominently associated with greater rates cardiovascular disease,
dyslipidemia and type 2 diabetes
o Decrease in average lifespan of 20 years
o Some diabetes risk associated with medications, increased rates of diabetes and insulin
resistance predate antipsychotics and may be related to shared genetics, lifestyle and/or
diet
o High suicide rate- 5%, however there was a study that showed that fewer suicide deaths
occurred during treatment with an antipsychotic versus non-use
o 90% have nicotine use disorder, smoke from cigarettes can cause CYP1A2 induction
 Treatment and relevant medication studies/trials 
o Pre-treatment assessment
 Baseline physical exam and neurological exam
 BMI
 Waist circumference
 Heart rate
 Blood pressure
 CBC, electrolytes, lipids, liver, renal and thyroid function tests
 WBC count with differential for clozapine
o Positive symptoms: antipsychotics reduce by 70%
 With the exception of clozapine, studies have not found convincing evidence
that any antipsychotic are more effective than others for positive symptoms in
acute schizophrenia
 Clozapine is more effective for patients who do not respond fully to other
antipsychotics
o Negative symptoms do not respond as well
 2017 clinical trial found cariprazine efficacious in reducing negative symptoms
when compares with risperidone

o Antipsychotic selection typically based on side effect profile and different formulations
o Patients should be observed on a stable dose of antipsychotic for 2-6 weeks before
concluding the drug is ineffective
o Switching antipsychotics is helpful when poor response is related to side effects
  Example: in CATIE trial, people who gained weight in first phase of treatment
lost weight when they were switched to ziprasidone
o Switching antipsychotics less clearly beneficial when the initial medication lacked
effectiveness, as most studies show that poor responders to one antipsychotic are likely
to be poor responders to another antipsychotic unless that other antipsychotic is
clozapine
o Little clinical evidence exists to support adding a second antipsychotic when patients
have suboptimal response to a single agent
o For patients who have recovered form an acute psychotic episode, it is recommended
that antipsychotic medication be continued indefinitely, even for patients who have
achieved remission from a first psychotic episode- recommended by PORT- the
schizophrenia patient outcomes research team
 ECT for acute psychosis
 Assertive Community Treatment (ACT)
 Family interventions/psychoeducation (NAMI & NIMH)
 Supported employment (Goodwill Industries)
 Cognitive behavioral therapy and supportive therapy
 Social skills training

Mesocortical
§ Cognitive impairments and negative symptoms
§ Blockade with D2 agents worsen these symptoms
Mesolimbic
§ Positive symptoms
§ Blockade alleviates hallucinations and delusions
Nigrostriatal
§ Blockade causes extrapyramidal symptoms (EPS)
Tuberoinfundibular
§ Blockade causes elevation in prolactin from pituitary

James Hardy, "Divine Madness: a History of Schizophrenia", History Cooperative, January 29,