last authored: April 2012, David LaPierre
last reviewed:




Schizophrenia is a leading worldwide health problem, affecting just under 1% of the world's population. Schizophrenia spectrum disorders bring this number up to ~5%. Schizophrenia is found in all societies, with a greater incidence in urban areas, even accounting for social drift. It also tends to be more severe in developed countries.


The Prisoner, Robert King

Because schizophrenia begins early in life, causes significant and long-lasting impairments, and require ongoing care, its costs are enormous and are estimated to exceed those of all cancers combined. In 1990, its direct and indirect costs were estimated to exceed $33 billion in the US (Kaplan and Sadok, 2007).


"You see, I am crazy. I take the newer medications,
but I still see things that are not here. I just choose
not to acknowledge them. Like a diet of the mind,
I choose not to indulge certain appetities. Like my
appetite of patterns. Perhaps my appetite to
imagine, to dream.
" - A Beautiful Mind




Signs, Symptoms, and Diagnosis

Schizophrenia has a broad array of symptoms, covering cognition, behaviour, and emotion.


Guidelines for assessing psychotic episodes are helpful in making a diagnosis of schizophrenia or other psychotic disorders.



DSM-IV criteria for schizophrenia are as follows:


A) two or more of the following, each present for a significant portion of time over 1 month (only one required if delusions are bizarre, if a voice is keeping a running commentary, or if two or more voices are conversing with each other):

B) loss of functioning in social or occupational settings, or self-care

C) continuous signs of disturbance for at least 6 months, including at least one month of active phase symptoms; this may include prodromal or residual phases

D) other psychotic and mood disorders, general medical conditions/substances excluded


The Scale for Assessment of Positive Symptoms (SAPS) and Scale for Assessment of Negative Symptoms (SANS) can be helpful in evaluating symptoms.


Other signs and symptoms include lack of insight, neurological soft signs (stereognosis, graphesthesia, balance, proprioreception), disorder in visual tracking, decreased sleep, decreased sexual drive, and constipation.


Subtypes of schizophrenia include:

paranoid: preoccupation with delusions or auditory hallucinations; other potential symptoms less significant

catatonic: at least two of the following:

disorganized: disorganized speech, behaviour, and flat or inappropriate affect

undifferentiated: no prominent other subtype

residual: absence of positive symptoms, but continued evidency of negative symptoms or attenuated positive symptoms




Causes and Risk Factors

A central question regarding the development of schizophrenia is whether it is neurodevelopmental, a failure in a developing brain, or neurodegenerative, altering a normally developed brain.



An estimated 80% of people with schizophrenia experience their first psychotic episode between the ages of 16-30. The mean age of onset is 22 for men and 27 for women. Women have a second smaller peak in their 40's, possibly due to loss of estrogen during menopause and its effects on dopamine.




Men develop symptoms earlier than women, but there is an equal distribution between genders over lifetime. Men also have more signficiant prodrome, psychotic symptoms, poorer premorbid functioning, greater evidence of morphological and cognitive problems, more negative symtoms and substance abuse, and poorer overall outcome.




Seems to be sufficient evidence to warn adolescents about the risk.

Also worsens outcome: increases non-adherence and aggression.

Substance abuse also causes an earlier onset of psychosis (avg 17-19). This time is normally when people are making important life changes, such as education, employment, and relationships. A substantial loss of function at this time can leave people with no stability. Alternatively, if onset occurs once people are married or have a job, these factors can assist in a faster return to stability.




The fact that monozygotic twins have 48% concordance rates of developing schizophrenia (ref) suggests there are genes that confer susceptibility to schizophrenia.


Disturbances in Family Relationships?

the schizoprenogenic mother; family - schism - skew.

Pseudomutauality;Emotional divorce;double-blind; scapegoating - someone in the family who got all the blame and mixed communications.


Socioeconomic Factors

there is a greater prevalence in lower socioeconomic classes, and in urban vs rural areas.

There may be higher rates in immigrants to Europe, though that could potentially be an association (due to isolation?)



Viruses appear to be worrying particularly in 2nd trimester of pregnancy.


Other risk factors

Other risk factors include obstetrical complications, malnutrition, and childhood trauma.


Historical Concepts




It has been difficult to determine if biological changes are the cause or effect of psycosis, or even of treatment.


Structural Changes

MRI studes have shown decreased gray matter in the prefrontal and temporal cortex and dorsomedial thalamic nucelus, changes in white fibre tracts, decreased volume in limbic system structures, and increased basal ganglia nuclei volume.


Reduction in temporal lobe volume is the most consistent, affecting 10%. But it is in no way diagnostic.


Problem with myelin

Myelin increases electrical signaling; losing it causes decreased activity and also leaves the axons susceptible to immune attack.

Decreased myelin intergrity in temporal and frontal lobes - loss of compactness, etc....

Say that young adults halt in their myelin deposition...

Niacin depletion appears connected with axonal degeneration, at least in mice...



Correlation appears to be present for duration of untreated psychosis (DUP)


Many postmortem examinations suggest cell loss, misalignment of cells, altered membrane and intracellular structure, or differing protein expression.


PET studies show decreased signaling on frontal and temporal lobes


Actively hallucinating patients can show functional changes in the language and anterior congulate basal ganglia thalamocortical neural circuits.


Dopamine Hypothesis


Neurodegenerative Hypothesis

Duration of untreated psychosis appears to be neurotoxic. There seems to be a critical period of maximum vulnerability of the first 5 years.


Stress vulnerability model

psychotic disorders can result from interaction between biological vulnerability and environmental stress


The dissociation (loss of association) between thought processes and among thought, emotion, and behaviour may underlie the diverse manifestations of schizophrenia. The single disease model suggests that all patients share similar etiology and pathophysiology, and depending on genetics, adaptive capacity, and environmental circumstances, secondary disease manifestations such as hallucinations, delusions, social withdrawal and diminished drive could occur.

The other major model suggests schizophrenia is a clinical syndrome. This view is supported by the numerous risk factors, implication of multiple genes, and variation in clinical presentation, treatment response, and clinical course.

Other less popular models include the societal reaction theory (a sane reaction to an insane world) or the idea that schizophrenia is a myth to manage deviant behaviour. These models cannot account for distribution of the disease among relatives, associated functional and structural brain changes, or normalizing effects of drug treatment.

Disease models suggesting a purely psychological or social mechanism exclude demonstrated genetic and immunovirological causal factors.


One Condition, or many?

There is heterogeniety in schizoprenia.

There are differences in symptoms (subtypes), response to treatment, course and outcome, and genetic underpinnings



Differential Diagnosis

Schizoaffective disorder, mood disorders: in schizophrenia, depression or mania develops after psychosis, or is brief

Schizophreniform disorder: schizophrenia is lengthier

Depression with psychosis


Personality disorder

anxiety disorders

pervasive developmental disorders





Antipsychotics (neuroleptics) can be used for acute and maintenance treatment, with or without anticonvulsants or anxiolytics.

Psychotherapy can be provided to individuals, families, or groups. It includes supportive or CBT.

Assertive community treatment can be provided along with social skills training and employment/housing programs.

Non-adherence can be a big problem in people on anti-psychotics.


Care has been shifting dramatically away from hospital care, usually into other means of custodial care such as nursing homes. These are often poorly supervised, with decreased treatment and rehabilitation services.


Other patients are released into the communities who may be unable or unwilling to provide adequate care. Fortunate patients receive family support, but this can create terrible hardship. Others may find themselves homeless, alone and hopeless, or in jail. An estimated 15-45% of homeless Americans have a diagnosis of schizophrenia (Kaplan and Sardok, 2007).



Course and Prognosis

quotes from 'A Beautiful Mind'

"they're not gone, and maybe they never will be.
But I've gotten used to ignoring them, and I think
as a result they've kinda given up on me. You think
that's what it's like with all our dreams and nightmares?
You've gotta keep feeding them for them to stay alive."




Over time, 1/3 improve, 1/3 remain the same, and 1/3 worsen.


Age: adolescence or early adulthood (12 – 30). The average age of a young person coming to
Family history of a psychotic disorder such as schizophrenia or bipolar disorder—particularly in a close or immediate relative (parent or sibling).
A history of difficulty making friends, along with unusual thoughts and odd or eccentric behaviors (schizotypal personality disorder).
A marked change in behavior, emotions, or thinking for a month or more, especially when accompanied by social withdrawal and deterioration in school or work performance.

Sub-threshold psychotic symptoms that include suspiciousness or irrational (delusional) thinking, sporadic or fleeting hallucinations, and/or confused, disorganized communication that may wander off topic easily. Young people presenting most of these features may be at high risk for experiencing an acute psychotic episode.


Prodromal Phase

The prodromal phase generally includes social withdrawal and lasts 1-2 years. Other prodomal symtoms include:

The Active Phase follows the prodrome, usually with hallucinations and delusions.

During the residual phase, active-phase symptoms are diminished or absent. However, decreased function, negative symptoms, or decreased positive symptoms may occur.


There is now a focus on defining 'at risk' people and enganging people early in their disease. The duration of untreated psychosis seems to affect the severity of disease, as psychotic symptoms appear to be neurotoxic.


There is wide variability in response to treatments, but remission is the goal. 10% have an intense onset and little or no response to any available treatments. Recovery involves maintenance of self-esteem and maximization of quality of life.


Greater than 80% of people recover from the first episode, which on average lasts 40-60 days. The majority of people have relapses within the first 5 years, with time of active symptoms increases with each episode. The illness process usually plateaus within the first 5-10 years of psychosis and does not involve progressive deterioration. Complete remission is the best outcome.


Long-Term Outcomes of Schizophrenia


Jobe and Harrow (2005) published a review article finding long term outcome is heterogenous. Few schizophrenia patients showed a progrsssive downhill course, and 21-57% of patients showed a 'good' outcome, depending on criteria used.


Neuman: Follow-up for up to 34 years of people with schizophrenia in Alberta: tremendously variable. Severity scole early on does not appear to predict long term. Approximately 20% of people have at most mild symptoms many years later. Using complex calculations, they determined up to 25 DALYs for someone diagnosed at age 15.




Problems accompanying schizophrenia

Schizophrenia causes severe disruption in patient's and families' lives. Comorbidities are extremely common, including depression and suicide (up to 10%). Substance abuse is near universal. Up to 90% of people with schizophrenia smoke. Rates of physical illness and accidents are higher, and there is also an increased risk of violence during untreated psychosis.


Good Prognostic Factors



Education and Resources

In many places, biological underpinnings are stressed, especially to families, to alleviate guilt.

Education of Family

High emotion-expressing people




Resources and References


Jobe and Harrow, 2005, Can J Psych