Schizophrenia

Schizophrenia is a mental disorder characterized by the presence of positive symptoms (delusions, hallucinations), disorganization, and negative symptoms (poverty of thought, amotivation).

Prevalence

Though conventional clinical wisdom is that the incidence of psychosis is the same across the world, this is not the case. The incidence of first episode psychosis can vary up to eightfold between different cities across the world.[1] The incidence of first episode psychosis is highest for men and women between the ages of 18 and 24. The incidence subsequently declines more rapidly in men but decreases more slowly in women, who experience a secondary peak at ages 50 to 54.

Suicide

Suicide is a major cause of mortality in patients with schizophrenia, most data suggests that 5–13% of patients die by suicide.[2]

Criterion A

At least 2 of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated). At least 1 of these must be (1), (2), or (3):

  1. Delusions
  2. Hallucinations
  3. Disorganized speech (e.g. - frequent derailment or incoherence)
  4. Grossly disorganized or catatonic behaviour
  5. Negative symptoms (i.e. - diminished emotional expression or avolition)
Criterion B

For a significant portion of the time since the onset of the disturbance, level of functioning in at least 1 major area, such as work, interpersonal relations, or self-care, is markedly below the level achieved prior to the onset (or when the onset is in childhood or adolescence, there is failure to achieve expected level of interpersonal, academic, or occupational functioning).

Criterion C

Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms (or less if successfully treated) that meet Criterion A (i.e. - active-phase symptoms) and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or by 2 or more symptoms listed in Criterion A present in an attenuated form (e.g. - odd beliefs, unusual perceptual experiences).

Criterion D

Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out because either:

  1. No major depressive or manic episodes have occurred concurrently with the active-phase symptoms, or
  2. If mood episodes have occurred during active-phase symptoms, they have been present for a minority of the total duration of the active and residual periods of the illness.
Criterion E

The disturbance is not attributable to the physiological effects of a substance (e.g. - a drug of abuse, a medication) or another medical condition.

Criterion F

If there is a history of autism spectrum disorder or a communication disorder of child hood onset, 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).

Specifiers

Episode Specifier

Specify if:

  • First episode, currently in acute episode: First manifestation of the disorder meeting the defining diagnostic symptom and time criteria. An acute episode is a time period in which the symptom criteria are fulfilled.
  • First episode, currently in partial remission: Partial remission is a period of time during which an improvement after a previous episode is maintained and in which the defining criteria of the disorder are only partially fulfilled.
  • First episode, currently in full remission: Full remission is a period of time after a previous episode during which no disorder-specific symptoms are present.
  • Multiple episodes, currently in acute episode: Multiple episodes may be deter mined after a minimum of two episodes (i.e., after a first episode, a remission and a minimum of one relapse).
  • Multiple episodes, currently in partial remission
  • Multiple episodes, currently in full remission
  • Continuous: Symptoms fulfilling the diagnostic symptom criteria of the disorder are remaining for the majority of the illness course, with subthreshold symptom periods be ing very brief relative to the overall course.
  • Unspecified

Severity Specifier

Specify if:

The term psychosis has been defined in various ways in the medical literature over time. The narrowest and current definition of psychosis is hallucinations and delusions, with the lack of reality testing or insight. A broader definition of psychosis would also include disorganized thought, emotions, and behaviour. This loose definition was more common in the past, and schizophrenia was often overdiagnosed as a result.

What is psychosis?

Comparison

Brief psychotic disorder
Onset Sudden
Length 1 day to 1 month
Psychotic Symptoms At least 1 of:
  • Delusions
  • Hallucinations
  • Disorganized speech
  • Grossly disorganized or catatonic behaviour
    Mood Symptoms No
    Functional Decline? Full resolution of symptoms
    Schizophreniform disorder
    Onset Can be prodromal
    Length 1 month to 6 months
    Psychotic Symptoms At least 2 of:
    • Delusions
    • Hallucinations
    • Disorganized speech
    • Grossly disorganized or catatonic behaviour
    • Negative symptoms
      Mood Symptoms No
      Functional Decline? Not required
      Schizophrenia
      Onset Can be prodromal
      Length > 6 months
      Psychotic Symptoms
      Mood Symptoms No
      Functional Decline? Required
      Schizoaffective disorder
      Onset Can be prodromal
      Length Major mood episode
      + 2 weeks of isolated psychotic symptoms
      Psychotic Symptoms
      • Delusions or hallucinations for 2 or more weeks
      • Must be in absence of a major mood episode (depressive or manic) during the lifetime duration of the illness
        Mood Symptoms Required
        Functional Decline? Not required
        Delusional disorder
        Onset Can be prodromal
        Length > 1 month
        Psychotic Symptoms One or more delusions, with no other psychotic symptoms.
        Mood Symptoms No
        Functional Decline? Normal function aside from impact of delusions
        Type Onset Length Psychotic Symptoms Mood Symptoms Functional Decline?
        Brief psychotic disorder Sudden 1 day to 1 month At least 1 of:
        • Delusions
        • Hallucinations
        • Disorganized speech
        • Grossly disorganized or catatonic behaviour
          No Full resolution of symptoms
          Schizophreniform disorder Can be prodromal 1 month to 6 months At least 2 of:
          • Delusions
          • Hallucinations
          • Disorganized speech
          • Grossly disorganized or catatonic behaviour
          • Negative symptoms
            No Not required
            Schizophrenia Can be prodromal > 6 months No Required
            Schizoaffective disorder Can be prodromal Major mood episode
            + 2 weeks of isolated psychotic symptoms
            • Delusions or hallucinations for 2 or more weeks
            • Must be in absence of a major mood episode (depressive or manic) during the lifetime duration of the illness
              Required Not required
              Delusional disorder Can be prodromal > 1 month One or more delusions, with no other psychotic symptoms. No Normal function aside from impact of delusions

              Various scales can be used to measure schizophrenia symptoms in an individual. Below are the most common ones, with an indication for each.

              Psychometric Scales for Schizophrenia

              Positive and Negative Syndrome Scale (PANSS)
              Rater Clinician
              Description The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports of family members or primary care hospital workers. It is a 45-minute clinical interview.
              Download PANSS Download
              Name Rater Description Download
              Positive and Negative Syndrome Scale (PANSS) Clinician The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports of family members or primary care hospital workers. It is a 45-minute clinical interview. PANSS Download
              Dopamine Hypothesis

              One theory in the pathophysiology of schizophrenia is that an increase dopamine activity causes the positive symptoms of schizophrenia. This is similar to how methamphetamines and cocaine increases dopamine activity, which can also cause psychosis. Therefore, antipsychotics target the mesolimbic pathway to decrease the incidence of positive symptoms. Antipsychotics work by binding to dopaminergic neuroreceptors. It is important to keep in mind that this is a theoretical model, and that the pathophysiology of schizophrenia remains poorly understood.

              What Exactly is 'Schizophrenia'?

              It is important to recognize that schizophrenia itself is very likely not a single disease entity with a single cause. Rather it a heterogenous with a variety of etiologies. Each patient with a diagnosis of schizophrenia will present with a different set or cluster of symptoms. Even the DSM and ICD each have different conceptualizations of the disease. Additionally, psychosis is a syndrome and not a diagnosis. For example, in rare cases, patients initially diagnosed with schizophrenia may in fact be misdiagnosed and have anti-NMDA Receptor Encephalitis.
              Toxoplasma gondii

              Since the 1950s, there have been multiple studies showing higher levels of Toxoplasma gondii antibodies in schizophrenia and other severe psychiatric disorders.[3] Exposure to cats (which are commonly infected) in childhood is also a risk factor for the development of schizophrenia.

              Influenza

              The association between influenza infection and psychosis has been observed since the early eighteenth century.[4] Some population studies on the timing of births show that individuals born in winter/spring are at higher risk for schizophrenia compared to those born in summer/autumn, which coincides with influenza season.[5] The etiology behind influenza infections and psychosis is thought to be linked to processes such as maternal immune activation, disruption of cytokine networks, and microglial activation of pathogenic processes that lead to schizophrenia. More recent theories also focus on neuronal autoimmunity and the NMDA receptor.[6]

              Visual Input

              Interestingly, individuals with congenital blindness are protected against psychosis and schizophrenia. There has been no documented cases of psychosis or schizophrenia in individuals with congenital blindness (born blind).[7] The hypothesis behind this is that individuals who cannot see at birth rely on the context extracted from other senses. This results in a model of the world that is less susceptible to false inferences (i.e. - delusions, hallucinations).[8][9]

              Degenerative Disease Model

              Traditionally, schizophrenia has been seen as a mental disorder with progressive deterioration.[10] Indeed, the diagnostic term dementia praecox proposed by Emil Kraepelin came under the assumption that schizophrenia was a form of juvenile dementia caused by a degenerative process. Indeed, one of the driving factors behind early intervention in psychosis clinics is meant to reduce the duration of untreated psychosis (and hence degree of neurodegeneration). However, one recent paper suggests that lead-time biases in research methodology confounds the association between untreated psychosis and illness course.[11] A more recent meta-analysis also showed there is minimal evidence that untreated psychosis damages brain structures.[12] However, increasing research suggests that schizophrenia is in fact not progressive and that neuropsychological function can remain stable over time.[13][14][15] It is important to recognize that individuals with schizophrenia can achieve a stable remission of symptoms and also achieve satisfaction and happiness.[16]

              Future Research

              There is some research suggests that synaptic pruning (i.e. - global neuronal dysfunction is responsible for the development of schizophrenia.[17] Sensory prediction deficits is also another theory of why psychotic symptoms develop, and why individuals with schizotypal personalities are more likely to be able to tickle themselves, compared to the general population.[18] Other theories include the HPA axis and endocrine disruption.[19]

              Antipsychotics are considered the gold-standard of treatment. It is increasingly important to realize that schizophrenia is not a homogenous disorder, and that individuals can be subtyped based on their response to antipsychotics. In particular, there are (1) patients who are responsive to antipsychotics, (2) those that fail first-line antipsychotics are require clozapine, and (3) those who are clozapine-resistant.[20] However, before labelling patients as treatment resistant, it is important to recognize that many patients may be on sub-therapeutic levels of antipsychotics.[21] Benzodiazepines can be prescribed for short-term management of acute agitation, but should not be used as long-term pharmacotherapy as it increases all-cause mortality.[22][23] Comprehensive care for first episode psychosis can improve functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.[24]

              In Canada, aripiprazole and lurasidone are the only antipsychotics indicated for children and adolescents with schizophrenia or bipolar disorder.
              Length of Antipsychotic Treatment

              How long should patients remain on antipsychotics for schizophrenia? The general consensus is that patients with chronic schizophrenia should remain on therapy long-term. However, there is some new evidence for first-episode psychosis patients that “less is more.”[25][26][27][28] This study observed that compared with a standard maintenance treatment regimen, dose reduction or supervised discontinuation of antipsychotic medication during the early phases of FEP led to a higher relapse rate initially, but improved long-term outcomes. This study has been criticized for its unequal distribution across diagnostic groups, high attrition rate, failure to separate the dose reduction and discontinuation groups, and the fact that most patients in each arm of the study did receive medication. Other studies have suggested that up to 40% of first episode psychosis patients are able to achieve good outcomes with either low or no doses of antipsychotics.[29]

              Practically speaking, however, clinicians and researchers are still unable to discern which populations will do well with an antipsychotic taper, and those who would worsen symptomatically. More studies are needed to investigate these very important clinical questions.[30][31] Other more recent studies have shown that the risk of relapse after antipsychotic discontinuation does not decrease over time, and that antipsychotic use is associated with increased survival.[32] Long-term antipsychotic use for treating first-episode schizophrenia for the majority of patients remains a the most evidence-based practice, as the relapse rates are greater than 80% with medication-discontinuation after several years. Relapse involves hospitalization, psychosis, and significant psychosocial impact, and this needs to be weighed carefully against discontinuation of medication.