• = A disorder characterized by disordered thinking, in which ideas are not logically related; faulty perceptions and attention; a lack of emotional expressiveness; and disturbances in behaviour, such as a disheveled appearance
  • Withdraw from other people and everyday reality, experience delusions and hallucinations
  • Substance use rates are high, suicide rates are high *12x more likely to die of suicide
  • Mortality rates are as high, or higher than people who smoke
  • 1% life prevalence, affects men more than women
  • Diagnosed more frequently among some groups: African Americans *may reflect diagnostic bias
  • Sometimes begins in childhood, usually appears in late adolescence/early adulthood *earlier in men than women o Late onset (30s) = more severe
  • 3 domains of symptoms: positive, negative, and disorganization DSM-5 Criteria:
  • 1) Two or more of the following symptoms for at least 1 month: one symptom should be either 1, 2, or 3 o Delusions, 2. Hallucinations, 3. Disorganized speech, 4. Disorganized/catatonic behaviour,
  1. Negative symptoms (diminished motivation or emotional expression)
  • 2) Functioning in work, relationships of self-care has declined since onset
  • 3) Signs of disorder for at least 6 months; o Or, if during a prodromal or residual phase, negative symptoms or 2+ symptoms 1-4 in less severe form Positive Symptoms
  • = Comprise excesses and distortions, and include hallucinations and delusions
  • Acute episodes are characterized by positive symptoms  Delusions:

o = Beliefs contrary to reality and firmly held in spite of disconfirming evidence o Precursory delusions (“CIA planted a listening device in my head”)  *found in 65% o Forms:

  • Thought insertion = belief that thoughts that are not his/her own have been placed in his/her mind by an external source
  • Thought broadcasting = belief that thoughts are broadcasted or transmitted, so that others know what one is thinking
  • Belief that an external force controls one’s feelings or behaviours

 

  • Grandiose delusions = an exaggerated sense of one’s own importance, power, knowledge or identity
  • Ideas of reference = incorporating unimportant events within a delusional framework and reading personal significance into the trivial activities of others  Hallucinations and other disturbances of perception:

o Hallucinations = sensory experiences in the absence of any relevant stimulation from the environment

 Most dramatic distortions of perception o More often auditory than visual (74% have auditory hallucinations) o Hear one’s own thoughts spoken by another voice o Hear voices arguing or commenting on one’s behaviour *increased activity in Broca’s area o Hallucinations believed to come from a known person are experienced more positively o Possible explanation: misattribute their own voice as someone else’s

o Greater activity in Broca’s area (frontal cortex) during auditory hallucinations *supports ability to produce speech

 And in Wernicke’s area (temporal cortex) *supports ability to understand speech **hearing voices Negative Symptoms

  • = Consist of behavioural deficits in motivation, pleasure, social closeness, and emotion expression
  • Tend to endure beyond an acute episode
  • Have profound effects on the lives of people with schizophrenia
  • Presence of negative symptoms is a strong predictor of a poor quality of life
  • Represent 2 domains: 1) experience: motivation, emotion, sociality & pleasure, 2) expression (outward expression of emotion)
  • Avolition = A lack of motivation and a seeming absence of interest in or an inability to persist in what are usually routine activities, including work or school, hobbies, or social activities o Spend much of their lifetime sitting around doing nothing o Less motivated by goals about autonomy, gaining new knowledge or skills, or praise by others o Equally motivated by goals that have to do with relatedness to others and with avoiding a negative outcome
  • Asociality = Severe impairments in social relationships o Few friends, poor social skills, very little interest in being with other people o May not desire close relationships with family/friends/romantic partners
  • Anhedonia = A loss of interest in or a reported lessening of the experience of pleasure o Consummatory pleasure = the amount of pleasure experienced in the moment or in the presence of something pleasurable
    • Anticipatory pleasure = the amount of expected or anticipated pleasure from future events or activities
    • Deficit in anticipatory pleasure, not in consummatory
  • Blunted affect = A lack of outward expression of emotion o Stare vacantly, face muscles motionless, eyes lifeless, toneless voice o Found in 66%

o Only refers to outward expression of emotion, not to inner experience (not impoverished)

  • Alogia = A significant reduction in the amount of speech o Do not talk much

Disorganized Symptoms

  • Include disorganized speech and disorganized behaviour

Disorganized Speech (formal thought disorder)

  • Disorganized speech = problems in organizing ideas and in speaking so that a listener can understand o Incoherence = inability to organize ideas
  • Loose associations/derailment = the person may be more successful in communicating with a listener but has difficulty sticking to one topic
  • Disorganized speech is associated with problems in executive functioning: problem solving, planning, and making associations between thinking and feeling
  • Also related to the ability to perceive semantic information

Disorganized Behaviour

  • Disorganized behaviour = may go into inexplicable bouts of agitation, dress in unusual clothing, act in a silly manner, hoard food, or collect garbage
  • Lose the ability to organize behaviour and make it conform to community standard  Difficulty performing tasks of everyday living

Movement Symptoms

  • Catatonia = gesture repeatedly, using peculiar and sometimes complex sequences of finger, hand, and arm movements, which often seem to be purposeful *excitable flailing of the limbs o Seldom seen today

o Similarity with encephalitis lethargica

  • Unusual increase in overall activity, much excitement, flailing of the limbs, great expenditure of energy similar to mania
  • (Catatonic) Immobility = adopt unusual postures and maintain them for very long periods of time  Waxy flexibility = limbs can be manipulated & posed by another person

Schizophrenia and the DSM-5

  • Symptoms must last at least 6 months, must include 1 month of an acute episode, or active phase = presence of at least 2 symptoms: delusions, hallucinations, disorganized speech, disorganized behaviour, and negative symptoms
  • Remaining time for diagnosis can occur before or after active phase
  • Removal of subtypes of schizophrenia (paranoid, disorganized, catatonic, undifferentiated) *poor reliability, questionable usefulness, poor predictive validity
  • Addition of severity ratings for each of the 5 symptoms
  • Part of category: Schizophrenia spectrum and other psychotic disorders o Schizophreniform disorder = same symptoms of schizophrenia, last only 1-6 months
    • Must include hallucinations, delusions, or disorganized speech o Brief psychotic disorder = lasts from 1 day to 1 month, often brought on by extreme stress
    • Symptoms MUST include hallucinations, delusions, or disorganized speech o Schizoaffective disorder = comprised of a mixture of symptoms of schizophrenia and mood disorders
    • Either depressive or manic episode required (mood symptoms present for majority of duration)

o Delusional disorder = troubled by delusions (persecution/jealousy, grandiose, erotomania, somatic delusions)

  • New category to “Conditions for Further Study”  attenuated psychosis syndrome Etiology

Genetic Factors

  • Genetically heterogeneous  genetic factors may vary from case to case, not likely caused by 1 gene
  • People with schizophrenia in their family histories have more negative symptoms that no family history o Negative symptoms may have stronger genetic component
  • Incidence of schizophrenia highest if both biological parents were diagnosed (27.3%), (7% if one parent)
  • Risk for MZ twins is 44.3%, 12,08% for DZ
  • Even with adopted children whose biological parent had schizophrenia, there is still a heightened risk for developing
  • Familial high-risk study = begins with 1 or 2 biological parents with schizophrenia, follow their offspring longitudinally to identify how many develop schizophrenia
  • 6x more likely to develop by age 40 if have a parent with schizophrenia
  • Predisposition is not transmitted by a single gene
  • Multiple common genes associated with schizophrenia and bipolar
  • 1) DTNBP1 & NGR1 – associated w/schizophrenia, 2) COMT & BDNF – associated w/cognitive deficits associated w/schizophrenia o DTNBP1 codes for a protein ‘dysbindin’ – impacts dopamine and glutamate NTM systems o COMT associated with cognitive control processes relying on the prefrontal cortex o BDNF – linked to cognitive functioning in people with and without schizophrenia

(polymorphism Val66Met) o ***These genes do not appear in GWAS

  • SNPs associated with schizophrenia are also associated with bipolar disorder
  • Genome-wide scans: identification of several gene mutations

The Role of Neurotransmitters  Dopamine theory:

  • Drugs effective in treating schizophrenia reduce dopamine activity (antipsychotic drugs) o Side effects resembling symptoms of Parkinson’s disease *caused by low dopamine in particular area of brain
  • Antipsychotic drugs block postsynaptic dopamine receptor D2, in the mesolimbic pathway o Amphetamines amplify dopamine activity, can produce state closely resembling schizophrenia
  • Only related to positive and disorganized symptoms of schizophrenia
  • Dopamine neurons in prefrontal cortex (mesocortical pathway) may be underactive & fail to inhibit dopamine neurons in subcortical brain areas **negative symptoms

 Antipsychotics do not have major effect on dopamine neurons in prefrontal cortex o Take several weeks for antipsychotics to lessen positive symptoms, although receptors are rapidly blocked

o To be effective, must reduce DA to below normal levels

  • New drugs related to serotonin, block D2 receptors, also block serotonin receptor 5HT2
  • GABA transmission in prefrontal cortex is disrupted in those with schizophrenia
  • Glutamate may also play a role *low levels in cerebrospinal fluid ***medication targeting glutamate shows promise o Also low levels of enzyme needed to produce glutamate
  • Elevated AA homocysteine – interacts with NMDA receptor in pregnant women whose child develops schizophrenia
  • PCP drug can induce positive and negative symptoms in people without schizophrenia

 

Brain Structure & Function  Enlarged ventricles: o 4 ventricles (spaces filled with cerebrospinal fluid) o Larger ventricles implies a loss of brain cells o Origin of enlarged ventricles may not be genetic

  • Correlated with impaired performance on neuropsychological tests, poor functioning prior to the onset of the disorder and poor response to medication treatment
  • Not specific to schizophrenia (bipolar, other psychotic features)  Prefrontal cortex:
  • Plays a role in speech, decision making, emotion and goal directed behaviour **all disrupted in schizophrenia
  • Reduction in grey matter and volume of prefrontal cortex = reduced connectivity o Perform more poorly on neuropsychological tests on working memory
    • Some declines occur before onset (late 30s) o Lower glucose metabolism in prefrontal cortex when performing neuropsychological tests

(PET scan) o Less blood flow to these areas during fMRI o Failure to show frontal activation related to severity of negative symptoms o Loss of dendritic spines, not loss of neurons *disrupts neuron communication = disconnection syndrome

  • Could lead to behavioural and speech disorganization symptoms  Temporal cortex:
  • Abnormalities in temporal gyrus, hippocampus, amygdala, anterior cingulate
  • Reduction in cortical grey matter, reduced volume in basal ganglia, hippocampus and limbic structures
  • Reduced hippocampus volume may reflected combination of genetic and environmental factors
    • Closely relates to HPA axis and chronic stress (reduction in volume)
    • More reactive to stress in schizophrenia, rather than experiencing more Connectivity in the Brain  3 types of connectivity:

o Structural/anatomical connectivity = how different structures of the brain are connected via white matter

  • Less white matter connectivity in schizophrenia in frontal and temporal lobes o Functional connectivity = connectivity between brain regions based on correlations between blood oxygen level dependent signal measured with fMRI
  • Particularly reduced connectivity in frontal cortex o Effective connectivity = combines both types of connectivity, shows correlations between

BOLD activations in different regions and the direction & timing of activations

  • Less connectivity in between brain networks, including frontoparietal and default-mode networks o Correlated with poor performance on cognitive tests

o Might be part of genetic diathesis

Environmental Factors Influencing the Developing Brain

  • Possible damage during gestation
  • High rates of delivery complications in those with schizophrenia o Reduced oxygen supply to brain, resulting in loss of cortical grey matter Maternal infections during pregnancy
  • Exposure to prenatal influenza (especially in 2nd trimester)
  • Stress linked to release of cortisol, cortisol related to increased dopamine activity in mesolimbic pathway
  • Development of symptoms in adolescence related to loss of synapses due to excessive pruning
  • Cannabis use in adolescence studied as a risk factor *associated with worsening of symptoms among those diagnosed o Greater risk of developing symptoms with cannabis use

Psychological Factors

  • Very reactive to stressors  Socioeconomic Status:
    • Found at all levels of SES o Highest rates in lowest SES group
    • Sociogenic hypothesis = stress associated with poverty such as low education, limited opportunities and stigma from others of high status contributes to development of schizophrenia
    • Social selection hypothesis = during the course of developing illness, people with schizophrenia drift into poor neighborhoods because their illness impairs their earning power, cannot afford to live elsewhere **research supports  Family-Related Factors:
    • Mother-son relationship (schizophrenogenic mother)
    • Vague communication between family members, high levels of family conflict o Expression of hostility towards schizophrenic family member
      • Critical comments, hostility, emotional overinvolevment = expression emotion (EE)
      • Linked to relapse rates o Negative symptoms most likely to elicit critical comments

o Expression of unusual thoughts by schizophrenia linked to higher critical comments, and higher critical comments lead to increased unusual thoughts *bidirectional

Developmental Factors

  • Retrospective studies = begin with a group of adults with schizophrenia (or other diagnosis) and follow back to childhood to unearth records and tests from their early years o Lower IQs as children, more often delinquent and withdrawn o Boys rated by teachers as disagreeable, girls as passive
    • Poorer motor skills, more expression of negative emotions as children *coding home videos  Prospective studies:
    • Look at identifying childhood characteristics associated with development of schizophrenia in early adulthood
    • Lower IQ scores as children predicted onset of schizophrenia in young adulthood (beginning at age 7)
    • Clinical high-risk study = identifies people with early, attenuated signs of schizophrenia, most often milder forms of hallucinations, delusions, or disorganization that causes impairment

Treatment

  • Most often includes combination of short-term hospitalization, medication and psychosocial treatment
  • Some schizophrenics lack insight into their impairments and refuse any treatment
  • Gender (female) and age (older) are predictors of better insight during first episode of illness Medications
  • Antipsychotic drugs = used to treat symptoms of schizophrenia (aka neuroleptics  produce side effects similar to symptoms of a neurological disease)  First generation antipsychotics:
    • Reduce positive and disorganized symptoms (also reduce agitation & violent behaviour), little or not effect on negative symptoms
    • Block dopamine D2 receptors
    • 30% do not respond favourably to first generation, 50% quit after 1 year, 75% quit before 2 years because of side effects
    • Side effects: sedation, dizziness, blurred vision, restlessness, sexual dysfunction, dystonia

(rigidity), dyskinesia (abnormal muscle motion), akasthesia (inability to remain still)  o Extrapyramidal side effects = resemble the symptoms of Parkinson’s disease (tremors, shuffle, drooling)

  • Tardive dyskinesia = mouth muscles involuntarily make sucking, lip-smacking and chinwagging motions

 Mainly in older people with schizophrenia who had been treated with 1st generation drugs

  • Neuroleptic malignant syndrome = (1% of cases) sometimes fatal, severe muscular rigidity develops, accompanied by fever  Second generation antipsychotics:
  • Approval of clozapine – therapeutic gains in those who didn’t respond well to 1st generation medication, produce fewer side effects, less relapse and treatment noncompliance *impacts serotonin receptors

 Side effects: impair immune system functioning, agranulocytosis (lower amount of

WBC), seizures, dizziness, fatigue, drooling, weight gain *fewer motor side effects

  • Olanzapine and risperidone – produce fewer side effects
  • Equally as effective in reducing positive and disorganized symptoms, slightly more effective in reducing negative symptoms and improving cognitive deficits
  • Less treatment noncompliance o No differences in relapse *reduces relapse? o Can also produce extrapyramidal side effects o Less often given to African-Americans
  • Medical review: 2nd generation not more effective, did not produce fewer unpleasant side effects, nearly ¾ stopped taking before study ended o Can lead to serious side effects: pancreatitis, weight gain, diabetes

Psychological Treatments

  • Psychosocial treatments are recommended alongside medication (Patient Outcome Research Team

“PORT” recommendation) o Skills training, CBT, family-based treatment

  • Social skills training = designed to teach people with schizophrenia how to successfully manage a wide variety of interpersonal situations o (Discussing medications with psychiatrist, ordering meals in a restaurant, filling out a job application, saying no to drug dealers, reading bus schedules)
    • Involves role-playing and other group exercises the practice skills (in therapy and real social situations)
    • Help achieve fewer relapses, better social functioning, higher quality of life o May also be effective in reducing negative symptoms Family therapies:
    • Developed to try and decrease expressed emotion within the family (hostility, critical comments and emotionally overinvolved)
    • 1) Education about schizophrenia – about genetic/neurobiological factors, cognitive problems associated, symptoms, and signs of relapse
    • 2) Information about antipsychotic medication – importance of taking, effects and side effects
    • 3) Blame avoidance and reduction – encourage family members not to blame themselves of their ill relative
    • 4) Communication and problem-solving skills – express feelings in constructive, empathic, nondemanding manner
    • 5) Social network expansion – encouraged to expand social contacts o 6) Hope – hope for improvement, not to return to hospital
  • CBT:
    • Encouraged to test out delusional beliefs
    • Helped to attach nonpsychotic meaning to paranoid symptoms to reduce intensity and aversive nature
    • Helps reduce negative symptoms *recognize & challenge expectations associated w/negative symptoms
  • Cognitive Remediation Therapies:
    • Improvement in basic cognitive processes hold promise for improving social and emotional lives of schizophrenics
    • Try to normalize attention and memory
    • Cognitive remediation training/cognitive enhancement therapy (CET) = seek to enhance basic cognitive functions such as verbal learning ability

 Effective in reducing symptoms and improving cognitive abilities, linked to good functional outcomes

  • Can include computer-based training in memory, problem solving and attention o Enriched supportive therapy (EST) = includes supportive and educational elements  Psychoeducation:
  • Educate patients about their illness, symptoms, time course, triggers, treatment strategies o Reduces relapse and rehospitalization
  • Case Management:
    • Case managers – familiar with the mental health system, able to connect people with schizophrenia to whatever services they required
    • Often provided direct clinical services
    • Multidisciplinary team that provides services in the community (medication, treatment for substance abuse, help in dealing with stressors, psychotherapy, vocational training, assistance in obtaining housing and employment
    • Has not shown improvement in social functioning  Residential Treatment:
    • “Halfway houses” – alternative for those who do not need to be in the hospital but are not well enough to live on their own or with family
    • Protected living units
    • Vocational rehabilitation – learn skills to help secure employment and return to the community
    • Staff may include psychiatrists/clinical psychologists o Often include group meetings