SCHIZOPHRENIA &

OTHER
PSYCHOTIC
DISORDERS

PSY 348
Introduction
• Schizophrenia is one of the most debilitating of illnesses
• Schizophrenia is typically diagnosed between 20 and 25 years of age, a time of life when many
gain independence from parents, develop relationships, and pursue education and a career (De
Lisi, 1992)
• Across cultures, estimates of the lifetime prevalence of schizophrenia range between 0.4%-1%
depending on the measurement criteria used (Arajarvi et al., 2005; Saha et al., 2005)
• Studies suggest better outcomes in developing nations (Kulhara & Chakrabarti, 2001), as well
as strong evidence for a link between migration and increased risk (Cantor-Graae & Selten,
2005)
Introduction Continued
• No single factor has been found to characterize all patients with schizophrenia, and the
etiology is complex; the consensus in the field is that:
1) Schizophrenia is a brain disease
2) Its etiology involves interactions between genetic and environmental factors
3) Multiple developmental pathways can lead to disease onset
4) Brain maturational processes play a role in the etiology
History and Phenomenology
• Descriptions of patients experiencing psychotic symptoms, similar to those of
what we now call schizophrenia, have been recorded since antiquity
• In the mid- to late- 19th century, European psychiatrists were investigating
various types of psychosis, which could comprise several different diagnoses
• At that time, the most common cause of psychosis was actually syphilis,
although researchers at that time were unaware of the link (Kohler & Johnson,
2005)
• Emil Kraepelin (1856-1926) was the first to differentiate schizophrenia, which
he referred to as dementia praecox (“dementia of the young”) from manic-
depressive psychosis (Kraepelin, 1913)
• Eugen Bleuler (1857-1939), a Swiss
psychiatrist, introduced the term schizophrenia
at the beginning of the 20th century: it is
derived from the Greek work schizo, meaning
‘to split,’ and phren, which refers to the
intellect or the mind
• Bleuler classified the symptoms of
schizophrenia into fundamental symptoms
(including disturbances of association and Conceptions and
affect, ambivalence, autism, abulia, and
dementia), and accessory symptoms (including
Classification of
delusions, hallucinations, movement
disturbances, somatic symptoms, and
Psychosis: Early
manic/melancholic states)
Conceptions
• Sigmund Freud (1856-1936) was also interested in
dementia praecox, which he saw as occurring when the
ego becomes overwhelmed by the demands of the id or
the guilt of the superego; patients with this disorder
regress to a state of primary narcissism
• In 1911, Freud analyzed the memoirs of Daniel Paul
Schreber, a German judge; Freud noted that
hallucinations reported by Schreber centered around his
physician Dr. Flechsig, then later around God; Freud
saw these as manifestations of repressed inner drives
which in his infancy had been oriented at his brother
and father
• In the 1950s and 1960s, psychologists including Kurt
Schneider and Gerd Huber provided further
refinements in the diagnostic criteria for schizophrenia
Early Conceptions
Continued
Modern Conceptions of Schizophrenia:
Positive Symptoms
• Kurt Schneider provided a list of “first rank symptoms” (also considered
positive symptoms) which were more detailed and specific than Bleuler’s
fundamental symptoms, including:
• Thought echoing or audible thoughts
• Thought broadcasting
• Though intrusion
• Thought withdrawal
• Somatic hallucinations
• Passivity feelings
• Delusional perception
Negative
Symptoms
Negative symptoms, in contrast, involve a
decrease in behavior:
• Blunted or flat affect
• Anhedonia
• Avolition
• Emotional withdrawal
• Social isolation
• Apathy
Negative
Symptoms
Continued
• Negative symptoms typically emerge several years prior
the onset of a psychotic disorder, in the prodromal phase
• Negative symptoms are associated with poor functional
outcome, are highly debilitating, and pose a substantial
burden on the families of those with schizophrenia as
well as health care systems (Milev et al., 2005)
• However, few interventions focus on the negative
symptoms, and therefore such symptoms can results in a
dramatic reduction in quality of life (Fusar-Poli et al.,
2015)
 Studies of individuals with schizophrenia have consistently

Social Processing shown them to be impaired in their ability to comprehend and

solve social problems, processing of emotions, social
perception, attribution of events, and theory of mind (Green &

Deficits Horan, 2010)

Social-cognitive imaging studies consistently show

abnormalities in brain regions associated with social processing
(Fujiwara et al., 2015)

Related to the negative symptom of blunted affect, individuals

with schizophrenia show abnormalities in the expression of
emotion in both their faces and verbal communication, and are
less accurate in their ability to label facial expressions of
emotions (Amminger et al., 2012)
Cognitive Deficits
• Neurocognitive deficits are found as early as the premorbid phase (prior to the prodromal phase
when symptoms emerge), and these deficits typically worsen over the disease course
• The NIMH defines seven cognitive domains affected in schizophrenia: processing speed,
attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem
solving, and social cognition (Neuchterlein et al., 2008)
• Patients with schizophrenia are slower in the initial processing of visual stimuli compared to
healthy controls, and tend not to be susceptible to certain optical illusions (such as perceiving
2-D objects as 3-D) (Keane et al., 2013)
• Some evidence that nicotine is beneficial to such cognitive impairments (Gee et al., 2017)
Current
Approaches to
Classification:
DSM-5
Criteria
Current Approaches Continued
• The DSM-5 also includes attenuated psychosis syndrome (APS), which identifies individuals who
do not meet full criteria for schizophrenia, but exhibit less intense symptoms with intact reality
testing
• Schizotypal personality disorder (SPD): also included in the personality disorders; involves social
anxiety or withdrawal, affective abnormalities, eccentric behavior, unusual ideas (e.g., belief in
ESP or aliens), and unusual sensory experiences; the genetic link between SPD and schizophrenia
has been demonstrated by twin and family history studies (Barantes-Vidal Grant & Kwapil, 2005)
• Schizophreniform disorder: individuals whose symptoms do not meet the six-month criterion;
frequently made as a prelude to the diagnosis of schizophrenia, but many recover completely
Origins of Kraepelin and Bleuler suggested that there may be a biological
cause for at least some cases of schizophrenia; studies have
found that the risk of schizophrenia is elevated in individuals
Schizophrenia: who have a biological relative with the disorder (Hilker et al.,
2018)

Genetics Among monozygotic twins of those with schizophrenia (who

share 100% of their genes), 25-50% will develop the disorder,
while about 10-15% of dizygotic twins of schizophrenics are
diagnosed with the illness (Sullivan et al., 2003)

Genetic studies indicate that the disorder involves multiple

genes rather than a single gene (Gottesman, 1991)
Origins of • Dopamine appears to be implicated in schizophrenia:
Schizophrenia: antipsychotic drugs work by blocking dopamine receptors,
especially the D2 subtype that is found in subcortical regions of
Neurotransmitter the brain

Alterations • Motor abnormalities observed in Parkinson’s disease are

related to low levels of dopamine; dopamine agonists can
induce psychotic symptoms (Hinkle et al., 2018)
• A pattern of hyperdopaminergic activity in subcortical areas of
the brain and hypodopaminergic activity in the prefrontal
cortex has been described in the research literature (Howes &
Kapur, 2009)
• There is also evidence of diminished glutamate activity in
schizophrenics, especially in the hippocampus, prefrontal
cortex, and thalamus
Origins of Schizophrenia: Abnormalities in
Brain Structure
• MRI studies have found decreased frontal, temporal, and whole brain volume among those with
schizophrenia (Lawrie & Abukmeil, 1998)
• Diffusion tensor imaging (DTI) studies have found deficient white matter, especially in the frontal-
temporal areas of the brain (Ellison-Wright & Bullmore, 2009), which may be related to the negative
symptoms of schizophrenia
• Longitudinal studies of high-risk individuals suggest a developmental pattern of decline in grey
matter in the frontal, temporal, insular, and parietal regions of the brain (Bartholomeusz et al., 2017)
• However, no specific abnormalities have been found to be completely unique to schizophrenia, or to
characterize all schizophrenia patients
Onset, Course, and
Prognosis: Prenatal
and Perinatal Factors • Patients with schizophrenia are more likely to have a
history of exposure to obstetric complications (Brown &
Derkits, 2010)
• Complications of pregnancy (bleeding, preeclampsia,
diabetes, and rhesus factor incompatibility) were most
strongly linked with later schizophrenia, followed by
abnormal fetal growth and development, and complications
of delivery (Cannon et al., 2002)
• A study found that prenatal maternal exposure to a wide
range of infections was associated with a 1.16-fold increase
in schizophrenia risk (Nielsen et al., 2016)
Prenatal and • Prenatal maternal stress can interfere with fetal brain
Perinatal Factors developmental and is associated with elevated
glucocorticoid risk and hippocampal abnormalities in
Continued offspring (Charil et al., 2010)
• Schizophrenia has been linked with various maternal
stressors during pregnancy, including bereavement, famine,
military invasion, exposure to terror attacks, floods,
earthquakes, and even daily life stressors
• Prenatal stress may trigger the release of maternal stressor
hormones, which disturb fetal neurodevelopment and
subsequent functioning of the hypothalamic-pituitary-
adrenal (HPA) axis, which influences behavior and
cognition
Premorbid Development
• Although schizophrenia is typically diagnosed in late adolescence/early
adulthood, children who go on to develop this disorder tend to perform lower in
cognitive functioning than their healthy siblings and classmates as evidenced by
poorer grades and lower childhood IQ (Aylward et al., 1984)
• Children who go on to develop schizophrenia are less responsive in social
situations, show less positive emotion, and have poorer social adjustment than
children with healthy adult outcomes (Done et al., 1994)
• Studies of childhood home movies found that children who develop
schizophrenia later in life showed more negative facial expression of emotion
than did their siblings as early as the first year of life (Walker et al., 1993)
Illness Onset
• Research supports a diathesis-stress model, meaning that a constitutional vulnerability
(diathesis) is influenced by external stressors
• Research suggests that episodes of schizophrenia follow periods of increased life stress
(Horan et al., 2005), although there is no evidence that those affected by schizophrenia
experience more stressful events than others
• Schizophrenia is associated with heightened HPA axis activity, which appears to be
reduced by antipsychotic medications
• Heavy, consistent cannabis use is associated with a threefold increase in schizophrenia risk,
earlier onset, and exacerbation of psychotic symptoms (Helle et al., 2016)
• Early intervention appears to be important: duration of untreated psychosis is a predictor of
outcome (Hill et al., 2012)
Prognosis
• Factors associated with a poorer prognosis for schizophrenia include being male, having a
gradual onset, an early age of onset, poor premorbid functioning, and a family history of
schizophrenia (Gottesman, 1991)
• Around 20% of individuals with schizophrenia may become homeless within the first year
of diagnosis (Folsom et al., 2005)
• Within the first five years of diagnosis, 13.7% achieve full symptom remission with
adequate functioning, and within 25 years, around 30% achieve a favorable long-term
outcome
• As many as 50% of all patients with schizophrenia meet criteria for substance use

• Suicide is the leading cause of death for those with schizophrenia; it is estimated that 50%
of patients attempt suicide and 4-5% successfully complete (Donker et al., 2013)
Evidence-Based
Interventions
• The first issue addressed is usually safety, due to the risk of self-
harm and potential for violence (McGirr et al., 2006)
• The treatment is divided into 3 phases (acute, stabilization, and
maintenance)
Acute phase (4-8 weeks): Goal is to reduce symptom severity
Stabilization phase (~6 months): Goal is to consolidate treatment
gains
Maintenance phase: Goal is to prevent relapse and improve
functioning
• One major challenge during maintenance phase is preventing
treatment discontinuation
Biological/Pharmacological Interventions
• The main pharmacological treatment for schizophrenia is
antipsychotic medication
• Typical antipsychotics (or neuroleptics), developed in the 1950s,
block dopamine activity, and tend to carry a high risk of
extrapyramidal effects (e..g motor abnormalities)
• Atypical (or second-generation) antipsychotics, developed in the
1990s, share a lower risk of movement disorders; all block
dopamine neurotransmission, but vary to the extent in which they
affect serotonin, glutamate, and other neurotransmitters
Psychosocial Treatments of Schizophrenia
• Research supports that use of family therapy, which includes
psychoeducation about symptoms, diagnosis, and prognosis, along with
modules focused on communication and problem-solving skills
• Assertive community training (ACT): a comprehensive treatment approach
for the seriously mentally ill living in the community; involves the use of a
multidisciplinary team who are available to the patient at all times
• CBT for schizophrenia: symptoms such as hallucinations, delusions, and
related problems are target for intervention by means of cognitive
restructuring; findings are mixed
Treatment for
Psychosis-Risk
Populations
• Antipsychotic medications as a pre-psychotic
intervention may delay the onset of psychosis, but there
is no indication that psychosis can be prevented (de
Koning et al., 2009)
• Fewer RCTs evaluating psychosocial treatments for
prodromal populations; research is underway to
examine whether family focused treatment may help to
delay or prevent the onset of psychosis (Schlosser et
al., 2012)
Cognitive Remediation and Other
Promising Interventions
• Cognitive remediation therapy: takes the form of computerized tasks aimed at enhancing
specific cognitive skills (e.g., attention, working memory, or planning)
• Evidence that cognitive remediation may allow for acquisition of new skills and improved
functioning when combined with other empirically supported interventions (Mueser et al.,
2013)
• One RCT found less conversion to psychosis in individuals who received treatment with
omega-3 fatty acids
• Exercise is also being investigated as an intervention, owing to research linking aerobic
activity with the reversal of brain abnormalities commonly seen in schizophrenia (i.e.,
increases in hippocampal grey matter following exercise)
 Concepts of schizophrenia have changed since its
Conclusion early identification in the 20th century to our current
understanding

No single cause has been identified, but there are

underlying genetic, neurodevelopmental, and
neurobiological abnormalities associated with risk

Future research may help to elucidate the interaction

between congenital vulnerability and subsequent life
stress, which can help to inform the next generation of
psychosocial and pharmacological preventative
interactions