Module 2: Schizophrenia and

Other Psychotic Disorders.

Schizophrenia occurs in people from all cultures and from all walks of life. The disorder is
characterized by an array of diverse symptoms, including extreme oddities in perception,
thinking, action, sense of self, and manner of relating to others. However, the hallmark of
schizophrenia is a significant loss of contact with reality, referred to as psychosis. Although
the clinical presentation of schizophrenia differs from one patient to another. The internal
suffering of the person with schizophrenia is often readily apparent, as are bizarre behaviour
and unusual appearance.

Origins of the Schizophrenia Construct

The first detailed clinical description of what we now recognize to be schizophrenia was
offered in 1810 by John Haslam, the apothecary at the Bethlem Hospital in London,
England. Haslam described the case of a patient who appears to have suffered from a variety
of symptoms— including delusions—that are typical of schizophrenia. Fifty years later, the
Belgian psychiatrist Benedict Morel described the case of a 13-year-old boy who had
formerly been the most brilliant pupil in his school but who gradually lost interest in his
studies; became increasingly withdrawn, lethargic, reclusive, and quiet; and appeared to have
forgotten everything he had learned. Morel thought the boy’s intellectual, moral, and
physical functions had deteriorated as a result of brain degeneration of hereditary origin. He
used the term démence précoce (mental deterioration at an early age) to describe the
condition and to distinguish it from the dementing disorders associated with old age.

It is the German psychiatrist Emil Kraepelin , who is best known for his careful description
of what we now regard as schizophrenia. Kraepelin used the Latin version
of Morel’s term (dementia praecox) to refer to a group of conditions that all seemed to
feature mental deterioration beginning early in life. Kraepelin, an astute observer of
clinical phenomena, described the patient with dementia praecox as someone who “becomes
suspicious of those around him, sees poison in his food, is pursued by the police, feels his
body is being influenced, or thinks that he is going to be shot or that the neighbours are
jeering at him”. Kraepelin also noted that the disorder was characterized by hallucinations,
apathy and indifference, withdrawn behavior, and an incapacity for regular work.

It was a Swiss psychiatrist named Eugen Bleuler who gave us the diagnostic term we still
use today. In 1911, Bleuler used schizophrenia (from the Greek roots of sxizo, pronounced
“schizo” and meaning “to split or crack,” and phren, meaning “mind”) because he believed
the condition was characterized primarily by disorganization of thought processes, a lack of
coherence between thought and emotion, and an inward orientation away (split off) from
reality. Although the term is often thought to reflect a “Jekyll and Hyde” split personality,
this is a major misconception. The splitting does not refer to multiple personalities (an
entirely different form of disorder, now called dissociative identity disorder). Instead, in
schizophrenia there is a split within the intellect, between the intellect and emotion, and
between the intellect and external reality. Interestingly, the subtitle of Bleuler’s
monograph was “The Group of Schizophrenias,” indicating that he believed this disorder
was not a single diagnostic entity.

Epidemiology

The risk of developing schizophrenia over the course of one’s lifetime is a little under 1
percent—actually around 0.7 percent. What this means is that approximately 1 out of every
140 people alive today who survive until at least age 55 will develop the disorder. Of
course, a statistic like this does not mean that everyone has exactly the same risk. This is an
average lifetime risk estimate. Some people (e.g., those who have a parent with
schizophrenia) have a statistically higher risk of developing the disorder than do others (e.g.,
people who come from families where there has never been a case of schizophrenia).
There are also other groups of people who seem to have an especially high risk of developing
schizophrenia. For example, people whose fathers were older (50 years or more) at the time
of their birth have an elevated risk of developing schizophrenia when they grow up. Having a
parent who works as a dry cleaner is also a risk factor.

Rates of schizophrenia are also higher than expected in first- and second generation
immigrants, particularly those from black Caribbean and black African countries who live in
majority white communities. Although the reasons for these differences are not well
understood, they are of great interest to researchers. The vast majority of cases of
schizophrenia begin in late adolescence and early adulthood, with 18 to 30 years of age being
the peak time for the onset of the illness. Although schizophrenia is sometimes found in
children, such cases are rare. Schizophrenia can also have its initial onset in middle age or
later, but again, this is not typical. The characteristic age of onset of schizophrenia differs in
men and women. In men, there is a peak in new cases of schizophrenia between ages 20 and
24. The incidence of schizophrenia in women peaks during the same age period, but the peak
is less marked than it is for men. After about age 35, the number of men developing
schizophrenia falls markedly, whereas the number of women developing schizophrenia does
not. Instead, there is a second rise in new cases that begins around age 40, as well as a third
spike in onset that occurs when women are in their early sixties.

In addition to being more likely to have an early age of onset, males also tend to have a more
severe form of schizophrenia. Brain-imaging studies show that schizophrenia-related
anomalies of brain structure are more severe in male patients than they are in female patients.
Gender-related differences in illness severity may also explain why schizophrenia is
more common in males than it is in females. The male-to female ratio is 1.4:1. So for every
three men who develop the disorder, only two women do so. If women have a less severe
form of schizophrenia, and if they also have more symptoms of depression, they may either
not be diagnosed at all or else be diagnosed with other disorders, thus giving rise to the sex
ratio imbalance. One possibility is that female sex hormones play some protective role. When
estrogen levels are low (as is true premenstrually) or are falling, psychotic symptoms in
women with schizophrenia often get worse. The protective effect of estrogen may therefore
help explain both the delayed onset of schizophrenia and the more favorable clinical course
of the disorder in females. Declining levels of estrogen around menopause might also explain
why late-onset schizophrenia is much more likely to strike women than men. There is some
evidence that this late-onset pattern in women is associated with a more severe clinical
presentation.

Clinical Picture
Diagnostic criteria are not fixed and immutable but instead change subtly over time as new
research findings become available. One change that occurred with DSM-5 was the
Elimination of the requirement that only one other symptom had to be present if delusions
were bizarre or if the auditory hallucinations were of a certain type. In isolation, however,
lists of symptoms convey little about the clinical essence of schizophrenia.

Delusions

A delusion is essentially an erroneous belief that is fixed and firmly held despite clear
contradictory evidence. The word delusion comes from the Latin verb ludere, which means
“to play.” In essence, tricks are played on the mind. People with delusions believe things that
others who share their social, religious, and cultural backgrounds do not believe. A delusion
therefore involves a disturbance in the content of thought. Not all people who have delusions
suffer from schizophrenia. However, delusions are common in schizophrenia, occurring in
more than 90 percent of patients at some time during their illness. In schizophrenia, certain
types of delusions or false beliefs are quite characteristic.

Prominent among these are beliefs that one’s thoughts, feelings, or actions are being
controlled by external agents (made feelings or impulses), that one’s private thoughts are
being broadcast indiscriminately to others (thought broadcasting), that thoughts are being
inserted into one’s brain by some external agency (thought insertion), or that some external
agency has robbed one of one’s thoughts (thought withdrawal). Also common are delusions
of reference, where some neutral environmental event (such as a television program or a song
on the radio) is believed to have special and personal meaning intended only for the person.
Other strange propositions, including delusions of bodily changes (e.g., bowels do not work)
or removal of organs, are also not uncommon. Sometimes delusions are not just isolated
beliefs. Instead they become elaborated into a complex delusional system.

Hallucinations

A hallucination is a sensory experience that seems real to the person having it, but occurs in
the absence of any external perceptual stimulus. This is quite different from an illusion,
which is a misperception of a stimulus that actually exists. The word comes from the Latin
verb hallucinere or allucinere, meaning to “wander in mind” or “idle talk.” Hallucinations
can occur in any sensory modality (auditory, visual, olfactory, tactile, or gustatory). However,
auditory hallucinations (e.g., hearing voices) are by far the most common. In a sample
recruited from seven different countries, auditory hallucinations were found in 75 percent of
patients with schizophrenia. In contrast, visual hallucinations were reported less frequently
(39 percent of patients), and olfactory, tactile, and gustatory hallucinations were even more
rare (1–7 percent). Even deaf people who are diagnosed with schizophrenia sometimes
report auditory hallucinations . As the World Around Us box illustrates, hallucinations can
even be induced in healthy people if they are under a lot of stress and drink a lot of caffeine.

Hallucinations often have relevance for the patient at some affective, conceptual, or
behavioral level. Patients can become emotionally involved in their hallucinations, often
incorporating them into their delusions. In some cases, patients may even act on their
hallucinations and do what the voices tell them to do. People who consider themselves
to be socially inferior tend to perceive the voices they hear as being more powerful than they
are and to behave accordingly. In a highly informative study of the phenomenology
of auditory hallucinations, Nayani and David (1996) interviewed 100 hallucinating patients
and asked them a series of questions about their hallucinatory voices. The majority of patients
(73 percent) reported that their voices usually spoke at a normal conversational volume.
Hallucinated voices were often those of people known to the patient in real life, although
sometimes unfamiliar voices or the voices of God or the Devil were heard.

Most patients reported that they heard more than one voice and that their hallucinations were
worse when they were alone. Most commonly, the hallucinated voices uttered rude and
vulgar expletives or else were critical (“You are stupid”), bossy (“Get the milk”), or abusive
(“Ugly bitch”), although some voices were pleasant and supportive (“My darling”).
Neuroimaging studies that compare hallucinating patients with non-hallucinating patients
suggest that patients with speech hallucinations have a reduction in brain (gray matter)
volume in the left hemisphere auditory and speech perception areas. Reduced brain volume in
these areas could lead to a failure to correctly identify internally generated speech,
erroneously tagging it as coming from an external source.

PET and fMRI studies that have looked at activity in the brains of patients when they are
actually experiencing auditory hallucinations provide further support for this idea. Rather
than showing an increase of activity in areas of the brain involved in speech comprehension
(e.g., Wernicke’s area in the temporal lobe), neuroimaging studies reveal that hallucinating
patients show increased activity in Broca’s area—an area of the temporal lobe that is
involved in speech production. In some cases, the pattern of brain activation that occurs when
patients experience auditory hallucinations is very similar to that seen when healthy
volunteers are asked to imagine that there is another person talking to them.

Indeed, if transcranial magnetic stimulation (in which a magnetic field passing through the
skull temporarily disrupts activity in underlying brain areas) is used to reduce activity in
speech production areas, hallucinating patients actually show a reduction in their auditory
hallucination. Such an approach could possibly have promise for the future as a novel form of
treatment. Overall, however, the research findings suggest that auditory hallucinations occur
when patients misinterpret their own self-generated and verbally mediated thoughts (inner
speech or self-talk) as coming from another source. Modern research approaches are thus
supporting a very old idea: Auditory hallucinations are really a form of misperceived
subvocal speech.

Disorganized Speech

Delusions reflect a disorder of thought content, or in the ideas being expressed. Disorganized
speech, on the other hand, is the external manifestation of a disorder in thought form.
Basically, an affected person fails to make sense, despite seeming to using language in a
conventional way and following the semantic and syntactic rules governing verbal
communication. The failure is not attributable to low intelligence, poor education, or cultural
deprivation. Years ago, Meehl (1962) aptly referred to the process as one of “cognitive
slippage”; others have referred to it as “derailment” or “loosening” of associations or, in its
most extreme form, as “incoherence.” In disorganized speech, the words and word
combinations sound communicative, but the listener is left with little or no understanding of
the point the speaker is trying to make. In some cases, completely new, made-up words
known as neologisms (literally, “new words”) appear in the patient’s speech. An example
might be the word detone, which looks and sounds like a meaningful word but is a
neologism. Formal thought disorder (a term clinicians use to refer to problems in the way
that disorganized thought is expressed in disorganized speech).

Disorganized Behaviour

Disorganized behavior can show itself in a variety of ways. Goal-directed activity is almost
universally disrupted in schizophrenia. The impairment occurs in areas of routine daily
functioning, such as work, social relations, and self-care, to the extent that observers note that
the person is not himself or herself anymore. For example, the person may no longer maintain
minimal standards of personal hygiene or may exhibit a profound disregard of personal safety
and health. In other cases, grossly disorganized behavior appears as silliness or unusual dress
(e.g., wearing an overcoat, scarf, and gloves on a hot summer day). Many researchers
attribute these disruptions of “executive” behavior to impairment in the functioning of the
prefrontal region of the cerebral cortex. Catatonia is an even more striking behavioral
disturbance. The patient with catatonia may show a virtual absence of all movement and
speech and be in what is called a catatonic stupor. At other times, the patient may hold an
unusual posture for an extended period of time without any seeming discomfort. A person
with catatonia may maintain an odd position for minutes or even hours.

Negative Symptoms

Since the days of Bleuler, two general symptom patterns, or syndromes, of schizophrenia
have been differentiated. These are referred to as positive- and negative-syndrome
schizophrenia. Researchers began to highlight the difference between positive and negative
symptoms in the 1980s (Andreasen, 1985) and this distinction is still relevant today.
Positive symptoms are those that reflect an excess or distortion in a normal repertoire of
behavior and experience, such as delusions and hallucinations. Disorganized thinking is also
thought of in this way. Negative symptoms, by contrast, reflect an absence or deficit of
behaviors that are normally present. Current thinking is that negative symptoms fall into
two broad domains. One domain involves reduced expressive behavior—either in voice,
facial expression, gestures or speech. This may show itself in the form of blunted affect or
flat affect or in alogia, which means very little speech. The other domain concerns
reductions in motivation or in the experience of pleasure. The inability to initiate or persist in
goal-directed activity is called avolition. For example, the patient may sit for long periods of
time staring into space or watching TV with little interest in any outside work or social
activities. Diminished ability to experience pleasure is called anhedonia. Although most
patients exhibit both positive and negative symptoms during the course of their disorders, the
presence of negative symptoms in the clinical picture is not a good sign for the patient’s
future outcome.
.
Even though patients with negative symptoms may seem emotionally unexpressive, how they
appear and how they are feeling are two different things. In an important early study, Kring
and Neale (1996) studied unmedicated male patients with schizophrenia while they were
watching film clips. Three different types of film clips were used, the scenes in them being
very positive, very negative, or neutral in terms of the emotions they were designed to
elicit in the viewers. Videotapes of how the patients looked while they were watching the
films were then coded by trained raters. As might be expected, the patients with
schizophrenia showed less facial expressiveness than a group of healthy controls.
What was surprising was that when the patients were asked about their emotional experiences
during the films, they reported as many emotional feelings as the controls— and sometimes
slightly more. Measures of autonomic arousal also showed that when they were watching the
films, the patients exhibited more physiological reactivity than the controls did. Although the
original research used only male patients, a recent study that includes women with
schizophrenia has replicated the results about diminished emotional expression. What the
findings suggest, therefore, is that even though patients with schizophrenia may sometimes
appear emotionally unexpressive, they are nonetheless experiencing plenty of emotion.

DSM-5 Criteria for Schizophrenia

A. Two (or more) of the following, each present for a significant portion of time during a 1-
month period (or less if successfully treated). At least one 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 behavior.
5. Negative symptoms (i.e., diminished emotional expression or avolition).

B. For a significant portion of the time since the onset of the disturbance, level of functioning
in one or more major areas, 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).

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 two or more symptoms listed in Criterion A present in an
attenuated form (e.g., odd beliefs, unusual perceptual experiences).

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.

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.

F. If there is a history of autism spectrum disorder or a communication disorder of childhood

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).
  Genetic and Biological Factors
No Single Cause: Genes + Environment
 Schizophrenia cannot be explained by one factor alone.
 The old idea of “nature vs. nurture” is overly simplistic—both interact.
 The disorder does not result from a single genetic “switch.”
 Instead, it arises from a complex interplay between genes and environmental
influences.
Schizophrenia is a complex psychiatric disorder influenced by genetic predisposition,
prenatal and early environmental exposures, and neurodevelopmental disruptions.
While symptoms usually appear in late adolescence or early adulthood, the underlying risk
factors often act from conception onward. Understanding schizophrenia requires examining
the interplay of genes, early environmental insults, and brain development, as well as the
behavioral and cognitive markers that emerge long before clinical diagnosis.
1. Molecular Genetics: The Genetic Basis of Schizophrenia
Schizophrenia Involves Multiple Genes
Schizophrenia is not caused by a single gene, unlike disorders such as Huntington’s disease.
Instead, it likely involves hundreds of genes, each contributing a small effect. Some genes
may directly lead to schizophrenia, while milder variants may result in related conditions,
such as schizotypal personality disorder.
Candidate Genes
Candidate genes are studied because they affect processes disrupted in schizophrenia:
 COMT (chromosome 22): Influences dopamine metabolism; linked to psychosis and
cannabis-induced psychosis in adolescence. People with velocardiofacial syndrome
(chromosome 22 deletion) show increased risk.
 Neuregulin 1 (chromosome 8)
 Dysbindin (chromosome 6)
 DISC1 (chromosome 1)
 Dopamine receptor genes
However, many candidate gene findings fail to replicate consistently, suggesting
schizophrenia arises from complex polygenic interactions.
Genome-Wide Association Studies (GWAS)
GWAS examine millions of genetic variants (SNPs) across the genome.
 A 2014 GWAS with over 150,000 participants identified 108 genetic loci associated
with schizophrenia, 83 of which were newly discovered.
 Findings implicate dopamine, glutamate, and immune system genes, especially on
chromosome 6.
 There is also genetic overlap with bipolar disorder.
 Rare alleles and copy number variations (CNVs) contribute to schizophrenia risk
and overlap with autism, ADHD, and intellectual disability.
2. Twin Studies: Evidence for Heritability
Identical Twins Show Higher Concordance
Identical (monozygotic, MZ) twins have 28% concordance for schizophrenia, compared to
6% for fraternal (dizygotic, DZ) twins and less than 1% in the general population. This
demonstrates that genes matter, but since MZ concordance is far from 100%, environment
also plays a crucial role.
  Being a twin does not increase risk; risk is determined by genetic similarity.
 Reducing shared genes from 100% (MZ) to 50% (DZ) decreases risk by roughly 80%.
Discordant Twins: Why Only One Twin Develops Schizophrenia
Studying MZ twins who are discordant (only one twin develops schizophrenia) reveals the
gene-environment interaction.
 Fischer (1970s) hypothesized that offspring of the healthy MZ twin should show the
same risk as offspring of the affected twin.
 Finding: Healthy MZ twin children had a 17.4% risk, similar to affected twin
children.
 Interpretation: Genetic predisposition can remain unexpressed unless triggered by
environmental factors.
3. Adoption Studies: Separating Genes from Environment
Twin studies may overestimate genetic effects because MZ twins often share more similar
environments than DZ twins. Adoption studies allow researchers to disentangle genetic risk
from environmental influences.
Heston’s Adoption Study (1966)
 47 children born to mothers with schizophrenia were adopted within 72 hours of birth.
 Results: 16.6% developed schizophrenia; control group (children of healthy mothers)
had 0% incidence.
 Additional findings: Increased rates of mental retardation, neurotic disorders,
antisocial traits, and criminal involvement, suggesting genetic risk may affect broader
behavioral tendencies.
Danish–American Adoption Studies
 Adults with schizophrenia who were adopted early were compared with biological
and adoptive relatives.
 Results: 13.3% of biological relatives had schizophrenia or spectrum disorders; only
1.3% of adoptive relatives did.
 Conclusion: Strong support for a genetic basis.
Gene × Environment Interaction
 High genetic risk + high communication deviance → high thought disorder.
 High genetic risk + low communication deviance → children were the healthiest of
all groups.
 Low genetic risk children did well regardless of communication deviance level.
Finish Adoptive Family Study (Tienari et al.)
 Studied children adopted from mothers hospitalized for schizophrenia.
 Findings: Genetic risk alone was insufficient; environmental factors played a critical
role, particularly communication deviance in the adoptive family.
o High genetic risk + high communication deviance → high risk of thought
disorder
o High genetic risk + low communication deviance → children were healthiest
o Low genetic risk → did well regardless of family environment
 Supports diathesis–stress model: genetic vulnerability + environmental stress =
disorder.
PRENATAL EXPOSURES & SCHIZOPHRENIA
1. How Prenatal Factors Influence Gene Expression
 Whether a genetic vulnerability “turns on” depends on biological and environmental
triggers.
 Environmental influences during pregnancy—like maternal stress—can alter gene
expression in a developing fetus.
 Several prenatal conditions may cause schizophrenia or trigger it in genetically
vulnerable individuals.
Viral Infection Certain infections during pregnancy may disrupt fetal brain development
and increase schizophrenia risk. Historical studies show elevated schizophrenia births in
winter months, possibly linked to seasonal viral infections.
 The 1957 Finnish influenza epidemic study found higher schizophrenia rates in
children whose mothers were in the second trimester during the epidemic.
 A 2004 study by Brown and colleagues confirmed maternal influenza exposure using
serum samples, finding a 7-fold increased risk for first-trimester exposure. First-half-
of-pregnancy exposure tripled risk.
Other infections, such as rubella and toxoplasmosis, may increase risk via maternal
antibodies, cytokine-induced inflammation, or direct viral effects on the developing brain.
Historical Idea
 The link between infection and schizophrenia is not new.
 Kraepelin (1919) suggested early-life infections might contribute to the disorder.
 More people with schizophrenia are born January–March in the Northern
Hemisphere → suggests seasonal factor, possibly viral.
Influenza Epidemic Evidence
1957 Finland Influenza Epidemic
 Mednick et al. (1988):
o Higher schizophrenia rates in children whose mothers were in their second
trimester during the epidemic.
 Later replication attempts had mixed results.
 Big problem: researchers didn’t always know if mothers actually had influenza.
Certain infections during pregnancy may disrupt fetal brain development and increase
schizophrenia risk. Historical studies show elevated schizophrenia births in winter months,
possibly linked to seasonal viral infections.
 The 1957 Finnish influenza epidemic study found higher schizophrenia rates in
children whose mothers were in the second trimester during the epidemic.
 A 2004 study by Brown and colleagues confirmed maternal influenza exposure using
serum samples, finding a 7-fold increased risk for first-trimester exposure. First-half-
of-pregnancy exposure tripled risk.
Other infections, such as rubella and toxoplasmosis, may increase risk via maternal
antibodies, cytokine-induced inflammation, or direct viral effects on the developing brain.
Link to Schizophrenia
 Hollister, Laing, & Mednick (1996):
o 2.1% schizophrenia rate in Rh-incompatible males.
o 0.8% in males without incompatibility (close to general population rate).
 Fun detail: Hollister’s sister was Rh-incompatible with their mother.
Possible Mechanisms
 May cause oxygen deprivation (hypoxia) during development.
  Fits with research linking schizophrenia to birth complications involving disrupted
oxygen.
 Rh incompatibility may also cause brain abnormalities associated with
schizophrenia (Freedman et al., 2011).
Rhesus (Rh) Incompatibility
Rh incompatibility between an Rh-negative mother and Rh-positive fetus can increase
schizophrenia risk, particularly in males. Rates were 2.1% in Rh-incompatible males versus
0.8% in compatible males. Mechanisms may include oxygen deprivation or brain
abnormalities due to maternal-fetal blood incompatibility.
Other Infections Linked to Schizophrenia
 Rubella (German measles)
 Toxoplasmosis (common parasitic infection)
 These also increase risk when they occur during pregnancy.
Possible Mechanisms
 Maternal antibodies may cross the placenta, affecting fetal brain development.
 Influenza may trigger inflammatory cytokines → neurodevelopmental damage.
 The virus may also directly harm the developing brain.
 These findings support growing interest in the infection–immunity model of
schizophrenia.
PREGNANCY & BIRTH COMPLICATIONS
Elevated Risk in Complicated Births
 People with schizophrenia are more likely to have had:
o Complicated pregnancies
o Difficult deliveries
 Many complications (breech birth, long labor, umbilical cord issues) affect oxygen
supply to the newborn.
 This again suggests brain damage during critical development periods may play a
role.
EARLY NUTRITIONAL DEFICIENCY
Dutch Hunger Winter (1944–1945)
 Severe famine due to Nazi blockade.
 Fertility drastically decreased, but some children were still born.
Key Findings
 Children conceived at the height of famine → 2× risk of schizophrenia later.
 Likely caused by prenatal nutritional deficiency.
 Not clear whether the key missing nutrient was general nutrition, folate, iron, or
something else.
 Again supports the idea that early developmental disruption increases schizophrenia
risk.
Pregnancy and Birth Complications
People with schizophrenia are more likely to have experienced obstetric complications, such
as:
 Breech birth
 Prolonged labor
 Umbilical cord around the neck
Many of these complications reduce the newborn’s oxygen supply, which can disturb brain
development during critical periods. Although not every complication leads to schizophrenia,
the overall pattern suggests prenatal oxygen deprivation plays a role.
Early Nutritional Deficiency
The Dutch Hunger Winter (1944–45) offered tragic evidence of the effects of starvation on
fetal development. Children conceived during this famine had double the risk of
schizophrenia later in life.
It remains unclear whether general malnutrition or specific nutrient deficiencies (e.g., folate,
iron) caused the problem, but the key point is that lack of adequate nutrients during early
pregnancy disrupted brain development.
Maternal Stress
Stress During Pregnancy Increases Risk
 Extremely stressful events in late first trimester or early second trimester increase
the child’s risk.
 Danish study (Khashan et al., 2008):
o Death of a close relative during mother’s first trimester → 67% increased
risk of schizophrenia in offspring.
Possible Mechanism
 Stress hormones (like cortisol) cross the placenta.
 These may negatively affect fetal brain development, though the exact mechanism is
still unclear.
Genes and Environment in Schizophrenia: A Combined Perspective
 Schizophrenia has a strong genetic foundation, but genetics alone cannot explain all
cases. The disorder emerges through two major genetic pathways:
Schizophrenia Runs in Families
Schizophrenia is familial, meaning it occurs more frequently among relatives of affected
individuals.
 First-degree relatives (parents, siblings, children): ~10% lifetime risk
 Second-degree relatives (aunts, uncles, grandchildren, half-siblings): ~3% lifetime
risk.
Strong Genetic Component
 Schizophrenia clearly has major genetic influences.
 Genetic risk appears in two main ways:
o (a) Many common genes:
 Possibly hundreds or thousands.
 Each contributes a tiny effect, but together they increase vulnerability.
o (b) Rare genetic mutations:
 More specific to certain families or individuals.
 Include microdeletions (missing DNA segments) or repeated
sequences.
Rethinking Heritability (Twin Studies)
 Concordance rates between twins might overestimate genetic influence.
 Reason: Prenatal environments differ between twin types.
o Two-thirds of MZ twins are monochorionic (share placenta + blood
supply).
 o Remaining MZ & all DZ twins are dichorionic (separate placentas).
 This means environmental sharing may partly explain higher MZ concordance.
 Research findings:
o Monochorionic MZ twins → ~60% concordance.
o Dichorionic MZ twins → ~11% concordance.
o The 11% is similar to DZ twin rates.
 Implication: Some of what appears “genetic” may actually be shared prenatal
environment, especially infection exposure.
Gene Expression Is Environmentally Sensitive
 Genes can be turned on or off by environmental experiences.
 MZ twins who differ in schizophrenia diagnosis show differences in gene
expression.
 Possible explanation:
o One twin experiences environmental “hits” that activate vulnerability genes.
o The other does not.
 Some environments may even prevent schizophrenia genes from being activated.
Gene Expression Depends on Environmental Triggers
Genes are not static—they can be activated or deactivated by environmental events.
Studies show that identical twins who differ in schizophrenia diagnosis also differ in gene
expression patterns.
Environmental events ("hits") may:
 Turn schizophrenia-related genes on in one twin
 Keep them off in the other
Some environments may even protect at-risk individuals.
Genetics Increases Sensitivity to Environmental Harm
 People with genetic risk react more strongly to environmental insults.
 Cannon et al. (1993):
o Brain abnormalities (e.g., enlarged ventricles) appeared only in:
 People with genetic history + birth complications.
o No abnormalities in:
 People with no family history, even with birth complications.
 Conclusion: Genetics may magnify damage from prenatal or birth-related issues.
Genetic Risk : Genetic susceptibility arises in two main ways:
1. Common genetic variants: Thousands of genes each contribute a small amount of
risk. Combined, they can predispose individuals to schizophrenia.
2. Rare mutations: Some individuals or families have unique mutations, such as
microdeletions or repeated DNA sequences, which significantly increase risk.
Monozygotic (MZ) twin studies show higher concordance than dizygotic (DZ) twins.
However, prenatal environment can inflate heritability estimates. Around two-thirds of MZ
twins are monochorionic (sharing a placenta), increasing shared exposure to infections.
Concordance rates are ~60% for monochorionic MZ twins versus ~11% for dichorionic MZ
twins—similar to DZ twins.
Gene-Environment Interaction
Genes can be activated or suppressed by environmental factors. For example:
 MZ twins discordant for schizophrenia show different gene expression patterns.
  Individuals with genetic risk are more sensitive to birth complications or other
environmental insults. For instance, children with a parent with schizophrenia and
birth complications show enlarged brain ventricles, while those without genetic risk
do not.
Neurodevelopmental Perspective
How Early Developmental Problems Lead to Later Onset
Risk may start with:
 Genetic vulnerabilities
 Prenatal infections
 Maternal stress
 Nutritional deprivation
 Birth complications
These factors can alter early brain development. Symptoms may not appear until:
 Later developmental “triggers” occur
 The brain matures (late teens or early 20s), revealing earlier abnormalities
 Onset usually in late adolescence/early adulthood,
but causes often occur before birth.
 Current view:
o Schizophrenia begins with very early disturbances in brain development.
o Genes + prenatal insults create abnormal neural development.
o Later brain maturation or stressors reveal these early problems.
How Brain Development Might Go Wrong
 Brain development is highly ordered; disruptions can alter connectivity.
 Example:
o If cell migration is disturbed, brain circuits may form incorrectly.
 Environmental toxins like organic solvents (e.g., dry-cleaning chemicals) may impair
fetal development.
 Some schizophrenia-linked genes lie in the MHC region, which:
o Regulates immune function.
o Also plays a role in brain development.
 Possible scenarios:
o Genetic vulnerability may mean greater vulnerability to infection.
o Infections can alter gene expression or disrupt neural development.
 Maternal infections & inflammation during pregnancy are highly implicated.
Early Behavioral Signs Seen in Childhood
Home Movie Studies (Walker et al.)
 Researchers reviewed old childhood videos of future schizophrenia patients.
 Compared with their healthy siblings, “preschizophrenic” children showed:
o More motor abnormalities (unusual hand movements).
o Less positive facial emotion.
o More negative facial emotion.
 Some signs appeared as early as age 2.
 Strength of design: avoids retrospective bias by using real-time recordings.
Prospective Long-Term Cohort Studies
 Jones et al. (1994) & Isohanni et al. (2001) followed entire birth cohorts.
 Found early indicators in future schizophrenia cases:
 o Delayed speech at age 2
o Delayed motor development at age 2
High-Risk Children (Genetically at Risk)
Background
 Studied children with at least one parent with schizophrenia.
 Though most schizophrenic individuals (89%) do not have a family history, these
samples still reveal valuable clues.

 Attention problems are consistent early markers.

 High-risk adolescents show:
o Lower social competence than teens at risk for mood disorders.
o Social problems may stem from attention difficulties.
Early Motor Abnormalities as Predictors
 New York High-Risk Study:
o 10 out of 51 high-risk children developed schizophrenia/psychosis.
o 80% of those showed unusual motor behaviors at ages 7–12.
 Another study:
o High-risk adolescents showed more facial tics, blinking, tongue thrusts than
controls.
o These abnormalities worsened over time and correlated more with psychotic
symptoms as adolescence progressed.
 Interpretation:
o Motor abnormalities and psychosis might share neural circuits.
o Problems appear first in motor systems, then later in cognitive/psychotic
systems as the brain matures.
Clinical High-Risk Studies
Shifting Focus to Prodromal Signs
 Instead of genetic risk, new studies target youth with clinical early warning signs.
 Aim: detect and possibly intervene early.
Attenuated Psychosis Syndrome (DSM-5 – Needs Further Study)
 Represents sub threshold psychotic symptoms.
 Helps identify people in the “pre-psychosis” phase.
Common Symptoms
 Confusion between dreams and reality.
 Losing control over thoughts.
 Feeling others view them negatively.
 Mild suspiciousness of friends/acquaintances.
 Hearing low-level sounds (buzzing, hissing, knocking).
 Symptoms are not yet full-blown psychosis, but signal elevated risk.

 Structural and Functional Brain

Abnormalities
Brain Abnormalities in Schizophrenia
Technological developments have revealed significant structural and functional abnormalities
in the brains of people with schizophrenia, alongside issues with neurotransmitter
activity (though the text focuses more on cognitive and structural/functional issues).

 Neurocognition (Functional Abnormalities)

Cognitive impairment is a core feature of schizophrenia, with patients performing

significantly worse (on average, almost a full standard deviation below) than healthy controls
on a broad range of neuropsychological tests.

* Broad Impairment: Almost all aspects of cognition are impaired, including attention,
language, and memory.

Early Onset and Progression:

* Cognitive difficulties appear early, even in young people at clinical high risk before a
diagnosable illness.
* They are unlikely due to hospitalization or medication.
* A lower IQ may be an independent risk factor for developing the disorder, while a higher
IQ may be protective.
* Pre-existing cognitive impairments become more prominent and extensive as the illness
progresses.
* A sharp decline in cognitive ability and IQ occurs during the transition from the premorbid
period into the full-blown illness (first psychotic episode).
* Cognitive decline appears to stabilize after the first episode, though a second period of
deterioration may begin around age 65.

Specific Cognitive Problems

Patients show deficits in specific cognitive tasks:
* Reaction Time: They perform poorly when asked to respond to a stimulus as quickly and
appropriately as possible.
* Attention Deficits (CPT): They show deficits on the Continuous Performance Test (CPT),
which requires sustained attention to detect an intermittently presented target stimulus.
* Working Memory: There are problems with working memory (the "mental blackboard").
* When engaging in working memory tasks, patients show less prefrontal brain
activity compared to healthy controls, suggesting a functional abnormality in this key brain
region.

Sensory Processing Deficits

Deficits are also apparent in the very earliest stages of sensory processing:
* Eye-Tracking Dysfunction (Smooth-Pursuit Eye Movement):
* Between 54% and 86% of people with schizophrenia show eye-tracking dysfunction,
meaning they are deficient in the ability to smoothly track a moving target (like a pendulum).
* This is far higher than the general population (6-8%).
* Approximately 50% of first-degree relatives of patients also show this problem, suggesting
a genetic basis and making eye-tracking a potential endophenotype for genetic studies.
* Auditory Sensory Gating (P50 Suppression):
* Patients show problems with a process called sensory gating.
* In a normal brain, when two clicks are heard close together, the electrical response to the
second click (P50 response) is dampened ("gated") to allow for habituation to repeated
stimuli.
* Many patients, in contrast, respond almost as strongly to the second click as to the first—a
problem called "poor P50 suppression."
* First-degree family members of patients are also more likely to have problems with P50
suppression.

 SOCIAL COGNITION

• When someone looks at your dessert and says it looks tasty you would normally think they
want a bite, this is an example of using social cognition
• Social cognition means how we understand and react to social information like other
peoples feelings intentions and hints
• People with schizophrenia have problems with basic thinking processes and also have
strong difficulties with social cognition
• They often miss social hints that most people understand easily
• They have trouble recognizing emotions in faces

• They also have trouble understanding emotion in speech

• They are less able to notice when someone makes a social mistake like forgetting a party is
supposed to be a surprise
• Social cognition problems are more serious in schizophrenia than in other disorders
• For example people with bipolar disorder usually do normal on social cognition tests when
they are not in an episode
• Good general thinking skills are needed for social cognition but social cognition and general
thinking are not the same
• Both general thinking and social cognition help explain how well a person functions in daily
life
• Social cognition is more important than general thinking skills for predicting social skills
and quality of life

 Loss of brain volume

• Schizophrenia is linked to clear changes in the brain in both structure and function
• One common finding is enlarged brain ventricles which are fluid filled spaces in the brain
• People with schizophrenia often have larger ventricles than healthy people and this may be
more common in men
• But enlarged ventricles do not appear in every patient and they are not unique to
schizophrenia. They can also occur in Alzheimer’s disease Huntington’s disease and long
term alcohol problems
• Larger ventricles mean there is less brain tissue because when brain tissue shrinks the empty
space fills with fluid and the ventricles look bigger
• MRI studies show that people with schizophrenia have about three percent less total brain
volume than healthy people

• This loss of brain volume appears very early even in people who just developed the illness
• Some studies show that people who have a high genetic risk for schizophrenia start to show
brain changes before the illness fully appears. This suggests these changes may help trigger
the illness
• Brain tissue loss gets worse over time in schizophrenia
• Studies show that gray matter which contains nerve cells decreases more and more during
the first year after diagnosis
• Over longer periods like five years adolescents with schizophrenia show greater gray matter
loss compared to healthy peers
• Brain deterioration continues for many years not just at the start of the illness
• Even identical twins where only one has schizophrenia show brain changes
in both twins which means the changes are likely influenced by genes and not just medication
• Overall schizophrenia is not only a disorder that begins with early brain development
problems but also a disorder in which the brain keeps losing tissue over time
• This ongoing brain deterioration matches the idea behind the old term dementia praecox
which meant early appearing brain decline

 AFFECTED BRAIN AREA

• Certain brain areas are especially affected in schizophrenia

• There is less volume in parts of the frontal and temporal lobes which are important for
memory decision making and processing sounds
• There is less volume in the amygdala which helps with emotion the hippocampus which is
important for memory and the thalamus which receives most sensory information

• Not every study shows only loss of gray matter. A large study on people who had their first
episode and had never taken medication showed increases in gray matter in several areas
• This means brain changes in schizophrenia are more complicated and may depend on things
like stage of illness and medication use
• Brain structure is clearly abnormal in schizophrenia but the type of abnormality can differ
• Gray matter loss means loss of brain cells

 PROBLEMS IN WHITE MATTER

• But schizophrenia also involves problems with white matter which contains nerve fibers
covered in myelin
• Myelin helps nerve signals travel quickly and efficiently so white matter is important for
good communication between brain regions
• Studies show people with schizophrenia have reduced white matter volume and structural
problems in white matter
• These problems appear early even in people having their first episode and even in those
who are at high genetic risk before becoming ill
• This suggests the problems are not caused by the illness itself or by medications

• The main issue seems to be dysconnectivity which means poor communication or weak
connections between brain areas especially involving the frontal lobes
• This may help explain symptoms For example a disconnect between language production
and language understanding areas could make a person hear their own inner speech as if it
were an outside voice
• White matter problems are linked to cognitive difficulties like problems with thinking and
planning
• In people at high risk changes in white matter in the temporal lobe can predict later social
difficulties
• Children of people with schizophrenia who are not ill themselves also show reduced volume
in the corpus callosum which connects the two brain hemispheres
• Overall white matter abnormalities and problems in how brain connections develop may be
key to understanding what goes wrong in schizophrenia

 BRAIN FUNCTIONING

• Brain functioning studies show how the brain works during tasks or while resting
• Since schizophrenia involves brain structure changes and thinking problems it makes sense
that brain functioning is also disrupted
• Some patients show low activity in the frontal lobe during difficult tasks like the Wisconsin
Card Sorting Test. This is called hypofrontality
• This means the frontal lobe does not activate properly when the person needs to think hard
• Other patients show too much frontal lobe activity which means they have to work extra
hard to do the same task
• In both cases the brain is not working efficiently
• Frontal lobe problems are found even in early stages of schizophrenia and in people at high
risk

• These problems are not found in all patients but they may help explain negative symptoms
and attention and thinking difficulties
• There are also problems in the temporal lobe although findings here are less consistent
• A major issue may be trouble coordinating activity between different brain regions
• When we relax the brain uses the default mode network a group of brain areas active during
rest
• When we start a task the default mode network should become less active so task related
brain areas can take over
• Healthy people can easily turn down the default mode network when needed
• People with schizophrenia have trouble doing this so they stay partly stuck in resting mode
even during tasks
• This makes it harder for them to focus and perform well which may explain many of their
cognitive difficulties

 Cytoarchitecture

• One idea about schizophrenia is that genes and prenatal problems may disturb how brain
cells move to their correct places during early development
• If brain cells do not reach their final destination the organization of the brain called
cytoarchitecture becomes abnormal
• This means some cells end up in the wrong layers or wrong areas of the brain
• Studies show that some brain areas in people with schizophrenia have more neurons packed
together than normal
• There are also problems in how cells are arranged in different layers of the cortex and the
hippocampus
• A very important finding is that people with schizophrenia are missing a type of neuron
called inhibitory interneurons or GABA interneurons
• These neurons help control and calm down the activity of other neurons
• Without these calming neurons the more active neurons may fire too much and too often
• This may cause the brain to become overactive in certain circuits and unable to regulate or
quiet down activity
• This helps explain why people with schizophrenia have trouble handling even normal
amounts of stress
• Research on this is possible because some people donate their brains after death to
psychiatric brain banks
• Studying donated brains is difficult because there are issues like the age of the brains
substance use and effects of medication
• Another challenge is that only a small number of schizophrenia brains and healthy brains
are donated so samples are limited

 Brain development in Adolescents

• Risk genes and prenatal problems can disrupt brain development even before birth
• But brain development does not stop there. The brain keeps changing through adolescence
and early adulthood
• Teenagers have extra synapses and these are normally pruned or reduced during
adolescence to make the brain work more efficiently
• During adolescence gray matter normally decreases white matter increases and the
hippocampus and amygdala get larger
• Excitatory synapses normally decrease and inhibitory synapses increase which helps the
brain become more balanced and adult like
• These changes are all part of normal healthy brain development
• If these processes do not happen correctly the brain may develop abnormally

• Problems like too much pruning too little white matter or reduced hippocampus volume
match what we see in schizophrenia
• So schizophrenia may come from abnormal brain maturation especially in how synapses are
pruned and how myelin develops
• Adolescence is a critical time, If something goes wrong during this stage it can lead to
schizophrenia
• Research shows that people who have had a head injury have a higher risk of developing
schizophrenia later
• The risk is even higher if the head injury happens between ages 11 and 15
• This suggests there are sensitive periods in brain development when the brain is especially
vulnerable to damage
• Some sensitive periods are early in life before birth and some are during adolescence
• Schizophrenia is complex but many causes may come from problems that happen in the
brain during these important developmental stages

 Synthesis

• In schizophrenia the brain is affected but the changes are often subtle not dramatic
• Some brain problems come from genetics while others come from environmental factors
• A study of identical and fraternal twins showed that twins with schizophrenia had smaller
brain volumes than their healthy co twins
• The healthy co twins also had smaller brain volumes than completely healthy twins from the
general population
• This suggests that genetic risk for schizophrenia may slow or reduce brain development
early in life even if the person never becomes ill
• The twin who develops schizophrenia seems to have extra brain problems on top of the
genetic risk these extra problems are likely caused by environmental events not genes
• Examples of harmful environmental events include lack of oxygen before birth or head
injury

• People with genetic risk are more vulnerable to these harmful events while people without
the genetic risk are less affected
• Even identical twins can end up different if only one experiences an environmental insult
the one who experiences it may develop schizophrenia while the other stays healthy
• Schizophrenia is not caused by one single problem in one part of the brain
• The brain works through functional circuits meaning different brain areas are connected and
depend on each other
• If any part of a circuit is damaged the whole circuit may not work properly
• Researchers are now studying how the brain is wired and how brain networks function or
switch between different networks
• Problems in important brain circuits or difficulty switching between them may disrupt
normal thinking and behavior in schizophrenia
• As science learns more about how the brain works we will better understand how it
becomes disrupted in schizophrenia

 NEUROCHEMISTRY

• Scientists began studying brain chemicals in schizophrenia after LSD was found to cause
major mental changes.
• The idea of chemical imbalance is general but means brain chemistry is different in
schizophrenia.
• Dopamine is the main neurotransmitter studied.
• The dopamine hypothesis came from three findings:
o Chlorpromazine helped schizophrenia and worked by blocking dopamine receptors.
o Amphetamines caused a state with too much dopamine and produced psychosis
similar to schizophrenia.
o L DOPA, which increases dopamine, caused psychotic symptoms in some patients.

• Too much dopamine may make people give too much importance to normal or unimportant
events. This is called aberrant salience.
• Aberrant salience can lead to hallucinations and delusions because the person tries to
explain these strange feelings and meanings.
• Too much dopamine activity can happen if the brain makes too much dopamine, releases
too much, breaks it down too slowly, reabsorbs it too slowly, or has too many or
oversensitive dopamine receptors.
• New brain imaging shows the main dopamine problem is presynaptic. People with
schizophrenia make and release about fourteen percent more dopamine.
• Slightly higher dopamine receptor numbers may be due to antipsychotic medication, not the
illness itself.
• Glutamate is another neurotransmitter involved in schizophrenia.
• PCP blocks glutamate receptors and causes schizophrenia-like symptoms and worsens
symptoms in patients.
• Ketamine does the same in healthy adults and in patients with schizophrenia, but not in
children or animals, suggesting brain maturity matters.

• Studies show lower glutamate levels in the prefrontal cortex and hippocampus of people
with schizophrenia.
• Low activity at NMDA glutamate receptors may cause symptoms and possibly slow neuron
damage.
• New treatments try to boost glutamate function using substances like glycine and D serine.
• Glutamate findings do not conflict with the dopamine hypothesis. Too much dopamine can
reduce glutamate activity. The two systems are connected.

 PSYCHOSOCIAL AND CULTURAL FACTORS

Do Bad Families Cause Schizophrenia?

Early theories blamed parents—especially mothers—for causing schizophrenia through

hostility, rejection, or inconsistent communication, leading to harmful stigma. Ideas such as
the “schizophrenogenic mother” or the double-bind hypothesis lacked scientific support and
are no longer accepted. Research now shows that family conflict is usually a consequence of
living with someone who is severely ill, not a cause of the illness. Some families display
communication deviance, but its impact is minimal unless the child already carries a genetic
vulnerability. Modern understanding emphasizes that schizophrenia arises from biological
and environmental interactions, not destructive parenting styles.

 Families and Relapse

Relapse patterns indicate that home environments significantly influence symptom return.
Patients living with parents or spouses show higher relapse rates than those living alone,
suggesting that everyday emotional climates matter. The construct of expressed emotion (EE)
—criticism, hostility, and emotional over involvement—strongly predicts relapse across
illness stages. High-EE environments more than double relapse risk, and reducing EE lowers
this risk, supporting its causal significance. Stress sensitivity plays a major role: high-EE
behaviors raise cortisol levels, affecting dopamine and glutamate systems involved in
psychosis. Studies show that critical responses trigger unusual thinking during interactions,
and neuroimaging findings suggest that critical comments activate brain regions differently in
vulnerable individuals, possibly influencing relapse.

 Urban Living

Growing up in urban environments significantly increases schizophrenia risk. Large-scale

studies show that those raised in cities are more than twice as likely to develop the disorder as
those from rural areas. If urban exposure were reduced, schizophrenia rates could drop
substantially. Increased stress, social adversity, and environmental pressures in cities may
partly explain this elevated risk.

 Immigration

Immigration is associated with higher schizophrenia risk, especially among first- and second-
generation immigrants. Theories attributing this to diagnostic bias or selective migration are
unsupported. Instead, social adversity—including discrimination and feelings of exclusion—
appears more explanatory. Higher risk among darker-skinned immigrants further suggests
that social defeat and chronic stress may trigger biological responses affecting dopamine
activity. These stressors can also increase vulnerability to substance misuse, linking
immigration-related stress to psychosis risk.

 Cannabis Use and Abuse

Cannabis use is significantly associated with schizophrenia, with heavy adolescent use linked
to much higher risk. Early cannabis use more than doubles the likelihood of later psychosis,
and the association persists even when early psychotic symptoms are considered. Cannabis
may accelerate symptom onset through dopamine activity and other neurochemical pathways.
Genetic predispositions may heighten vulnerability, though evidence is mixed. Brain imaging
studies show greater long-term tissue loss in patients who continue using cannabis,
suggesting it may worsen illness progression.

 A Diathesis–Stress Model of Schizophrenia

The diathesis–stress perspective explains schizophrenia as the result of genetic vulnerability

interacting with environmental stressors. Biological predispositions can be intensified or
mitigated by prenatal complications, infections, stress, and life circumstances. Rather than
being genetically predetermined, schizophrenia emerges from complex pathways involving
multiple risks across development. Attempts to identify a single cause have failed because
many different genetic and environmental combinations can lead to similar outcomes. Human
brain complexity and developmental variability mean that some individuals become
vulnerable by chance, highlighting schizophrenia as a multifactorial disorder shaped by both
biology and environment.

SUBTYPES OF SCHIZOPHRENIA

Types of Schizophrenia
Subtypes
The subtypes of Schizophrenia are defined by the predominant symptomatology at the time
of evaluation. Five subtypes of schizophrenia have been described based predominantly on
clinical presentation: Paranoid, Disorganized, Catatonic, Undifferentiated, and Residual.
DSM-5 no longer uses these subtypes but they are listed in the 10th revision of the
International Statistical Classification of Diseases and Related Health Problems (ICD-10).
The diagnosis of a particular subtype is based on the clinical picture that occasioned the most
recent evaluation or admission to clinical care and may therefore change over time. Not
infrequently, the presentation may include symptoms that are characteristic of more than one
subtype.
 1. Paranoid Type*
● The paranoid type of schizophrenia is characterized by preoccupation with one or
more delusions or frequent auditory hallucinations.
● Delusions are typically persecutory or grandiose, or both, but delusions with other
themes (e.g., jealousy, religiosity, or somatization) may also occur. The delusions
may be multiple, but are usually organized around a coherent theme.
● Hallucinations are also typically related to the content of the delusional theme.
● The persecutory themes may predispose the individual to suicidal behavior, and the
combination of persecutory and grandiose delusions with anger may predispose the
individual to violence.
● Symptoms characteristic of the Disorganized and Catatonic Types (e.g., disorganized
speech, flat or inappropriate affect, catatonic or disorganized behavior) are not
prominent.
● Onset tends to be later in life than the other types of Schizophrenia, and the
distinguishing characteristics may be more stable over time. Patients with paranoid
schizophrenia usually have their first episode of illness at an older age than do
patients with catatonic or disorganized schizophrenia.
● Patients in whom schizophrenia occurs in the late 20s or 30s have usually established
a social life that may help them through their illness, and the ego resources of
paranoid patients tend to be greater than those of patients with catatonic and
disorganized schizophrenia.
● Patients with the paranoid type of schizophrenia show less regression of their mental
faculties, emotional responses, and behaviour than do patients with other types of
schizophrenia.
● Patients with paranoid schizophrenia are typically tense, suspicious, guarded,
reserved, and sometimes hostile or aggressive, but they can occasionally conduct
themselves adequately in social situations. Their intelligence in areas not invaded by
their psychosis tends to remain intact.
● These individuals usually show little or no impairment on neuropsychological or other
cognitive testing.
● Some evidence suggests that the prognosis for the Paranoid Type may be considerably
better than for the other types of Schizophrenia, particularly with regard to
occupational functioning and capacity for independent living.

Diagnostic criteria for Paranoid Type

A type of Schizophrenia in which the following criteria are met:
A. Preoccupation with one or more delusions or frequent auditory hallucinations. B. None of
the following is prominent: disorganized speech, disorganized or catatonic behavior, or flat or
inappropriate affect.
 2. Disorganized Type

● The disorganized type of schizophrenia is characterized by a marked regression to

primitive, disinhibited, and unorganized behavior.
● The essential features of the Disorganized Type of Schizophrenia are disorganized
speech, disorganized behavior, and flat or inappropriate affect. The disorganized
speech may be accompanied by silliness and laughter that are not closely related to
the content of the speech. The behavioral disorganization (i.e., lack of goal
orientation) may lead to severe disruption in the ability to perform activities of daily
living (e.g., showering, dressing, or preparing meals). Associated features include
grimacing, mannerisms, and other oddities of behavior.
● The onset of this subtype is generally early and insidious, occurring before age 25
years. This subtype is also usually associated with poor premorbid personality, and a
continuous course without significant remissions.
● Disorganized patients are usually active but in an aimless, non constructive manner.
● Their thought disorder is pronounced, and their contact with reality is poor. Their
personal appearance is dishevelled, and their social behaviour and their emotional
responses are inappropriate.
● They often burst into laughter without any apparent reason. Incongruous grinning and
grimacing are common in these patients, whose behaviour is best described as silly or
fatuous.
● Criteria for the Catatonic Type of Schizophrenia are not met, and delusions or
hallucinations, if present, are fragmentary and not organized into a coherent theme.
● Impaired performance may be noted on a variety of neuropsychological and cognitive
tests. Historically, and in other classification systems, this type is termed hebephrenic.

Diagnostic criteria for Disorganized Type

A type of Schizophrenia in which the following criteria are met:
A. All of the following are prominent:
(1) disorganized speech
(2) disorganized behavior
(3) flat or inappropriate affect
B. The criteria are not met for Catatonic Type.

3. Catatonic Type*

● The essential feature of the Catatonic Type of Schizophrenia is a marked psychomotor

disturbance that may involve motoric immobility, excessive motor activity, extreme
negativism, mutism, peculiarities of voluntary movement, echolalia, or echopraxia.
 ● Sometimes the patient shows a rapid alteration between extremes of excitement and
stupor.
● Motoric immobility may be manifested by catalepsy (waxy flexibility) or stupor. The
excessive motor activity is apparently purposeless and is not influenced by external
stimuli.
● There may be extreme negativism that is manifested by the maintenance of a rigid
posture against attempts to be moved or resistance to all instructions.
● Peculiarities of voluntary movement are manifested by the voluntary assumption of
inappropriate or bizarre postures or by prominent grimacing.
● Echolalia is the pathological, parrotlike, and apparently senseless repetition of a word
or phrase just spoken by another person.
● Echopraxia is the repetitive imitation of the movements of another person.
● Additional features include stereotypies, mannerisms, and automatic obedience or
mimicry.
● Mutism is particularly common.
● During catatonic excitement, patients need careful supervision to prevent them from
hurting themselves or others.
● Medical care may be needed because of malnutrition, exhaustion, hyperpyrexia, or
self-inflicted injury.
● To diagnose this subtype, the individual's presentation must first meet the full criteria
for Schizophrenia and not be better accounted for by another etiology: substance
induced (e.g., Neuroleptic-Induced Parkinsonism), a general medical condition, or a
Manic or Major Depressive Episode.

Diagnostic criteria for Catatonic Type

A type of Schizophrenia in which the clinical picture is dominated by at least
two of the following:
(1) motoric immobility as evidenced by catalepsy (including waxy flexibility) or stupor
(2) excessive motor activity (that is apparently purposeless and not influenced by external
stimuli)
(3) extreme negativism (an apparently motiveless resistance to all instructions or maintenance
of a rigid posture against attempts to be moved) or mutism
(4) peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of
inappropriate or bizarre postures), stereotyped movements, prominent mannerisms, or
prominent grimacing
(5) echolalia or echopraxia

4. Undifferentiated Type*
● Frequently, patients who clearly have schizophrenia cannot easily fit into one type or
another.
 ● These patients are classified as having schizophrenia of the undifferentiated type.
● The essential feature of the Undifferentiated Type of Schizophrenia is the presence of
symptoms that meet Criterion A of Schizophrenia but that do not meet criteria for the
Paranoid, Disorganized, or Catatonic Type.

5. Residual Type
● The Residual Type of Schizophrenia should be used when there has been at least one
episode of Schizophrenia, but the current clinical picture is without prominent
positive psychotic symptoms (e.g., delusions, hallucinations, disorganized speech or
behavior).
● There is continuing evidence of the disturbance as indicated by the presence of
negative symptoms (e.g., flat affect, poverty of speech, or avolition) or two or more
attenuated positive symptoms (e.g., eccentric behavior, mildly disorganized speech, or
odd beliefs).
● If delusions or hallucinations are present, they are not prominent and are not
accompanied by strong affect.
● The course of the Residual Type may be time limited and represent a transition
between a full-blown episode and complete remission. However, it may also be
continuously present for many years, with or without acute exacerbations.
● The residual type of schizophrenia is also characterized by continuing evidence of the
schizophrenic disturbance in the absence of a complete set of active symptoms or of
sufficient symptoms to meet the diagnosis of another type of schizophrenia.
● Emotional blunting, social withdrawal, eccentric behavior, illogical thinking, and mild
loosening of associations commonly appear in the residual type.

Diagnostic criteria for Residual Type

A type of Schizophrenia in which the following criteria are met:
A. Absence of prominent delusions, hallucinations, disorganized speech, and grossly
disorganized or catatonic behavior.
B. There is continuing evidence of the disturbance, as indicated by the presence of negative
symptoms or two or more symptoms listed in Criterion A for Schizophrenia, present in an
attenuated form (e.g., odd beliefs, unusual perceptual experiences).

Other Subtypes
The subtyping of schizophrenia has had a long history; other subtyping schemes
appear in the literature, especially literature from countries other than the United
States.
1. Bouffée Délirante (Acute Delusional Psychosis). This French diagnostic concept
differs from a diagnosis of schizophrenia primarily on the basis of a symptom
duration of less than 3 months. The diagnosis is similar to the DSM-5 diagnosis of
schizophreniform disorder. French clinicians report that about 40 percent of patients
with a diagnosis of bouffée délirante progress in their illness and are eventually
classified as having schizophrenia.

2. Latent*. The concept of latent schizophrenia was developed during a time when
theorists conceived of the disorder in broad diagnostic terms. Currently, patients must
be very mentally ill to warrant a diagnosis of schizophrenia, but with a broad
diagnostic concept of schizophrenia, the condition of patients who would not
currently be thought of as severely ill could have received a diagnosis of
schizophrenia. Latent schizophrenia, for example, was often the diagnosis used for
what are now called borderline, schizoid, and schizotypal personality disorders. These
patients may occasionally show peculiar behaviors or thought disorders but do not
consistently manifest psychotic symptoms. In the past, the syndrome was also termed
borderline schizophrenia.

3. Oneiroid*. The oneiroid state refers to a dream-like state in which patients may be
deeply perplexed and not fully oriented in time and place. The term oneiroid
schizophrenia has been used for patients who are engaged in their hallucinatory
experiences to the exclusion of involvement in the real world. When an oneiroid state
is present, clinicians should be particularly careful to examine patients for medical or
neurological causes of the symptoms.

4. Paraphrenia*. The term paraphrenia is sometimes used as a synonym for paranoid

schizophrenia or for either a progressively deteriorating course of illness or the
presence of a well-systemized delusional system. The multiple meanings of the term
render it ineffectual in communicating information.

5. Pseudoneurotic Schizophrenia*. Occasionally, patients who initially have such

symptoms as anxiety, phobias, obsessions, and compulsions later reveal symptoms of
thought disorder and psychosis. These patients are characterized by symptoms of
pananxiety, panphobia, panambivalence, and sometimes chaotic sexuality. Unlike
persons with anxiety disorders, pseudoneurotic patients have free-floating anxiety that
rarely subsides. In clinical descriptions, the patients seldom become overtly and
severely psychotic. This condition is currently diagnosed as borderline personality
disorder.

6. Simple Deteriorative Disorder (Simple Schizophrenia). Simple deteriorative disorder

is characterized by a gradual, insidious loss of drive and ambition. Patients with the
 disorder are usually not overtly psychotic and do not experience persistent
hallucinations or delusions. Their primary symptom is withdrawal from social and
work-related situations. The syndrome must be differentiated from depression, a
phobia, dementia, or an exacerbation of personality traits. Clinicians should be sure
that patients truly meet the diagnostic criteria for schizophrenia before making the
diagnosis.

7. Postpsychotic Depressive Disorder of Schizophrenia. After an acute schizophrenia

episode, some patients become depressed. The symptoms of postpsychotic depressive
disorder of schizophrenia can closely resemble the symptoms of the residual phase of
schizophrenia and the adverse effects of commonly used antipsychotic medications.
The diagnosis should not be made if they are substance induced or part of a mood
disorder due to a general medical condition. These depressive states occur in up to 25
percent of patients with schizophrenia and are associated with an increased risk of
suicide.

8. Early-Onset Schizophrenia. A small minority of patients manifest schizophrenia in

childhood. Such children may at first present diagnostic problems, particularly with
differentiation from mental retardation and autistic disorder. Recent studies have
established that the diagnosis of childhood schizophrenia may be based on the same
symptoms used for adult schizophrenia. Its onset is usually insidious, its course tends
to be chronic, and the prognosis is mostly unfavorable.

9. Late-Onset Schizophrenia. Late-onset schizophrenia is clinically indistinguishable

from schizophrenia but has an onset after age 45 years. This condition tends to appear
more frequently in women and tends to be characterized by a predominance of
paranoid symptoms. The prognosis is favorable, and these patients usually do well on
antipsychotic medication.

10. Deficit Schizophrenia. In the 1980s, criteria were promulgated for a subtype of
schizophrenia characterized by enduring, idiopathic negative symptoms. These
patients were said to exhibit the deficit syndrome. This group of patients is now said
to have deficit schizophrenia. Patients with schizophrenia with positive symptoms are
said to have nondeficit schizophrenia. The symptoms used to define deficit
schizophrenia are strongly interrelated, although various combinations of the six
negative symptoms in the criteria can be found.

OTHER PSYCHOTIC DISORDER

Schizophrenia is a form of psychotic disorder, but it is not the only one. There are a number
of other types of psychotic disorders, such as schizoaffective disorder, schizophreniform
disorder, delusional disorder, and brief psychotic disorder.

Schizoaffective Disorder
The DSM-5 recognizes a diagnostic category called schizoaffective disorder. This diagnosis
is conceptually something of a hybrid, in that it is used to describe people who have features
of schizophrenia and severe mood disorder. In other words, the person not only has psychotic
symptoms that meet criteria for schizophrenia but also has marked changes in mood for a
substantial amount of time. Because mood disorders can be unipolar or bipolar in type, these
are recognized as subtypes of schizoaffective disorder.

DSM-5 CRITERIA
A. An uninterrupted period of illness during which there is a major mood episode (major
depressive or manic) concurrent with Criterion A of schizophrenia.
A1: Depressed mood.
B. 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.
C. Symptoms that meet criteria for a major mood episode are present for the majority of the
total duration of the active and residual portions of the illness.
D. The disturbance is not attributable to the effects of a substance (e.g., a drug of abuse, a
medication) or another medical condition.

In general, the prognosis for patients diagnosed with schizoaffective disorder is somewhere
between that of patients with schizophrenia and that of patients with mood disorders.
Research suggests that the long-term (10-year) outcome is much better for patients with
schizoaffective disorder than it is for patients with schizophrenia.

Schizophreniform Disorder
Schizophreniform disorder is a category reserved for schizophrenia-like psychoses that last at
least a month but do not last for 6 months and so do not warrant a diagnosis of
schizophrenia . It may include any of the symptoms described in the preceding sections.
Because of the possibility of an early and lasting remission after a first psychotic breakdown,
the prognosis for schizophreniform disorder is better than that for established forms of
schizophrenia.

DSM-5 CRITERIA
A. Two (or more) of the following, each present for a significant
portion of time during a 1-month period (or less if successfully
treated). At least one 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 behavior.
5. Negative symptoms (i.e., diminished emotional expression or avolition).
B. An episode of the disorder lasts at least 1 month but less than 6 months. When the
diagnosis must be made without waiting for recovery, it should be qualified as “provisional.”
C. 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.
D. The disturbance is not attributable to the physiological effects of a substance (e.g., a drug
of abuse, a medication) or another medical condition.

Delusional disorder
Patients with delusional disorder, like many people with schizophrenia, hold beliefs that are
considered false and absurd by those around them. Unlike individuals with schizophrenia,
however, people given the diagnosis of delusional disorder may otherwise behave quite
normally. One interesting subtype of delusional disorder is erotomania. Here, the theme of
the delusion involves great love for a person, usually of higher status. Some evidence
suggests that a significant proportion of female stalkers are diagnosed with erotomania.

DSM-5 CRITERIA
A. The presence of one (or more) delusions with a duration of 1 month or longer.
B. Criterion A for schizophrenia has never been met.
C. Apart from the impact of the delusion(s) or its ramifications, functioning is not markedly
impaired, and behavior is not obviously bizarre or odd.
D. If manic or major depressive episodes have occurred, these have been brief relative to the
duration of the delusional periods.
E. The disturbance is not attributable to the physiological effects of a substance or another
medical condition and is not better explained by another mental disorder, such as body
dysmorphic disorder obsessive-compulsive disorder.
SHARED PSYCHOTIC DISORDER
Shared psychotic disorder (also referred to over the years as shared paranoid disorder,
induced psychotic disorder, folie impose, and double insanity) was first described by two
French psychiatrists, Lasegue and Falret, in 1877, who named it folie á deux. In DSM-5, this
disorder is referred to as “Delusional Symptoms in Partner of Individual with Delusional
Disorder,” an unnecessary nomenclature change in the view of most psychiatrists.
It is probably rare, but incidence and prevalence figures are lacking, and the literature
consists almost entirely of case reports. The disorder is characterized by the transfer of
delusions from one person to another. Both persons are closely associated for a long time and
typically live together in relative social isolation.

Brief Psychotic Disorder

Brief psychotic disorder is exactly what its name suggests. It involves the sudden onset of
psychotic symptoms or disorganized speech or catatonic behavior. Even though there is often
great emotional turmoil, the episode usually lasts only a matter of days (too short to warrant a
diagnosis of schizophreniform disorder). After this, the person returns to his or her former
level of functioning and may never have another episode again.
Cases of brief psychotic disorder are infrequently seen in clinical settings, perhaps because
they remit so quickly. Brief psychotic disorder is often triggered by stress, as illustrated in the
following case.

DSM-5 CRITERIA
A. Presence of one (or more) of the following symptoms. At least one 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 behavior.
Note: Do not include a symptom if it is a culturally sanctioned response.
B. Duration of an episode of the disturbance is at least 1 day but less than 1 month, with
eventual full return to premorbid level of functioning.
C. The disturbance is not better explained by major depressive or bipolar disorder with
psychotic features or another psychotic disorder such as schizophrenia or catatonia, and is not
attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or
another medical condition.
History
Brief psychotic disorder has been poorly studied in psychiatry in the United States, partly
because of the frequent changes in diagnostic criteria during the past 15 years. The diagnosis
has been better appreciated and more completely studied in Scandinavia and other Western
European countries than in the United States. Patients with disorders similar to brief
psychotic disorder were previously classified as having reactive, hysterical, stress, and
psychogenic psychoses.
Reactive psychosis was often used as a synonym for good-prognosis schizophrenia, but a
diagnosis of brief psychotic disorder is not meant to imply a relation with schizophrenia. In
1913, Karl Jaspers described several essential features for the diagnosis of reactive psychosis,
including an identifiable and extremely traumatic stressor, a close temporal relation between
the stressor and the development of the psychosis, and a generally benign course for the
psychotic episode. Jaspers also stated that the content of the psychosis often rejected the
nature of the traumatic experience and that the development of the psychosis seemed to serve
a purpose for the patient, often as an escape from a traumatic condition.

PSYCHOTIC DISORDER NOT OTHERWISE SPECIFIED

Under the umbrella of psychosis not otherwise specified is a variety of clinical presentations
that do not fit within current diagnostic rubrics. It includes psychotic symptomatology (i.e.,
delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior)
about which there is inadequate information to make a specific diagnosis or about which
there is contradictory information. It also includes disorders with psychotic symptoms that do
not meet the criteria for any specific psychotic disorder, such as patients who present to
hospital with persistent auditory hallucinations that are not accompanied by mood
disturbances and that are not pathognomonic for schizophrenia.

Autoscopic Psychosis
Although not included in DSM-5, autoscopic psychosis is of clinical interest. The
characteristic symptom of autoscopic psychosis is a visual hallucination of all or part of the
person’s own body. The hallucinatory perception, which is called a phantom, is usually
colorless and transparent, and because the phantom imitates the person’s movements, it is
perceived as though appearing in a mirror. The phantom tends to appear suddenly and
without warning.
Motility Psychosis
Motility psychosis is not considered an “oϫcial” DSM-5 diagnosis but is of clinical
significance. It is probably a variant of brief psychotic disorder. The two forms of motility
psychosis are akinetic and hyperkinetic. The akinetic form of motility psychosis has a clinical
presentation similar to that of catatonic stupor. In contrast to the catatonic type of
schizophrenia, however, akinetic motility psychosis has a rapidly resolving and favourable
course that does not lead to personality deterioration. In its hyperkinetic form, motility
psychosis can resemble manic or catatonic excitement. As with the akinetic form, the
hyperkinetic form usually has a rapidly resolving and favorable course. Patients may switch
from the akinetic to hyperkinetic form rapidly and may represent a danger to others during
the excited phase. Mood is extremely labile in these patients.
Postpartum Psychosis
Postpartum psychosis (sometimes called puerperal psychosis) is an example of psychotic
disorder not otherwise speciϧed that occurs in women who have recently delivered a baby;the
syndrome is most often characterized by the mother’s depression, delusions, and thoughts of
harming either her infant or herself.

PSYCHOTIC DISORDERS DUE TO A GENERAL MEDICAL CONDITION AND

SUBSTANCE- OR MEDICATION-INDUCED PSYCHOTIC DISORDER
The evaluation of a patient with psychotic disorders requires consideration of the possibility
that the psychotic symptoms result from a general medical condition such as a brain tumor or
the ingestion of a substance such as phencyclidine (PCP) or medication such as cortisol.

Substance- or Medication-Induced Psychotic Disorder

The diagnostic category of substance-induced psychotic disorder is reserved for those with
psychotic symptoms and impaired reality testing caused by substances or medications. People
with substance-induced psychotic symptoms but with intact reality testing should be
classified as having a substance-related disorder . The full diagnosis of substance-induced
psychotic disorder should include the type of substance or medication involved, the stage of
substance use when the disorder began (e.g., during intoxication or withdrawal), and the
clinical phenomena (e.g., hallucinations or delusions).

Clinical Features

Hallucinations
● Hallucinations can occur in one or more sensory modalities. Tactile hallucinations
are characteristic of cocaine use. Auditory hallucinations are usually associated with
psychoactive substance abuse; auditory hallucinations can also occur in persons who
are deaf. Olfactory hallucinations can result from temporal lobe epilepsy; visual
hallucinations can occur in persons who are blind because of cataracts. Hallucinations
are either recurrent or persistent and are experienced in a state of full wakefulness and
alertness; a hallucinating patient shows no significant changes in cognitive functions.
Visual hallucinations often take the form of scenes involving diminutive human
figures or small animals. Rare musical hallucinations typically feature religious songs.
Patients with psychotic disorder caused by a general medical condition and substance-
induced psychotic disorder may act on their hallucinations. In alcohol-related
hallucinations, threatening, critical, or insulting third-person voices speak about the
 patients and may tell them to harm either themselves or others. Such patients are
dangerous and are at significant risk for suicide or homicide.
● Patients may or may not believe that the hallucinations are real.

Delusions
● Secondary and substance-induced delusions are usually present in a state of full
wakefulness. Patients may appear confused, disheveled, or eccentric, with tangential
or even incoherent speech. Hyperactivity and apathy may be present, and an
associated dysphoric mood is thought to be common. The delusions can be
systematized or fragmentary, with varying content, but persecutory delusions are the
most common.

References:-
American Psychiatric Association (2000). Diagnostic and Statistical Manual of mental
disorders (4th ed, text rev.). American Psychiatric Association.
Butcher, J. N., Hooley, J. M., &Mineka, S. (2014). Abnormal Psychology (16th ed.). U.S.A :
Pearson Education, Inc.
Sadock, B. J., Sadock, V. A., & Ruiz, P. (2015). Kaplan &Sadock’s Synopsis of Psychiatry
Behavioral Sciences/ Clinical Psychiatry ( 11th ed.). U.S.A :Wolters Kluwer.