• SCHIZOPHRENIA

• Clinical Symptoms

• It is the German psychiatrist Emil Kraepelin, who is best known for his careful description of
what we now regard as schizophrenia.

• He referred to the condition as ‘dementia praecox’ -“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”

• It was a Swiss psychiatrist named Eugen Bleuler who gave us the diagnostic term we still use
today.

• 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.

• Hallmark symptoms of this major form of psychotic disorder:

1. Delusions

• A delusion is essentially an erroneous belief that is fixed and firmly held despite clear
contradictory evidence.

• It 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 (Cutting,1995).

• Prominent delusions 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)

✓ That some external agency has robbed one of one’s thoughts (thought withdrawal).

✓ 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.

2. 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.

• Hallucinations can occur in any sensory modality (auditory, visual, olfactory, tactile, or
gustatory).

• Auditory hallucinations (e.g., hearing voices) are by far the most common.

• In a sample recruited from 7 different countries, auditory hallucinations were found in 75

percent of patients with schizophrenia (Bauer et al., 2011). 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).

• 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”).

• Imaging studies reveal that hallucinating patients show increased activity in Broca’s Area.

• 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 (Shergill et al., 2000).

• Overall, 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.

• 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
hallucinations (Hoffman et al.,2005)!
 • Modern research approaches are thus supporting a very old idea: Auditory hallucinations are
really a form of misperceived subvocal speech (Gould, 1949).

3. Disorganized Speech and Behavior

• Disorganized speech, is the external manifestation of a disorder in thought form.

• Basically, an affected person fails to make sense, despite seeming to conform to 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 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.

✓ 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 (Lenzenweger & Dworkin, 1998).

• 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.

4. Positive and Negative Symptoms

 • Disordered speech and disorganized behavior that were previously thought to reflect
positive symptoms might be better separated from “true” positive symptoms like
hallucinations and delusions.

• A disorganized symptom pattern is now also recognized (Lenzenweger et al.,1991).

• Positive symptoms are those that reflect an excess or distortion in a normal repertoire of
behavior and experience, such as delusions and hallucinations.

Positive Symptoms

• Hallucinations

• Delusions

Negative Symptoms

• Emotional flattening

• Poverty of speech

• Asociality

• Apathy

• Anhedonia

Disorganized Symptoms

• Bizarre behavior

• Disorganized speech

• Negative symptoms, by contrast, reflect an absence or deficit of behaviors that are normally
present.

• Important negative symptoms in schizophrenia include flat affect, or blunted emotional

expressiveness, and alogia, which means very little speech, avolition, or the inability to
initiate or persist in goal-directed activities. 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.

• A preponderance of negative symptoms in the clinical picture is not a good sign for the
patient’s future outcome (e.g., Fenton & McGlashan, 1994; Milev et al., 2005).

• 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.
 • Findings of the study suggested that even though patients with schizophrenia may
sometimes not look very emotionally expressive, they are nonetheless experiencing plenty
of emotion.

DSM 5

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. Impairment in level of 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.

D. Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been
ruled out.

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

• DSM-IV-TR Diagnostic Criteria for Schizophrenia Subtypes

1. 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.

[Link] 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

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

A type of Schizophrenia in which symptoms that meet Criterion A are present, but the criteria are
not met for the Paranoid, Disorganized, or Catatonic Type.

5. 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)

• Unfortunately, research using the subtyping approach did not yield major insights into the
etiology or treatment of the disorder. Reflecting this, subtypes of schizophrenia are no
longer included in DSM-5.

• Other Psychotic Disorders

1. Schizoaffective Disorder

• It is used to describe people who have features of schizophrenia and severe mood disorder.

• Because mood disorders can be unipolar or bipolar in type, these are recognized as subtypes
of schizoaffective disorder.

• The reliability of schizoaffective disorder tends to be quite poor, and clinicians often do not
agree about who meets the criteria for the diagnosis.
 • In an effort to improve this, in DSM-5 it is specified that mood symptoms have to meet
criteria for a full major mood episode and also have to be present for more than 50% of the
total duration of the illness.

• This clarification should help improve the reliability of this diagnosis and possibly also
decrease the number of people who receive it.

• The prognosis for patients diagnosed with schizoaffective disorder is somewhere between
that of patients with schizophrenia and that of patients with mood disorders (Walker et al.,
2004).

DSM 5

A. An uninterrupted period of illness during which there is a major mood episode (major depressive
or manic) concurrent with Criterion A of schizophrenia.

• Note: The major depressive episode must include Criterion 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.

2. Schizophreniform Disorder

• 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

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):

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

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.

3. 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.

• Their behavior does not show the gross disorganization and performance deficiencies
characteristic of schizophrenia, and general behavioral deterioration is rarely observed in
this disorder, even when it proves chronic.

• One interesting subtype of delusional disorder is erotomania.

• Here, the theme of the delusion involves great love for a person, usually of higher status.

DSM 5

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
or obsessive-compulsive disorder.

4. 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.

• 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.

DSM 5
A. Presence of one (or more) of the following symptoms. At least one of these must be (1), (2), or
(3):

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.

• SCHIZOPHRENIA- ETIOLOGY

• Etiology

• No one factor can fully explain why schizophrenia develops.

• Psychiatric disorders are not the result of a single genetic switch being flipped. Rather, a
complex interplay between genetic and environmental factors is responsible.

I. BIOLOGICAL FACTORS

1. Genetic Factors

• Disorders of the schizophrenia type are “familial” and tend to “run in families.”

• There is overwhelming evidence for higher-than-expected rates of schizophrenia among

biological relatives of patients.

• There is a strong association between the closeness of the blood relationship (i.e., level of
gene sharing or consanguinity) and the risk for developing the disorder.

• Just because something runs in families does not automatically implicate genetic factors.
The terms familial and genetic are not synonymous.

• To disentangle the contributions of genes and environment, we need twin and adoption
studies.

• Concordance rates for identical twins are routinely and consistently found to be significantly
higher than those for fraternal twins or ordinary siblings.

• E. Fuller Torrey and his colleagues (1994) have published a review of the major literature
worldwide on twin studies of schizophrenia. The overall pair wise concordance rate is 28
percent in MZ twins and 6 percent in DZ twins.

• Concordance rates vary from one twin study to another.

• Two conclusions can therefore be drawn:

✓ First, genes undoubtedly play a role in causing schizophrenia.

✓ Second, genes themselves are not the whole story. Twin studies provide some of the most
solid evidence that the environment plays an important role in the development of
schizophrenia.

• Some of the studies found that predisposition to schizophrenia may remain “unexpressed”
(as in the twins without schizophrenia in discordant pairs) unless “released” by unknown
environmental factors.

• If children with high risk are raised in a benign environment, even children who are at
genetic risk for schizophrenia appear to do very well.

• Only those children who were raised in dysfunctional families and had high genetic risk for
schizophrenia went on to develop schizophrenia-related disorders themselves.

• Children at high genetic risk who were raised in healthy family environments did not
develop problems any more frequently than did children at low genetic risk.

• Thus, family studies tell us that schizophrenia runs in families, and twin and adoption studies
help us explore the relative contributions of genes and environment.

• Some of the studies found that predisposition to schizophrenia may remain “unexpressed”
(as in the twins without schizophrenia in discordant pairs) unless “released” by unknown
environmental factors.

• If children with high risk are raised in a benign environment, even children who are at
genetic risk for schizophrenia appear to do very well.

• Only those children who were raised in dysfunctional families and had high genetic risk for
schizophrenia went on to develop schizophrenia-related disorders themselves.

• Children at high genetic risk who were raised in healthy family environments did not
develop problems any more frequently than did children at low genetic risk.

• Thus, family studies tell us that schizophrenia runs in families, and twin and adoption studies
help us explore the relative contributions of genes and environment.

• Molecular Genetics: Schizophrenia probably involves many genes working together to

confer susceptibility to the illness.

• Studies are suggesting specific regions on certain chromosomes that may contribute to
schizophrenia. Currently, there is a great deal of interest in regions on chromosomes 1, 2, 6,
8, 13, and 22 among others.

• E.g. COMT (catechol-O-methyltransferase) gene, located on chromosome 22, involved in

dopamine metabolism(implicated in psychosis).

• Major collaborative studies designed to explore different endophenotypes (discrete, stable,

and measurable traits that are thought to be under genetic control), which will help
researchers to get closer to specific genes that might be important in schizophrenia, are now
under way.
2. Prenatal Exposures

• Viral Infection: Risk of schizophrenia seems to be greatest when the mother gets the flu in
the fourth to seventh month of gestation. One possibility is that the mother’s antibodies to
the virus cross the placenta and somehow disrupt the neurodevelopment of the fetus.

• Rhesus Incompatibility: Rhesus (Rh) Incompatibility occurs when an Rh-negative mother

carries an Rh-positive fetus. Rh incompatibility also seems to be associated with increased
risk for schizophrenia.

• Hollister, Laing, and Mednick (1996) have shown that the rate of schizophrenia is about 2.1
percent in males who are Rh-incompatible with their mothers. For males who have no such
incompatibility with their mothers, the rate of schizophrenia is 0.8 percent.

• Pregnancy and Birth Complications: Research points toward damage to the brain during
delivery time due obstetric complications (e.g., breech delivery, prolonged labour, or the
umbilical cord around the baby’s neck) to risk of developing schizophrenia.

• Nutritional Deficiency: Early prenatal nutritional deficiency appears to have been the cause.
Whether the problem was general malnutrition or the lack of a specific nutrient such as
folate or iron is not clear. But again, something seems to have compromised the
development of the fetus during a critical stage contributing to risk of later developing
schizophrenia (Brown, 2011).

• Maternal Stress: If a mother experiences an extremely stressful event late in her first
trimester of pregnancy or early in the second trimester the risk of schizophrenia in her child
is increased (King et al., 2010). Currently, it is thought that the increase in stress hormones
that pass to the fetus via the placenta might have negative effects on the developing brain.

3. A Neurodevelopmental Perspective

• Schizophrenia typically strikes people in late adolescence or early adulthood. Yet in the
sections above, we saw that some of the factors thought to cause schizophrenia occur very
early in life—in some cases before birth.

• Current thinking is that schizophrenia is a disorder in which the development of the brain is
disturbed very early on.

• Nonetheless, problems may not be apparent until other triggering events take place or until
the normal maturation of the brain reveals them.

• Studies revealed that the “preschizophrenia” children showed more motor abnormalities
including unusual hand movements than their healthy siblings; they also showed less
positive facial emotion and more negative facial emotion.

• Both groups of researchers found evidence of delayed speech and delayed motor
development at age 2 in children who later went on to develop schizophrenia.
 • Children with a genetic risk for schizophrenia are more deviant than control children on
research tasks that measure attention, lower social competence in adolescence, early motor
abnormalities, unusual motor behaviour, personality or behavioural problems.

4. Structural and Functional Brain Abnormalities

• Positron emission tomography (PET), magnetic resonance imaging (MRI), and other even
more sophisticated approaches are in wide use. They are revealing abnormalities in the
structure and function of the brain as well as in neurotransmitter activity in people who
suffer from schizophrenia.

• Neurocognition: Schizophrenia patients experience many problems with their

neurocognitive functioning. For example, they perform much worse than healthy controls on
a broad range of neuropsychological tests.

• Cognitive difficulties can be seen right from the start of the illness

• Poor reaction time (prefrontal brain activity), poor smooth-pursuit eye movement, poor P50
suppression (specific receptors in the hippocampus of the medial temporal lobe) are shown
by schizophrenia patients.

• Loss of Brain Volume: Compared with controls, patients with schizophrenia have enlarged
brain ventricles, with males possibly being more affected than females.

• Apparent only in a significant minority of patients.

• Enlarged brain ventricles also are not specific to schizophrenia and can be seen in patients
with Alzheimer’s disease, Huntington’s disease, and chronic alcohol problems.

• Enlarged brain ventricles are important because they are an indicator of a reduction in the
amount of brain tissue.

• MRI studies of patients with schizophrenia show about a 3 percent reduction in whole brain
volume relative to that in controls.

• This decrease in brain volume is present very early in the illness. Even patients with a recent
onset of schizophrenia have lower overall brain volumes than controls (not as a
consequence of taking neuroleptic medications; play a causal role in the onset of
symptoms.)

• Studies showed that the volume of gray matter declined significantly over time in the
patients but not in the controls. More specifically, there was almost a 3 percent decrease in
the volume of gray matter in the patients in the 1-year period between the first and the
second scans.

• Theses suggest that in addition to being a neurodevelopmental disorder, schizophrenia is

also a neuroprogressive disorder characterized by a loss of brain tissue over time (cannot be
explained by the influence of antipsychotic medications and may instead be under genetic
control).
• Affected Brain Areas : There is evidence of reductions in the volume of regions in the frontal
and temporal lobes. These brain areas play critical roles in memory, decision making, and in
the processing of auditory information.

• More specifically, there is a reduction in the volume of such medial temporal areas as the
amygdala—which is involved in emotion, the hippocampus—which plays a key role in
memory, and the thalamus—a relay center that receives almost all sensory input.

• However, the alterations in brain structure that are found in schizophrenia are not specific
only to this diagnosis.

• White Matter Problems: Evidence is growing that schizophrenia also involves problems with
white matter.

• If there are disruptions in the integrity of white matter, there will be problems in how well
the cells of the nervous system can function.

• Studies of patients with schizophrenia show that they have reductions in white matter
volume as well as structural abnormalities in the white matter itself.

• White matter abnormalities have been shown to be correlated with cognitive impairments.

• Another interesting recent finding is that children of people with schizophrenia, even though
they are not psychotic themselves, have a reduction in the volume of the corpus callosum—
a massive tract of white matter fibres that connects the two hemispheres of the brain
(Francis et al., 2011).

• Brain Functioning: Neuroimaging research is showing us just how disrupted brain

functioning is in patients with this disorder.

• Again, however, it is important to remember that such alterations in functioning are not
characteristic of all patients.

• Nonetheless, frontal lobe dysfunction is believed to account for some of the negative
symptoms of schizophrenia and perhaps to be involved in some attentional-cognitive
deficits.

• Abnormally low frontal lobe activation, hyperactivation in frontal brain areas etc. were seen
when asked to do various tasks.

• Dysfunction of the temporal lobe is also found, although here the findings are often not very
consistent.

• Cytoarchitecture: One hypothesis about schizophrenia is that genetic vulnerabilities,

perhaps combined with prenatal insults, can lead to-

✓ disruption of the migration of neurons in the brain

✓ cells will fail to arrive at their final destinations

✓ overall organization of cells in the brain (the brain’s cytoarchitecture) will be compromised.

• Some researchers have reported an increase in neuronal density in some areas of the brains
of patients with schizophrenia

• There are also abnormalities in the distribution of cells in different layers of the cortex and
hippocampus

• There are that patients with schizophrenia are missing particular types of neurons known as
“inhibitory interneurons”, which are responsible for regulating the excitability of other
neurons.

• Their absence may mean that bursts of activity by excitatory neurons in the brain go
unchecked may be less (unable to regulate or dampen down overactivity).

• Brain Development in Adolescence:The brain continues to develop and mature through

adolescence and into young adulthood.

• But development fails to occur in a normal way in schziophrenics resulting in reduced gray
matter volume, less white matter, reduced volume of the hippocampus etc.

• Neurochemistry: alterations in brain chemistry may be associated with abnormal mental

states.

• The most well-studied neurotransmitter implicated in schizophrenia is dopamine.

• Activity in the dopamine system may play a role in determining how much salience we give
to internal and external stimuli.

• Dysregulated dopamine transmission may actually make us pay more attention to and give
more significance to stimuli that are not especially relevant or important. This is called
“aberrant salience”

• The person will struggle to make sense of everyday experiences that were previously in the
background but that now have become inappropriately important and worthy of attention,
developing delusions or experience hallucinations.

• Current thinking is that people with schizophrenia are supersensitive to dopamine (Seeman,
2011).

• This arises because they have greater numbers of a form of D2 receptor that has a very high
affinity for dopamine.

• Animal studies suggest that anoxia (oxygen deprivation) at the time of birth can lead to
dopamine supersensitivity.

• It is like a bridge between problems with dopamine system and some of the prenatal
problems (e.g., birth complications) that we discussed earlier.

• Glutamate is an excitatory neurotransmitter that is widespread in the brain.

 • Researchers suspect that a dysfunction in glutamate transmission might be involved in
schizophrenia.

• PCP, or angel dust, is known to block glutamate receptors. PCP also induces symptoms (both
positive and negative) that are very similar to those of schizophrenia. Moreover, when
people with schizophrenia take PCP, it exacerbates their symptoms.

• Like PCP, ketamine, which is an anesthetic, blocks glutamate receptors.

• Glutamate levels were low in postmortem brains of patients with schizophrenia (prefrontal
cortex and the hippocampus) as well as the brains of living patients who have schizophrenia

• Diminished activity at certain types of glutamate receptors (known as “NMDA” receptors)

may not only trigger schizophrenia- like symptoms but may also cause the degeneration of
neurons in key brain areas.

• Also, an overactive dopaminergic system could result in excessive suppression of glutamate,

leading to the underactivity of the NMDA receptors.

I. BIOLOGICAL FACTORS

1. Genetic Factors

• Familial

• Twin studies

• Adoption studies

• Molecular Genetics

• Endophenotypes

2. Prenatal Exposures

• Viral Infection

• Rhesus Incompatibility

• Pregnancy and Birth Complications

• Nutritional Deficiency

• Maternal Stress

3. A Neurodevelopmental Perspective

• development of the brain is disturbed very early on

• “preschizophrenia” children

4. Structural and Functional Brain Abnormalities

 • revealing abnormalities in the structure

• Neurocognition

• Loss of Brain Volume

• a neuroprogressive disorder

• Affected Brain Areas: frontal and temporal lobes

• White Matter Problems

• Brain Functioning-frontal lobe dysfunction

• Cytoarchitecture

• Brain Development in Adolescence

• Neurochemistry: Dopamine, Glutamate

• SCHIZOPHRENIA- TREATMENT/MANAGEMENT

• Men with schizophrenia die 14.6 years earlier than would be expected based on national
norms in UK.

• For women with schizoaffective disorder the reduction in lifespan is 17.5 years (Chang et al.,
2011).

• Some of the factors implicated in the early deaths of patients with schizophrenia and
schizophrenia-related illnesses are long term use of antipsychotic medications, obesity,
smoking, poor diet, use of illicit drugs, and lack of physical activity.

• The risk of suicide in patients with schizophrenia is also high compared to the general
population, with about 12 percent of patients ending their lives in this way (Dutta et al.,
2010).

• In general, overall mortality is lower in patients who are treated with antipsychotic
medications compared to untreated patients.

1. Pharmacological Approaches

• Medications are widely used in the treatment of schizophrenia.

• Over 60 different antipsychotic drugs have been developed.

• The common property that they all share is their ability to block dopamine D2 receptors in
the brain (Seeman, 2011).

First-Generation Antipsychotics

• They are medications like chlorpromazine (Thorazine) and haloperidol (Haldol), which were
among the first to be used to treat psychotic disorders.
• Sometimes referred to as neuroleptics (literally, “seizing the neuron”), these medications
revolutionized the treatment of schizophrenia when they were introduced in the 1950s.

• Can be regarded as one of the major medical advances of the twentieth century (Sharif et
al., 2007).

• Large numbers of clinical trials have demonstrated the efficacy and effectiveness of these
drugs (Sharif et al.,2007).

• Also, the earlier patients receive these medications, the better they tend to do over the
longer term.

• First-generation antipsychotics are thought to work because they are dopamine antagonists.

• They block the action of dopamine, primarily by blocking (occupying) the D2 dopamine
receptors.

• Some clinical change can be seen within the first 24 hours of treatment (Kapur et al., 2005).

• How a patient does on a particular medication in the first 2 to 4 weeks of treatment is a

good predictor of how much he or she will benefit overall.

• First-generation antipsychotics work best for the positive symptoms of schizophrenia.

• Common side effects of these medications include drowsiness, dry mouth, and weight gain.

• Many patients on these antipsychotics also experience what are known as extrapyramidal
side effects (EPS-involuntary movement abnormalities (muscle spasms, rigidity, shaking) that
resemble Parkinson’s disease.

• Some patients who have been treated with neuroleptics for long periods of time may also
develop tardive dyskinesia – involves marked involuntary movements of the lips and tongue
(and sometimes the hands and neck).

• Rates of tardive dyskinesia are about 56 percent when patients have taken neuroleptics for
10 years or more, with females being especially susceptible.

• Finally, in very rare cases there is a toxic reaction to the medication that is called neuroleptic
malignant syndrome (Strawn et al., 2007) - characterized by high fever and extreme muscle
rigidity, and if left untreated it can be fatal.

• Second-Generation Antipsychotics

• In the 1980s a new class of antipsychotic medications began to appear.

• The first of these to be used clinically was clozapine (Clozaril).

• Although initially reserved for use with treatment-refractory patients (those who were not
helped by other medications), clozapine is now used widely.
• Other examples of second-generation antipsychotic medications are risperidone (Risperdal),
olanzapine (Zyprexa), quetiapine (Seroquel), and ziprasidone (Geodon). More recent
additions include aripiprazole (Abilify) and lurasidone (Latuda).

• reason why these medications are called “second-generation antipsychotics” is that they
cause fewer extrapyramidal symptoms than the earlier antipsychotic medications.

• Although it was initially believed that second-generation antipsychotics were more effective
at treating the symptoms of schizophrenia, recent research findings provide no support for
this view (Lieberman & Stroup, 2011; Tandon et al., 2010).

• The exception here concerns clozapine, which does seem to be more valuable than other
medications for treatment refractory patients.

• Drowsiness and considerable weight gain are very common.

• Diabetes is also a very serious concern (Sernyak et al., 2002).

• In rare cases, clozapine also causes a life-threatening drop in white blood cells known as
agranulocytosis.

• For this reason, patients taking this medication must have regular blood tests.

• Women with schizophrenia tend to do better than men.

• They have a later age of onset and, often, seem to have a less severe form of the illness.

• This has prompted some researchers to explore the potentially beneficial role of estrogen in
the treatment of the disorder.

• The results of one of the studies (Kulkarni et al., 2008)suggested that estrogen has
antipsychotic effects and that providing supplemental estrogen to women with
schizophrenia may give them additional clinical benefits.

• Research using PET also shows that increased blockade of D2 dopamine receptors is
associated with patients reporting more negative subjective experiences such as feeling tired
and depressed even when other side effects (such as movement problems) are absent
(Mizrahi et al., 2007).

• This highlights the need for better medications and for using lower dosages wherever this is
clinically feasible.

• II. Family-Oriented Therapies

• Patients with schizophrenia are often discharged in an only partially remitted state-family to
which a patient returns can often benefit from a brief but intensive (as often as daily) course
of family therapy.

• The therapy should focus on the immediate situation and should include identifying and
avoiding potentially troublesome situations.
• When problems do emerge with the patient in the family, the aim of the therapy should be
to resolve the problem quickly.

• Family members often encourage a relative with schizophrenia to resume regular activities
too quickly, both from ignorance about the disorder and from denial of its severity.

• Therapists must help both the family and the patient understand and learn about
schizophrenia and must encourage discussion of the psychotic episode and the events
leading up to it.

• Ignoring the psychotic episode, a common occurrence, often increases the shame associated
with the event and does not exploit the freshness of the episode to understand it better.

• Psychotic symptoms often frighten family members, and talking openly with the psychiatrist
and with the relative with schizophrenia often eases all parties.

• Therapists can direct later family therapy toward long-range application of stress reducing
and coping strategies and toward the patient’s gradual reintegration into everyday life.

• Therapists must control the emotional intensity of family sessions with patients with
schizophrenia.

• The excessive expression of emotion during a session can damage a patient’s recovery
process and undermine potentially successful future family therapy.

• Several studies have shown that family therapy is especially effective in reducing relapses.

• National Alliance on Mental Illness (NAMI). The NAMI and similar organizations offer
support groups for family members and friends of patients who are mentally ill and for
patients themselves.

• These organizations offer emotional and practical advice about obtaining care in the
sometimes complex health care delivery system and are useful sources to which to refer
family members.

• NAMI has also waged a campaign to destigmatize mental illness and to increase government
awareness of the needs and rights of persons who are mentally ill and their families.

• Cognitive Behavioral Therapy

• Cognitive behavioral therapy has been used in schizophrenia patients to improve cognitive
distortions, reduce distractibility, and correct errors in judgment.

• There are reports of ameliorating delusions and hallucinations in some patients using this
method.

• Patients who might benefit generally have some insight into their illness.

• Cognitive-behavioral therapy (CBT) approaches are widely used in the treatment of mood
and anxiety disorders as well as many other conditions (Beck, 2005).
 • Until fairly recently, however, researchers did not consider using them for patients with
schizophrenia, no doubt because patients with schizophrenia were considered too impaired.

• Pioneered by researchers and clinicians in the United Kingdom, cognitive-behavioral

approaches have gained momentum in the treatment of schizophrenia.

• The goal of these treatments is to decrease the intensity of positive symptoms, reduce
relapse, and decrease social disability.

• Working together, therapist and patient explore the subjective nature of the patient’s
delusions and hallucinations, examine evidence for and against their veracity or veridicality,
and subject delusional beliefs to reality testing.

• Although the results from the early research studies were encouraging, whether CBT is an
effective treatment for schizophrenia is now the subject of some debate.

• Current data suggest that CBT is not very helpful for negative symptoms (Tandon et al.,
2010).

• A recent meta-analysis also suggests that CBT is no better than control interventions (often
supportive counselling) in the treatment of schizophrenia (Lynch et al., 2010).

• Nonetheless, the possibility that CBT works very well for some subgroups of patients is still a
very real possibility.

• Delivery of CBT in schizophrenia needs specialised training and is often conducted as an

adjunct to psychopharmacological therapy.

Behaviour Therapy

1. Social Skills Training

• Social skills training is sometimes referred to as behavioral skills therapy.

• Along with pharmacological therapy, this therapy can be directly supportive and useful to
the patient.

• In addition to the psychotic symptoms seen in patients with schizophrenia, other noticeable
symptoms involve the way the person relates to others,

- poor eye contact

- unusual delays in response

- odd facial expressions

- lack of spontaneity in social situations

- inaccurate perception or lack of perception of emotions in other people.

 • Behavioral skills training addresses these behaviors through the use of videotapes of others
and of the patient, role playing in therapy, and homework assignments for the specific skills
being practiced.

• Social skills training has been shown to reduce relapse rates as measured by the need for
hospitalization.

2. Assertive Community Treatment

• The Assertive Community Treatment (ACT) program was originally developed by researchers
in Madison, Wisconsin, in the 1970s, for the delivery of services for persons with chronic
mental illness.

• Patients are assigned to one multidisciplinary team (e.g., case manager, psychiatrist, nurse,
general physicians).

• The team has a fixed caseload of patients and delivers all services when and where needed
by the patient, 24 hours a day, 7 days a week.

• This is mobile and intensive intervention that provides treatment, rehabilitation, and
support activities.

• These include home delivery of medications, monitoring of mental and physical health, in
vivo social skills, and frequent contact with family members.

• There is a high staff-to-patient ratio (1:12).

• ACT programs can effectively decrease the risk of re-hospitalization for persons with
schizophrenia, but they are labor-intensive and expensive programs to administer.

3. Group Therapy

• Group therapy for persons with schizophrenia generally focuses on real-life plans, problems,
and relationships.

• Groups may be behaviorally oriented, psychodynamically or insight oriented, or supportive.

• Some investigators doubt that dynamic interpretation and insight therapy are valuable for
typical patients with schizophrenia.

• But group therapy is effective in reducing social isolation, increasing the sense of
cohesiveness, and improving reality testing for patients with schizophrenia.

• Groups led in a supportive manner appear to be most helpful for schizophrenia patients.

4. Personal Therapy

• A flexible type of psychotherapy called personal therapy is a recently developed form of

individual treatment for schizophrenia patients.

• Its objective is to enhance personal and social adjustment and to reduce relapse.
 • It is a select method using social skills and relaxation exercises, psycho-education, self-
reflection, self-awareness, and exploration of individual vulnerability to stress.

• The therapist provides a setting that stresses acceptance and empathy.

• Patients receiving personal therapy show improvement in social adjustment (a composite

measure that includes work performance, leisure, and interpersonal relationships) and have
a lower relapse rate after 3 years than patients not receiving personal therapy.

5. Dialectical Behavior Therapy

• This form of therapy, which combines cognitive and behavioral theories in both individual
and group settings, has proved useful in borderline states and may have benefit in
schizophrenia.

• Emphasis is placed on improving interpersonal skills in the presence of an active and

empathic therapist.

6. Vocational Therapy

• A variety of methods and settings are used to help patients regain old skills or develop new
ones.

• These include sheltered workshops, job clubs, and part-time or transitional employment
programs.

• Enabling patients to become gainfully employed is both a means toward, and a sign of,
recovery.

• Many schizophrenia patients are capable of performing high-quality work despite their
illness. Others may exhibit exceptional skill or even brilliance in a limited field as a result of
some idiosyncratic aspect of their disorder.

7. Art Therapy

• Many schizophrenia patients benefit from art therapy, which provides them with an outlet
for their constant bombardment of imagery.

• It helps them communicate with others and share their inner, often frightening world with
others.

Cognitive Training

• Cognitive training or cognitive remediation is a technique introduced recently for the

treatment of schizophrenia.

• It uses computerized training, such as sophisticated brain games, to target specific neural
pathways, such as memory, learning and auditory-based senses, to beneficially alter the way
they process information.
 • It has proven effective for mild to moderate forms of schizophrenia under carefully
controlled conditions, it remains unclear whether the approach might benefit patients with
chronic, refractory schizophrenia treated in non-academic settings, such as those cared for
in locked residential rehabilitation centers.

• The field is in its infancy and further work and replication of studies is needed; however, it is
a technique that is easily learned and administered and holds great promise.

Halfway Homes

• Most people with serious mental illnesses — in most communities across the nation —
housing choices are either limited or, more often, nonexistent. Either choices are made for
them (by others) or choices are made impossible by virtue of the scarcity of available
housing options.

• By definition, halfway houses is temporary and available only for a limited time.

• Usually, the expectation is that the person will “graduate” to permanent housing. Programs
funded by HUD, for example, have a 24-month limit.
Transitional programs provide care in between an inpatient stay and independent or
supportive living in the community.

• They are generally intended for people who require services and support before they’re able
to live independently, so there’s often a requirement that residents take advantage of the
services they provide.

• These may include 24/7 assistance with the activities of daily living, vocational rehabilitation,
medication management, social-skills training, provision of cafeteria-style meals, substance-
abuse services, and so on.

• Transitional housing can take place in a large congregate care setting (such as a community
residence) or in a smaller group home that is shared by two or more unrelated adults who
may or may not have their own bedrooms.

Day Hospitals

• The goal of treatment of psychotic patients is rehabilitation and return to living and
functioning in the community.

• To these ends was created the Psychiatric Day Hospital and Continuing Day Treatment.

• Psychiatric day hospitals offer care that is less restrictive than inpatient care but more
intense than outpatient care.

• Day hospitals can be used to provide more intense/specialised outpatient care to people
resistant to treatment (day treatment programmes) or to those needing long-term care (day
care centres). They can also bridge the gap between inpatient and outpatient care
(transitional day hospitals).
Vocational rehabilitation

• Vocational role with the right support can be of great benefit to people with psychosis and
schizophrenia in terms of health, social functioning and financial reward

• Within mental health services, the negative attitudes of mental health professionals towards
people with mental disorders may lead to pessimism and thus reduce aspirations and the
subsequent provision of services.

• Societal stigma and discrimination, the diagnostic label, fear of loss of or changes to
benefits, and lack of skills in exploring and putting in place employment support within
mainstream services are other factors that contribute to the problem.

• It is a reasonable assumption that back to work and in work support should be regarded as
an essential element of interventions for people with psychosis and schizophrenia in
recovery

• The longer the period of non-engagement with a role the greater the limitations of such
roles later in life

• Assessment and interventions relating to vocational rehabilitation may be offered by

occupational therapists and specialist employment advisors.

• To aid speed of access and a link to other clinical interventions, the person providing
employment interventions is based in the clinical multidisciplinary team.

• The predictors for gaining employment for people with psychosis and schizophrenia are a
work history and the desire to work, and there is evidence that the presence of positive
symptoms has a more advantageous influence on work outcomes compared with negative
symptoms.

• Upon gaining employment, it is important that people are supported to manage disclosure
at work, and negotiate reasonable adjustments and funding in order to provide the
appropriate support to the employer and employee.

• Many different types of vocational rehabilitation programs have been developed and
implemented. These are classified as follows (Bond and Boyer 1988): (1) hospital-based
programs; (2) sheltered work; (3) assertive case management; (4) psychosocial
rehabilitation, including prevocational training, transitional employment, and volunteer
placements; (5) supported employment; and (6) counselling and education.

• The outcomes targeted by vocational rehabilitation interventions are divided into two broad
categories. Vocational outcomes include full-time competitive employment, acquisition of
job-related skills, acquisition of any job (paid or volunteer), percentage of time in paid
employment (full-time or part-time, competitive or sheltered), total job earnings, level of job
(unskilled, skilled, etc.), job satisfaction, and job performance.

• Vocational rehabilitation also may enhance outcomes other than work. These therapeutic
outcomes include treatment compliance and symptom reduction, functional status in other
 areas (activities of daily living, maintenance of living situation, etc.), self-esteem, and
subjective quality of life.

• Vocational rehabilitation has assumed increasing importance as part of the array of services
available for persons with schizophrenia. Work not only provides financial remuneration but
is a normalizing experience, allowing individuals to participate in society, and may promote
self-esteem and quality of life. Furthermore, the vast majority of persons with severe mental
illnesses identify paid employment as one of their goals