Schizophrenia

• The symptoms of mental disorders include

deficient or inappropriate social behaviors;
illogical, incoherent, or obsessional thoughts;
inappropriate emotional responses, including
depression, mania, or anxiety; and delusions and
hallucinations.
• Research in recent years indicates that many of
these symptoms are caused by abnormalities in
the brain, both structural and biochemical.
• Schizophrenia is a serious mental disorder that
afflicts approximately 1 percent of the world's
population.
• Its monetary cost to society is enormous; in
the United States this figure exceeds that of
the cost of all cancers (Thaker and Carpenter,
2001).
• The major symptoms of schizophrenia are
universal, and clinicians have developed criteria
for reliably diagnosing the disorder in people of
a wide variety of cultures (Flaum and Andreasen,
1990).
• Schizophrenia is probably the most misused
psychological term in existence. The word
literally means "split mind," but it does not imply
a split or multiple personality.
• The man who invented the term, Eugen Bleuler
(1911/1950), intended it to refer to a break with
reality caused by disorganization of the various
functions of the mind, such that thoughts and
feelings no longer worked together normally.
• Schizophrenia is characterized by two
categories of symptoms: positive and negative
(Crow, 1980; Andreasen, 1995).
• Positive symptoms make themselves known by
their presence. They include thought disorders,
hallucinations, and delusions.
• In contrast to the positive symptoms, the
negative symptoms of schizophrenia are
known by the absence of normal behaviors:
flattened emotional response, poverty of
speech, lack of initiative and persistence,
inability to experience pleasure, and social
withdrawal.
• Negative symptoms are not specific to
schizophrenia; they are seen in many neurological
disorders that involve brain damage, especially to
the frontal lobes.
• Research suggests that these two sets of symptoms
are caused by different abnormalities in the brain:
Positive symptoms appear to involve excessive
activity in some neural circuits that include
dopamine as a neurotransmitter, and negative
symptoms appear to be caused by developmental
or degenerative processes that impair the normal
functions of some regions of the brain.
• Recent evidence suggests that these two sets of
symptoms may involve a common set of underlying
causes.
• Heritability
• One of the strongest pieces of evidence that schizophrenia
is a biological disorder is that it appears to be heritable.
• Both adoption studies (Kety et al., 1968, 1994) and
• twin studies (Gottesman and Shields, 1982; Tsuang,
Gilbertson, and Faraone, 1991) indicate that schizophrenia
is a heritable trait.
• If schizophrenia were a simple trait produced by a single
gene, we would expect to see this disorder in at least 75
percent of the children of two schizophrenic parents if the
gene were dominant. If it were recessive, all children of two
schizophrenic parents should become schizophrenic.
• However, the actual incidence is less than 50 percent, which
means either that several genes are involved or that having
a schizophrenia gene" imparts a susceptibility to develop
schizophrenia, the disease itself being triggered by other
factors.
Neurotransmitters based explanations
of schizophrenia
• Glutamate hypothesis:
• Glutamate is an important neurotransmitter present
in over 90% of all brain synapses and is a naturally
occurring molecule that nerve cells use to send
signals to other cells in the central nervous system.
Glutamate plays an essential role in normal brain
functioning and its levels must be tightly regulated.
Abnormalities in glutamate function can disrupt
nerve health and communication, and in extreme
cases may lead to nerve cell death.
• Deficiency in the release of glutamate may contribute
towards schizophrenia. (Especially at prefrontal cortex,
hippocampus leads to deterioration of memory and
reasoning.
• GABA hypothesis:
• GABA is considered an inhibitory neurotransmitter
because it blocks, or inhibits, certain brain signals and
decreases activity in your nervous system.
• When GABA attaches to a protein in your brain known as a
GABA receptor, it produces a calming effect. This can help
with feelings of anxiety, stress, and fear. It may also help to
prevent seizures.
• As a result of these properties, GABA has also become a
popular supplement in recent years. This is partly because
it isn’t available from many food sources. The only foods
that contain GABA are fermented (yogurt, olives) ones
(relieve in anxiety, high blood pressure, insomnia, fatigue,
stress)
• GABA supplements on Amazon
• Deficiency in the release of GABA may also contribute
towards schizophrenia.
• Serotonin hypothesis:
• Serotonin is found mostly in the digestive system, although it’s also in blood
platelets and throughout the central nervous system.
• Moreover, serotonin has been implicated in a variety of behaviors and
somatic functions that are disturbed in schizophrenia (eg, perception,
attention, mood, aggression, sexual drive, appetite, motor behavior, and
sleep).
• Serotonin is made from the essential amino acid tryptophan. This amino acid
must enter your body through your diet and is commonly found in foods
such as nuts, cheese, and red meat. Tryptophan deficiency can lead to lower
serotonin levels. This can result in mood disorders, such as anxiety or
depression.
• selective serotonin reuptake inhibitor (SSRI) by doctors when its low OR
naturally……Exposure to bright light (treating seasonal depression!),
Exercise, healthy diet (eggs, cheese, nuts, salmon, tofu, and pineapple).
• Meditation: Meditating can help relieve stress and promote a positive
outlook on life, which can greatly boost serotonin levels.
• Serotonin neurons regulate Dopamine neurons in the mesolimbic system. So
the interaction between Serotonin and Dopamine may be critical in
understanding Schizophrenia. It was also found that some new drugs that
treat schizophrenia bind to Serotonin receptors.
 Pharmacology of Schizophrenia:
The Dopamine Hypothesis
• Schizophrenia is caused by over activity of
dopaminergic synapses, probably those in the
mesolimbic pathway, which projects from the
ventral tegmental area to the nucleus
accumbens and amygdala.
• Almost fifty years ago, a French surgeon
named Henri Laborit discovered that a drug
used to prevent surgical shock seemed also to
reduce anxiety (Snyder, 1974).
MFB=Medial Forebrain Bundle, ATV= Aire Tegmental Ventricle
• A French drug company developed a related
compound called chlorpromazine, which
seemed to be even more effective. The
discovery of the antipsychotic effects of
chlorpromazine profoundly altered the way in
which physicians treated schizophrenic
patients and made prolonged hospital stays
unnecessary for many of them (the patients,
that is).
• Since the discovery of chlorpromazine, many
other drugs have been developed that relieve
the positive symptoms of schizophrenia.
• They block dopamine receptors (Creese, Burt,
and Snyder, 1976). Other drugs that interfere
with dopaminergic transmission, such as
reserpine (which prevents the storage of
monoamines in synaptic vesicles) or a-methyl
p-tyrosine (which blocks the synthesis of
dopamine), either facilitate the antipsychotic
action of drugs such as chlorpromazine or
themselves exert antipsychotic effects
(Tamminga et al., 1988).
• Thus, the positive symptoms of schizophrenia
are reduced by a variety of drugs with one
common effect: antagonism (interference in
or inhibition of the physiological action of a
chemical substance by another having a
similar structure) of dopaminergic
transmission.
• Another category of drugs has the opposite effect,
namely, production of the positive symptoms of
schizophrenia. The drugs that can produce these
symptoms have one known pharmacological effect
in common: They act as dopamine agonists.
• These drugs include amphetamine, cocaine, and
methylphenidate (which block the reuptake of
dopamine) and L-DOPA (which stimulates the
synthesis of dopamine).
• The symptoms that these drugs produce can be
alleviated with antipsychotic drugs, a result that
further strengthens the argument that the
antipsychotic drugs exert their therapeutic effects
by blocking dopamine receptors.
• Snyder (1974) notes that schizophrenics often
report feelings of elation and euphoria at the
beginning of a schizophrenic episode, when
their symptoms flare up.
• Presumably, this euphoria is caused by
hyperactivity of dopaminergic neurons
involved in reinforcement.
• The positive symptoms of schizophrenia also
include disordered thinking and unpleasant,
often terrifying delusions.
• The disordered thinking may be caused by
disorganized attentional processes; the
indiscriminate activity of the dopaminergic
synapses in the nucleus accumbens makes it
difficult for the patients to follow an orderly,
rational thought sequence.