1. VOICES IN HER HEAD
She hears them,
And she always has said,
"They whisper when they're mad,
and they scream when they are just barely there.
They hurt my thoughts,
and destroy my brain."
This poor girl lies awake at night,
As she wonders to herself,
"Are schizophrenics messengers of God?
Is there even a God?
I'm doubting myself,
The only person I know I can trust.
At least,
I thought I knew.
Now maybe I am just insane."
She goes about day to day,
Acts like everything is fine,
But the voices linger there,
Even controlled by medicine.
She still has stress,
She still has fear,
She still has anxiety,
She still has schizophrenia.
- Kimberly Anne

2. Presented by: Chairperson:
Priya Puri & Aditi Majumdar Dr. Sujit Sarkhel
1st Year Trainees Assistant Professor
Dept. of Clinical Psychology IOP, Kolkata
IOP, Kolkata
Date: 05-03-2012

3.  The schizophrenic disorders are characterized in general by
fundamental and characteristic distortions of thinking and perception,
and affects that are inappropriate or blunted. Clear consciousness and
intellectual capacity are usually maintained although certain cognitive
deficits may evolve in the course of time.
 The most important psychopathological phenomena include:
• thought echo
• thought insertion or withdrawal
• thought broadcasting
• delusional perception and delusions of control
• influence or passivity
• hallucinatory voices commenting or discussing the patient in the third
person
• thought disorders and negative symptoms.

4.  Schizophrenia occurs with regular frequency nearly everywhere in the
world in 1 % of population and begins mainly in young age (mostly
around 16 to 25 years).
 Schizophrenia is defined by
◦ a group of characteristic positive and negative symptoms
◦ deterioration in social, occupational, or interpersonal relationships
◦ continuous signs of the disturbance for at least 6 months

5.  Morel (1852): Reported a series of cases of severe intellectual
deterioration starting in adolescence and he called it “demence précoce”
 Emil Kraepelin (1899): This illness develops relatively early in life, and its
course is likely deteriorating and chronic; deterioration reminded
dementia (“Dementia praecox”), but was not followed by any organic
changes of the brain, detectable at that time.
 Eugen Bleuler (1911): He renamed Kraepelin‟s dementia praecox as
schizophrenia he recognized the cognitive impairment in this illness,
which he named as a “splitting”” of mind.
 Kurt Schneider: He emphasized the role of psychotic symptoms, as
hallucinations, delusions and gave them the privilege of “the first rank
symptoms” even in the concept of the diagnosis of schizophrenia.

6. History (cont…)
 disturbance of association
 autism
 ambivalence
 affective blunting
 Schneider‟s First-Rank Symptoms
 Audible thoughts
 Voices arguing or discussing
 Voices commenting on patient's actions
 Somatic passivity
 Thought withdrawal
 Thought insertion
 Thought broadcasting
 Made feelings
 Made impulses or drives
 Made volitional acts
 Delusional perception

7.  Diagnostic manuals:
 lCD-10 (“International Classification of Disease”, WHO)
 DSM-IV-TR (“Diagnostic and Statistical Manual”, APA)
 Clinical picture of schizophrenia is according to lCD-10, defined from
the point of view of the presence and expression of primary and/or
secondary symptoms (at present covered by the terms negative and
positive symptoms):
 the negative symptoms are represented by cognitive disorders,
having its origin probably in the disorders of associations of
thoughts, combined with emotional blunting and small or missing
production of hallucinations and delusions
 the positive symptom are characterized by the presence of
hallucinations, delusions, disorganised speech and disorganised
behaviour.

11. BIOLOGICAL
APPROACHES……

12. BIOLOGICAL APPROACHES
 Genetics of Schizophrenia…
 Genetic investigations are done in three ways:
 Family studies
 Twin studies
 Adoption studies

13. Family studies:
 The first systematic family study was carried out in Kraeplin‟s
department by Ernst Rudin, who showed that the rate of dementia
praecox was higher among the siblings of probands than in the
general population.
 About 5-10 percent average life-time risk was seen in first-degree
relatives of schizophrenics.

14.  Table showing approximate lifetime risk of developing schizophrenia for
relatives of a proband with schizophrenia
Relationship Life-time risk (%)
Parents 4.4%
All siblings 8.5%
Siblings (one parent schizophrenic) 13.8%
Children 12.3%
Children (both parents schizophrenic) 36.6%
Half siblings 3.2%
Nephews and nieces 2.2%

15. Twin Studies:
 Twin studies have also come to the conclusion that schizophrenia is
heritable to some extent.
 Luxenberger (1928) found concordence in 11 of his 19 MZ pairs and in
none of his 13 DZ pairs.
 Cardno and Gottesman (2000) found 50% concordence rates in MZ
twins and 10% for DZ twins.
 A recent meta-analysis study by Sullivan et al., (2003) found the
heritability (the proportion of liability to a disorder in a population that
is attributed to genes) of schizophrenia to be about 73-90 per cent.

16. Adoption studies:
Genetically related to Not Genetically related
Study schizophrenics to schizophrenics
Heston 1966, 5 out of 47 adoptees (10.6%) None out of 50 developed
Wender, 1974 13 out of 69 (18.8%) 3 out of 28 (10.7%)
Tienari 2000 17 out of 164 (10.4%) 4 out of 197 (2%)
Adoption studies have therefore convincingly supported the
results of family and twin studies in demonstrating the significant
role of genetic factors in schizophrenia.

17.  What are Neurotransmitters : Neurotransmitters are chemical base
balls being tossed between the neurons back & forth. They are
endogenous chemicals that transmit signals from a neuron to a target
cell across a synapse . They are also found at the axon endings of
motor neurons, where they stimulate the muscle fibres.
Neurotransmitters also communicate information throughout our
brain and body. In other words, they tell the nerve cells next in line
what to do, ie. Whether it should or not pass a message along. They
also influence the production of other chemicals inside the neurons.
They are produced by some glands such as pituitary and the adhrenal
gland.

18. Neurotransmitters can be classified on the basis of excitatory and
inhibitory actions & on the basis of molecular size.
 Excitatory : Dopamine, Acetylcholine, Norepinephrine, Epinephrine,
Nitric oxide, glutamate
 Inhibitory : Serotonin,GABA, Dopamine, Acetylcholine, Nor
epinephrine,
 4 classes of small molecules of neurotransmitters : Amino acids,
Monoamines, soluble gases, Acetylcholine,
 One class of large molecule neurotransmitters : Neuro peptides

20.  Plays role in cognition (D1 &D4 receptors) voluntary movement ( D2
receptor), anticipatory desire & motivation, punishment, reward, sleep,
mood.
 Has inhibitory role on the function of prolactin.
 Dopamine medication acts on sympathetic NS producing effects
such as increased heart rate & BP
 In frontal lobe, DA controls the flow of information from other areas of
the brain.
 Aggression stimulates DA release
 Libido can be increased by the drugs that affect DA
 Has a role in nausea & vomiting via interaction in the
chemo receptor trigger zone
 DA induces sodium loss in kidney
 DA has a role in social anxiety. Decreased D2 receptor
binding found in people with social anxiety

21.  Help long term potentiation , neural plasticity involving learning &
memory
 Free glutamatic acid present in cheese, soya sauce, & responsible for
umami, one of the 5 basic tastes of human being – also found in food
additives and flavor enhancers
 Precursor for the synthesis of inhibitory GABA
 Found in meat, egg ,fish, diary products

24. Key dopamine pathways in the brain
 4 well-defined dopamine pathways in the brain involved in
schizophrenia.They include-mesolimbic, mesocortical, nigrostriatal,and
tuberoinfiindibular dopamine DA pathways.
 Mesolimbic dopamine pathway and the positive symptoms of
schizophrenia
 This pathway projects from dopaminergic cell bodies in the ventral
tegmental area of the brainstem to axon in the ventral striatum . terminals
of nucleus accumbens
 have an important role in several emotional behaviors, including the
positive symptoms of psychosis, such as delusions and hallucinations.
 also important for motivation, pleasure, and reward. It has been observed
that diseases or drugs that increase dopamine will enhance or produce
positive psychotic symptoms, whereas drugs that decrease dopamine will
decrease or stop positive symptoms. For eg, stimulant drugs such as
amphetamine and cocaine release dopamine and, if given repetitively, can
cause a paranoid psychosis virtually indistinguishable from the positive
symptoms of schizophrenia.
 All known antipsychotic drugs capable of treating positive psychotic
symptoms are blockers of the D2 dopamine receptor.
 Hyperactivity of this pathway hypothetically accounts for positive
psychotic symptoms.
 Hyperactivity of mesolimbic dopamine neurons may also play a role in
aggressive and hostile symptoms in schizophrenia and related illnesses,
especially if serotonergic control of dopamine is aberrant in patients who
lack impulse control.

26. Mesocortical dopamine pathway
 This pathway projects from the ventral tegmental area but projects to
the areas of the prefrontal cortex.
 Branches of this pathway into the dorsolateral prefrontal cortex are
hypothesized to regulate cognition and executive functioning whereas
areas projecting to ventromedial parts of prefrontal cortex are
hypothesized to regulate emotions and affect.
 many researchers believe that cognitive and some negative symptoms
of schizophrenia may be due to a deficit of dopamine activity in
mesocortical projections to dorsolateral
 whereas affective and other negative symptoms of schizophrenia may
be due to a deficit of dopamine activity in mesocortical projections to
ventromedial prefrontal

28. Affective
-ve
Symptom
symptoms

29.  Theoretically, increasing dopamine in the mesocortical dopamine pathway
might improve the negative, cognitive, and affective symptoms of
schizophrenia. However, since there is hypothetically an excess of
dopamine elsewhere in the brain within the mesolimbic dopamine pathway,
any further increase of dopamine in that pathway would actually worsen
positive symptoms. Thus, this state of affairs for dopamine activity in the
brain of schizophrenic patients poses a therapeutic dilemma: how do we
increase dopamine in the mesocortical pathway while, at the same time,
also decreasing dopamine activity in the mesolimbic dopamine pathway?
 Mesolimbic dopamine pathway, reward, and negative symptoms
 Dopamine function in schizophrenia may be more complicated than just
"too high" in mesolimbic areas and "too low" in mesocortical areas. Instead,
they may be better characterized as "out of tune" or "chaotic." A similar
phenomenon may be occurring in the mesolimbic dopamine system, with
one subset of mesolimbic dopamine neurons out of tune and hyperactive,
mediating positive symptoms, and another set of mesolimbic dopamine
neurons out of tune but hypoactive, mediating some negative symptoms
and malfunctioning reward mechanisms.
 The mesolimbic dopamine pathway is not only the postulated site for the
positive symptoms of psychosis but is also thought to be the site of the
brains reward system or pleasure center.
 When a patient with schizophrenia loses motivation and interest and has
anhedonia and lack of pleasure, such symptoms could also implicate a
deficient functioning of the mesolimbic dopamine pathway not just deficient
functioning in the mesocortical dopamine pathway.

30. Nigrostriatal dopamine pathway
 nigrostriatal dopamine pathway, projects from dopaminergic cell
bodies in the brainstem substantia nigra via axons terminating in the
basal ganglia or striatum.
 The nigrostriatal dopamine pathway is a part of the extrapyramidal
nervous system, and controls motor movements.
 Deficiencies in dopamine in this pathway cause movement disorders,
including Parkinson's disease. Dopamine deficiency in the basal
ganglia can also produce akathisia (a type of restlessness) and
dystonia (twisting movements, especially of the face and neck).
 These movement disorders can be replicated by drugs that block
dopamine-2 receptors in this pathway.
 Hyperactivity of dopamine in the nigrostriatal pathway is thought to
underlie various hyperkinetic movement disorders such as chorea,
dyskinesias, and tics.
 Chronic blockade of dopamine-2 receptors in this pathway may result
in a hyperkinetic movement disorder known as neuroleptic-induced
tardive dyskinesia.
 Thus in schizophrenia, the nigrostriatal pathway in untreated patients
may be relatively preserve.

31.  Tuberoinfundibular dopamine pathway
 project from the hypothalamus to the anterior pituitary .
 Normally, these neurons are active and inhibit prolactin release.
 If the functioning of tuberoinfundibular dopamine neurons is
disrupted by lesions or drugs, prolactin levels can also rise. Elevated
prolactin levels are associated with galactorrhea (breast secretions),
amenorrhea (loss of ovulation and menstrual periods), and possibly
other problems such as sexual dysfunction.
 Such problems can occur after treatment with many antipsychotic
drugs that block dopamine-2 receptors
 Thus in untreated schizophrenia, the function of the
tuberoinfundibular pathway may be relatively preserved

33.  Amphetamine releases dopamine at the synapse and causes positive
symptoms of schizophrenia in non schizophrenic individuals
 Levodopa increases central dopamine concentrations and causes
positive symptoms of schizophrenia in non schizophrenic individuals
 Disulfiram inhibits dopamine metabolism and exacerbates
schizophrenia
 All effective anti psychotic drugs are dopamine2 receptor
antagonists
 Antipsychotic efficacy correlates significantly with D2 receptor
occupancy
 Increased and asymmetric brain D2 receptor densities have been
reported in living schizophrenic patients, using PET
 Increased concentrations of D2 receptors and of dopamine have been
found in postmortem brain tissue from schizophrenic patients.

34.  Key glutamate pathways in the brain and the NMDA receptor hypofunction hypothesis of
schizophrenia
 Glutamate is a excitatory neurotransmitter & is sometimes called the Master Switch as it is
capable of exciting almost all neurons in the brain.There are five glutamergic pathways, all
relate to glutamatergic pyramidal neurons in the prefrontal Cortex.
 Corticobrainstem glutamate pathways and the NMDA receptor hypofunction hypothesis of
schizophrenia
 descending glutamatergic pathway projects from cortical pyramidal neurons to brainstem
neurotransmitter centers, including the raphe for serotonin, the ventral tegmental area
(VTA) and substantia nigra for dopamine, and the locus coeruleus for norepinephrine.
 This pathway is a key regulator of neurotransmitter release.
 It acts as a brake on the mesolimbic dopamine pathway.
 This normally results in inhibition of dopamine release from the mesolimbic pathway.
 A major current hypothesis for schizophrenia involves NMDA receptors in this pathway
 when NMDA receptors are made hypofunctional by means of the NMDA receptor
antagonist phencyclidine (PCP)- produces a psychotic condition in normal humans very
similar to the positive symptoms of schizophrenia.
 To a lesser extent, the NMDA receptor antagonist ketamine can also produce a
schizophrenia-like psychosis in normals.
 This has led to the hypothesis that NMDA receptors specifically in the corticobrainstem
glutamate projection might be hypoactive in untreated schizophrenia & thus cannot do
their job of inhibiting mesolimbic dopamine neurons.
 This led to mesolimbic dopamine hyperactivity as a result.
 That is, mesolimbic dopamine hyperactivity that produces positive symptoms of
schizophrenia may actually be the consequence of NMDA receptor hypoactivation in
corticobrainstem glutamate projections.

36.  NMDA receptors in corticobrainstem glutamate projections that
regulate mesocortical dopamine pathways may also be hypoactive in
schizophrenia.
 As it has been seen PCP also mimics the cognitive, negative and
affective symptoms of schizophrenia. That is, normal humans who
take PCP and render their NMDA receptors hypofunctional not only
experience positive symptoms but also affective symptoms such as
blunted affect, negative symptoms &cognitive symptom.
 Normally, these descending corticobrainstem glutamate neurons act
as accelerators to mesocortical dopamine neurons.
 This means that corticobrainstem glutamate neurons normally
function as accelerators of these mesocortical dopamine neurons;
therefore they excite them.
 The consequence of this neuronal circuitry is that when
corticobrainstem projections to mesocortical dopamine neurons have
NMDA receptor hypoactivity, they lose their excitatory drive and
become hypoactive.
 This could hypothetically explain why mesocortical dopamine
neurons are hypoactive and thus their link to the cognitive,negative,
and affective symptoms of schizophrenia.

37. NMDA Receptor
NMDA Receptor regulation of Hypofuncn. In Cortico-
Mesocortical DA pathways: Brainstem Projection :
Excitation Hypoactivity of
Mesocortical OA pathways

38.  Thalamocortical glutamate pathways
 An ascending glutamate pathway starts from the thalamus and
innervates pyramidal neurons
 and is known as the thalamocortical pathway
 A properly functioning thalamic filter prevents too much sensory input
from penetrating the thalamus into the cortex, so that information
processing can occur in an orderly manner
 when descending corticobrainstem glutamate pathways have
hypofunctioning NMDA receptors in the ventral tegmental area, this
creates mesolimbic dopamine hyperactivity and positive symptoms of
psychosis.

39.  dopamine hyperactivity reduces the thalamic filter and permits the escape of excessive
sensory information coming into the thalamus, thus allowing it to get into the cortex by
means of ascending thalamocortical neurons.
 There is hypothetical NMDA receptor hypofunction in the descending corticostriatal
glutamate pathway as well.
 This reduces the excitatory drive on the GABA neurons that create the thalamic filter.
 Coupled with the excessive dopamine drive from mesolimbic neurons, the thalamic filter
fails, and too much information escapes diffusely into the cortex, where it can cause
cortical manifestations of hallucinations or may also create other cortical symptoms such
as cognitive, affective, & negative symptoms of schizophrenia.
 Corticothalamic glutamate pathways
 A third descending glutamatergic pathway, projects directly to the thalamus, where it may
provide sensory and other types of inputs
 Hypofunction of NMDA receptors at this level may also cause Dysregulation of the
information that arrives in the cortex due to sensory overload and a malfunctioning of
cortical glutamate input directly to the thalamic filter.
 Corticocortical glutamate pathways
 Inn this pathway one pyramidal neuron communicates with another via the
neurotransmitter glutamate.
 When NMDA receptor function normally,corticocortical glutamate loops communicate
effectively &p process info effectively.
 NMDA receptor hypofunction in cortical pyramidal neurons can impair communication
between neurons by causing hypoactivation of loop(bet DLPFC &
VMPFC),hyperactivation of loop(OFC& VMPFC)or partial hypo or hyperactivation of these
loops.

40. NMDA Receptor Regulation of Cortical Pyramidal
Neurons:
Efficient Information Processing

41.  Most common ways of examining 5HT functions in schizophrenia have
been based on studying 5 Hydroxy-indole acetic acid (5-HIAA) levels in
CSF, 5HT uptake in platelets and 5HT receptor functions by various 5HT
receptor binding ligands in the experimental animals, through
neuroimaging in vivo and post-mortem human brains.
The results of CSF 5-HIAA level studies have been inconsistent.Most of
the studies did not notice any change in schizophrenics as compared with
the normal.
Earlier studies did notice a decreased level of 5-HIAA in schizophrenic
brains(Ashcroft et al.,1966).
In the suicidal schizophrenic patients CSF 5-HIAA levels have been
significantly low in comparison with that of non-suicidal patients.(Cooper
et al.,1992;vanPrag,1983) A mild increase in the platelet 5HT2A receptor
has been seen in suicidal schizophrenic patients.
In some other studies 5-HIAA levels were also found inversely related to
the cerebral atrophy.
Some studies have found elevated CSF 5-HIAA levels in the patients with
a family history of schizophrenia .
Other studies have found a positive correlation of CSF 5-HIAA with
peculiar mannerism and posturing in schizophrenic patients.

42.  In addition,reduced levels of 5-HIAA and 5HT in various brain areas like
hypothalamus,hippocampus have also been found.
 Most of the post-mortem human brain studies have found down regulation
of the 5HT2A receptor in the frontal lobe.
 The positive psychotic symptoms can also be due to the serotonin-
dopamine interactions.Serotonin hypofunction in the prefrontal cortex of
schizophrenic brains is quite evident(Harrison,1999).Serotonin
hypofunction can disinhibit the striatal and other subcortical dopamenergic
neurons leading to the emergence of positive symptoms.
OTHER NEUROTRANSMITTER STUDIES
 Norepinepinephrine-neuronal degeneration within the norepinephrine
reward system could account for Anhedonia.
 GABA-has a regulatory effect on dopamine activity,& the loss of inhibitary
GABAergic neurons could lead to hyperactivity of dopaminergic neurons.
 Acetylcholine and Nicotine-decreased muscarnic and nicotonic receptors
in the caudate putamen,hippocampus &selected regions of the prefrontal
cortex have been found.These receptors play role in the regulation of
neurotransmitter systems involved in cognition,which is impaired in
schizophrenia.

43. Limbic System :
Reduced volume of hippocampus, amygdale & parahippocampal
gyrus are found as well as left temporal horn enlargement. It may be
related to reduced cell no. or cell size in
hippocampus/parahippocampal gyrus /entorhinal cortex. White matter
in hippocampal gyrus is also reduced. The cytoarchitecure is
disturbed, there being increased vertical axon numbers & deficits in
small interneurons in the cingulate gyrus & abnormal cell
arrangements in the hippocampus.

44.  In the basal ganglia, some researchers find no changes in areas such as
caudate, putamen, nucleus accumbens and external segment of the globas
pallidus; others have reported increased striated volume and reduced globus
pallidus ( internal segment) volume. Increased striatal volume is thought to be
an effect of treatment with antipsychotics

45.  In the thalamus, there is volume and cell number reductions or smaller
whole thalamic volume.

46. 1. Lateral & 3rd ventricular
enlargement has been found in
structural neuro images.
2. In the brain stem, a reduced nigral
volume and a trend for reduced
locus coeruleus volume are taken
as an indication of a dopaminergic/
nonadhrenergic underactivity.

47. In the cortex, contradictory results are
reported in whether there is reduction of
cortical volume . There appears to be shape
abnormalities in the corpus callosum with the
corpus callosum being thicker in female &
thinner in male.
 Data regarding cortical sulcal enlargement are split,
with some reporting sulcal enlargement in the frontal and
temporal lobes whereas others have found more diffuse
enlargement . more specific measures of cortical volume
typically show reduction of temporal & less consistently,
frontal lobe volume.

48.  The notion that the temporal & frontal lobes may play a particularly
important role in Schizophrenia has been supported by findings from
other areas. For example, neurological damage to the temporal lobes
sometimes produces positive psychotic symptoms such as
hallucinations, while damage to the frontal lobes is associated with
negative symptoms such as apathy, social withdrawal and blunted
effect. In neuropsychological testing, patients with Schizophrenia
typically show impaired frontal & temporal lobe functions.
 Magnetic Resonance Spectroscopy has seen specific reductions in N-
acetyl aspartate in dorsolateral prefrontal cortex and hippocampal
area, probably reflecting neuronal pathology in these locations. An
imbalance between phosphomondesters and phosdiesters has been
described in the frontal cortex. These studies, combined with
volumetric data, lend support to the theory that there may be selective
deficits in frontal and temporal regions.

49. Other structural neuroimaging findings:
 Decrease in brain weight, brain length and volume of the
cerebral hemisphere
 Grey matter appears to be reduced more than white matter
 Structural abnormalibility of the cerebellum.

50.  Reduced frontal blood flow has been found
 Hypofrontality – Decreased activity in the frontal lobe, particularly in
dorsolateral pre frontal cortex- related to cognitive impairment & -ve
symptoms.
 Elevated and reduced blood flow has been reported in temporal lobe
 The most common finding is an association between resting blood
flow and +ve psychotic symptoms. For example :
1. One report found a correlation between increased psychopathology
and blood flow to the left parahippocampal gyrus
2. A second found a similar correlation between +ve symptoms and left
temporal lobe blood flow.
3. More specific correlation have been seen for auditory hallucinations
and activation of Broca‟s area and medical temporal region

51.  Positive symptoms are associated with medial temporal flow
 Affective and negative symptoms of schizophrenia may involve areas of the
prefrontal cortex, such as orbital, medial, and ventral areas.These brain
areas, along with the amygdala, nucleus accumbens, and other regions,
comprise a "ventral"system involved in emotional processing. This ventral
system interacts with "dorsal"system that includes the DLPFC and modulates
the output from the ventral system
 ventral system includes orbital, ventral, and medial areas of prefrontal cortex,
amygdala and nucleus accumbens- brain regions that are all important for the
identification and appraisal of emotional stimuli and for generating an
appropriate emotional response.
 dorsal system includes not just the DLPFC but also the hippocampus.the
dorsal system maintain the emotional response from the ventral system &
modulate it.
 it selects an appropriate behavioral output in response not only to emotions
but also to demands from the environment and from theindividual's internal
goals.
 Schizophrenia has long been recognized as having impairments in the ability
to identify and accurately interpret emotions from overt sources, including
facial expressions. This may be due to inefficient information processing
within the ventral system and can be measured by imaging the response of the
amygdala to emotional input, especially from facial expressions.
 Whereas normals may activate the amygdala in response to scary or fearful or
emotionally charged faces.patients with schizophrenia may not.

52.  This may represent distortion of reality as well as an impairment in
recognizing negative emotions and in decoding negative emotions in
schizophrenia. Failure to mount the "normal"emotional response to a
scary face can also represent an inability to interpret social cues and may
lead to distortions in judgment and reasoning in schizophrenia.
 neutral face or neutral stimulus may provoke little activation of the
amygdala in a normal person.but overreaction in a schizophrenic patient
is seen,who may mistakenly judge people negatively or conclude wrongly
that another holds strong unfavorable impressions of him or her or may
even be threatening. The activation of emotional processing in the
amygdala when it is inappropriate may accompany the symptom of
paranoia and lead to impaired interpersonal functioning, including
problems in social communication.
 Psychomotor proverty syndrome is associated with underactivity of
prefrontal cortex andleft parietal cortex & overactivity of bilateral caudate
nuclei.

53. NEUROPSYCHOLOGICAL
APPROACHES……

54. NEUROPSYCHOLOGICAL
APPROACHES……
 It is noteworthy that the first sentence of the description of
schizophrenia in DSM-IV-TR includes references to
neurocognitive disturbances:
“the characteristics of schizophrenia involve a range of
cognitive and emotional dysfunctions that include perception,
inferential thinking, language and communication, behavioral
monitoring, affect, fluency, and production of thought and
speech, hedonic capacity, volition and drive, and attention.”

55. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 What is Neuropsychology???
 Neuropsychology studies the structure and function of
the brain as they relate to specific psychological processes
and behaviors.

56. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 What is „Neurocognition‟???
Sensation Perception Cognition
 Cognition - Set of interwoven processes such as memory ,language &
problem solving , that we bring to bear to generate structures and strategies
to apply to our perception.
 Neurocognition - A term used to describe cognitive functions closely
linked to the function of particular areas, neural pathways, or cortical
networks in the brain.

57. NEUROPSYCHOLOGICAL APPROACHES (cont…)
attention
 Deficits in primary processes
Information processing
Memory
 Deficits in secondary processes
Executive functions
Thought disorder
 Deficits in meta-processes
insight

58. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Vigilance refers to the ability to maintain attention over time.
 A standard vigilance test used in many studies is the Continuous
Performance Test (CPT)
 patients with schizophrenia have moderately severe vigilance impairments
 Impairments in vigilance can result in:
 difficulty following social conversations
 social deficits,
 Problems in community functioning
 Impairment in skills acquisition

59. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Information processing refers to the processing of stimuli by the organism
such that the meaning of the stimuli is extracted and the appropriate
response is made.
 Schizophrenia is characterized by problems in stimulus processing and
response programming stages of information processing
 Hallucinated voices may arise from disrupted speech perception

60. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Memory impairment is often the most striking feature of neurocognitive
impairment in schizophrenia
 Verbal memory functioning includes, but is not limited to, abilities
associated with learning new information, retaining newly learned
information over time, and recognizing previously presented material.
 In general, patients show larger deficits in learning than in retention
 Can be understood by the connectionist theory. In schizophrenics network
size does not affect the recall but connectivity does.

61. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Executive ability is the capacity to plan and implement goal directed
action. The components of executive functions are:
 Working memory
 Inhibition
 Contextual processing
 Set shifting
 Planning

62. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Immediate/Working Memory deficits…
 Immediate memory refers to the ability to hold a limited amount of
information “online” for a brief period of time (usually a few seconds).
For example: digit forward.
 Some investigators consider working memory to be synonymous with
immediate memory, whereas others describe that it should require some
manipulation of the information being held online. For example: digit
backward.
 Schizophrenics performed worse than normal controls on tests of
working memory.

63.  Immediate/Working Memory deficits (cont…)
 Working memory impairment accounted for impairment in strategic
memory and not in recognition memory, indicating that it is an
important component of impaired cognition in schizophrenia.
 Impairment in working memory emphasizes:
o fronto-temporal dysfunction in schizophrenia
o Dysfunctional neural network involving prefrontal and posterior
brain regions

64. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Inhibition deficits…
 From a cognitive perspective, „„inhibition‟‟ is critical to the ability to
control and regulate mental representations (thoughts) and
behaviors.
 Control is the ability of the cognitive system to flexibly adapt its
behaviour to the demands of particular tasks, favouring the
processing of task-relevant information over other sources of
competing information, and mediating task-relevant bahaviour over
habitual or otherwise prepotent responses (Cohen et al, 1996)

65.  Reduced inhibition was seen in patients with positive symptoms and
may underlie the reality distortion and disorganization symptoms in
schizophrenia.
 deficient inhibitory control has been assumed to play a pivotal role in
the onset of hallucinations.
 new findings confirm that hallucinations are significantly associated
with a deficit of intentional inhibition, while automatic inhibition
remains intact.

66.  Consequences of impaired inhibition:
increased efforts to
inhibit spontaneous
recurrence
unwanted cognitions
of hallucinations
(hallucinations)
Paradoxically
increased sense of
involuntariness

67. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Contextual processing:
 It is a combination of both working memory and inhibition processes.
 The processing of context is closely linked to the concept of cognitive
control
 Several performance deficits in schizophrenia may be understood in
terms of functional impairment in maintaining contextual information
over time and in using that information to inhibit inappropriate
responses.
 Schizophrenic patients have been found to be performing poorly in
context-sensitive conditions.

68. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Set shifting deficits:
 Set shifting refers to the ability to shift a cognitive set without explicit
verbal instructions
 Wisconsin Card Sorting Test (WCST) is the most widely used test for
set shifting ability.
 Schizophrenics are found to have specific deficit in concept formation
and set-shifting (irrespective of intellectual deficit).

69. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Planning deficits:
 Planning is the capacity to undertake goal directed action to solve a
novel task.
 Tower of London is a classic test employed to assess planning.
 Schizophrenics took more number of moves and their response speed
was also slower
 Planning was not slower if adjusted to for overall slowing, but
planning was inaccurate, suggesting deficits in problem solving ability
in schizophrenics.

70. NEUROPSYCHOLOGICAL APPROACHES (cont…)
Cognitive deficits in the areas of source memory, semantic processing
self monitoring, response inhibition and theory of mind are associated
with different aspects of thought disorder.
 Source memory:
 Memory for source of information is deficient in schizophrenia
 Schizophrenics tended to ascribe the word to an external source when
they were in doubt
 Bias of misattributing internal events to external sources
 Misattribution was more prominent for emotionally salient words.

71. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Semantic processing:
 A direct relation was seen between impairment in verbal fluency and
severity of thought disorder
 Schizophrenics are more cognitively biased towards emotional themes
underlying their delusions.
 Comprehension, response monitoring and inhibition:
 Difficulties in comprehension, response monitoring and inhibition of
irrelevant responses leads to confabulation in schizophrenia.
 Amount of confabulation is related to formal thought disorder and the
inability to supress inappropriate responses.

72. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Theory of mind:
 Theory of mind is the capacity to infer another person‟s mental state.
 Theory of mind is deficient in schizophrenics.
 There is problem in meta-representation or an inability to divine
another person‟s intention.
 These deficits are greater in schizophrenics with poorer premorbid IQ.

73. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Insight of patient towards symptoms of the illness is associated with cognitive
dysfunctions
 It is related to impairment of executive functions
 Poor insight is correlated with higher perseveration and poorer abstract flexibility
on WCST.
 Insight was present at moderate level of cognitive functioning but poor at either
extremes.
 Low insight with low cognitive functioning is associated with poor abstraction
 Low insight with high cognitive functioning is associated defensive attitude
towards illness.
 Associated with bilateral parietal deficits.

74. NEUROPSYCHOLOGICAL APPROACHES (cont…)
 Cognitive deficits are useful in identifying individuals at a higher risk for
schizophrenia
 Deficits in intelligence, executive functions, mental control, learning and
memory were found in first degree relatives of schizophrenics.

75. Executive community/daily
function activities
Episodic
Social problem
memory
solving/instrument
al skills
Immediate
verbal memory
Psychosocial skills
acquisition
Vigilance
N.B.:- A BLACK arrow indicates that at least four studies found a significant relationship
between the neurocognitive construct and the outcome domain;
a BLUE arrow indicates that significant relationships were uncovered in two or three
studies.

76.  By knowing the neuropsychological factors it becomes relatively easy
to predict future possibilities of having schizophrenia.
 It helps in the management.
 Biological factors help us to know the role of different brain areas in
the symptom manifestation.

77. Thank You