Psychotic disorders. Schizophrenia

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Psychotic disorders. Schizophrenia

Содержание

3. Schizophrenia Only one criteria needed if delusions bizarre or hallucinations consist of a voice keeping a
4. Schizophrenia subtypes Paranoid: preoccupation with one or more delusions or frequent auditory hallucinations Disorganized: disorganized speech,
8. Clinical characteristics Positive signs- excess of function Negative signs- deficiency of function Disorganization of thought process
9. Positive signs= psychosis Disorders of perception=hallucinations Disorders of thought=delusions
10. Hallucinations Auditory 19 51 Voices commenting 22 12 Voices conversing 27 12 Somatic-tactile 10 6 Olfactory
11. Domains of neurocognitive function Attention- WSCT Perceptual motor processing- Finger taping, STROOP Executive function tower of
12. Types of cognitive disorders Lower than normal baseline IQ- premorbid in 25% of patients Cognitive dysfunction
13. Negative symptoms Restricted emotional output Poverty of thought Poverty of speech Loss of ability to plan,
14. Negative symptoms Affective flattening Unchanging facial expression 54 33 Decreased spontaneous movements 37 14 Paucity of
15. Alogia Poverty of speech 20 20 Poverty of content of speech 33 6 Blocking 12 3
16. Bizarre behavior Clothing, appearance 8 4 Social, sexual behavior 17 7 Aggressive/agitated behavior 14 6 Repetitive/stereotyped
17. DDX of negative symptoms Parkinsonian side effects of antipsychotic typical medications Pharmacological sedation Postpsychotic or comorbid
18. Affective symptoms Secondary to the disease Reactive to the disease and to the frightening psychotic symptoms
19. Features of Schizophrenia Positive symptoms Delusions Hallucinations Disorganized speech Cognitive deficits Attention Memory Verbal fluency Executive
20. DDX of schizophrenia Schizophreniform Disorder Brief Psychotic Disorder Delusional Disorder Schizoaffective Disorder Schizoid Personality Schizotypal Personality
21. Clinical course Prodrome Psychotic episodes with or without inter- episode residual symptoms Chronically active course Residual
22. Clinical course Generally marked by chronic course with superimposed episodes of symptom exacerbation 1/3 have severe
23. A 20th-century artist, Louis Wain, who was fascinated by cats, painted these pictures over a period
24. Gestation/Birth 10 20 30 40 50 Premorbid Prodromal Onset/ Deterioration Residual/ Stable Stages Of Illness Healthy
25. Prognosis 5-10 years after the first episode: 10-20% stable improvement 10-20% partial improvement 50% deterioration 40-60%-
26. Factors affecting course and prognosis Age of onset Sex Previous levels of function Acute vs. slow
27. Etiology Studies of monozygotic twins -40-50% concordance 50% genetic risk Estimated: the other 50% due to
28. Etiology Possibly due to aberrant neuro-developmental processes such as increase in normal age-associated pruning frontoparietal synapses
29. Genetics
30. Genetic Loci Linked to Schizophrenia
31. Neurodegenerative disorder Progressive after each psychotic episode No gliosis Structural pathology prior to the first episode
32. Candidate Neurodevelopmental Molecules and Schizophrenia HOX - homeotic genes; EGF - epidermal growth factor; FGF -
33. Neuroimaging findings
35. [18F]fluorodopa uptake in the striatum and the vetral striatum of schizophrenics and normals McGowan et al.
36. The Energy Metabolism Hypothesis of Schizophrenia Decreased cerebral blood flow in frontal cortex and an increase
37. The Involvement of Mitochondria in Schizophrenia Reduced oxygen uptake in brain biopsies (Takahashi, 1954). Deformation and
38. Dopamine pathways
39. Dopamine involvement Increased mwsolimbic DA activity - Delusions – Hallucinations -Aggression Decreased mesocortical DA activity Negative
40. Neuroimaging PET scans from a study of identical (monozygotic) twins, who are discordant for schizophrenia (only
41. DA receptors
42. Receptor Binding Profiles of Conventional and Atypical APDs J Pharmacol Exp Ther 1996;277:968;J Clin Pharmacol 1999;39:1S;
43. DA pathways induced side effects of antipsychotics
44. Evidence of Serotonin Involvement in Schizophrenia Pathophysiology Postmortem Studies in Schizophrenics Increase in 5-HT transmission and
45. DA- 5HTreceptors effects of antipsychotics 5HT inhibits DA release in the basal ganglia and prefrontal cortex
46. Dopaminergic neurons have inhibitory projections to glutamatergic neurons. Glutamatergic neurons directly excite GABAergic neurons, which inhibit
47. Glutamate receptors subunits
48. Glutamate in schizophrenia Clinical Data Lower concentrations of glutamate in the prefrontal cortex and the hippocampus.
49. NMDA receptor Glycine and D-serine increase glutamate transmission A clinical study reports improvement in negative symptoms
50. Cortical-subcortical glutamate/ GABA/ DA cycle In schizophrenia
51. GABA IN SCHIZOPHRENIA
52. Mortality and Cardiovascular Morbidity Among Patient With Schizophrenia Death risk 3.7 to 4.6 times higher than
53. The metabolic syndrome x- syndrome Obesity Hyperlipidemia Hypertension Diabetes smoking
54. Smoking 80 % of smoking among individuals diagnosed with schizophrenia Self treatment- nicotin decreases auditory hallucinations
55. Issues in Treating Schizophrenia ~30% respond poorly to treatment Noncompliance rate ~50% at 1 year High
57. Schizophrenia and addiction 47 % have met criteria for some form of a drug/ETOH abuse/addiction The
58. Treatment Positive symptoms respond better than negative to medications Antipsychotics are mainstay of treatment, affect sometimes
59. Length of treatment 1 psychotic episode + full pharmacological remission- minimal period of treatment is 2
60. Adjunctive methods of treatment Rehabilitation programs! Lifestyle modification Avoidance of substances of abuse Supportive psychotherapy, spiritual
61. Take home points Schizophrenia is a severe, genetic, neurodevelopmental disorder that negatively affects every single level
63. Скачать презентацию

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Schizophrenia
Only one criteria needed if delusions bizarre or hallucinations consist of

a voice keeping a running commentary or two voices talking to each other
Must cause significant social/occupational dysfunction
Continuous signs of disturbance for 6 months
< 6 months = schizophreniform

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Schizophrenia subtypes
Paranoid: preoccupation with one or more delusions or frequent auditory

hallucinations
Disorganized: disorganized speech, behavior and flat or inappropriate affect are all present
Catatonic: motoric immobility or excessive activity, extreme negativism, peculiar movements, echolalia or echopraxia

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Clinical characteristics
Positive signs- excess of function
Negative signs- deficiency of function
Disorganization of

thought process and behavior
Cognitive dysfunction
Affective changes

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Positive signs= psychosis
Disorders of perception=hallucinations
Disorders of thought=delusions

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Hallucinations
Auditory 19 51
Voices commenting 22 12
Voices conversing 27 12
Somatic-tactile 10 6
Olfactory 5 1

Visual 16 15
Delusions
Persecutory 19 47
Jealousy 2 1
Guilt, sin 16 2
Grandiose 15 15
Religious 12 11
Somatic 11 11
Delusions of reference 13 21
Delusions of being controlled 25 12
Delusions of mind reading 19 14
Thought broadcasting 11 2
Thought insertion 15 4
Thought withdrawal 11 6

% of Patients w Positive and Negative symptoms

Mild

Severe

Positive

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Domains of neurocognitive function
Attention- WSCT
Perceptual motor processing- Finger taping, STROOP
Executive

function tower of London, WSCT,
Memory- WMS CVLT
Vigilance- CPT
Verbal memory and fluency- REY
working memory-Digit span backwards
Semantic memory
social cognition- affect perception

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Types of cognitive disorders
Lower than normal baseline IQ- premorbid in 25%

of patients
Cognitive dysfunction after the emergence of the disease- 50% of patients
Mainly- executive function, attention, long term memory
Cognitively intact- 25% of patients, mostly those who commenced early pharmacological treatment

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Negative symptoms
Restricted emotional output
Poverty of thought
Poverty of speech
Loss of ability to

plan, to exhibit orderly consecutive function, to distinguish between important and unimportant, to make dicisions
Narrowing of interests and hobbies
Loss of motivation and initiative
Loss of social needs and interpersonal interactions
20% with medications, 100% without medications
The accumulation of negative symptoms=“deficit”
Destruction of frontal lobe neurons
Irreversible with medications

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Negative symptoms
Affective flattening
Unchanging facial expression 54 33
Decreased spontaneous movements 37 14
Paucity of

expressive gestures 34 24
Poor eye contact 39 16
Affective nonresponsivity 18 18
Inappropriate affect 29 22
Lack of vocal inflections 40 9

Mild

Severe

% of Patients w Positive and Negative symptoms

Negative

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Alogia
Poverty of speech 20 20
Poverty of content of speech 33 6
Blocking 12

3
Increased response latency 17 6
Avolition-apathy
Grooming and hygiene 33 41
Impersistence at work or school 13 74
Physical anergia 36 31
Anhedonia-asociality
Recreational interests, activities 38 41
Sexual interest, activity 11 23
Intimacy, closeness 24 35
Relationship with friends, peers 25 63
Attention
Social inattentiveness 25 32
Inattentiveness during testing 33 19

Mild

Severe

% of Patients w Positive and Negative symptoms

Negative

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Bizarre behavior
Clothing, appearance 8 4
Social, sexual behavior 17 7
Aggressive/agitated

behavior 14 6
Repetitive/stereotyped behavior 7 4
Positive formal thought disorder
Derailment 30 4
Tangentiality 28 4
Incoherence 9 1
Illogicality 10 1
Circumstantiality 14 0
Pressure of speech 14 0
Distractible speech 12 1
Clanging 1 0

% of Patients w Positive and Negative symptoms

Mild

Severe

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DDX of negative symptoms
Parkinsonian side effects of antipsychotic typical medications
Pharmacological sedation
Postpsychotic

or comorbid depression
Active psychosis
Anxiety
Adjustment reaction to the illness

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Affective symptoms
Secondary to the disease
Reactive to the disease and to the

frightening psychotic symptoms
Depressogenic mnedications (haloperidol)

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Features of Schizophrenia
Positive symptoms Delusions Hallucinations Disorganized speech
Cognitive deficits Attention Memory
Verbal fluency Executive function (eg, abstraction)
Functional Impairments Work Interpersonal

relationships Self-care

Negative symptoms Anhedonia
Affective flattening Avolition Social withdrawal
Alogia

Mood symptoms Depression/Anxiety Aggression/Hostility
Suicidality

Disorganization
- speech
- behavior

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DDX of schizophrenia
Schizophreniform Disorder
Brief Psychotic Disorder
Delusional Disorder
Schizoaffective Disorder
Schizoid Personality
Schizotypal Personality Disorder
Paranoid

Personality Disorder
Mood Disorders with Psychotic Features
Major Depression
Bipolar Disorder
Other Disorders
substance induced (e.g. PCP, amphetamine, cocaine, hallucinogens, cannabis, alcohol, a variety of prescribed medications
most diseases affecting the central nervous system

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Clinical course
Prodrome
Psychotic episodes with or without inter- episode residual symptoms
Chronically active

course
Residual course

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Clinical course
Generally marked by chronic course with superimposed episodes of symptom

exacerbation
1/3 have severe symptoms & social/vocational impairment and repeated hospitalizations
1/3 have moderate symptoms & social/vocational impairment and occasional hospitalizations
1/3 have no further hospitalizations but typically have residual symptoms, chronic interpersonal difficulties and most cannot maintain employment
M- 18Y, F 25-30Y and another peak around menopause, but can stert at any age including children
Without treatment- progressive deterioration, negative symptoms and cognitive decline
With time- less positive and more negative symptoms
Earlier pharmacological treatment- prevents functional deterioration and cognitive deterioration, decreases suicidality. Medications are neuroprotective!!!
Possible periods of symptom remission
Possible severe and chronically deteriorating course
Rare cases of spontaneous remission and return to mormal premorbid function
A low % of patients do not improve with any medication
Cases of excellent reaction to medications- stop medications- recurrence- no reaction to medications
With full compliance- could become completely asymptomatic and preserve normal function and cognitive ability

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A 20th-century artist, Louis Wain, who was fascinated by cats, painted

these pictures over a period of time in which he developed schizophrenia. The pictures mark progressive stages in the illness and exemplify what it does to the victim's perception

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Gestation/Birth
10
20
30
40
50
Premorbid
Prodromal
Onset/ Deterioration
Residual/ Stable
Stages Of Illness
Healthy
↑
↓
Worsening Severity Of Signs And Symptoms
Natural History Of Schizophrenia
Years

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Prognosis
5-10 years after the first episode:
10-20% stable improvement
10-20% partial improvement
50% deterioration
40-60%-

some form of deficit

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Factors affecting course and prognosis
Age of onset
Sex
Previous levels of function
Acute vs.

slow onset
Family history
Triggers
Duration of symptoms prior to initiation of pharmacological treatment
Substance use
Number of psychotic episodes- the more- the worse is the outcome

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Etiology
Studies of monozygotic twins -40-50% concordance
50% genetic risk
Estimated: the other

50% due to as of yet unidentified environmental factors including in utero exposure

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Etiology
Possibly due to aberrant neuro-developmental processes such as increase in normal

age-associated pruning frontoparietal synapses that occur in adolescence and young adulthood
Excessive activity in mesocortical and mesolimbic dopamine pathways
Genetic
Peripartum complications
Intrauterine infections (toxoplasmosis, influenza)
Cannabis use
Othe substances use
Possible stressor before the first episode (that is- without the stressor the episode could have appeared significantly later)

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Genetics

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Genetic Loci Linked to Schizophrenia

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Neurodegenerative disorder
Progressive after each psychotic episode
No gliosis
Structural pathology prior to the

first episode
Brain development genes
Ventricular enlargement
Gray matter loss
Structural deficits in the limbic system and in medial temporal lobe
Changes in neurone connectivity and in neurone size
Loss of mitochondria

Neurodevelopmental theory

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Candidate Neurodevelopmental Molecules and Schizophrenia
HOX - homeotic genes; EGF - epidermal

growth factor; FGF - fibroblast growth factor; NCAM - neural cell adhesion molecule; LAMP - limbic associated membrane protein; GAP - growth associated protein; BDNF - brain derived neurotrophic factor.

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Neuroimaging findings

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[18F]fluorodopa uptake in the striatum and the vetral striatum of schizophrenics

and normals

McGowan et al. Arch Gen Psychiatry. 2004

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The Energy Metabolism Hypothesis of Schizophrenia
Decreased cerebral blood flow in frontal

cortex and an increase in limbic regions (Franzen & Ingvar, 1975, Cohen et al.,1988).
Abnormal glucose utilization in frontal, temporolimbic and diencephalic regions (Bauchsbaum,1990).
Reduced ATP in the prefrontal cortex and the temporal lobe (Fujimoto et al., 1992, Riehemann et al., 2000).

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The Involvement of Mitochondria in Schizophrenia
Reduced oxygen uptake in brain biopsies

(Takahashi, 1954).
Deformation and reduction in the number of mitochondria in anterior limbic cortex and in striatum (Uranova & Aganova, 1989, Kung L., 1999).
Dysfunction of the oxidative phosphorylation system in the frontal cortex, basal ganglia and platelets. (Cavalier et al., 1995, Maurer & Moller, 1997, Burkhardt et al., 1993, Whateley et al., 1998, Ben-Shachar et al., 1999, Dror et al., 2002).
Altered mitochondrial related gene expression including those of complex I subunits (Mulcrone et al., 1995, Whatley et al., 1996, Dror et al., 2002, Middleton, 2002, Prabakaran et al., 2004, Altar et al., 2005).

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Dopamine pathways

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Dopamine involvement
Increased mwsolimbic DA activity
- Delusions
– Hallucinations
-Aggression
Decreased mesocortical DA activity
Negative

symptoms and functional/ cognitive deterioration

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Neuroimaging
PET scans from a study of identical (monozygotic) twins, who are

discordant for schizophrenia (only one has the disorder) demonstrate that individuals with schizophrenia have reduced brain activity in the frontal lobes (top of scan). D. Weinberger. E. F. Torrey, K. Berman

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DA receptors

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Receptor Binding Profiles of Conventional and Atypical APDs
J Pharmacol Exp Ther

1996;277:968;J Clin Pharmacol 1999;39:1S; Psychopharmacology 1993;112:S60;Am J Psychiatry 1997;154:782.

Haloperidol

Clozapine

Risperidone

Olanzapine

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DA pathways induced side effects
of antipsychotics

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Evidence of Serotonin Involvement in Schizophrenia Pathophysiology
Postmortem Studies in Schizophrenics
Increase in

5-HT transmission and 5-HT-transporter density in subcortical regions, but no change or decrease in cortical regions.
Decrease or no change in 5-HT2-receptor density in prefrontal cortex.
Agonist-Challenge Studies
Administration of m-chlorophenylpiperazine (mCPP) a partial 5-HT agonist exacerbates symptoms in unmedicated schizophrenics
5-HT agonist LSD produces hallucinations and other psychotic symptoms

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DA- 5HTreceptors effects of antipsychotics
5HT inhibits DA release in the basal

ganglia and prefrontal cortex but not in the mesolimbic system.

5HT inhibits DA release in the basal ganglia (EPS) and prefrontal cortex (negative symptoms) but not in the mesolimbic system.
If 5HT is blocked, it increases DA release, thus reversing the effect of D2 blockade

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Dopaminergic neurons have inhibitory projections to glutamatergic neurons.
Glutamatergic neurons directly excite

GABAergic neurons, which inhibit the release of dopamine.
Dopaminergic neurons (IPSPs) often compete with glutamatergic neurons (EPSPs).

Glutamate Dopamine interaction

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Glutamate receptors subunits

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Glutamate in schizophrenia Clinical Data
Lower concentrations of glutamate in the prefrontal cortex

and the hippocampus.
Increase in KA receptors in the prefrontal cortex
Increase in AMPA receptors in the medial temporal lobe.
Lower levels of mRNA encoding AMPA and KA receptor subunits in the hippocampus and parahippocampus.
NMDA abnormalities
Correlation – amount of glutamate receptor deficiency is related to deterioration of memory and reasoning

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NMDA receptor
Glycine and D-serine increase glutamate transmission
A clinical study reports

improvement in negative symptoms in an add-on strategy.

D-serine

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Cortical-subcortical glutamate/ GABA/ DA cycle
In schizophrenia

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GABA IN SCHIZOPHRENIA

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Mortality and Cardiovascular Morbidity Among Patient With Schizophrenia
Death risk 3.7 to

4.6 times higher than in general population
The risk of MI in 5-fold higher with Typicals
Causes- asphyxion, arrhythmias, thromboembolic events, seizures, pulmonary causes, agranulocytosis

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The metabolic syndrome x- syndrome
Obesity
Hyperlipidemia
Hypertension
Diabetes
smoking

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Smoking
80 % of smoking among individuals diagnosed with schizophrenia
Self treatment- nicotin

decreases auditory hallucinations

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Issues in Treating Schizophrenia
~30% respond poorly to treatment
Noncompliance rate ~50% at

1 year
High relapse rate per year
treated ~25%
untreated/poor compliance ~70%

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Schizophrenia and addiction
47 % have met criteria for some form of

a drug/ETOH abuse/addiction
The odds of having an alcohol addiction- X3 than general population
The odds of drug assiction- X6 than general population

Regier et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990 Nov 21;264(19):2511-8.

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Treatment
Positive symptoms respond better than negative to medications
Antipsychotics are mainstay

of treatment, affect sometimes also negative symptoms
Typical APS- highly effective for positive symptoms but motor SE
Atypical APS: highly effective for positive symptoms, can sometimes be effective for negative symptoms, (but can lead to metabolic syndrome
Risk of TD approximately 3-5% per year for typical antipsychotics
Highest in older women with affective disorders
Risk of dystonic reaction highest in young males
Clozapine- the most effective antipsychotic medication of all, effective in treatment resistant cases, improves general function, decreases suicide rate. Risk- agranulocytosis 1%
Long acting preparations increase compliance

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Length of treatment
1 psychotic episode + full pharmacological remission- minimal period

of treatment is 2 years
2 and more episodes- chronic treatment is recommended (70% relapse after 2 episodes, almost 100% relapse after 3 episodes)
Chronic treatment is neuroprotective and prevents negative symptoms

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Adjunctive methods of treatment
Rehabilitation programs!
Lifestyle modification
Avoidance of substances of abuse
Supportive psychotherapy,

spiritual support for those who request it, alternative medicine for those who request it- are not a substitute for treatment!
Remember that the mainstream of treatment is pharmacological!

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Take home points
Schizophrenia is a severe, genetic, neurodevelopmental disorder that negatively

affects every single level of functioning and causes serious disability
Many factors affect its development and clinical course
The only effective treatment for the symptoms and for the prevention of deterioration is pharmacological
Rehabilitation, compliance and ligstyle affect prognosis

Psychotic disorders. Schizophrenia

Содержание

SchizophreniaOnly one criteria needed if delusions bizarre or hallucinations consist of

Schizophrenia subtypesParanoid: preoccupation with one or more delusions or frequent auditory

Clinical characteristicsPositive signs- excess of functionNegative signs- deficiency of functionDisorganization of

Positive signs= psychosisDisorders of perception=hallucinationsDisorders of thought=delusions

Hallucinations Auditory 19 51 Voices commenting 22 12 Voices conversing 27 12 Somatic-tactile 10 6 Olfactory 5 1

Domains of neurocognitive functionAttention- WSCTPerceptual motor processing- Finger taping, STROOP Executive

Types of cognitive disorders Lower than normal baseline IQ- premorbid in 25%

Negative symptomsRestricted emotional outputPoverty of thoughtPoverty of speechLoss of ability to

Negative symptomsAffective flattening Unchanging facial expression 54 33 Decreased spontaneous movements 37 14 Paucity of

Alogia Poverty of speech 20 20 Poverty of content of speech 33 6 Blocking 12

Bizarre behavior Clothing, appearance 8 4 Social, sexual behavior 17 7 Aggressive/agitated

DDX of negative symptomsParkinsonian side effects of antipsychotic typical medicationsPharmacological sedationPostpsychotic

Affective symptomsSecondary to the diseaseReactive to the disease and to the

Features of SchizophreniaPositive symptoms Delusions Hallucinations Disorganized speech Cognitive deficits Attention MemoryVerbal fluency Executive function (eg, abstraction)Functional Impairments Work Interpersonal

DDX of schizophreniaSchizophreniform DisorderBrief Psychotic DisorderDelusional DisorderSchizoaffective DisorderSchizoid PersonalitySchizotypal Personality DisorderParanoid

Clinical courseProdromePsychotic episodes with or without inter- episode residual symptomsChronically active

Clinical courseGenerally marked by chronic course with superimposed episodes of symptom

A 20th-century artist, Louis Wain, who was fascinated by cats, painted

Gestation/Birth1020304050PremorbidProdromalOnset/ DeteriorationResidual/ StableStages Of IllnessHealthy↑↓Worsening Severity Of Signs And Symptoms Natural History Of SchizophreniaYears

Prognosis5-10 years after the first episode:10-20% stable improvement10-20% partial improvement50% deterioration40-60%-

Factors affecting course and prognosisAge of onsetSexPrevious levels of functionAcute vs.

EtiologyStudies of monozygotic twins -40-50% concordance50% genetic risk Estimated: the other

EtiologyPossibly due to aberrant neuro-developmental processes such as increase in normal

Genetics

Genetic Loci Linked to Schizophrenia

Neurodegenerative disorderProgressive after each psychotic episodeNo gliosisStructural pathology prior to the

Candidate Neurodevelopmental Molecules and SchizophreniaHOX - homeotic genes; EGF - epidermal

Neuroimaging findings

[18F]fluorodopa uptake in the striatum and the vetral striatum of schizophrenics

The Energy Metabolism Hypothesis of SchizophreniaDecreased cerebral blood flow in frontal

The Involvement of Mitochondria in SchizophreniaReduced oxygen uptake in brain biopsies

Dopamine pathways

Dopamine involvementIncreased mwsolimbic DA activity- Delusions – Hallucinations-AggressionDecreased mesocortical DA activityNegative

NeuroimagingPET scans from a study of identical (monozygotic) twins, who are

DA receptors

Receptor Binding Profiles of Conventional and Atypical APDsJ Pharmacol Exp Ther

DA pathways induced side effects of antipsychotics

Evidence of Serotonin Involvement in Schizophrenia PathophysiologyPostmortem Studies in SchizophrenicsIncrease in

DA- 5HTreceptors effects of antipsychotics5HT inhibits DA release in the basal

Dopaminergic neurons have inhibitory projections to glutamatergic neurons.Glutamatergic neurons directly excite

Glutamate receptors subunits

Glutamate in schizophrenia Clinical DataLower concentrations of glutamate in the prefrontal cortex

NMDA receptor Glycine and D-serine increase glutamate transmissionA clinical study reports

Cortical-subcortical glutamate/ GABA/ DA cycleIn schizophrenia

GABA IN SCHIZOPHRENIA

Mortality and Cardiovascular Morbidity Among Patient With SchizophreniaDeath risk 3.7 to

The metabolic syndrome x- syndromeObesityHyperlipidemiaHypertensionDiabetes smoking

Smoking80 % of smoking among individuals diagnosed with schizophreniaSelf treatment- nicotin

Issues in Treating Schizophrenia~30% respond poorly to treatmentNoncompliance rate ~50% at

Schizophrenia and addiction47 % have met criteria for some form of

TreatmentPositive symptoms respond better than negative to medications Antipsychotics are mainstay

Length of treatment1 psychotic episode + full pharmacological remission- minimal period

Adjunctive methods of treatmentRehabilitation programs!Lifestyle modificationAvoidance of substances of abuseSupportive psychotherapy,

Take home pointsSchizophrenia is a severe, genetic, neurodevelopmental disorder that negatively

Похожие презентации

Schizophrenia
Only one criteria needed if delusions bizarre or hallucinations consist of

Schizophrenia subtypes
Paranoid: preoccupation with one or more delusions or frequent auditory

Clinical characteristics
Positive signs- excess of function
Negative signs- deficiency of function
Disorganization of

Positive signs= psychosis
Disorders of perception=hallucinations
Disorders of thought=delusions

Hallucinations
Auditory 19 51
Voices commenting 22 12
Voices conversing 27 12
Somatic-tactile 10 6
Olfactory 5 1

Domains of neurocognitive function
Attention- WSCT
Perceptual motor processing- Finger taping, STROOP
Executive

Types of cognitive disorders
Lower than normal baseline IQ- premorbid in 25%

Negative symptoms
Restricted emotional output
Poverty of thought
Poverty of speech
Loss of ability to

Negative symptoms
Affective flattening
Unchanging facial expression 54 33
Decreased spontaneous movements 37 14
Paucity of

Alogia
Poverty of speech 20 20
Poverty of content of speech 33 6
Blocking 12

Bizarre behavior
Clothing, appearance 8 4
Social, sexual behavior 17 7
Aggressive/agitated

DDX of negative symptoms
Parkinsonian side effects of antipsychotic typical medications
Pharmacological sedation
Postpsychotic

Affective symptoms
Secondary to the disease
Reactive to the disease and to the

Features of Schizophrenia
Positive symptoms Delusions Hallucinations Disorganized speech
Cognitive deficits Attention Memory
Verbal fluency Executive function (eg, abstraction)
Functional Impairments Work Interpersonal

DDX of schizophrenia
Schizophreniform Disorder
Brief Psychotic Disorder
Delusional Disorder
Schizoaffective Disorder
Schizoid Personality
Schizotypal Personality Disorder
Paranoid

Clinical course
Prodrome
Psychotic episodes with or without inter- episode residual symptoms
Chronically active

Clinical course
Generally marked by chronic course with superimposed episodes of symptom

Gestation/Birth
10
20
30
40
50
Premorbid
Prodromal
Onset/ Deterioration
Residual/ Stable
Stages Of Illness
Healthy
↑
↓
Worsening Severity Of Signs And Symptoms
Natural History Of Schizophrenia
Years

Prognosis
5-10 years after the first episode:
10-20% stable improvement
10-20% partial improvement
50% deterioration
40-60%-

Factors affecting course and prognosis
Age of onset
Sex
Previous levels of function
Acute vs.

Etiology
Studies of monozygotic twins -40-50% concordance
50% genetic risk
Estimated: the other

Etiology
Possibly due to aberrant neuro-developmental processes such as increase in normal

Neurodegenerative disorder
Progressive after each psychotic episode
No gliosis
Structural pathology prior to the

Candidate Neurodevelopmental Molecules and Schizophrenia
HOX - homeotic genes; EGF - epidermal

The Energy Metabolism Hypothesis of Schizophrenia
Decreased cerebral blood flow in frontal

The Involvement of Mitochondria in Schizophrenia
Reduced oxygen uptake in brain biopsies

Dopamine involvement
Increased mwsolimbic DA activity
- Delusions
– Hallucinations
-Aggression
Decreased mesocortical DA activity
Negative

Neuroimaging
PET scans from a study of identical (monozygotic) twins, who are

Receptor Binding Profiles of Conventional and Atypical APDs
J Pharmacol Exp Ther

DA pathways induced side effects
of antipsychotics

Evidence of Serotonin Involvement in Schizophrenia Pathophysiology
Postmortem Studies in Schizophrenics
Increase in

DA- 5HTreceptors effects of antipsychotics
5HT inhibits DA release in the basal

Dopaminergic neurons have inhibitory projections to glutamatergic neurons.
Glutamatergic neurons directly excite

Glutamate in schizophrenia Clinical Data
Lower concentrations of glutamate in the prefrontal cortex

NMDA receptor
Glycine and D-serine increase glutamate transmission
A clinical study reports

Cortical-subcortical glutamate/ GABA/ DA cycle
In schizophrenia

Mortality and Cardiovascular Morbidity Among Patient With Schizophrenia
Death risk 3.7 to

The metabolic syndrome x- syndrome
Obesity
Hyperlipidemia
Hypertension
Diabetes
smoking

Smoking
80 % of smoking among individuals diagnosed with schizophrenia
Self treatment- nicotin

Issues in Treating Schizophrenia
~30% respond poorly to treatment
Noncompliance rate ~50% at

Schizophrenia and addiction
47 % have met criteria for some form of

Treatment
Positive symptoms respond better than negative to medications
Antipsychotics are mainstay

Length of treatment
1 psychotic episode + full pharmacological remission- minimal period

Adjunctive methods of treatment
Rehabilitation programs!
Lifestyle modification
Avoidance of substances of abuse
Supportive psychotherapy,

Take home points
Schizophrenia is a severe, genetic, neurodevelopmental disorder that negatively