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annualmeeting
ANNUAL MEETING
May 14-18, 2016 • Atlanta
APA Annual Meeting,
Atlanta, May 14-18, 2016
TRAINING PRACTITIONERS
TO USE A PSYCHOPATHOLOGY CLINICAL
RATING SCALE
Ahmed Aboraya, MD, Dr.PH
Henry Nasrallah, MD
Daniel Elswick, MD
TRAINING PRACTITIONERS TO USE A PSYCHOPATHOLOGY
CLINICAL RATING SCALE
Ahmed Aboraya, MD, Dr.PH
Chief of Psychiatry
(Sharpe Hospital)
Clinical Professor of Psychiatry
(West Virginia School of Osteopathic Medicine)
Adjunct Faculty
(West Virginia University School of Public Health)
House Keeping
• 1. Welcome attendees, Dr. Nasrallah and Dr. Elswick.
• 2. All attendees should have 3 handouts:
Handout A
Handout B
Handout C
1
Course Agenda
•
•
•
•
•
•
•
•
Part I: 1:00 PM to 2:45 PM
Dr. Aboraya:
_Introduction and General Overview.
_ Approaches to psychiatric diagnoses.
_ Introduction to the Standard for Clinicians’ Interview in
Psychiatry (SCIP) as a new practical diagnostic interview.
Dr. Nasrallah:
_Assessment of schizophrenia using clinical rating scales.
Break (15 minutes)
Part II: 3:00 PM to 5:00 PM
Dr. Elswick:
_ Phases of psychiatric diagnosis: interview, etiological
search, and disorder classification.
_A videotape demonstration of a SCIP interview.
Dr. Aboraya:
_Creating a SCIP database, SCIP dimensions and a
descriptive psychopathology code (DPC).
_Review of what we have learned.
Dr. Aboraya Presentation
• PART I
Future of Psychiatry
• Axis I: Experimental Psychopathology
• Axis II: Personalized Psychiatry
• Axis III: Research Domain Criteria
2
Descriptive Psychopathology
• The science of symptoms and
signs of behavioral disorders
Descriptive Psychopathology
• Descriptive psychopathology has long been
the foundation for psychiatric diagnosis.
Delineation of behavioral syndromes
remains centered on accurate description of
their characteristic symptoms and signs
despite advances in neuroscience.
•
(Taylor MAV, N.A.: Descriptive Psychopathology, the signs and symptoms of behavioral disorders.
New York, Cambridge University Press; 2009)
Discussion with Attendees
• Do clinicians receive adequate training in
Descriptive Psychopathology (DP)?
3
Training Practitioners in DP
• Standardized Diagnostic Interviews (SDIs):
• 1. Structured interviews
• 2. Semi-structured interviews
• Rating scales
Standardized Diagnostic
Interviews (SDIs)
• 1. With success of DSM III in 1980, SDIs
gained popularity and use.
• 2. Definition of SDIs:
–
–
–
–
SDIs dictate how to ask questions.
SDIs dictate how to rate answers.
SDIs guide how to diagnose mental disorders.
SDIs can be fully structured or semi-structured.
Standardized Diagnostic
Interviews (SDIs)
• Common SDIs:
- Schedules for Clinical Assessment in
Neuropsychiatry (SCAN)
- Structured Clinical Interview for DSM-IV Axis I
Disorders (SCID-I)
- Mini International Neuropsychiatric Interview (MINI)
- WHO Composite International Diagnostic Interview
(CIDI)
4
Discussion with Attendees
• Do psychiatrists use SDIs in clinical
settings?
Why don’t Psychiatrists use
SDIs?
1. Time-consuming
2. Complicated, rigid rules
3. Many require extensive training
4. Interfere with developing rapport with
patient
5. Do not fit with Clinicians’ style of
interviews
Rating Scales
•
•
•
•
Positive and Negative Syndrome Scale (PANSS)
Young Mania Rating Scale (YMRS)
Hamilton Depression Rating Scale (HAM-D)
Montgomery-Asberg Depression Rating Scale
(MADRS).
5
Discussion with Attendees
• Do psychiatrists use rating scales in clinical
settings?
Answer
- Most psychiatrists do not use rating scales.
- Lack of time was the most common reason
cited for not using these tools. (Nasrallah,
2009)
Serious gaps in the literature
1. Lack of a practical diagnostic interview designed
for psychiatrists.
2. Lack of comprehensive reliable measurement of
psychiatric symptoms and signs (core of DP).
3. Lack of reliable dimensions of psychopathology.
6
The Standard for Clinicians’ Interview in
Psychiatry (SCIP) Development
The SCIP addresses 3 serious gaps:
1. SCIP is designed for use in clinical settings.
2. The SCIP measured kappa for 150
symptoms and signs.
3. The SCIP created 16 reliable dimensions.
Three Approaches to
Psychiatric Diagnosis
1. “top-down” approach
2. “bottom-up” approach
3. “bottom first then top (BFTT)”
approach
“Top-down” approach
• Classic Examples:
- Structured Clinical Interview for DSM-IV
AXIS I Disorders (SCID-I).
- Mini International Neuropsychiatric
Interview (MINI).
7
“Bottom-up” approach
• Classic Examples:
– Schedules for Clinical Assessment in
Neuropsychiatry (SCAN).
– Present State Examination (PSE)
“Bottom first then top (BFTT)”
approach
• Classic Examples:
- Good psychiatric interview
- The Standard for Clinicians’ Interview
in Psychiatry (SCIP)
“Bottom first then top (BFTT)”
approach
• Describe
8
SCIP Principles of Creating
Reliable Questions
1. Questions are worded to be simple and easily understood by patients regardless of their
intellectual level.
2. Questions simulate what seasoned psychiatrists usually ask in clinical interviews.
3. The meaning of the questions and examples are embedded in the questions so that each
question and the response reflect the criterion being examined.
4. Questions’ responses have the least subcategories of symptoms severity (LSSS) and
reflect the clinical significance of the symptom. The fewer the subcategories reflecting
symptom severity, the more efficient the interview, and the more likely that clinicians
will use the questions.
5. Absent or mild symptoms are coded “0” in the SCIP.
Examples
Example: PANIC ATTACKS WITHOUT PHOBIA
kappa
Have you gotten suddenly anxious and frightened for a short
period of time (up to 60 minutes)?
0.92
During that time, did you feel that your heart was racing or
pounding, or did you start shaking or sweating, or did you feel you
were choking?
0
1
Patient had no panic attacks.
Patient had panic attacks.
Examples
Example: Hopelessness
Kappa
Have you felt hopeless about your future?
0
0.82
Patient has no feelings of
hopelessness.
1
Patient feels
2
Patient feels
hopeless less than
half the time.
hopeless more than
half the time.
9
Examples
Example: Frequency of auditory hallucinations
How often do you hear any noises (like music, whispering sounds) or
voices talking to you when there is no one around?
0
1
kappa
0.93
No auditory hallucination
1-4 days / month
2
5-14 days / month
3
15-30 days / month
SCIP Definitions
• The SCIP is a process of psychiatric assessment: rapport
with patient, CC, HPI, screening questions, specific
questions.
• The SCIP process of psychiatric assessment has 3
components:
I. SCIP interview (Dimensional Component)
II. Etiological search (Etiological Component)
III. Disorders search (Categorical Component)
• The SCIP manual describes the process.
SCIP Specifics
1. The SCIP process (SCIP manual).
2. SCIP interview: questions were developed and tested
(highly recommended to use).
3. SCIP questions were designed to reflect clinically
significant symptoms and signs.
4. The SCIP assessment captures the dimensional part of
psychopathology.
5. The clinician’s skill captures the diagnoses based on all the
information available (human mind algorithm vs. computer
algorithm).
10
Unique features of the SCIP
1. Only tool designed for psychiatrists.
2. Only tool that generates automatic data from routine clinical interview.
3. Only tool that uses categorical and dimensional models simultaneously:
– Generates 14 dimensions (anxiety, posttraumatic stress,
depression, mania, delusions, hallucinations, Schneiderean
symptoms, disorganized thoughts, disorganized behavior, negative
symptoms, alcohol addiction, drug addiction, attention deficit and
hyperactivity).
– Generates diagnoses (DSM, ICD).
The SCIP Project
• The SCIP validity and reliability were tested in an
international multisite study (3 hospitals and 3
clinics) in three countries (USA, Canada and
Egypt).
• 1,004 subjects tested over 12 years.
• The SCIP project is the largest validity and
reliability study of a diagnostic interview.
SCIP Translation
•
•
•
•
•
English
Arabic
Spanish
Hindi
Chinese
11
Sample Size
•
•
•
•
•
•
•
Sharpe Hospital
780
CRC (outpatient)
30
Fairmont Office (outpatient) 42
Ain Shams Hospital
52
Mansoura Hospital
69
Rothbart Center (outpatient) 31
_______________________________
• Total
1,004
Reliability of the SCIP
1. Inter-rater (Kappa)
2. Internal consistency (Cronbach’s alpha)
•3. Aboraya A, El-Missiry A, Barlowe J, John C, Ebrahimian A, Muvvala S, Brandish J, Mansour H,
Zheng W, Chumber P, Berry J, Elswick D, Hill C, Swager L, Abo Elez W, Ashour H, Haikal A, Eissa A,
Rabie M, El-Missiry M, El Sheikh M, Hassan D, Ragab S, Sabry M, Hendawy H, Abdel Rahman R,
Radwan D, Sherif M, Abou El Asaad M, Khalil S, Hashim R, Border K, Menguito R, France C, Hu W,
Shuttleworth O, Price E. The reliability of the standard for clinicians' interview in psychiatry (SCIP): a
clinician-administered tool with categorical, dimensional and numeric output. Schizophrenia research.
2014;156:174-183.
SCIP Nine Principles of Creating
Reliable Dimensions
• Principle 1:
• Reliable dimensions require reliable
symptoms and signs.
12
SCIP Nine Principles of Creating Reliable Dimensions
(continued)
• Principle 2:
• Each symptom is given one score,
regardless of the number of questions
exploring the symptom.
SCIP Nine Principles of Creating Reliable Dimensions
(continue)
• Principle 3:
• Dimensions are built upon significant
symptoms and signs.
SCIP Nine Principles of Creating Reliable Dimensions
(continue)
• Principle 4:
• The principle of least subcategories of
symptom severity (LSSS).
13
SCIP Nine Principles of Creating Reliable Dimensions
(continue)
•
•
•
•
•
•
Principle 5:
The frequency of symptoms
Principle 6:
The duration of symptoms
Principle 7:
The recency of a symptom
SCIP Nine Principles of Creating Reliable Dimensions
(continue)
• Principle 8:
• The quality of symptoms.
• Principle 9:
• Summation Principle.
Discussion with attendees
• Reading break:
• Read the SCIP modules in Handout B.
14
Discussion with attendees
• Anxiety Dimension (0-7)
– Handout B, page 12
Discussion with attendees
• PTSD Dimension (0-21)
– Handout B, page 13
Discussion with attendees
• Depression Dimension (0-38)
– Handout B, page 17
15
Discussion with attendees
• Mania Dimension (0-21)
– Handout B, page 21
Reliability of SCIP items
(Symptoms & Signs)
• Stable Kappa was measured for 150 SCIP items.
• 6 SCIP items (4%) had poor reliability (K<0.5).
•
28 SCIP items (18.7%) had fair reliability (K from 0.5 to
0.7).
• 116 SCIP items (77.3%) had good reliability (K>0.7)
SCIP Items with Poor Reliability
•
•
•
•
•
•
Clanging
Other delusions
Bizarreness of delusions
Incoherent speech
Illogical speech
Agitation
K=0.49
K=0.4
K=0.43
K=0.41
K=0.25
K=0.48
16
Reliability of the SCIP
Dimensions
• All SCIP dimensions had
substantial Cronbach’s alpha
(>0.7) with the exception of
disorganized thoughts (Cronbach’s
alpha = 0.38).
Validity of the SCIP
• Validity of SCIP diagnosis was tested
against the gold standard diagnosis.
• Gold standard diagnosis: SCAN diagnosis
(31 patients) and expert diagnosis (80
patients).
Validity of the SCIP
• The agreement (Kappa) between the SCIP Axis I
diagnoses and the gold standard diagnoses was fair to good
(Kappa > 0.4) for 12 diagnoses: generalized anxiety
disorder, panic disorder, posttraumatic stress disorder,
major depression, bipolar I disorder, schizoaffective
disorder, schizophrenia, alcohol, cannabis, cocaine, opioid
and sedative abuse/dependence.
• Kappa was poor (< 0.4) for bipolar I, mixed and
polysubstance dependence.
17
SCIP Computer Program
1. Generate database.
2. Generate graphs.
3. Generate reports (psychiatric evaluations,
progress notes….)
Relationship between routine psychiatric
Interview and the SCIP
• Good psychiatric interview = SCIP.
• Ways to use the SCIP:
1. Read the SCIP manual and questions.
2.Do your psychiatric interview----come back and compare
with the SCIP standard.
3. Use the SCIP questions as you interview the patient.
• Use of electronic medical records (EMR) is
now a must.
Dr. Aboraya Presentation
• PART II
18
Creating SCIP Database from
the Video Interview
Use Handout C
1. Attendees will practice creating a SCIP
database.
2. Review and discussion of the SCIP
database.
Descriptive Psychopathology
Code (DPC)
• Definition: The descriptive psychopathology
code (DPC) is a comprehensive psychological
assessment (symptoms, signs and dimensions) of
an individual at one point in time, done by a
clinician using the SCIP methodology.
Descriptive Psychopathology
Map (DPM)
• Definition: Two or more descriptive
psychopathology codes (DPCs) obtained over
time by the same or different clinicians.
19
Characteristics of DPC
1. DPC is the equivalent of a mental fingerprint of an
individual at one point in time.
2. Each individual can have multiple descriptive
psychopathology codes (DPCs) as the individual is
assessed at different times by the same or different
assessors.
Characteristics of DPC
(continue)
3. The descriptive psychopathology code (DPC) of
an individual is constant at one point in time and is
dynamic over time as symptoms and signs abate with
treatment and new symptoms and signs emerge.
4. Based upon the SCIP study, the DPC has almost
250 items measuring the psychological status of
adults.
Characteristics of DPC
(continue)
5. The number of DPC items can increase in the
future as new studies explore domains not studied in
the current SCIP study (e.g. eating disorders,
personality disorders and child psychiatry).
6. If the individual has no symptoms, all of the DPC
items are zeroes except for ID #, date of evaluation,
date of birth and gender.
20
Discussion with attendees
• Use Handout C
• Practice creating a DPC from the SCIP
interview
DPC for the Video Patient
• SS2(1) SS7(1) SS9(1) SS11(2) SS13(1) SS14(1)
SS19(1)
• MA1(1) MA4(1) MA6(1,2,3) MA11(1)
• PTSD1(1) PTSD2(1)
• MB1(1) MB6(1) MB19(1) MB20 (1) MB21(1)
MB22(1)
• MB28(2) MB30(2) MB32(2) MB40(1) MB41(1)
Back to the Future
• Axis I: Experimental Psychopathology
• Axis II: Personalized Psychiatry
• Axis III: Research Domain Criteria
21
Conclusions
• SCIP publications are available.
• Computer program: good progress!
• Data generated by the SCIP is priceless.
Discussion with attendees
• What we have learned from the course.
Test
22
Course Evaluation
Acknowledgements
•Ahmed El-Missiry, MD, MRCPsych; Johnna Barlowe, MA; Collin John, MD, MPH; Alireza
Ebrahimian, Psy. D.; Srinivas Muvvala, MD, MPH; Ja’me Brandish, MA; Hader Mansour, MD, PhD;
Wanhong Zheng, MD; Paramjit Chumber, MD; James Berry, DO; Daniel Elswick, MD; Cheryl Hill, MD,
PhD; Lauren Swager, MD; Warda Abo elez, MD; Hala Ashour, MD; Amal Haikal, MD; Ahmed Eissa,
MD; Menan Rabie, MD; Marwa El-Missiry, MD; Mona El Sheikh, MD; Dina Hassan, MD; Sherif
Ragab, MD; Mohamed Sabry, MD; Heba Hendawy, MD; Rola Abdel Rahman, MD; Doaa Radwan, MD;
Mohamed Sherif, MD; Marwa Abou El Asaad, MD; Sherien Khalil, MD; Reem Hashim, MD; Katherine
Border, LGSW; Roberto Menguito, MD; Cheryl France, MD; Wei Hu, MD; Olivia Shuttleworth, LICSW;
Elizabeth Price, MA
• Thank You
23
24
The Phases of Psychiatric Diagnosis
Daniel E. Elswick, MD
Assistant Professor and Residency Director WVU Dept. of Behavioral Medicine and Psychiatry
Disclosure
• I have no actual or potential conflict of interest in relation to this presentation
• No off label use of medications will be discussed
Psychiatric Assessment
• The process of psychiatric assessment (diagnosis) includes:  Establishing rapport with patient
 Information gathering: chief complaints, history of present illness, screening questions, specific questions.  More information: family history, medical history…etc.
1
Phases of Psychiatric Diagnosis
• The process of psychiatric diagnosis has 3 phases (components):
I. II. III.
Interview (Dimensional Component).
Etiological search (Etiological Component).
Disorders search (Categorical Component).
• The SCIP manual describes the process.
I. Interview Phases
• 1. Initial part: greeting and establishing rapport, C/C, HPI.
• 2. Middle part: screening for areas of psychopathology, exploring causes of symptoms.
• 3. Final part: more specific information gathering, provisional diagnosis, diff. diagnosis.
II. Etiological Search
• Causal specifies:
• 1. Definite etiopathies.
• 2. Factors contributing to the manifestation of the disorder (contributing factors). 2
II. Etiological Search
(Continues)
• Definite etiopathy: a factor that is determined to be the cause of a mental disorder. • Example: a 45‐year‐old lawyer with no psychiatric problems sustains a head trauma in a car accident. The MRI after the car accident shows a subdural hematoma. A mental status evaluation and neuropsychological testing show significant memory deficits. The final diagnosis is amnestic disorder due to head trauma. II. Etiological Search
(Continues)
• Factors contributing to the manifestation of the mental disorder (contributing factors): These contributing factors (biological, environmental, social, developmental or others) play a part in contributing to the manifestations of the illness, but they stop short of being definite etiopathies. III. Disorders Search
3
Relationship between routine psychiatric Interview and the SCIP
• Good psychiatric interview = SCIP
• (or)SCIP = Good psychiatric interview
• Using the SCIP:
1. Read the SCIP manual and questions.
2.Do your psychiatric interview‐‐‐‐come back and compare with the SCIP standard.
3. Use the SCIP questions as you interview the patient.
Instructions for Observing the Video Interview
• 1. Pay attention to the process of the interview.
• 2. pay attention to the questions asked and the patient’s responses.
• 3. You may take brief notes if you wish.
4
SCHIZOPHRENIA:
The Spectrum of Symptom Domains
Henry A Nasrallah, MD
The Sydney W. Souers Endowed Chair
Professor and Chairman
Department of Neurology and Psychiatry
Saint Louis University School of Medicine
Disclosures: Henry A. Nasrallah, M.D.
 Speaker Bureau

Consultant

Boehringer Ingelheim GmbH

FORUM Pharmaceuticals

Genentech, Inc., a Member
of the Roche Group

H. Lundbeck A/S

Hoffmann-La Roche Inc.

Janssen Pharmaceuticals, Inc.

Merck & Co., Inc.

Novartis Corporation




Janssen Pharmaceuticals, Inc.

Merck & Co., Inc.

Novartis Corporation

Otsuka Pharmaceutical Co., Ltd.

Sunovion Pharmaceuticals Inc.
 Grant/Research Support

FORUM Pharmaceuticals

Genentech, Inc., a Member
of the Roche Group
Otsuka Pharmaceutical Co., Ltd.

Hoffmann-La Roche Inc.
Sunovion Pharmaceuticals Inc.

Otsuka Pharmaceutical Co., Ltd.

Shire PLC
Teva Pharmaceutical Industries Ltd.
2
Clinical Features of Schizophrenia
Positive Symptoms
• Delusions
• Hallucinations
• Disorganized speech
• Catatonia
Negative Symptoms
• Affective flattening
• Alogia
• Avolition
• Anhedonia
• Social withdrawal
Social/Occupational Dysfunction
• Work
• Interpersonal relationships
• Self-care
Cognitive Deficits
• Attention
• Memory
• Executive functions
( planning, decision
making, abstraction)
Comorbid
Substance Abuse
Originally published in: Maguire GA. Am J Health-Syst Pharm. 2002;59(17 Suppl 5): S4-S11.
© 2002. All rights reserved. Reprinted with permission. (R1203)
Mood Symptoms
• Depression
• Hopelessness
• Suicidality
• Anxiety
• Agitation
• Hostility
Clinical Features of Schizophrenia
1.
Psychotic symptoms

False beliefs (delusions)

Perceptual abnormalities (hallucinations)
Agitation, bizarre behavior

2.
Disorganization
Speech disorganization

Thought disorder/derailment

3.
Deficits (negative symptoms)

Avolition

Apathy, amotivation

Alogia

Affect blunting or incongruity

Failure to recognize facial affect of others

Aprosody
Nasrallah et al: Epidemiology and
Psychiatric Science 2011
Clinical Features of Schizophrenia
4.
Cognitive Deficits
a.
Neurocognitive impairments

Memory (verbal, short, and working memory)

Learning

Executive Functions (planning, set shifting)

Attention

Processing speed
b.
5.
Social cognition

Social skills

Theory of mind

Mating behavior

Reading and recognizing social cues
Mood Symptoms

Dysphoria, depression, hopelessness, suicidality

Anger, hostility, aggression, homicidality
Nasrallah et al 2011
Clinical Features of Schizophrenia
6.
7.
Neuromotor Symptoms

Catatonia (various degrees)

Stereotypies

Dystonia, akathisia, dyskinesia, and Parkinsonism (in the
never-medicated state, not due to AP medication)
Disorders of Self Recognition and Integrity

Depersonalization

Derealization

Loss of self-other boundaries

Lack of sense of agency

Lack of insight
Nasrallah et al 2011
Clinical Features of Schizophrenia
8.
Minor Physical Anomalies

Furrowed tongue

High arched palate

Abnormal dermatoglyphics

Malformed or low set ears

Single transverse palmar crease
Small head circumference

9.
Soft Neurologic Signs

Right-left confusion

Mirroring

Dysiodokinesia

Clumsiness

Agraphesthesia

Astereognosis

Two-point discrimination
Nasrallah et all 2011
Clinical Features of Schizophrenia
10.
Psychiatric Comorbidities
1)
2)
11.
Axis I

Substance abuse (nicotine, alcohol, stimulants, etc)

Depression

Anxiety (GAD, social phobia, panic)

OCD

Eating disorders

Sleeping disorders

Sexual disorders
Axis II

Schizoid

Schizotypical

Paranoid
Medical Comorbidities

Obesity

Diabetes

Hypertension

Dyslipidemia

Pain insensitivity

COPD

Infections
Nasrallah et al 2011
Types of Hallucinations
• Auditory:
hearing voice(s) with no one around
1. Single voice or multiple voices
2. Familiar or unfamiliar
3. Talk to the person or about the person (commentary)
4. Insulting or praising or arguing
5. Command hallucinations
1.To harm or kill self
2.To harm or kill others
3.To behave in some way
Types of Hallucinations
•
Olfactory: perceiving an odor, usually foul (also: seizure aura)
•
Gustatory: perception of tastes (often unpleasant)
•
Visual: seeing persons or images or inanimate objects or
animals. Lilliputian visual hallucinations (reduced size but
normal in details) can occur with substance use
•
Somatic: odd sensation(s) in the body
•
Hypnapompic: occurs during transition from sleep to partial
wakefulness
•
Hypnagogic: occurs when falling asleep , with awareness
Types of Delusions
(Fixed False Beliefs)
•
Bizarre: (e.g. The earth is morphing into a reptile)
•
Capgras: (e.g. A familiar person is actually an identical imposter)
•
Reference (e.g. Perceiving a “ meaning” in random events)
•
Jealousy: (e.g. The spouse / partner is unfaithful)
•
Parasitosis (e.g. being infested with parasites)
•
Erotomania: (e.g. A celebrity is in love with the patient->stalking)
•
Grandiose: (e.g. Having extraordinary powers or abilities)
•
Nihilistic: (e.g. Part of a person’s body or the universe has
ceased to exist, or that one is dead (Cotard delusion)
Types of Delusions
(Fixed False Beliefs)
•
Persecutory: (e.g. That a person is being threatened, harassed
or attacked by others)
•
Passivity: (e.g. being controlled by an outside power)
•
Hypochondriacal: (e.g. a body part has changed)
•
Thought control (e.g. Thoughts are being inserted or withdrawn
from someone’s mind or broadcast to everyone)
Thought and Speech Disorders
•
Clang associations: rhyming words
•
Derailment: Knight’s-move thinking …
•
Flight of ideas: jumping rapidly from topic to topic, along with
rapid speech
•
Loose associations: shifts in train of thought without adequate
logical connection
•
Verbigeration: excessive vagueness, useless repetition,
meaningless phrases or cliches
•
Word salad: associations so loose, the speech is incoherent or
incomprehensible
Abnormalities of Thought Progression
•
Blocking: sudden involuntary complete interruption of speech or
thought
•
Circumstantiality: tendency to digress and to insert irrelevant
information or explanations and qualifications before a thought
is completed
•
Perseveration: repetition or persistence or a thought when it I
sno longer appropriate
•
Racing thoughts: thoughts so rapid they are experienced as
almost out of control
•
Tangentiality: digression and irrelevancy so severe, the intended
goal is never reached
Abnormalities of Thought Progression
•
Driveling: copious but meaningless speech
•
Wooliness of thought: despite adequate amount of
speech, little information is contained. Statements
are vague or excessively abstract or concrete
Abnormalities of Grammar and
Vocabulary
•
Mannerisms: odd or eccentric expression, used recurrently
•
Neologism: a new word or phrase that seems to have a private
or special meaning, and whose derivation is not readily apparent
•
Paraphasia: used erroneous words that are phonetically or
semantically related to the target word
•
Stereotypy: frequent, mechanical repetitions of a word or
phrase, without an apparent purpose. May seem automatic, even
involuntary
•
Word approximation: idiosyncratic word usage that seems
stilted or peculiar but whose meaning is evident.
Abnormalities of Logic and Reasoning
•
Concrete thinking: excessive literalness, inability to understand
broader meaning or symbolism
•
Non-sequitor: conclusions not logically supported by the
premises
•
Over-inclusive thinking: inability to maintain conceptual
boundaries, incorporating irrelevant elements making it less
understandable
•
Past-pointing / approximate answers: person answers questions
correctly but in a way that suggests that the incorrectness is
intentional and that the correct answer may be known
Symptoms of Catatonia
•
Automatic obedience: person complies like a robot to
commands
•
Catalepsy / Catatonic Stupor: generalized immobility with
markedly diminished responsiveness to stimuli despite normal
consciousness
•
Catatonic excitement: severe, apparently purposeless
hyperactivity not influenced by external stimuli
•
Catatonic mutism: inability to speak, usually accompanies
catalepsy
•
Catatonic negativism: purposeless resistance to instructions or
rigid maintenance of posture against attempts to be moved
•
Catatonic posturing: prolonged involuntary maintenance or
fixed posture even if awkward
Symptoms of Catatonia
•
Catatonic rigidity: waxy flexibility and part of posturing
•
Echolalia: morbid, parrot-like repetition of another persons
speech and seems automatic and involuntary
•
Echopraxia: morbid mimicking of another persons movements
and posture. Seems automatic and involuntary
•
Stereotypy: frequent mechanical repetition of speech or pattern
of motor activity
•
Waxy flexibility: prolonged maintenance of a posture imposed
by another person
Primary and Secondary Negative
Symptoms
Primary Negative Symptoms of Schizophrenia
 These are the enduring negative symptoms that are
present at the onset of the first psychotic episode
 Primary negative symptoms may precede the onset
of positive symptoms by months or years
 Poor pre-morbid functioning is often associated with
a high level of negative symptoms
Nasrallah and Smeltzer 2011
Primary Negative Symptoms of Schizophrenia
(The following symptoms fall on a continuum of severity)
1. Affect Pathology

Flat, blunted, restricted or shallow affect as
well as incongruous or silly affect at times

Decreased spontaneous movements

Poor eye contact

Lack of vocal inflection

Failure to recognize the facial affect of
others
Primary Negative Symptoms of Schizophrenia
(The following symptoms fall on a continuum of severity)
2. Alogia

Reduction in the quantity of thought

Decreased fluency and productivity of speech

Poverty of speech amount as well as brief, concrete,
and unelaborated verbalizations

Poverty of speech content: vague, generalized, and
conveying little information

Blocking: interruption in the train of thought

Prolonged response latency: long pauses before
responding
Primary Negative Symptoms of Schizophrenia
(The following symptoms fall on a continuum of severity)
3. Anhedonia

Loss or reduction in capacity for
experiencing pleasure

Manifested by lack of interest in enjoyable
activities

Decrease in sexual interest, activity or
enjoyment

Not reversible (like the anhedonia of
depression)
Primary Negative Symptoms of Schizophrenia
(The following symptoms fall on a continuum of severity)
4. Asociality

Absence or reduction of interest in
relationships or interaction with other
persons

Inability to feel intimacy and closeness
Primary Negative Symptoms of Schizophrenia
(The following symptoms fall on a continuum of severity)
5. Avolition/apathy

Loss or reduction of the ability to initiate and
persist in goal directed activities

Typically includes poor grooming,
impersistence at work or school and
physical avergia

Often manifested by doing nothing all day
which may be misconstrued as “laziness”
Primary Negative Symptoms of Schizophrenia
(The following symptoms fall on a continuum of severity)
6. Inattentiveness

Inability to maintain task involvement or
engagement for a reasonable period of time

Appears engrossed in an internal world to
the exclusion of external tasks
Primary Negative Symptoms of Schizophrenia
(The following symptoms fall on a continuum of severity)
7. Anosognosia (non-awareness of illness)

Lack of insight into one’s illness or disability
can be considered both a negative symptom
or a cognitive deficit

Lack of insight precludes seeking help or
attempting to solve personal problems
arising from schizophrenia

Lack of insight can be reversible or
irreversible
Two Major Subdivisions of Negative Symptoms

DIMINISHED EXPRESSION (DE) :
includes alogia and affective flattenting

APATHY / AVOLITION (AA):
includes amotivation and asociality
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
2. Strauss GP, et al. J Psychiatr Res. 2013;47(6):783‐790. 3. Kirkpatrick B, et al. Schizophr Bull. 2006;32(2):214‐219. 4. Liemburg E, et al. J Psychiatr Res. 2013;47(6):718‐725. 5. Stahl SM, Buckley PF. Acta Psychiatr Scand. 2007;115(1):4‐11
Neurocognitive Deficits
of
Schizophrenia
Cognitive Deficits in First-Episode
Schizophrenia
Z Score
Neuropsychological Performance in Schizophrenia
Bilder RM et al. Neuropsychology of first-episode schizophrenia: initial characterization and clinical
correlates. Am J Psychiatry. 2000;157:549-559.
Neuropsychological Profile for Drug-Naïve
First-Episode and Previously Treated Patients
Normative
Level
Z-Score
First-episode patients (N=
Chronic treated patients
(N=65)
Neuropsychological Function
ATT=attention vigilance. ABS=abstraction-flexibility. VBL=verbal intelligence and language function.
SPT=spatial organization. VBM=verbal memory and learning. VIM=visual memory. VSM=speeded
visual-motor processing and attention. MOT=fine manual motor functions.
Saykin AJ et al., Arch Gen Psychiatry. 1994;51(2):124-131.
Normative Data Compared With a Schizophrenia Sample:
Total Scale Score Distribution
% of Cases
100
100
35
Schizophrenia (N=575)
Normal controls (N=540)
30
from standardization sample
25.0%
25
22.8%
20
16.5% 16.0%
15
10
7.2%
16.0%
7.9%
7.0%
5
0
25.0%
22.6%
20.6%
0%
<50-50
0.4%
51-60
61-70
7.0%
2.2%
1.6%
0.4%
71-80
81-90
91-100
101-110
111-120
1.6%
0%
121-130
0%
131-140
Total Scale Score
RBANS=Repeatable Battery for Assessment of Neuropsychological Status.
Randolph C. RBANS Manual-Repeatable Battery for the Assessment of Neuropsychological Status, 1998.
Wilk CM et al. Schizophr Res. 2004;70(2-3):175-186.
0%
0.4%
140+
Neurocognitive Deficits and
Functional Ability in Schizophrenia
Community Functioning
Instrumental and
Problem-Solving Skills
Neurocognitive
Deficits
Psychosocial Rehabilitation
Programs
p<.0001
Large
Medium
Small
Verbal
Memory
Immediate
Memory
Executive
Functions
Vigilance
Summary
Scores
Green MF et al., Schizophr Bull. 2000;26(1):119-136.
Impaired Social Cognitive Domains in
Schizophrenia
Social Cognition
Tasks
1.
Emotional processing
Facial Emotion Identification Test, Voice Emotion
Identification Test, Awareness of Social Influence Test
2.
Social perception
Profile of Non-verbal Sensitivity, Social Cue
Recognition Test
3.
Social knowledge
Situational Features Recognition Test
4.
Attributional bias
Attributional Style Questionnaire, Internal, Personal
and Situational Attribution Questionnaire, Ambiguous
Intentions Hostility Questionnaire
5.
Theory of Mind
False Belief Stories, False Belief Picture Sequencing,
Hinting Tasks, Reading the Mind in the Eyes Test
6.
Empathy
Empathy Tests
Schizophrenia Dimensions in DSM-5
(To be rated on 0-4 scale)
• Reality distortion: delusions
• Reality distortion: hallucinations
• Negative symptoms (avolition-apathy and
restricted affect)
• Disorganization
• Impaired cognition
• Depression
• Mania
• Psychomotor symptoms
Tandon et al. Schizophrenia Research 2013; 150: 3-10
Unmet Needs in Schizophrenia
Therapuetics
 Negative Symptoms
 Cognitive Deficits
 Preventing conversion from the prodrome
stage to psychosis
 Studies are underway, but no breakthrough
findings yet
Negative Symptoms of
Schizophrenia:
No Approved
Treatment yet!
Primary Negative Symptoms
 Affect Pathology
 Alogia
 Anhedonia
 Apathy
 Asociality
 Avolition
 Anosognosia
Secondary Negative Symptoms
of Schizophrenia
 Psychosis
 Excessive Dopamine blockade
 Depression
 Obstructive sleep apnea (OSA)
 Cortical / subcortical lesions
 Lack of external stimulation
 Demoralization / dicouragement
Nasrallah HA:
Current Psychiatry 2011
Treatment Options for Primary
Negative Symptoms
Augmentation
5‐HT2A blockers and dopamine D2 agonists (stimulants, modafinil, armodafinil)
Antidepressants, glycine transporter inhibitor (N‐methylglycine [sarcosine]), RG16781 N‐acetyl cysteine, rTMS, and exercise therapy
NMDA‐glutamate agonists (glycine, cycloserine, D‐serine, D‐
cycloserine), male sex steroids, female sex steroids, and MAO‐B inhibitors (selegiline)
Results
Suggestive efficacy
Suggestive efficacy
Mixed results
Second antipsychotic, lithium, valproate, topiramate, carbamazepine, benzodiazepines, and beta‐blockers
Lack of efficacy
CBT
Lack of efficacy
Group I and Group II / III metabotropic glutamate agonists, 5‐HT2A antagonists, ion‐channel blockers, histamine‐3 receptor antagonists, PDE10A blockers, and minocycline
Experimental (novel mechanisms of action, phase 2 or 3 studies underway)
Cognitive Impairment in
Schizophrenia:
No Approved Treatments
Yet!
The MATRICS MCCB was Accepted by the FDA as a Primary End
Point for Clinical Trials in Cognition
The MCCB includes 10 tests in 7 cognitive domains
Speed of processing
•
Verbal learning
•
Category Fluency, animal naming
• BACS Symbol Coding
• Trail Making, Part A
Visual learning
Attention/vigilance
•
•
Continuous Performance Test—
Identical Pairs version
Working memory
•
• Letter-Number Span
WMS Spatial Span Subtest
Hopkins Verbal Learning Test,
immediate recall
Brief Visuospatial Memory Test
Reasoning and problem solving
•
NAB mazes
Social cognition
•
MSCEIT Managing Emotions
BACS, Brief Assessment of Cognition in Schizophrenia; MSCEIT, Mayer-Salovey-Caruso Emotional Intelligence Test; NAB, Neuropsychological
Assessment Battery; WMS, Wechsler Memory Scale.
Nuechterlein KH, et al. Am J Psychiatry. 2008;165(2):203-213.
MATRICS: promising molecular targets for
cognitive enhancement
Potential Mechanistic Targets for Treatment of
Cognitive Impairment in Schizophrenia
DOPAMINERGIC
•
Dopamine D1 receptor
GLUTAMATERGIC
• AMPA glutamatergic receptor
• NMDA glutamatergic receptor
– Glycine reuptake
• Metabotropic glutamate receptor
CHOLINERGIC
•
OTHER
• α7 Receptor
Muscarinic M1 mAChR
•
α2 Adrenergic receptor
• GABAA R subtype
AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; GABA, gamma-aminobutyric acid; mAChR, muscarinic acetylcholine receptor; NMDA, N-methyl-Daspartate.
Marder SR. Focus. 2008;6(2):180-183.
MATRICS Ranking of Targets
 TARGET
 Alpha 7 nicotinic receptor agonists
 D1 receptor agonists
 AMPA glutamatergic receptor agonists
 Alpha 2-adrenergic receptor agonists
 NMDA glutamatergic receptor agonists
Tactics to Improve Secondary Cognitive Deficits
in Patients with Schizophrenia
 Avoid using anticholinergic drugs
 Avoid long term use of benzodiazepines
 Help the patient lose weight
 Prescribe regular exercise [walking 30 minutes a
day]
 Avoid sedating medications during the day
 Lower the patients blood pressure if high
 Treat Obstructive Sleep Apnea
 Encourage stimulating activities
 Omega-3 fatty acid and N-Acetyl Cysteine
THANK YOU !