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ANNUAL MEETINGMay 14-18, 2016 • Atlanta

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APA Annual Meeting,Atlanta, May 14-18, 2016

TRAINING PRACTITIONERS

TO USE A PSYCHOPATHOLOGY CLINICAL

RATING SCALE

Ahmed Aboraya, MD, Dr.PHHenry Nasrallah, MDDaniel 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

2

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

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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)?

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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)

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• Do psychiatrists use SDIs in clinical

settings?

Why don’t Psychiatrists useSDIs?

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).

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• 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 literature1. 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.

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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).

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“Bottom-up” approach


– Schedules for Clinical Assessment in Neuropsychiatry (SCAN).

– Present State Examination (PSE)

“Bottom first then top (BFTT)” approach


- Good psychiatric interview

- The Standard for Clinicians’ Interview

in Psychiatry (SCIP)

“Bottom first then top (BFTT)” approach

• Describe

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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)?

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 Patient had no panic attacks.1 Patient had panic attacks.

0.92

Examples

Example: HopelessnessKappa

Have you felt hopeless about your future?

0 Patient has no feelings of hopelessness.

1 Patient feels hopeless less than

half the time.

2 Patient feels hopeless more than

half the time.

0.82

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Examples

Example: Frequency of auditory hallucinations kappa

How often do you hear any noises (like music, whispering sounds) or voices talking to you when there is no one around?

0 No auditory hallucination

1 1-4 days / month

2 5-14 days / month

3 15-30 days / month

0.93

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).

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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

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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.

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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.


• Principle 4:

• The principle of least subcategories of symptom severity (LSSS).

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• Principle 5:

• The frequency of symptoms

• Principle 6:

• The duration of symptoms

• Principle 7:

• The recency of a symptom


• Principle 8:

• The quality of symptoms.

• Principle 9:

• Summation Principle.

Discussion with attendees

• Reading break:

• Read the SCIP modules in Handout B.

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• Anxiety Dimension (0-7)

– Handout B, page 12


• PTSD Dimension (0-21)



• Depression Dimension (0-38)


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• Mania Dimension (0-21)


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 K=0.49

• Other delusions K=0.4

• Bizarreness of delusions K=0.43

• Incoherent speech K=0.41

• Illogical speech K=0.25

• Agitation K=0.48

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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.

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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

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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.

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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.

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• 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

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Conclusions

• SCIP publications are available.

• Computer program: good progress!

• Data generated by the SCIP is priceless.


• What we have learned from the course.

Test

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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

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1

The Phases of Psychiatric Diagnosis

Daniel E. Elswick, MDAssistant 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.

2

Phases of Psychiatric Diagnosis

• The process of psychiatric diagnosis has 3 phases (components):

I. Interview (Dimensional Component).

II. Etiological search (Etiological Component).

III. 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).

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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

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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.

Henry A Nasrallah, MDThe Sydney W. Souers Endowed Chair

Professor and Chairman

Department of Neurology and Psychiatry

Saint Louis University School of Medicine

SCHIZOPHRENIA:

The Spectrum of Symptom Domains

Disclosures: Henry A. Nasrallah, M.D.

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

Otsuka Pharmaceutical Co., Ltd.

Sunovion Pharmaceuticals Inc.

Teva Pharmaceutical Industries Ltd.

Speaker Bureau Janssen Pharmaceuticals, Inc.

Merck & Co., Inc.

Novartis Corporation


Sunovion Pharmaceuticals Inc.

Grant/Research Support FORUM Pharmaceuticals

Genentech, Inc., a Memberof the Roche Group

Hoffmann-La Roche Inc.


Shire PLC

2

Social/Occupational Dysfunction• Work• Interpersonal relationships• Self-care

Positive Symptoms• Delusions• Hallucinations• Disorganized speech• Catatonia

Negative Symptoms• Affective flattening• Alogia• Avolition• Anhedonia• Social withdrawal

Cognitive Deficits• Attention• Memory• Executive functions

( planning, decision making, abstraction)

ComorbidSubstance Abuse

Mood Symptoms• Depression• Hopelessness• Suicidality• Anxiety• Agitation• HostilityOriginally published in: Maguire GA. Am J Health-Syst Pharm. 2002;59(17 Suppl 5): S4-S11.

© 2002. All rights reserved. Reprinted with permission. (R1203)

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

AprosodyNasrallah et al: Epidemiology and

Psychiatric Science 2011

Clinical Features of Schizophrenia4. Cognitive Deficits

a. Neurocognitive impairments

Memory (verbal, short, and working memory)

Learning

Executive Functions (planning, set shifting)

Attention

Processing speed

b. Social cognition

Social skills

Theory of mind

Mating behavior

Reading and recognizing social cues

5. Mood Symptoms

Dysphoria, depression, hopelessness, suicidality

Anger, hostility, aggression, homicidalityNasrallah et al 2011


6. Neuromotor Symptoms

Catatonia (various degrees)

Stereotypies

Dystonia, akathisia, dyskinesia, and Parkinsonism (in the never-medicated state, not due to AP medication)

7. 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


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


10. Psychiatric Comorbidities

1) Axis I

Substance abuse (nicotine, alcohol, stimulants, etc)

Depression

Anxiety (GAD, social phobia, panic)

OCD

Eating disorders

Sleeping disorders

Sexual disorders

2) Axis II

Schizoid

Schizotypical

Paranoid

11. Medical Comorbidities

Obesity

Diabetes

Hypertension

Dyslipidemia

Pain insensitivity

COPD

InfectionsNasrallah 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 withdrawnfrom 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


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


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)


4. Asociality

Absence or reduction of interest in relationships or interaction with other persons

Inability to feel intimacy and closeness


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”


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


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 Deficitsof

Schizophrenia

Cognitive Deficits in First-Episode Schizophrenia

Bilder RM et al. Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. Am J Psychiatry. 2000;157:549-559.

Neuropsychological Performance in Schizophrenia

Z S

core

Neuropsychological Profile for Drug-NaïveFirst-Episode and Previously Treated Patients

First-episode patients (N=

Chronic treated patients(N=65)

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.

Neuropsychological Function

Z-S

core

NormativeLevel

Normative Data Compared With a Schizophrenia Sample:Total Scale Score Distribution

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.

from standardization sample

100

0.4% 0% 0% 0%

16.5%

7.2%

22.8%

20.6%

22.6%

7.9%

2.2%0.4%

1.6%

7.0%

16.0%

25.0%

0%

16.0%

0.4%1.6%

7.0%

25.0%

0

5

10

15

20

25

30

35

<50-50 51-60 61-70 71-80 81-90 91-100 101-110 111-120 121-130 131-140 140+

Total Scale Score

% o

f C

ases

Schizophrenia (N=575)Normal controls (N=540)

100

Green MF et al., Schizophr Bull. 2000;26(1):119-136.

VerbalMemory

ImmediateMemory

ExecutiveFunctions

Vigilance SummaryScores

Large

Medium

Small

NeurocognitiveDeficits

Community Functioning

Instrumental andProblem-Solving Skills

Psychosocial Rehabilitation Programs

p<.0001

Neurocognitive Deficits and Functional Ability in Schizophrenia

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 symptomsTandon 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 / dicouragementNasrallah HA: Current Psychiatry 2011

Treatment Options for PrimaryNegative Symptoms

Augmentation Results

5‐HT2A blockers and dopamine D2 agonists (stimulants, modafinil, armodafinil)

Suggestive efficacy

Antidepressants, glycine transporter inhibitor (N‐methylglycine [sarcosine]), RG16781 N‐acetyl cysteine, rTMS, and exercise therapy

Suggestive efficacy

NMDA‐glutamate agonists (glycine, cycloserine, D‐serine, D‐cycloserine), male sex steroids, female sex steroids, and MAO‐B inhibitors (selegiline)

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

• Category Fluency, animal naming• BACS Symbol Coding• Trail Making, Part A

Attention/vigilance

• Continuous Performance Test—Identical Pairs version

• Letter-Number Span• WMS Spatial Span Subtest

Working memory

Verbal learning

Visual learning

Reasoning and problem solving

Social cognition

• Hopkins Verbal Learning Test, immediate recall

• Brief Visuospatial Memory Test

• NAB mazes

• 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

• α7 Receptor• Muscarinic M1 mAChR

• AMPA glutamatergic receptor• NMDA glutamatergic receptor

– Glycine reuptake• Metabotropic glutamate receptor

CHOLINERGIC

GLUTAMATERGIC• Dopamine D1 receptor

• α2 Adrenergic receptor• GABAA R subtype

DOPAMINERGIC

OTHER

AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; GABA, gamma-aminobutyric acid; mAChR, muscarinic acetylcholine receptor; NMDA, N-methyl-D-aspartate.

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 !

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