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Personality traits and neurodegenerationin multiple sclerosis

Ralph HB Benedict, PhD

Professor of Neurology

University at Buffalo, State University of New York

Research Support from the NIH, National MS Society, and Industry

Acknowledgements:

Bianca Weinstock‐Guttman MD

Robert Zivadinov MD

Murali Ramanathan PhD

Channa Kolb MD, David Hojnacki MD, Meg Bucello NP

Jonathan Rodgers PhD, Audrey Smerbeck PhD, Adam Booth MA, Seth Frndek BS, Carrie Fisher BA, Allison Drake BA, Victoria Kordovski BA, Claire Modica BS, Maria Pollack, Kelly Couglin, Joy Parrish PhD

Disclosures:Accorda, Bayer, Biogen Idec, EMD Serono, Genzyme, Genentech, Novartis, Questor

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Objectives

Understand the differences between various forms of depressive disorder in MS and underlying personality traits

Know how to assess personality traits

Appreciate and recognize signs of maladaptive personality characteristics in MS patients

Humorism Theory

A surplus or imbalance of one fluid impacts personality and physical health.

[Hippocrates 400 BC; Galen 162 AD]

Blood AirLiver

PhlegmWaterBrain

Black BileEarthGall Bladder

Yellow Bile FireSpleen

blood - hopeful amorousyellow bile - bad temperedblack bile - despondent sleeplessphlegm - calm detached

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PropensitiesAdhesivenessAlimentivenessAmativenessAcquisitivenessCausalityCautiousnessCombativenessConcentrativenessConstructivenessDestructivenessIdealityLove of lifePhiloprogenitivenessSecretiveness

SentimentsBenevolenceConscientiousnessFirmnessHopeIdealityImitationVenerationWit or MirthfulnessWonder

Phrenology: mapping of cognitive and personality attributes on to cranium. Appreciation of individual differences and interventions. [Gall 1801]

Positives: Individual Differences,  schools for slow learnersRehabilitation of criminals with mental defects

Papurt, M. (1930).  A study of the Woodworth Psychoneurotic Inventory with suggested revision.  Journal of Abnormal and Social Psychology, 25(3), 335‐352

Woodworth Psychoneurotic Inventory

Do you worry too much about little things? YES  NO Are you ever bothered by the feeling that people are reading your thoughts?  YES  NO Do you think you have too much trouble in making up your mind? YES  NO Have you ever seen a vision? YES  NO Do you get rattled easily? YES  NO Can you sit still without fidgeting? YES  NO Does your mind wander badly so that you lose track of what you are doing? YES  NO Does some particular useless thought keep coming into your mind to bother you? YES  NO Are you afraid of responsibility? YES  NO 

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Personality Traits

• Neurotic

• Introverted

• Psychotic Prone

• Warm

• Task Oriented

• Open Minded

Psychopathology

• Narcissistic Personality Disorder

• Borderline Personality Disorder

• Bipolar/Cyclothymic

• Obsessive Compulsive Disorder

• Psychotic Disorder

• Depression

Major Depression:  Primary symptoms are dysphoria and anhedonia, must be accompanied by 5 of insomnia, appetite suppression, anergia, fatigue, low self‐esteem. diminished concentration, suicidal ideation.

Minor Depression:  aka adjustment disorder w depressed mood, depression less severe without anhedonia, follows a stressor.

Dysthymic Disorder:  aka neurotic depression or depressive personality, chronic dysphoria not meeting criteria for major depression, now called persistent depressive disorder

Dimensional models of personality: the five‐factor model and the DSM‐5Timothy J. Trull, PhD; Thomas A. Widiger, PhD.  Dialogues Clin Neurosci. 2013;15:135‐146.

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NEO Five Factor Inventory (NEOFFI)

• 60 item test with self‐ and informant‐report forms

• Factor analysis shows 5 factors consistent with the FFM [Costa & McCrae 1992]

• Test‐retest reliability from r = 0.86 to 0.90 [McCrae & Costa 2004]

NEOFFI Neuroticism

I am not a worrier SD D N A SA

I often feel tense of jittery SD D N A SA

I often get angry at the way people treat me

SD D N A SA

D = disagree, A = agree, SD = strongly disagree, SA = strongly agree, N = neutral

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NEOFFI Extraversion

My life is fast paced SD D N A SA

I usually prefer to do things alone SD D N A SA

I often feel as though I’m bursting with energy

SD D N A SA

D = disagree, A = agree, SD = strongly disagree, SA = strongly agree, N = neutral

NEOFFI Openness

I am intrigued by the patterns I find in art and nature

SD D N A SA

I seldom notice the moods or feelings that different environments produce

SD D N A SA

Sometimes, when reading poetry of looking at a work of art, I feel a chill or wave of excitement

SD D N A SA

D = disagree, A = agree, SD = strongly disagree, SA = strongly agree, N = neutral

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NEOFFI Agreeableness

I try to be courteous to everyone I meet SD D N A SA

I would rather cooperate with others than compete with them

SD D N A SA

Most people will take advantage of you if you let them

SD D N A SA

D = disagree, A = agree, SD = strongly disagree, SA = strongly agree, N = neutral

NEOFFI Conscientiousness

I never seem to be able to get organized SD D N A SA

I’m pretty good at pacing myself so that I get things done on time

SD D N A SA

I have a clear set of goals and work toward them in an orderly fashion

SD D N A SA

D = disagree, A = agree, SD = strongly disagree, SA = strongly agree, N = neutral

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Neuroticism

• Negative emotion, pessimism, worry.

• BENEFITS: ↑ detection of threatening stimuli, ↓ engagement in fearful behaviors, ↑ competitiveness, ↑ motivation to improve oneself

• RISKS: ↑ risk of psychiatric disorder, ↑ stress-related medical illness, ↑ chance relationship failure

Extraversion

• Positive emotion, exploratory activity, sensation seeking. Dopamine mediated reward circuits

• BENEFITS: ↑ mating partners, ↑ social support

• RISKS: ↑ exposure to danger and accidents, ↑ antisocial behavior, ↑ divorce

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Conscientiousness

• Orderliness, self control, achievement striving, organization

• BENEFITS: ↑ delay of gratification to achieve LT goal, ↑ health behavior

• RISKS: ↑ OCD, ↓ opportunities for spontaneous adaptive behavior

Chapman et al. Personality and Medical Illness Burden Among Older Adults in Primary Care. Psychosom Med. 2007;69:277‐282

• 449 gen practice patients age 65‐97

• Cumulative Illness Rating Scale (CIRS) – aggregate composite of medical morbidity, coded by experienced physician based on chart review. 0 to 4, higher = severe burden.

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n = 44 exclude major depressive episode, current 86% female median EDSS = 2.75, range 1.0 to 7.0 27 RR, 17 SP/RP mean disease duration = 12+7.1 years collateral source: 28 spouse or domestic partner; 9 parent; 7 other family member. Mean years known 29.3+14.8.

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Minimal Assessment of Cognitive Function in MS (MACFIMS)

‐Memory Composite z score – CVLT2, BVMTR

‐ Processing Speed Composite z score – PASAT, SDMT

‐ Executive Function Composite z – DKEFS Sorting Test

Beck Depression Inventory Fast Screen (BDIFS)

Representative images of normalized cortical volumes (NCV) segmented with SIENAX automated method in NC age 42, NCV = 598.2 ml (upper row), RR (middle row) age 44 NCV = 555.4 ml and SP patient age 62 NCV=512.5 ml (lower row). From left to right are shown: original 3D‐T1‐SPGR image, standard skull‐stripped space image, cerebrospinal fluid mask, cortical gray matter mask, cortical white matter mask and three tissue classes image showing cerebrospinal fluid (slightly gray), cortical gray matter (dark gray) and cortical white matter (mid gray).

Mean SD Range

Age 45.4 9.6 23 – 62

Median EDSS 2.75 0.0 – 7.0

Disease Duration 11.8 7.0 01 – 28

Processing Speed Composite z score ‐1.31 1.21 ‐3.50 – 0.78

Memory Composite z score ‐1.47 1.09 ‐4.49 – 0.56

Executive Composite z score ‐0.95 3.09 ‐3.46 – 1.23

Beck Depression Inventory Fast Screen raw score 2.89 3.10 0 – 10

T2 Lesion Volume in ml 17.0 20.3 4.2 – 101.6

Neocortical Volume in ml 539.4 65.8 326.5 – 657.3

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VocationalStatus

FatigueAge,

Education, etc

DiseaseFeatures

PhysicalDisability

Cognitive Function

MoodDisorder

PersonalityBehavior Disorder

MSQOL-54

Benedict et al. J Neurol Sci. 2005;231;29‐34

Linear regression analysis in 120 MS patients

Tridimensional Personality Questionnaire (TPQ)

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[In] most of the patients affected by multi-locularsclerosis whom I have had occasion to observe … there is marked enfeeblement of the memory; conceptions are formed slowly; the intellectual and emotional faculties are blunted in their totality. The dominant feeling in the patients appears to be a sort of almost cheerful indifferencein reference to all things.

Jean-Martin Charcot (1877)

30Benedict & Bobholz. Seminars in Neurology, Vol 27, 78-85

Age 51; Male; 16 years Education SDMT < 1st %ile; PASAT < 1st %ile

Former Teacher, SSDI CVLT2 TL < 1st %ile; BVMTR TL 1st %ile

Euphoria; Disinhibition; Poor Empathy Valproic acid; risperdone; paroxetine

CASE CG

Patient reports average Neuroticism and ConscientiousnessWife reports elevated Neuroticism, and very low Agreeableness and Conscientiousness

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Pts with low Conscientiousness more likely to lose cognitive ability after MS Dx, and those with high Conscientiousness more likely to remain stable.

Conscientiousness explains how GMV leads to euphoria in al MS pts

GMV → Euphoria effect is influenced by Neuro cism only in high Neuroticism patients. High neuroticism induces chronically high emotionality and dysregulation of the hypothalamic‐pituitary‐adrenal axis.

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Conclusions

Personality can be distinguished from psychopathology, as in Neuro cism → Dysthymic Disorder → Major Depression

There are psychometric tests for personality, NEOFFI is validated in MS

↑ in Neuro cism and ↓ in Extraversion and Conscientiousness are risk factors for poor adaptation

Personality is affected in some MS patients

Thank You

Bianca Weinstock-Guttman MD

Robert Zivadinov MD; Murali Ramanathan PhD

David Hojnacki MD; Channa Kolb MD

Margaret Bucello NP; Audrey Smerbeck PhD

Jonathan Rodgers PhD, Natalie Emmert BA