1. Handwriting Movement Kinematics for Quantifying Antipsychotic-Induced EPS
Michael Caligiuri, Ph.D.
Hans-Leo Teulings, Ph.D.
Charles Dean, M.D.
Alexander Niculescu, M.D., Ph.D.
James Lohr, M.D.
2009 INTERNATIONAL CONGRESS ON SCHIZOPHRENIA RESEARCH,
28 March - 01 April, Manchester Grand Hyatt, San Diego, California, USA Session: Side-effects of Antipsychotic Drugs: Epidemiology, Mechanisms of Action, Measurement, and Treatment

2. Haase’s original publication

3. Statement of the Problem & Purpose of Study
Handwriting is sensitive to the neuromotor side effects of antipsychotics; however
Classic studies were subjective
Modern studies involved small samples
Aim is to test quantitative analyses of handwriting movements
Useful in identifying and monitoring EPS &
Effects of different antipsychotics.

4. Study Design 132 Subjects: Clinical assessments: Handwriting movements
Schizophrenia (60), Schizoaffective (20), Bipolar (7) patients
Healthy comparison subjects (45)
Clinical assessments:
EPS severity ratings, PANSS, Medication inventory
Handwriting movements
Sequences of 8 continuous 2-cm loops, written L-R (3 trials each).
Acquired and analyzed using Movalyzer software.
Kinematic variables: Vertical Loop Size, Peak Velocity, Relative Time to Peak Velocity, Pen Contact Duration, Average Normalized Jerk
Per up or down stroke
Per primary, ballistic submovement
Per secondary, corrective submovement

5. Example of Handwriting Task -- Control
Control Subject
1: Apparatus
2: Raw waveform
3: Vertical Velocity
4: Submovements
Coloring: Red=low jerk (=small force changes), Blue=high jerk (= big force changes)

6. Example of Handwriting Task -- Patient
Schizophrenia Patient
1: Apparatus
2: Raw waveform
3: Vertical Velocity
4: Submovements
Coloring: Red=low jerk (=small force changes), Blue=high jerk (= big force changes)

7. Subject CharacteristicsN
Age
Gender
M:F
PANSS
Total
SAEPS
Controls 45
42.1 (9.3)
14:31
---
0.21 (0.45)
EPS - 31
46.9 (9.6)
22:9
66.4 (13.4)
1.16 (0.89)
EPS + * 40
48.6 (8.6)
25:15
69.6 (14.7)
5.85 (2.51)
aripiprazole
risperidone
quetiapine
olanzapine 13 31 12 8 n
* EPS+ based on total SAEPS score of 3 or higher

8. Vertical Size
p=0.002

9. Time to Peak Velocity
p=0.05

10. Pen Contact Duration
p=0.01

11. Average Normalized Jerk
p>0.10

12. Medication Effects Peak Vertical Velocity (cm/s) Total SAEPS *
ARI RIS QUE OLA
ARI RIS QUE OLA
Handwriting Kinematics shows
medication effect (p=0.005)
* OLA> ARI (p=0.01) and >RIS (p=0.02)
Clinical EPS Rating shows
no medication effect (p>0.1)

13. Pearson Coefficients (r) for Handwriting Kinematics vs Clinical State in Schizophrenia (n=60)
Vertical Size
Time to Peak Velocity
Pen Contact Duration
ANJ
SAEPS
Age
-0.12
0.01
0.14
0.25
PANSS Pos
0.21
0.06
0.02
PANSS Neg
-0.15
-0.08
-0.03
0.31*
PANSS Total
0.03
0.18
* p=0.02

14. Summary Assessment of handwriting kinematics
Simple, fast, and naturalistic quantitative measure of EPS in psychosis patients
Sensitive to differences between various antipsychotic medications (often missed using traditional severity ratings)
Independent of age and psychopathology
Handwriting kinematics useful evaluating medication changes in patients with pre-existing EPS.

15. Project Team San Diego Indianapolis
Michael Caligiuri, Ph.D. Alexander Niculescu, M.D., Ph.D.
James Lohr, M.D. Nasbeel Yehyawi
Todd May Craig Dike
Jeremy Davis
Dave Bertram
Minneapolis Phoenix
Charles Dean, M.D. Hans-Leo Teulings, Ph.D.
James Tacklind Somesh Chakrabarti
Jean Russell Aditya Choukulkar
Supported by DHHS Grant R44-MH073192

16. Complete Handwriting Experimental Protocol: 2007-2009
Left-Right Loops: lllllllll
1, 2, and 4 cm
Overlay Loops: O
LH and RH
Complex Loops: lleelllee
Overlay Loops at Max Speed: O
Sentence: Today is a nice day

17. Discussion
Given superior sensitivity for differences in movement side effects by different medications:
How can this technology be adopted in psychiatric clinics?