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, 2009 Manchester Grand Hyatt, San Diego, California, USA Session: Side-effects of Antipsychotic Drugs: Epidemiology, Mechanisms of Action, Measurement, and Treatment

Haase’s original publication

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.

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

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)

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)

Subject Characteristics N 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

Vertical Size p=0.002

Time to Peak Velocity p=0.05

Pen Contact Duration p=0.01

Average Normalized Jerk p>0.10

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)

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

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.

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

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

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