1. Influence of cyclothymic and hyperthymic temperaments on clinical features and treatment response of acute mania Giulio Perugi Institute of Behavioural sciences G De Lisio, Pise, Italy

2. Course of Mania in 1890 Clouston, 1892 15% 30 % 5%

3. Course of Mania in 2000 Tohen et al., 2003 72% 28%

4. Symptom, Remission Functional Remission Low socio-economical levelXX Premorbid general adjustmentXX Premorbid work adjustmentXX Social adjustmentX_ Low educational level_X Male genderX_ Early onsetX_ Course of manic episode Socio-demographic variables Haro et al., 2011; Vieta et al., 2004; Van Riel et al., 2008; Ketter et al., 2010; Kemp et al., 2011.

5. Symptom. Remission Functional Remission Childhood psychopatology XX CGI Severity XX YMRS Severity X_ > 2 depressive symptoms X_ Psychotic features _X Mixed mania __ Course of manic episode Symtomatological variables Haro et al., 2011; Vieta et al., 2004; Van Riel et al., 2008; Ketter et al., 2010; Kemp et al., 2011.

6. Symptom, Remission Functional Remission Substance Use Disorders XX Comorbiduty X_ Multiple Episodes XX Duration of the hospitalization XX Duration odf the episode __ N. of previou episodes X_ Course of manic episode Other clinical variables Haro et al., 2011; Vieta et al., 2004; Van Riel et al., 2008; Ketter et al., 2010; Kemp et al., 2011.

7. Mixed Mania Reduced treatment response Hospitalizations Retarded response Increased relapse probability Chronicity Continuous cycling Swann et al., 1997; Gonzalez-Pinto et al., 2007

8. Major Episodes and affective temperament Mania+Depressive Temp.Mixed Mania Depression+Hypert. Temp.Mixed Depression Akiskal e Benazzi, 2003

10.  Cyclothymic-sensitive  More females  Anxious-impulsive comorbidity  Borderline features  FH BD and Anxiety disorders  More suicide attempts  Hyperthymic  More males  More manic episodes and hospitalizations  Drug/alcohol abuse and antisocial behaviour Cyclothymic and Hyperthymic bipolar I disorder subtypes

11. Oster Study Perspective, longitudinal study - observational, naturalistic 34 centers 194 patients Mania (DSM-IV-TR, APA 2000) Rated: baseline Weeks 1, 3, 8 e 12 (± 1 week) Board: Perugi G (Pisa), Fagiolini A. (Siena), De Bartolomeis (Napoli), Maina G (Torino).

12. Aim of the OSTER Study Predictors of response Socio-demographic features Clinical characteristics Affective temperaments Childhood trauma Manic Symptoms Functional remission

13. Clinical response in 227 manic patients Perugi et al., preliminary results 82% 18%

14. Secondary Analisys Affective temperaments on clinical presentation and course of mania Manic Symptoms Functional remission Socio-demographic features Childhood trauma

15. Rating Scales YMRS : Young Mania Rating Scale MADRS : Montgomery and Asberg Depression Rating Scale CGI-BD : Clinical Global Impression Scale-Bipolar Illness FAST : Functioning Assessment Short Test CTQ : Childhood Trauma Questionnaire briefTEMPS-M : Temperament Evaluation of Memphis, Pisa, Paris and San Diego brief-version

16. *p<0.01 Temperamenti DepressiveCyclothymicHyperthyimicIrritableAnxious Depressive 1 0.52* -0.14 0.43*0.56* Cyiclothymic 0.52* 1-0.16 0.50*0.46* Hyperthymic -0.14-0.161 0.21* -0.01 Irritable 0.43*0.50*0.21* 1 0.42* Anxious 0.56*0.46* -0.01 0.42* 1 CTQ total 0.30*0.22* 0.16 0.36*0.26* Correlations among affective temperaments (briefTEMPS-M) and total CTQ scores in 194 manic patients

17. CyclothymicHyperthymic Depressive 0.82 -0.18 Cyclothymic 0.82 -0.09 Hyperthimic -0.08 0.95 Irritable 0.730.43 Anxious 0.78 0.02 Eingen 2.481.13 %Variance 49.6522.67 Factorial analysis of the affective temperaments (briefTEMPS-M) scores in 194 manic patients

18. High correlations between temperaments Irritable Cyclothymic Anxious Depressive Hyperthymic Data for N=153 remitted bipolar patients, only correlations >0.5 are shown Brieger et al. JAD 2004

19. ScaleCyclothymicIrritableAnxious Depressive 0.563 * 0.380 * 0.547 * Cyclothymic 0.618 * 0.652 * Irritable 0.595 * Lebanese-Arabic TEMPS-A & Correlations * p<0.001 by Pearson Bivariate Correlation Hyperthymic was not correlated with any of the other four affective temperaments Karam EG et al. J Affect Disord 2005;87:169-183

20. Two temperamental dimensions in bipolar I patients High Energy – Mood Stability (Emotional intensity) CyclothymicIrritable Hyperthymic Low Energy-Mood reactivity (Emotional instability) Separation anxiety CYCLOTHYMIA HYPERTHYMIA Depressive Interpersonal Sensitivity

21. Grundzüge der physiologischen Psychologie. 5. Auflage, Wilhelm Engelmann, Leipzig (1902-3) Stärke der Gemütsbewegung Strength of affective movement Schnelligkeit des Wechsels der Gemütsbewegung Velocity of change of affective movement Wilhelm Wundt (1832-1920)

22. Temperaments according to Wundt strength of affective movement velocity of change of affective movement x y 84th percentile 16th percentile Cyclothymia Hyperthymia

23. Hyperthymic (n=101) Cyclothymic (n=93) p Gender (males) 46 (45.5)39 (41.9)ns Age48.90 (14.37)47.52 (12.85)ns Age At onset33.97 (13.65)32.66 (11.99)ns Education (<8 years) 9 (8.9)9 (9.7)ns Married 44 (43.6)32 (34.4)ns Work: unoccupied 24 (23.8)20 (21.5)ns Absence from work 19 (18.8)15 (16.1)ns Hospitalized 60 (59.4)46 (49.5)ns Family hystory of BD 49 (48.5)30 (32.3) 0.02 Demographic and clinical features

24. Hyperthymic (n=101) Cyclothymic (n=93) p Anxiety Disorders33 (32.7)28 (30.1)ns Borderline PD4 (4.0)3 (3.2)ns Eating Disorders7 (6.9)7 (7.5)ns Alcohol24 (23.8)20 (21.5)ns Substances22 (21.9)27 (29.1)ns Rapid Cycling2 (2.0)7 (7.5)0.07 Psychotic features61 (60.4)60 (64.5)ns Suicide Attempts17 (16.8)10 (10.8)ns N. Depressive episodes3.19 (5.32)3.33 (4.37)ns N. Manic episodes3.98 (5.40)3.67 (3.75)ns N. Mixed episodes0.97 (2.62)1.30 (2.60)ns Dominant Polarity Depressive Manic None 15 (14.9) 56 (55.4) 25 (24.8) 20 (21.5) 44 (47.3) 28 (30.1) ns Comorbidity and course

25. YMRS baseline Mean (sd) p Hyperthymic (n=101) Cyclothymic (n=93) Total score 1. elated mood 2. increased activity/energy 3. Sexual interes 4. sleep 5. Irritability 6. language 7. thought 8. thoght content 9. aggression 10. appearence 11. insight 28.97 (9.78) 2.72 (0.83) 2.67 (0.86) 1.38 (1.18) 2.54 (1.05) 4.12 (1.69) 4.39 (1.69) 1.82 (0.87) 3.81 (2.41) 2.33 (1.77) 1.39 (1.06) 1.82 (1.48) 26.99 (9.34) 2.45 (0.81) 2.46 (0.92) 1.47 (1.16) 2.19 (1.15) 3.91 (1.66) 3.91 (1.54) 1.71 (0.90) 3.87 (2.17) 1.94 (1.50) 1.20 (1.09) 1.89 (1.57) ns 0.02 ns 0.03 ns 0.04 ns

26. MADRS Baseline Mean (sd) p Hyperthymic (n=101) Cyclothymic (n=93) MADRS Baseline Total Score 1. Sadness appearence 2. Sadness reported 3. Tension 4. Insomnia 5. Appetite 6. Concentration 7. Titredness 8. Anedonia 9. Pessimistic thoughts 10. Suiicidality 12.91 (5.86) 0.58 (0.88) 0.60 (0.99) 2.34 (1.20) 3.92 (1.75) 0.75 (1.23) 2.69 (1.56) 0.81 (1.32) 0.50 (0.90) 0.58 (1.12) 0.16 (0.46) 12.87 (7.11) 0.57 (1.12) 0.59 (1.07) 2.59 (1.01) 3.48 (1.90) 0.86 (1.40) 2.77 (1.52) 0.66 (1.28) 0.44 (1.01) 0.61 (1.22) 0.29 (0.84) ns

27. Mean (sd) p Hyperthymic (n=101) Cyclothymic (n=93) Baseline Total Score Autonomy Work Cognitive Financial Social Leisure 38.64 (17.13) 6.20 (3.71) 8.97 (5.14) 7.94 (4.36) 3.67 (1.89) 9.62 (4.85) 3.15 (1.94) 40.02 (15.40) 6.49 (3.39) 9.44 (4.62) 8.21 (3.83) 3.49 (1.95) 9.82 (4.52) 3.41 (2.08) ns Final Total Score Autonomy Work Cognitive Financial Social Leisure 17.38 (13.96) 2.47 (2.84) 5.11 (4.55) 2.92 (3.32) 1.27 (1.54) 4.07 (3.68) 1.79 (1.62) 25.34 (15.92) 3.76 (3.23) 7.41 (4.95) 4.57 (3.58) 1.83 (1.95) 6.10 (4.09) 2.57 (1.85) 0.00 0.03 0.00 Social Functionning (Fast)

28. History of trauma (CTQ) Mean (sd) p Ipertimic (n=101) Cyclothymic (n=93) CTQ Total Score Abuse emotional physical sexual Neglect Emotional physical 44.80 (10.74) 8.25 (3.69) 6.61 (2.93) 6.09 (2.59) 12.00 (4.17) 11.85 (2.07) 48.73 (13.33) 9.73 (4.44) 7.41 (3.95) 6.41 (3.04) 13.26 (4.82) 12.02 (2.37) 0.03 0.01 ns 0.05 ns

29. Conclusions Brief TEMPS-M Hyperthymic Cyclothymic No-difference demographic features, Axis I and II comorbidity course characteristics Different YMRS profile at baseline Cyclothymic More FH of BD Childhood history of emotional abuse and neglect Reduced Social Functioning

30. .…Their mode of expression is clever and lively.. … They charm us by their intellectual mobility, their wealth of ideas, their ready accessibility,…their good nature,… and their cheery, sunny mood.  …From youth up there exists in the patients a special susceptibility for the cares, the difficulties, the disappointments of life.. …Frequently ….a capricious, irritable, unfriendly, repellent behaviour is developed. Emil Krapelin, 1921