1. Impact of transient and persistent personality disturbance on the outcome of anxiety and depressive disorders Professor Peter Tyrer (Imperial College, London) Dr Boliang Guo (University of Nottingham) Professor Min Yang (University of Sichuan, Chengdu, China)

2. Aims To summarise the hypotheses of the Nottingham Study of Neurotic Disorder (NSND) To summarise previous opinions on the course of personality disorder and its influence on the outcome of anxiety and depression To compare the outcome of patients in NSND by transient and persistent personality disorder status over a 12 year period   To explain why the results are important

3. Nottingham study of Neurotic Disorder (1983-2019) Hypotheses: (1) outcome of common anxiety and depressive disorders is dependent on personality status, not on treatment (2) Personality and clinical status in the form of the general neurotic syndrome (mixed anxiety and depression and dependent/anankastic personality) would have the worst outcome (3) These differences would become greater over time

4. Brief summary of design Patients seen between 1983 and 1987 in general practice clinics in Nottingham if they (i) were on no treatment, (ii) had a diagnosis of dysthymia (chronic depression), generalised anxiety, or panic disorder (DSM-III), (iii) agreed to randomisation to diazepam, dothiepin, placebo, CBT or self-help for 6 weeks with all treatment tailed off by 10 weeks. Patients seen between 1983 and 1987 in general practice clinics in Nottingham if they (i) were on no treatment, (ii) had a diagnosis of dysthymia (chronic depression), generalised anxiety, or panic disorder (DSM-III), (iii) agreed to randomisation to diazepam, dothiepin, placebo, CBT or self-help for 6 weeks with all treatment tailed off by 10 weeks. 210 recruited 210 recruited

5. Assessments at baseline and subsequently Baseline, 2, 12 and 30 years – Personality assessment using Personality Assessment Schedule (Tyrer & Alexander, Br J Psychiatry (1979), 135, 163-67. Baseline, 2, 12 and 30 years – Personality assessment using Personality Assessment Schedule (Tyrer & Alexander, Br J Psychiatry (1979), 135, 163-67. At baseline, 2, 4, 6, 10, 16, 32 and 52 weeks, and at 2, 12, and 30 years – Comprehensive Psychopathological Rating Scale (CPRS), Montgomery & Asberg Depression Rating Scale (MADRS), Brief Anxiety Scale (BAS), Hospital Anxiety and Depression Rating Scale (HADS-A and HADS-D) At baseline, 2, 4, 6, 10, 16, 32 and 52 weeks, and at 2, 12, and 30 years – Comprehensive Psychopathological Rating Scale (CPRS), Montgomery & Asberg Depression Rating Scale (MADRS), Brief Anxiety Scale (BAS), Hospital Anxiety and Depression Rating Scale (HADS-A and HADS-D) All psychotropic medication recorded (0-30 years) All psychotropic medication recorded (0-30 years) Social function (SFQ) recorded at 12 and 30 years Social function (SFQ) recorded at 12 and 30 years Neurotic Disorder Outcome Scale (NDOS)(12 and 30 years, plus self-harm history, GP and hospital contacts Neurotic Disorder Outcome Scale (NDOS)(12 and 30 years, plus self-harm history, GP and hospital contacts SCID (DSM diagnosis) at baseline, 10, 16, 32, 52 wks and at 2, 12 and 30 years SCID (DSM diagnosis) at baseline, 10, 16, 32, 52 wks and at 2, 12 and 30 years

6. Summary of findings Diazepam inferior to other treatments, including placebo after 10 weeks (Tyrer et al, Lancet (1988), 332, 235-40) Diazepam inferior to other treatments, including placebo after 10 weeks (Tyrer et al, Lancet (1988), 332, 235-40) After 2 years patients with the general neurotic syndrome had a significantly worse outcome than other groups (Tyrer et al, Acta Psychiat Scand (1992), After 2 years patients with the general neurotic syndrome had a significantly worse outcome than other groups (Tyrer et al, Acta Psychiat Scand (1992), 85, 201-06. Personality status had no influence on outcome at 10 weeks (Tyrer et al, Psychol Med, 1990, 20, 423-31. Personality status had no influence on outcome at 10 weeks (Tyrer et al, Psychol Med, 1990, 20, 423-31. but had a negative effect at 5 and 12 years (Tyrer et al, Psychol Med, (2004) but had a negative effect at 5 and 12 years (Tyrer et al, Psychol Med, (2004) 34: 1385-1394.

7. Personality disorder at baseline had no effect on 10 week outcome

8. Reasons for recording personality status both at baseline and two years To determine whether any of the treatments had a positive effect on personality status To determine whether any of the treatments had a positive effect on personality status To assess the long-term temporal reliability of personality disorder using the PAS, as short-term reliability had been shown to be good (Tyrer et al, Psychol Med, (1983) To assess the long-term temporal reliability of personality disorder using the PAS, as short-term reliability had been shown to be good (Tyrer et al, Psychol Med, (1983) 13, 393-98. To determine whether the diagnostic criteria for the general neurotic syndrome were still met at 2 years To determine whether the diagnostic criteria for the general neurotic syndrome were still met at 2 years (None of these hypotheses has been tested as the second personality assessment fell by the wayside)

9. Reason why the analysis of personality data at 2 years has become important We now know that personality shifts greatly over time and is not nearly as persistent as first thought The reasons for this include (i) difficulty in distinguishing personality from mental state (so that when mental state improved personality may also), (ii) environmental changes may reduce or increase impact of personality abnormality (iii) social functioning tends to remain poor even if symptoms improve in personality disorder (Shea et al,2004) (iv) developing general view that a single assessment of personality is not enough to confirm diagnosis of personality disorder (iv) developing general view that a single assessment of personality is not enough to confirm diagnosis of personality disorder

10. Why are these hypotheses important? They are important scientifically as if personality, independently of mental state, does show evidence of increasing increasing (2) Personality and clinical status in the form of the general neurotic syndrome (mixed anxiety and depression and dependent/anankastic personality) would have the worst outcome (3) These differences would become greater over time

11. Hypotheses in present investigation 1. 1. Those who have personality disorder at both baseline and two years (ie persistent disorder) have true personality disorder and would have a worse long term outcome than those who had personality disorder only at baseline (transient personality disorder) 2. 2. Those who had personality disorder at 2 years only would have the same outcome as those with personality disorder at baseline only 3. 3. Social function would be more impaired in personality disorders than psychiatric symptoms

12. BIGSPD Leeds 2015 This is the persistent pd group

13. BIGSPD Leeds 2015 ----------------------------------------------------- Threshold for pathology Message – Long-term outcome of depression is good unless personality disorder is persistent Persistent pd

14. BIGSPD Leeds 2015 CPRS 0 PD at both 0 &2yr 21.54 7.44 13.40 8.888.7110.28 0.2084 PD both 0 &2year25.64 8.18 21.80 11.184.0210.44 PDbase 0 2year20.39 8.99 13.66 11.547.2812.80 0 base pd 2year19.32 6.52 12.18 8.227.059.49 HADSA 0PD at 0 &2year13.93 3.74 8.05 5.106.144.83 0.0232* PD both 0 &2year14.67 3.53 11.80 5.223.244.96 PDbase 0 2year13.12 4.01 7.35 5.006.065.31 0 base pd 2year13.93 3.83 8.91 5.145.184.99

15. BIGSPD Leeds 2015 outcomegroup Mean (bsl) Sd (base) Means (12 yr) Sds (12 year change Sd (chg) P Value of change comparison HADS-D No pd ever 9.564.476.025.12 3.90 5.10 0.2390 persistent PD both 0 &2year 11.624.099.465.31 2.12 5.17 transient PD base 0 2year 9.554.126.106.06 3.52 5.97 transient 0 base pd 2year 9.364.314.453.83 4.36 3.17 MADRS No pd ever 19.158.1411.339.59 8.40 12.58 0.0702 persistent PD both bsl & 2yr 20.897.8718.9611.57 1.80 12.65 transient PD bsl 0 2year 17.188.0611.6312.70 6.09 13.64 transient 0 base pd 2year 16.327.349.648.49 7.05 8.81

16. Additional Findings with social functioning (SFQ) SFQ * none No PD at 0 or at 2 yr 6.05 4.42 pers PD both 0 &2year 10.88 5.23 trans PDbase 0 2year 7.75 5.90 trans 0 base pd 2year 6.91 4.80 0.0001 BIGSPD Leeds 2015 12 yr mean Sd P value of compariso n SFQ – higher scores indicate worse social function. Population mean is 4.6, a score of 10 or more indicates poor social function

17. Conclusions Persistent personality disorder impairs the outcome of anxiety and depressive disorders to the extent that no significant symptomatic improvement is shown over 12 years Persistent personality disorder impairs the outcome of anxiety and depressive disorders to the extent that no significant symptomatic improvement is shown over 12 years Transient personality disorder is associated with the same outcomes as those with no personality disorder at baseline and two years Transient personality disorder is associated with the same outcomes as those with no personality disorder at baseline and two years