ADHD, bipolar and borderline personality disorder

Transcription

1 ADHD, bipolar and borderline personality disorder Philip Asherson MRCPsych, PhD Professor of Molecular Psychiatry & Honorary Consultant Psychiatrist, MRC Social Genetic Developmental Psychiatry, Institute of Psychiatry, UK MRC Social Genetic and Developmental Psychiatry

2 Relationship of ADHD to borderline and Question Borderline Bipolar Co-occurrence rates? Increased Increased Shared familial risks? Probable Yes Shared genetic risks? Probable Yes Developmental precursor? Neurobiology associations? bipolar disorder Yes (risk factor) Unknown No Largely distinct Common treatments? No No Diagnostic criteria overlap? Yes Yes Skirrow, Hosang, Farmer, Asherson, JAD, in press; Philipsen 2008;

3 Similarities Differences ADHD specific Borderline Childhood or adolescent onset Developmentally inappropriate behaviours Chronic trait like course Pervasive across situations Impulsivity Impaired social relationships Emotional/mood instability ** Irritability ** Frantic efforts to avoid real or imagined abandonment Identify disturbance Recurrent suicidal behaviour Chronic feelings of emptiness Transient stress-related paranoid thoughts Inattention Overactivity Bipolar Overactivity Pressured/incessant speech Impulsive Irritability ** Emotional/mood instability ** Distractibility Short attention span Depressive episodes (not uncommon in ADHD) Sleep problems Episodic course ** Post-pubertal onset Grandiose or elated mood Often lacks insight Psychosis Trait-like course Early childhood onset Insight

4 Traditional criteria for ADHD HIDE: Hyperactivity Impulsivity Distractibility Emotional lability Gabrielle Carlsson, personal communication (Cantwell) Eric Cantwell DSM-IV ADHD: Hyperactivity Impulsivity Inattention Emotional dysregulation: - mood instability - affective lability

5 History of Adult ADHD THE FIRST PUBLISHED STUDY OF ADHD in ADULTS: Wood DR, Reimherr FW, Wender PH, Johnson GE. Diagnosis and treatment of minimal brain dysfunction in adults: a preliminary report. Archives Gen Psychiatry It showed that, compared to children with ADHD, adults had: A similar pattern of core symptoms Associated impairment A similar pattern of comorbidities A similar response to stimulant medication Similar associations with cognitive performance measures

6 Characterising mood instability in ADHD Mood fluctuations from day to day and within the day Many children have a short fuse or low boiling point, reacting easily and persistently to everyday frustrations Wender (1985) Feelings of irritability and frequent outbursts of short duration. Patients experiencing affective lability often experience definite shifts from normal mood to depression or mild excitement. Reimherr et al. (2005) The characteristic mood is highly volatile from one part of the day to the next, changing around four- to five-times a day mood is up and down, often for an hour or a few hours. Asherson (2005).

7 Assessment of adult ADHD Wender-Reimherr Interview (Wender 1995) 3 subscores related to ADHD core symptoms Inattention Hyperactivity Impulsivity 3 subscores related to Emotional Dysregulation Affective Lability Temper Control Emotional Over-reactivity Stress Intolerance

8 Wender-Reimherr Interview for ADHD Emotional Dysregulation Scale 1. Affective Lability: Mood fluctuations Dysphoric periods Boredom Overstimulation 2. Temper Control: Irritability Temper outbursts Lack of control 3. Emotional Over-reactivity: Overwhelmed, emotional Emotional reactivity

9 Atomoxetine Treatment in adult ADHD Decline of WRI subscores and HAM-D at week 10 0 Inattention Hyperactivity Emotional Dysregulation HAM-D p=.004 ES.51 p=.026 ES.40 p=.001 ES.66 p=.10 ES ATX Placebo Reimherr et al. 2005

10 Treatment response to methylphenidate (Cohen s d) Reimherr et al., 2007, JCP

11 Emotional dysregulation co-varies with ADHD symptoms during MPH treatment response Correlation (r) Inattention Hyperactivity / impulsivity Reimherr et al., 2007, JCP

12 Assessment of adult ADHD Frequency of Symptoms according to WRI (>80%) Rösler et al AL A3 Ü1 HT1 8 of the 19 most frequent symptoms of ADHD are emotional Symptoms HT2 AL1 EO3 A5 EO1 Emotional Dysregulation EO2 DO1 I1 Ü3 Inattention Hyperactivity Impulsivity T3 D5 Ü2 Disorganization A4 A1 A %

13 MPH Treatment in adult ADHD Decline of Wender-Reimherr Interview sub-scores at week WRI-INN WRI-HYPER WRI-IMP WRI-ED p=.0002 ES.41 p=.009 ES.30 p=.02 ES.27 P<.001 ES.37 MPH-ER Placebo Rösler et al. 2009, 2010

14 The MIRIAD project Mood Instability Research In ADHD Caroline Skirrow, Philip Asherson Funded by NIHR RISC program

15 MIRIAD project Highly Patients: selected sample with no comorbidity and medication free

16 ADHD case-control differences in psychopathology Skirrow & Asherson 2012 (submitted)

17 Affective Lability Scale (ALS) One minute I can be feeling OK and then the next minute I m tense, jittery, and nervous. I frequently switch from being able to control my temper very well to not being able to control it very well at all. Many times I feel nervous and tense and then I suddenly feel very sad and down. Frequently, I will be feeling OK but then I suddenly get so mad that I could hit something. There are times when I feel absolutely wonderful about myself but soon afterwards I often feel that I am just about the same as everyone else. There are times when I am so mad that I can barely stop yelling and other times shortly afterwards when I wouldn t think of yelling at all. I shift back and forth from feeling perfectly calm to feeling uptight and nervous. I switch back and forth between being extremely energetic and having so little energy that it s a huge effort just to get where I am going. Oliver & Simons (2005).

18 CNS-LS People have told me at times that I seem to get upset very easily or that I get upset over little things. I ve noticed that I get upset very easily. Others have told me that I seem to get frustrated very easily or that I seem to get frustrated over little things. I can quickly go from feeling calm to feeling very angry over little things or for no reason at all. At times I can be feeling no more impatient than others but then I ll suddenly become very impatient over something small or for no reason at all. People have told me at times that I seem to get impatient very easily or that I seem to get impatient over little things. Others have told me that I seem to get nervous very easily or that I seem to become nervous over little things. Sometimes I can be feeling fine one minute and then I ll yell or raise my voice in an angry way the next. Moore et al (1997).

19 Average Score (+/- 1 SD) Case-control differences for emotional lability scores Control ADHD 0 CNS-LS Mean ALS-SF Mean Anxious-depressed Depressed-Elated Anger All p<.001 Skirrow & Asherson 2012 (submitted)

20 Predictors of functional impairment in adults with ADHD Impairment/predictors Beta R R 2 p Family Emotional lability (CNS-LS) <.001 School Emotional lability (CNS-LS) Life Skills Emotional lability (CNS-LS) <.001 Self concept Comorbid symptoms (CIS-R) <.001 Social problems Emotional lability (CNS-LS) Hyperactivity-impulsivity (BRS) <.001 <.001 Risk (inverse transformed) Hyperactivity-impulsivity (BRS) Skirrow & Asherson 2012 (submitted)

21 The Experience sampling method (ESM) Participant wears a watch which vibrates at varying intervals Then they fill out a questionnaire on the PDA Responses collected 8 times a day for a working week (mon-fri)

22 imonitor Momentary Version How do you feel NOW? Negative mood: Frustrated, Angry, Irritable Positive mood: Happy, Excited Rated on a scale of 0 (not at all) to 100 (extremely) Did any good things happen to you in the last hour Did any bad things happen to you in the last hour - How much are you effected now by the good/bad thing that happened

23 Anger ratings for individuals with ADHD and healthy controls over the 5-day period ADHD n=35 Controls N=44 Subjective rating of angry (Matched for age, IQ and years in education)

24 Mean ratings of emotion items P-value: <.001 <.003 <.003 ns ns Mean ratings of irritable, angry and frustrated were highly correlated; r > 0.81

25 MSSD: Mean Square Successive Difference Series1 Series Successive reports Series 1 Series 2 Mean SD MMSD

26 MSSD of emotion items over 5-day period P-value: <.001 <.001 <.001 <.02 ns

27 Reported anger +/- 1SE Impact of bad events on reported anger ADHD Control (T-1) (T) (T+1) (T+2) Average duration from reporting of bad event (mins)

28 Treatment

29 Treatment algorithm Chronic (trait-like) Emotional lability Screen for ADHD No ADHD Establish alternative diagnosis and treat accordingly (e.g. Bipolar disorder, personality disorder/odd, anxiety/depression, alcohol/drug abuse, severe mood dysregulation) Yes ADHD No comorbidity or comorbid personality disorder ** Drug treatment for ADHD (stimulants or atomoxetine) Significant depression, bipolar disorder, other condition Treat comorbid disorder first in most cases Review and consider additional treatments: CBT, anger management, other medication

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31 Mean score Treatment Response Baseline Follow-up Change scores CNSLS ALS Inattention Hyperactivity- Impulsivity CNSLS ALS Inattention Hyperactivity- Impulsivity 1

32 ADHD Childhood or adolescent onset Defined by impairment Chronic trait like course Pervasive across situations Behavioural symptoms out of keeping for developmental stage Affective lability (can be severe) Impulsive Hyperactivity Inattention n/a n/a n/a n/a n/a Borderline Personality disorder Personality disorder Childhood or adolescent onset Defined by impairment Chronic trait like course Pervasive across situations Behavioural symptoms out of keeping for developmental stage Affective lability Impulsive n/a n/a Frantic efforts to avoid real or imagined abandonment Identity disturbance Recurrent suicidal behaviour Chronic feelings of emptiness Transient, stress-related paranoid thoughts

33 Childhood onset Trait like course Excitable ADHD Reports inability to function Low self-esteem (and depression) are common Usually has insight Complains of insomnia Complains of short attention span/distractibility Inconsistent performance unrelated to mood Motor restlessness: fidgety, prefers to be moving around Bored easily Bipolar (mania/hypomania) Post-pubertal onset Episodic course Grandiose or elated Bipolar disorder Reports high levels of function Depressive episodes are common Often has no insight Reduced need for sleep Subjective sense of sharpened mental activity Poor function during episodes of depression or mania Overactivity unable to slow down often linked to unrealistic plans Not bored easily

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35 Cross-disorder polygenic prediction: genetic evidence for aetiological overlap between ADHD and bipolar disorder 6 ASD ADHD Test set MDD BPD SCH = significant = non-significant = non-significant 0 0 SCH 1 BPD 2 MDD 3 ADHD 4 5 ASD 6 n=9379 n=6690 n=9227 n=2787 n=4949 Discovery set Cross disorder group of the GWAS consortium, 2012