Early recognition of bipolar spectrum disorders
Ralph Kupka, MD PhD Professor of Bipolar Disorders Masterclass Netwerk Vroege Psychoase Utrecht, 10 februari 2017 Disclosure Ralph Kupka
Over the past 5 years, I have an interest in relation with one or more organisations that could be perceived as a possible conflict of interest in the context of the subject of this presentation. The relationships are summarised below:
Interest Name of organisation Grant NWO
Advisory boards n/a
Share holder n/a
Other involvement • Honoraria for lectures on symposia sponsored by AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Lundbeck • Royalties from UpToDate, De Tijdstroom Bipolar basics
Age of onset of bipolar disorder
Staging models for bipolar disorder
Is there a bipolar prodrome?
Early intervention in bipolar disorder
Some conclusions Bipolar basics
Age of onset of bipolar disorder
Staging models for bipolar disorder
Is there a bipolar prodrome?
Early intervention in bipolar disorder
Some conclusions Mood pathology
• depressed mood • no energy / drive / pleasure • feeling useless and worthless • no initiative Depression • can not sleep suicide • suicidal ideas / behavior Mood pathology
• euphoric/irritable mood Mania • increased activity / energy • feeling great severe • reckless behavior • need not sleep Hypomania damage • no insight Mood pathology
• euphoric/irritable mood Mania • increased activity / energy • feeling great severe • reckless behavior • need not sleep Hypomania damage • no insight
• depressed mood • no energy / drive / pleasure • feeling useless and worthless • no initiative Depression • can not sleep suicide • suicidal ideas / behavior Mania and Melancholia through the ages
Hippocrates Aretaeus of Robert Herman of Kos Cappadocia Burton Boerhaave
Francois Jean-Pierre Karl Emil Karl Jules Baillarger Falret Kahlbaum Kraepelin Leonhard Angst Manic-depressive illness is separated from dementia praecox (schizophrenia) Bipolar disorder is separated from unipolar depression
Karl Leonhard Jules Angst George Winokur (Ger, 1957) (CH, 1966) (USA, 1969) The debate goes on Young & MacQueen, 1999 The problem of defining hypomania Goodwin, 2002 Prevalence of major depressive disorder versus bipolar spectrum disorder (Angst et al, 2003)
Angst et al (2003) Eur.Neuropsychopharmacology DSM-5 mixed features specifier
Manic episode, with mixed features Bipolar disorder
Hypomanic episode, with mixed features
Major depressive episode, with mixed features
Major depressive disorder, Bipolar disorder, if no lifetime mania / hypomania if lifetime mania / hypomania Bipolar Disorder: single and biphasic episodes NIMH-LifeCharts® from the Stanley Foundation Bipolar Network
Patient a
Patient b
Patient c
Patient d
Patient e
1 year Bipolar Disorder: rapid cycling and mixed episodes NIMH-LifeCharts® from the Stanley Foundation Bipolar Network
Patient f
Patient g
Patient h
1 year Bipolar disorder has a heterogenous longitudinal course
Patient 1
Patient 2
Patient 3
Patient 4
5 years Bipolar basics
Age of onset of bipolar disorder
Staging models for bipolar disorder
Is there a bipolar prodrome?
Early intervention in bipolar disorder
Some conclusions Age at onset of bipolar disorder (data from 7 studies including N=2968 patients; Goodwin & Jamison 2007) Age at onset of bipolar disorder
Stanley Foundation Bipolar Network N = 539 Age range 18 - 82 Mean age 42.5 (SD 11.5) Data from 7 studies including N=2968 patients Mean age of onset 23.4 (SD = 10.7) (Goodwin & Jamison 2007)
Retrospective assessments Age at first symptoms (N=495 BP I and BP II) (Stanley Foundation Bipolar Network)
Depression first Depression and 80 (hypo)mania at N= 267 (53%) same age 70 N= 156 (32%)
60
50
40
30
20
(hypo)mania first 10 N= 72 (15%)
age (hypo)manic symptoms first 0 0 10 20 30 40 50 60 70
age first depressive symptoms Retrospective assessments Bipolar basics
Age of onset of bipolar disorder
Staging models for bipolar disorder
Is there a bipolar prodrome?
Early intervention in bipolar disorder
Some conclusions Scott et al Br J Psychiatry, 2013 McGorry et al. Can J Psychiatry, 2010 Long-term staging of bipolar disorder (Berk et al, Bipolar Disorders, 2007; 9: 671- 678) Three models for staging of bipolar disorder
Berk et al, 2007
pro at risk dro Focus on recurrence of episodes mal First Stage 0 episode recurrent bipolar 1a/b chronic/ 2 resistant 3a 3b 3c
Age of onset 4
(Berk et al, Bipolar Disorders, 2007; 9: 671- 678)
Duffy, 2014
Focus on prodromal / early stages
Kapczinski et al, 2010
Focus on functional impairment/ later stages Long-term staging of bipolar disorder (Berk et al, Bipolar Disorders, 2007; 9: 671- 678)
Stage 0 Stage 1 Stage 2 Stage 3 Stage 4
UHR
, ,
specific
-
Prodromal Mild, non Mild,
pro at risk dro mal First Stage 0 episode recurrent bipolar 1a/b chronic/ 2 resistant 3a 3b 3c
Age of onset 4
Time Illness progression LongNo problem-term ifstaging bipolar disorder of bipolar starts withdisorder mania (Berk et Diagnosisal, Bipolar Disorders, 2007; 9: 671- 678) Bipolar disorder
pro at risk dro mal First Stage 0 episode recurrent bipolar 1a/b chronic/ 2 resistant 3a 3b 3c
Age of onset 4
(Berk et al, Bipolar Disorders, 2007; 9: 671- 678) HowLong to deal-term with staging first depression(s) of bipolarin bipolar disorder disorder? (BerkUnipolar et al, BipolarDiagnosis Disorders, 2007; 9: 671- 678) or Bipolar Bipolar disorder disorder??
pro at risk dro mal First Stage 0 episode recurrent bipolar 1a/b chronic/ 2 resistant 3a 3b 3c
Age of onset 4
(Berk et al, Bipolar Disorders, 2007; 9: 671- 678) Proposal for staging of bipolar disorder (modified from Berk et al, Bipolar Disorders, 2007; 9: 671- 678)
Unipolar Diagnosis Interepisodic depression Bipolar impairment disorder (Rapid) cycling Full recovery
Bipolar I recurrent Bipolar II XXX at risk prodromal (hypo-) Stage 0 mania chronic/ recurrent bipolar 1a 1b 1c 1d resistant/ 2 cycling 3a 3b 3c
Age of onset 4
Kupka & Hillegers, Tijdschrift voor Psychiatrie, 2012 (further modified 2015/2016) Age at first mood symptoms (N=495 BP I and BP II) (Stanley Foundation Bipolar Network)
Depressive symptoms Depressive and first 80 manic symptoms N= 267 (54%) at same age 70 N= 156 (32%)
60
50
40
30
20 Manic symptoms first 10 N= 72 (15%)
age (hypo)manic symptoms first 0 0 10 20 30 40 50 60 70
age first depressive symptoms Retrospective assessments Retrospective and prospective course of illness NIMH-LifeCharts from the Stanley Foundation Bipolar Network (1995-2002) Depression at onset age 20 first depression
1984 - 1989
age 23 first mania
1990 - 1995
500-007: female, born 1967; negative first degree family history of bipolar disorder SFBN-NFS study entry: october 1995 Retrospective and prospective course of illness NIMH-LifeCharts from the Stanley Foundation Bipolar Network (1995-2002) Mania at onset age 26 1972 - 1977
1978 - 1983
1984 - 1989
1990 - 1995
500-011: male, born 1949; negative first degree family history of bipolar disorder SFBN-NFS study entry: december 1995 Stage 2: first diagnosis of bipolar disorder SFBN/NL, N=98 BP-I, retrospective LifeCharts Duffy. Can J Psychiatry, 2014 Duffy. Can J Psychiatry, 2014 Kapczinski’s model for staging of bipolar disorder
Kapczinski et al, 2010
Focus on functional impairment
Stage Emphasis on interepisodic functioning
0 Increased risc, only mild symptoms
I Euthymic between episodes, return to premorbid functioning
II Psychiatric symptoms between episodes III Marked cognitive and functional impairment between episodes
IV Unable to function independently due to severe cognitive and functional impairment Bipolar basics
Age of onset of bipolar disorder
Staging models for bipolar disorder
Is there a bipolar prodrome?
Early intervention in bipolar disorder
Some conclusions
Dutch Bipolar Offspring Study (Nolen, Reichart, Hillegers, Wals, Mesman, et al) Development of psychopathology in bipolar offspring (N=140) (Dutch Bipolar Offspring Study, Mesman & Hillegers et al, Am J Psych 2013)
12-21 year 22-32 year Development of psychopathology in bipolar offspring (N=140) (Dutch Bipolar Offspring Study; Mesman & Hillegers et al, in press)
Subthreshold manic symptoms predict conversion from depression to bipolar disorder Bipolar basics
Age of onset of bipolar disorder
Staging models for bipolar disorder
Is there a bipolar prodrome?
Early intervention in bipolar disorder
Some conclusions How early is an early intervention? asymptomatic at risk? aspecific symptoms? specific symptoms (UHR)? first depression? first mania? early recurrent? Berk et al. Bipolar Disorders 2007
Bipolar basics
Age of onset of bipolar disorder
Staging models for bipolar disorder
Is there a bipolar prodrome?
Early intervention in bipolar disorder
Some conclusions The boundaries of bipolar disorder are still open Subsyndromal manic symptoms define the prodrome for bipolar disorder Balancing early detection versus overdiagnosing mental illness in ‘high-risk’groups ?
+ -
Amelioration of symptoms Labelling
Minimizing disability and Stigma cognitive impairment Side-effects of interventions Preventing illness progression
Ratheesh et al. Early Interv Psychiatry 2016
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