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Pediatric Bipolar Disorder

Pediatric Bipolar Disorder. Andel V. Nicasio , MSEd University of Central Florida 7936 Child Psychopathology October 9, 2013. Aims of this presentation. Review the current DSM-5 definition and criteria for bipolar disorder

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Pediatric Bipolar Disorder

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  1. Pediatric Bipolar Disorder Andel V. Nicasio, MSEd University of Central Florida 7936 Child Psychopathology October 9, 2013

  2. Aims of this presentation Review the current DSM-5 definition and criteria for bipolar disorder Highlight major historical developments in the scientific understanding of bipolar disorder Illustrate the evolution of bipolar diagnosis on the DSM Review the literature on pediatric bipolar disorder Present a new theoretical model for pediatric bipolar disorder

  3. Aim 1 Review the current DSM-5 definition and criteria for bipolar disorder

  4. What is Bipolar Disorder? • “Also known as manic-depressive illness, is a brain disorder that causes unusual shifts in mood, energy, activity levels, and the ability to carry out day-to-day tasks.” NIH

  5. DSM-5 Classification of BP • Bipolar I – (Depression & Mania) • Bipolar II – (Depression and Hypomania) • Cyclothymic Disorder • Substance/Medication-Induced Bipolar and Related Disorders • Bipolar and Related Disorder Due to Another Medical Condition • Other Specified Bipolar and Related Disorder • Unspecified Bipolar and Related Disorder

  6. Bipolar Disorder in the DSM-5 • DSM-5 highlights that children and adolescents who experience bipolar-like symptoms may not meet criteria for BP-I, BP-2, and cyclothymic disorders. However, they may meet criteria for Other Specified Bipolar and Related Disorder.

  7. Bipolar I – DSM-5 Criteria • Manic Episode – may have been preceded by and many be followed by hypomanic or MD episodes. • A. A distinct period of abnormally and persistently elevated, expansive or irritable mood and persistently increased goal-directed activity or energy, lasting at least 1 week and present most day, nearly every day. • B. During the period of mood disturbance and increased energy or activity (three or more) of the following symptoms (4 if the mood is only irritable) are present…

  8. Bipolar I – Manic Episode • Inflated self-esteem or grandiosity • Decreased need for sleep • More talkative than usual or pressure to keep talking • Flight of ideas or subjective experience that thoughts are racing. • Distractibility • Increase in goal-directed activity or psychomotor agitation • Excessive involvement in activities that have a high potential for painful consequences • C. The mood disturbance is sufficient severe to cause marked impairment in social or occupational functioning or requires hospitalization…or there are psychotic features. • D. The episode is attributable to the physiological effects of a substance or another medical condition.

  9. Hypomanic Episode • A. A distinct period of abnormality and persistently elevated, expansive or irritable mood and persistently increased goal-directed activity energy or energy, lasting at least 1 week4 consecutive days and present most day, nearly every day. • B. During the period of mood disturbance and increased energy or activity (three or more) of the following symptoms (4 if the mood is only irritable) are present… • Same list of symptoms as Mania • C. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic.

  10. Cont…Hypomania • D. The disturbance in mood and the change in functioning are observable by others. • E. Episode is not severe enough to cause marked impairment in social or occupational functioning or necessitate hospitalization… • F. Episode is not attributable to the use of a substance…

  11. Features a child who has been playing since 1:30am - 10:30am. Video taken around 10:30am http://www.youtube.com/watch?v=Y4GYwymtbUU Child with Bipolar Disorder VIDEO

  12. Manic Depressive Episode • A. Five (or more) of the following symptoms have been present the same 2-week period and represent a change in previous functioning; at least one of the Sxs is depressed mood or loss of interest or pleasure. • Depressed mood most of the day • Markedly lost of interest or pleasure in all, or almost all • Significant weight lost • Insomnia or hypersomnia • Psychomotor agitation or retardation nearly everyday • Fatigue or loss of energy • Feelings of worthlessness...guilt • Diminished ability to think or concentrate... • Recurrent thoughts of death, suicidal ideation... • B. Sxscause significant distress or impairment… • C. The episode is not attributable to a substance or another medical condition.

  13. Bipolar II Disorder • Criteria have been met for at least one hypomanic episode and at least one MD episode… • There has never been a manic episode. • The occurrence of hypomanic and MD is not better explained by schizoaffective disorder… • The Sxs of depression or the alternation between periods (MD and hypomania) causes clinically significant distress or impairment…

  14. Diagnostic Coding • Specifiers for BP-I and BP-II*: • Current or Most Recent Episode* • Severity: Mild, Moderate, Severe* • With psychotic features • In partial remission, full remission* • With anxious distress* • With mixed features* • With rapid cycling* • With melancholic features • With atypical features • With mood-congruent psychotic features* • With mood-incongruent psychotic features* • With catatonia* • With peripartum onset* • With seasonal pattern*

  15. Other Specified Bipolar and Related Disorder • This Dx is used when Sxs of Bipolar Disorder Spectrum are present, but do not meet criteria for any one in particular. • Clinicians can specify the reasons why Sxs do not meet criteria for other BPs, by using the other specified designation: • Short-duration hypomanic episodes (2-3 days) and MD episodes • Hypomanic episodes with insufficient Sxs and MD episodes • Hypomanic episode without prior major depressive episode • Short-duration cyclothymia (less than 24 months)

  16. DSM-5 Model

  17. What is the prognosis of child diagnosed with bipolar disorder?http://www.youtube.com/watch?v=WYxO8IjpF9k Dr. Gabrielle Carlson (Feb. 2013) VIDEO

  18. Aim 2 & 3 • Highlight major historical developments in the scientific understanding of bipolar disorder • Illustrate the evolution of bipolar diagnosis on the DSM

  19. History - Hippocrates (460–337 BC) • Probably the first to systematically describe melancholia and mania. • Formulated the first classification of mental disorders: melancholia, mania, and paranoia. • Suggested a connection between mania and melancholia using humoral theories. • ‘‘Black bile’’ could generate a variety of phenomena, depending on the temperature. Marneros , A. & Angst, J. (2000)

  20. History – Relationship between Manic and Melancholic States • Aretaeus of Cappadocia (2nd Century AD) - considered the ‘‘father of bipolar disorder.’’ First to clearly described mania and melancholia as being two components of one disease. • ‘‘It appears to me that melancholy is the commencement and a part of mania.’’ • Jean-Pierre Falret (1854) - “foliecirculaire” - formally described the sequential change from mania to melancholia and vice versa and the symptom-free interval in between as a separate disease. • Jules Baillarger (1857) - ‘‘folie _a double forme’’ - mania and melancholia changed into one another, but the interval between was felt to have no meaning. • Falretand Baillarger(1894) - credited for discovering the bipolar disorder. Marneros, A. & Angst, J. (2000)

  21. History – Manic-depressive Illness • Emil Kraepelin (1921) • Dichotomized the ‘‘endogeneous’’ psychoses into ‘‘dementia praecox’’ and manic-depressive insanity. • Conducted systematic observations of over 900 patients suffering from "manic-depressive insanity“. • First to raise the possibility that children could develop mania. • Children – prevalence rate higher among 15-20 y/o and only 0.4% in children < 10 y/o. Kraepelin E. (1921). “Manic-depressive insanity and paranoia”

  22. History – Unipolar vs. Bipolar • Karl Leonhard (1957) – classified Unipolar Disorder (major depressive disorder) and Bipolar Disorder. • Research by Karl Leonhard (German), Jules Angst (Swiss), and Carlo Perris (Scandinavian) supported: • The nosology and family hxdifferentiation between unipolar and bipolar. • There is no unanimity even now about the validity of these separations.

  23. Manic Depression in US • Psychiatry was heavily influenced by Psychoanalytic theories and the theories of Adolf Meyer • Meyer (first half of 1900s) emphasized the interaction between an individual’s biologic and genetic characteristics and the social environment. • This notion is included in the DSM-1 (1952), which includes a diagnosis of ‘‘manic-depressive reaction.’’ Kanner L. (1935).

  24. DSM-I (1952) DEPRESSION • Psychotic Disorders • Involutional psychotic reaction • Affective reactions • Manic depressive reactions • Manic depressive reaction, manic type • Manic depressive reaction, depressed type • Manic depressive reaction, other • Psychotic depressive reaction • Psychoneurotic Disorders • Depressive reaction

  25. DSM-II (1968) Psychoses Not Attributed To Physical Conditions • 296 Major affective disorders • Manic-depressive illnesses • Manic-depressive illness, manic type • Manic-depressive illness, depressed type • Manic-depressive illness, circular type • Manic-depressive illness, circular type, manic • Manic-depressive illness, circular type, depressed

  26. US vs European Countries • Results from the landmark US/UK comparison study (1972): • Indicated that Bipolar disorder in the US was markedly under-recognized as compared with European diagnostic systems. • Sparked an increased interest in developing systematic/operational diagnostic criteria to improve the reliability of diagnosis. • Operationalized diagnostic criteria were developed: • ResearchDiagnostic Criteria • DSM-II-R Cooper, J. E., Kendall, R. E., Gurland, B. J., et al. (1972)

  27. Developing a diagnostic criteria for children • First attempt to develop diagnostic criteria for manic-depressive psychosis in children was done by Anthony and Scott (1960): • Reviewed 28 papers (1884-1954) and created a 10 criteria for manic • Only 3 in 60 cases met the developed criteria. • These criteria basically eradicated the diagnosis of manic depression in children, until subsequent studies using Lithium appeared. Anthony, E. J. & Scott, P. (1960)

  28. Cont…Developing a diagnostic criteria for children • Psychopharmacologic studies in the 1970s restored the concept of childhood-onset bipolar disorder Weinberg, W. A. & Brumback, R. A. (1976); Davis, R. E. (1979); Coll, P. G. & Bland, M. B. (1979)

  29. DSM-III (1980) & DSM-III-R (1987) • “Manic-depression” substituted by “Bipolar” • Mania symptoms required to be present for a week. • DSM-III-R Bipolar Disorder-Mixed, Bipolar Disorder-Manic, Bipolar Disorder-Depressed, Bipolar Disorder-Not Otherwise Specified, and Cyclothymia.

  30. DSM-IV & DSM-IV-R (1987) • DSM-IV to DSM-IV-TR - no major changes. • DSM-5 • Criterion A for manic and hypomanic episodes includes an emphasis on changes in activity and energy as well as mood. • Bipolar I, mixed episode eliminated; instead a new specifier is included: “with mixed features”. • Anxious Distress Specifier (new) • NOS eliminated; instead “Other Specified Bipolar and Related Disorder”

  31. Aim 4 • Review the literature on pediatric bipolar disorder

  32. Bipolar Disorder Runs in Families…

  33. BP Runs in Families… • One of the most hereditable psychiatric conditions as evidenced by twins and other studies. • Higher concordances for BP among MZ twins, compared with DZ twins; estimated heritability >80% (Craddock and Jones, 1999). • If one parent has BP, the risk of a child to have BP is between 10-25%; higher risk if both parents have BP (Goldstein et al., 2010; Goldwin & Jamison, 2007). • Risk increases during young adulthood (Birmaheret al., 2009) . • First-degree relatives of youth with BP are at higher risk of developing BP…compared with families of health children or children with MDD or ADHD (Geller et al., 2006)

  34. Genetics • The study with the largest sample of pedigrees with BP found: • Two chromosomal regions that meet stringent criteria for genomewide significance (P<.05) on chromosomes 17q and 6q, and • Three regions with suggestive evidence of linkage (P<.10) on chromosomes 2p, 3q, and 8q. • Sample: 1,152 individuals and 250 families; 10 sites. Dick et al., 2003

  35. Perinatal Risk Factors • Prenatalexposure to drugs or birth complications, increase the risk of having a child with BP diagnosis more than six-fold(Pavuluri et al., 2006).

  36. BP Brain Plasticity • Voxelwise meta-analysis, included 21 studies, 660 BD patients and 770 healthy control subjects (Bora et al., 2010). • Found gray matter deficits in BD, but only in two regions (right fronto-insular and left anterior cingulate). • Another studies reported cerebellar vermalsize was smaller in multiple-episode patients with BP compared with first-episode and healthy subjects (Del Bello et al. 1999, ; Mills et al. , 2005)

  37. Cont…Brain Plasticity • Serum Brain-Derived Neurotrophic Factor (BDNF) levels were significantly lower in both medicated and unmedicated patients with bipolar disorder, compared with healthy controls (P<0.0001). • 22 adults with bipolar disorder; medication-free, • 22 medicated adults with bipolar disorder, and • 22 healthy controls • Another study reported that BDNF levels were decreased only in patients with bipolar disorder with late stage of illness. (de Oliveira et al., 2009; Kauer-Sant’Anna et al., 2009)

  38. Cont…Brain Plasticity • A study compared the progression of abnormalities in white matter tract integrity • 10 children with BP; 7 children at risk for BP (first-degree relative with BP); 8 healthy controls • Compared with health children, children with BP exhibited decreased fractional anisotropy (FA) in right and left superior frontal tracts, left orbital frontal, and right corpus callosum (P<0.05) Frazier, J. A. et al. 2007

  39. Cont… Brain Plasticity Frazier, J. A. et al. 2007

  40. Cont … Brain Plasticity Frazier, J. A. et al. 2007

  41. Pediatric BD Onset • > 50% of adults with bipolar report onset of Sxs in childhood (Perlis et al., 2009). • Age 15 to 19 years old (Goodwin & Jamison, 2007). • Average age of onset in US is reported as 19.4 years versus 25.2 years in European samples (Post et al., 2008). • However, BP has a lifelong onset; condition could flourish in children and adults as old as over 60 y/o

  42. Prevalence • 1996 – BP was the least frequent diagnosis (in-patient children), BUT in 2004 – was the most frequent diagnosis (Blader & Carlson, 2007). • Based on a recent meta-analysis the rate of BP spectrum disorders in youth is 1.8%, and for BP-I 1.2%; no significant rate difference among UK and US (Van Meter, Moreira, Youngstrom, 2011). • 1-3% prevalence rate (Birmaher, 2013) • This is consistent with other studies (Stringaris et al., 2010; Kozloff et al., 2010) • Bipolar I and Bipolar NOS are more common in children than Bipolar II (Birmaheret al., 2006)

  43. Depression or Mania…Which Emerges First? • Depression seems to flourish first in youth, and the rate of conversion to BP is 32%–50% (Ghaemi, 2008; Lewinsohn et al., 2000). • This is higher than the conversion rate for adults (12.6% to 20%) (Akiskal et al., 1995; Ghaemi, 2008). • A prospective study followed 1,037 subjects from childhood through age 26 (Kim-Cohen et al., 2003). • Clinical interviews at age 11, 13, 15, 16, 18, 21, and 26. • Diagnoses between ages 11 and 15 for those becoming manic included: conduct disorder (38%), anxiety (35%), and depression (20%).

  44. Comorbidity • Bipolar disorder is often accompanied by other psychiatric disorders (20%-80%). • Disruptive Behavior Disorders • ADHD • Anxiety Disorders • Substance Abuse Disorders Children vs. Adolescents C. ADHD and Oppositional Defiant Disorder > common A. Conduct and Substance Abuse Disorders > common Birmaher, 2013)

  45. (Axelson et al., 2006)

  46. Comorbidity – Anxiety Disorder • Common comorbidity in children and youth with BP: • N=446, 7-17 y/o; BP 1=260, BP 2=32, BP NOS=154 • At least 1 lifetime AD (44%), most commonly separation anxiety (24%), and GAD (16%) • 2 or more AD, nearly 20% • AD predated the onset of BP; those with BP 2 were more likely to have comorbid AD, longer duration of sxs, more severe ratings of depression, and family hx of depression. Sala, R. et al. (2010)

  47. Comorbidity: Conduct Disorder & Psychosis CD • High rates of conduct disorder reported among youth with BP (Weller et al., 2004). • 42%-69% of clinic-referred youth with BP also had CD. Psychosis • Co-occurrence rate is between 16% to 60% (Pavuluri et al., 2004) • Delusional grandiosity, persecutory and religious delusions, hallucinations, and thought disorder.

  48. Comorbidity - ADHD • Most common comorbid condition among youths with BP; studies report 60%-98% rates (Evans et al., 2005; Geller et al.,1998). • Uncommon in children with ADHD: (Hassan, A. et al., 2011) • UK sample: n=200, 170 M, 30 F; 6-18 y/o, mean 11.15, SD 2.95 • Only a 9-year-old boy, met diagnostic criteria for both ICD–10 hypomania and DSM–IV bipolar disorder not otherwise specified.

  49. Main Features of BP in Youth • Tend to show mixed episodes rather than distinct episodes of mania and depression. Tend to describe their mood episodes as feeling “tired but wired”(Biederman et al., 2004). • Sample: 298 children with BP, none with clear-cut mania or depressive episodes. • Tend to cycle fairly frequently from one mood state to the next. Family members describe it as “mood swings”(Biederman et al., 2004; Geller et al., 2000). • Onset – typically develops slowly over time. • Often show chronic and continuous mood problems.

  50. Cost to Society and Individuals with BP • High rates of suicide, substance abuse, and neurocognitive deficits associated with poor school functioning (Pavuluriet al 2005; Tolan and Dodge 2005). • Risk of suicide attempt is increased by severe features of BP illness and comorbidity (Goldstein et al., 2005). • Nearly one-half of individuals with bipolar disorder attempt suicide (Jamison, 1999). • Worldwide, it currently accounts for 14 million years of healthy life lost owing to mortality and disability, nearly as much as schizophrenia (WHO, World Health Report 2002).

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