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Home , Affective spectrum

Affective Disorders in CYPS

Dr Shakeel Ahmed Clinical

Changes in mood, in thinking and in activity, sufficient to cause impairment in personal and/or social functioning.  Mood changes typically include and/or accompanied by a loss of , even in cherished interests.  Cognitive changes generally lead to inefficient thinking, usually with a pronounced self-critical focus.  Physically, depressed people become less active, although this may be concealed by the presence of or agitation. Goodyer, I.M. & Cooper, P.J. (1993) A community study of depression in adolescent girls. II: The clinical features of identified disorder. British Journal of , 163, 374–380. Language of development in symptom expression

“SAD” versus feeling grumpy, low, irritable, miserable etc   Feeling no good, worthless  Loss of

Epidemiology

 The 12-month period prevalence estimates for depression: approximately 1% for pre-pubertal children and 3% for post- pubertal adolescents.  No sex difference in pre-pubertal age: Increase prevalence in girls thereafter.  Children and young people with emotional disorders, were nearly twice as likely to be living with a lone parent (28% versus 15%), more than twice as likely to be with both parents being unemployed (27% versus 12%), and more likely to have parents who were on low incomes, had fewer qualifications and living in social sector housing. Affective

 Genetic predisposition  More of Alcohol dependence and harmful use as well as Antisocial PD in male relatives  Somatoform disorders and Dissociative Disorders in female relatives  , Depression and Suicide in any relative Settings of Childhood Depression

 School refusal (more associated with depression in adolescent girls than boys)  Onset of behavioural difficulties in young people, following a disciplinary crisis  Children or young people who have been maltreated or experienced very traumatic events such as rape  Children or young people who repeatedly harm themselves  Young people engaged in chronic family disputes  Young people with persistent drug and alcohol problems. Comorbidity and Differential Diagnosis

 Depression rarely occurs in in C&YPs  Between 50 and 80% of depressed cases will also meet criteria for another non-depressive disorder.  20-25 %- ADHD  25% Conduct Disorder  15-18% OCD  5% Eating Disorders  25-30% various Anxiety Disorders

 Relation between and depression in CYPs is complex

Dysthymia

has been described as a chronic mood disturbance of young people characterised by: long-standing gloom and , brooding about feeling unloved and affective dysregulation. The dominant negative cognition is self-deprecation or negative self- esteem. There are high rates of irritability and in everyday circumstances, occurring as a hyperemotional response to social problems in the everyday environment  Dysthymia is distinguished from depression by the virtual absence and significantly lower prevalence of anhedonia and social withdrawal; and comparatively lower levels of , morbid preoccupation and impaired concentration. Practically none of the dysthymic children had reduced appetite and few had hyposomnia or fatigue Kovacs, M., Akiskal, H.S., Gatsonis, C., et al. (1994) Childhood-onset dysthymic disorder. Clinical features and prospective naturalistic outcome. Archives of General Psychiatry, 51, 365–374.

Assessment

 Clinical presentation with due acknowledgement of Developmental Factors  Talk to everyone involved with the child’s care- parents, school, social services  TALK TO THE CHILD  Use of rating scales can be helpful Management

 Self help  Medication  Psychological Therapies: CBT, IPT, Supportive Therapy, Play Therapy, Systemic Family work  Supportive matrix for environmental/contextual factors including support for any Special Educational Needs, bullying, family stressors etc Medication http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON019494

Fluoxetine Citalopram Fluvoxamine Paroxetine Venlafaxine Mirtazapine Drug class SSRI SSRI SSRI SSRI (active SSRI SSRI Serotonin and Noradrenergic and specific constituent of noradrenaline serotonergic antidepressant citalopram) reuptake inhibitor (SNRI) Licensed None Obsessive None None Obsessive None None None indications compulsive compulsive children and disorder disorder adolescents Efficacy in Demonstrated in Not demonstrated Not consistently No data from clinical No data from Not demonstrated Not demonstrated Not demonstrated in controlled clinical major controlled clinical in controlled demonstrated in trials clinical trials in controlled in controlled trials depressive trials clinical trials controlled clinical clinical trials clinical trials disorder (MDD) trials in children and adolescents Safety profile in and Rate of events Increased rate of No data from clinical No data from Increased rate of Increased rate of No increased rate of self-harm and MDD trials in more including self-harm trials clinical trials self-harm and self-harm and suicidal thoughts compared with children and frequently agitation, compared with suicidal thoughts suicidal thoughts placebo adolescents reported than in anorexia, placebo in 1 of 2 compared with compared with adults, perhaps as and trials placebo placebo a result of differing suicidal thoughts inclusion criteria in and self harm clinical trials. No increased increased rate of compared with self-harm and placebo suicidal thoughts compared with placebo

CSM advice in Risk/benefit Risk/benefit Risk/benefit Risk/benefit balance Risk/benefit Risk/benefit Risk/benefit Risk/benefit balance is unfavourable relation to MDD balance is balance is balance is is presumed balance is not balance is balance is in children and favourable unfavourable unfavourable unfavourable. assessable - unfavourable unfavourable adolescents (Extrapolation from safety and efficacy citalopram.) in adults cannot be extrapolated to under 18 year olds Pediatric :

Is it a USA Phenomenon? Issues

 Rise in clinical practice related to of diagnosis of Early onset Bipolar Affective Disorder (BPAD) - 40 fold rise in consultations for children with BPAD (Moreno et al 2007) - 25/100000 consultations in 1994-95 to 1003/100000 in 2002-2003 ( with doubling of diagnosis of BPAD in adults in same period) - Increased diagnosis in pre-adolescent and even pre- school age groups.

Issues

 Disagreement in diagnostic criteria- differences between ICD10 and DSM 4  Rate of rise in diagnosis as an American phenomenon  Issues of misdiagnosis, over diagnosis and under diagnosis  Developmental concerns and co-morbidity as confounding factors in diagnosis  Formative influence of the pharmaceutical industry

Epidemiology  Inadequate data relating to prevalence rates in different countries. Methodological differences including differences in definition of the BPAD, age of studied population  The prevalence of bipolar spectrum disorder in young adults in Switzerland is 11%.  In Holland the 6-month prevalence of mania in adolescents was 1.9% and of hypomania 0.9%.  Only 1.2% of hospitalized youth (<15 years) in Denmark and 1.7% of adolescents in Finland had BD.  In Spain, the prevalence of DSM-IV BD in children 5-18 years old is 4%, and of any mood disorders 27% (Soutolo et al, 2005)

Epidemiology continued

 Diagnostic rates in clinical populations: - USA 6- 28 % ( Perlis et al 2004; Leverich and Post 2006) - England – 1.7/100000 per year (Sigurdsson et al, 1999) - Ireland- 2.2/ 100000 per year (Scully et al 2004); - Brazil- 7.2% (Tramontina et al 2004) - Far Below the US diagnostic rates in India, Spain, Finland, Korea, Denmark and Germany ( Parens and Johnston, 2010) Diagnosis and Nosology

 Can we have Meaningful Diagnosis using DSM 4 and ICD 10  Different developmental phenotypes- pre-school, pre- pubescent, adolescent (Goldstein and Levitt, 2006)  Developments in DSM 5: Temper regulation disorder with Dysphoria  Paediatric Mental Health Care Dysfunction Disorder (Parens, Johnston and Carlsson, 2010)

Etiology and Neuro-biology

 Organic phenotypes- Frontal Cortex, Amygdala, Neuro- psychological substrates  Phenotype of increased genetic loading , increased co- morbidity ( Rende, Birmaher, Axelson et al, 2007)  No endophenotype that is specifically linked to early onset BPAD DRD4 Gene

Gene codes for a type of dopamine receptor in the brain One variant (allele) associated with novelty- seeking (specifically, the traits of being exploratory and excitable) 1% of East Asians have the novelty-seeking variant 32% of North Americans have it 42% of Central Americans have it 78% of South American Indians have it Think about prehistoric migration routes… 32 1 % % 42 %

78 % European Lifetime Prevalence Rates- Adults

BP Country BP I Spectrum Citation per 1000 per 1000 England 33 - Kennedy, et al., 2005 Spain 18 38 Soutullo, et al., 2005* Hungary 16 50 Szadoczky, et al., 1998 Netherlands 13.1 19 ten Have, et al., 2002 Switzerland 6 31 , et al., 2005 Italy 4.7 55 Faravelli, et al., 2006 Almost all are higher Belgium - 17 Baruffol and Thilmany, 1993 than Norway Kringlen, et al., 2001 - 16 “convention ” Germany - 10 Jacobi, et al., 2004 of ~1% Ireland 3 4 Scully, et al., 2004 Iceland 2 7 Stefansson, et al., 1991 Rates of Bipolar Diagnosis Increasing in Asia

 Treated prevalence increased 8x in Taiwan from 1996 to 2003 (Bih et al., 2008)  Singapore:  Most adults with bipolar had adolescent onset  First episode depressed in 80% (Peh et al., 2008)  Korean epidemiological study focused on bipolar I (no report of bipolar II, cyclothymic) Meta-Analysis of Child Epidemiological Studies

 How common is the bipolar spectrum in youths around the world?  Is the rate increasing in the community over the same time frame that clinical diagnosis has changed?  Is it more common in the USA than the rest of the world? Average Rate of Pediatric Bipolar Spectrum: 2%

Prevalence of Bipolar Include NOS Spectrum

No increase No difference over time USA rate vs. World

Non-USA

USA Van Meter, Moreira, & Youngstrom, in press, J Clin Psychiatry

USA not driving increase of PBD 1.2%

2.8% 2.1% 0%

1.9% 2.4%

2.5%

1.8% Relationship among different classifications Only if elated or grandiose “Narrow”

BP-I “Intermediate” (DSM-IV) BP-II Severe ??? Mood Dysreg. “Broad” Bipolar NOS (SMD) Bipolar I DSM is most heavily researched, greatest validityOnly if elated or grandiose “Narrow”

BP-I “Intermediate” (DSM-IV) BP-II Severe Cyclothymia??? Mood “Broad” Dysreg. Bipolar NOS (SMD) Bipolar NOS (DSM-IV)

 Manic symptoms that don’t fit into any of the previous diagnostic categories  Some ways to earn a residual diagnosis  Manic or hypomanic sx of insufficient duration (including very rapid cycling)  Repeated hypomania without a depressive episode  Manic symptoms, but insufficient number co-occurring Clinical Take Home Messages  Bipolar often onsets in adolescence  Will present as depressed episode  Affects at least 1 in 100 in general European population  Spectrum at least 5x as common, highly impairing (1 in 20 in general population)  Clinical rates higher  if diagnosing much below 1 in 20, re-consider methods

Risk Factors

 Tsuchiya et al. (2004) review the literature on risk factors- They conclude that only family history of (esp. bipolar disorder) is robust enough to be clinically useful at present.  Family history of bipolar disorder  Early onset depression:  (1/3 of adolescent depression may be bipolar)  Psychotic features  (bipolar much more common than early schizophrenia)  Episodic aggression & mood dysregulation  Episodicity suggests mood disorder  Medication coincident mania

Recommended rules of thumb

 Clear bipolar in one parent = 5x risk  Studies including adult offspring estimate 6.1x lifetime risk (Zuckerman, 1999, p. 164)  (more liberal estimate would be 9x risk = 5.4% in offspring / 0.6% epidemiological rate)  Bipolar in bio grandparent, aunt, uncle = 2.5x risk (~50% shared genes * 5x = 2.5)  “Fuzzy” bipolar or clear mood history in parents = up to 2x risk Risk Factors triggering assessment

 Family history of bipolar disorder  Early onset depression  (1/3 of adolescent depression may be bipolar)  Psychotic features  (bipolar much more common than early schizophrenia)  Episodic aggression & mood dysregulation  Episodicity suggests mood disorder  Medication coincident mania Case Vignette

 Discussion with Stockton CAMHS regarding potential referral  Referral from Middlesbrough GP Practice- An initial referral to Middlesbrough CAMHS had seen no psychiatric morbidity. A second-opinion referral to Stockton CAMHS has advised a referral to myself( as a specialist resource)(!!)  Discussion with managers  Discussion with medics at Middlesbrough CAMHS  Sub text Agreements

 Managers agreed that I could carry out an assessment even though the referral was from out-of-area GP Practice. Following the assessment and implementing of a management plan, I would transfer care to local CAMHS team  Medic of Middlesbrough CAMHS team agreeable for this to happen. He will carry out a brief assessment prior to continuing my management plan.  This plan agreed upon with carer at my C&B appointment.

Clinical assessment

 9 year old girl with no significant past or personal history.  Temperamentally described as impulsive, inattentive and having oppositional behaviours and obsessional preoccupations. None of these were of adequate severity, pervasiveness or causing dysfunction to merit a diagnosis of psychiatric morbidity.  Family history of:  Bipolar disorder, Depressive disorder, , Phobic Anxiety Disorder  ADHD, Substance abuse and significant Conduct Difficulties  Epilepsy, Cerebro-vascular Accident including stroke HOPI

 About 18 months ago started having prolonged periods of irritability, dysphoric and poor tolerance which would slowly build up to explosive anger outbursts.  Intermittent periods of silly/ overly cheerful mood with increased speech output, unrealistic ideas of personal ability (can fly out of cars, can lift up house- no further descriptions available), reduced need for sleep and worsening of easy distractibility as well as fluctuating appetite. These periods range from 1 hour to 2 days in duration.  This gradually affected academic, interpersonal and social functioning. HOPI- contd

 About 12 months after this picture there has been an amelioration in the anger outbursts with persistence of mood swings, sleep and appetite disturbances,  Re-emergence of obsessional preoccupations.  Frequent occasions of school refusal despite improvement in academic and interpersonal functioning.  Mother’s ability to cope with difficulties improved but still found it stressful  The inadequacies in assessment was seen as a greater source of stress by mother

Further assessments

 Individual sessions with child using non-directive play as a tool of engagement and observation.  Telephone discussion with school teacher and PSA who knew the child well.  School observation could not be organised due to logistical difficulties- not clear as to which team would carry this out. Assessment Tools

 Kiddie SADS- screening chapter and subsection on affective disorders and anxiety disorders.  Suggested precence of affective symptoms including dysphoria, depressive cognitions, as well as hypomanic episodes and obsessive phenomena.

Use of structured tools

 Use of parent YMRS and face page of FIGS as screening tool. This was based on a hypothesis that a combination of family history and screening for affective disorder has good strength as screening tool.  Clear bipolar in one parent = 5x risk  Studies including adult offspring estimate 6.1x lifetime risk (Zuckerman, 1999, p. 164)  (more liberal estimate would be 9x risk = 5.4% in offspring / 0.6% epidemiological rate)  Bipolar in bio grandparent, aunt, uncle = 2.5x risk (~50% shared genes * 5x = 2.5)  “Fuzzy” bipolar or clear mood history in parents = up to 2x risk

History & Interview: GRAPES

– especially unstable self-esteem   Activity – episodes of goal-directed activity  Pressured speech  Elated, expansive, euphoric mood  Sleep – Decreased need (getting less, and does not miss it)

Youngstrom, 2009 Structured tools

 Childhood Bipolar Questionnaire- CBQ is a 65 question screening instrument is that it collects information not only on the symptoms of bipolar disorder, but for many other comorbid disorders including separation anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, oppositional defiant disorder, conduct disorder and attention deficit disorder. Further, it allows that information to be reported in degrees of severity rather than simply “present” or “absent”.The screening yields a core phenotype for pediatric Bipolar Disorder.  It has good validity and reliability. (Papolos et al, 2006)

Use of Structured Tools

 The Jeannie/Jeffrey Interview for children: The Jeannie and Jeffrey Illustrated Interview for Children (J/J) is the pediatric companion instrument to the CBQ. It is the first assessment tool for bipolar disorder designed specifically for children.  The J/J is a survey developed for use by children ages 5 to 12 years old. It takes approximately 15 minutes to answer the questions.  The J/J has comic-strip style illustrations that engage the child’s while diminishing the threat of self-disclosure. This format promotes the child’s willingness and ability to reveal mood states, , suicidal thoughts and/or that he or she may be unwilling to talk about with the parent and clinician.  Psychometric standards are still being evaluated. http://www.jbrf.org/the-jeannie-jeffrey-illustrated-interview-for-children/

Structured interviews

 Kiddie SADS PL: The gold standard for diagnosis of Early Onset Bipolar Disorder and yields diagnosis by DSM IV (TR) algorithms.  Lengthy instrument and not meant for routine clinical use Kaufman et al , 1997  Potential use of the Development and Well-Being Assessment (DAWBA) http://www.dawba.info but not used. Ford et al, 2003

Diagnosis

 Based on the assessment the diagnosis which came through was one of Bipolar Disorder NOS. The course indicative of partial remission.  The absence of clear episodic nature of manic and depressive episodes ruled out diagnosis of BPAD I.  Comorbid Anxiety Disorders including Generalised Anxiety Disorder and Obsessive Compulsive Disorder also present.

Management

 Psychoeducation spread over 3 sessions with information drawn from NICE CG38 and NIMG guidance on Early Onset Bipolar Disorders  Option of atypical for mood stabilisation. Protocol of physical examination as well as baseline investigations being within normal limits, trial of Quetiapine started. Early course suggestive of good response in form of attenuation in anger/ irritability, attentional difficulties as well as improvement in interpersonal and social functioning. No treatment emergent adverse effects at last review. Currently on Tab Quetiapine 150 mg two times a day. What next ?

 After stabilisation of medication regimen plan is to transfer care to Middlesbrough CAMHS. Mother reluctant to do this. However mother convinced regarding this need keeping in mind need for involvement of local services  Is there a need for specialised services in assessment and management of early onset bipolar disorder.  The prevalence of Early onset BPAD-NOS in England could be 1.1% by parent report and 1.5% by youth report (Stringaris , 2010). Is there ia serious risk of under-diagnosis of early onset BPAD in the UK. Does specialised services run the risk of overdiagnosis- which is the more serious situation. References

 Youngstrom EA, Freeman AJ and Jenkins MM( 2009). The assessment of children & adolescents with bipolar disorder. Child and Adolescent Psychiatric Clinics of North America. 18:353-390.  Papolos D, Hennen J, Cockerham MS et al ( 2006). The CBQ: a dimensional approach to screening for Paediatric Bipolar Disorder. Journal of Affective Disorders. 95:149-158.  Stringaris A, Santosh P, Leibenluft E and Goodman R (2011). Youth meeting symptom and impairment criteria for mania like episodes lasting less than 4 days: an epidemiological enquiry. Journal of Child Psychology and Psychiatry. 51: 31-38.  Kaufman J, Birmaher B, Brent D et al(1997). Schedule for affective disorders and schizophrenia for school-age children—present and lifetime version (K-SADS-PL): initial reliability and validity data. Journal of THE American Academy of Child AND Adolescent Psychiatry.36:980–988.  Ford T, Goodman R & Meltzer H(2003). The British child and adolescent mental health survey 1999: the prevalence of DSM-IV disorders. Journal of the American Academy of Child and Adolescent Psychiatry, 42(10), 1203.