Prognostic Factors in Child and Adolescent Psychiatry.

Prognostic Factors in Child Prognostic Factors in Child and Adolescent Psychiatry. and Adolescent Psychiatry.

A. JamesA. James

Oxford University. Oxford University.

Continuities.Continuities.

Childhood and Adolescent Childhood and Adolescent Psychiatric DisordersPsychiatric Disorders

as Predictors of Young Adult as Predictors of Young Adult DisordersDisorders

Copeland et al, Arch Gen Copeland et al, Arch Gen Psych 2009.Psych 2009.

Childhood and Adolescent Psychiatric DisordersChildhood and Adolescent Psychiatric Disordersas Predictors of Young Adult Disordersas Predictors of Young Adult DisordersCopeland, et al Arch Gen Psych, Copeland, et al Arch Gen Psych, 66 200966 2009

To study homotypic and heterotypic To study homotypic and heterotypic

continuities while controlling for continuities while controlling for

comorbidities, and examining child comorbidities, and examining child

and adolescent predictors separately.and adolescent predictors separately.


Adolescent depression significantly Adolescent depression significantly

predicted young adult depressionpredicted young adult depression, but , but

this effect was entirely accounted for this effect was entirely accounted for

by by comorbiditycomorbidity of adolescent of adolescent

depression with adolescent depression with adolescent

oppositional defiant disorder, anxiety, oppositional defiant disorder, anxiety,

and substance disorders in adjusted and substance disorders in adjusted

analyses.analyses.


Generalized anxiety and depressionGeneralized anxiety and depression cross cross predicted each other, and oppositional predicted each other, and oppositional defiant disorder (but not conduct disorder) defiant disorder (but not conduct disorder) predicted later anxiety disorders and predicted later anxiety disorders and depression.depression.

Evidence of Evidence of homotypic predictionhomotypic prediction was was supported for substance use disorders, supported for substance use disorders, antisocial personality disorder (from antisocial personality disorder (from conduct disorder), andconduct disorder), andanxiety disorders, although this effect was anxiety disorders, although this effect was primarily accounted for by primarily accounted for by DSM-III-R DSM-III-R overanxious disorderoveranxious disorder

AN BN

EDNOS

Transdiagnosis

Eating Disorders

Improvement or merely Improvement or merely change?change?

Early-Onset Early-Onset Schizophrenia.Schizophrenia.

Factors associated with poor prognosis Factors associated with poor prognosis in EOSin EOS

Compared with the adult-onset form Compared with the adult-onset form of schizophrenia EOS, and in of schizophrenia EOS, and in particular the most early onset particular the most early onset cases, may be associated with worse cases, may be associated with worse prognosis prognosis

(Jacobsen et al, 1998). (Jacobsen et al, 1998).


Most follow up studies have found Most follow up studies have found

the majority of young persons being the majority of young persons being

chronically ill, with very few having chronically ill, with very few having

good functioning, and the majority good functioning, and the majority

showing poor or very poor outcomes showing poor or very poor outcomes

on clinical measures. on clinical measures.

More optimistic outcomes have also More optimistic outcomes have also

been reported (Asarnow et al, 1994; been reported (Asarnow et al, 1994;

Russell, 1994; Pencer et al, 2005) Russell, 1994; Pencer et al, 2005)

with up to around 60% showing with up to around 60% showing

significant improvement at follow up. significant improvement at follow up.


Premorbid developmental delay.Premorbid developmental delay.

Premorbid function. Premorbid function.

Mode and age of onset. Mode and age of onset. Degree of recovery and negative Degree of recovery and negative

symptoms. symptoms.

Lay et al. (2000)Lay et al. (2000)

65 EOS patients over a period of more 65 EOS patients over a period of more than 10 years than 10 years

83% of the patients as having at least 83% of the patients as having at least one further episode needing one further episode needing hospitalisation 74% being under hospitalisation 74% being under psychiatric treatment. psychiatric treatment.

At least moderate educational and At least moderate educational and occupational impairment was noted in occupational impairment was noted in 57% of this sample and serious social 57% of this sample and serious social disability was found in 66%. disability was found in 66%.

Eggers and Bunk, 1997; Remschmidt et al, Eggers and Bunk, 1997; Remschmidt et al, 20062006

Eggers and Bunk 1977 44 EOS Eggers and Bunk 1977 44 EOS

patients, patients,

50% were found to have continuous 50% were found to have continuous

symptoms and 25% to be in partial symptoms and 25% to be in partial

remission. remission.

Remschmidt et al (2006) Remschmidt et al (2006)

38 patients retrospective ICD-10 diagnosis 42 38 patients retrospective ICD-10 diagnosis 42 years after the initial presentationyears after the initial presentation

The overall prognosis of this cohort was poor: The overall prognosis of this cohort was poor: less than a sixth have a favourable outcome less than a sixth have a favourable outcome 60% have a poor outcome. 60% have a poor outcome. More than 70% did not graduate from school More than 70% did not graduate from school

and were unemployed at the time of follow and were unemployed at the time of follow up. up.

Significantly raised total death rate. Significantly raised total death rate.

ADAPT Study (ADAPT Study (Br J Psychiatry. 2009, 194:334-Br J Psychiatry. 2009, 194:334-41).41).

There is great heterogeneity of clinical There is great heterogeneity of clinical presentation and outcome in paediatric presentation and outcome in paediatric depressiondepression..

MethodMethod RCT 192 adolescents with unipolar major RCT 192 adolescents with unipolar major Participants were treated for 28 weeks Participants were treated for 28 weeks

with routine psychosocial care and with routine psychosocial care and selective serotonin reuptake inhibitors selective serotonin reuptake inhibitors (SSRIs), with half also receiving cognitive-(SSRIs), with half also receiving cognitive-behavioural therapy (CBT). behavioural therapy (CBT).


Depression at 28 weeks was Depression at 28 weeks was predicted by the additive effects of predicted by the additive effects of severity, obsessive-compulsive severity, obsessive-compulsive disorder and suicidal ideation at disorder and suicidal ideation at entry together with presence of at entry together with presence of at least one disappointing life event least one disappointing life event over the follow-up period. over the follow-up period.


CONCLUSIONS: Clinicians should CONCLUSIONS: Clinicians should assess for severity, suicidality and assess for severity, suicidality and comorbid obsessive-compulsive comorbid obsessive-compulsive disorder at presentation and should disorder at presentation and should monitor closely for subsequent life monitor closely for subsequent life events during treatment.events during treatment.

The OPUS trial in Denmark and the The OPUS trial in Denmark and the Lambeth Early Onset (LEO) in the UKLambeth Early Onset (LEO) in the UK

Trial compared specialist multidisciplinary teams with Trial compared specialist multidisciplinary teams with standard care in community mental health settings. standard care in community mental health settings.

OPUS trial, specialist care included assertive community OPUS trial, specialist care included assertive community treatment, low-dose atypical antipsychotic medication, treatment, low-dose atypical antipsychotic medication, social skills training, multifamily psychoeducation.social skills training, multifamily psychoeducation.

More of those randomized to specialist treatment had More of those randomized to specialist treatment had independent living arrangements, and fewer were independent living arrangements, and fewer were homeless, better global functioning at 2-year follow-up.homeless, better global functioning at 2-year follow-up.

More participants in the intervention group had resumedMore participants in the intervention group had resumedformal education and there was a greater reduction informal education and there was a greater reduction inpositive and negative symptoms and less comorbid drugpositive and negative symptoms and less comorbid drugand alcohol abuse or dependence.and alcohol abuse or dependence.

Eating DisordersEating Disorders.(Steinhausen et al .(Steinhausen et al 2009).2009).

In AN, there are an almost 18-fold increase In AN, there are an almost 18-fold increase in mortality including a high suicide rate. in mortality including a high suicide rate.

Chronic courses in approximately 20 per Chronic courses in approximately 20 per cent of the cases. cent of the cases.

More than half of the patients show either More than half of the patients show either a complete or a partial eating disorder in a complete or a partial eating disorder in combination with another psychiatric combination with another psychiatric disorder or another psychiatric disorder disorder or another psychiatric disorder without an eating disorder. without an eating disorder.

Eating DisordersEating Disorders.(Steinhausen et al .(Steinhausen et al 2009).2009).

Vomiting, bulimia and purgative Vomiting, bulimia and purgative abuse, chronicity, and obsessive-abuse, chronicity, and obsessive-compulsive features represent compulsive features represent unfavourable prognostic factors. unfavourable prognostic factors.

Mitigating factorsMitigating factors of the outcome of the outcome include onset of the disorder during include onset of the disorder during adolescence and longer duration of adolescence and longer duration of follow-upfollow-up. .

Eating Disorders Eating Disorders (Papadopoulos et al,(Papadopoulos et al, BJP BJP 2009).2009).

The overall SMR for anorexia nervosa was 6.2 The overall SMR for anorexia nervosa was 6.2 (95% CI 5.5-7.0). Anorexia nervosa, psychoactive (95% CI 5.5-7.0). Anorexia nervosa, psychoactive substance use and suicide had the highest SMR.substance use and suicide had the highest SMR.

The SMR was significantly increased for almost all The SMR was significantly increased for almost all natural and unnatural causes of death. natural and unnatural causes of death.

The SMR 20 years or more after the first The SMR 20 years or more after the first hospitalisation remained significantly high. hospitalisation remained significantly high.

Lower mortality was found during the last two Lower mortality was found during the last two decades. decades.

Younger age and longer hospital stay at first Younger age and longer hospital stay at first hospitalisation was associated with better hospitalisation was associated with better outcome, and psychiatric and somatic outcome, and psychiatric and somatic comorbidity worsened the outcomecomorbidity worsened the outcome

OCD. OCD. Ginsburg et al, JAACAP 2009Ginsburg et al, JAACAP 2009

Meta-analysis (6 cognitive-behavioral therapy, 13 Meta-analysis (6 cognitive-behavioral therapy, 13 medication, and 2 combination studies).medication, and 2 combination studies).

Among all of the studies, there was little evidence Among all of the studies, there was little evidence that sex, age, or duration of illness (age at onset) that sex, age, or duration of illness (age at onset) was associated with treatment response. was associated with treatment response.

Baseline severity of obsessive-compulsive Baseline severity of obsessive-compulsive symptoms and family dysfunction were symptoms and family dysfunction were associated with poorer response to cognitive-associated with poorer response to cognitive-behavioural therapy, behavioural therapy,

Comorbid tics and externalizing disorders were Comorbid tics and externalizing disorders were associated with poorer response in medication-associated with poorer response in medication-only studies.only studies.

OCD: OCD: ((Masi et al, 2009)Masi et al, 2009)

Paediatric obsessive-compulsive disorder (OCD) Paediatric obsessive-compulsive disorder (OCD) can cause substantial impairment in academic, can cause substantial impairment in academic, social and family functioning. social and family functioning.

Evaluation of cognitive-behavioural therapy (CBT)Evaluation of cognitive-behavioural therapy (CBT)+/- enhancement in a consecutive series of 257 +/- enhancement in a consecutive series of 257 patients (174 males and 83 females; mean age patients (174 males and 83 females; mean age 13.6+/-2.7 years) diagnosed with OCD.13.6+/-2.7 years) diagnosed with OCD.

37 children improved significantly after 37 children improved significantly after psychotherapy and were excluded. The psychotherapy and were excluded. The remaining 220 patients were included in the remaining 220 patients were included in the study. study.

Eighty-nine patients (40.5%) were managed with Eighty-nine patients (40.5%) were managed with SRI monotherapy and 131 with an SRI in SRI monotherapy and 131 with an SRI in combination with another medication. combination with another medication.

OCDOCD

Compared with those who needed Compared with those who needed polypharmacy, patients managed with SRI polypharmacy, patients managed with SRI monotherapy were younger at the time of monotherapy were younger at the time of the first consultation, had less severe the first consultation, had less severe symptoms at baseline, and more symptoms at baseline, and more frequently presented with co-occurring frequently presented with co-occurring anxiety and depressive disorders. anxiety and depressive disorders.

Patients receiving polypharmacy Patients receiving polypharmacy presented with higher rates of bipolar presented with higher rates of bipolar disorder, tic disorder and disruptive disorder, tic disorder and disruptive behaviour disorders. behaviour disorders.

OCDOCD

135 patients (61.4%) achieved a positive 135 patients (61.4%) achieved a positive clinical response and were considered clinical response and were considered responders. responders.

Responders had Responders had less severe disease at less severe disease at baseline, were younger at the time of the baseline, were younger at the time of the first consultation, more frequently first consultation, more frequently presented with the contamination/cleaning presented with the contamination/cleaning phenotypephenotype and less frequently presented and less frequently presented with the hoarding phenotype.with the hoarding phenotype.

Cytochrome P450 2D6 Genotyping: Cytochrome P450 2D6 Genotyping: Potential Role in Improving Treatment Potential Role in Improving Treatment

Outcomes in Psychiatric DisordersOutcomes in Psychiatric Disorders

Irritability: Stringaris et al, AGP Irritability: Stringaris et al, AGP 20092009

Loeber Loeber

1. Factor analyses suggest that two ODD 1. Factor analyses suggest that two ODD factors exist, one of negative affect and the factors exist, one of negative affect and the other representing defiance.other representing defiance.

2. The negative affect but not the defiant 2. The negative affect but not the defiant component of ODD predicts later depression.component of ODD predicts later depression.

3. ODD rather than CD may explain the 3. ODD rather than CD may explain the comorbidity between CD and depression.comorbidity between CD and depression.

4. It is not clear whether and how child 4. It is not clear whether and how child temperament may be distinguished from temperament may be distinguished from ODDODDsymptoms.symptoms.

Psychopathic features in childhood are about as Psychopathic features in childhood are about as stable as ODD/CD symptoms, but stable as ODD/CD symptoms, but developmental changes have also been noted.developmental changes have also been noted.

Psychopathic features independently predict Psychopathic features independently predict later conduct problems and antisocial behaviorlater conduct problems and antisocial behaviorbeyond earlier initial conduct problem severity.beyond earlier initial conduct problem severity.

Aetiological factors of psychopathic features Aetiological factors of psychopathic features appear similar to those factors associatedappear similar to those factors associatedwith ODD and CD, but there is a need to with ODD and CD, but there is a need to document etiological factors that are uniquedocument etiological factors that are uniqueto psychopathic features.to psychopathic features.

Research on developmental pathways shows that Research on developmental pathways shows that ODD and CD symptoms appear to be stepping ODD and CD symptoms appear to be stepping stones to serious forms of delinquency.stones to serious forms of delinquency.

Loeber’s pathway model shows three pathways Loeber’s pathway model shows three pathways (overt, covert, and authority conflict) to serious (overt, covert, and authority conflict) to serious delinquency. Children can be on more than one delinquency. Children can be on more than one pathway.pathway.

Research on developmental trajectories often Research on developmental trajectories often shows four groups: shows four groups:

problem behavior remains high over time, problem behavior remains high over time, problem behavior remains low, problem behavior remains low, problem behavior increases, problem behavior increases, behavior decreases between childhood and early behavior decreases between childhood and early

adulthood.adulthood.

Most of the risk factors predicting Most of the risk factors predicting delinquency also predict symptoms of delinquency also predict symptoms of disruptive behavior.disruptive behavior.

There is replicated evidence of a dose-There is replicated evidence of a dose-response relationship between children and response relationship between children and adolescents’ exposure to an accumulation adolescents’ exposure to an accumulation of risk factors across multiple domains and of risk factors across multiple domains and an increased probability of later adverse an increased probability of later adverse outcomes.outcomes.

It is probable that the most salient risk It is probable that the most salient risk window of children’s exposure to risk factors window of children’s exposure to risk factors is prior to adolescence.is prior to adolescence.

The sum of promotive and risk factors is a The sum of promotive and risk factors is a better predictor of later problems better predictor of later problems compared to knowledge of risk or compared to knowledge of risk or promotive factors only.promotive factors only.

Promotive factors tend to buffer the impact Promotive factors tend to buffer the impact of risk factors.of risk factors.

The natural occurring balance between risk The natural occurring balance between risk and promotive factors may change over and promotive factors may change over time; time;

The prevalence of promotive factors The prevalence of promotive factors appears highest in middle childhood, and appears highest in middle childhood, and risk compared to promotive factor tends to risk compared to promotive factor tends to be more dominant during adolescence.be more dominant during adolescence.

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Prognostic Factors in Child and Adolescent Psychiatry.

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