Epigenetics: common pathways of psychosocial and biological treatment

Gene functional activity not structure (DNA sequence) changed by environmental factors

Epigenetics

- maternal care via tactile stimulation/nurture of rat pups (week 1)

- low maternal care methylation andhistone deacetylation

- close up chromatin and decrease binding translational factors

- increase CRF

- this process can be reversed by dietary methionine(a histone deacetylase inhibitor) in adult rats

Epigenetics: common pathways of psychosocial and biological treatment

- medication and psychosocial treatments mayhave common pathways of action

- children’s minds and brains may both be changed- notions consistent with emerging understandings ofneural plasticity

- 6 months required for new habit formation

Psychosocial treatment

- structured interventions that are able to be replicated- prior focus on key comorbid conditions associatedwith ADHD: oppositional defiant disorder/conduct disorder,anxiety disorders, depressive disorders, learning disorders,developmental coordination disorder

- increasing focus on core ADHD symptoms with success- developmental stage main determinant nature of psychosocial treatment

- generalisability key current issue

Psychosocial treatment

- primary aim: consistent and reinforced strategies across home,school and wider social environments

- parent training based on behaviour modification principlesincludes psychoeducation, positive reinforcement,response cost, cognitive behavioural techniques such as anxiety and mood regulation, anger management

- teacher training includes the above as well as environmentalchanges and modifying curricula

Psychosocial treatment

- child training: mainly social skills training focused on making and keeping friends and

psychoeducation, positive reinforcement, response cost, anxiety and mood regulation, anger management techniques

Seminal research study Werner & Smith (1982, 1992, 2001)

Conclusion: Protective factors can make a more profound impact on the life course than a specific risk factor

Individual coping styles

-Social Competence-Problem Solving Skills-Autonomy-Sense of purpose, belief in a bright future

Environmental factors

-Caring Relationships-High Expectations-Opportunities for participation

A medication approach (Australian perspective)

- stimulant medication is the first line treatment

short-acting forms: methylphenidate, dexamphetamine long-acting forms: OROS-methylphenidate, LA-methylphenidate

clear and substantial evidence for methylphenidate efficacy up toa dose of 60mg daily for treatments periods of approximately 12 months

methylphenidate and dexamphetamine similar efficacy and adverse effects profile although individual preferences manifest

A medication approach (Australian perspective)

- Stimulant medication benefits

decrease core symptoms of ADHDdecrease aggressionincrease quality of social interactionsincrease compliance

- Stimulant medication indications

ADHD diagnosis and psychosocial interventions insufficient

A medication approach (Australian perspective)

- Stimulant medication adverse effects

initial insomnia,appetite suppression

nervousness, restlessness, dysphoria,easy crying, agitation, depressive symptoms, stomach acheheadache, dizziness, rash, motor tics, mannerisms

in overdose: delirium, sweating, tremor, twitching, vomiting

A medication approach (Australian perspective)

- Stimulant medication adverse effects

growth retardation (MTA 3y f/u: 2cm /2.7kg )weight loss

epileptic seizures not adverse effects but careful psychotic episodes monitoring neededabuse potential in vulnerable patients

A medication approach (Australian perspective)

- Atomoxetine is the second line treatment

specific potent noradrenaline re-uptake inhibitor indicated when stimulant medication ineffective,associated with significant adverse effects

helpful for school and home effects, esp. adolescencecan take 8-10 weeks for full clinical effect

common adverse effects: nausea, drowsiness, initialinsomnia, appetite suppression

A medication approach (Australian perspective)

- Imipramine is a third line treatmenttricyclic compound similar to atomoxetine(a phenylpropanolamine derivative) but with lessspecific noradrenaline effect and significant cardiac adverse effects

- Clonidine is a third line treatmentcentral α-2 noradrenergric agonistsignificant effect; primarily hyperactivity/impulsivenesssignificant drowsiness, hypotensive and cardiac adverse effectsgradual withdrawal because of rebound hypertension and tics

A medication approach (Australian perspective)

- Neuroleptic medication is a third line treatmentatypical neuroleptic medication: eg risperidone / aripiprazolelow doses (up to risperidone 1.5mg daily equivalent)severe aggression, affective lability, PDD, ID

typical neuroleptic medication: eg pericyazine - thioridazineequivalent (now withdrawn)

third line treatments only used with careful monitoring and involvement in a treatment-resistant unit

A medication approach (Australian perspective)Conclusion

- start low, go slow, finish slow, although ensure optimal dosesare used

- medication facilitates each child’s ability to learn in the classroom, playground and home environment: new habitscan take 6 months to evolve

- Comprehensively assess and treat with approved medicationand/or psychosocial treatments all comorbid conditions

Synergies between the two: A model for intervention-a practical approach

[A] psychological and social treatment approach implementedfor 4-6 weeks (may take 6 months of new habit formation beforesustained behavioural change)

key elements are the interpersonal and the intra-individual milieuinterpersonal: positive reinforcement, response cost, token economy, contingency planning (turn taking, active listening, active ignoring, empathy skills, etc), making and keeping friendsintra-individual: controlled breathing, muscle biofeedback,guided visual imagery

Synergies between the two: A model for intervention

- a practical approach

[B] key other vulnerabilities addressed – vision, hearing, specific verbal and/or visuospatial learning difficulties, developmental coordination difficulties, speech and language difficulties

Synergies between the two: A model for intervention

- a practical approach

[C] medication use to facilitate availability of the young person to learn from the psychological and social interventions through

better arousal regulation better mood regulationbetter executive functioning

Synergies between the two: A model for interventionSummary- medication can aid a child’s ability to invest ina psychosocial treatment program and learn from this program

- can take 6 months of practice before new habits are formed

- biological and psychosocial treatments maximize resilienceand minimize risk factors through shared effects on the brainand the mind