The issue of chronic medication use during childhood is sometimes controversial, particularly in regard to psychotropic medication (Lancet, 2008). Little is known about the long-term effects of psychotropic drug use in children and evidence for efficacy can be scant. One of the commonest chronic medications prescribed for children are inhaled corticosteroids which are the mainstay of preventive treatment for asthma. It is estimated that between 4- 9% of children under 12 in the UK are prescribed medication for asthma (Turner et al, 2009). Many children remain on inappropriately high doses of steroids for longer than is necessary (Turner et al, 2009). Although there is awareness of adverse effects of steroids such as growth retardation, adrenal insufficiency and ocular and skin effects (Lipworth , 1999; Covar et al, 2000) there appears to be little awareness of the potential adverse effects of these medications on children's mental health.

Clinically, from our work in liaison psychiatry, it is evident that steroid treatment commonly results in psychotic-type symptoms in the general hospital setting. Case studies on adult patients have demonstrated a wide range of behavioural and psychiatric side effects resulting from corticosteroid treatment, including disturbances of mood, cognition, aggression, hyperactivity and psychosis (Warrington and Bostwick, 2006). However, there is little data available for paediatric populations. One randomised controlled trial on the efficacy of high dose corticosteroids in the treatment of acute lymphoblastic leukaemia in children has reported on psychiatric side effects. These included severe depression, violence towards self and others, mood swings and lability, and psychosis (Mitchell et al., 2005). In fact, "behavioural toxicity" was the most significant side effect recorded in the study. It is not known whether psychotropic effects would be seen with low-dose corticosteroids (such as the normal doses for inhaled steroids). To our knowledge, no research to date has been conducted to formally assess psychiatric symptomatology among children using corticosteroid medication. As a result, the true side effect profile of this medication is unknown.

Our application to ALSPAC is prompted by an intriguing (unpublished) finding from analysis of our Challenging Times study data (Lynch et al., 2004; Kelleher et al., 2008) which showed a significant association between a diagnosis of asthma and psychotic-type symptoms in children aged 12-15 years of age. Fourteen percent (n=29) of the adolescents interviewed had a history of asthma. 58.6% of these participants had been treated with corticosteroid medication in the course of their illness. Further analyses revealed that the adolescents who had received corticosteroid therapy for their asthma were significantly more likely to have experienced psychotic symptoms than the adolescents who had a history of asthma but no corticosteroid use. The numbers in our study are small, however, and the ALSPAC data would allow more careful analysis of this important research question. We would like to examine other psychiatric symptoms also as potential adverse effects of steroids.

We are also interested in adverse side effects of stimulant medication use in children, in particular the possible association between stimulant use and psychotic-type symptoms. Stimulant medication has been commonly used for treatment of Attention Deficit Hyperactivity Disorder (ADHD) although concerns are increasingly being expressed about its use as a first line treatment (Kendall et al, 2008) There are few studies that have examined the behavioural and psychiatric side effects of stimulant medication use in children (Barkley et al., 1990). The few data available on methylphenidate have shown side effects including depression, irritability, violent behaviour and mania (Schachar et al., 1997). Psychotic reactions have also been documented in the literature (Cherland and Fitzpatrick, 1999), but this has been noted as a result of obvious psychotic disturbance and not a result of systematic investigation of psychotic symptoms. It, thus, likely represents an underestimation of the true side effect profile of stimulant medication.

In order to address our research questions, the following psychological variables would be needed for all time points available:

Exposure information:

- Medication use in childhood and adolescence

- Medical and psychiatric illness diagnosed in childhood and adolescence

Principal outcome measure:

- Psychotic symptoms: PLIKS age 12 (interview) , PLIKS (questionnaires) ages 13, 14, 15, 16

Secondary outcome measures:

- Other Psychopathology: DAWBA (ages 7,10,13, 15); SDQ (age 4, 6,8,9,11,13); MFQ (ages 9,10,11,12,13); Antisocial behaviour (ages 8,10, 12), borderline personality interview (age 12).

- Measures of cognitive function and educational attainment:

IQ test scores (4,8,15); Attention measures (age 8,11); Exam scores SATS ages 7,11,14, GCSEs age 16

Possible Confounders:

- SES; gender, family history of psychiatric disorder

Analysis:

Analysis will be performed in STATA (v9). We will study repeated measures of psychopathology in relation to commencement (and discontinuation) of medication. Our main outcome of interest is psychotic-type symptoms but we will also measure the changes in other psychopathology and cognitive ability in relation to medication use. We will take account of possible confounders such as social class, gender and family history of psychiatric illness.

References:

Barkley RA, McMurray MB, Edelbrock CS, Robbins K (1990) Side effects of methylphenidate in children with attention deficit hyperactivity disorder: a systemic, placebo-controlled evaluation. Pediatrics, 86 (2): 184 - 192

Cherland E and Fitzpatrick R (1999) Psychotic side effects of psychostimulants: a 5-year review. Canadian Journal of Psychiatry, 44 (8): 811 - 813

Covar RA, Leung DY, McCormack D et al (2000) Risk factors associated with glucocorticosteroid induced adverse effects in children with severe asthma. J Allergy clin Immunol, 106: 651-9

Kelleher I, Harley M, Lynch F, Arseneault L, Fitzpatrick C and Cannon M (2008) Associations between childhood trauma, bullying and psychotic symptoms among a school-based adolescent sample. British Journal of Psychiatry, 193: 378 - 382

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Lynch F, Mills M, Daly I, Fitzpatrick C (2004) Challenging Times: a study to detect Irish adolescents at risk of psychiatric disorders and suicidal ideation. J Adolesc, 27: 441 - 451

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Panico L, Bartely M, Marmot M, Nazroo JY, Sacker A, Kelly YJ. (2007) Ethinic variation in childhood asthma: findings from the Millenium cohort. Int J Epid 36:1093-1102.

Schachar RJ, Tannock R,Cunningham C, Corkum PV (1997) Behavioural, situational and temporal effects of treatment of ADHD with methylphenidate. Journal of the American Academy of Child and Adolescent Psychiatry, 36 (6): 754-763

Turner S, Thomas M, von Ziegenweidt J, Price D (2009) Prescribing trends in asthma: a longitudinal study, Arch Dis Child; 94:16-22

Warrington TP and Bostwick JM (2006) Psychiatric adverse effects of corticosteroids. Mayo Clin Proc, 81 (10): 1361 - 1367.