The social, psychological, genetic and neurobiological context of pediatric OCD and OCD treatment response

Obsessive-compulsive disorder (OCD) has a relatively low prevalence (0,5-3,0%) in children and adolescents but is very serious illness causing suffering and impairment. About half of adults with OCD report significant OCD symptoms as children, and OCD is according to WHO the 10th worst disorder leading to years with impairment (including somatic illness). Since the early 1980ies young persons with OCD have been diagnosed increasingly and effective treatments been developed for this group. Whether this will lead to better long-term outcome is still unclear as the durability of these treatments is unknown. First line treatment in pediatric OCD is cognitive behavior therapy (CBT) with exposure and response prevention (ERP) as essential components. If the children or parents do not wish to use CBT or do not respond to CBT, guidelines recommend adding or switching to selective serotonine reuptake inhibiting drugs (SSRI antidepressants). These guidelines are based on expert consensus rather than empirical findings. In addition, is it not clear how many hours/weeks of CBT are necessary or suitable before a switch. In research studies the number of CBT sessions have varied from about 10 - 16. However, it is conceivable that more patients would respond if more sessions were used. Possibly may children with more severe OCD, or with co-morbid anxiety and depression as well respond better to more sessions. The Nordic Long-term OCD Treatment Study (NordLOTS) is a treatment study based at the Regional Centre for child mental health east and south (RBUP) in Oslo. The study is meant to strengthen the treatment options available for children and adolescents with OCD in Norway, Sweden and Denmark. The goal is to train and supervise therapists in the use of ERP and offer a stepwise treatment based on the clinical guidelines and to evaluate the outcome when using these guidelines. Furthermore, we aimed to study genetical and neurobiological aspekcts of OCD and OCD treatment outcome. In the study were 269 OCD patients offered CBT with ERP. More than 70% responded to treatment and about half were in remission as well. About 30% responded weakly or not at all following 14 weeks with ERP and were consequently randomized to drug treatment with sertralin (an SSRI) or CBT revised based on a new case formulation, both groups received 16 additional weeks of treatment. However, both groups responded so that based on these two treatment steps, in total 80% of the patients had responded, a very encouraging outcome. As a previous study had shown that a co-morbid tic disorder could attenuate SSRI treatments (though not CBT) we examined the outcome based on the presence or absence of a comorbid tic disorder. However. our findings went contrary to earlier studies in that children with OCD+tics responded better to SSRI than those with OCD only. We found no influence on CBT outcome, nor was the outcome of CBT in the first treatment step affected. There is little knowledge of the long-term outcome or durability and risk of relapse from these treatments. Thus, we followed up our patients up to three years following the first CBT step. At 6 and 12 month follow-up of those who responded to CBT with ERP most became better still and somewhat more than 90% of our patients had improved. However, about 20% had had a relapse although half of these got better again following more CBT. Data on the long-term outcome (24 and 36 months following step 1 CBT show that 3 out of 4 were in remission and that 9 out of 10 had responded to the treatment. These results are more encouraging than previous findings, showing that it is worthwhile to treat young people with OCD. Imaging using magnet resonance in a sub-group was delayed so that the outcome is not available yet.

OCD is a serious often chronic condition with mostly pediatric onset entailing considerable suffering and impairment. AIn adult OCD 50-80% report childhood onset, and it is the 10:th most common reason for disability from illness. Treatment with CBT and Serotonin Re-uptake Inhibitors (SSRI) have proven efficacy (3 months), but little is known about long-term benefits, nor what treatment to use in CBT non-responders (about 30%). Patients with moderate severe OCD were treated with CBT (n=269) to identify poor CBT responders (n=69). These were randomized to intensive, enhanced CBT (to problems in step 1) or to Sertraline (a sertonin active drug) plus CBT support. Step2 CBT non-responders were treated with Sertraline and CBT+Sertraline non-response could be augmented with aripiprazole (however, so few patients were included in that step that we cannot report the data). Out of the 269 patients that were treated with CBT, more than 70% responded and about half remitted. Preliminary follow-up data which is currently being published point to excellent durability of treatment gains in most. However, a few relapse so that at 1 year follow-up, about 20% have had a relapse either earlier or currently. Follow-up assessments at 24 and 36 months are made, the data are currently analysed and will be published during the coming year. Assessements used were: social factors (e.g . expressed emotion, family accomodation, school adaptation/problems); psychological factors (temperament); and psychiatric problems (e.g. OCD symptom profile, co-morbidity). Semistructured interviews, scales, speech samples were used. Genetic screening of glutamate and monoamines was made from saliva samples (financed separately). However, neurochemical assessment (using Magnet Resonance Spectroscopy (MRS)) had to be replaced with a volumetric assessment and an assessment using fMRI of the "resting state" before treatment. We had to exclude MRS due to assessment problems. Moreover, this caused a delay so that the revised neurobiological assessment of OCD versus controls and as predictor of CBT has to be made in a separate cohort from the pediatric OCD clinics in "Helseregion East & South" and which now has started. A doctoral student studied step 2 outcome and factors predicting step 2 treatment response, all now published. Continued CBT was as good as drug treatment with sertraline to obtain response and remission. This means that for patients with OCD 80% will have responded to CBT and/or sertraline when considering both the two treatment steps. Moreover 55% will have remitted. Furthermore, could we show that a life-time co-morbid tic disorder moderated step 2 outcome in that those who were randomized to sertralin responded better if they had tics, while for those who were randomized to CBT, co-morbid tics did not affect outcome. The outcome of our stepped care study is very positive and goes against the old dogma that pediatric OCD is difficult to treat. Still, 20% did not respond to treatment and about 20% showed elevated risk of relapse following response, indicating that these treatments still need to be improved. The interaction of genetic, neurobiological and psychosocial aspects intended to elucidate pathogenic processes, and, as part of a treatment study, to enable the study of OCD as a dynamic system has been modified as described above with regard to the neurobiological assesssment. The genetics of CBT response is done in cooperation with another researcher group in the UK. Neurobiological aspects will be studied through a MR protocol used in the study of early onset psychosis in children and adolescents in cooperation with the NORMENT group at Oslo University. The attached files are the documents that were used to ask for prolonged access to the grant. They contain a more detailed description of the NordLOTS study and the neurobiological co-study as described here. The currently ongoing neurobiological assessment is part of a collaboration with an identical study in Halmstad and Göteborg, Sweden to enhance our statistical and measurement power in targeting parts of brain loops that, we believe, are the physical basis of OCD symptoms. The CBT treatment used is identical with that of the NordLOTS study proper as described above.