Environmental factors acting on young animals affect neurodevelopmental trajectories and impact adult brain function and behavior. Psychiatric disorders may be caused or worsen by environmental factors, but early interventions can improve performance. Understanding the possible mechanisms acting upon the developing brain could help identify etiological factors of psychiatric disorders and enable advancement of effective therapies. Research has focused on the long-lasting effects of environmental factors acting during the perinatal period, therefore little is known about the impact of these factors at later ages when neurodevelopmental pathologies such as autism spectrum disorder (ASD) are usually diagnosed. Here we show that handling mice during the juvenile period can rescue a range of behavioral and cellular effects of prenatal valproic acid (VPA) exposure. VPA-exposed animals show reduced sociability and increased repetitive behaviors, along with other autism-related endophenotypes such as increased immobility in the forced swim test and increased neuronal activity in the piriform cortex (Pir). Our results demonstrate that briefly handling mice every other day between postnatal days 22 and 34 can largely rescue these phenotypes. This effect can also be observed when animals are analyzed across tests using an “autism” factor, which also discriminates between animals with high and low Pir neuron activity. Thus, we identified a juvenile developmental window when environmental factors can determine adult autism-related behavior. In addition, our results have broader implications on behavioral neuroscience, as they highlight the importance of adequate experimental design and control of behavioral experiments involving treating or testing young animals.

IntroductionNeglected tropical diseases (NTDs) are an important global health challenge, however, little is known about how to effectively finance NTD related services. Integrated management in particular, is put forward as an efficient and effective treatment modality. This is a background study to a broader health economic evaluation, seeking to document the costs of integrated care management of NTDs versus standard care in Liberia. In the current study, we document barriers and facilitators to NTD care from a health financing perspective.MethodsWe carried out key informant interviews with 86 health professionals and 16 national health system policymakers. 46 participants were active in counties implementing integrated case management and 40 participants were active in counties implementing standard care. We also interviewed 16 patients and community members. All interviews were transcribed and analysed using the thematic framework approach. FindingsWe found that decentralization for NTD financing is not yet achieved – financing and reporting for NTDs is still centralized and largely donor-driven as a vertical programme; government involvement in NTD financing is still minimal, focused mainly on staffing, but non-governmental organisations (NGOs) or international agencies are supporting supply and procurement of medications. Donor support and involvement in NTDs are largely coordinated around the integrated case management. Quantification for goods and budget estimations are specific challenges, given the high donor dependence, particularly for NTD related costs and the government’s limited financial role at present. These challenges contribute to stockouts of medications and supplies at clinic level, while delays in payments of salaries from the government compromise staff attendance and retention. For patients, the main challenges are high transportation costs, with inflated charges due to fear and stigma amongst motorbike taxi riders, and out-of-pocket payments for medication during stockouts and food/toiletries (for in-patients).ConclusionOur findings contribute to the limited work on financing of SSSD services in West African settings and provide insight on challenges and opportunities for financing and large costs in accessing care by households, which is also being exacerbated by stigma.