David Cohen

, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

BACKGROUND: Assessment of mother-child interactions is a core issue of early child development and psychopathology. This paper focuses on the concept of "synchrony" and examines (1) how synchrony in mother-child interaction is defined and operationalized; (2) the contribution that the concept of synchrony has brought to understanding the nature of mother-child interactions. METHOD: Between 1977 and 2013, we searched several databases using the following key-words: "synchrony" "interaction" and "mother-child". We focused on studies examining parent-child interactions among children aged 2 months to 5 years. From the 63 relevant studies, we extracted study description variables (authors, year, design, number of subjects, age); assessment conditions and modalities; and main findings. RESULTS: The most common terms referring to synchrony were mutuality, reciprocity, rhythmicity, harmonious interaction, turn-taking and shared affect; all terms were used to characterize the mother-child dyad. As a consequence, we propose defining synchrony as a dynamic and reciprocal adaptation of the temporal structure of behaviors and shared affect between interactive partners. Three main types of assessment methods for studying synchrony emerged: (1) global interaction scales with dyadic items; (2) specific synchrony scales; and (3) micro-coded time-series analyses. It appears that synchrony should be regarded as a social signal per se as it has been shown to be valid in both normal and pathological populations. Better mother-child synchrony is associated with familiarity (vs. unknown partner), a healthy mother (vs. pathological mother), typical development (vs. psychopathological development), and a more positive child outcomes. DISCUSSION: Synchrony is a key feature of mother-infant interactions. Adopting an objective approach in studying synchrony is not a simple task given available assessment tools and due to its temporality and multimodal expression. We propose an integrative approach combining clinical observation and engineering techniques to improve the quality of synchrony analysis.