In this meta-analysis, the impact of writing interventions on the quality of writing produced by students with learning disabilities (LD) was assessed. Ancestral and electronic searches were used to locate experimental, quasi-experimental, and within-subjects design studies with participants in Grades 1-12 with documented LD. The effects of writing interventions on participants' writing quality were averaged across 43 eligible studies to calculate an average weighted mean effect size (ES). Average weighted mean ES were also calculated for six writing treatment subgroups that contained four or more studies each (i.e., strategy instruction, dictation, procedural facilitation, prewriting, goal setting, and process writing). Overall, writing interventions had a statistically significant positive impact on the writing quality of students with LD (ES = 0.74). All writing treatment subgroups also had positive average weighted ES, but only four were statistically different from zero (i.e., strategy instruction ES = 1.09, dictation ES = 0.55, goal setting ES = 0.57, and process writing ES = 0.43). In addition, treatments designed specifically to enhance writing processes (e.g., planning, revising) were only effective when instruction was provided. Implications for the types of writing treatments and the types of instruction that may be most beneficial to students with LD are discussed and directions for future research are provided.

BackgroundSchizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry. This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes.MethodA systematic literature search was conducted, using PubMed, EMBASE, PsycInfo, CINAHL and OpenGrey databases, to identify all studies which compared treatment-resistant schizophrenia (defined as either a lack of response to two antipsychotic trials or clozapine prescription) to treatment-responsive schizophrenia (defined as known response to non-clozapine antipsychotics).ResultsNineteen studies of moderate quality met inclusion criteria. The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities, a lack of dopaminergic abnormalities, and significant decreases in grey matter compared to treatment-responsive patients. Treatment-resistant patients were also reported to have higher familial loading; however, no individual gene-association study reported their findings surviving correction for multiple comparisons.ConclusionsTentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia. However, research is limited and confirmation will require replication and rigorously controlled studies with large sample sizes and prospective study designs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-1177-y) contains supplementary material, which is available to authorized users.

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We performed a systematic analysis of blood DNA methylation profiles from 4,483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1,048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.