Schizophrenia Bulletin Open最新文献

Studies of the genetic heritability of schizophrenia and bipolar disorder examining single nucleotide polymorphisms (SNPs) and copy number variations have failed to explain a large portion of the genetic liability, resulting in substantial missing heritability. Long interspersed element 1 (L1) retrotransposons are a type of inherited polymorphic variant that may be associated with risk for schizophrenia and bipolar disorder. We performed REBELseq, a genome wide assay for L1 sequences, on DNA from male and female persons with schizophrenia and controls (n = 63 each) to identify inherited L1 insertions and validated priority insertions. L1 insertions of interest were genotyped in DNA from a replication cohort of persons with schizophrenia, bipolar disorder, and controls (n = 2268 each) to examine differences in carrier frequencies. We identified an inherited L1 insertion in ARHGAP24 and a quadallelic SNP (rs74169643) inside an L1 insertion in SNTG2 that are associated with risk for developing schizophrenia and bipolar disorder (all odds ratios ~1.2). Pathway analysis identified 15 gene ontologies that were differentially affected by L1 burden, including multiple ontologies related to glutamatergic signaling and immune function, which have been previously associated with schizophrenia. These findings provide further evidence supporting the role of inherited repetitive genetic elements in the heritability of psychiatric disorders.

Background: Social anxiety disorder (SAD) commonly occurs among individuals at clinical high-risk (CHR) for psychosis. Extant research has yet to examine the prevalence and clinical/functional correlates of SAD in this population compared to a community control (CC) sample. This comparison may improve the generalizability that traditional nonpsychiatric control samples cannot provide. Additionally, it remains unknown how SAD contributes to symptom severity and social impairments in individuals at CHR for psychosis.

Methods: Both CHR and CC groups were recruited from general community sources; CC participants were not excluded in this analysis on the basis of any psychopathology except psychosis. A total of 245 adolescents and young adults (CHR = 81; CC = 164) were administered the Social Phobia Scale, the Structured Interview for Psychosis-risk Syndromes, Structured Clinical Interview for DSM-5 Research Version, and the Social Functioning Scale.

Results: The CHR group was at increased risk for having SAD relative to CC (42% CHR; 13% CC; RR = 3.28) and, to a lesser degree, a non-SAD anxiety disorder (41% CHR; 29% CC; RR = 1.42). Greater social anxiety was related to higher levels of negative (r = 0.29) but not positive (r = 0.05) symptoms within the CHR group. Furthermore, elevated social anxiety was found to be linked with poor social functioning in the CHR group (r = -0.31).

Conclusions: These findings demonstrate the specificity of SAD over and above other anxiety disorders in individuals at CHR for psychosis and the critical target of SAD to treat subclinical psychotic symptoms and social functioning.

Deficits in goal-directed decision making and motivation are hallmark characteristics of several neuropsychiatric disorders, including schizophrenia (SZ) and major depressive disorder (MDD). Studies using effort-based decision-making tasks have shown that both patients with SZ and MDD invest less physical effort in order to obtain rewards. However, how these motivational deficits relate to clinically assessed symptom dimensions such as apathy remains controversial. Using a grip-strength-based effort discounting task we assessed effort-based decision-making behavior in healthy controls (HC) (N = 18), patients with SZ (N = 42), and MDD (N = 44). We then investigated how effort discounting relates to different symptom dimensions. There were no differences in effort discounting between HC participants and patients with SZ or MDD. In addition, we did not observe a correlation between effort discounting and negative symptoms (NS) in patients with SZ or MDD. In conclusion, the current study does not support an association between effort discounting and NS in SZ or MDD. Further studies are needed to investigate effort discounting and its relation to psychopathological dimensions across different neuropsychiatric disorders.

[This corrects the article DOI: 10.1093/schizbullopen/sgaa054.].

Background: Health services have advocated a stratified medicine approach in mental health, but little is known about whether service users would accept this approach.

Aims: To explore service users' views of the acceptability of stratified medicine for treatment-resistant schizophrenia compared to the traditional "trial-and-error" approach.

Methods: A mixed methods observational study that explored questionnaire responses on acceptability and whether these responses were affected by demographic or clinical variables. We also investigated whether treatment responsiveness or experience of invasive tests (brain scans and blood tests) affected participants' responses. Questionnaire generated qualitative data were analyzed thematically. Participants (N108) were aged 18-65, had a diagnosis of schizophrenia, and were adherent to antipsychotic medication.

Results: Acceptability of a stratified approach was high, even after participants had experienced invasive tests. Most rated it as safer (62% vs 43%; P < .01 [CI: -1.69 to 2.08]), less risky (77% vs 44%; P < .01 [CI: -1.75 to 1.10]), and less painful (90% vs 73%; P < 0.01 [CI: -0.84 to 0.5]) and this was not affected by treatment responsiveness or test experience. Although not statistically significant, treatment nonresponders were more willing to undergo invasive tests. Qualitatively, all participants raised concerns about the risks, discomfort, and potential side effects associated with the invasive tests.

Conclusions: Service users were positive about a stratified approach for choosing treatments but were wary of devolving clinical decisions to purely data-driven algorithms. These results reinforce the value of service user perspectives in the development and evaluation of novel treatment approaches.

The successful treatment of schizophrenia entails improvement across a spectrum of symptoms. The aim of this post hoc analysis was to characterize the short- and long-term effects of brexpiprazole on Positive and Negative Syndrome Scale (PANSS) 'Marder factors.' Data were included from three 6-week, randomized, double-blind, placebo-controlled studies; a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study; and two 52-week open-label extension (OLEx) studies-all in schizophrenia (DSM-IV-TR criteria). Patients receiving oral brexpiprazole were dosed at 2-4 mg/day (short-term studies) or 1-4 mg/day (long-term studies). At Week 6, least squares mean differences (LSMDs, with 95% confidence limits [CLs]) for brexpiprazole (n = 868) vs placebo (n = 517) were: Positive symptoms: -1.55 (-2.30, -0.80), P < .0001, Cohen's d effect size (ES) = 0.27; Negative symptoms: -1.12 (-1.63, -0.61), P < .0001, ES = 0.29; Disorganized thought: -1.26 (-1.78, -0.74), P < .0001, ES = 0.32; Uncontrolled hostility/excitement: -0.76 (-1.15, -0.37), P = .0002, ES = 0.26; Anxiety/ depression: -0.56 (-0.91, -0.22), P = .0014, ES = 0.22. At last visit of the maintenance study, LSMDs (95% CLs) for brexpiprazole (n = 96) vs placebo (n = 104) were: Positive symptoms: -3.44 (-4.99, -1.89), P < .0001, ES = 0.62; Negative symptoms: -1.23 (-2.52, 0.07), P = .063, ES = 0.27; Disorganized thought: -1.69 (-2.81, -0.56), P = .0035, ES = 0.42; Uncontrolled hostility/excitement: -1.26 (-2.12, -0.39), P = .0046, ES = 0.41; Anxiety/depression: -0.72 (-1.47, 0.03), P = .061, ES = 0.27. In the OLEx studies, improvements were maintained over 58 (6 + 52) weeks of brexpiprazole treatment. In conclusion, these data suggest that brexpiprazole treats the continuum of schizophrenia symptoms, in the short- and long-term. Trial Registration: Data used in this post hoc analysis came from ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380, NCT01668797, NCT01397786, NCT01810783.