Schizophrenia Bulletin最新文献

Background and hypothesis: Early auditory processing (EAP) has increasingly become a focus of efforts to identify markers of treatment response in people with schizophrenia spectrum disorders. Assessment of baseline need provides an opportunity for cognitive remediation (CR) programs that include EAP training to personalize treatment and optimize its impact. CR has been shown to help reduce negative symptoms, but less is known about how EAP tailoring may influence this relationship. This study hypothesized a differential benefit of EAP training on negative symptom reduction for those with and without baseline EAP deficits as defined by performance on the Tone Matching Test.

Study design: 150 outpatient adults diagnosed with schizophrenia or schizoaffective disorder were classified as having intact (44.7%) or impaired (55.3%) EAP and were randomly assigned to CR that either included EAP training (N = 77) or did not (N = 73). Negative symptom improvement was measured via the Positive and Negative Syndrome Scale posttreatment and 3 months later.

Study results: CR resulted in significant negative symptom improvement in the sample overall. Only EAP impaired participants demonstrated significant negative symptom benefit from EAP training. EAP impaired participants who did not receive embedded auditory training had near-zero reductions in negative symptom severity.

Conclusions: These findings extend prior research on cognitive remediation as treatment for negative symptoms in people with schizophrenia spectrum disorders. Accumulating evidence suggests that routine assessment of EAP is critical for personalizing and optimizing a response to CR that is clinically significant for both cognitive and negative symptoms.

Background and hypothesis: The pathogenesis of tardive dyskinesia (TD) remains unclear, involving multiple biological pathways. This study aimed to explore biomarkers of TD through untargeted metabolomics for the early identification of TD.

Study design: This study recruited 84 schizophrenia (SZ) patients with TD and 160 SZ patients without TD. TD diagnosis was based on the Schooler-Kane criteria, and the severity of TD and psychiatric symptoms were assessed using the Abnormal Involuntary Movement Scale and the Positive and Negative Syndrome Scale. Fasting blood samples were collected from all patients and subjected to untargeted metabolomics analysis using Ultra-high-performance liquid chromatography-high resolution mass spectrometry, allowing for the quantification and profiling of 699 metabolites. Data were analyzed with orthogonal partial least squares discriminant analysis, and receiver-operating characteristic curves.

Study results: In TD, 57 metabolites exhibited significant changes (variable importance of projection > 1, false discovery rate-adjusted P < .05), primarily involving amino acids and lipids. These changes predominantly affected the phenylalanine, tyrosine, and tryptophan pathway (impact = 0.5, P = .0252), as well as the phenylalanine metabolism pathway (impact = 0.36, P = .0498). N-Acetyl-l-phenylalanine (B = 2.249, t = 4.56, P < .001, 95% CI, 1.302-3.286) and Succinylcarnitine (AcCa(4:0-DC)) (B = 1.009, t = 3.07, P = .002, 95% CI, 0.362-1.656) are negatively related to the total abnormal involuntary movement scale score. Additionally, 5 differential metabolites had area under the curve (AUC) values greater than 0.7 for diagnosing TD, with the combined diagnostic capability exceeding 0.8 (AUC = 0.817, 95% CI, 0.759-0.875).

Conclusions: In TD, disruptions in amino acid and lipid metabolism were predominantly observed. Amino acids and lipid metabolites may be involved in the development of TD. Additionally, a biomarker panel composed of amino acids and lipids can be used for the differential diagnosis of TD.

Background and hypothesis: Relapsing after a first episode of schizophrenia (FES) is a main predictor of clinical and functional prognosis. Brain-derived neurotrophic factor (BDNF) plays a critical role in neuronal development and plasticity, and its signaling may be altered by successive relapses.

Design: We assessed the impact of first relapse in the expression of the 2 isoforms of the BDNF tropomyosin-related kinase B (TrkB) receptor (active full-length TrkB-F and inactive truncated TrkB-T) in peripheral blood mononuclear cells from 53 FES patients in clinical remission followed up for 3 years.

Results: The group of participants that relapsed (n = 24) during the follow-up presented a significant decrease in the expression of the active TrkB-F receptor compared to baseline (M = 100 ± 28.13 vs. M = 83.42 ± 33.84, t = 2.5, P = .02), with no changes in the inactive TrkB-T receptor expression nor in BDNF plasma levels. This decrease also led to a significant decline in the F/T ratio (M = 1.13 ± 0.38 vs. 0.94 ± 0.36, t = 2.17, P = .041). No significant differences were found in the receptors' expression nor in plasma levels in the group of cases that remained in remission (n = 29). These results were not associated with baseline differences between the groups in terms of the BDNF signaling pathway biomarkers, clinical or treatment variables.

Conclusions: These findings highlight the biological impact that a relapse produces over the systemic BDNF-TrkB signaling pathway, potentially undermining crucial neuronal functions. Identifying the actors involved can help design specific interventions for relapse prevention and improve the functional prognosis of people in the early stages of schizophrenia.