Schizophrenia Bulletin最新文献

Background and hypothesis: Since a prior systematic review and meta-analysis reported an association between psychotic experiences (PEs) and suicidal thoughts and behaviors, a large number of new studies have been published on the topic, including several novel studies on the association between PEs and transition from suicidal ideation to attempt.

Study design: Two authors independently searched PubMed, Embase, CINAHL, and PsycINFO databases from inception until July 2023, conducted data extraction, and assessed study quality using the Newcastle-Ottawa Quality Assessment Scale. Random-effects models were used to calculate pooled odds ratios (ORs) for the association of PEs and subsequent suicide ideation, suicide attempts, suicide death, and transition from suicidal ideation to attempt, first for the total population, and second stratified by age group. Secondary analyses assessed the mediating role of co-occurring psychopathology.

Study results: Twenty studies from 18 different samples (n = 81,861) were identified. Individuals who reported PEs had increased odds of subsequent suicidal ideation (k = 12, OR = 1.90, 95% CI = 1.65-2.19), suicide attempt (k = 13, OR = 2.95, 95% CI = 2.21-3.94), transition from suicidal ideation to suicide attempt (k = 3, OR = 2.83, 95% CI = 1.60-4.99), and suicide death (k = 1, OR = 4.39, 95% CI = 1.63-11.80). This heightened risk was stable across childhood, adolescence, and adulthood. PEs predicted suicide attempts over and above co-occurring psychopathology (k = 8, OR = 2.85, 95% CI = 2.06-3.95).

Conclusions: Individuals reporting PEs are at increased risk of all types of suicidal thoughts and behaviors. In addition, PEs are particularly important risk markers for future suicidal behaviors, including in individuals already reporting suicidal ideation. This risk is in excess of what is explained by co-occurring psychopathology.

Background and hypothesis: The efficacy of yoga as an adjunctive treatment for schizophrenia spectrum disorders (SSD) has garnered interest. While yoga may positively influence various symptom domains, further investigation is needed due to the limited number, quality, and generalizability of studies. This study assessed the feasibility and acceptability (primary outcome) of a yoga-based group intervention (YoGI) developed in a participatory approach and explored its preliminary effectiveness.

Study design: In addition to the primary outcomes, this preregistered randomized controlled trial examined rater-blinded general psychopathology, positive- and negative symptoms, and self-rated depression, anxiety, stress, body mindfulness, mindfulness, psychological flexibility, cognition, social functioning, quality of life, and medication regime at baseline and postintervention as secondary outcomes.

Study results: Fifty inpatients with SSD received either TAU (n = 25) or YoGI + TAU (n = 25) for four weeks. Outcomes showed 95% protocol adherence of YoGI, feasibility, and retention rates of 91% and 94%, respectively, and a dropout rate of 6%. ANCOVA revealed significant between-group postintervention improvements for YoGI + TAU in positive symptoms, depression, cognitive fusion, and a mindfulness subscale. Medium-to-large pre- to postintervention effects were found for body mindfulness, positive, negative, and general psychopathology, cognitive fusion, depression, anxiety, stress, quality of life, and attention in YoGI + TAU, while within-group changes were consistently smaller in TAU. No severe adverse events were reported.

Conclusions: This trial supports the feasibility and acceptability of YoGI for inpatients with SSD and provides preliminary evidence of YoGI's benefits beyond TAU. Further robust, multicentric RCTs are warranted to deepen our understanding of YoGI's therapeutic potential and inform clinical interventions for SSD.

Background and hypothesis: The amygdala, crucial for mood, anxiety, fear, and reward regulation, shows neuroanatomical and molecular divergence in psychiatric disorders like schizophrenia, bipolar disorder and major depression. This region is also emerging as an important regulator of metabolic and immune pathways. The goal of this study is to address the paucity of molecular studies in the human amygdala. We hypothesize that diagnosis-specific gene expression alterations contribute to the unique pathophysiological profiles of these disorders.

Study design: We used a cohort of subjects diagnosed with SCZ, BPD or MDD, and nonpsychiatrically ill control subjects (n = 15/group), together with our bioinformatic 3-pod analysis consisting of full transcriptome pathway analysis, targeted pathway analysis, leading-edge gene analysis and iLINCS perturbagen analysis.

Study results: We identified altered expression of metabolic pathways in each disorder. Subjects with SCZ displayed downregulation of mitochondrial respiration and nucleotide metabolism pathways. In comparison, we observed upregulation of mitochondrial respiration pathways in subjects with MDD, while subjects with BPD displayed enrichment of pathways involved in carbohydrate metabolism. Several pathways associated with brain metabolism including immune system processes and calcium ion transport were also differentially altered between diagnosis groups.

Conclusion: Our findings suggest metabolic pathways, including downregulation of energy metabolism pathways in SCZ and upregulation of energy metabolism pathways in MDD, are uniquely altered in the amygdala in these disorders, which may impact approaches for therapeutic strategies.

Anti-leucine-rich glioma-inactivated 1 (LGI1) antibody-associated encephalitis is a rare but clinically significant form of autoimmune encephalitis, predominantly affecting middle-aged men. Its heterogeneous clinical presentation often leads to misdiagnosis, commonly as other neurological or psychiatric disorders. This report details the case of a 46-year-old male who initially presented with depressive symptoms, personality changes, and visual hallucinations. Over time, his condition progressed to include memory impairment, disorganized behavior, and seizures. Initially misdiagnosed with schizophrenia, the correct diagnosis of LGI1 antibody-associated encephalitis was eventually established through positive serum and cerebrospinal fluid (CSF) tests for LGI1 antibodies. Neuroimaging findings revealed characteristic bilateral temporal lobe lesions. The patient demonstrated marked improvement following treatment with methylprednisolone and intravenous immunoglobulin, ultimately achieving significant recovery. This case highlights the critical importance of comprehensive antibody testing and neuroimaging in patients presenting with nonspecific psychiatric and neurological symptoms to prevent misdiagnosis and delays in appropriate treatment. The article also reviews the pathogenesis, clinical manifestations, diagnostic approaches, and therapeutic strategies for LGI1 antibody-associated encephalitis, aiming to enhance clinical awareness and optimize patient outcomes.

Background: The majority of individuals at ultra-high risk (UHR) for psychosis do not transition to a full threshold psychotic disorder. It is therefore important to understand their longer-term clinical and functional outcomes, particularly given the high prevalence of comorbid mental disorders in this population at baseline.

Aims: This study investigated the prevalence of non-psychotic disorders in the UHR population at entry and long-term follow-up and their association with functional outcomes. Persistence of UHR status was also investigated.

Study design: The sample comprised 102 UHR young people from the Personal Assessment and Crisis Evaluation (PACE) Clinic who had not transitioned to psychosis by long-term follow-up (mean = 8.8 years, range = 6.8-12.1 years since baseline).

Results: Eighty-eight percent of participants at baseline were diagnosed with at least one mental disorder, the majority of which were mood disorders (78%), anxiety disorders (35%), and substance use disorders (SUDs) (18%). This pattern of disorder prevalence continued at follow-up, though prevalence was reduced, with 52% not meeting criteria for current non-psychotic mental disorder. However, 35% of participants developed a new non-psychotic mental disorder by follow-up. Presence of a continuous non-psychotic mental disorder was associated with poorer functional outcomes at follow-up. 28% of participants still met UHR criteria at follow-up.

Conclusions: The study adds to the evidence base that a substantial proportion of UHR individuals who do not transition to psychosis experience persistent attenuated psychotic symptoms and persistent and incident non-psychotic disorders over the long term. Long-term treatment and re-entry into services is indicated.

Background and hypothesis: Psychosis-associated diagnostic codes are increasingly being utilized as case definitions for electronic health record (EHR)-based algorithms to predict and detect psychosis. However, data on the validity of psychosis-related diagnostic codes is limited. We evaluated the positive predictive value (PPV) of International Classification of Diseases (ICD) codes for psychosis.

Study design: Using EHRs at 3 health systems, ICD codes comprising primary psychotic disorders and mood disorders with psychosis were grouped into 5 higher-order groups. 1133 records were sampled for chart review using the full EHR. PPVs (the probability of chart-confirmed psychosis given ICD psychosis codes) were calculated across multiple treatment settings.

Study results: PPVs across all diagnostic groups and hospital systems exceeded 70%: Mass General Brigham 0.72 [95% CI 0.68-0.77], Boston Children's Hospital 0.80 [0.75-0.84], and Boston Medical Center 0.83 [0.79-0.86]. Schizoaffective disorder PPVs were consistently the highest across sites (0.80-0.92) and major depressive disorder with psychosis were the most variable (0.57-0.79). To determine if the first documented code captured first-episode psychosis (FEP), we excluded cases with prior chart evidence of a diagnosis of or treatment for a psychotic illness, yielding substantially lower PPVs (0.08-0.62).

Conclusions: We found that the first documented psychosis diagnostic code accurately captured true episodes of psychosis but was a poor index of FEP. These data have important implications for the case definitions used in the development of risk prediction models designed to predict or detect undiagnosed psychosis.

Background and hypothesis: Cognitive control deficits are prominent in individuals with psychotic psychopathology. Studies providing evidence for deficits in proactive control generally examine average performance and not variation across trials for individuals-potentially obscuring detection of essential contributors to cognitive control. Here, we leverage intertrial variability through drift-diffusion models (DDMs) aiming to identify key contributors to cognitive control deficits in psychosis.

Study design: People with psychosis (PwP; N = 122), their first-degree biological relatives (N = 78), and controls (N = 50) each completed 120 trials of the dot pattern expectancy (DPX) cognitive control task. We fit full hierarchical DDMs to response and reaction time (RT) data for individual trials and then used classification models to compare the DDM parameters with conventional measures of proactive and reactive control.

Study results: PwP demonstrated slower drift rates on proactive control trials suggesting less efficient use of cue information. Both PwP and relatives showed protracted nondecision times to infrequent trial sequences suggesting slowed perceptual processing. Classification analyses indicated that DDM parameters differentiated between the groups better than conventional measures and identified drift rates during proactive control, nondecision time during reactive control, and cue bias as most important. DDM parameters were associated with real-world functioning and schizotypal traits.

Conclusions: Modeling of trial-level data revealed that slow evidence accumulation and longer preparatory periods are the strongest contributors to cognitive control deficits in psychotic psychopathology. This pattern of atypical responding during the DPX is consistent with shallow basins in attractor dynamic models that reflect difficulties in maintaining state representations, possibly mediated by excess neural excitation or poor connectivity.

Background: To provide precision cognitive remediation therapy (CR) for schizophrenia, we need to understand whether the mechanism for improved functioning is via cognition improvements. This mechanism has not been rigorously tested for potential moderator effects.

Study design: We used data (n = 377) from a randomized controlled trial using CIRCuiTS, a therapist-supported CR, with participants from first-episode psychosis services. We applied structured equation modeling to test whether: (1) CR hours explain the goal attainment functional outcome (GAS) at posttreatment, (2) global cognitive improvement mediates GAS, and if (3) total symptoms moderate the CR hours to cognitive improvement pathway, and/or negative symptoms moderate the cognition to functioning pathway, testing moderator effects via the mediator or directly on CR hours to functioning path.

Study results: CR produced significant functioning benefit for each therapy hour (Coeff = 0.203, 95% CI 0.101-0.304, P < .001). The mediated path from CR hours to cognition and cognition to functioning was small and nonsignificant (Coeff = 0.014, 95% CI = -0.010, 0.037, P = .256). Total symptoms did not moderate the path to cognition (P = .211) or the direct path to outcome (P = .896). However, negative symptoms significantly moderated the effect of cognitive improvements on functioning (P = .015) with high negative symptoms reducing the functional gains of improved cognition.

Conclusions: Although cognitive improvements were correlated with functioning benefit, they did not fully explain the positive effect of increased therapy hours on functioning, suggesting additional CR factors also contribute to therapy benefit. Negative symptoms interfere with the translation of cognitive improvements into functional gains so need consideration.