Within-Person Relationship between Attenuated Positive Symptoms and Suicidal Ideation among Individuals at Clinical High Risk for Psychosis.

Individuals at clinical high-risk for psychosis (CHR-P) are at increased risk for suicide. However, the relationship between attenuated positive symptoms and suicidal ideation are not well understood, particularly as they interact over time. The current study addressed this gap in the literature. We hypothesized that greater attenuated symptoms would be concurrently and prospectively associated with suicidal ideation. Further, we hypothesized that suspiciousness and perceptual abnormalities would have the strongest relationship with suicidal ideation. Within-person variation in symptoms and suicidal ideation were examined across 24 treatment sessions for individuals at CHR-P. Attenuated positive symptoms (unusual thought content, suspiciousness, grandiose ideas, perceptual abnormalities, and disorganized communication) and suicidal ideation were assessed at each session. Logistic mixed effect models examined concurrent and time-lagged relationships between symptoms and suicidal ideation among 36 individuals at CHR-P. Results indicated that suicidal ideation was more likely during weeks when participants reported more severe total attenuated positive symptoms. Further, suspiciousness was uniquely associated with suicidal ideation, both concurrently and at the following session. Post hoc models examined the reverse direction of this relationship, demonstrating that suicidal ideation also prospectively predicted suspiciousness at the following session. These results suggest that within-person attenuated symptoms, particularly suspiciousness, are associated with suicidal ideation among individuals at CHR-P. However, the bidirectional relationship between suspiciousness and suicidal ideation raises questions about causal nature of this relationship. Further research is needed to examine the dynamic interplay of suspiciousness and suicidal ideation.

Variability in suicidal ideation during treatment for individuals at clinical high risk for psychosis: The importance of repeated assessment.

AIM: Suicide risk is elevated among individuals at clinical high risk for psychosis (CHR-P). The current study examined variability in suicidal ideation during treatment for individuals at CHR-P. METHODS: A retrospective chart review was used to examine the course of suicidal ideation during 16 sessions of individual psychotherapy for 25 individuals at CHR-P. RESULTS: Suicidal ideation was reported by 24% of participants at session 1 and 16% at session 16, with minimal within-subject change in the presence of suicidal ideation across the two time points. However, a more fine-grained investigation at each session indicated that 60% of individuals at CHR-P experienced suicidal ideation at least once during treatment. Additionally, there was great variability in suicidal ideation both within and between participants over the course of the 16 sessions. CONCLUSIONS: These findings highlight the importance of repeated assessment when examining suicidal ideation as a treatment outcome for individuals at CHR-P.

Symptomatic and Functional Outcomes Among Individuals at High Risk for Psychosis Participating in Step-Based Care.

Validated, multicomponent treatments designed to address symptoms and functioning of individuals at clinical high risk for psychosis are currently lacking. The authors report findings of a study with such individuals participating in step-based care-a program designed to provide low-intensity, non-psychosis-specific interventions and advancement to higher-intensity, psychosis-specific interventions only if an individual is not meeting criteria for a clinical response. Among individuals with symptomatic or functional concerns at enrollment, 67% met criteria for a symptomatic response (median time to response=11.1 weeks), and 64% met criteria for a functional response (median time to response=8.9 weeks).

Transcriptomic profiling of human choriodecidua during term labor: inflammation as a key driver of labor.

PROBLEM: Inflammation is a driver of labor in myometrium and cervix; however, the involvement of decidua is poorly defined. We have reported decidual leukocyte infiltration prior to and during labor; the regulators of these inflammatory processes are unknown. METHOD OF STUDY: Choriodecidua RNA obtained after term labor or elective cesarean delivery was applied to Affymetrix GeneChips. Pathway analysis and gene validation were performed. RESULTS: Extensive inflammatory activation was identified in choriodecidua following labor, predominantly upregulation of genes regulating leukocyte trafficking and cytokine signalling. Genes governing cell fate, tissue remodelling, and translation were also altered. Upregulation of candidate genes (ICAM1, CXCR4, CD44, TLR4, SOCS3, BCL2A, and IDO) was confirmed. NFκB, STAT1&3, HMGB1, and miRNA-21, miRNA-46, miRNA-141, and miRNA-200 were predicted upstream regulators. CONCLUSION: This study confirms inflammatory processes are major players in labor events in choriodecidua, as in other gestational tissues. Suppressing uterine inflammation is likely to be critical for arresting premature labor.

Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour.

Current therapies for preterm labour (PTL) focus on arresting myometrial contractions but are largely ineffective, thus alternative therapeutic targets need to be identified. Leukocytes infiltrate the uterus around the time of labour, and are in particularly abundant in decidua (maternal-fetal interface). Moreover, decidual inflammation precedes labour in rat pregnancies and thus may contribute to initiation of labour. We hypothesized that chemokines mediate decidual leukocyte trafficking during preterm labour (PTL) and term labour (TL), thus representing potential targets for preventing PTL. Women were recruited into 4 groups: TL, term not in labour (TNL), idiopathic PTL and PTL with infection (PTLI). Choriodecidual RNA was subjected to a pathway-specific PCR array for chemokines. Differential expression of 12 candidate chemokines was validated by real time RT-PCR and Bioplex assay, with immunohistochemistry to confirm cellular origin. 25 chemokines were upregulated in choriodecidua from TL compared to TNL. A similar pattern was detected in PTL, however a distinct profile was observed in PTLI consistent with differences in leukocyte infiltration. Upregulation of CCL2, CCL4, CCL5, CXCL8 and CXCL10 mRNA and protein was confirmed in TL, with CCL8 upregulated in PTL. Significant correlations were detected between these chemokines and decidual leukocyte abundance previously assessed by immunohistochemical and image analysis. Chemokines were primarily expressed by decidual stromal cells. In addition, CXCL8 and CCL5 were significantly elevated in maternal plasma during labour, suggesting chemokines contribute to peripheral inflammatory events during labour. Differences in chemokine expression patterns between TL and idiopathic PTL may be attributable to suppression of chemokine expression by betamethasone administered to women in PTL; this was supported by in vitro evidence of chemokine downregulation by clinically relevant concentrations of the steroid. The current study provides compelling evidence that chemokines regulate decidual leukocyte recruitment during labour. The 6 chemokines identified represent potential novel therapeutic targets to block PTL.