Complex post-traumatic stress disorder (CPTSD) of ICD-11 in youths with childhood maltreatment: Associations with age of exposure and clinical outcomes.

BACKGROUND: Exposure to childhood maltreatment (CM) increases the risk of psychiatric morbidity in youths. The new Complex Post-Traumatic Stress Disorder (CPTSD) diagnosis captures the heterogeneity and complexity of clinical outcomes observed in youths exposed to CM. This study explores CPTSD symptomatology and its association with clinical outcomes, considering the impact of CM subtypes and age of exposure. METHODS: Exposure to CM and clinical outcomes were evaluated in 187 youths aged 7-17 (116 with psychiatric disorder; 71 healthy controls) following the Tools for Assessing the Severity of Situations in which Children are Vulnerable (TASSCV) structured interview criteria. CPTSD symptomatology was explored by confirmatory factor analysis, considering four subdomains: post-traumatic stress symptoms, emotion dysregulation, negative self-concept and interpersonal problems. RESULTS: Youths exposed to CM (with or without psychiatric disorders) showed greater internalizing, externalizing and other symptomatology, worse premorbid adjustment and poorer overall functioning. Youth with psychiatric disorder and exposed to CM reported more CPTSD symptomatology, psychiatric comorbidity and polypharmacy and earlier onset of cannabis use. Different subtypes of CM and the developmental stage of exposure differentially impact CPTSD subdomains. LIMITATIONS: Small percentage of resilient youths was studied. It was not possible to explore specific interactions between diagnostic categories and CM. Direct inference cannot be assumed. CONCLUSIONS: Gathering information on type and age of exposure to CM is clinically useful to understand the complexity of psychiatric symptoms observed in youths. Inclusion of the CPTSD diagnosis should increase the implementation of early specific interventions, improving youths' functioning and reducing the severity of clinical outcomes.

NOD2 receptors in adenopituitary folliculostellate cells: expression and function.

Folliculostellate cells (FS cells) are non-endocrine cells from the pituitary gland that respond to bacterial endotoxins by producing cytokines. In immune cells, an important component of bacterial recognition are the toll-like receptors (TLRs). Previously, we showed that FS cells express TLR4. The TLR4 ligand lipopolysaccharide (LPS) stimulates interleukin-6 (IL6) production through nuclear factor kappaB (NFKB) induction. Binding of IL6 to gp130 receptor activates signal transducer and activator of transcription 3 (STAT3), an important mediator of inflammatory response. Another family involved in innate immune response following bacterial infection is the nucleotide-binding oligomerisation domain (NOD) intracellular receptor family. Herein, we describe for the first time the expression and function of NOD receptors in human pituitary and FS TtT/GF cell line. The NOD2 agonist muramyl dipeptide (MDP) increased Nf kappa b1-transcriptional activity, -protein expression and IL6 secretion in TtT/GF cells. Furthermore, these effects were potentiated by the combination of MDP and LPS. Silencing NOD2 abolished the action of LPS on NFKB transcriptional activity and IL6 production, indicating that, in TtT/GF cells, TLR4 transduces its signal through NOD2 receptor. We show here that in TtT/GF cells, Nod2 overexpression or stimulation by MDP increased STAT3 transcriptional activity. Furthermore, silencing STAT3 inhibited basal, LPS and MDP stimulated NFKB protein expression and overexpression of protein inhibitor of activated STAT3 (Pias3) markedly decreased basal NFKB activity. These data suggest that in TtT/GF cells, STAT3 acting upstream to NFKB mediates NOD2 receptor signalling pathway. In conclusion, the present study demonstrates that NOD molecules play a modulatory role in the pituitary by regulating the function and activation of FS cells in response to bacterial components.