Impairments in Peripheral Blood T Effector and T Regulatory Lymphocytes in Bipolar Disorder Are Associated with Staging of Illness and Anti-cytomegalovirus IgG Levels.

There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined Teff/Treg subsets both before and after ex vivo anti-CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 symptomatic remitted BD patients and 21 healthy controls and assessed human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of unstimulated CD3 + CD8 + CD71+ and CD4 + CD25 + FOXP3 and increased CD4 + CD25 + FOXP3 + CD152+ frequencies and with lowered stimulated frequencies of CD3 + CD8 + CD71+, CD4 + CD25 + FOXP3 + CD152+, and CD4 + CD25 + FOXP3 + GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3 + CD4 + CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4 + CD25 + FOXP+GARP T phenotypes. In conclusion, in BD patients, immune injuries, staging, and HCMV seropositivity interact and cause CIRS dysfunctions and exaggerated IRS responses, which play a key role in parainflammation and neuroaffective toxicity. HCMV seropositivity contributes to an immune-risk phenotype in BD.

Self-reported data for mental workload modelling in human-computer interaction and third-level education.

Mental workload (MWL) is an imprecise construct, with distinct definitions and no predominant measurement technique. It can be intuitively seen as the amount of mental activity devoted to a certain task over time. Several approaches have been proposed in the literature for the modelling and assessment of MWL. In this paper, data related to two sets of tasks performed by participants under different conditions is reported. This data was gathered from different sets of questionnaires answered by these participants. These questionnaires were aimed at assessing the features believed by domain experts to influence overall mental workload. In total, 872 records are reported, each representing the answers given by a user after performing a task. On the one hand, collected data might support machine learning researchers interested in using predictive analytics for the assessment of mental workload. On the other hand, data, if exploited by a set of rules/arguments (as in [3]), may serve as knowledge-bases for researchers in the field of knowledge-based systems and automated reasoning. Lastly, data might serve as a source of information for mental workload designers interested in investigating the features reported here for mental workload modelling. This article was co-submitted from a research journal "An empirical evaluation of the inferential capacity of defeasible argumentation, non-monotonic fuzzy reasoning and expert systems" [3]. The reader is referred to it for the interpretation of the data.

Peripheral levels of superoxide dismutase and glutathione peroxidase in youths in ultra-high risk for psychosis: a pilot study.

IntroductionOxidative stress has been documented in chronic schizophrenia and in the first episode of psychosis, but there are very little data on oxidative stress prior to the disease onset. OBJECTIVE: This work aimed to compare serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in young individuals at ultra-high risk (UHR) of developing psychosis with a comparison healthy control group (HC). METHODS: Thirteen UHR subjects and 29 age- and sex-matched healthy controls (HC) were enrolled in this study. Clinical assessment included the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and the Global Assessment of Functioning (GAF) scale. Activities of SOD and GPx were measured in serum by the spectrophotometric method using enzyme-linked immunosorbent assay kits. RESULTS: After adjusting for age and years of education, there was a significant lower activity of SOD and lower GPX activity in the UHR group compared to the healthy control group (rate ratio [RR]=0.330, 95% CI 0.187; 0.584, p<0.001 and RR=0.509, 95% CI 0.323; 0.803, p=0.004, respectively). There were also positive correlations between GAF functioning scores and GPx and SOD activities. CONCLUSION: Our results suggest that oxidative imbalances could be present prior to the onset of full-blown psychosis, including in at-risk stages. Future studies should replicate and expand these results.

Differential Impact of Obesity on CD69 Expression in Individuals with Bipolar Disorder and Healthy Controls.

Preliminary evidence suggests that premature immunosenescence is involved in bipolar disorder (BD) pathophysiology. The cellular marker CD69 is expressed in T lymphocyte surface during their activation and its expression is negatively correlated with age. The objective of this study was to assess the moderating effects of obesity on the reduction of expression of CD69, a marker of immunosenescence. Forty euthymic patients with BD type I, aged 18-65 years, were included in this study. The healthy comparison group consisted of 39 volunteers who had no current or lifetime history of mental disorders, no use of psychotropic medications, and no known family history of mood disorders or psychosis. Peripheral blood mononuclear cells from BD patients and healthy controls were collected and isolated. The cells were allowed to grow in culture and stimulated for 3 days. CD69 was marked and read in flow cytometry. We found that the lower expression of CD69 in BD patients was moderated by body mass index (BMI) in both CD4+ (RR = 0.977, 95% CI 0.960-0.995, p = 0.013) and CD8+ cells (RR = 0.972, 95% CI 0.954-0.990, p = 0.003). Our findings indicate that BMI could potentially influence the process of premature aging in BD.

An immunological age index in bipolar disorder: A confirmatory factor analysis of putative immunosenescence markers and associations with clinical characteristics.

OBJECTIVES: The study aims to generate an immunological age (IA) trait on the basis of immune cell differentiation parameters, and to test whether the IA is related to age and disease characteristics. METHODS: Forty-four euthymic type I bipolar disorder patients were included in this study. Five immunosenescence-related parameters were assessed: proportions of late-differentiated cells (e.g., CD3+CD8+CD28-CD27- and CD3-CD19+IgD-CD27-), and the expression of CD69, CD71, and CD152 after stimulation. Confirmatory factor analysis was applied to generate an IA trait underling the 5 measures. RESULTS: The best-fit model was constituted by 4 parameters that were each related to an underlying IA trait, with 1 cell population positively correlated (CD3+CD8+CD28-CD27- [λ = 0.544, where λ represents the loading of the parameter onto the IA trait] and 3 markers negatively correlated (CD69 [λ = -0.488], CD71 [λ = -0.833], and CD152 [λ = -0.674]). The IA trait was associated with chronological age (ß = 0.360, p = .013) and the number of previous mood episodes (ß = 0.426, p = .006). In a mediation model, 84% of the effect between manic episodes, and IA was mediated by body mass index. CONCLUSION: In bipolar disorder type I, premature aging of the immune system could be reliably measured using an index that validated against chronological age, which was related to adverse metabolic effects of the disease course.

Leukocyte telomere length variation in different stages of schizophrenia.

Recent research has demonstrated that telomere maintenance might be a key integrating point for the cumulative effect of genetic and environmental factors in patients with first-episode psychosis (FEP) and schizophrenia (SCZ). Eighty-one participants with antipsychotic-naïve FEP, 173 with SCZ and 438 HC were enrolled in this study. Psychiatric diagnosis was assessed using the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I). The Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS) and Calgary Depression Scale for Schizophrenia (CDSS) were used to measure symptoms severity. Telomere length (TL) was determined using a multiplex qPCR assay. After adjustment for age, years of education, and smoking status, we found that patients with SCZ had longer TL (relative ratio (RR) = 1.08) than the HC group (RR = 1.00, Wald χ2 = 12.48, p = 0.002). Further, non-remitted SCZ patients presented longer TL (RR = 1.00) compared to remitted SCZ (RR = 0.88, Wald χ2 = 7.20, p = 0.007). TL in patients also correlated to psychopathology assessment in terms of total (p = 0.003) and positive PANSS scores (p = 0.001). No correlation with negative PANSS, YMRS, and CDSS or effects of medication was found on TL. Although the exact pathways underlying longer TL in SCZ patients remain unclear, these findings raise more questions than answers and suggest that TL may be of immense value on SCZ progression. Further studies are required to investigate the association of TL in FEP and SCZ.

A preliminary study of bipolar disorder type I by mass spectrometry-based serum lipidomics.

The present study aimed at investigating possible alterations in the serum lipid profile of euthymic patients with bipolar disorder type I (BD) compared to healthy controls (HC). Thirty-five individuals from both genders were recruited, with 14 diagnosed and treated as BD patients (BD group) and 21 healthy subjects (HC group). Clinical assessment was based on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Young Mania Rating Scale (YMRS), and 17-items of Hamilton Depression Rating Scale (HDRS-17) data, which were used to confirm diagnosis, to verify psychiatric comorbidities, and to estimate the severity of manic and depressive symptoms. Ultra-high performance liquid chromatography (UHPLC) coupled to high resolution mass spectrometry (HRMS) was applied to analyze the lipids extracted from all serum samples from both studied groups. In this pioneer and exploratory study, we observed different serum lipid profiles for BD and HC groups, especially regarding glycerophospholipid, glycerolipid, and sphingolipid distribution. Multivariate statistical analyses indicated that 121 lipids were significantly different between BD and HC. Phosphatidylinositols were identified as the most altered lipids in BD patient sera. The results of this preliminary study reinforce the role of lipid abnormalities in BD and offer additional methodological possibilities for investigation in the field.

Plasma copeptin and metabolic dysfunction in individuals with bipolar disorder.

AIM: This study aimed to compare plasma copeptin levels, the c-terminal of provasopressin, between individuals with bipolar disorder (BD) and healthy controls and to assess the relation between copeptin and metabolic parameters. METHODS: We measured plasma levels of copeptin in individuals with BD (n = 55) and healthy controls (n = 21). Information related to psychiatric/medical history, as well as to metabolic comorbidities and laboratorial parameters was also captured. Insulin resistance and ß-cell function in basal state were calculated from fasting plasma glucose and C-peptide using the HOMA2 calculator. Impaired glucose metabolism was defined as pre-diabetes or type 2 diabetes mellitus. Copeptin, adiponectin, and leptin plasma levels were determined by enzyme-linked immunosorbent assay. RESULTS: Plasma copeptin levels were lower in individuals with BD, relative to healthy controls (P < 0.001). There were significant interactions between BD and plasma copeptin on ß-cell function (rate ratio [RR] = 1.048; P = 0.030) and on leptin levels (RR = 1.087; P = 0.012), indicating that there was a positive correlation between these markers in the BD group, but a negative one in healthy controls. Finally, in individuals with BD only, the association between ß-cell function, body mass index (RR = 1.007; P < 0.001), and insulin resistance (RR = 1.001; P = 0.037) was moderated by copeptin levels. CONCLUSION: Copeptin levels were lower in individuals with BD than in healthy controls. There were differential associations between copeptin and metabolic parameters within the BD and healthy control subgroups, suggesting an association between abnormal copeptin and metabolic dysregulation only in the BD population.

1H-NMR, 1H-NMR T2-edited, and 2D-NMR in bipolar disorder metabolic profiling.

BACKGROUND: The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. METHODS: Metabolomic profiling, employing 1H-NMR, 1H-NMR T2-edited, and 2D-NMR spectroscopy and chemometrics of human blood serum samples from patients with bipolar disorder (n = 26) compared with healthy volunteers (n = 50) was performed. RESULTS: The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids (N-acetyl-L-phenyl alanine, N-acetyl-L-aspartyl-L-glutamic acid, L-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology. CONCLUSIONS: The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up.

Shorter leukocyte telomere length in patients at ultra high risk for psychosis.

Telomere length attrition has been demonstrated in schizophrenia but not in individuals in ultra high risk (UHR) for psychosis. The present study aimed to compare the leukocyte telomere length (TL) between patients at UHR for psychosis and healthy controls (HC). Twenty-two participants with UHR and 88 HC were enrolled in this study. Telomere lengths were determined using a multiplex qPCR assay. After adjustment for age, sex, ethnicity, and education, patients in UHR, compared with HC groups, had shorter telomere length (RR: 0.929, p=0.031). Shorter leukocyte telomere length in UHR could represent early signs of accelerated aging in this population.

Metabolomics and lipidomics analyses by 1H nuclear magnetic resonance of schizophrenia patient serum reveal potential peripheral biomarkers for diagnosis.

Using 1H NMR-based metabolomics in association to chemometrics analysis, we analyzed here the metabolic differences between schizophrenia patients (SCZ) compared to healthy controls (HCs). HCs and SCZ patients underwent clinical interview using the Structured Clinical Interview for DSM Disorders (SCID). SCZ patients were further assessed by Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning Scale (GAF), and Clinical Global Impressions Scale (CGI). Using the principal component analysis (PCA) and supervised partial least-squares discriminate analysis (PLS-DA) in obtained NMR data, a clear group separation between HCs and SCZ patients was achieved. Interestingly, all metabolite compounds identified as exclusively present in the SCZ group, except for the gamma-aminobutyric acid (GABA), were never previously associated with mental disorders. Although the initial perception of an absence of obvious biological link among the different key molecules exclusively observed in each group, and no identification of any specific pathway yet, the present work represents an important contribution for the identification of potential biomarkers to inform diagnosis, as it was possible to completely separate the affected SCZ patients from HCs, with no outliers or exceptions. In addition, the data presented here reinforced the role of the modulation of glycolysis pathway and the loss of GABA interneuron/hyperglutamate hypothesis in SCZ.

Selfish brain and selfish immune system interplay: A theoretical framework for metabolic comorbidities of mood disorders.

According to the "selfish brain" theory, the brain regulates its own energy supply influencing the peripheral metabolism and food intake according to its needs. The immune system has been likewise "selfish" due to independent energy consumption; and it may compete with the brain (another high energy-consumer) for glucose. In mood disorders, stress in mood episodes or physiological stress activate homeostasis mechanisms from the brain and the immune system to solve the imbalance. The interaction between the selfish brain and the selfish immune system may explain various conditions of medical impairment in mood disorders, such as Metabolic Syndrome (MetS), obesity, type 2 diabetes mellitus (T2DM) and immune dysregulation. The objective of this study is to comprehensively review the literature regarding the competition between the brain and the immune system for energy substrate. Targeting the energetic regulation of the brain and the immune system and their cross-talk open alternative treatments and a different approach in the study of general medical comorbidities in mood disorders, although more investigation is needed.

The effect of the severity of obstructive sleep apnea syndrome on telomere length.

Aging is associated with an increase in the prevalence of obstructive sleep apnea syndrome (OSAS) as well as the shortening of telomeres. It is known that OSAS-related factors are stimuli that can contribute to the acceleration of cellular senescence. Thus, the present study aimed to compare the leukocyte telomere length (LTL) between OSAS patients and controls, as well as to verify the correlation between LTL and sleep parameters. We used DNA extracted of 928 individuals from EPISONO to measure the LTL by the quantitative real-time polymerase chain reaction. All individuals were subjected to one full-night polysomnography. LTL was significantly shorter in OSAS patients compared to controls. The results showed negative correlations between LTL and the following variables: apnea-hypopnea index, respiratory disturbance index, desaturation index and wake after sleep onset. LTL was positively correlated with sleep efficiency, total sleep time, basal, minimum and maximum oxygen saturation. Lastly, it was observed that OSAS severity was associated with shorter LTL even after adjusting for sex, age, years of schooling, body mass index, diabetes, stroke and heart attack. In conclusion, our study indicates the presence of an association between LTL and OSAS and a significant impact of severity of OSAS in telomeres shortening.

Inter-relation between brain-derived neurotrophic factor and antioxidant enzymes in bipolar disorder.

OBJECTIVES: Accumulating evidence indicates that oxidative stress and neurotrophins have a bidirectional relationship. In this post hoc, exploratory analysis, we investigated the association between plasma brain-derived neurotrophic factor (BDNF) levels and activities of the antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD) in individuals with bipolar disorder (BD) and healthy controls. METHODS: We measured plasma levels of BDNF and activities of GPx and SOD in individuals with BD (n=59) and healthy controls (n=26). Information related to current and past psychiatric/medical history, as well as to metabolic comorbidities, was also reported. RESULTS: There were negative correlations between BDNF, GPx (r=-.449, P≤.001) and GPx/SOD ratio (r=-.503, P<.001), and a positive correlation between BDNF and SOD (r=.254, P=.020). There was a moderating effect of body mass index (BMI) on the association between BDNF and GPx/SOD rate ratio [(RR)=1.002, P=.034]; interactions between impaired glucose metabolism (IGM), GPx (RR=1.016, P=.033), and GPx/SOD ratio (RR=1.026, P=.002) were also observed. These results were significant in models that included age, gender, alcohol, tobacco and medication use. CONCLUSIONS: There was a robust and independent correlation between peripheral BDNF and antioxidant enzyme activities in individuals with BD, which was moderated by metabolic comorbidities. These results reinforce the concept that these systems are associated and further extend knowledge of the putative effect of metabolic comorbidities in the pathophysiological substrates of BD.

Peripheral immuno-inflammatory abnormalities in ultra-high risk of developing psychosis.

BACKGROUND: Immuno-inflammatory imbalances have been documented in schizophrenia, but very little is known about the immunological changes prior to the onset of disease. OBJECTIVE: This work aimed to compare serum levels of pro- and anti-inflammatory cytokines in young subjects at ultra-high risk (UHR) of developing psychosis with age- and sex-matched healthy controls. METHODS: A total of 12 UHR and 16 age- and sex-matched healthy controls (HC) subjects were enrolled in this study. Clinical profile was assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS), Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and Global Assessment of Functioning (GAF) scale. Serum interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, IFN-γ, and IL-17 were measured by flow cytometry using the Th1/Th2/Th17 cytometric bead array. RESULTS: Compared with the healthy control group, patients in UHR showed increased IL-6 levels (Z=-2.370, p=0.018) and decreased IL-17 levels in serum (Z=-1.959, p=0.050). Levels of IL-17 positively correlated to the values in GAF symptoms (rho=0.632, p=0.028). CONCLUSION: Our results suggest that immunological imbalances could be present in the early stages of psychosis, including in at-risk stages. Future studies should replicate and expand these results.

Bipolar disorder course, impaired glucose metabolism and antioxidant enzymes activities: A preliminary report.

This study aimed to examine the role of oxidative stress in bipolar disorder (BD) by evaluating the relationship among antioxidant enzymes activities, impaired glucose metabolism (IGM) and illness course. We measured the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPx) in individuals with BD (N = 55) and healthy controls (N = 28). Information related to current and past psychiatric/medical history, as well as prescription of any pharmacological treatments was captured. Impaired glucose metabolism was operationalized as pre-diabetes or type 2 diabetes mellitus. Our results showed that, after adjustment for age, gender, alcohol use, smoking and current medication, both BD (p < 0.001) and IGM (p = 0.019) were associated with increased GPx activity, whereas only BD was associated with decreased SOD activity (p = 0.008). We also observed an interaction between BD and IGM on SOD activity (p = 0.017), whereas the difference between BD and controls was only significant in individuals with IGM (p = 0.009). IGM, GPx and SOD activity were independently associated with variables of illness course. Moreover, IGM moderated the association between SOD activity and number of mood episodes (p < 0.001), as a positive correlation between SOD activity and mood episodes was observed only in participants with IGM. In conclusion, BD and IGM are associated with independent and synergistic effects on markers of oxidative stress. The foregoing observations suggest that the heterogeneity observed in previous studies evaluating antioxidant enzymes in BD may be a function of concurrent IGM; and that imbalances in the oxidative system may subserve the association between BD and IGM, as well as its relationship with illness course.

Crack cocaine addiction, early life stress and accelerated cellular aging among women.

BACKGROUND: Early life stress (ELS) and addiction are related to age-related diseases and telomere shortening. However, the role of telomere length (TL) in crack cocaine addiction remains unknown. The purpose of this study was to investigate the TL in a sample of crack cocaine dependent-women who reported an ELS history and in a community-based sample of elderly women as a reference group for senescence. METHODS: This study included treatment seeking crack cocaine dependents women (n=127) and elderly women without a psychiatric diagnosis (ELD, n=49). The crack cocaine sample was divided in two groups according to their Childhood Trauma Questionnaire (CTQ) scores: presence of history of childhood abuse and neglect (CRACK-ELS) and absence of ELS history (CRACK). TL was assessed by T/S ratio obtained from peripheral blood DNA using quantitative PCR assay. RESULTS: CRACK and CRACK-ELS subjects exhibited shortened TL in comparison to the ELD group, despite their younger age. Among crack cocaine sample, CRACK-ELS group had significantly shorter telomeres than the CRACK group. Correlation analysis within crack cocaine group indicated that TL was negatively correlated with emotional abuse scores. CONCLUSIONS: These results support previous findings associating telomere shortening with both ELS and drug addiction. This study suggests new evidence of a distinct biological phenotype for drug-dependent women with ELS. The results support the biological senescence hypothesis underpinning ELS experience.

Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course.

OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism (IGM) on plasma levels of BDNF in individuals with BD, and on the relationship between BDNF and variables of illness course. METHODS: We measured and compared the plasma levels of BDNF in individuals with BD (n=57) and healthy controls (n=26). IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured. RESULTS: Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (P<.001), psychiatric hospitalizations (P=.001) and suicide attempts (P=.021). IGM moderated the association between BDNF and the number of previous mood episodes (P<.001), wherein there was a positive correlation in euglycemic participants and a negative correlation in individuals with IGM. CONCLUSIONS: BD is independently associated with lower levels of BDNF; IGM may modify the relationship between BDNF and BD course, suggesting an interactive effect of BDNF with metabolic status on illness progression.

Association of serum interleukin-6 with mental health problems in children exposed to perinatal complications and social disadvantage.

There is consistent evidence that inflammation is involved in mental disorders pathogenesis. Herein, using data from the High Risk Cohort Study for Psychiatric Disorders, we investigated the relationship between parental mood disorders (PMD), environmental factors, serum interleukin-6 (IL6) and mental health problems in children aged 6-12. We measured the serum levels of IL6 in 567 children. Information related to socio-demographic characteristics, mental health problems and multiple risk factors, as well as parent's psychiatric diagnosis, was captured. We evaluated two groups of environmental risk factors (i.e. perinatal complications and social disadvantage) using a cumulative risk model. Results showed that higher serum levels of IL6 were associated with PMD (RR=1.072, p=0.001), perinatal complications (RR=1.022, p=0.013) and social disadvantage (RR=1.024, p=0.021). There was an interaction between PMD and social disadvantage (RR=1.141, p=0.021), as the effect of PMD on IL6 was significantly higher in children exposed to higher levels of social disadvantage. Moreover, there was a positive correlation between IL6 and mental health problems (RR=1.099, p=0.026), which was moderated by exposure to perinatal complications or social disadvantage (RR=1.273, p=0.015 and RR=1.179, p=0.048, respectively). In conclusions, there is evidence of a differential inflammatory activation in children with PMD and exposure to environmental risk factors, when compared to matched peers. Systemic inflammation may be involved in the pathway linking familial risk and mental health problems.

Serum copeptin in children exposed to maltreatment.

AIM: Childhood maltreatment (CM) has been related to a persistent reprograming of stress-response. Copeptin is a marker of hypothalamic-pituitary-adrenal axis activation; however, few studies have examined copeptin levels in children exposed to CM. The aim of this study was to compare serum copeptin levels in children reporting child abuse and/or neglect and children with no history of CM. METHODS: This study included 65 children with a positive history of moderate to severe CM, as reported by themselves and their parent(s) during a clinical interview, and 71 children with no history of CM as a comparison group. CM was considered moderate to severe based on the child-reported frequency of being exposed to events related to sexual abuse, physical abuse, emotional abuse, emotional neglect, and/or physical neglect. Child psychopathology symptoms were assessed using the Child Behavior Checklist (CBCL). We measured serum copeptin concentration using enzyme-linked immunosorbent assay. RESULTS: Children exposed to CM exhibited higher levels of serum copeptin compared to children without CM when controlling for sex, age, and psychiatric morbidity. The CBCL total score, including internalizing and externalizing symptoms, was higher in children with CM. We found no correlation between copeptin and CBCL scores for internalizing symptoms and externalizing symptoms. CONCLUSION: CM is associated with copeptin serum levels independently of age, sex, and symptom severity. Copeptin is a promising new biomarker for children with a history of abuse and/or neglect.