Systemic Elevation of n-3 Polyunsaturated Fatty Acids (n-3-PUFA) Is Associated with Protection against Visual, Motor, and Emotional Deficits in Mice following Closed-Head Mild Traumatic Brain Injury.

Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration leading to various pathological complications such as motor and sensory (visual) deficits, cognitive impairment, and depression. N-3 polyunsaturated fatty acid (n-3 PUFA) containing lipids are known to be anti-inflammatory, whereas the sphingolipid, ceramide (Cer), is an inducer of neuroinflammation and degeneration. Using Fat1+-transgenic mice that contain elevated levels of systemic n-3 PUFA, we tested whether they are resistant to mild TBI-mediated sensory-motor and emotional deficits by subjecting Fat1-transgenic mice and their WT littermates to focal cranial air blast (50 psi) or sham blast (0 psi, control). We observed that visual function in WT mice was reduced significantly following TBI but not in Fat1+-blast animals. We also found Fat1+-blast mice were resistant to the decline in motor functions, depression, and fear-producing effects of blast, as well as the reduction in the area of oculomotor nucleus and increase in activated microglia in the optic tract in brain sections seen following blast in WT mice. Lipid and gene expression analyses confirmed an elevated level of the n-3 PUFA eicosapentaenoic acid (EPA) in the plasma and brain, blocking of TBI-mediated increase of Cer in the brain, and decrease in TBI-mediated induction of Cer biosynthetic and inflammatory gene expression in the brain of the Fat1+ mice. Our results demonstrate that suppression of ceramide biosynthesis and inflammatory factors in Fat1+-transgenic mice is associated with significant protection against the visual, motor, and emotional deficits caused by mild TBI. This study suggests that n-3 PUFA (especially, EPA) has a promising therapeutic role in preventing neurodegeneration after TBI.

The Association between Plasma ERVWE1 Concentrations and Affective Symptoms during Pregnancy: Is This a Friendly Alien?

Human endogenous retroviruses (HERVs) comprise 8% of the human genome, and HERV DNA was reported to be essential in human embryonic development. Specifically, HERV-W encodes a protein, syncytin-1, alternatively known as ERVWE1 (Human Endogenous Retrovirus W EnvC7-1 Envelope Protein), participating in human placental morphogenesis and having a role in immune system regulation. Syncytin-1 activity is increased in neuropsychiatric disorders, autoimmune diseases, and cancer. In our study, forty-four women in the third trimester of pregnancy were tested for ERVWE1 plasma levels. In concomitance with blood samples the following rating scales were administered to women: the Edinburgh Postnatal Depression Scale (EPDS), State Anxiety Inventory (STAI-S), Trait Anxiety Inventory (STAI-T), and Prenatal Attachment Inventory (PAI). We found that higher ERVWE1 protein plasma levels were significantly associated with higher PAI scores (p = 0.02), an earlier gestational age at the time of blood collection (p = 0.01), a longer duration of symptoms (p = 0.03), and fewer lifetime attempted suicides (p = 0.02). Our results seem to support the role of ERVWE1 in maintaining clinical psychiatric symptoms as a result of potential prolonged inflammation. At the same time, this protein may have a protective role in pregnant women by a reduction of suicidal behavior and a better mother-fetus relationship.

Alexithymia, suicide ideation, affective temperaments and homocysteine levels in drug naïve patients with post-traumatic stress disorder: an exploratory study in the everyday 'real world' clinical practice.

Objective: The present exploratory study aimed to investigate relationships between alexithymia, suicide ideation, affective temperaments and homocysteine levels among drug-naïve adult outpatients with Post-Traumatic Stress Disorder (PTSD) in an everyday 'real world' clinical setting.Method: Sixty-four adult outpatients with PTSD were evaluated using the Davidson Trauma Scale (DTS), the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI), the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego-Autoquestionnaire. As well, homocysteine levels were measured.Results: Alexithymic subjects showed higher values on all scales but not homocysteine levels. Partial correlations showed that almost all studied variables were correlated with each other, except homocysteine levels. Regression analysis showed that higher disorder severity as measured by DTS and TAS-20 'Difficulty in Identifying Feelings' dimension was associated with higher SSI scores.Conclusions: In conclusion, alexithymic PTSD outpatients may be characterised by higher disorder severity and difficulty in identifying feelings that may be linked to increased suicide ideation, regardless of affective temperaments or homocysteine levels. Homocysteine levels were not related to any studied variable. However, study limitations are discussed and must be considered. KeypointsPatients with alexithymia showed increased PTSD severity, a higher score on TEMPS-A subscales, and more severe suicide ideation.The Difficulty in Identifying Feelings (DIF) dimension of TAS-20 was associated with suicide ideation in patients with PTSD.Homocysteine did not correlate with any studied variables.This study was exploratory and cross-sectional: further larger and prospective studies are needed.

Elevated Gestational IL-13 During Fetal Development Is Associated With Hyperactivity and Inattention in Eight-Year-Old Children.

Maternal immune activation (MIA) during fetal development leads to behavioral and psychological disorders in the offspring. Concomitantly, insufficient supply of polyunsaturated fatty acids (PUFAs) is suspected to contribute to early neuronal maldevelopment due to the immune modulatory capabilities of PUFAs. However, human data are missing considering both of these aspects and their impact on children's behavioral outcomes. In line, this study aimed to elucidate the influence of gestational cytokines and PUFA-containing lipids during late pregnancy on behavioral sequelae in childhood, particularly focusing on an immune activation shaped by a history of maternal atopic diseases instead of a pathogen-mediated immune response. Based on the prospective mother-child cohort LINA we assessed the unstimulated blood cytokine profiles and concentrations of PUFA-containing lipids of 293 mothers at the 34th week of pregnancy. Maternal history of atopic diseases was obtained from questionnaires and behavior in eight-year-old children was assessed by the standardized Strength and Difficulties Questionnaires (SDQ) generating scores for hyperactivity/inattention, emotional symptoms, conduct problems, and peer relationship problems. Elevated IL-13 increased the risk for the child to show behavioral difficulties, in particular, hyperactive/inattentive behavior [adj. OR (95% CI): 2.47 (1.51-4.02), n = 255 vs. 38] at the age of eight years. Although the presence of maternal atopic dermatitis (AD) was associated with increased gestational IL-13 concentrations [adj. MR (95% CI): 1.17 (1.04-1.32)], no effect on children's behavioral difficulties was observed. However, a decrease in the PUFA containing lipid species PC aa C38:6 was not only associated with an increased gestational IL-13 concentration but also mediated the indirect effect of low PC aa C38:6 concentrations on children's abnormal behavior independent of maternal AD. We additionally assessed whether maternal IL-13 and PC aa C38:6 concentrations translate their effect by altering children's cord blood PC aa C38:6 and IL-13. While also the children's cord blood IL-13 was related to children's behavior, no effect of children's PC aa C38:6 was observed. This is the first study demonstrating that elevated gestational IL-13 increases the risk for children to develop behavioral difficulties. Analyses suggest that a reduced supply of gestational PC aa C38:6 contributes to elevated gestational IL-13 leading to behavioral sequelae in the offspring.

IL-18 Serum Levels and Variants of the Serotonin Transporter Gene Are Related to Awareness of Emotions in Healthy Subjects: A Preliminary Study.

OBJECTIVE: Interaction between the nervous and immune systems may influence emotions, ultimately affecting human health. Cytokines may play a role in developing emotional dysregulation as in alexithymia, a personality construct characterized by the subclinical inability to identify and describe emotions, often associated with several psychiatric and psychosomatic disorders. The proinflammatory cytokine IL-18, with a recognized role in brain functions, may influence serotonin metabolism and appears to be associated with alexithymia. Healthy individuals carrying the long allele (L) of the serotonin transporter gene polymorphic region (5-HTTLPR), and thus having lower concentrations of serotonin in the synaptic cleft, show a greater tendency toward alexithymia, with some gender differences. To explore a potential physiological interaction between IL-18, serotonin neurotransmission, and alexithymia, we investigated whether IL-18 serum levels and 5-HTTLPR are linked to alexithymic traits in healthy subjects. METHODS: We measured IL-18 serum levels in 115 Italian-Caucasian healthy subjects genotyped for 5-HTTLPR allele variants, divided by gender and assessed for alexithymia scores using the 20-item Toronto Alexithymia Scale. RESULTS: IL-18 levels are significantly more elevated in individuals with the LL genotype (n = 25) than in carriers of the short allele (n = 90, p = 0.0073). Specifically, in LL males (n = 11), i.e., the group with the most relevant increase in IL-18, cytokine values positively correlated with difficulty identifying feelings, which is a component of alexithymia (r = 0.634, p = 0.036). CONCLUSIONS: These results indicate a possible novel interaction between IL-18 and the serotoninergic system to mediate emotional unawareness, suggesting putative biological predictors of emotional dysregulation, which in turn can act as a risk factor for a variety of medical conditions in susceptible subjects.

Emotional hyper-reactivity and cardiometabolic risk in remitted bipolar patients: a machine learning approach.

OBJECTIVE: Remitted bipolar disorder (BD) patients frequently present with chronic mood instability and emotional hyper-reactivity, associated with poor psychosocial functioning and low-grade inflammation. We investigated emotional hyper-reactivity as a dimension for characterization of remitted BD patients, and clinical and biological factors for identifying those with and without emotional hyper-reactivity. METHOD: A total of 635 adult remitted BD patients, evaluated in the French Network of Bipolar Expert Centers from 2010-2015, were assessed for emotional reactivity using the Multidimensional Assessment of Thymic States. Machine learning algorithms were used on clinical and biological variables to enhance characterization of patients. RESULTS: After adjustment, patients with emotional hyper-reactivity (n = 306) had significantly higher levels of systolic and diastolic blood pressure (P < 1.0 × 10-8 ), high-sensitivity C-reactive protein (P < 1.0 × 10-8 ), fasting glucose (P < 2.23 × 10-6 ), glycated hemoglobin (P = 0.0008) and suicide attempts (P = 1.4 × 10-8 ). Using models of combined clinical and biological factors for distinguishing BD patients with and without emotional hyper-reactivity, the strongest predictors were: systolic and diastolic blood pressure, fasting glucose, C-reactive protein and number of suicide attempts. This predictive model identified patients with emotional hyper-reactivity with 84.9% accuracy. CONCLUSION: The assessment of emotional hyper-reactivity in remitted BD patients is clinically relevant, particularly for identifying those at higher risk of cardiometabolic dysfunction, chronic inflammation, and suicide.

The relationship between inflammatory state and quantity of affective episodes in bipolar disorder.

OBJECTIVES: Immunological/inflammatory processes have been proposed to play an important role in the pathophysiology of mood disorders, including bipolar disorder (BD). The present study aimed to examine the influence of immune activation, measured on the basis of inflammatory markers, on the course of illness, proxied by the number of affective episodes, in patients with BD. METHODS: We investigated the relationship between high-sensitive CRP (hsCRP) and Interleukin 6 (IL-6), two inflammatory markers and characteristics of course of illness (e.g. number of affective episodes, depressive and manic symptoms) amongst a group of 190 individuals with BD. RESULTS: Among females with BD, there was a positive correlation between levels of hsCRP and the number of manic and depressive episodes. Moreover, levels of hsCRP and IL-6 were positively correlated with current manic symptoms, as measured by Young-Mania-Rating-Scale. There were no significant correlations between levels of the foregoing inflammatory markers, and manic and depressive symptoms in male individuals with BD. Furthermore, compared to their untreated counterparts, female patients treated with lithium demonstrated higher levels of hsCRP and male patients treated with atypical antipsychotics lower levels of hsCRP, respectively. CONCLUSIONS: Our results are suggesting that the association between inflammatory state and affective response in patients with BD may be gender-dependent. A future research would be to evaluate whether or not these gender differences can be observed in other inflammatory pathways associated with BD.

Catechol-O-methyltransferase Val158Met polymorphism associates with affect and cortisol levels in women.

Introduction: We tested the extent to which the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with affective state and evening cortisol levels. We limited our study to women as previous research suggests that the link between COMT genotype and psychological health is entangled by sex differences. Materials and Methods: The participants were assessed on measures of anxiety, mood disturbance, depressive symptomatology, and perceived stress. We also evaluated participants on a quality of life measures that included two emotion domains and two physical domains (physical health and environment). Results: We found that under normal (nonstress) conditions, the COMT A allele (Met carriers, higher dopamine) associates with healthier affect and lower afternoon cortisol levels in women. These effects were limited to affective measures and not to physical or environmental quality of life. Conclusions: These findings help to shed light on the complex nature of COMT and emotion, and suggest that both sex and task condition (stress vs. nonstress) should be considered when examining the relationship between COMT genotype and emotion.

[EVALUATION OF QUALITY OF LIFE IN PATIENTS WITH METABOLIC SYNDROME].

The aim of the research - to assess physical and psychological state of health of patients with metabolic syndrome. The total number of participants in the study was 300 people. All respondents were divided into three groups. The first group included 100 people practically healthy, the second group 100 people without MS and the third group 100 people with a reliable diagnosis of the metabolic syndrome. To assess the physical and psychological components of the QOL, the «SF-36 Health Status Survery¼ questionnaire was used. The results of the study showed that the indices of the physical and psychological components of QOL in patients with metabolic syndrome were reduced by 3 (p<0.05) compared to the control group, which indicated the effect of the metabolic syndrome on QL. In patients with MS compared with the control group (1 group), the psychological component as a vital activity was reduced by 45%, role functioning due to emotional state by 55%, mental health by 33%, social functioning by 50%. The results of the questionnaire on the Special Questionnaire of the Hospital Scale of Anxiety and Depression (HADS) for the purpose of a detailed analysis of anxiety and depression showed that the level of anxiety and depression on the HADS scale depended on the duration and components of the MS. Indices of the physical and psychological component of QL in patients with MS significantly lower (p <0.05) comparing with the control group (practical healthy) and with the group without MS. The decrease in the physical (66.5%) and psychological (74%) state of QL health depends on the duration of the disease and on the components of the metabolic syndrome.

Neuroactive Steroids and Affective Symptoms in Women Across the Weight Spectrum.

3α-5α-Tetrahydroprogesterone, a progesterone metabolite also known as allopregnanolone, and 5α-androstane-3α,17ß-diol, a testosterone metabolite also known as 3α-androstanediol, are neuroactive steroids and positive GABAA receptor allosteric modulators. Both anorexia nervosa (AN) and obesity are complicated by affective comorbidities and hypothalamic-pituitary-gonadal dysregulation. However, it is not known whether neuroactive steroid levels are abnormal at the extremes of the weight spectrum. We hypothesized that serum allopregnanolone and 3α-androstanediol levels would be decreased in AN compared with healthy controls (HC) and negatively associated with affective symptoms throughout the weight spectrum, independent of body mass index (BMI). Thirty-six women were 1 : 1 age-matched across three groups: AN, HC, and overweight/obese (OW/OB). AN were amenorrheic; HC and OW/OB were studied in the follicular phase. Fasting serum neuroactive steroids were measured by gas chromatography/mass spectrometry. Mean Hamilton depression and anxiety scores were highest in AN (p<0.0001). Mean serum allopregnanolone was lower in AN and OW/OB than HC (AN 95.3±56.4 vs OW/OB 73.8±31.3 vs HC 199.5±167.8 pg/ml, p=0.01), despite comparable mean serum progesterone. Allopregnanolone levels, but not progesterone levels, were negatively associated with depression and anxiety symptom severity, independent of BMI. Serum 3α-androstanediol levels did not differ among groups and were not associated with depression or anxiety scores, despite a significant negative association between free testosterone levels and both anxiety and depression severity. In conclusion, women at both extremes of the weight spectrum have low mean serum allopregnanolone, which is associated with increased depression and anxiety severity, independent of BMI. Neuroactive steroids such as allopregnanolone may be potential therapeutic targets for depression and anxiety in traditionally treatment-resistant groups, including AN.

State-dependent alterations of lipid profiles in patients with bipolar disorder.

Objective Serum lipid levels may be associated with the affective severity of bipolar disorder, but data on lipid profiles in Asian patients with bipolar disorder and the lipid alterations in different states of opposite polarities are scant. We investigated the lipid profiles of patients in the acute affective, partial, and full remission state in bipolar mania and depression. Methods The physically healthy patients aged between 18 and 45 years with bipolar I disorder, as well as age-matched healthy normal controls were enrolled. We compared the fasting blood levels of glucose, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein of manic or depressed patients in the acute phase and subsequent partial and full remission with those of their normal controls. Results A total of 32 bipolar manic patients (12 women and 20 men), 32 bipolar depressed participants (18 women and 14 men), and 64 healthy control participants took part in this study. The mean cholesterol level in acute mania was significantly lower than that in acute depression (p < 0.025). The lowest rate of dyslipidemia (hypertriglyceridemia or low high-density lipoprotein cholesterol) was observed in acute bipolar mania. Conclusion Circulating lipid profiles may be easily affected by affective states. The acute manic state may be accompanied by state-dependent lower cholesterol and triglyceride levels relative to that in other mood states.

Living alone and activation of the renin-angiotensin-aldosterone-system: Differential effects depending on alexithymic personality features.

OBJECTIVE: Living alone is considered as a chronic stress factor predicting different health conditions and particularly cardiovascular disease (CVD). Alexithymia is associated with increased psychological distress, less social skills and fewer close relationships, making alexithymic subjects particularly susceptible to chronic stress imposed by "living alone". Only few studies investigated the renin-angiotensin-aldosterone-system (RAAS) activity in response to chronic stress. We aimed at evaluating the effects of "living alone" as a paradigm for chronic stress on RAAS activity and putatively differential effects depending on alexithymic personality features. METHODS: Alexithymia and serum concentrations of renin and aldosterone were measured in 944 subjects from the population-based SHIP-1 study. Subgroups were formed using the median of the Toronto Alexithymia Scale-20 (TAS-20) and a cohabitation status of "living alone" or "living together". Analyses were adjusted for various psychosocial, behavioral and metabolic risk factors. RESULTS: "Living alone" was associated with elevated plasma renin (p<0.01, ß=0.138) but not aldosterone concentrations in the total sample. On subgroup level, we found associations of "living alone" and elevated renin concentrations only in subjects low in TAS-20 scores (p<0.01, ß=0.219). Interactional effects of alexithymia×cohabitation status were found for the aldosterone-to-renin ratio (p=0.02, ß=-0.234). CONCLUSIONS: The association of chronic stress imposed by "living alone" with increased RAAS activity contributes to explain the relationship of this psychosocial stress condition and increased risk for CVD. In contrast, alexithymic subjects may be less affected by the deleterious effects of "living alone".

The levels of monoamine neurotransmitters and measures of mental and emotional health in HCV patients treated with ledipasvir (LDV) and sofosbuvir (SOF) with or without ribavirin (RBV).

Mental and emotional health (MEH) impairment is commonly encountered in hepatitis C patients. Although the exact mechanism remains unknown, alterations in neurotransmitter and cytokine levels maybe associated with hepatitis C virus (HCV)-related MEH issues.The aim of the study was to assess association of serum biomarkers with self-reports of MEH in HCV patients before treatment and after achieving sustained virologic response (SVR).The HCV genotype-1-infected patients who achieved SVR at 12 weeks after treatment with ledipasvir (LDV)/sofosbuvir (SOF) ±â€Šribavirin (RBV) were selected. Frozen serum samples from baseline, end of treatment (EOT), and posttreatment week 4 (PTW4) were used to assay 16 cytokines and monoamine neurotransmitters. Validated self-reports were used to assess MEH.Hundred patients were evaluated. Mean age was 53 years (57% male, 86% white). Compared with baseline, emotional well-being and emotional health significantly increased by EOT, and role emotional, emotional well-being, and emotional health significantly increased at PTW4 in the RBV-containing arm (P < 0.05). In patients taking LDV/SOF + RBV, serotonin levels were significantly decreased at PTW4 compared with baseline (P = 0.046). Compared with baseline, there were significant decreases in interleukin (IL)-10 levels at EOT and PTW4 in both treatment groups. The changes in IL-8 also differed significantly between LDV/SOF + RBV and LDV/SOF groups (P < 0.05). Changes in dopamine and tryptophan levels at EOT correlated with increasing emotional health scores, whereas changes in monocyte chemoattractant protein-1 at EOT and IL-8 at PTW4 correlated with increasing mental health scores. The neurotransmitters and cytokines were found to be independent predictors of MEH scores in multiple regression analysis.Cytokine and neurotransmitter changes are associated with mental and emotional health. Patient-reported outcome scores change during and after treatment.

Relationships between anhedonia, alexithymia, impulsivity, suicidal ideation, recent suicide attempt, C-reactive protein and serum lipid levels among 122 inpatients with mood or anxious disorders.

Several studies have explored the relationship between C-reactive protein (CRP), serum lipid levels, risk of suicide and alexithymia or impulsivity in mood or anxiety disorders. However, to date, no study has evaluated the effects of anhedonia on these parameters. The aim of the study was to evaluate the relationship between anhedonia, alexithymia, impulsivity, suicidal ideation, recent suicide attempt, C-reactive protein (CRP) and lipid levels in patients with mood or anxiety disorders. One hundred and twenty-two inpatients with mood or anxiety disorders were recruited. Alexithymia and impulsivity were rated by the 20-item Toronto Alexithymia Scale (TAS-20) and the Barratt impulsivity scale (BIS-10), respectively. Anhedonia and depression were rated by the Temporal Experience Pleasure Scale (TEPS) and the Beck Depression inventory (BDI-II). The TEPS contained two subscales rating anticipatory and consummatory anhedonia. From the BDI-II an anhedonia subscale was extracted rating anhedonia-state. Trait consummatory anhedonia and state anhedonia were associated with low levels of total cholesterol or HDL and low levels of triglycerides respectively. Trait anticipatory anhedonia and state anhedonia were associated with suicidal ideations. The difficulty of identifying feelings component of alexithymia was associated with low levels of total cholesterol and LDL. A high level of suicidal ideation was associated with low levels of HDL. Higher levels of CRP were found in inpatients having recently attempted suicide compared with inpatients who had not attempted suicide. In mood and anxiety disorders, anhedonia and the "difficulty of identifying feelings" component of alexithymia (which has previously been found to be associated with suicide risk) could explain the relationship between serum lipid levels and higher suicide risk.

Externally Oriented Thinking Predicts Phosphorus Levels in Dialyzed Patients.

BACKGROUND: The aim of the present study was to investigate the association between alexithymia scores and biological markers of adherence in dialyzed patients. The hypothesis was that higher scores of alexithymia would be associated with lower adherence to treatment. METHODS: Fifty-four adult dialyzed patients were enrolled during a follow-up visit. Participants were asked to complete a self-report questionnaire, namely, the Toronto Alexithymia Scale (TAS-20). Moreover, biological markers levels of adherence to treatment (phosphorus, creatinine, and serum uric acid) were measured. RESULTS: A positive correlation was found between phosphorous levels and TAS-F2 (r = 0.28; P = .04) and TAS-F3 (r = -0.31; P = .02). Stepwise regression with TAS-F2 and TAS-F3 as predictors of adherence to treatment showed a significant model, adjusted R(2) = 0.08, F(1,52) = 5.4; P < .02, where only TAS-F3 was able to predict phosphorous levels (P = .02). CONCLUSIONS: Findings showed that external oriented thinking was able to predict a biological marker of adherence to treatment in dialyzed patients.

Mood disturbance during experimental endotoxemia: Predictors of state anxiety as a psychological component of sickness behavior.

Lipopolysaccharide (LPS) administration is a well-established model to assess afferent immune-to-brain communication and behavioral aspects of inflammation. Nevertheless, only few studies in comparatively small samples have assessed state anxiety as a psychological component of sickness behavior despite possible clinical implications for the pathophysiology of neuropsychiatric conditions. Thus, the goal of the present analyses carried out in a large, pooled dataset from two independent study sites was to analyze the state anxiety response to LPS administration and to investigate predictors (i.e., cytokine changes; pre-existing anxiety and depression symptoms assessed with the Hospital Anxiety and Depression Scale) of the LPS-induced state anxiety changes at different time points after LPS administration. Data from 186 healthy volunteers who participated in one of six randomized, placebo-controlled human studies involving intravenous administration of LPS at doses of 0.4-0.8ng/kg body weight were combined. State anxiety as well as circulating interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10 concentrations were significantly increased 2h and 3h after LPS administration, with a peak at 2h, and returned to baseline 6h after administration. Greater changes in IL-6 from baseline to 3h after LPS administration significantly and independently predicted a more pronounced LPS-induced state anxiety response. In addition, higher pre-existing subclinical anxiety symptoms significantly predicted a lower increase in state anxiety 3h and 6h after LPS-administration, which was mediated by TNF-α changes. In conclusion, our findings give additional support for a putative role of inflammatory mechanisms in the pathophysiology of stress-related and anxiety disorders and give new insight on the potential role of pre-existing subclinical affective symptoms.

Heart rate variability and serum level of insulin-like growth factor-1 are correlated with symptoms of emotional disorders in patients suffering a mild traumatic brain injury.

OBJECTIVE: Patients who have experienced a mild traumatic brain injury (mTBI) are susceptible to symptoms of anxiety or depression. To explore the potential biomarkers for emotional disorders in mTBI patients, we analyzed the frequency domain of heart rate variability (HRV) and serum concentrations of four neurohormones. METHODS: We assessed mTBI patients on their first visit and follow-up. Symptoms were evaluated by the Beck Anxiety Inventory and the Beck Depression Inventory, respectively. Serum levels of adrenocorticotropic hormone (ACTH), melatonin, cortisol, and insulin-like growth factor (IGF)-1 and HRV follow-ups were measured and compared. RESULTS: mTBI patients were more vulnerable to symptoms of anxiety or depression than healthy controls. Reduced HRV was noted in mTBI patients compared to healthy controls. The mTBI patients demonstrated higher serum levels of ACTH, lower IGF-1 compared to healthy controls. In correlation analysis, only IGF-1 was positively correlated with HRV in mTBI patients. Both HRV and IGF-1 were correlated with symptom of depression while only HRV was correlated with symptom of anxiety in mTBI patients. CONCLUSIONS: We infer that HRV may be more significantly correlated with emotional disorders than is IGF-1 in mTBI patients. SIGNIFICANCE: The study is relevant for specific diagnostic markers in mTBI patients.

Alexithymia, more than depression, influences glycaemic control of type 2 diabetic patients.

PURPOSE: Psychiatric disorders could affect the patients' abilities to cope with diabetes. The objectives of this study were to assess the prevalence of depression and alexithymia among type 2 diabetic patients and investigate the possible correlations between these psychopathological phenomena and glycaemic control assessed through glycated hemoglobin (HbA1c). METHODS: All the patients were evaluated through 20-item Toronto Alexithymia Scale (TAS-20), Hamilton rating scale for depression and Quality of Life Index. HbA1c values, diabetes duration, therapy and socio-demographic characteristics were recorded. RESULTS: One hundred and twenty-eight patients (75 males and 53 female, mean age 64.7 ± 11.2 years) were enrolled. Alexithymic patients, compared to non-alexithymic ones, presented a significantly higher HbA1c (7.7 ± 1.5 vs. 7 ± 1.5, p = 0.016). No statistically significant difference was found when comparing the HbA1c of depressed versus non-depressed patients. Considering the raw values of HbA1c, the higher percentage was recorded among patients suffering from depression plus alexithymia (comorbidity group) followed by patients presenting alexithymia only, patients with neither depression nor alexithymia (control group) and, finally, those presenting depression only. The comorbidity group presented a significantly higher value of HbA1c (7.7 ± 1.2) than the control group (7 ± 1.6, p < 0.04) and the depressed patients (6.9 ± 1.3, p = 0.04). At the logistic regression, the HbA1c was found to be significantly associated only with alexithymia (TAS-20 total score) and insulin therapy. CONCLUSIONS: Alexithymia more than depression influences glycaemic control. When evaluating a diabetic patient, a rapid screening for psychopathological alterations would guarantee a more accurate management. The treatment of any associated psychiatric disorders would improve the patients' quality of life.

Blood manganese levels in relation to comorbid behavioral and emotional problems in children with attention-deficit/hyperactivity disorder.

Patients with attention-deficit/hyperactivity disorder (ADHD) appear to be more vulnerable to the development of other psychiatric disorders than the general population. The proposed neurotoxic mechanisms of manganese involve striatal dopamine neurotransmission, implicated in the pathophysiology of ADHD. We investigated whether the adverse impact of manganese is particularly pronounced in children with ADHD. Blood manganese concentration and diagnosis of ADHD were assessed in a general population of 890 children, aged 8-11 years. The main outcome measure was the Child Behavior Checklist (CBCL). A significant interaction was found between ADHD status and blood manganese level in predicting CBCL total problems score as well as anxiety/depression, social problems, delinquent behavior, aggressive behavior, internalizing problems, and externalizing problems. The directions of the interactions indicated that blood manganese level was more positively correlated with CBCL scores in ADHD children than in the healthy population. In ADHD children, only the fifth quintile of blood manganese concentration was significantly associated with the CBCL total problems score. ADHD children may be more vulnerable than the general school-age population to the neurotoxic effects of manganese exposure, which lead to an elevated risk of developing comorbid mental conditions.