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.

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.

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.

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.

[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.

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.

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.

Val66Met polymorphism and serum brain-derived neurotrophic factor in bipolar disorder: an open-label trial.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is consistently associated with acute mood episodes in bipolar disorder, but there is a lack of longitudinal data to support this hypothesis. In this 16-week open-label clinical trial, we tested the predictive role of BDNF Val66Met polymorphism on serum BDNF levels and the relationship of serum BDNF and clinical response in people with bipolar disorder during an acute illness episode. METHOD: Sixty-four people with bipolar disorder who were medication-free at baseline and in an acute mood episode were recruited. They were matched with 64 healthy controls. Clinical evaluation, serum BDNF, and BDNF Val66Met polymorphism were determined at baseline, and change in serum BDNF was assessed in patients at weeks 2, 4, 8 and 16. RESULTS: There were no differences between patients and controls in serum BDNF or in frequencies of the BDNF Val66Met polymorphism genotype at baseline. The multivariable model showed that Met carriers had a significantly different change in BDNF levels compared with Val homozygotes. Not achieving a complete remission was also associated with lower prospectively assessed BDNF levels. CONCLUSION: This study provides the first longitudinal evidence that both the BDNF Val66Met polymorphism and remission status predict change in circulating BDNF levels.

Reduced serum adiponectin levels in alexithymia.

OBJECTIVES: Clinical studies have demonstrated that circulating cytokine profiles may differ between alexithymic and non-alexithymic subjects. We examined whether the levels of adiponectin (µg/ml) and resistin (ng/ml) are independently related to alexithymic features in a population-based sample. METHODS: In 2005, clinical data including laboratory assessments were obtained from a sub-sample (n = 308) of the Kuopio Depression Study general population study including subjects aged 25-64 years. Based on the Toronto Alexithymia Scale score in 1998, 1999, 2001 and 2005, a group of subjects with high alexithymic features (n = 85) was formed and compared with non-alexithymic controls (n = 206). RESULTS: Serum adiponectin levels were significantly lower in subjects with alexithymic features than in non-alexithymic control subjects. No difference was found in resistin levels. Similarly, in a logistic regression model adjusted for age, gender and body mass index (BMI), lowered levels of adiponectin, but not resistin, were associated with an increased likelihood of belonging to the group with alexithymic features. Further adjustments for cardiovascular risk factors (i.e. smoking, BMI, metabolic syndrome, alcohol use, and coronary heart disease), depressive symptoms (Hamilton Depression Rating Scale with 17 items) and the use of antidepressants in addition to age and gender did not change these patterns. CONCLUSIONS: Our findings suggest that a disturbed anti-inflammatory balance may characterize alexithymia. In addition, our results widen the concept of alexithymia and highlight the role of immune system alterations and stress in alexithymic individuals.

Alexithymia is associated with low level of vitamin D in young healthy adults.

OBJECTIVE: Vitamin D plays an important role in brain development and functioning. Low levels of vitamin D have been described in several psychiatric and neurologic conditions including autism spectrum disorder. Alexithymia that shows high comorbidity with autism is also present in the general population as well as hypovitaminosis D. METHODS: Here we assessed the relation between alexithymia as measured by the Toronto Alexithymia Scale-20 and vitamin D level in healthy young adults. Results We found an inverse correlation between the levels of alexithymia and vitamin D. DISCUSSION: These data suggest the association between disturbed emotional processing and low levels of vitamin D to be present in young healthy subjects.

The contribution of alexithymia, childhood maltreatment, impulsivity, C-reactive protein, lipid profile, and thyroid hormones to aggression and psychological distress (depression and anxiety) in schizophrenia.

There are individual effects of alexithymia, childhood maltreatment, impulsivity, and some biological markers on aggression and psychological distress in schizophrenia. However, the combined effects of these psychological and biological markers have not yet been fully studied. This study therefore aimed to investigate the influence of these psychological and biological markers on aggression and psychological distress (e.g., depression and anxiety) in inpatients with schizophrenia (n = 355). Participants completed self-report and clinician-rated scales, and blood samples were collected. There were no significant differences between patients with and without alexithymia regarding biological markers. Patients with childhood maltreatment exhibited higher levels of free triiodothyronine (FT3) and C-reactive protein (CRP), as well as lower total cholesterol (TC) levels, compared to non-traumatized individuals. Aggression was positively predicted by psychological distress, alexithymia, childhood maltreatment, impulsivity, CRP, and FT3, and negatively by TC and low-density lipoprotein cholesterol. Negative symptoms, childhood maltreatment, alexithymia, aggression, and CRP positively, and high-density lipoprotein cholesterol negatively emerged as predictors of psychological distress. The study highlights the connections between childhood maltreatment, alexithymia, impulsivity, and potentially related biological dysregulation in explaining aggression and negative mood states as a bio-psychological model of aggression and mood in schizophrenia.

Affective symptoms and change in diabetes self-efficacy and glycaemic control.

AIMS: To examine the role of baseline depression, anxiety and stress symptoms on post-intervention diabetes self-efficacy and glycaemic control (HbA(1c)). METHODS: The current study analysed data from patients (n = 85) with treated but uncontrolled Type 2 diabetes who participated in a comparative effectiveness study of two diabetes self-management interventions. Hierarchical linear regression was used to examine the relationships between baseline affective symptoms and post-intervention diabetes self-efficacy and the moderating effects of baseline affective symptoms on the relationship between changes in diabetes self-efficacy and post-intervention HbA(1c). RESULTS: Baseline depression was inversely associated with post-intervention diabetes self-efficacy (P = 0.0001) after adjusting for baseline characteristics including diabetes self-efficacy. In contrast, normal-mild levels of stress were associated with higher post-intervention diabetes self-efficacy (P = 0.04). Anxiety and stress symptoms significantly and independently moderated the relationship between changes in diabetes self-efficacy and post-intervention HbA(1c) (P = 0.02 and P = 0.03, respectively). Further evaluation of these interactions demonstrated that changes in diabetes self-efficacy were associated with lower post-intervention HbA(1c), but only among those with higher baseline affective symptoms. CONCLUSIONS: We found a moderating effect across affective symptoms on the relationship between diabetes self-efficacy changes and post-intervention HbA1c in the context of a self-management intervention. Results suggest that patients with poorly controlled diabetes who have higher levels of depression, anxiety and stress symptoms may derive greater benefits from self-management interventions known to improve diabetes self-efficacy.

Alexithymia, suicide risk and serum lipid levels among adult outpatients with panic disorder.

To elucidate the relationships between alexithymia, suicide ideation and serum lipid levels in drug-naïve adult outpatients with a DSM-IV diagnosis of Panic Disorder (PD), 72 patients were evaluated. Measures were the Panic Attack and Anticipatory Anxiety Scale, the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI) and the Montgomery Åsberg Depression Rating Scale (MADRS). Alexithymic patients showed higher scores on all rating scales and altered serum lipid levels than non-alexithymics. In the hierarchical regression model, the presence of lower HDL-C and higher VLDL-C levels and Difficulty in Identifying Feelings dimension of TAS-20 were associated with higher suicide ideation. In conclusion, alexithymic individuals with PD may show a cholesterol dysregulation that may be linked to suicide ideation. The authors discuss study limitations and future research needs.

Psychologic and biologic factors associated with fatigue in patients with persistent radiculopathy.

Fatigue is a common symptom associated with neuropathic pain (NP) and can have negative consequences on psychosocial functioning, physical endurance, and quality of life. Recent evidence indicates that immune activation modulated through the increased release of proinflammatory cytokines can predict fatigue in some patient populations. Although earlier studies have shown that immune activation is a pathophysiologic feature of NP, there have been no studies to examine the relationship between immune activation and fatigue in persons with NP. Therefore, the purpose of this exploratory study was to: 1) determine the relationships among fatigue, pain, psychosocial factors, and selected biologic markers of immune activation (interleukin [IL] 6 and soluble IL-6 receptor [sIL-6R]) in participants with persistent radiculopathy; and 2) determine the differences in these variables based on fatigue severity. Participants (n = 80) were classified according to their level of fatigue as low (27.5%), moderate (32.5%), or high (40%), and significant differences were found between fatigue categories (p = .001). Multivariate analyses of variance revealed that individuals with moderate to high levels of fatigue differed from those with the lowest levels of fatigue in psychologic distress, depressive symptoms, IL-6, and sIL-6R, whereas the differences between moderate and high levels of fatigue were significant for psychologic distress and sIL-6R only. The findings suggest that immune activation affects fatigue severity and possibly other behavioral responses, offering important information when providing care to patients with persistent radiculopathy. The integration of biobehavioral nursing interventions in pain management may have a greater impact on quality of life than treatment focused only on pain.

Relationship between adiposity, emotional status and eating behaviour in obese women: role of inflammation.

BACKGROUND: Obesity is characterized by chronic low-grade inflammation that may lead to emotional distress and behavioural symptoms. This study assessed the relationship between adiposity, low-grade inflammation, eating behaviour and emotional status in obese women awaiting gastric surgery and investigated the effects of surgery-induced weight loss on this relationship. METHOD: A total of 101 women with severe or morbid obesity awaiting gastric surgery were recruited. Assessments were performed before and at 1 year post-surgery and included the measurement of neuroticism and extraversion using the revised Neuroticism-Extraversion-Openness personality inventory (NEO-PI-R) and eating behaviour using the Three-Factor Eating Questionnaire (TFEQ). Blood samples were collected for the measurement of serum inflammatory markers [interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP)] and adipokines (leptin, adiponectin). RESULTS: At baseline, body mass index (BMI) was positively correlated with inflammatory markers and adipokines. Regression analyses adjusting for age and diabetes revealed that baseline concentrations of IL-6 and hsCRP were associated with the depression and anxiety facets of neuroticism, with higher inflammation predicting higher anxiety and depression. This association remained significant after adjusting for BMI. Gastric surgery induced significant weight loss, which correlated with reduced inflammation. After controlling for BMI variations, decreases in inflammatory markers, notably hsCRP, were associated with reduced anxiety and TFEQ-cognitive restraint scores. CONCLUSIONS: These findings indicate strong associations between adiposity, inflammation and affectivity in obese subjects and show that surgery-induced weight loss is associated concomitantly with reduced inflammation and adipokines and with significant improvement in emotional status and eating behaviour. Inflammatory status appears to represent an important mediator of emotional distress and psychological characteristics of obese individuals.

Detection of plasma autoantibodies to brain tissue in young children with and without autism spectrum disorders.

Autism spectrum disorders (ASDs) are characterized by impaired language and social skills, often with restricted interests and stereotyped behaviors. A previous investigation of blood plasma from children with ASDs (mean age=5½ years) demonstrated that 21% of samples contained autoantibodies that reacted intensely with GABAergic Golgi neurons of the cerebellum while no samples from non-sibling, typically developing children showed similar staining (Wills et al., 2009). In order to characterize the clinical features of children positive for these autoantibodies, we analyzed plasma samples from children enrolled in the Autism Phenome Project, a multidisciplinary project aimed at identifying subtypes of ASD. Plasma from male and female children (mean age=3.2 years) was analyzed immunohistochemically for the presence of autoantibodies using histological sections of macaque monkey brain. Immunoreactivity to cerebellar Golgi neurons and other presumed interneurons was observed for some samples but there was no difference in the rate of occurrence of these autoantibodies between children with ASD and their typically developing peers. Staining of neurons, punctate profiles in the molecular layer of the dentate gyrus, and neuronal nuclei were also observed. Taken together, 42% of controls and subjects with ASD demonstrated immunoreactivity to some neural element. Interestingly, children whose plasma reacted to brain tissue had scores on the Child Behavior Checklist (CBCL) that indicated increased behavioral and emotional problems. Children whose plasma was immunoreactive with neuronal cell bodies scored higher on multiple CBCL scales. These studies indicate that additional research into the genesis and prevalence of brain-directed autoantibodies is warranted.

The relationship between alexithymia and circulating cytokine levels in subjects undergoing upper endoscopy.

OBJECTIVE: Despite emerging evidence suggesting a link between alexithymia and immune function, previous studies yielded contrasting results. The proposed link between alexithymia and immune function remains controversial as does the role, in this relationship, of anxiety, depression and subjective stress. The aim of the study is to investigate the possible association between alexithymia and circulating levels of cytokines in subjects awaiting an upper endoscopy, a stressful procedure, controlling for anxiety levels, depression and subjective stress. METHODS: Participants were recruited from among consecutive patients referred for routine diagnostic upper endoscopy. All participants completed the Toronto Alexithymia Scale (TAS-20), the Hospital Anxiety and Depression Scale, and the Stress-related Vulnerability Scale. Serum levels of IL-1ß, IL-4, IL-6, IL-10, TNF-α and IFN-γ were measured by ELISA. RESULTS: Of the 90 subjects initially approached, 68 completed the study. The TAS-20 identified 22 alexithymic and 36 non-alexithymic patients. ELISA detected significantly lower IL-4 and IL-6 concentrations in alexithymic than in non-alexithymic patients. According to multiple linear regression analysis, alexithymia predicted low IL-4 and IL-6 levels in the sample overall, independently of stress, anxiety, depression and other possible confounders. No between-group differences were found in serum levels of IFN-γ, IL-1ß, and TNF-α. CONCLUSION: These findings argue against an isolated shift towards pro-inflammatory or anti-inflammatory mediators and suggest that circulating cytokine profiles differ in alexithymic and non-alexithymic subjects.

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.

Differences in glucose tolerance between deficit and nondeficit schizophrenia.

Some studies suggest that schizophrenia is associated with an increased risk of diabetes independently of antipsychotic use. People with deficit schizophrenia, which is characterized by primary (or idiopathic), enduring negative symptoms, differ from those with nondeficit schizophrenia on course of illness, treatment response, risk factors, and biological correlates. We hypothesized that deficit and nondeficit subjects would also differ with regard to glucose tolerance. Newly diagnosed, antipsychotic-naïve subjects with nonaffective psychosis and matched control subjects were administered a 75 g oral glucose tolerance test (GTT). Two-hour glucose concentrations were significantly higher in the nondeficit patients (N=23; mean [SD] of 121.6 [42.0]) than in deficit (N=23; 100.2 [23.1]) and control subjects (N=59; 83.8 [21.9]); the deficit subjects also had significantly higher two-hour glucose concentrations than did the control subjects. These results provide further support that the deficit group has a distinctive etiopathophysiology.