Fear memory regulation by the cAMP signaling pathway as an index of reexperiencing symptoms in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder associated with traumatic memory, yet its etiology remains unclear. Reexperiencing symptoms are specific to PTSD compared to other anxiety-related disorders. Importantly, reexperiencing can be mimicked by retrieval-related events of fear memory in animal models of traumatic memory. Recent studies revealed candidate PTSD-associated genes that were related to the cyclic adenosine monophosphate (cAMP) signaling pathway. Here, we demonstrate the tight linkage between facilitated cAMP signaling and PTSD by analyzing loss- and gain-of-cAMP signaling effects on fear memory in mice and the transcriptomes of fear memory-activated mice and female PTSD patients with reexperiencing symptoms. Pharmacological and optogenetic upregulation or downregulation of cAMP signaling transduction enhanced or impaired, respectively, the retrieval and subsequent maintenance of fear memory in mice. In line with these observations, integrative mouse and human transcriptome analysis revealed the reduced mRNA expression of phosphodiesterase 4B (PDE4B), an enzyme that degrades cAMP, in the peripheral blood of PTSD patients showing more severe reexperiencing symptoms and the mouse hippocampus after fear memory retrieval. Importantly, more severe reexperiencing symptoms and lower PDE4B mRNA levels were correlated with decreased DNA methylation of a locus within PDE4B, suggesting the involvement of methylation in the mechanism of PTSD. These findings raise the possibility that the facilitation of cAMP signaling mediating the downregulation of PDE4B expression enhances traumatic memory, thereby playing a key role in the reexperiencing symptoms of PTSD patients as a functional index of these symptoms.

Blood mRNA expression levels of glucocorticoid receptors and FKBP5 are associated with depressive disorder and altered HPA axis.

BACKGROUND: While depression has been associated with alterations in the hypothalamic-pituitary adrenal (HPA) axis function, there is still controversy regarding the nature and extent of the dysfunction, such as in the debate about hypercortisolism vs. hypocortisolism. It may therefore be necessary to understand whether and how HPA axis function in depression is linked to mRNA expression of key genes regulating this system. METHODS: We studied 163 depressed outpatients, most of whom were chronically ill, and 181 healthy controls. Blood mRNA expression levels of NR3C1 (including GRα, GRß, and GR-P isoforms), FKBP4, and FKBP5 were measured at baseline. HPA axis feedback sensitivity was measured by the dexamethasone (Dex)/corticotropin-releasing hormone (CRH) test. The association between mRNA expression levels and HPA axis feedback sensitivity was examined. RESULTS: Compared to controls, patients showed significantly higher expression of GRα and lower expression of FKBP5, and higher post-Dex cortisol levels, even after controlling for age and sex. FKBP5 expression was significantly positively correlated with cortisol levels in patients, while GRα expression was significantly negatively correlated with cortisol levels in controls. LIMITATIONS: Most patients were taking psychotropic medications. The large number of correlation tests may have caused type I errors. CONCLUSIONS: The tripartite relationship between depression, mRNA expression of GR and FKBP5, and HPA axis function suggests that the altered gene expression affects HPA axis dysregulation and, as a result, impacts the development and/or illness course of depressive disorder. The combination of increased GRα expression and decreased FKBP5 expression may serve as a biomarker for chronic depression.

Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions.

Background: The immune system has major roles in the brain and related psychopathology. Disrupted interleukin-6 secretion and aberrant amygdala emotional reactivity are well-documented in stress-related mental disorders. The amygdala regulates psychosocial stress-related interleukin-6 affected by related genes. These led us to comprehensively examine the relationship between interleukin-6, amygdala activity, and stress-related mental symptoms under gene-stressor interactions. Methods: One hundred eight nonclinical participants with various levels of anxiety/depression underwent magnetic resonance imaging scans during an emotional face task for amygdala activity and saliva collection (at 10-time points across 2 days) for the total output and diurnal patterns of interleukin-6. Gene-stressor interactions between rs1800796 (C/G) and rs2228145 (C/A) and stressful life events for the biobehavioral measures were explored. Results: The blunting of interleukin-6 diurnal pattern was associated with hypoactivation of the basolateral amygdala in response to fearful (vs. neutral) faces (t = 3.67, FWE-corrected p = 0.003), and was predominantly observed in individuals with rs1800796 C-allele homozygotes and negative life changes in the past year (F = 19.71, p < 0.001). When considered in a comprehensive model, the diminished diurnal pattern predicted greater depressive symptoms (ß = -0.40), modulated by the amygdala hypoactivity (ß = 0.36) and rs1800796-stressor interactions (ß = -0.41; all p < 0.001). Conclusion: Here we show that the blunted interleukin-6 diurnal rhythm predicts depressive symptoms, modulated by amygdala emotional hyporeactivity and gene-stressor interactions. These findings indicate a potential mechanism underlying vulnerability to depressive disorders, suggesting their early detection, prevention, and treatment through the understanding of immune system dysregulation.

Suicidality in civilian women with PTSD: Possible link to childhood maltreatment, proinflammatory molecules, and their genetic variations.

Background: Posttraumatic stress disorder (PTSD) is a robust risk factor for suicide. Studies have suggested an association between suicide and elevated inflammatory markers, although such evidence in PTSD is scarce. Suicide risk, PTSD, and inflammatory molecules are all shown to be associated with childhood maltreatment and genetic factors. Methods: We examined the association between suicidal ideation/risk and inflammatory markers in 83 civilian women with PTSD, and explored the possible influence of childhood maltreatment and inflammatory genes. Suicidal ideation and risk were assessed using the Beck Depression Inventory-II and the Mini-International Neuropsychiatric Interview. Childhood maltreatment history was assessed with the Childhood Trauma Questionnaire (CTQ). Blood levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and high-sensitivity tumor necrosis factor-α were measured. Genetic polymorphisms of CRP rs2794520 and IL6 rs1800796 were genotyped. Results: Suicidal ideation was significantly positively correlated with hsCRP (p = 0.002) and IL-6 (p = 0.015) levels. Suicide risk weighted score was significantly positively correlated with hsCRP (p = 0.016) levels. The risk alleles of CRP rs2794520 and IL6 rs1800796 leading to increased respective protein levels were dose-dependently associated with higher risk of suicide (p = 0.007 and p = 0.029, respectively). The CTQ total score was significantly correlated with suicidal ideation and risk, but not with inflammatory marker levels. Furthermore, a multivariate regression analysis controlling for PTSD severity and potential confounders revealed that rs2794520 and rs1800796, but not hsCRP or IL-6 levels, significantly predicted suicidal ideation (p < 0.001) and risk (p = 0.007), respectively. Conclusion: Genetic variations within inflammatory genes might be useful in detecting PTSD patients at high risk of suicide.

Analyzing schizophrenia-related phenotypes in mice caused by autoantibodies against NRXN1α in schizophrenia.

The molecular pathological mechanisms underlying schizophrenia remain unclear; however, genomic analysis has identified genes encoding important risk molecules. One such molecule is neurexin 1α (NRXN1α), a presynaptic cell adhesion molecule. In addition, novel autoantibodies that target the nervous system have been found in patients with encephalitis and neurological disorders. Some of these autoantibodies inhibit synaptic antigen molecules. Studies have examined the association between schizophrenia and autoimmunity; however, the pathological data remain unclear. Here, we identified a novel autoantibody against NRXN1α in patients with schizophrenia (n = 2.1%) in a Japanese cohort (n = 387). None of the healthy control participants (n = 362) were positive for anti-NRXN1α autoantibodies. Anti-NRXN1α autoantibodies isolated from patients with schizophrenia inhibited the molecular interaction between NRXN1α and Neuroligin 1 (NLGN1) and between NRXN1α and Neuroligin 2 (NLGN2). Additionally, these autoantibodies reduced the frequency of the miniature excitatory postsynaptic current in the frontal cortex of mice. Administration of anti-NRXN1α autoantibodies from patients with schizophrenia into the cerebrospinal fluid of mice reduced the number of spines/synapses in the frontal cortex and induced schizophrenia-related behaviors such as reduced cognition, impaired pre-pulse inhibition, and reduced social novelty preference. These changes were improved through the removal of anti-NRXN1α autoantibodies from the IgG fraction of patients with schizophrenia. These findings demonstrate that anti-NRXN1α autoantibodies transferred from patients with schizophrenia cause schizophrenia-related pathology in mice. Removal of anti-NRXN1α autoantibodies may be a therapeutic target for a subgroup of patients who are positive for these autoantibodies.

Discrepancy between Clinician-rated and Self-reported Depression Severity is Associated with Adverse Childhood Experience, Autistic-like Traits, and Coping Styles in Mood Disorders.

Objective: This study aimed to determine if the discrepancy between depression severity rated by clinicians and that reported by patients depends on key behavioral/psychological features in patients with mood disorders. Methods: Participants included 100 patients with mood disorders. First, we examined correlations and regressions between scores on the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI). Second, we divided the participants into those who provided 1) greater ratings for the BDI compared with the HAMD (BDI relative- overrating, BO) group, 2) comparable ratings for the BDI and HAMD (BDI relatively concordant, BC) group, or 3) less ratings for the BDI (BDI relative-underrating, BU) group. Adverse childhood experiences, autistic-like traits, and coping styles were evaluated with a six-item short version of the Childhood Trauma Questionnaire (CTQ-6), the Social Responsiveness Scale for Adults (SRS-A), and the Ways of Coping Checklist (WCCL), respectively. Results: A significant correlation was found between HAMD and BDI scores. Total and emotional abuse subscale scores from the CTQ-6, and the self-blame subscale scores from the WCCL were significantly higher for the BO group compared with the BU group. The BO group also elicited significantly higher SRS-A total scores than did the other groups. Conclusion: These findings suggest that patients with adverse emotional experiences, autistic-like traits, and self-blame coping styles perceive greater distress than that evaluated objectively by clinicians. The results indicate the need for inclusion of subjective assessments to effectively evaluate depressive symptoms in patients deemed to have these psycho- behavioral concerns.

Association between vegetable, fruit, and flavonoid-rich fruit consumption in midlife and major depressive disorder in later life: the JPHC Saku Mental Health Study.

We evaluated the association between vegetable and fruit consumption - particularly flavonoid-rich fruits - in mid-life and major depressive disorder (MDD) in later life. We also evaluated the association of nutrients in fruits and vegetables with MDD. Vegetable and fruit consumption and nutrient intake for 1204 individuals were averaged from data obtained in 1995 and 2000. MDD was diagnosed by certified psychiatrists in 2014-2015. Logistic regression was used to examine the odds of MDD according to quintile of vegetable and fruit consumption and quartile of nutrient intake. We fitted two regression models, using hierarchical adjustment for age, sex, employment status, alcohol consumption, current smoking, and physical activity. Bias-corrected and accelerated bootstrap confidence intervals were used to obtain accurate information. In fully adjusted models, the highest quintile of total fruit consumption excluding juice and flavonoid-rich fruit consumption showed decreased odds of MDD compared with the lowest quintile (OR = 0.34, 95% CI = 0.15-0.77; OR = 0.44, 95% CI = 0.20-0.97, respectively). No significant association was found for total vegetables and fruits, total vegetables, or total fruits. No significant association was found for any nutrient. This study provides novel information on the association between MDD and flavonoid-rich fruits.

Skills Training in Affective and Interpersonal Regulation Narrative Therapy for women with ICD-11 complex PTSD related to childhood abuse in Japan: a pilot study.

Background: Skills Training in Affective and Interpersonal Regulation (STAIR) Narrative Therapy (SNT) has shown efficacy in alleviating symptoms of posttraumatic stress disorder (PTSD) and improving emotion regulation and interpersonal skills among individuals with complex trauma, such as childhood abuse. Although this therapy is expected to be effective for patients with complex PTSD (CPTSD), no study has directly assessed diagnostic and symptom outcomes. Moreover, the potential of therapy to achieve good outcomes in non-Western countries remains unclear. Objective: This pilot study examined the feasibility, safety, and outcomes of SNT for CPTSD among women with a history of childhood abuse in a Japanese clinical setting. Methods: Ten women aged 21-54 years (M = 29.1 years) with childhood-abuse-related ICD-11 CPTSD were enrolled in this study. The International Trauma Interview and International Trauma Questionnaire were administered to diagnose CPTSD and assess its severity. Symptoms of dissociation and depression, difficulties in emotion regulation and interpersonal relationships, quality of life, and negative cognitions were assessed pretreatment, midtreatment (after the STAIR phase), and immediately posttreatment (after the Narrative Therapy phase), in addition to 3 months after treatment. Results: Seven of the 10 participants completed the treatment. The therapists' adherence to the therapy protocol was 96.4%, ranging from 93.6% to 100% across therapists. Serious adverse events were not observed. Among the seven completers, six at posttreatment and all at follow-up no longer met CPTSD diagnosis. Exploratory analyses using the linear mixed-effects model showed significant improvements at posttreatment and follow-up for almost all the variables. Conclusions: The results provide preliminary evidence for the feasibility and safety of SNT for CPTSD in a Japanese clinical setting. This study is the first to report the use of SNT for individuals diagnosed with ICD-11 CPTSD using reliable clinician and self-report measures. HIGHLIGHTS: This study examined the feasibility and safety of STAIR Narrative Therapy for women with ICD-11 CPTSD related to childhood abuse in a Japanese clinical setting.High therapy adherence was observed.No serious adverse events occurred.

Antecedentes: La terapia narrativa (SNT en su sigla en inglés) de Entrenamiento de habilidades en regulación afectiva e interpersonal (STAIR en su sigla en inglés) ha demostrado eficacia en el alivio de los síntomas del trastorno de estrés postraumático (TEPT) y mejorar regulación emocional y las habilidades interpersonales entre individuos con trauma complejo, como el abuso en la infancia. Aunque esta terapia se espera que sea efectiva para pacientes con TEPT complejo (TEPT-C), ningún estudio ha evaluado directamente su estado diagnóstico y síntomas. Además, el potencial de la terapia para alcanzar resultados parecidos en países no Occidentales sigue sin estar claro.Objetivo: Este estudio piloto examinó la viabilidad, seguridad y resultados de la SNT para TEPTC en mujeres con historia de abuso en la infancia en un contexto clínico japonés.Métodos: Se inscribieron en este estudio diez mujeres de edad entre los 21­54 años (M = 29.1) con TEPT-C según la CIE-11 relacionado con abuso infantil. Se aplicó la Entrevista Internacional de Trauma y el Cuestionario Internacional de Trauma para diagnosticar TEPT-C y evaluar su gravedad. Los síntomas de disociación y depresión, dificultades en la regulación emocional y relaciones interpersonales, calidad de vida y cogniciones negativas se evaluaron durante el pretratamiento, a la mitad del tratamiento (después de la fase STAIR) e inmediatamente postratamiento (después de la fase de Terapia Narrativa), además de a los 3 meses después del tratamiento.Resultados: Siete de las 10 participantes completaron el tratamiento. La adherencia de los terapeutas al protocolo de la terapia fue del 96.4%, con una variación del 93.6% al 100% entre terapeutas. No se observaron eventos adversos serios. Entre las siete que completaron el tratamiento, seis en el postratamiento y todas al seguimiento ya no cumplían con el diagnóstico de TEPT-C. Los análisis exploratorios que utilizaron el modelo lineal de efectos mixtos mostraron una mejoría significativa en el postratamiento y seguimiento para casi todas las variables.Conclusiones: Los resultados entregan evidencia preliminar para la viabilidad y seguridad de la SNT para TEPT-C en un contexto clínico japonés. Este estudio es el primero en reportar el uso de la SNT para individuos diagnosticados con TEPT-C según la CIE-11 usando medidas clínicas y de auto-reporte confiables.

The Depression Anxiety Stress Scale 8-Items Expresses Robust Psychometric Properties as an Ideal Shorter Version of the Depression Anxiety Stress Scale 21 Among Healthy Respondents From Three Continents.

To examine the cultural limitations and implications in the applicability of the Depression Anxiety Stress Scale 8-items (DASS-8)-a shortened version of the DASS-21 recently introduced in an Arab sample-this study evaluated its psychometric properties, including measurement invariance, among healthy subjects from the United States, Australia, and Ghana. Confirmatory factor analysis revealed good fit of the DASS-8 relative to a 12-item version (DASS-12). Both the DASS-8 and the DASS-12 were invariant at all levels across genders, employment status, and students vs. non-students. The DASS-8/DASS-12 also expressed invariance at the configural and metric levels across all countries, albeit scalar invariance was not maintained due to misspecification of the factor loadings in the Ghanian sample. Mann-Whitney U test revealed significantly lower levels of mental symptomatology on the DASS measures among Ghanian students than in English-speaking respondents (both students and non-students). The DASS-8 expressed excellent internal consistency (coefficient alpha = 0.89), good convergent validity-noted by high values of item-total correlations (r = 0.87 to 0.88), good predictive validity-indicated by significantly strong correlation with the DASS-21 and its subscales (r = 0.95 to 0.80), and adequate discriminant validity-indicated by heterotrait-monotrait ratio of correlations <0.85. The DASS-8 correlated with the Internet Gaming Disorder-9, the Adult attention-deficit/hyperactivity disorder Self-Report Scale, and the Individualism and Collectivism Scale/Culture Orientation Scale at the same level as the DASS-21 and the DASS-12, denoting its adequate criterion validity. The DASS-8 can be used as a brief alternative to the DASS-21 to screen for mental symptomatology in English-speaking and African cultures. However, the same scores on the DASS-8 and the DASS-12 may not always indicate the same level of symptom severity in subjects from different countries. Further inter-cultural evaluations of the DASS-8 are needed.

Neurobiology of early life adversity: A systematic review of meta-analyses towards an integrative account of its neurobiological trajectories to mental disorders.

Adverse childhood experiences (ACEs) may leave long-lasting neurobiological scars, increasing the risk of developing mental disorders in later life. However, no review has comprehensively integrated existing evidence across the fields: hypothalamic-pituitary-adrenal axis, immune/inflammatory system, neuroimaging, and genetics/epigenetics. We thus systematically reviewed previous meta-analyses towards an integrative account of ACE-related neurobiological alterations. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a total of 27 meta-analyses until October 2021 were identified. This review found that individuals with ACEs possess blunted cortisol response to psychosocial stressors, low-grade inflammation evinced by increased C-reactive protein levels, exaggerated amygdalar response to emotionally negative information, and diminished hippocampal gray matter volume. Importantly, these alterations were consistently observed in those with and without psychiatric diagnosis. These findings were integrated and discussed in a schematic model of ACE-related neurobiological alterations. Future longitudinal research based on multidisciplinary approach is imperative for ACE-related mental disorders' prevention and treatment.

Association of childhood maltreatment history with salivary interleukin-6 diurnal patterns and C-reactive protein in healthy adults.

Childhood maltreatment has been associated with increased inflammation, as indicated by elevated levels of proinflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). Studies in humans show that secretion of IL-6 follows a clear circadian rhythm, implying that its disturbed rhythm represents an important aspect of dysregulated inflammatory system. However, possible alterations in diurnal secretion patterns of IL-6 associated with childhood maltreatment have not been studied. Here we investigated this association in 116 healthy adults. Diurnal levels of IL-6 were examined using saliva samples collected at 5 times a day across 2 consecutive days. Salivary CRP levels were also determined by averaging measurements at 2 times a day for 2 days. Different types of childhood maltreatment were assessed with the Childhood Trauma Questionnaire (CTQ). CTQ total and emotional abuse scores were significantly correlated with smaller IL-6 diurnal variation as indexed by lower standard deviation across the measurement times (p = 0.024 and p = 0.008, respectively). Individuals with emotional abuse, as defined by a cut-off score of CTQ, showed flatter IL-6 rhythm than those without (p = 0.031). These results, both correlation and group comparison, remained significant after controlling for age, sex, and body mass index. Childhood maltreatment was not associated with total output of IL-6 or CRP. Our findings indicate that childhood trauma can have a long-term negative effect on the circadian rhythm of inflammatory system. The findings are consistent with those of previous studies on adulthood trauma, suggesting that the disrupted IL-6 rhythmicity may be associated with a broad range of trauma-related conditions.

Hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system in adulthood PTSD and childhood maltreatment history.

Accumulated evidence shows that psychological trauma and posttraumatic stress disorder (PTSD) are associated with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis. Besides the HPA axis hormones, recent evidence suggests that the renin-angiotensin-aldosterone (RAA) system and genetic factors may be involved in trauma/PTSD as well as in HPA axis regulation. This study attempted to better understand the HPA axis function in relation to PTSD and childhood maltreatment by simultaneously examining RAA system and genetic polymorphisms of candidate genes. Here we studied 69 civilian women with PTSD and 107 healthy control women without DSM-IV-based traumatic experience. Childhood maltreatment history was assessed with the Childhood Trauma Questionnaire. PTSD severity was assessed with the Posttraumatic Diagnostic Scale. Functional disability was assessed with the Sheehan Disability Scale. HPA axis was examined by measuring blood levels of cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone-sulphate (DHEA-S). RAA system was examined by measuring blood renin and aldosterone levels. The FKBP5 rs1360780 and CACNA1C rs1006737 polymorphisms were genotyped. No significant differences were seen between patients and controls in any of the five hormone levels. DHEA-S levels were significantly negatively correlated with overall PTSD severity (p = 0.003) and functional disability (p = 0.008). A two-way analysis of variance with diagnostic groups and genotypes as fixed factors revealed that patients with the rs1006737 A-allele had significantly lower DHEA-S levels than patients with the GG genotype (p = 0.002) and controls with the A-allele (p = 0.006). Childhood maltreatment history was not significantly correlated with any of the five hormone levels. These results were generally unchanged after controlling for the potentially confounding effect of age, depression, and anxiety. Our findings suggest that lower DHEA-S levels could indicate more severe subtype of PTSD, the association of which might be partly modified by the CACNA1C polymorphism.

Implicit and explicit emotional memory recall in anxiety and depression: Role of basolateral amygdala and cortisol-norepinephrine interaction.

Anxiety and depression are linked to both explicit and implicit memory biases, which are defined as the tendency to preferentially recall emotionally negative information at conscious and subconscious levels, respectively. Functional connectivity (FC) of the basolateral amygdala (BLA) and related stress hormones (i.e., cortisol and norepinephrine) are purportedly implicated in these biases. However, previous findings on memory biases in anxiety and depression have been inconsistent, likely due to their symptomatic complications. Therefore, the underlying neurobiological mechanism remains unclear. We thus investigated whether anxiety and depression as premorbid predispositions are related to the memory biases, and whether FC of BLA, cortisol, and 3-methoxy-4-hydroxyphenylglycol (MHPG: a major metabolite of norepinephrine) would affect the anxiety/depression-related biased memory recall in 100 participants without psychiatric symptomatology. Psycho-behavioral assessment, resting-state fMRI scans, and saliva collection at 10-points-in-time across two days were conducted. Correlations of memory biases with anxiety/depression and neurobiological markers were explored. As a result, neither anxiety nor depression were correlated with explicit memory bias to negative (vs. positive) information, although depression was associated with better recall of the negative stimuli only when they were perceived as self-relevant. In contrast, both anxiety and depression were correlated with implicit memory bias; however, the effects were solely explained by anxiety. Furthermore, FC of the BLA with subgenual anterior cingulate cortex (sgACC) and the synergetic effect of cortisol and MHPG uniquely affected the implicit memory bias. These findings suggest that anxiety facilitates an initial snapshot of negative information and can be accompanied by depression when the information creates negative semantic associations with the self. The BLA-sgACC neural connectivity and cortisol-norepinephrine interaction that are associated with the implicit memory bias might be one of the important neurobiological targets in the prevention and treatment for comorbid anxiety and depressive disorders.

Predictors of Nutritional Status, Depression, Internet Addiction, Facebook Addiction, and Tobacco Smoking Among Women With Eating Disorders in Spain.

Eating disorders (EDs) are a complex group of psychiatric conditions that involve dysfunctional eating patterns, nutritional alterations, and other comorbid psychopathologies. Some women with EDs may develop problematic internet use while they attempt to get information on dieting/weight control or get online support from people with similar problems. They may also drift toward tobacco smoking as a method to regulate their weight or to cope with their weight-related dysphoria. The occurrence of these conditions in EDs may prolong disease course and impede recovery. This study used structural equation modeling to investigate nutritional status (noted by body mass index, BMI), depression psychopathology, internet addiction (depicted by the Internet Addiction Test), Facebook addiction (depicted by the Bergen Facebook Addiction Scale), and smoking among 123 Spanish women diagnosed with EDs (mean age = 27.3 ± 10.6 years). History of hospitalization, marital status, age, and the level of education predicted BMI in certain ED groups. BMI did not predict depression, but it predicted internet addiction, Facebook addiction, and smoking in certain ED groups. Depression did not predict BMI, internet/Facebook addition, or smoking in any ED group. Some sociodemographic and clinical variables had indirect effects on depression, internet addiction, and Facebook addiction while age was the only variable expressing a direct effect on all outcome measures. Age, education, and history of prolonged treatment predicted smoking in certain ED patients. The findings signify that a considerable target for interventional strategies addressing nutritional and addictive problems in EDs would be women with high BMI, history of hospitalization, history of prolonged treatment, who are particularly young, single, and less educated. Replication studies in larger samples, which comprise various subtypes of EDs from both genders, are warranted to define the exact interaction among the addressed variables.

The Depression Anxiety Stress Scale 21: Development and Validation of the Depression Anxiety Stress Scale 8-Item in Psychiatric Patients and the General Public for Easier Mental Health Measurement in a Post COVID-19 World.

Despite extensive investigations of the Depression Anxiety Stress Scales-21 (DASS-21) since its development in 1995, its factor structure and other psychometric properties still need to be firmly established, with several calls for revising its item structure. Employing confirmatory factor analysis (CFA), this study examined the factor structure of the DASS-21 and five shortened versions of the DASS-21 among psychiatric patients (N = 168) and the general public (N = 992) during the COVID-19 confinement period in Saudi Arabia. Multigroup CFA, Mann Whitney W test, Spearman's correlation, and coefficient alpha were used to examine the shortened versions of the DASS-21 (DASS-13, DASS-12, DASS-9 (two versions), and DASS-8) for invariance across age and gender groups, discriminant validity, predictive validity, item coverage, and internal consistency, respectively. Compared with the DASS-21, all three-factor structures of the shortened versions expressed good fit, with the DASS-8 demonstrating the best fit and highest item loadings on the corresponding factors in both samples (χ2(16, 15) = 16.5, 67.0; p = 0.420, 0.001; CFI = 1.000, 0.998; TLI = 0.999, 0.997; RMSEA = 0.013, 0.059, SRMR = 0.0186, 0.0203). The DASS-8 expressed configural, metric, and scalar invariance across age and gender groups. Its internal consistency was comparable to other versions (α = 0.94). Strong positive correlations of the DASS-8 and its subscales with the DASS-21 and its subscales (r = 0.97 to 0.81) suggest adequate item coverage and good predictive validity of this version. The DASS-8 and its subscales distinguished the clinical sample from the general public at the same level of significance expressed by the DASS-21 and other shortened versions, supporting its discriminant validity. Neither the DASS-21 nor the shortened versions distinguished patients diagnosed with depression and anxiety from each other or from other psychiatric conditions. The DASS-8 represents a valid short version of the DASS-21, which may be useful in research and clinical practice for quick identification of individuals with potential psychopathologies. Diagnosing depression/anxiety disorders may be further confirmed in a next step by clinician-facilitated examinations. Brevity of the DASS-21 would save time and effort used for filling the questionnaire and support comprehensive assessments by allowing the inclusion of more measures on test batteries.

Profiling of Cerebrospinal Fluid Lipids and Their Relationship with Plasma Lipids in Healthy Humans.

Lipidomics provides an overview of lipid profiles in biological systems. Although blood is commonly used for lipid profiling, cerebrospinal fluid (CSF) is more suitable for exploring lipid homeostasis in brain diseases. However, whether an individual's background affects the CSF lipid profile remains unclear, and the association between CSF and plasma lipid profiles in heathy individuals has not yet been defined. Herein, lipidomics approaches were employed to analyze CSF and plasma samples obtained from 114 healthy Japanese subjects. Results showed that the global lipid profiles differed significantly between CSF and plasma, with only 13 of 114 lipids found to be significantly correlated between the two matrices. Additionally, the CSF total protein content was the primary factor associated with CSF lipids. In the CSF, the levels of major lipids, namely, phosphatidylcholines, sphingomyelins, and cholesterolesters, correlated with CSF total protein levels. These findings indicate that CSF lipidomics can be applied to explore changes in lipid homeostasis in patients with brain diseases.

Childhood trauma affects autobiographical memory deficits through basal cortisol and prefrontal-extrastriate functional connectivity.

BACKGROUND: Psychological trauma can damage the brain, especially in areas where glucocorticoid receptors are expressed, via perturbed secretion of cortisol. Childhood trauma is associated with blunted basal cortisol secretion, brain alterations, and autobiographical memory deficits referred to as overgeneral autobiographical memory (OGM). However, it remains unknown whether childhood trauma affects OGM through altered cortisol and brain alterations. METHODS: Using resting-state fMRI in 100 healthy humans, we examined whether childhood trauma affects OGM through its related basal cortisol and brain functional connectivity (FC). Trauma and OGM were assessed using the Childhood Trauma Questionnaire (CTQ) and Autobiographical Memory Test (AMT), respectively. Basal cortisol levels were measured by 10 points-in-time across two days. Multiple mediation analysis was employed. RESULTS: CTQ was associated with greater semantic-associate memory of OGM, a retrieval tendency toward semantic content with no specific contextual details of an experienced event, as well as blunted basal cortisol levels. While CTQ was correlated with decreased FC between the hippocampus and medial prefrontal cortex (PFC), it showed a more predominant correlation with increased FC between the lateral and anteromedial PFC and extrastriate cortex. Importantly, the increased prefrontal-extrastriate FC completely mediated the relationship between CTQ and semantic-associate memory, affected by hyposecretion of cortisol. CONCLUSION: Childhood trauma may lead to the lack of visuoperceptual contextual details in autobiographical memory by altering basal cortisol secretion and connectivity of the prefrontal-hippocampal-extrastriate regions. The intensified prefrontal-extrastriate connectivity may contribute to OGM formation by strengthening the semantic content in memory retrieval. Understanding the mechanisms underlying the trauma-cortisol-brain-memory link will provide important clinical implications for trauma-related mental disorders.

The efficacy of memantine in the treatment of civilian posttraumatic stress disorder: an open-label trial.

Background: Currently, there is a paucity of pharmacological treatment options for posttraumatic stress disorder (PTSD), and the development of a novel pharmacotherapeutic approach has become a matter of great interest. Objective: We conducted a 12-week open-label clinical trial to examine the efficacy and safety of memantine, an N-methyl-D-aspartate receptor antagonist, in the treatment of civilian PTSD. Method: Thirteen adult patients with DSM-IV PTSD, all civilian women, were enrolled. They were monitored at an ambulatory care facility every week until 4 weeks and then every 4 weeks until 12 weeks. Memantine was added to each patient's current medication, with the initial dosage of 5 mg/day and then titrated. Concomitant medications were essentially kept unchanged during the trial. The primary outcome was PTSD diagnosis and severity assessed with the Posttraumatic Diagnostic Scale (PDS). Results: Of the 13 cases, one dropped out and two were discarded due to the protocol deviation, and the analysis was done for the remaining 10. Mean PDS total scores decreased from 32.3 ± 9.7 at baseline to 12.2 ± 7.9 at endpoint, which was statistically significant with a large effect (paired t-test: p = .002, d = 1.35); intrusion, avoidance, hyperarousal symptoms were all significantly improved from baseline to endpoint. Six patients no longer fulfilled the diagnostic criteria of PTSD at endpoint. Some adverse, but not serious, effects possibly related to memantine were observed, including sleep problems, sleepiness, sedation, weight change and hypotension. Conclusions: Memantine significantly reduced PTSD symptoms in civilian female PTSD patients and the drug was well tolerated. Future randomized controlled trials are necessary to verify the efficacy and safety of memantine in the treatment of PTSD.

Antecedentes: Actualmente, hay escasez de opciones de tratamiento farmacológico para el trastorno de estrés postraumático (TEPT), y el desarrollo de un enfoque farmacoterapéutico nuevo se ha transformado en materia de gran interés.Objetivo: Llevamos a cabo un ensayo clínico abierto de 12 semanas para examinar la eficacia y seguridad de memantina, un antagonista del receptor de N-metil-d-aspartato, en el tratamiento del TEPT en civiles.Método: Se inscribieron trece pacientes adultas con TEPT según DSM-IV, todas mujeres civiles. Fueron monitoreadas en un centro de atención ambulatoria semanalmente por 4 semanas, y luego cada 4 semanas hasta las 12 semanas. Se agregó memantina al tratamiento farmacológico actual de cada paciente, con dosis inicial de 5 mg/día y titulación posterior. Los fármacos concomitantes fueron mantenidos esencialmente sin cambios durante el estudio. El objetivo primario fue el diagnóstico de TEPT y su severidad, evaluada con la Escala de Diagóstico Postraumático (PDS, por su sigla en inglés).Resultados: De los 13 casos, uno abandonó y 2 fueron descartados debido a desvío del protocolo, y el análisis fue realizado con los 10 restantes. El puntaje total promedio de PDS disminuyó de 32.3 ± 9.7 en el basal a 12.2 ± 7.9 al término, lo que fue estadísticamente significativo con un tamaño de efecto grande (prueba t pareada: p=.002, d=1.35); los síntomas de intrusión, evitación e hiperactivación mejoraron todos en forma al término respecto a la basal. Seis pacientes dejaron de cumplir los criterios de TEPT al término. Se observaron algunos efectos adversos, pero no serios, posiblemente relacionados a memantina, que incluyeron problemas del sueño, somnolencia, sedación, cambios en el peso e hipotensión.Conclusiones: La memantina redujo significativamente los síntomas de TEPT en pacientes mujeres civiles con TEPT y el fármaco fue bien tolerado. Se requieren ensayos controlados aleatorizados en el futuro para verificar la eficacia y seguridad de la memantina en el tratamiento del TEPT.

Childhood maltreatment history and attention bias variability in healthy adult women: role of inflammation and the BDNF Val66Met genotype.

Childhood maltreatment has been associated with greater attention bias to emotional information, but the findings are controversial. Recently, a novel index of attention bias, i.e., attention bias variability (ABV), has been developed to better capture trauma-related attentional dysfunction. However, ABV in relation to childhood trauma has not been studied. Here, we examined the association of childhood maltreatment history with attention bias/ABV in 128 healthy adult women. Different types of childhood maltreatment were assessed with the Childhood Trauma Questionnaire. Attention bias/ABV was measured by the dot-probe task. Possible mechanisms whereby childhood maltreatment affects attention bias/ABV were also explored, focusing on blood proinflammatory markers and the BDNF Val66Met polymorphism. We observed a significant positive correlation between childhood emotional abuse and ABV (P = 0.002). Serum high-sensitivity tumor necrosis factor-α levels were significantly positively correlated with ABV (P < 0.001), but not with childhood maltreatment. Jonckheere-Terpstra trend test showed a significant tendency toward greater ABV with increasing numbers of the BDNF Met alleles (P = 0.021). A two-way analysis of variance further revealed that the genotype-by-emotional abuse interaction for ABV was significant (P = 0.022); individuals with the Val/Met and Met/Met genotypes exhibited even greater ABV when childhood emotional abuse was present. These results indicate that childhood emotional abuse can have a long-term negative impact on emotional attention control. Increased inflammation may be involved in the mechanism of ABV, possibly independently of childhood maltreatment. The BDNF Met allele may dose-dependently increase ABV by interacting with childhood emotional abuse.