Depression and cognition are associated with lipid dysregulation in both a multigenerational study of depression and the National Health and Nutrition Examination Survey.

Chronic dysregulation of peripheral lipids has been found to be associated with depression and cognition, but their interaction has not been investigated. Growing evidence has highlighted the association between peripheral lipoprotein levels with depression and cognition with inconsistent results. We assessed the association between peripheral lipids, depression, and cognition while evaluating their potential interactions using robust clinically relevant predictors such as lipoprotein levels and chronic medical disorders that dysregulate lipoproteins. We report an association between peripheral lipids, depression, and cognition, suggesting a common underlying biological mechanism driven by lipid dysregulation in two independent studies. Analysis of a longitudinal study of a cohort at high or low familial risk for major depressive disorder (MDD) (n = 526) found metabolic diseases, including diabetes, hypertension, and other cardiovascular diseases, were associated with MDD and cognitive outcomes. Investigating a cross-sectional population survey of adults in the National Health and Nutrition Examination Survey 2011-2014 (NHANES) (n = 2377), depression was found to be associated with high density lipoprotein (HDL) and cognitive assessments. In the familial risk study, medical conditions were found to be associated with chronic lipid dysregulation and were significantly associated with MDD using the structural equation model. A positive association between chronic lipid dysregulation and cognitive scores was found in an exploratory analysis of the familial risk study. In a complementary study, analysis of NHANES revealed a positive association of HDL levels with cognition. Further analysis of the NHANES cohort indicated that depression status mediated the interaction between HDL levels and cognitive tests. Importantly, the protective effect of HDL on cognition was absent in those with depressive symptoms, which may ultimately result in worse outcomes leading to cognitive decline. These findings highlight the potential for the early predictive value of medical conditions with chronic lipid dyshomeostasis for the risk of depression and cognitive decline.

Type I interferon signaling genes in recurrent major depression: increased expression detected by whole-blood RNA sequencing.

A study of genome-wide gene expression in major depressive disorder (MDD) was undertaken in a large population-based sample to determine whether altered expression levels of genes and pathways could provide insights into biological mechanisms that are relevant to this disorder. Gene expression studies have the potential to detect changes that may be because of differences in common or rare genomic sequence variation, environmental factors or their interaction. We recruited a European ancestry sample of 463 individuals with recurrent MDD and 459 controls, obtained self-report and semi-structured interview data about psychiatric and medical history and other environmental variables, sequenced RNA from whole blood and genotyped a genome-wide panel of common single-nucleotide polymorphisms. We used analytical methods to identify MDD-related genes and pathways using all of these sources of information. In analyses of association between MDD and expression levels of 13 857 single autosomal genes, accounting for multiple technical, physiological and environmental covariates, a significant excess of low P-values was observed, but there was no significant single-gene association after genome-wide correction. Pathway-based analyses of expression data detected significant association of MDD with increased expression of genes in the interferon α/ß signaling pathway. This finding could not be explained by potentially confounding diseases and medications (including antidepressants) or by computationally estimated proportions of white blood cell types. Although cause-effect relationships cannot be determined from these data, the results support the hypothesis that altered immune signaling has a role in the pathogenesis, manifestation, and/or the persistence and progression of MDD.

Religiosity and resilience in persons at high risk for major depression.

BACKGROUND: Few studies have examined religiosity as a protective factor using a longitudinal design to predict resilience in persons at high risk for major depressive disorder (MDD). METHOD: High-risk offspring selected for having a depressed parent and control offspring of non-depressed parents were evaluated for psychiatric disorders in childhood/adolescence and at 10-year and 20-year follow-ups. Religious/spiritual importance, services attendance and negative life events (NLEs) were assessed at the 10-year follow-up. Models tested differences in relationships between religiosity/spirituality and subsequent disorders among offspring based on parent depression status, history of prior MDD and level of NLE exposure. Resilience was defined as lower odds for disorders with greater religiosity/spirituality in higher-risk versus lower-risk offspring. RESULTS: Increased attendance was associated with significantly reduced odds for mood disorder (by 43%) and any psychiatric disorder (by 53%) in all offspring; however, odds were significantly lower in offspring of non-depressed parents than in offspring of depressed parents. In analyses confined to offspring of depressed parents, those with high and those with average/low NLE exposure were compared: increased attendance was associated with significantly reduced odds for MDD, mood disorder and any psychiatric disorder (by 76, 69 and 64% respectively) and increased importance was associated with significantly reduced odds for mood disorder (by 74%) only in offspring of depressed parents with high NLE exposure. Moreover, those associations differed significantly between offspring of depressed parents with high NLE exposure and offspring of depressed parents with average/low NLE exposure. CONCLUSIONS: Greater religiosity may contribute to development of resilience in certain high-risk individuals.

Are suicide attempters who self-mutilate a unique population?

OBJECTIVE: Individuals who mutilate themselves are at greater risk for suicidal behavior. Clinically, however, there is a perception that the suicide attempts of self-mutilators are motivated by the desire for attention rather than by a genuine wish to die. The purpose of this study was to determine differences between suicide attempters with and without a history of self-mutilation. METHOD: The authors examined demographic characteristics, psychopathology, objective and perceived lethality of suicide attempts, and perceptions of their suicidal behavior in 30 suicide attempters with cluster B personality disorders who had a history of self-mutilation and a matched group of 23 suicide attempters with cluster B personality disorders who had no history of self-mutilation. RESULTS: The two groups did not differ in the objective lethality of their attempts, but their perceptions of the attempts differed. Self-mutilators perceived their suicide attempts as less lethal, with a greater likelihood of rescue and with less certainty of death. In addition, suicide attempters with a history of self-mutilation had significantly higher levels of depression, hopelessness, aggression, anxiety, impulsivity, and suicide ideation. They exhibited more behaviors consistent with borderline personality disorder and were more likely to have a history of childhood abuse. Self-mutilators had more persistent suicide ideation, and their pattern for suicide was similar to their pattern for self-mutilation, which was characterized by chronic urges to injure themselves. CONCLUSIONS: Suicide attempters with cluster B personality disorders who have a history of self-mutilation tend to be more depressed, anxious, and impulsive, and they also tend to underestimate the lethality of their suicide attempts. Therefore, clinicians may be unintentionally misled in assessing the suicide risk of self-mutilators as less serious than it is.

A comparison of three scales for assessing social functioning in primary care.

OBJECTIVE: Assessment of functional status is increasingly important in clinical trials and outcome research. Although several scales for assessing functioning are widely used, they vary in coverage, and direct comparisons among them are rare. Comparative information is useful in guiding selection of appropriate scales for research applications. METHOD: Results from three scales that measure functioning-the Medical Outcomes Study 36-item Short-Form Health Survey, the Social Adjustment Scale Self-Report, and the Social Adaptation Self-Evaluation Scale-were compared in a consecutively selected sample of 211 patients coming to primary care. Patients also received psychiatric assessments. RESULTS: All three scales were acceptable to patients, showed few significant correlations with demographic variables, and were able to differentiate psychiatrically ill and well patients. Correlations among scales, even among scale items that assessed similar domains of functioning, were modest. CONCLUSIONS: Although all three scales are presumed to assess functional status, their item content and coverage differ. Selection of a scale requires a review of the scale items and consideration of research priorities and the characteristics of the study group. If functional status is a critical outcome measure, use of more than one scale may be necessary.

Association of aggressive behavior with altered serotonergic function in patients who are not suicidal.

OBJECTIVE: The purpose of this study was to determine whether aggression and serotonergic dysfunction are related in the absence of a history of suicidal behavior. Although serotonergic dysfunction has been implicated in aggressive and impulsive behavior, most studies of such behavior have included individuals with a history of suicide attempts. Low concentrations of CSF 5-hydroxyindoleacetic acid (5-HIAA) have been consistently associated with suicidal behavior, presenting a potential confound in the link between aggression and serotonergic dysfunction. METHOD: The authors examined the association between aggression and CSF 5-HIAA concentrations in a group of 64 patients who had different DSM-III-R axis I diagnoses and no past suicidal behavior. Aggressive (N=35) and nonaggressive (N=29) groups were defined by a median split on a six-item history of adulthood aggressive behavior. RESULTS: The aggressive group had significantly lower CSF 5-HIAA concentrations than the nonaggressive group. Aggressive individuals also scored significantly higher on self-report measures of hostility, impulsiveness, and sensation seeking. CSF 5-HIAA concentrations, however, did not correlate with self-reported hostility and impulsivity. CONCLUSIONS: There is an association between aggressive behavior and serotonergic dysfunction independent of suicidal behavior in patients with axis I disorders who exhibit relatively milder forms of aggressive behavior. Analogous to findings with suicidal behavior, a low concentration of CSF 5-HIAA is related to aggressive behavior but does not show the same relationship to the continuum of aggressive feelings and thoughts.