Evidence suggests several causes for depression, including traumatic life events, disease, poison, and nutritional deficiencies. Many of these causes are associated with elevated levels of inflammatory biomarkers in the blood, which may in turn lead to inflammatory changes in the brain. Our authors examine what the latest research reveals about the link between inflammation in the brain and depression, and how a better understanding of that link can play a critical first step in the personalization of care.
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Michael Suttie;
Leah Wetherill;
Sandra W. Jacobson;
Joseph L. Jacobson;
H. Eugene Hoyme;
Elizabeth R. Sowell;
Claire Coles;
Jeffrey R. Wozniak;
Edward P. Riley;
Kenneth L. Jones;
Tatiana Foroud;
Peter Hammond
Background: Our objective is to help clinicians detect the facial effects of prenatal alcohol exposure by developing computer-based tools for screening facial form. Methods: All 415 individuals considered were evaluated by expert dysmorphologists and categorized as (i) healthy control (HC), (ii) fetal alcohol syndrome (FAS), or (iii) heavily prenatally alcohol exposed (HE) but not clinically diagnosable as FAS; 3D facial photographs were used to build models of facial form to support discrimination studies. Surface curvature-based delineations of facial form were introduced. Results: (i) Facial growth in FAS, HE, and control subgroups is similar in both cohorts. (ii) Cohort consistency of agreement between clinical diagnosis and HC-FAS facial form classification is lower for midline facial regions and higher for nonmidline regions. (iii) Specific HC-FAS differences within and between the cohorts include: for HC, a smoother philtrum in Cape Coloured individuals; for FAS, a smoother philtrum in Caucasians; for control-FAS philtrum difference, greater homogeneity in Caucasians; for control-FAS face difference, greater homogeneity in Cape Coloured individuals. (iv) Curvature changes in facial profile induced by prenatal alcohol exposure are more homogeneous and greater in Cape Coloureds than in Caucasians. (v) The Caucasian HE subset divides into clusters with control-like and FAS-like facial dysmorphism. The Cape Coloured HE subset is similarly divided for nonmidline facial regions but not clearly for midline structures. (vi) The Cape Coloured HE subset with control-like facial dysmorphism shows orbital hypertelorism. Conclusions: Facial curvature assists the recognition of the effects of prenatal alcohol exposure and helps explain why different facial regions result in inconsistent control-FAS discrimination rates in disparate ethnic groups. Heavy prenatal alcohol exposure can give rise to orbital hypertelorism, supporting a long-standing suggestion that prenatal alcohol exposure at a particular time causes increased separation of the brain hemispheres with a concomitant increase in orbital separation.
Children's external locus of control has been linked to a wide variety of negative academic achievement, personality, and social adjustment outcomes. The purpose of this study was to discover which features of early home environment may facilitate the development of external as opposed to internal control expectancies in children. We use an exposome approach to analyze data from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort study, a longitudinal study starting in pregnancy in England in 1990-1992. Details of parents and their study children were collected prospectively, and children's locus of control was assessed at age 8 using an abbreviated form of the most frequently used measure of children's locus of control (Nowicki-Strickland Internal External locus of control scale). A series of stepwise logistic regression analyses were undertaken to determine the strongest independent associations. The final model (n = 4,075 children) comprised 13 variables - those with the strongest associations with the child becoming externally oriented were two that were positive indicators of the mother being distracted (TV on almost the whole time, and a consideration that pets should be treated as members of the family), three that were indicators of protective (negative) effects of interaction between mother and child (child was breast fed, mother read stories to the child, mother cuddled the baby when he/she woke at night), and two divergent indicators of maternal health behavior (more frequent cleaning of the child's hands before a meal which was associated with a heightened risk of become external, and providing a healthy-type of diet, which was associated with a reduced risk of becoming external). The findings suggest that inadequate early maternal interaction with the child is associated with an increased risk of the child being externally oriented by the age of 8.
Introduction The Department of Veterans Affairs (VA) provides health care to approximately 300,000 patients with dementia. Recognizing the critical role caregivers play in veterans' health, the Cognitive Disorders Specialty Care Education Center of Excellence (COE) at the Atlanta VA Health Care System implemented a suite of caregiver support services, including formal programs and resource linkages. We evaluated the effectiveness of these services and identified caregiver-perceived gaps in them. Methods We conducted 11 semistructured interviews from November 2016 through February 2017 with caregivers of veterans seen in the COE who had participated in support services. After coding transcripts, we established a codebook of 9 major themes and conducted a thematic analysis of all transcripts. Results Caregivers spoke positively of COE caregiver services that offered information on dementia, social support, an emphasis on caregiver well-being and self-efficacy, and methods for behavioral change. Gaps identified included the need for additional dementia information and practical support in such matters as advanced directives and eligibility for VA benefits. Conclusion Our findings will inform future improvements to COE caregiver support services, such as an expansion of COE's caregiver educational content and capacity building of existing components such as resource referrals. These results also highlight opportunities for COE to interface with internal and external organizations to enhance existing caregiver services.
Objective: The current study examined the prospective effects of exposure to stressful conditions in early childhood on physical health in young adulthood, and explored continuing exposure to stressors, as well as depression, in adolescence as possible mechanisms of this relationship.
Design: A prospective longitudinal design was used to examine 705 mother-child pairs from a community-based sample, followed from offspring birth through age 20.
Main Outcome Measures: Mothers provided contemporaneous assessments of early adverse conditions from offspring birth through age 5. Offspring responses to the UCLA Life Stress Interview, Structured Clinical Interview for DSM Disorders (SCID), Physical Functioning subscale of the SF-36 Health Survey, and questions about the presence of chronic disease were used to assess youth stress at age 15, depression from ages 15 to 20, and physical health at age 20.
Results: Early adversity conferred risk for elevated levels of social and non-social stress at youth age 15, as well as depression between ages 15 and 20. Social and non-social stress in turn had effects on physical health at age 20, directly and indirectly via depression.
Conclusions: Findings suggest that early adverse conditions have lasting implications for physical health, and that continued exposure to increased levels of both social and non-social stress in adolescence, as well as the presence of depression, might be important mechanisms by which early adversity impacts later physical health.
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Krishnapriya Ramanujam;
Michael B. Himle;
Loran P. Hayes;
Douglas W. Woods;
Lawrence Scahill;
Denis G. Sukhodolsky;
Sabine Wilhelm;
Thilo Deckersbach;
Alan L. Peterson;
Matt Specht;
John T. Walkup;
Susanna Chang;
John Piacentini
Although tics are the defining feature of chronic tic disorders (CTD), many children experience comorbid internalizing and externalizing problems that contribute to impairment across several domains, including family functioning. The current study examined clinical correlates and predictors of caregiver strain in parents of children with CTD. Participants were 123 children and adolescents diagnosed with a CTD who participated in a randomized-controlled trial of behavior therapy for reducing tics. Results showed that a combination of disruptive behavior, inattention/hyperactivity, and tic intensity best explained objective strain, and a combination of inattention/hyperactivity and tic intensity were the best predictors of subjective caregiver strain. Implications of these findings for care providers are discussed.
Brain areas implicated in the stress response include the amygdala, hippocampus, and prefrontal cortex. Traumatic stress can be associated with lasting changes in these brain areas. Traumatic stress is associated with increased cortisol and norepinephrine responses to subsequent stressors. Antidepressants have effects on the hippocampus that counteract the effects of stress. Findings from animal studies have been extended to patients with post-traumatic stress disorder (PTSD) showing smaller hippocampal and anterior cingulate volumes, increased amygdala function, and decreased medial prefrontal/anterior cingulate function. In addition, patients with PTSD show increased cortisol and norepinephrine responses to stress. Treatments that are efficacious for PTSD show a promotion of neurogenesis in animal studies, as well as promotion of memory and increased hippocampal volume in PTSD.
The American Heart Association (AHA) recently developed the Cardiovascular Health Index (CVHI), a health metric consisting of 7 modifiable risk factors. The relationship of the CVHI with preclinical markers, such as carotid intima-media thickness (CIMT) has not been assessed. We examined 490 male monozygotic and dizygotic twins without overt cardiovascular disease. CIMT was measured using B-mode ultrasonography. Each of the 7 CVHI components (blood pressure, fasting glucose, total cholesterol, body mass index, physical activity, healthy diet, and smoking) was given a point score of 0, 1, or 2 to represent poor, intermediate, or ideal health, respectively. A CVHI summation score was computed (range 0 to 14) and categorized as inadequate (0 to 4), average (5 to 9), or optimum (10 to 14) cardiovascular health. Mixed-model regression was used to examine the association of the CVHI with CIMT. The mean age of the twins was 55.4 years, and 61% were monozygotic. The mean CIMT was 0.75 (± 0.11) mm and the mean CVHI score was 7.7 (± 2.1). There was an inverse correlation between CVHI and CIMT (Spearman r=-0.22, P<0.01). For every 5-unit increase in overall CVHI score (indicating better cardiovascular health category), CIMT decreased by 0.045 mm (P<0.001) after adjusting for demographic variables and other confounders. Within monozygotic twin pairs, a 5-unit increment in CVHI score was associated with a 0.05 mm lower CIMT (P<0.001). The CVHI is independently associated with CIMT and the association is not confounded by shared genetic and other familial factors.
Data will be reviewed using the acoustic startle reflex in rats and humans based on our attempts to operationally define fear vs anxiety. Although the symptoms of fear and anxiety are very similar, they also differ. Fear is a generally adaptive state of apprehension that begins rapidly and dissipates quickly once the threat is removed (phasic fear). Anxiety is elicited by less specific and less predictable threats, or by those that are physically or psychologically more distant. Thus, anxiety is a more long-lasting state of apprehension (sustained fear). Rodent studies suggest that phasic fear is mediated by the amygdala, which sends outputs to the hypothalamus and brainstem to produce symptoms of fear. Sustained fear is also mediated by the amygdala, which releases corticotropin-releasing factor, a stress hormone that acts on receptors in the bed nucleus of the stria terminalis (BNST), a part of the so-called ‘extended amygdala.' The amygdala and BNST send outputs to the same hypothalamic and brainstem targets to produce phasic and sustained fear, respectively. In rats, sustained fear is more sensitive to anxiolytic drugs. In humans, symptoms of clinical anxiety are better detected in sustained rather than phasic fear paradigms.
Interferon (IFN)-α treatment for infectious diseases and cancer is associated with significant depressive symptoms that can limit therapeutic efficacy. Multiple mechanisms have been implicated in IFN-α-induced depression including immune, neuroendocrine and neurotransmitter pathways. To further explore mechanisms of IFN-α-induced depression and establish associated genetic risk factors, single nucleotide polymorphisms in genes encoding proteins previously implicated in IFN-α-induced depression were explored in 2 self-reported ethnic groups, Caucasians (n=800) and African Americans (n=232), participating in a clinical trial on the impact of three pegylated IFN-α treatment regimens on sustained viral response in patients with chronic hepatitis C. Prior to treatment, all subjects were free of psychotropic medications and had a score ≤20 on the Center for Epidemiologic Studies Depression Scale (CES-D), which was used to assess depressive symptom severity throughout the study. In Caucasians, a polymorphism (rs9657182) in the promoter region of the gene encoding indoleamine-2,3-dioxygenase (IDO1) was found to be associated with moderate or severe IFN-α-induced depressive symptoms (CES-D >20) at 12 weeks of IFN-α treatment (p=0.0012, p<0.05 corrected). Similar results were obtained for treatment weeks 24, 36 and 48. In subjects homozygous for the risk allele (CC, n=150), the odds ratio for developing moderate or severe depressive symptoms at treatment week 12 was 2.91 (CI: 1.48–5.73) compared to TT homozygotes (n=270). rs9657182 did not predict depression in African Americans, who exhibited a markedly lower frequency of the risk allele at this locus. The findings in Caucasians further support the notion that indoleamine-2,3-dioxygenase plays an important role in cytokine-induced behavioral changes.