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.
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.
by
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.
An increase in corticotropin-releasing factor (CRF) is a putative factor in the pathophysiology of stress-related disorders. As CRF expression in the central nucleus of the amygdala (CeA) is important in adaptation to chronic stress, we hypothesized that unrestrained synthesis of CRF in CeA would mimic the consequences of chronic stress exposure and cause dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, increase emotionality and disrupt reproduction. To test this hypothesis, we used a lentiviral vector to increase CRF-expression site specifically in CeA of female rats. Increased synthesis of CRF in CeA amplified CRF and arginine vasopressin peptide concentration in the paraventricular nucleus of the hypothalamus, and decreased glucocorticoid negative feedback, both markers associated with the pathophysiology of depression. In addition, continuous expression of CRF in CeA also increased the acoustic startle response and depressive-like behavior in the forced swim test. Protein levels of gonadotropin-releasing hormone in the medial preoptic area were significantly reduced by continuous expression of CRF in CeA and this was associated with a lengthening of estrous cycles. Finally, sexual motivation but not sexual receptivity was significantly attenuated by continuous CRF synthesis in ovariectomized estradiol-progesterone-primed females. These data indicate that unrestrained CRF synthesis in CeA produces a dysregulation of the HPA axis, as well as many of the behavioral, physiological and reproductive consequences associated with stress-related disorders.
The high prevalence of trauma exposure and subsequent negative consequences for both survivors and society as a whole emphasize the need for secondary prevention of posttraumatic stress disorder. However, clinicians and relief workers remain limited in their ability to intervene effectively in the aftermath of trauma and alleviate traumatic stress reactions that can lead to chronic PTSD. The scientific literature on early intervention for PTSD is reviewed, including early studies on psychological debriefing, pharmacological, and psychosocial interventions aimed at preventing chronic PTSD. Studies on fear extinction and memory consolidation are discussed in relation to PTSD prevention and the potential importance of immediate versus delayed intervention approaches and genetic predictors are briefly reviewed. Preliminary results from a modified prolonged exposure intervention applied within hours of trauma exposure in an emergency room setting are discussed, along with considerations related to intervention reach and overall population impact. Suggestions for future research are included. Prevention of PTSD, although currently not yet a reality, remains an exciting and hopeful possibility with current research approaches translating work from the laboratory to the clinic.
Identified for its role in development, β-catenin has been implicated in neuronal synapse regulation and remodeling. We examined β-catenin expression in the adult mouse brain and its role in amygdala-dependent learning and memory. We found alterations in β-catenin mRNA and protein phosphorylation during fear memory consolidation. Such alterations correlated with a change in the association of β-catenin with cadherin. Pharmacologically, this consolidation was enhanced with lithium-mediated facilitation of β-catenin. Genetically, the role of β-catenin was confirmed with site-specific deletions of floxed β-catenin in the amygdala. Baseline locomotor, anxiety-related behaviors, and the acquisition or expression of conditioned fear were normal. However, amygdala-specific deletion prevented the normal transfer of newly formed fear learning into long-term memory. Thus, β-catenin within the amygdala may be required for the normal consolidation, but not acquisition, of fear memory. This suggests a general role for β-catenin in synaptic remodeling and stabilization underlying long-term memory in adults.
The theoretical debate over the relative contributions of nature and nurture to sexual differentiation of behavior has increasingly moved towards an interactionist explanation requiring both influences. In practice, however, nature and nurture have often been seen as separable, influencing human clinical sex assignment decisions, sometimes with disastrous consequences. Decisions about sex assignment of children born with intersex conditions have been based almost exclusively on the appearance of the genitals and how other’s reactions to the gender role of the assigned sex affects individual gender socialization. Effects of the social environment and gender expectations in human cultures are ubiquitous, overshadowing potential underlying biological contributions in favor of the more observable social influences. Recent work in nonhuman primates showing behavioral sex differences paralleling human sex differences, including toy preferences, suggests that less easily observed biological factors also influence behavioral sexual differentiation in both monkeys and humans. We review research, including Robert W. Goy’s pioneering work with rhesus monkeys which manipulated prenatal hormones at different gestation times and demonstrated that genital anatomy and specific behaviors are independently sexually differentiated. Such studies demonstrate that for a variety of behaviors, including juvenile mounting and rough play, individuals can have the genitals of one sex but show the behavior more typical of the other sex. We describe another case, infant distress vocalizations, where maternal responsiveness is best accounted for by the mother’s response to the genital appearance of her offspring. Together these studies demonstrate that sexual differentiation arises from complex interactions where anatomical and behavioral biases, produced by hormonal and other biological processes, are shaped by social experience into the behavioral sex differences that distinguish males from females.
Rationale
The progression of addiction from controlled to compulsive drug use leads to serious adverse consequences, including a greater propensity to relapse to drug use after sustained periods of abstinence.
Objective
The present study assessed the potential effects of cocaine self-administration history on the magnitude and persistence of cocaine-induced reinstatement in rhesus monkeys (n=6).
Methods
During a 3-month period of limited access to cocaine self-administration under a second-order schedule, subjects could take a maximum of 0.5 mg/kg per session 5 days per week. During a subsequent 3-month period of extended access to cocaine self-administration, subjects could take an additional 3.0 mg/kg under a fixed-ratio 20 schedule 3 days per week. Reinstatement effects were evaluated on six separate occasions that included limited and extended access conditions. Saline was substituted for cocaine, and once extinction criteria were met (response rates <20% of cocaine-maintained rates), response-independent cocaine (0.1 mg/kg) was administered i.v. prior to extinction sessions. Reinstatement was defined as a restoration of drug-appropriate responding above extinction criteria. Reinstatement experiments were conducted repeatedly on a daily basis until response rates returned to extinction levels. Peak response rates provided a measure of reinstatement magnitude whereas number of sessions required to meet extinction levels provided a measure of reinstatement persistence.
Results
Both the magnitude and persistence of reinstatement were consistent across all determinations regardless of drug history.
Conclusions
The results indicate that reinstatement under the second-order schedule is remarkably stable even when supplemental drug intake is provided over several months.
Linear dominance hierarchies organize and maintain stability in female rhesus macaque (Macaca mulatta) social groups regardless of group size. As a consequence of their low social status, subordinate females suffer from an array of adverse outcomes including reproductive compromise, impaired immune function, and poor cardiovascular health. However, data that differentiate limbic-hypothalamic-pituitary adrenal axis (LHPA) parameters between dominant from subordinate female monkeys are inconsistent, bringing into question whether social subordination alters the LHPA axis in female macaques. One difficulty in examining LHPA function in macaques may be the confounding effects of cycling ovarian steroids that are known to modulate LHPA activity. The current study used ovariectomized dominant and subordinate female rhesus monkeys to examine the effect that social subordination has on LHPA function by measuring morning and diurnal serum cortisol levels, dexamethasone (Dex) suppression of cortisol, metabolic clearance of Dex, and ACTH stimulation of adrenal cortisol release and cortisol response following exposure to acute social isolation. Compared to dominant females, subordinate females showed diminished morning peak cortisol secretion, weakened glucocorticoid negative feedback, and decreased adrenal cortisol response to an ACTH challenge as well as a restrained cortisol response following social isolation. However, the metabolism of Dex did not account for differences in Dex suppression between dominant and subordinate females. These results indicate that the ability to mount and limit glucocorticoid release is significantly reduced by psychosocial stress in female rhesus macaques, suggesting a hyporesponsive LHPA phenotype which resembles that observed in several human psychopathologies.
Background: In this study, we investigated the mechanism(s) by which delta opioids induce their potent activation of extracellular signal-regulated protein kinases (ERKs) in different cell lines expressing the cloned δ-opioid receptor (δ-OR). While it has been known for some time that OR stimulation leads to the phosphorylation of both ERK isoforms, the exact progression of events has remained elusive. Results: Our results indicate that the transphosphorylation of an endogenous epidermal growth factor receptor (EGFR) in the human embryonic kidney (HEK-293) cell line does not occur when co-expressed δ-ORs are stimulated by the δ-opioid agonist, D-Ser-Leu-enkephalin-Thr (DSLET). Moreover, neither pre-incubation of cultures with the selective EGFR antagonist, AG1478, nor down-regulation of the EGFR to a point where EGF could no longer activate ERKs had an inhibitory effect on ERK activation by DSLET. These results appear to rule out any structural or catalytic role for the EGFR in the δ-opioid-mediated MAPK cascade. To confirm these results, we used C6 glioma cells, a cell line devoid of the EGFR. In δ-OR-expressing C6 glioma cells, opioids produce a robust phosphorylation of ERK 1 and 2, whereas EGF has no stimulatory effect. Furthermore, antagonists to the RTKs that are endogenously expressed in C6 glioma cells (insulin receptor (IR) and platelet-derived growth factor receptor (PDGFR)) were unable to reduce opioid-mediated ERK activation. Conclusion: Taken together, these data suggest that the transactivation of resident RTKs does not appear to be required for OR-mediated ERK phosphorylation and that the tyrosine-phosphorylated δ-OR, itself, is likely to act as its own signalling scaffold.