The glutamatergic drive to breathe is reduced in severe but not moderate hypoxia in Damaraland mole-rats.

Damaraland mole-rats (Fukomys damarensis) are a hypoxia-tolerant fossorial species that exhibit a robust hypoxic metabolic response (HMR) and blunted hypoxic ventilatory response (HVR). Whereas the HVR of most adult mammals is mediated by increased excitatory glutamatergic signalling, naked mole-rats, which are closely related to Damaraland mole-rats, do not utilize this pathway. Given their phylogenetic relationship and similar lifestyles, we hypothesized that the signalling mechanisms underlying physiological responses to acute hypoxia in Damaraland mole-rats are like those of naked mole-rats. To test this, we used pharmacological antagonists of glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-d-aspartate receptors (NMDARs), combined with plethysmography, respirometry and thermal RFID chips, to non-invasively evaluate the role of excitatory AMPAR and NMDAR signalling in mediating ventilatory, metabolic and thermoregulatory responses, respectively, to 1 h of 5 or 7% O2. We found that AMPAR or NMDAR antagonism have minimal impacts on the HMR or hypoxia-mediated changes in thermoregulation. Conversely, the 'blunted' HVR of Damaraland mole-rats is reduced by either AMPAR or NMDAR antagonism such that the onset of the HVR occurs in less severe hypoxia. In more severe hypoxia, antagonists have no impact, suggesting that these receptors are already inhibited. Together, these findings indicate that the glutamatergic drive to breathe decreases in Damaraland mole-rats exposed to severe hypoxia. These findings differ from other adult mammals, in which the glutamatergic drive to breathe increases with hypoxia.

Alienation Appraisals Mediate the Relationships between Childhood Trauma and Multiple Markers of Posttraumatic Stress.

Rates of posttraumatic stress are elevated in individuals who have experienced childhood and/or cumulative trauma, and trauma appraisals have been suggested as a possible mediator of this effect. This study tested the proposed mediating role of trauma appraisals between both childhood and cumulative trauma, and two markers of trauma-related distress; posttraumatic stress and depression. Mediation models were developed and tested with data collected from a sample of trauma-exposed, treatment receiving adults (N = 106). Trauma appraisals fully mediated relationships between childhood trauma and PTSD/depression. Appraisals also mediated the relationships between cumulative trauma and depression. When appraisal subscales were simultaneously entered, alienation appraisals were the only significant mediator of these relationships. The study found support for the proposed mediating role of trauma appraisals between different forms of trauma and trauma related distress. Alienation appraisals were particularly emphasised.

A Meta-Analysis of the Association Between Appraisals of Trauma and Posttraumatic Stress in Children and Adolescents.

Cognitive models of posttraumatic stress disorder (PTSD) place an emphasis on the role of negative appraisals of traumatic events. It is suggested that the way in which the event is appraised determines the extent to which posttraumatic stress symptoms will be experienced. Therefore, a strong relationship between trauma appraisals and symptoms of PTSD might be expected. However, this relationship is not as firmly established in the child and adolescent literature. A systematic literature review of this relationship returned 467 publications, of which 11 met full eligibility criteria. A random effects meta-analysis revealed a large effect size for the relationship between appraisals and PTSD symptoms in children and adolescents, r = .63, 95% CI [.58, .68], Z = 17.32, p < .001, with significant heterogeneity present. A sensitivity analysis suggested that this relationship was not contingent on 1 specific measure of appraisals. Results were consistent with the cognitive behavioral theory of PTSD, demonstrating that appraisals of trauma are strongly related to posttraumatic stress in children and adolescents. However, this relationship was not observed in a sample of 4- to 6-year-olds, indicating that further research is required to explicate cognitive processing of trauma in very young children.

Mindfulness-based cognitive therapy (MBCT) reduces the association between depressive symptoms and suicidal cognitions in patients with a history of suicidal depression.

OBJECTIVE: In patients with a history of suicidal depression, recurrence of depressive symptoms can easily reactivate suicidal thinking. In this study, we investigated whether training in mindfulness, which is aimed at helping patients "decenter" from negative thinking, could help weaken the link between depressive symptoms and suicidal cognitions. METHOD: Analyses were based on data from a recent randomized controlled trial, in which previously suicidal patients were allocated to mindfulness-based cognitive therapy (MBCT), an active control treatment, cognitive psychoeducation (CPE), which did not include any meditation practice, or treatment as usual (TAU). After the end of the treatment phase, we compared the associations between depressive symptoms, as assessed through self-reports on the Beck Depression Inventory-II (Beck, Steer, & Brown, 1996), and suicidal thinking, as assessed through the Suicidal Cognitions Scale (Rudd et al., 2001). RESULTS: In patients with minimal to moderate symptoms at the time of assessment, comparisons of the correlations between depressive symptoms and suicidal cognitions showed significant differences between the groups. Although suicidal cognitions were significantly related to levels of symptoms in the 2 control groups, there was no such relation in the MBCT group. CONCLUSION: The findings suggest that, in patients with a history of suicidal depression, training in mindfulness can help to weaken the association between depressive symptoms and suicidal thinking, and thus reduce an important vulnerability for relapse to suicidal depression.

Memory specificity and mindfulness jointly moderate the effect of reflective pondering on depressive symptoms in individuals with a history of recurrent depression.

In previously depressed individuals, reflective thinking may easily get derailed and lead to detrimental effects. This study investigated the conditions in which such thinking is, or is not, adaptive. Levels of mindfulness and autobiographical memory specificity were assessed as potential moderators of the relationship between reflective thinking and depressive symptoms. Two hundred seventy-four individuals with a history of three or more previous episodes of depression completed self-report measures of depressive symptoms, rumination-including subscales for reflection and brooding-and mindfulness, as well as an autobiographical memory task to assess memory specificity. In those low in both mindfulness and memory specificity, higher levels of reflection were related to more depressive symptoms, whereas in all other groups higher levels of reflection were related to fewer depressive symptoms. The results demonstrate that the relation between reflective pondering and depressive symptoms varies depending on individual state or trait factors. In previously depressed individuals, the cognitive problem-solving aspect of reflection may be easily hampered when tendencies toward unspecific processing are increased, and awareness of mental processes such as self-judgment and reactivity is decreased.

Trait mindfulness as a limiting factor for residual depressive symptoms: an explorative study using quantile regression.

Mindfulness has been suggested to be an important protective factor for emotional health. However, this effect might vary with regard to context. This study applied a novel statistical approach, quantile regression, in order to investigate the relation between trait mindfulness and residual depressive symptoms in individuals with a history of recurrent depression, while taking into account symptom severity and number of episodes as contextual factors. Rather than fitting to a single indicator of central tendency, quantile regression allows exploration of relations across the entire range of the response variable. Analysis of self-report data from 274 participants with a history of three or more previous episodes of depression showed that relatively higher levels of mindfulness were associated with relatively lower levels of residual depressive symptoms. This relationship was most pronounced near the upper end of the response distribution and moderated by the number of previous episodes of depression at the higher quantiles. The findings suggest that with lower levels of mindfulness, residual symptoms are less constrained and more likely to be influenced by other factors. Further, the limiting effect of mindfulness on residual symptoms is most salient in those with higher numbers of episodes.

A comparison of vulnerability factors in patients with persistent and remitting lifetime symptom course of depression.

BACKGROUND: Research has suggested fundamental differences between patients with persistent and those with remitting courses of depression. This study investigated whether patients with different lifetime symptom course configurations differ in early risk and cognitive vulnerability factors. METHODS: Patients with at least three previous episodes who were currently in remission were categorized based on visual timelines of their lifetime symptom course and compared with regard to a number of different indicators of vulnerability including questionnaire measures of childhood trauma and experiential avoidance. RESULTS: Of the N=127 patients, n=47 showed a persistent course of the disorder with unstable remissions and symptoms most of the time, and n=59 showed a course with more stable, lasting remissions. Group comparisons indicated that patients with a more persistent course were significantly more likely to have suffered from childhood emotional abuse, and reported higher levels of experiential avoidance as well as related core beliefs. Experiential avoidance partially mediated the effect of childhood emotional abuse on persistence of symptoms. LIMITATIONS: The study is cross-sectional and does not allow conclusions with regard to whether differentiating variables are causally related to chronicity. Self-report measures may be subject to reporting biases. CONCLUSIONS: The results highlight the detrimental effects of childhood adversity and suggest that experiential avoidance may play an important role in mediating such effects.

Mindfulness-based cognitive therapy for preventing relapse in recurrent depression: a randomized dismantling trial.

OBJECTIVE: We compared mindfulness-based cognitive therapy (MBCT) with both cognitive psychological education (CPE) and treatment as usual (TAU) in preventing relapse to major depressive disorder (MDD) in people currently in remission following at least 3 previous episodes. METHOD: A randomized controlled trial in which 274 participants were allocated in the ratio 2:2:1 to MBCT plus TAU, CPE plus TAU, and TAU alone, and data were analyzed for the 255 (93%; MBCT = 99, CPE = 103, TAU = 53) retained to follow-up. MBCT was delivered in accordance with its published manual, modified to address suicidal cognitions; CPE was modeled on MBCT, but without training in meditation. Both treatments were delivered through 8 weekly classes. RESULTS: Allocated treatment had no significant effect on risk of relapse to MDD over 12 months follow-up, hazard ratio for MBCT vs. CPE = 0.88, 95% CI [0.58, 1.35]; for MBCT vs. TAU = 0.69, 95% CI [0.42, 1.12]. However, severity of childhood trauma affected relapse, hazard ratio for increase of 1 standard deviation = 1.26 (95% CI [1.05, 1.50]), and significantly interacted with allocated treatment. Among participants above median severity, the hazard ratio was 0.61, 95% CI [0.34, 1.09], for MBCT vs. CPE, and 0.43, 95% CI [0.22, 0.87], for MBCT vs. TAU. For those below median severity, there were no such differences between treatment groups. CONCLUSION: MBCT provided significant protection against relapse for participants with increased vulnerability due to history of childhood trauma, but showed no significant advantage in comparison to an active control treatment and usual care over the whole group of patients with recurrent depression.

Developmental outcomes of children with congenital diaphragmatic hernia: a multicenter prospective study.

PURPOSE: To determine developmental outcomes and associated factors in patients with congenital diaphragmatic hernia (CDH) at 2 years of age. METHODS: This is a multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland Adaptive Behavior Scales (VABS-II) were performed at 2 years of age. RESULTS: BSID-III and VABS-II assessments were completed on 48 and 49 children, respectively. The BSID-III mean cognitive, language, and motor scores were significantly below the norm mean with average scores of 93 ± 15, 95 ± 16, and 95 ± 11. Ten percent (5/47) scored more than 2 standard deviations below the norm on one or more domains. VABS-II scores were similar to BSID-III scores with mean communication, daily living skills, social, motor, adaptive behavior scores of 97 ± 14, 94 ± 16, 93 ± 13, 97 ± 10, and 94 ± 14. For the BSID-III, supplemental oxygen at 28 days, a prenatal diagnosis, need for extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of discharge were associated with lower scores. At 2 years of age, history of hospital readmission and need for tube feeds were associated with lower scores. Lower socioeconomic status correlated with lower developmental scores when adjusted for significant health factors. CONCLUSION: CDH patients on average have lower developmental scores at 2 years of age compared to the norm. A need for ECMO, oxygen at 28 days of life, ongoing health issues and lower socioeconomic status are factors associated with developmental delays.

Pre-adult onset and patterns of suicidality in patients with a history of recurrent depression.

BACKGROUND: This report assesses the association between age of onset of major depression and later suicidality in a sample of 276 recurrently depressed patients recruited for the Oxford/Bangor Staying Well after Depression (SWAD) Trial, and interviewed when in remission. METHODS: The study enrolled adult patients with a history of at least three episodes of non-psychotic major depressive disorder from primary care and psychiatric care practices and through community advertisements. At study entry, all participants estimated the age of their first onset of a major depressive episode and completed both self-report and interview-based assessments of past and current suicidal ideation and behavior. Participants were divided into pre-adult and adult onset groups using a cut-off age of 18. RESULTS: Forty-eight percent of the sample reported a pre-adult age of onset. Pre-adult age of onset was significantly associated with suicidality, both from self-report and from interviewer assessment even when adjusting for differences in age, gender, employment status, length of the disorder and early adversity. LIMITATIONS: Relevant variables were all assessed through retrospective reports. CONCLUSIONS: Pre-adult age of onset is closely associated with risk for and severity of later suicidality, replicating, in a sample of patients assessed when in remission, findings from studies that assessed patients when currently depressed. The association of pre-adult age of onset with suicidality is not due to differences in sociodemographic variables, length of the disorder and early adversity.