Children with maltreatment exposure exhibit rumination-like spontaneous thought patterns: association with symptoms of depression, subcallosal cingulate cortex thickness, and cortisol levels.

BACKGROUND: Childhood maltreatment is associated with pervasive risk for depression. However, the immediate cognitive and neural mechanisms that mediate this risk during development are unknown. We here studied the impact of maltreatment on self-generated thought (SGT) patterns and their association with depressive symptoms, subcallosal cingulate cortex (SCC) thickness, and cortisol levels in children. METHODS: We recruited 183 children aged 6-12 years, 96 of which were exposed to maltreatment. Children performed a mind wandering task to elicit SGTs. A subgroup of children underwent structural magnetic resonance imaging (N = 155) for SCC thickness analyses and saliva collection for quantification of free cortisol concentrations (N = 126) was collected. Using network analysis, we assessed thought networks and compared these networks between children with and without maltreatment exposure. Using multilevel analyses, we then tested the association between thought networks of children with maltreatment exposure with depressive symptoms, SCC thickness, and cortisol levels. RESULTS: Children exposed to maltreatment generated fewer positively valenced thoughts. Network analysis revealed rumination-like thought patterns in children with maltreatment exposure, which were associated with depressive symptoms, SCC thickness, and cortisol levels. Children with maltreatment exposure further exhibited decreased future-self thought coupling, which was associated with depressive symptoms, while other-related and past-oriented thoughts had the greatest importance within the network. CONCLUSIONS: Using a novel network analytic approach, we provide evidence that children exposed to maltreatment exhibit ruminative clustering of thoughts, which is associated with depressive symptoms and neurobiological correlates of depression. Our results provide a specific target for clinical translation to design early interventions for middle childhood. Targeting thought patterns in children with maltreatment exposure may be an effective strategy to effectively mitigate depression risk early in life.

Impaired empathic functioning in chronic depression: Behavioral evidence for the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) model.

The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) model proposes preoperational functioning as a core feature of persistent depressive disorders (PDD). Empathy deficits comprise one aspect. Resulting from childhood maltreatment, empathy deficits may aggravate social isolation, a key factor in the maintenance of depression. CBASP targets empathy by teaching patients to disengage from past experiences and to engage successfully in present social interactions. However, behavioral evidence for empathy deficits in PDD has remained elusive. We reasoned that deficits become apparent only under stress and that these deficits improve after CBASP-treatment. Twenty-two patients and 21 controls performed two parallel versions of the Multifaceted Empathy Test. For stress induction, a negative autobiographical event was presented before performing the task. A neutral event served as control. Fifteen patients performed the experiment twice, before and after a 12-week inpatient CBASP-treatment. Supporting our hypotheses, patients showed reduced empathy under stress, while no group difference was found in the absence of stress. Reduced empathy correlated with the level of re-experiencing negative memories. Pre-post-treatment comparison revealed that the stress-induced empathy deficit improved in patients over time. Post-treatment empathic capacity correlated positively with clinical improvement. Our findings provide empirical support for the CBASP model, but highlight an important new aspect: Empathy is not generally deficient in PDD but becomes impaired under stress. In real-life situations, stress-induced empathy impairments may exacerbate interpersonal conflicts. CBASP's interpersonal focus improved empathy, accompanied by clinical improvement as the model predicts.

Measurement of cortisol in saliva: a comparison of measurement error within and between international academic-research laboratories.

OBJECTIVE: Hundreds of scientific publications are produced annually that involve the measurement of cortisol in saliva. Intra- and inter-laboratory variation in salivary cortisol results has the potential to contribute to cross-study inconsistencies in findings, and the perception that salivary cortisol results are unreliable. This study rigorously estimates sources of measurement variability in the assay of salivary cortisol within and between established international academic-based laboratories that specialize in saliva analyses. One hundred young adults (Mean age: 23.10 years; 62 females) donated 2 mL of whole saliva by passive drool. Each sample was split into multiple- 100 µL aliquots and immediately frozen. One aliquot of each of the 100 participants' saliva was transported to academic laboratories (N = 9) in the United States, Canada, UK, and Germany and assayed for cortisol by the same commercially available immunoassay. RESULTS: 1.76% of the variance in salivary cortisol levels was attributable to differences between duplicate assays of the same sample within laboratories, 7.93% of the variance was associated with differences between laboratories, and 90.31% to differences between samples. In established-qualified laboratories, measurement error of salivary cortisol is minimal, and inter-laboratory differences in measurement are unlikely to have a major influence on the determined values.

Mitochondrial hexokinase II (HKII) and phosphoprotein enriched in astrocytes (PEA15) form a molecular switch governing cellular fate depending on the metabolic state.

The metabolic state of a cell is a key determinant in the decision to live and proliferate or to die. Consequently, balanced energy metabolism and the regulation of apoptosis are critical for the development and maintenance of differentiated organisms. Hypoxia occurs physiologically during development or exercise and pathologically in vascular disease, tumorigenesis, and inflammation, interfering with homeostatic metabolism. Here, we show that the hypoxia-inducible factor (HIF)-1-regulated glycolytic enzyme hexokinase II (HKII) acts as a molecular switch that determines cellular fate by regulating both cytoprotection and induction of apoptosis based on the metabolic state. We provide evidence for a direct molecular interactor of HKII and show that, together with phosphoprotein enriched in astrocytes (PEA15), HKII inhibits apoptosis after hypoxia. In contrast, HKII accelerates apoptosis in the absence of PEA15 and under glucose deprivation. HKII both protects cells from death during hypoxia and functions as a sensor of glucose availability during normoxia, inducing apoptosis in response to glucose depletion. Thus, HKII-mediated apoptosis may represent an evolutionarily conserved altruistic mechanism to eliminate cells during metabolic stress to the advantage of a multicellular organism.