Sex differences in rapid nonclassical action of 17β‐oestradiol on intracellular signalling and oestrogen receptor α expression in basal forebrain cholinergic neurones in mouse

Rapid nonclassical effects of 17β‐oestradiol (E₂) on intracellular signalling have been identified in the basal forebrain, although the extent to which these actions may be different in males and females is unknown. Previous work has shown that E₂ rapidly phosphorylates cAMP responsive element binding protein (CREB) via ΕRα in female cholinergic neurones. Using this indicator, the present study examined whether nonclassical actions of E₂ occur in a sexually dimorphic manner within basal forebrain cholinergic neurones in mice. In addition, we investigated the expression and intracellular distribution of oestrogen receptor (ΕR)α in cholinergic neurones in female and male mice. Animals were gonadectomised and treated 2 weeks later with E₂. The number of CREB‐expressing cholinergic neurones was not altered in any of the brain regions after E₂ treatment in both males and females. However, E₂ treatment rapidly (< 15 minutes) increased (P < 0.05) the number of cholinergic neurones expressing phosphorylated CREB (pCREB) in the substantia innominata and medial septum but not in the striatum in female mice. By contrast, E₂ did not change pCREB expression in cholinergic neurones in male mice at any time point (15 minutes, 1 hour, 4 hours), irrespective of the neuroanatomical location. We also observed that, in females, more cholinergic neurones expressed nuclear ΕRα in all regions, whereas males showed more cholinergic neurones with cytoplasmic or both nuclear and cytoplasmic expression of ΕRα. Taken together, these results demonstrate a marked sex difference in the E₂‐induced nonclassical effect and intracellular distribution of ΕRα in basal forebrain cholinergic neurones in vivo.     

Prefrontal theta modulates sensorimotor gamma networks during the reorienting of attention

The ability to execute a motor plan involves spatiotemporally precise oscillatory activity in primary motor (M1) regions, in concert with recruitment of “higher order” attentional mechanisms for orienting toward current task goals. While current evidence implicates gamma oscillatory activity in M1 as central to the execution of a movement, far less is known about top‐down attentional modulation of this response. Herein, we utilized magnetoencephalography (MEG) during a Posner attention‐reorienting task to investigate top‐down modulation of M1 gamma responses by frontal attention networks in 63 healthy adult participants. MEG data were evaluated in the time–frequency domain and significant oscillatory responses were imaged using a beamformer. Robust increases in theta activity were found in bilateral inferior frontal gyri (IFG), with significantly stronger responses evident in trials that required attentional reorienting relative to those that did not. Additionally, strong gamma oscillations (60–80 Hz) were detected in M1 during movement execution, with similar responses elicited irrespective of attentional reorienting. Whole‐brain voxel‐wise correlations between validity difference scores (i.e., attention reorienting trials—nonreorienting trials) in frontal theta activity and movement‐locked gamma oscillations revealed a robust relationship in the contralateral sensorimotor cortex, supplementary motor area, and right cerebellum, suggesting modulation of these sensorimotor network gamma responses by attentional reorienting. Importantly, the validity difference effect in this distributed motor network was predictive of overall motor function measured outside the scanner and further, based on a mediation analysis this relationship was fully mediated by the reallocation response in the right IFG. These data are the first to characterize the top‐down modulation of movement‐related gamma responses during attentional reorienting and movement execution.     

Toll‐like receptor 4 differentially regulates adult hippocampal neurogenesis in an age‐ and sex‐dependent manner

Toll‐like receptor 4 (TLR4) is primarily responsible for initiating an immune response following pathogen recognition. However, TLR4 is also expressed on neural progenitor cells and has been reported to regulate hippocampal neurogenesis as young male TLR4 knockout mice show increases in cell proliferation and doublecortin positive cells. Whether these effects occur in both sexes and are sustained with normal aging is currently unknown. The present study evaluated whether TLR4 deficiency alters adult hippocampal neurogenesis in young (3–4 months) and aged (18–20 months), male and female, TLR4 deficient (TLR4?/?; B6.B10ScN‐Tlr4lps‐del/JthJ) and wild type (WT) mice. Additionally, neurogenesis within the dorsal and the ventral hippocampal subdivisions was evaluated to determine if TLR4 has differential effects across the hippocampus. Bromodeoxyuridine (BrdU) was administered to quantify new cell survival as well as cell differentiation. Ki‐67 was measured to evaluate cell proliferation. Results show that young TLR4?/? females had higher rates of proliferation and neuronal differentiation in both the dorsal and ventral hippocampus relative to WT females. Young TLR4?/? males show elevated proliferation and neuronal differentiation mainly in the ventral hippocampus. While young TLR4?/? mice show enhanced neurogenesis compared to young WT mice, the increase was not apparent in the aged TLR4?/? mice. Both aged WT and TLR4?/? mice showed a decrease in proliferation, new cell survival, and neuronal differentiation compared to young WT and TLR4?/? mice. The data collectively indicate that TLR4 regulates hippocampal neurogenesis in young adults, but that these effects are region‐specific in males and that females show broader changes in neurogenesis throughout the hippocampus.     

Childhood maltreatment and poor functional outcomes at the transition to adulthood: a comparison of prospective informant- and retrospective self-reports of maltreatment

Purpose

Growing evidence suggests that prospective informant-reports and retrospective self-reports of childhood maltreatment may be differentially associated with adult psychopathology. However, it remains unknown how associations for these two maltreatment reporting types compare when considering functional outcomes. The present study compared associations between childhood maltreatment and functional outcomes at age 18 years using these two methods.

Methods

We used data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of 2232 children born in England and Wales in 1994–1995. Maltreatment prior to age 12 years was assessed prospectively (during multiple home visits between birth and age of 12 years based on interviews with caregivers, researcher observations, and information from practitioners where child protection referrals were made) and retrospectively (at age 18 via self-report on the Childhood Trauma Questionnaire). Nine functional outcomes were measured at age 18, forming two variables capturing: (i) psychosocial and (ii) vocational disadvantage.

Results

Among the 2054 participants with available data, childhood maltreatment was associated with poorer functional outcomes regardless of whether this was reported only prospectively, only retrospectively, or both. Stronger associations with psychosocial disadvantage arose in the context of retrospective recall by participants (OR = 8.25, 95% CI 4.93–13.82) than prospective reports by informants (OR = 2.03, 95% CI 1.36–3.04) of maltreatment. Conversely, associations with vocational disadvantage were comparable for both prospective informant-reports (OR = 2.19, 95% CI 1.42–3.38) and retrospective self-reports (OR = 1.93, 95% CI 1.33–2.81) of maltreatment.

Conclusion

Results highlight the importance of considering the maltreatment report type used when interpreting the functional consequences of childhood maltreatment.

     

Predictive validity of the HCR-20V3 in a sample of Australian forensic psychiatric patients

The Historical Clinical Risk Management-20 Version 3 is the latest iteration in the HCR-20 series, adopting novel changes such as the addition of Relevance ratings and non-requirement to include the Psychopathy Checklist–Revised. This study aimed to examine these changes and compare the predictive validity of the HCR-20^V3 to the HCR-20^V2. The sample comprised of 100 forensic psychiatric patients, retrospectively followed up for a maximum period of approximately 13 years post-discharge from the Thomas Embling Hospital. Recidivism data were sourced from official police records. Results indicated good to excellent inter-rater reliability. The HCR-20^V3 significantly predicted violent recidivism (area under the curve = .70 to .77), levels of accuracy that were not significantly different from the HCR-20^V2. HCR-20^V3 Relevance ratings failed to add incremental validity above Presence ratings; however, the PCL–R improved upon the HCR-20^V3’s validity. The study represented one of the first evaluations of the HCR-20^V3 in Australia.     

Factors Associated with Use of Evidence-Based Practice Strategies in Usual Care Youth Psychotherapy

The purpose of this study was to gain an understanding of how therapists providing usual care (UC) psychotherapy are using elements of treatment common to evidence-based practices (EBPs) for children with disruptive behavior disorders (DBPs) and to identify client and therapist characteristics that may be associated with EBP strategies directed toward children and those directed to their caregivers. Results indicate that certain child, family, and therapist characteristics are associated with use of EBP strategies; however, much of the variability in practice was not explained by the variables examined. These findings highlight the complexity of UC psychotherapy and provide directions for future research on implementation of EBPs in UC.     

Metabolic consequences of sleep and sleep loss

Reduced sleep duration and quality appear to be endemic in modern society. Curtailment of the bedtime period to minimum tolerability is thought to be efficient and harmless by many. It has been known for several decades that sleep is a major modulator of hormonal release, glucose regulation and cardiovascular function. In particular, slow wave sleep (SWS), thought to be the most restorative sleep stage, is associated with decreased heart rate, blood pressure, sympathetic nervous activity and cerebral glucose utilization, compared with wakefulness. During SWS, the anabolic growth hormone is released while the stress hormone cortisol is inhibited. In recent years, laboratory and epidemiologic evidence have converged to indicate that sleep loss may be a novel risk factor for obesity and type 2 diabetes. The increased risk of obesity is possibly linked to the effect of sleep loss on hormones that play a major role in the central control of appetite and energy expenditure, such as leptin and ghrelin. Reduced leptin and increased ghrelin levels correlate with increases in subjective hunger when individuals are sleep restricted rather than well rested. Given the evidence, sleep curtailment appears to be an important, yet modifiable, risk factor for the metabolic syndrome, diabetes and obesity. The marked decrease in average sleep duration in the last 50 years coinciding with the increased prevalence of obesity, together with the observed adverse effects of recurrent partial sleep deprivation on metabolism and hormonal processes, may have important implications for public health.