Prevalence Rates of Mental Disorders in Chilean Prisons

PMCID: PMC371883

Selective blockade of interferon-α and -β reveals their non-redundant functions in a mouse model of West Nile virus infection

Although type I interferons (IFNs) were first described almost 60 years ago, the ability to monitor and modulate the functional activities of the individual IFN subtypes that comprise this family has been hindered by a lack of reagents. The major type I IFNs, IFN-β and the multiple subtypes of IFN-α, are expressed widely and induce their effects on cells by interacting with a shared heterodimeric receptor (IFNAR). In the mouse, the physiologic actions of IFN-α and IFN-β have been defined using polyclonal anti-type I IFN sera, by targeting IFNAR using monoclonal antibodies or knockout mice, or using Ifnb-/- mice. However, the corresponding analysis of IFN-α has been difficult because of its polygenic nature. Herein, we describe two monoclonal antibodies (mAbs) that differentially neutralize murine IFN-β or multiple subtypes of murine IFN-α. Using these mAbs, we distinguish specific contributions of IFN-β versus IFN-α in restricting viral pathogenesis and identify IFN-α as the key mediator of the antiviral response in mice infected with West Nile virus. This study thus suggests the utility of these new reagents in dissecting the antiviral and immunomodulatory roles of IFN-β versus IFN-α in murine models of infection, immunity, and autoimmunity

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

Omega-3 supplementation from pregnancy to postpartum to prevent depressive symptoms: a randomized placebo-controlled trial

Background: Low n-3 polyunsaturated fatty acids (PUFAs) has been linked to depression, but the preventive effect of n-3PUFAs supplementation on maternal depression needs further investigation. We aimed to evaluate the efficacy of a daily dose of n-3 PUFAs supplementation (fish oil) on the prevention of postpartum depression (PPD). Methods: A randomized, placebo-controlled, double blind trial was designed and nested into a cohort study conducted in Rio de Janeiro, Brazil. Sixty pregnant women identified as being at risk for PPD were invited and randomly assigned to receive fish oil capsules [1.8 g (1.08 g of Eicosapentaenoic (EPA) and 0.72 g of Docosapentaenoic (DHA) acids)] or placebo (control). The Edinburgh Postnatal Depression Scale (EPDS) was scored at 5–13 (T0, baseline), 22–24 (T1), 30–32 weeks of gestation (T2) and 4–6 weeks’ postpartum (T3). Supplementation started at week 22–24 of gestation (T1) and lasted for 16 weeks. Serum fatty acids were assayed to evaluate compliance. Prevalence of EPDS ≥11 was the primary outcome, and mean and changes in EPDS score, length of gestation, and birth weight the secondary outcomes. Linear mixed-effect (LME) and random-intercept logistic regression models were performed to test the effect of fish oil supplementation on prevalence of EPDS ≥11 and EPDS scores variation. Results: In intention-to-treat (ITT) analysis, at 30–32 weeks’ gestation women in the fish oil presented higher serum concentration of EPA, DHA and lower n-6/n-3 ratio comparing to the control group. There were no differences between intervention and control groups in the prevalence of EPDS ≥11, EPDS scores over time, or in changes in EPDS scores from pregnancy to postpartum in either the ITT or per-protocol analyses. Women in the fish oil group with previous history of depression presented a higher reduction on the EPDS score from the second to the third trimester in the fish oil comparing to the control group in the ITT analyses [−1.0 (−3.0–0.0) vs. -0.0 (−1.0–3.0), P = 0.038). These results were confirmed on the LME model (β = −3.441; 95%CI: -6.532– -0.350, P = 0.029). Conclusion: Daily supplementation of 1.8 g of n-3 PUFAs during 16 weeks did not prevent maternal depressive symptoms in a sample of Brazilian women

Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans

DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene (KITLG; cg27512205) showed the strongest association with cortisol stress reactivity (P=5.8 � 10?6). Replication was obtained in two independent samples using either blood (N=45, P=0.001) or buccal cells (N=255, P=0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability

Treatment and outcomes of an Australian cohort of outpatients with bipolar 1 or schizoaffective disorder over twenty-four months : implications for clinical practice

Background The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with &lsquo;real-world&rsquo; treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication.Methods Participants prescribed either conventional mood stabilizers (CMS; n&thinsp;=&thinsp;155) alone, or olanzapine with, or without, CMS (olanzapine&thinsp;&plusmn;&thinsp;CMS; n&thinsp;=&thinsp;84) were assessed every 3&thinsp;months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale &ndash; Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data.Results On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24&thinsp;months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine&thinsp;&plusmn;&thinsp;CMS (61%;) cohorts.Conclusions Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.<br /

Mitochondria and neuroplasticity

The production of neurons from neural progenitor cells, the growth of axons and dendrites and the formation and reorganization of synapses are examples of neuroplasticity. These processes are regulated by cell-autonomous and intercellular (paracrine and endocrine) programs that mediate responses of neural cells to environmental input. Mitochondria are highly mobile and move within and between subcellular compartments involved in neuroplasticity (synaptic terminals, dendrites, cell body and the axon). By generating energy (ATP and NAD+), and regulating subcellular Ca2+ and redox homoeostasis, mitochondria may play important roles in controlling fundamental processes in neuroplasticity, including neural differentiation, neurite outgrowth, neurotransmitter release and dendritic remodelling. Particularly intriguing is emerging data suggesting that mitochondria emit molecular signals (e.g. reactive oxygen species, proteins and lipid mediators) that can act locally or travel to distant targets including the nucleus. Disturbances in mitochondrial functions and signalling may play roles in impaired neuroplasticity and neuronal degeneration in Alzheimer's disease, Parkinson's disease, psychiatric disorders and stroke

Modern Clinical Research on LSD

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry

Research led by participants: a new social contract for a new kind of research

In recent years, there have been prominent calls for a new social contract that accords a more central role to citizens in health research. Typically, this has been understood as citizens and patients having a greater voice and role within the standard research enterprise. Beyond this, however, it is important that the renegotiated contract specifically addresses the oversight of a new, path-breaking approach to health research: participant-led research. In light of the momentum behind participant-led research and its potential to advance health knowledge by challenging and complementing traditional research, it is vital for all stakeholders to work together in securing the conditions that will enable it to flourish