Risk Factor For Psychiatric Disorders Research Articles

O49. Ketamine Promotes Fear Extinction and Rescues Dysfunction of Glutamate Release in a Rat Model of PTSD

Stress represents a major risk factor for psychiatric disorders, including Post Traumatic Stress Disorder (PTSD). Recently we dissected the destabilizing effects of acute stress in prefrontal cortex (PFC), with particular relevance to the glutamate system.

T12. Freezing is Associated With Higher Amygdala Metabolism in Female Adolescent Monkeys

Although freezing to potential threats is an evolutionarily conserved defense mechanism across species, excessive freezing during adolescence is a risk factor for psychiatric disorders like anxiety and depression. Neuroimaging studies on this risk have implicated a network of regions including the central nucleus of the amygdala (Ce). Here, we extend these previous studies, by utilizing the unique opportunity provided by the California National Primate Research Center to study animals that have been reared in large, outdoor, naturalistic social groups.

Melatonergic agonist regulates circadian clock genes and peripheral inflammatory and neuroplasticity markers in patients with depression and anxiety

ObjectiveCircadian dysfunction is a core manifestation and a risk factor for psychiatric disorders. Ramelteon (RMT), a melatonin receptor agonist, has been shown to induce sleep phase shifts and has been used to normalize sleep onset time. RMT has been used in sleep disorders, depression and anxiety. In this study, we aimed to investigate the effects of RMT in regulating gene expression profiles of the circadian clock and peripheral markers of inflammation and neuroplasticity. MethodsSixteen patients with a diagnosis of primary insomnia comorbid with depression and anxiety and ten healthy controls were recruited in an 8-week open-label trial. The patients with primary insomnia received RMT 8 mg/day. The morning expression profiles of 15 core clock genes from peripheral blood mononuclear cells (PBMCs), urine and plasma levels of melatonin and its metabolite levels, and plasma inflammatory markers and neurotrophin levels were evaluated at baseline, 4th and 8th week of RMT treatment. ResultsRMT treatment was associated with significant clinical improvement in depression scores at 8th week (Hamilton depression rating scale scores (Mean ± SEM) from 21.5 ± 2.44 to 14.31 ± 2.25, p ≤ 0.05). The overall poor sleep quality (Pittsburgh sleep quality index) of the patient group significantly improved (p ≤ 0.05) following RMT treatment. The mRNA level analysis showed a significant association between RMT treatment and alterations of the nine core circadian genes (CLOCK, PER1, PER2, CRY1, CRY2, NR1D1, NR1D2, DEC1 and TIMELESS) in the patient group when compared with the control group (p ≤ 0.05). Compared with the controls, the patient group had a decrease in neurotrophins (brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and beta-nerve growth factor; p ≤ 0.05) but an increase in pro-inflammatory cytokine levels (interleukin-6, interleukin-1b, tumour necrosis factor-alpha and interferon gamma; p ≤ 0.05); RMT treatment normalized the levels of neurotrophins and cytokine levels. ConclusionRMT treatment is able to restore phase-shifted melatonin markers, normalized the altered expression of the circadian genes, the levels of inflammatory cytokines and neurotrophins in patients with insomnia comorbid anxiety and depression.

Inflammation-dependent ISG15 upregulation mediates MIA-induced dendrite damages and depression by disrupting NEDD4/Rap2A signaling

BackgroundMaternal immune activation (MIA) is an independent risk factor for psychiatric disorders including depression spectrum in the offsprings, but the molecular mechanism is unclear. Recent studies show that interferon-stimulated gene-15 (ISG15) is involved in inflammation and neuronal dendrite development; here we studied the role of ISG15 in MIA-induced depression and the underlying mechanisms. MethodsBy vena caudalis injecting polyinosinic: polycytidylic acid (poly I:C) into the pregnant rats to mimic MIA, we used AAV or lentivirus to introduce or silence ISG15 expression. Synaptic plasticity was detected by confocal microscope and Golgi staining. Cognitive performances of the offspring were measured by Open field, Forced swimming and Sucrose preference test. ResultsWe found that MIA induced depression-like behaviors with dendrite impairments in the offspring with ISG15 level increased in the offsprings' brain. Overexpressing ISG15 in the prefrontal cortex of neonatal cubs (P0) could mimic dendritic pathology and depressive like behaviors, while downregulating ISG15 rescued these abnormalities in the offsprings. Further studies demonstrated that MIA-induced upregulation of inflammatory cytokines promoted ISG15 expression in the offspring’ brain which suppressed Rap2A ubiquitination via NEDD4 and thus induced Rap2A accumulation, while upregulating NEDD4 abolished ISG15-induced dendrite impairments. ConclusionsThese data reveal that MIA impedes offsprings' dendrite development and causes depressive like behaviors by upregulating ISG15 and suppressing NEDD4/Rap2A signaling. The current findings suggest that inhibiting ISG15 may be a promising intervention of MIA-induced psychiatric disorders in the offsprings.

Umwelt und Epigenetik

Environmental factors are among the strongest risk factors for psychiatric disorders. Differences in exposure to such environments have been associated with lasting biological changes. In recent years epigenetic mechanisms have been brought to the forefront as central in mediating alasting embedding of environmental risk factors. This article first summarizes the different levels of epigenetic regulation and then focuses on mechanisms transducing environmental signals into lasting epigenetic changes. This is followed by examples of how environmentally induced epigenetic changes relate to risk and resilience to psychiatric disorders and their treatment.

CACNA1C risk variant affects microstructural connectivity of the amygdala.

Deficits in perception of emotional prosody have been described in patients with affective disorders at behavioral and neural level. In the current study, we use an imaging genetics approach to examine the impact of CACNA1C, one of the most promising genetic risk factors for psychiatric disorders, on prosody processing on a behavioral, functional and microstructural level. Using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) we examined key areas involved in prosody processing, i.e. the amygdala and voice areas, in a healthy population. We found stronger activation to emotional than neutral prosody in the voice areas and the amygdala, but CACNA1C rs1006737 genotype had no influence on fMRI activity. However, significant microstructural differences (i.e. mean diffusivity) between CACNA1C rs1006737 risk allele carriers and non carriers were found in the amygdala, but not the voice areas. These modifications in brain architecture associated with CACNA1C might reflect a neurobiological marker predisposing to affective disorders and concomitant alterations in emotion perception.

Association of Genetic Risk Factors for Psychiatric Disorders and Traits of These Disorders in a Swedish Population Twin Sample

Psychiatric traits associated with categorically defined psychiatric disorders are heritable and present to varying degrees in the general population. It is commonly assumed that diagnoses represent the extreme end of continuously distributed traits in the population, but this assumption has yet to be robustly tested for many psychiatric phenotypes. To assess whether genetic risk factors associated with psychiatric disorders are also associated with continuous variation in milder population traits. This study combined a novel twin analytic approach with polygenic risk score (PRS) analyses in a large population-based twin sample. Phenotypic and genetic data were available from the Child and Adolescent Twin Study in Sweden. Inpatient data were available for January 1, 1987, to December 31, 2014, and outpatient data for January 1, 2001, to December 31, 2013. The last day of follow-up was December 31, 2014. Data analysis was performed from January 1, 2017, to September 30, 2017. Questionnaires that assessed traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, tic disorders (TDs), obsessive-compulsive disorder (OCD), anxiety, major depressive disorder (MDD), mania, and psychotic experiences were administered to a large Swedish twin sample. Individuals with clinical psychiatric diagnoses were identified using the Swedish National Patient Register. Joint categorical/continuous twin modeling was used to estimate genetic correlations between psychiatric diagnoses and continuous traits. The PRSs for psychiatric disorders were calculated based on independent discovery genetic data. The association between PRSs for each disorder and associated continuous traits was tested. Phenotype data were available for 13 923 twin pairs (35.1% opposite sex and 31.7% same-sex females) at 9 years of age, 5165 pairs (36.9% opposite sex and 34.0% same-sex females) at 15 years of age, and 4273 pairs (36.5% opposite sex and 34.4% same-sex females) at 18 years of age. Genetic data were available for 13 412 individuals (50.2% females). Twin genetic correlations between numerous psychiatric diagnoses and corresponding traits ranged from 0.31 to 0.69. Disorder PRSs were associated with related population traits for ASD (β [SE] = 0.04 [0.01] at 9 years of age), ADHD (β [SE] = 0.27 [0.03] at 9 years of age), TDs (β [SE] = 0.02 [0.004] at 9 years of age), OCD (β [SE] = 0.13 [0.05] at 18 years of age), anxiety (β [SE] = 0.18 [0.08] at 9 years of age; β [SE] = 0.07 [0.02] at 15 years of age; and β [SE] = 0.40 [0.17] at 18 years of age), MDD (β [SE] = 0.10 [0.03] at 9 years of age; β [SE] = 0.11 [0.02] at 15 years of age; and β [SE] = 0.41 [0.10] at 18 years of age), and schizophrenia (β [SE] = 0.02 [0.01] at 18 years of age). Polygenic risk scores for depressive symptoms were associated with MDD diagnoses (odds ratio, 1.16; 95% CI, 1.02-1.32). These results suggest that genetic factors associated with psychiatric disorders are also associated with milder variation in characteristic traits throughout the general population for many psychiatric phenotypes. This study suggests that many psychiatric disorders are likely to be continuous phenotypes rather than the categorical entities currently defined in diagnostic manuals, which has strong implications for genetic research in particular.

The Impact of an Occupational Injury on Developing Psychiatric Disorders in Taiwan

Background: Injuries are known to be a relevant risk factor for psychiatric disorders. Psychiatric disorders were found increased after occupational injury, and such increase was observed up to six...

Alterations of GABAergic Neuron-Associated Extracellular Matrix and Synaptic Responses in Gad1-Heterozygous Mice Subjected to Prenatal Stress.

Exposure to prenatal stress (PS) and mutations in Gad1, which encodes GABA synthesizing enzyme glutamate decarboxylase (GAD) 67, are the primary risk factors for psychiatric disorders associated with abnormalities in parvalbumin (PV)-positive GABAergic interneurons in the medial prefrontal cortex (mPFC). Decreased expression of extracellular matrix (ECM) glycoproteins has also been reported in patients with these disorders, raising the possibility that ECM abnormalities may play a role in their pathogenesis. To elucidate pathophysiological changes in ECM induced by the gene–environment interaction, we examined heterozygous GAD67-GFP (Knock-In KI; GAD67+/GFP) mice subjected to PS from embryonic day 15.0 to 17.5. Consistent with our previous study, we confirmed a decrease in the density of PV neurons in the mPFC of postnatal GAD67+/GFP mice with PS, which was concurrent with a decrease in density of PV neurons surrounded by perineuronal nets (PNNs), a specialized ECM important for the maturation, synaptic stabilization and plasticity of PV neurons. Glycosylation of α-dystroglycan (α-DG) and its putative mediator fukutin (Fktn) in the ECM around inhibitory synapses has also been suggested to contribute to disease development. We found that both glycosylated α-DG and the mRNA level of Fktn were reduced in GAD67+/GFP mice with PS. None of these changes were detected in GAD67+/GFP naive mice or wild type (GAD67+/+) mice with PS, suggesting that both PS and reduced Gad1 gene expression are prerequisites for these changes. When assessing the function of interneurons in the mPFC of GAD67+/GFP mice with PS through evoked inhibitory post-synaptic currents (eIPSCs) in layer V pyramidal neurons, we found that the threshold stimulus intensity for eIPSC events was reduced and that the eIPSC amplitude was increased without changes in the paired-pulse ratio (PPR). Moreover, the decay rate of eIPSCs was also slowed. In line with eIPSC, spontaneous IPSC (sIPSC) amplitude, frequency and decay tau were altered. Thus, our study suggests that alterations in the ECM mediated by gene-environment interactions might be linked to the enhanced and prolonged GABA action that compensates for the decreased density of PV neurons. This might be one of the causes of the excitatory/inhibitory imbalance in the mPFC of psychiatric patients.

Seasonal Allergies and Psychiatric Disorders in the United States.

Seasonal allergies have been associated with mental health problems, though the evidence is still emergent, particularly in the United States. We analyzed data from the National Comorbidity Survey Replication and the National Latino and Asian American Survey (years 2001–2003). Multivariable logistic regression models were used to examine the relations between lifetime allergies and lifetime psychiatric disorders (each disorder in a separate model), adjusting for socio-demographic variables (including region of residence) and tobacco use. Analyses were also stratified to test for effect modification by race and sex. A history of seasonal allergies was associated with greater odds of mood disorders, anxiety disorders, and eating disorders, but not alcohol or substance use disorders, after adjusting for socio-demographic characteristics and tobacco use. The associations between seasonal allergies and mood disorders, substance use disorders, and alcohol use disorders were particularly strong for Latino Americans. The association between seasonal allergies and eating disorders was stronger for men than women. Seasonal allergies are a risk factor for psychiatric disorders. Individuals complaining of seasonal allergies should be screened for early signs of mental health problems and referred to specialized services accordingly.

Bio Psychosocial Risk Factors of Depression in the Menopausal Transition: A Narrative Review

Context: As the most common psychiatric disorder associated with menopause, depression is associated with significant morbidity and mortality consequences. Given the importance of identifying risk factors of depression in the menopausal period, this study aims to determine bio psychosocial risk factors of depression during the menopausal transition. Evidence Acquisition: For this narrative review, electronic databases including Google Scholar, Magiran, Scientific Information Database (SID), PubMed, Web of Science, Scopus, Ovid, Science Direct, and ProQuest were searched. Articles published between 1978 and 2017 were retrieved, and an abstract and full-text appraisal was conducted. A total of 71 articles were selected for this review. The inclusion criteria included articles focusing on depression in menopausal-aged women that were published in scientific journals and English and Farsi language articles conducted in menopausal aged women. Results: The bio psychosocial risk factors of depression were divided into three major categories: biological, psychological, and social risk factors. Conclusions: Given the important role of psychological health in menopausal-aged women, it is recommended that mental health and risk factors of psychiatric disorders in menopause are evaluated at menopause clinics and that every high-risk woman is referred to a psychiatrist for pharmacological or non-pharmacological intervention. Keywords: Biological; Depression; Menopause; Psychiatric Disorders; Psychosocial Factors

Prevalence and risk factors of psychiatric disorders in early adolescence: 2004 Pelotas (Brazil) birth cohort

PurposeThe present study aimed to evaluate the prevalence of psychiatric disorders in early adolescence, to examine the distribution of psychiatric disorders by maternal and child characteristics and to evaluate the occurrence of psychiatric comorbidities.MethodsThis was a prospective cohort study of all live births in the city of Pelotas, Brazil, in 2004 (n = 4231). A total of 3562 subjects were evaluated at 11 years of age. Psychiatric disorders were assessed using the Development and Well-Being Assessment. Crude and adjusted logistic regression was used to investigate risk factors for any psychiatric disorder.ResultsAccording to DSM-5 criteria, the overall prevalence of psychiatric disorders was 13.2% (n = 471), 15.6% among the boys and 10.7% among the girls. The most common disorders were anxiety disorders (4.3%), any attention deficit/hyperactivity disorder (4.0%) and any conduct/oppositional disorder (2.8%). Low maternal education, smoking during pregnancy, the presence of moods symptoms during pregnancy or maternal chronic and severe depressive symptoms in the first years of the adolescent´s life, male gender, 5-min Apgar score < 7 at birth and preterm birth were associated with higher odds of any psychiatric disorder at age 11. Psychiatric comorbidities were observed in 107 subjects (22.7%), of whom 73, 24, and 10 had two, three, and four psychiatric diagnoses, respectively.ConclusionsOur results underscore the importance of psychiatric disorders as a prevalent condition in early adolescence, which has a direct impact on the planning of public policies and specific mental health care services in this age group.

S55. Neural Responses to Reward in Childhood Predict Stress Reactivity in Early Adolescence

Altered responses to both reward and acute stress are a well-known risk factor for psychiatric disorders, including depression and anxiety. Whereas some studies have examined changes in neural reward processing under or after stress conditions, few studies have tested whether such responses are related to stress reactivity later in life, especially in sensitive developmental periods such as early adolescence.

T4. IDENTIFICATION OF NEUROANATOMICAL SURROGATE MARKERS OF CHILDHOOD TRAUMA

BackgroundChildhood trauma (CT) plays an important role in psychiatric disorders. It is associated with an increased risk for psychiatric disorders like major depression, anxiety disorders, dependency, post-traumatic stress disorders and even psychosis. There is a high incidence of CT in patients with psychosis, especially for physical and sexual abuse. Already in UHR-individuals increased CT could be observed. A study of Thompson and colleagues showed that 97% of their UHR sample reported a trauma in the past. 83% of the cases were physical abuse, 67% emotional abuse and 27% sexual abuse. Our aim was to investigate if there are neurobiological surrogate markers of trauma existing which can be detected by a multi pattern analysis.MethodsPRONIA (‘Personalized Prognostic Tools for Early Psychosis Management’) is a prospective collaboration project funded by the European Union under the 7th Framework Programme (grant agreement n° 602152). Considering a broad set of variables (sMRI, rsMRI, DTI, psychopathological, life event related and sociobiographic data, neurocognition, genomics and other blood derived parameters) as well as advanced statistical methods, PRONIA aims at developing an innovative multivariate prognostic tool enabling an individualized prediction of illness trajectories and outcome. Seven clinical centers in five European countries and in Australia participate in the evaluation of three clinical groups (subjects clinically at high risk of developing a psychosis [CHR], patients with a recent onset psychosis [ROP] and patients with a recent onset depression [ROD]) as well as healthy controls; planned sample size is n=1680. CT was assessed by the Childhood Trauma Questionnaire (CTQ). To identify neuroanatomical and functional surrogate markers of CT, a multi pattern analysis via Neurominer (NM) was conducted. An additional VBM analysis was performed to evaluate the results of the NM analysis.ResultsWe found that patients and HC could be separated very well by the CTQ pattern. Moreover, the classification among the patient groups yielded results that were not much better than a random classification. This finding underlines that CT is an overarching risk factor for mental diseases and not specific for single clinical entities. Furthermore, the decision scores that were conducted in the first NM analysis revealed highly significant negative correlations with grey matter changes in frontotemporal cortical areas, the anterior cingulate and the insular cortex. These areas are already discussed for CT in the literature.DiscussionCT seems to be a global risk factor for psychiatric disorders. Moreover, we could re-examine the results of our multi variate analysis successfully in a VBM procedure.

Risk factors associated with newly psychiatric disorder in spinal cord injury: A retrospective cohort study.

To predict the risk factors related to newly diagnosed psychiatric disorders resulting from spinal cord injuries (SCIs). SCIs are a common result of devastating accidents; they can have an essential negative impact on the psychological health of those so afflicted. Psychiatric disorders commonly occur worldwide and are often associated with pain and disability; however, few studies have investigated the risk factors of psychiatric disorders among persons with SCIs. A retrospective cohort study design with data obtained from the Taiwan Health Insurance Research Database (THIRD). THIRD involves the claims data on recipients recorded in the Taiwan National Health Insurance (TNHI), which was set up in 1995 and covers about 99% of the 23 million persons in Taiwan. We used THIRD to predict the risk factors related to newly diagnosed psychiatric disorders among victims of spinal cord injury. The majority of persons with SCI were men (51.2%), and their average age was 52.8years. All 5,828 newly diagnosed psychiatric disorders were included from 1997-2009 in 64,907 SCI in the THIRD data set. These results demonstrated notable differences in hazard risk (HR); the injured persons were inspected for the level of SCI, age, hypertension and chronic obstructive pulmonary disease (HR: 1.637, 95% CI: 1.452-1.844, p<.0001; HR: 1.005, 95% CI: 1.002-1.009, p=.0019; HR: 0.724, 95% CI: 0.642-0.816; HR: 1.267, 95% CI: 1.105-1.454, p=.0007; HR: 1.368, 95% CI: 1.183-1.582, p<.0001, respectively); the persons with SCI exhibited significant independent associations with psychiatric disorders. The results revealed that the level of SCI, female gender and age, respectively, affects the incidence of newly diagnosed psychiatric disorder related to SCI. This study showed that psychiatric disorders may be associated with the development of SCI, and that this risk was more predominant in females with SCI. Our results are of direct clinical relevance as they are meant to assist clinical assessment, counselling, guidance of symptomatic monitoring and early clinical intervention.

Evolutionary Perspectives on Genetic and Environmental Risk Factors for Psychiatric Disorders

Evolutionary medicine uses evolutionary theory to help elucidate why humans are vulnerable to disease and disorders. I discuss two different types of evolutionary explanations that have been used to help understand human psychiatric disorders. First, a consistent finding is that psychiatric disorders are moderately to highly heritable, and many, such as schizophrenia, are also highly disabling and appear to decrease Darwinian fitness. Models used in evolutionary genetics to understand why genetic variation exists in fitness-related traits can be used to understand why risk alleles for psychiatric disorders persist in the population. The usual explanation for species-typical adaptations-natural selection-is less useful for understanding individual differences in genetic risk to disorders. Rather, two other types of models, mutation-selection-drift and balancing selection, offer frameworks for understanding why genetic variation in risk to psychiatric (and other) disorders exists, and each makes predictions that are now testable using whole-genome data. Second, species-typical capacities to mount reactions to negative events are likely to have been crafted by natural selection to minimize fitness loss. The pain reaction to tissue damage is almost certainly such an example, but it has been argued that the capacity to experience depressive symptoms such as sadness, anhedonia, crying, and fatigue in the face of adverse life situations may have been crafted by natural selection as well. I review the rationale and strength of evidence for this hypothesis. Evolutionary hypotheses of psychiatric disorders are important not only for offering explanations for why psychiatric disorders exist, but also for generating new, testable hypotheses and understanding how best to design studies and analyze data.

Characteristics of foster care history as risk factors for psychiatric disorders among youth in care.

This study evaluates foster care history characteristics as risk factors for psychopathology. We examine characteristics of youths' foster care histories separately and as a gestalt (i.e., identification of latent classes). Six mental health disorders and lifetime suicide attempt were assessed via in-person interviews with a representative sample of older adolescents in California foster care (n = 706). Information on respondents' foster care histories were obtained from state administrative data. Half of the sample (47.3%) screened positive for a psychiatric disorder and 1/4 (25.2%) had attempted suicide. When assessed individually, placement instability predicted posttraumatic stress disorder (PTSD), alcohol and substance use problems, and suicide attempt. Primary placement type and maltreatment type were also associated with 1 or more psychiatric disorders. When foster care characteristics were considered in concert, 6 latent classes were identified: veterans, returners, treated stayers, midrangers, late stayers, and disquieted drifters. Three latent classes (returners, late stayers, and disquieted drifters) were at increased risk of psychiatric problems relative to 1 or more of the other latent classes. Both separate foster care characteristics and the gestalt of youths' foster care histories identified risks of psychiatric problems. Results from these analyses can inform the development of risk assessment tools. (PsycINFO Database Record

Rising incidence of psychiatric disorders before diagnosis of immune-mediated inflammatory disease.

After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population. Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year. We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30-1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12-1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10-2.40). The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology.

Depression and sterile inflammation: Essential role of danger associated molecular patterns

Stress is a major risk factor for psychiatric disorder including major depressive disorder (MDD) and can induce inflammation, which is known to be dysregulated in depression. Several clinical and pre-clinical studies have demonstrated a strong association between depressive symptoms and the expression of factors that increase inflammation. Conversely, administration of anti-inflammatory agents has been shown to ameliorate depressive symptoms, demonstrating the importance of inflammation as a mediator of depression. Although it is clear that inflammation plays a role in the pathophysiology of depression, the mechanism by which inflammation is activated in mood disorders remains unclear. To address this issue, studies have investigated the role of pattern recognition receptor (PRR) activation in stress-induced inflammation and mood disorders. However, the identification of the endogenous factors, referred to as danger-associated molecular patterns (DAMP) that activate these receptors remains understudied. Here we review the role of DAMPs in depression and highlight the clinical evidence for elevation of DAMP signaling in MDD patients and in pre-clinical animal stress models of depression.

Adolescents hospitalisés dans les services de psychiatrie adulte : une étude descriptive à la lumière des problématiques relevant de la protection de l’enfance

BackgroundAdolescents hospitalized in adult mental health departments are many, and an important part of them benefit from a child welfare system. Many teenagers hospitalized at the adult psychiatric services have symptoms of auto- or hetero-aggressive behaviours. The aim of our study was to describe the population of adolescents supported by these services by analyzing their demographic and psychiatric characteristics and their links with the areas of child protection and disability. MethodsWe performed a retrospective descriptive study based on the analysis of hospital records of teenagers supported by the adult psychiatric services. Criteria for the analysis include sociodemographic, psychiatric morbidity and schooling data, data on the terrain, and those related to child protection or disability. Then subpopulations were analyzed in order to compare the different criteria whether or not within the child welfare system. ResultsSixty teenagers were included in our study. An analysis of the total population shows that these adolescents wer exposed to risk factors for psychiatric disorders: lower socioeconomic conditions, psychiatric family history and traumatic life events. Many were also school-leavers compared to the general population. Furthermore, a majority of the teenagers benefited from a child protection measure (n=33) and were institutionalized. The subpopulation analysis helped realize the particular vulnerability of adolescents under the care of child protection. Indeed, we significantly emphasized among them an increased prevalence of parental isolation (P=0.001), of psychiatric family history (P=0.001) and of having experienced traumatic events (P<0.0001). Concerning psychiatric disorders, we also found by the child welfare system that mild to moderate mental retardation was significantly more frequent among teens (P=0.003). In addition, our results show that these adolescents were significantly more often hospitalized (P=0.013). Finally, still in comparison with the other adolescents, these teens were significantly more school-leavers (P=0.032), mostly in specialized or adapted course of study (P<0.001), and more subject to disability (P<0.001), implying a double care. ConclusionThis study has allowed us to better know the youth population supported by adult psychiatric services. It has also enlightened the specific vulnerability of the teenagers under the child protection care who need psychiatric treatment. It offers interesting discussion topics to develop new modalities of care for these young people.