Risk Factor For Psychiatric Disorders Research Articles

Mechanisms and Effects of Dietary Restriction on CNS and Affective Disorders

Abstract Neuropsychiatric disorders, including depression contribute significantly to global disability and possess high social and health burden. Management is dominated by pharmacotherapy and psychotherapy; nevertheless, such treatments prevent or treat less than half of the patients, suggesting that alternative approaches are required. Emerging data suggest that diet may be an adjustable risk factor for psychiatric disorders. Caloric restriction (CR) possesses protective effects in almost all organs including the brain. However, the precise molecular pathways of these effects remain uncertain. In this review, we will discuss the putative neurobiological mechanisms of CR on the brain. The article will address also the molecular basis of the antidepressant effects of CR, primarily including ghrelin signaling, CREB neurotropic effects and ketone bodies production. Then we will highlight the probable effect of CR on the neuroinflammation, which emerges as a key pathogenetic factor for the majority of neuropsychiatric disorders. Finally, we discuss the so called caloric restriction mimetics, compounds that reproduce properties of CR. Further research will be required to verify the safety and efficacy of CR before a general approval can be proposed to introduce it and its mimetics in clinical practice for the treatment of neuropsychiatric disorders.

The role of social cognition skills and social determinants of health in predicting symptoms of mental illness

Social factors, such as social cognition skills (SCS) and social determinants of health (SDH), may be vital for mental health, even when compared with classical psycho-physical predictors (demographic, physical, psychiatric, and cognitive factors). Although major risk factors for psychiatric disorders have been previously assessed, the relative weight of SCS and SDH in relation to classical psycho-physical predictors in predicting symptoms of mental disorders remains largely unknown. In this study, we implemented multiple structural equation models (SEM) from a randomized sample assessed in the Colombian National Mental Health Survey of 2015 (CNMHS, n = 2947, females: 1348) to evaluate the role of SCS, SDH, and psycho-physical factors (totaling 17 variables) as predictors of mental illness symptoms (anxiety, depression, and other psychiatric symptoms). Specifically, we assessed the structural equation modeling of (a) SCS (emotion recognition and empathy skills); (b) SDH (including the experience of social adversities and social protective factors); (c) and classical psycho-physical factors, including psychiatric antecedents, physical–somatic factors (chronic diseases), and cognitive factors (executive functioning). Results revealed that the emotion recognition skills, social adverse factors, antecedents of psychiatric disorders and chronic diseases, and cognitive functioning were the best predictors of symptoms of mental illness. Moreover, SCS, particularly emotion recognition skills, and SDH (experiences of social adversities, familial, and social support networks) reached higher predictive values of symptoms than classical psycho-physical factors. Our study provides unprecedented evidence on the impact of social factors in predicting symptoms of mental illness and highlights the relevance of these factors to track early states of disease.

Relations Between Trauma Exposure and Irritability-Related Amygdala Connectivity in Youth

Irritability, an increased proneness to anger relative to peers, is prevalent across pediatric psychiatric diagnoses and is associated with aberrant reward processing. Trauma exposure is a risk factor for psychiatric disorders that have irritability features, including depression and post-traumatic stress disorder. However, little is known about how early traumatic experience relates to aberrant irritability-related reward processing. Here, we examine how irritability-related neural patterns (i.e., amygdala connectivity) during reward processing task relates to childhood trauma exposure.

Youth Exposed to Maltreatment Show Age-Related Alterations in Hippocampal-Fronto-Amygdala Function During Extinction Recall

Exposure to childhood trauma is a major risk factor for psychiatric disorders. Delineating the neurodevelopmental mechanisms linking early-life trauma to psychopathology is critical for the early identification of risk and optimizing interventions to promote resilience. Maltreatment-exposed youth show alterations in fear conditioning and related hippocampal-frontoamygdala circuitry, yet much remains unknown about extinction and extinction recall, which are central to discriminating threat from safety following trauma.

Youth Exposed to Maltreatment Show Age-Related Alterations in Hippocampal-Fronto-Amygdala Function During Extinction Recall

Exposure to childhood trauma is a major risk factor for psychiatric disorders. Delineating the neurodevelopmental mechanisms linking early-life trauma to psychopathology is critical for the early identification of risk and optimizing interventions to promote resilience. Maltreatment-exposed youth show alterations in fear conditioning and related hippocampal-frontoamygdala circuitry, yet much remains unknown about extinction and extinction recall, which are central to discriminating threat from safety following trauma.

Psychiatric Disorders Among Older Black Americans: Within- and Between-Group Differences.

Psychiatric disorders impose significant personal, social, and financial costs for individuals, families, and the nation. Despite a large amount of research and several journals focused on psychiatric conditions, there is a paucity of research on psychiatric disorders among Black Americans (i.e., African Americans and Black Caribbeans), particularly older Black Americans. The present literature review examines research on psychiatric disorders among older Black Americans and provides a broad overview of research findings that are based on nationally representative studies. Collectively, this research finds: (1) older African Americans have lower rates of psychiatric disorders than younger African Americans; (2) family support is not protective of psychiatric disorders, whereas negative interaction with family members is a risk factor; (3) everyday discrimination is a risk factor for psychiatric disorders; (4) both older African Americans and African American across the adult age range have lower prevalence rates of psychiatric disorders than non-Latino whites; (5) Black Caribbean men have particularly high rates of depression, posttraumatic stress disorder, and suicide attempts; and (6) a significant proportion of African American older adults with mental health disorders do not receive professional help. This literature review also discusses the “Race Paradox” in mental health, the Environmental Affordances Model, and the importance of investigating ethnicity differences among Black Americans. Future research directions address issues that are directly relevant to the Black American population and include the following: (1) understanding the impact of mass incarceration on the psychiatric disorders of prisoners’ family members, (2) assessing the impact of immigration from African countries for ethnic diversity within the Black American population, (3) examining the impact of racial identity and racial socialization as potential protective factors for psychiatric morbidities, and (4) assessing racial diversity in life-course events and their impact on mental health.

Psychosocial triggers associated with major depressive episodes in women applying to psychiatric outpatient clinic

Aim: Factors such as personality traits, self-esteem, interpersonal relations and cognitive skills are considered among the risk factors of psychiatric disorders particularly for mood disorders. Presence of a single risk factor is not enough for the disease to emerge. The present study aimed to evaluate the presence of psychosocial triggering factors prior to the episodes of major depressive disorder (MDD) in female patients. Materials and Methods: This retrospective study included a total of 62 female patients, who visited the psychiatry policlinic and have been diagnosed with MDD alone according to SCID-I. After the diagnostic evaluation of the patients, detailed clinical interview was conducted to assess the presence of triggering factors for depressive episode. All of the participants described triggering factors for major depressive disorder. Results: Regarding the psychosocial factors as the potential triggers, 26 patients mentioned about the problem of communication and compliance with the spouse (42%), 10 mentioned about the presence of illness in the first-degree relatives (16%) and 10 mentioned about the conflict with the mother-in-law or other relatives (16%). When we collect “communication/compliance problem with the spouse” + “conflict with the mother-in-law/other family members” + “breaking up with the beloved one” + “husband’s cheating on her” stressor groups as a “relationship conflict” group, the mean of BDI and BAI scores of “relationship conflict” group were highest among the all groups. Conclusions: In the light of these outcomes, it can be concluded that particularly psychosocial factors associated with interpersonal relations play significant role as the triggering factors for depressive episodes in female patients. Among these factors, the problem of communication and compliance with the spouse is particularly striking.

The Role of Social Cognition Skills (SCS) and Social Determinants of Health (SDH) in Predicting Symptoms of Mental Illness

Background: Social factors, such as social cognition skills (SCS) and social determinants of health (SDH), may be vital for mental health, even when compared with classical psycho-physical predictors (demographic, physical, psychiatric, and cognitive factors). Although major risk factors for psychiatric disorders have been previously assessed, the relative weight of SCS and SDH in relation to classical psycho-physical predictors in predicting symptoms of mental disorders remains largely unknown. Methods: In this study, we implemented multiple structural equation models (SEM) from a randomized sample assessed in the Colombian National Mental Health Survey of 2015 (CNMHS, n=2,947) to evaluate the role of SCS, SDH and psycho-physical factors (totaling 17 variables) as predictors of mental illness symptoms (anxiety, depression and other psychiatric symptoms). Specifically, we assessed the structural equation modeling of (a) SCS (emotion recognition and empathy skills); (b) SDH (including the experience of social adversities and social protective factors); (c) and classical psycho-physical factors, including psychiatric antecedents, physical-somatic factors (chronic diseases), and cognitive factors (executive functioning). Findings: Results revealed that emotion recognition skills, social adverse factors, past medical history of psychiatric disorders, the presence of chronic diseases and cognitive functioning were the best predictors of symptoms of mental illness. Moreover, SCS, particularly emotion recognition skills, and SDH (experiences of social adversities, familial and social support networks) reached higher predictive values of symptoms of mental illness than classical psycho-physical factors. Interpretation: Our study provides unprecedented evidence on the impact of social factors in predicting symptoms of mental illness and highlights the relevance of these factors to track early states of disease. Funding Statement: AI is partially supported by CONICET, CONICYT/FONDECYT (Regular 1170010 and 1171200), FONDAP (15150012), the INECO Foundation, PICT (2017-1818 and 2017- 1820), the Inter-American Development Bank (IDB), the Global Brain Health Institute (GBHI), GBHI ALZ UK-20-639295, and NIH/NIA R01 AG057234. This study has been partially supported by Colciencias Colombia and the Ministerio de Salud Colombia, Grant 762-201. Declaration of Interests: The authors declare neither competing financial interests nor other conflicts of interest. Ethics Approval Statement: The study was approved by the institutional ethics committee.

Characterization of a schizophrenia patient with a rare RELN deletion by combining genomic and patient-derived cell analyses

Genetic studies have identified rare RELN variants as risk factors for psychiatric disorders. However, additional genetic factors appear to be necessary for disease onset. Detailed genetic information and the use of patient-derived neuronal cells may thus enable to discover these disease-related additional factors. Here, we performed whole-genome sequencing of a schizophrenia patient with a rare RELN deletion and his healthy mother, and examined the phenotypes of 3D-cultured neuronal cells derived from induced pluripotent stem cells of this patient. Our results revealed that, along with the RELN deletion, neuronal death was promoted in this patient; thus, neuronal death may be a vulnerable factor for schizophrenia.

The effects of early life adversity on growth, maturation, and steroid hormones in male and female rats.

Early life adversity is a risk factor for psychiatric disorders, yet the mechanisms by which adversity increases this risk are still being delineated. Here, we used a limited bedding and nesting (LBN) manipulation in rats that models a low resource environment to examine effects on growth, developmental milestones, and endocrine endpoints. In LBN, dams and pups, from pups' postnatal days 2-9, are exposed to an environment where dams lack proper materials to build a nest. This manipulation is compared to control housing conditions, where rat dams have access to ample nesting materials and enrichment throughout pups' development. We found that the LBN condition altered maternal care, increasing pup-directed behaviors while reducing self-care. This, perhaps compensatory, increase in nursing and attention to pups did not mitigate against changes in metabolism, as LBN reduced weight gain in both sexes and this effect persisted into adulthood. Although adult stress hormone levels in both sexes and vaginal opening and estrous cycle length in females were not disrupted, there was other evidence of endocrine dysregulation. Compared to controls, LBN rats of both sexes had shortened anogenital distances, indicating reduced androgen exposure. LBN males also had higher plasma estradiol levels in adulthood. This combination of results suggests that LBN causes a demasculinizing effect in males that could contribute to lasting changes in the brain and behavior. Importantly, alterations in metabolic and endocrine systems due to early life adversity could be one mechanism by which stress early in life increases risk for later disease.

Investigating the factor structure of the child behavior checklist dysregulation profile in children and adolescents with autism spectrum disorder.

Dysregulation has been identified as an important risk factor for the development of psychiatric disorders in individuals with autism spectrum disorder (ASD). Therefore, it is necessary to empirically characterize dysregulation and identify psychometrically sound and readily available assessment methods in the ASD population. We sought to evaluate the factor structure of the Child Behavior Checklist-Dysregulation Profile (CBCL-DP), an established dysregulation measure in neurotypical children that is derived from the CBCL, in a large, clinically referred sample of children, ages 6-18 years, with ASD (n = 727). Confirmatory factor analysis was used to characterize dysregulation and assess the validity of the CBCL-DP in children with ASD. Our findings support a bi-factor model of dysregulation in which dysregulation is a broad and distinct syndrome that is associated with the three subdomains of the CBCL-DP, anxiety/depression (AD), attention problems (AP), and aggressive behavior (AGG). Dysregulation was associated with most items in the AD and AGG domains and few items in the AP domain. This association with AD and AGG indicates that dysregulation in ASD may be conceptualized as the combined experience of internalized, negative mood states and externalized, reactive behaviors. These findings provide support as well as important caveats for the use of the CBCL-DP as a measure of dysregulation in the ASD population. Autism Res 2020, 13: 436-443. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Dysregulation is a risk factor for psychiatric disorders in ASD. This study examined if the CBCL-DP, an established measure of dysregulation in neurotypical children, can be used to assess dysregulation in children with ASD. Findings provide evidence that in ASD, dysregulation is a broad construct that exists alongside anxiety/depression, attention problems, and aggression. These findings indicate that the CBCL-DP can be considered a valid measure of dysregulation in the ASD population and could be used in clinical settings.

Adverse childhood experiences and clinical severity in bipolar disorder and schizophrenia: A transdiagnostic two-step cluster analysis

BackgroundAdverse childhood experiences (ACEs) are risk factors for psychiatric disorders, but evidence about their relationship with clinical severity is limited. We aimed to classify patients according to ACEs and to compare these clusters with regards to the clinical severity. MethodsSeventy-four patients with Bipolar Disorder (BD) and 91 patients with a diagnosis within the Schizophrenia Spectrum Disorders (SSDs) were interviewed. The Childhood Experience of Care and Abuse scale (CECA) and the Positive and Negative Symptoms Scale (PANSS) were administered. A two-step cluster analysis was run to identify clusters according to ACEs. PANSS average scores were compared between clusters. ResultsThree clusters emerged; significant differences in ACEs distribution were evident. Cluster 1 was characterized by very low frequency of ACEs. ACEs related to lack of support/isolation were more frequent within Cluster 2, instead ACEs related to abuse/neglect were over represented in Cluster 3. The comparison of PANSS through ANOVA demonstrated that Cluster 3 not only had significantly higher scores in all dimensions than Cluster 1 and 2 but also a higher average number of ACEs. LimitationsCECA is a self-report scale and is subject to recall bias. ConclusionsSpecific ACEs are related to clinical severity among BD and SSD patients. Early life adversities related to abuse and neglect are associated to greater symptomatic severity than those related to lack of support/isolation. Our findings suggest that a history of ACEs could be used to identify patients at higher risk of unfavorable clinical features.

Various socioeconomic factors as predictors of internalizing and externalizing disorders in children and adolescents

Various socioeconomic factors as predictors of internalizing and externalizing disorders in children and adolescents Abstract. Objective: Socioeconomic status (SES) is an important risk factor for psychiatric disorders in children and adolescents. Various SES parameters are included in research efforts. This paper investigates the predictive value of different individual SES measures and the combination thereof regarding internalizing and externalizing disorders in children and adolescents. Method: We used data from N = 381 8- to 14-year-olds who had been recruited in child and adolescent psychiatric facilities and in the general population. Based on a diagnostic parent interview (K-SADS-PL), we divided the sample into internalizing and externalizing groups and a healthy control group. The SES data of both parents were collected. Education, occupational status, and income were integrated as single factors as well as combined factor to form the SES index. Additionally, we assessed unemployment. Results: Using multivariate analyses, we controlled for age and sex. All single factors turned out to be significant risk factors for internalizing and externalizing disorders. Occupational status was the most important single factor. The explained variance for the SES index was as high as for occupational status. Unemployment was not predictive when examined simultaneously with the SES index. Conclusion: Future studies should integrate the SES as risk factor and use the SES index or occupational status as single factor. The integration of unemployment is not necessarily needed.

Schizophrenia, Not a Psychotic Disorder: Bleuler Revisited.

Current diagnostic criteria delineate schizophrenia as a discrete entity essentially defined by positive symptoms. However, the role of positive symptoms in psychiatry is being questioned. There is compelling evidence that psychotic manifestations are expressed in the population in a continuum of varying degrees of severity, ranging from normality to full-blown psychosis. In most cases, these phenomena do not persist, but they constitute risk factors for psychiatric disorders in general. Psychotic symptoms are also present in most non-psychotic psychiatric diagnoses, being a marker of severity. Research revealed that hallucinations and delusions appear to have distinct, independent biological underpinnings—in the general population, in psychotic, and in non-psychotic disorders as well. On the other hand, negative symptoms were seen to be far more restricted to schizophrenia, have other underlying pathophysiology than positive symptoms, predict outcome and treatment response in schizophrenia, and start before the first psychotic outbreak. The current work discusses the concept of schizophrenia, suggesting that a greater emphasis should be put on cases where psychotic symptoms emerge in a premorbid subtly increasing negative/cognitive symptoms background. In those cases, psychosis would have a different course and outcome while psychosis occurring in the absence of such background deterioration would be more benign—probably having no, or a milder, underlying degenerative process. This reformulation should better drive psychopathological classification, face positive symptoms as epiphenomenon of the schizophrenia process, and dishevel stigma from schizophrenia and from delusions and hallucinations.

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.