Risk Factor For Psychiatric Disorders Research Articles

Psychopathology after epilepsy surgery: a retrospective study

IntroductionIn patients submitted to refractory epilepsy surgery, psychiatric comorbidity is high (affecting 1 in every 3 patients), with descriptions of improvement, worsening and emergence of de novo psychopathology.ObjectivesIdentifying the prevalence of psychopathology and associated risk factors in a group of patients submitted to refractory epilepsy surgery.MethodsRetrospective observational study. Non systematic literature review.ResultsWe observed 42 patients, 45.2% female and 54.8% male, with an average age of 46.5 years (SD±11.6). The average age of presentation of epilepsy was 18.8 years (SD±12.7), 97.6% with temporal lobe epilepsy and 2.4% with parietal lobe epilepsy, 50% in each hemisphere. 19% had surgical complications and 40.5% had post-surgical recurrence of crisis. 45.2% presented with pre-surgical psychopathology (33.3% affective disorders, 16.7% anxiety disorders, 2.4% psychotic disorders, 2.4% neurodevelopmental disorders and 2.4% substance use disorders). Post-surgically, 50% improved, 20.8% maintained and 29.2% worsened their psychopathology and 21.4% had de novo psychopathology. We didn’t find associations between the analyzed variables and the worsening or appearance of de novo psychopathology.ConclusionsThe worsening or appearance of de novo psychopathology is a well known phenomenon in patients submitted to refractory epilepsy surgery. In our sample there were cases of improvement, maintenance, worsening and emergence of de novo psychopathology, however we weren’t able to identify the factors associated with these different outcomes. Our study was retrospective and had a small sample, as limitations. Further, better-designed studies are necessary to identify risk factors for psychiatric disorders, allowing their effective prevention and treatment.DisclosureNo significant relationships.

Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure.

Adolescent binge drinking is a major risk factor for psychiatric disorders later in life including alcohol use disorder. Adolescent alcohol exposure induces epigenetic reprogramming at the enhancer region of the activity-regulated cytoskeleton-associated protein (Arc) immediate-early gene, known as synaptic activity response element (SARE), and decreases Arc expression in the amygdala of both rodents and humans. The causal role of amygdalar epigenomic regulation at Arc SARE in adult anxiety and drinking after adolescent alcohol exposure is unknown. Here, we show that dCas9-P300 increases histone acetylation at the Arc SARE and normalizes deficits in Arc expression, leading to attenuation of adult anxiety and excessive alcohol drinking in a rat model of adolescent alcohol exposure. Conversely, dCas9-KRAB increases repressive histone methylation at the Arc SARE, decreases Arc expression, and produces anxiety and alcohol drinking in control rats. These results demonstrate that epigenomic editing in the amygdala can ameliorate adult psychopathology after adolescent alcohol exposure.

Early life adversity accelerates epileptogenesis and enhances depression-like behaviors in rats

ObjectiveEarly life stressors are well-established risk factors for psychiatric disorders, and evidence also suggests that these promote vulnerability to epilepsy. Given the high prevalence of psychiatric disorders in epilepsy, early life stress may represent a common driver for these comorbidities. We used animal modelling to investigate the effects of early life stress on epileptogenesis and depressive behaviors, also exploring HPA axis programming as a potential associative mechanism. MethodsFrom post-natal day 2–9, Wistar rat dams (n = 3) and their offspring were exposed to the Limited Bedding and Nesting (LBN) model of early life adversity. Control dams (n = 3) were undisturbed. Maternal care was video-recorded, and behavior scored. As adults, rats (n = 7/group) underwent kainic acid-induced status epilepticus (SE), to trigger epilepsy development. Spontaneous seizures, depression-like behavior and HPA axis function were quantified. ResultsLBN significantly altered aspects of maternal care, including markedly reducing the consistency of care (p < 0.05), compared to control conditions. Following SE, LBN rats exhibited significantly accelerated epileptogenesis (p = 0.01) and greater disease severity (p = 0.001), compared to control rats. Anhedonia and behavioral despair were observed in epileptic rats exposed to LBN. LBN rats showed significantly dampened HPA axis responsivity, but epileptic rats showed greater corticosterone responses to CRH administration (all p < 0.05). SignificanceEarly life adversity promotes a vulnerability to experimental epileptogenesis. These two ‘hits’ (early life stress and epilepsy) interact to create a depressive-like phenotype, but effects on HPA axis are complex and contrasting. This has implications for the mechanisms underpinning the increased prevalence of psychiatric disorders observed in people with epilepsy.

Acute Ketamine Facilitates Fear Memory Extinction in a Rat Model of PTSD Along With Restoring Glutamatergic Alterations and Dendritic Atrophy in the Prefrontal Cortex.

Stress represents a major risk factor for psychiatric disorders, including post-traumatic stress disorder (PTSD). Recently, we dissected the destabilizing effects of acute stress on the excitatory glutamate system in the prefrontal cortex (PFC). Here, we assessed the effects of single subanesthetic administration of ketamine (10 mg/kg) on glutamate transmission and dendritic arborization in the PFC of footshock (FS)-stressed rats, along with changes in depressive, anxious, and fear extinction behaviors. We found that ketamine, while inducing a mild increase of glutamate release in the PFC of naïve rats, blocked the acute stress-induced enhancement of glutamate release when administered 24 or 72 h before or 6 h after FS. Accordingly, the treatment with ketamine 6 h after FS also reduced the stress-dependent increase of spontaneous excitatory postsynaptic current (sEPSC) amplitude in prelimbic (PL)-PFC. At the same time, ketamine injection 6 h after FS was found to rescue apical dendritic retraction of pyramidal neurons induced by acute stress in PL-PFC and facilitated contextual fear extinction. These results show rapid effects of ketamine in animals subjected to acute FS, in line with previous studies suggesting a therapeutic action of the drug in PTSD models. Our data are consistent with a mechanism of ketamine involving re-establishment of synaptic homeostasis, through restoration of glutamate release, and structural remodeling of dendrites.

Toward a generalized developmental model of psychopathological liabilities and psychiatric disorders.

Most psychiatric disorders are associated with several risk factors, but a few underlying psychopathological dimensions account for the common co-occurrence of disorders. If these underlying psychopathological dimensions mediate associations of the risk factors with psychiatric disorders, it would support a trans-diagnostic orientation to etiological research and treatment development. An analysis was performed of the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III), a US nationally representative sample of non-institutionalized civilian adults, focusing on respondents who were aged ⩾21 (n = 34 712). Structural equation modeling was used to identify the psychopathological dimensions underlying psychiatric disorders; to examine associations between risk factors, psychopathological dimensions and individual disorders; and to test whether associations of risk factors occurring earlier in life were mediated by risk factors occurring later in life. A bifactor model of 13 axis I disorders provided a good fit (CFI = 0.987, TLI = 0.982, and RMSEA = 0.011) including an overall psychopathology factor as measured by all 13 disorders and 2 specific factors, one for externalizing disorders and one for fear-related disorders. A substantial proportion of the total effects of the risk factors occurring early in life were indirectly mediated through factors occurring later in life. All risk factors showed a significant total effect on the general psychopathology, externalizing and fear-related factors. Only 23 of 325 direct associations of risk factors with psychiatric disorders achieved statistical significance. Most risk factors for psychiatric disorders are mediated through broad psychopathological dimensions. The central role of these dimensions supports trans-diagnostic etiological and intervention research.

Recognizing the importance of childhood maltreatment as a critical factor in psychiatric diagnoses, treatment, research, prevention, and education.

Childhood maltreatment is the most important preventable risk factor for psychiatric disorders. Maltreated individuals typically develop psychiatric disorders at an earlier age, have a more pernicious course, more comorbidities, greater symptom severity, and respond less favorably to treatments than non-maltreated individuals with the same primary DSM-5 diagnosis. Furthermore, maltreated individuals have alterations in stress-susceptible brain regions, hypothalamic-pituitary-adrenal response, and inflammatory marker levels not discernible in their non-maltreated counterparts. Hence, maltreated and non-maltreated individuals with the same primary DSM-5 diagnoses appear to be clinically and neurobiologically distinct. The failure to embody this distinction in DSM-5 has interfered with our ability to discover novel treatments, to recommend currently available treatments most likely to be efficacious, and has been a largely unrecognized confound that has thwarted our ability to identify the biological basis for major psychiatric disorders. Incorporating this distinction into DSM will help transform this sign and symptom-based classification system to a more etiologically informed nosology. We discuss several diagnostic alternatives and recommend the inclusion of a Developmental Trauma Disorder diagnosis for severely dysregulated individuals, of all ages, with numerous comorbidities, who experienced interpersonal victimization and disruptions in attachment, such as emotional maltreatment or neglect. For less severely affected maltreated individuals, we suggest using conventional diagnostic categories, such as major depression, but with an essential modifier indicating a history of childhood maltreatment, or early life stress, to delineate the ecophenotypic variant. Implementing this strategy should improve our ability to effectively diagnose and treat individuals with psychiatric disorders and to accelerate discovery.

Prevalence, Structure, and Risk Factors for Mental Disorders in Older People

This review focuses on assessing the prevalence and risk factors of mental disorders in older people in the modern era, including the COVID-19 pandemic. A systematic review of the literature was conducted in PubMed, Elsevier, and Google using keywords over the past 10 years. Substantial discrepancy of data on the prevalence of psychiatric disorders has been shown in the elderly population. The significant incidence of mental disorders among nursing home residents is highlighted. The relevance of nonpsychotic depressive and anxiety disorders is demonstrated for the elderly, along with the difficulty of diagnosing mental disorders associated with physical pathology and cognitive impairments. The risk factors for mental disorders in older adults are socio-demographic but also economic, psychological, and physical. The problem of mental health of the elderly is characterized for the conditions of the COVID-19 pandemic associated with specific risk factors for psychiatric disorders. The shortage of evidence-based research in the treatment of mental disorders in the elderly and the urgency to improve the organization of psychiatric care for such patients are noted. Understanding the structure and prevalence of mental disorders among the elderly will allow optimizing the functioning of healthcare systems.

Genetic liability to suicide attempt, suicide death, and psychiatric and substance use disorders on the risk for suicide attempt and suicide death: a Swedish national study.

How does genetic liability to suicide attempt (SA), suicide death (SD), major depression (MD), bipolar disorder (BD), schizophrenia (SZ), alcohol use disorder (AUD), and drug use disorder (DUD) impact on risk for SA and SD? In the Swedish general population born 1932-1995 and followed through 2017 (n = 7 661 519), we calculate family genetic risk scores (FGRS) for SA, SD, MD, BD, SZ, AUD, and DUD. Registration for SA and SD was assessed from Swedish national registers. In univariate and multivariate models predicting SA, FGRS were highest for SA, AUD, DUD, and MD. In univariate models predicting SD, the strongest FGRS were AUD, DUD, SA, and SD. In multivariate models, the FGRS for SA and AUD were higher in predicting SA while the FGRS for SD, BD, and SZ were higher in predicting SD. Higher FGRS for all disorders significantly predicted both younger age at first SA and frequency of attempts. For SD, higher FGRS for MD, AUD, and SD predicted later age at SD. Mediation of FGRS effects on SA and SD was more pronounced for SD than SA, strongest for AUD, DUD, and SZ FGRS and weakest for MD. FGRS for both SA and SD and for our five psychiatric disorders impact on risk for SA and SD in a complex manner. While some of the impact of genetic risk factors for psychiatric disorders on risk for SA and SD is mediated through developing the disorders, these risks also predispose directly to suicidal behaviors.

Polygenic burden could explain high rates of affective disorders in a community with restricted founder population

This study investigates if genetic factors could contribute to the high rate of mood disorders reported in a U.S. community known to have a restricted early founder population (confirmed here through runs of homozygosity analysis). Polygenic scores (PGSs) for eight common diseases, disorders, or traits, including psychiatric disorders, were calculated in 274 participants (125 mood disorder cases) who each reported three or four grandparents born in the community. Ancestry-matched controls were selected from the UK Biobank (UKB; three sets of N= 1,822 each). The mean PGSs were significantly higher in the community for major depression PRS (p= 2.1× 10-19 , 0.56 SD units), bipolar disorder (p= 2.5× 10-15 , 0.56 SD units), and schizophrenia (p= 3.8× 10-21 , 0.64 SD units). The PGSs were not significantly different between the community participants and UKB controls for the traits of body mass index, Type 2 diabetes, coronary artery disease, and chronotype. The mean PGSs for height were significantly lower in the community sample compared to controls (-0.21 SD units, p= 1.2× 10-5 ). The results are consistent with enrichment of polygenic risk factors for psychiatric disorders in this community.

Relationships Between Telomere Length, Plasma Glucagon-like Peptide 1, and Insulin in Early-Life Stress–Exposed Nonhuman Primates

BackgroundEarly-life stress is associated with alterations in telomere length, a marker of accumulated stress and aging, and a risk factor for psychiatric disorders. Nonhuman primate maternal variable foraging demand (VFD) is a validated early-life stress model, resulting in anxiety- and depressive-like symptoms in offspring. Previous studies reported increased plasma glucagon-like peptide 1 (pGLP-1) along with insulin resistance in this model. We investigated whether VFD rearing related to adult telomere length and to these neuroendocrine markers. MethodsAdult leukocyte telomere length was measured in VFD-reared (12 males, 13 females) and non-VFD–reared (9 males, 26 females) bonnet macaques. Associations between adult telomere length and adolescent fasting pGLP-1 or insulin resistance in VFD-reared versus non-VFD–reared groups were examined using regression modeling, controlling for sex, weight, and age. ResultsVFD subjects had relatively longer telomeres than non-VFD subjects (p = .017), and females relatively longer than males (p = .0004). Telomere length was positively associated with pGLP-1 (p = .0009) and with reduced insulin sensitivity (p < .0001) in both sexes, but not as a function of rearing group. ConclusionsUnexpectedly, VFD was associated with longer adult telomere length. Insulin resistance may lead to higher pGLP-1 levels in adolescence, which could protect telomere length in VFD offspring as adults. Associations between adult telomere length and adolescent insulin resistance and high pGLP-1 may reflect an adaptive, compensatory response after early-life stress exposure.

STUDY OF THE ASSOCIATION OF CHILDHOOD TRAUMA WITH SCHIZOPHRENIA AND BIPOLAR DISORDER IN A SAMPLE OF ADULT PATIENTS

Schizophrenia is a clinical syndrome of variable, but profoundly disruptive, psychopathology that involves cognition, emotion, perception, and other aspects of behavior. The hallmark symptom of schizophrenia is psychosis, such as experiencing auditory hallucinations (voices) and delusions (fixed false beliefs).It carries a lifetime risk of around 1%, and its early onset and tendency to chronicity mean that its prevalence is relatively high.(1) In the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders, (DSM-IV), bipolar disorder constitutes a spectrum of mood disorders that includes BPI (bipolar affective disorder type I), BPII (bipolar affective disorder type II), cyclothymia and are thought to be a “bridge” between schizophrenia spectrum disorders and depressive disorders in terms of the symptomology, family history and genetics.Childhood trauma is considered as a risk factor for psychiatric disorders across diagnostic boundaries. Childhood trauma is most likely interacting with genetic factors in the development of psychiatric disorders.

Phosphorylation-dependent control of Activity-regulated cytoskeleton-associated protein (Arc) protein by TNIK.

Activity-regulated cytoskeleton-associated protein (Arc) is an immediate early gene product that support neuroplastic changes important for cognitive function and memory formation. As a protein with homology to the retroviral Gag protein, a particular characteristic of Arc is its capacity to self-assemble into virus-like capsids that can package mRNAs and transfer those transcripts to other cells. Although a lot has been uncovered about the contributions of Arc to neuron biology and behavior, very little is known about how different functions of Arc are coordinately regulated both temporally and spatially in neurons. The answer to this question we hypothesized must involve the occurrence of different protein post-translational modifications acting to confer specificity. In this study, we used mass spectrometry and sequence prediction strategies to map novel Arc phosphorylation sites. Our approach led us to recognize serine 67 (S67) and threonine 278 (T278) as residues that can be modified by TNIK, which is a kinase abundantly expressed in neurons that shares many functional overlaps with Arc and has, along with its interacting proteins such as the NMDA receptor, and been implicated as a risk factor for psychiatric disorders. Furthermore, characterization of each residue using site-directed mutagenesis to create S67 and T278 mutant variants revealed that TNIK action at those amino acids can strongly influence Arc's subcellular distribution and self-assembly as capsids. Together, our findings reveal an unsuspected connection between Arc and TNIK. Better understanding of the interplay between these two proteins in neuronal cells could lead to new insights about apparition and progression of psychiatric disorders. Cover Image for this issue: https://doi.org/10.1111/jnc.15077.

High Potential of Facial Biomarkers to Diagnose Psychotic Disorders

Schizophrenia (SCZ) and Bipolar Disorder (BP) are severe psychiatric disorders (PD) that affect more than 3% of the world's population and are among the leading causes of disability worldwide. Current diagnostic systems represent these PD as independent categorical entities. However, recent studies propose that both disorders would be two different manifestations of the same psychotic spectrum continuum. Differential diagnosis is mainly based on their clinical presentation, and reliable biomarkers remain an unmet clinical need. Since the brain and the face are derived from the same ectodermal origins and their development is intimately integrated through common genetic signaling, facial biomarkers emerge as one of the most promising biological risk factors for PD. Here, we assessed the potential of facial anatomy in predicting the diagnosis of SCZ and BP. Analyses were performed in a sample of 180 adults distributed in three groups of BP patients (n=46), SCZ patients (n=67), and CNT (n=67) matched by age and premorbid IQ. Faces were manually annotated from reconstructions of magnetic resonance scans. Facial shape correctly discriminated patients with BP and SCZ, even when facial differences between patients and CNT were so subtle that are not recognizable to the untrained eye or by exploratory multivariate statistical techniques. After cross-validation, 62-65% of patients were correctly diagnosed based on face shape. This percentage is similar to the discriminatory power of other genetic and brain biomarkers. Using Artificial Neural Networks, we tested a machine learning algorithm based on facial morphology to diagnose SCZ. The overall accuracy in diagnostic classification was greater than 90%, whereas the precision ranged between 70-95% depending on the model. We also trained a Support Vector Machine classification algorithm to diagnose BP. Results showed that BP is harder to diagnose from facial biomarkers than SCZ, achieving a 72% accuracy. Euclidean Distance Matrix Analysis (EDMA) detected local facial differences involving the eyes, nose and mouth, and the relative separation/position between them. Facial anomalies were more abundant in SCZ patients, with 43-48% distances across the whole face significantly different from control subjects. In BP, the percentage of facial anomalies was lower, 24-32%, especially in women. Some facial differences were common to SCZ and BP, although the sense of change could be different among disorders. Remarkably, EDMA showed facial patterns that are disorder and gender-specific. These results demonstrate that an analysis of the spectrum of psychotic disorders under a gender perspective is crucial to further understand these disorders and to identify reliable biomarkers that can lead to early PD diagnosis.

Hospital Contacts for Psychiatric Disorders in Parents of Children With Cancer in Denmark.

BackgroundHaving a child diagnosed with cancer is a devastating experience that may affect parents’ mental health. We aimed to assess the risk of hospital contacts for psychiatric disorders in parents of children with cancer.MethodsWe conducted a nationwide population-based cohort study using Danish registry data. Parents of children diagnosed with cancer between 1982 and 2014 (n = 6689 mothers, n = 5509 fathers) were matched with comparison parents of cancer-free children (n = 67 544 mothers, n = 55 756 fathers). We used Cox proportional hazards models to estimate the risk of hospital contacts for any psychiatric disorder and specific disorders. Cox models were also used to investigate sociodemographic and cancer-related risk factors for psychiatric disorders.ResultsIncidence rates of hospital contacts for any psychiatric disorder were 426 per 100 000 person-years in mothers of children with cancer and 345 per 100 000 person-years in comparison mothers. For fathers, the respective incidence rates were 260 and 262 cases per 100 000 person-years. Compared with parents of cancer-free children, mothers of children with cancer were at an increased risk of hospital contacts for any psychiatric disorder (hazard ratio = 1.23, 95% confidence interval = 1.12 to 1.36), whereas no elevated risk was seen in fathers (hazard ratio = 0.99, 95% confidence interval = 0.87 to 1.13). Among mothers, risks were particularly elevated for affective and stress-related disorders. Parents of deceased children and children diagnosed at a younger age were at particular risk of hospital contacts for psychiatric disorders.ConclusionHospital contacts for psychiatric disorders were overall rare. Health-care professionals should draw attention to subgroups of vulnerable parents to meet their needs of support and adequate treatment.

¿Do immigrant psychotic patients receive less psychotherapy assessment compared to non-immigrant psychotic patients?

IntroductionMigration is a highly defining life event which can lead to mental distress. It constitutes an overall risk factor for psychiatric disorders. However, psychotherapeutic treatment in immigrant patients is considered to be more complex, and the outcome appears to be less favorable than in patients without a migration background.ObjectivesThe aim of this study is to compare psychotherapy assessment between immigrant and non-immigrant psychotic patients in Barcelona.MethodsPatients who have presented, according DSM-V criteria, one or more non-affective psychotic episodes, were recruited in Acute and Chronic inpatients units at Hospital del Mar (Barcelona), leading to a total sample of 77 patients. Demographic characteristics of patients, clinical data and main pharmacological treatment were recorded through a questionnaire. Database information was completed with electronic medical records. Comparative analysis was performed with IBM SPSS using Chi-Square and t-Student testResults From a total of 77 patients, 43 were immigrants and 34 were non-immigrants. From the total immigrants only 30,2% received psychotherapy compared to 79,4% from the non-immigrants. The most prevalent therapy received in both groups was cognitive behavioural therapy. From the immigrants group only 2,3% received psychoeducation compared to 11,8% from the non-immigrant group.ConclusionsAccording to our results, there are important and significant differences in psychotherapy assessment in migrant psychotic patients. In order to improve the mental health treatment of immigrant patients, the reasons for this poor outcome need to be investigated. These results should be considered by clinicians in order to design assessment program for this population.DisclosureNo significant relationships.

Unique effects of social defeat stress in adolescent male mice on the Netrin-1/DCC pathway, prefrontal cortex dopamine and cognition (Social stress in adolescent vs. adult male mice).

For some individuals, social stress is a risk factor for psychiatric disorders characterized by adolescent onset, prefrontal cortex (PFC) dysfunction and cognitive impairments. Social stress may be particularly harmful during adolescence when dopamine (DA) axons are still growing to the PFC, rendering them sensitive to environmental influences. The guidance cue Netrin-1 and its receptor, DCC, coordinate to control mesocorticolimbic DA axon targeting and growth during this age. Here, we adapted the accelerated social defeat (AcSD) paradigm to expose male mice to social stress in either adolescence or adulthood and categorized them as “resilient” or “susceptible” based on social avoidance behavior. We examined whether stress would alter the expression of DCC and Netrin-1 in mesolimbic DA regions and would have enduring consequences on PFC DA connectivity and cognition. While in adolescence the majority of mice are resilient but exhibit risk-taking behavior, AcSD in adulthood leads to a majority of susceptible mice without altering anxiety-like traits. In adolescent, but not adult mice, AcSD dysregulates DCC and Netrin-1 expression in mesolimbic DA regions. These molecular changes in adolescent mice are accompanied by changes in PFC DA connectivity. Following AcSD in adulthood, cognitive function remains unaffected, but all mice exposed to AcSD in adolescence show deficits in inhibitory control when they reach adulthood. These findings indicate that exposure to AcSD in adolescence versus adulthood has substantially different effects on brain and behavior and that stress-induced social avoidance in adolescence does not predict vulnerability to deficits in cognitive performance.

Gene-based association analysis identifies 190 genes affecting neuroticism

Neuroticism is a personality trait, which is an important risk factor for psychiatric disorders. Recent genome-wide studies reported about 600 genes potentially influencing neuroticism. Little is known about the mechanisms of their action. Here, we aimed to conduct a more detailed analysis of genes that can regulate the level of neuroticism. Using UK Biobank-based GWAS summary statistics, we performed a gene-based association analysis using four sets of within-gene variants, each set possessing specific protein-coding properties. To guard against the influence of strong GWAS signals outside the gene, we used a specially designed procedure called “polygene pruning”. As a result, we identified 190 genes associated with neuroticism due to the effect of within-gene variants rather than strong GWAS signals outside the gene. Thirty eight of these genes are new. Within all genes identified, we distinguished two slightly overlapping groups obtained from using protein-coding and non-coding variants. Many genes in the former group included potentially pathogenic variants. For some genes in the latter group, we found evidence of pleiotropy with gene expression. Using a bioinformatics analysis, we prioritized the neuroticism genes and showed that the genes that contribute to neuroticism through their within-gene variants are the most appropriate candidate genes.

Heartbeat evoked potentials in patients with post-traumatic stress disorder: an unaltered neurobiological regulation system?

ABSTRACT Background: Early life maltreatment is a risk factor for psychiatric disorders, including post-traumatic stress disorder (PTSD). Post-traumatic stress disorder is a severe and heterogeneous disorder with fluctuating states of emotional over- and undermodulation, including hypervigilance, dissociation, and emotion regulation deficits. The perception and regulation of emotions have been linked to interoception, the cortical representation and sensing of inner bodily processes. Although first therapeutic approaches targeting bodily sensations have been found effective in patients with PTSD, and deficits in interoceptive signal representation have been reported in other trauma-related disorders, such as borderline personality disorder (BPD), the role of interoception remains largely unexplored for PTSD. Objective: The objective was to investigate the cortical representation of cardiac interoceptive signals in patients with PTSD and its associations with early life maltreatment, trait dissociation, and emotion dysregulation. Methods: Twenty-four medication-free patients with PTSD and 31 healthy controls (HC) completed a 5-min resting electrocardiogram (ECG) with parallel electroencephalogram (EEG). Heartbeat evoked potential (HEP) amplitudes as a measure for cortical representation of cardiac interoceptive signals were compared between groups and correlated with self-report questionnaires. Results: We did not find significantly different mean HEP amplitudes in patients with PTSD compared to HC, although HEPs of patients with PTSD were descriptively higher. No significant associations between mean HEP amplitudes and early life maltreatment, trait dissociation or emotion dysregulation were obtained within the groups. Conclusion: The current finding does not indicate deficits in interoceptive signal representation at rest in individuals with PTSD. Whether patients with PTSD show altered HEP modulations during emotion regulation tasks and might benefit from therapeutic approaches aiming at changing the perception of bodily signals, needs to be investigated in future studies.

Clinical features and risk factors of psychiatric disorders among maltreated children

Objective: In this survey, we intended to study the clinical features and possible risk factors including types of maltreatment, family factors, and psychopathology of maltreated children. Methods: We reviewed the clinical case reports of comprehensive assessment in annual projects of maltreated children placed in the children's homes between 1997 and 2016. The comprehensive assessment included history of maltreatment, family condition, psychiatric interview, physical examination, and psychological assessment. We divided maltreated children into Axis I psychiatric disorder and non-Axis I psychiatric disorder groups for comparing the difference in clinical features and risk factors. Results: Among the 377 participants, the average age was 9.1 ± 3.0 years. The majority were male (60.5%) and pupils of elementary school (69.9%). Only 22.5% of their parents still maintained as married in marital status. In Axis I psychiatric disorder group, both age (p < 0.05) and full intelligence (p < 0.001) were significantly lower than non-Axis I psychiatric disorder group. Besides, the study participants in the Axis I psychiatric disorder group had significantly more times of changes in placement (p < 0.05) and stayed longer in a placement (p < 0.05). In both groups, around 40% of all the participants were 25 percentile or less in height. The feature was not found in weight dimension. Conclusion: While the problem of psychiatric disorder adds complexity to child maltreatment issues, the promotion, protection, and restoration of mental health can be regarded as a vital concern in these vulnerable children.

The Burden of Psychiatric Disorders Associated With Orofacial Cleft Pathology Among Children in Ontario, Canada

Background: Individuals with orofacial cleft (OFC) may be at higher risk of developing psychiatric disorders(PD). We determined the risk of psychiatric diagnoses in children with OFC in Canada. Methods: This population-based retrospective cohort study used health administrative data from the province of Ontario, Canada. Children with OFC who were born from April 1, 1994 to March 31, 2017 in Ontario were each matched to five non-OFC children based on sex, date of birth and mother’s age. We determined rate of events and time-to-event for first diagnosis of PD in children aged ≥3 years(y), and for intellectual developmental delay (IDD) from birth. Risk factors for PD and IDD were assessed using 1-way ANOVA for means, Kruskal-Wallis for medians, χ 2 test for categorical variables. Outcomes: There were 3,051 children with OFC (matched to 15,255 controls), of whom 2,515 OFC patients had complete follow-up to the third birthday (matched to 12,575 controls). The mean age to first PD diagnosis was 8.6±4.2y for OFC patients; the cleft palate group had a higher risk (HR 1.33, 95% CI 1.18-1.49). The OFC patients had a higher risk of IDD diagnosis (HR 8.08, 95% CI 7.28-8.97, p<001), especially those with other congenital malformations (HR 4.57, 95% CI 3.95-5.28 p<0.001). Geography (place of living) was a significant risk factor for PD and IDD. Interpretation: Children born with OFC in Ontario had a higher risk of psychiatric diagnosis and IDD compared to controls. Further research is required to better understand the cause of geographical variation and identify potential areas for intervention. Funding: Claudia Malic was supported by the ICES Faculty Scholars Program. Eric Benchimol was supported by a New Investigator Award from the Canadian Institutes of Health Research, Canadian Association of Gastroenterology, and Crohn’s and Colitis Canada. He was also supported by the Career Enhancement Program of the Canadian Child Health Clinician Scientist Program. Conflict of Interest: Simone Vigod reports royalties from UpToDate Inc for authorship of chapters related to depression and pregnancy. The remaining authors have no conflicts of interest to disclose. Ethical Approval: The Research Ethics Board of the Children’s Hospital of Eastern Ontario approved this study and informed consent was not required as per Ontario privacy law.