Risk Factor For Psychiatric Disorders Research Articles

High Incidence of Psychiatric Disorders Associated with Cycloserine Treatment of Multidrug-Resistant Tuberculosis Patients: A Cohort Study in Beijing, China.

ObjectiveCycloserine (CS) is a group B anti-tuberculosis (TB) drug endorsed by the World Health Organization (WHO) for the treatment of drug-resistant (DR)-TB. Despite CS widespread acceptance and known efficacy, the high potential of drug-associated psychiatric disorders is a major concern to multidrug-resistant (MDR)-TB patients. In this study, we investigated CS-associated psychiatric disorders in a cohort of MDR-TB patients in Beijing, China. Our aim was to determine psychiatric disorder prevalence rates and associated risk factors in this population.MethodsThis MDR-TB cohort study was conducted at Beijing Chest Hospital between February 2018 and February 2021. All patients received individualized treatment regimens that included CS at some point during the full treatment course. Patient psychological status was assessed using the Symptom Checklist (SCL-90) questionnaire during the post-treatment follow-up period.ResultsTwo hundred and thirty-seven MDR-TB patients were included in the final analysis. Overall, psychiatric disorders were recorded in 22 (9.28%) of the 237 patients in our cohort, with severity grades of 1 or 2 observed for the majority (8.44%) of psychiatric adverse events. As compared to results obtained for control group patients who were ≥40 years of age, patients who were <40 years of age (77.3%, 17/22) were more likely to experience psychiatric disorders [adjusted odds ratio (aOR) = 3.060; 95% CI (1.060–8.828)]. Additionally, patients with body mass index (BMI)s of <18.5 kg/m2 [aOR = 3.824; 95% CI (1.502–9.739)] had significantly higher odds of being afflicted with psychiatric disorders as compared with patients with BMIs that were ≥18.5 kg/m2.ConclusionOur results demonstrated that approximately one-tenth of Chinese MDR-TB patients experienced psychiatric disorders during CS treatment, with the majority of adverse events of moderate severity. In addition, low BMI and age <40 years were identified as independent risk factors for psychiatric disorders in MDR-TB patients receiving CS therapy.

Intolerance of uncertainty predicts altered threat expectancy ratings during reinstatement

Intolerance of uncertainty (IU) is a transdiagnostic risk factor for psychiatric disorders, and plays an important role in fear and threat learning under uncertainty. The ‘reinstatement of fear/threat’ is an understudied phenomenon thought to represent clinical symptom relapse. Reinstatement of conditioned responding can be captured in the laboratory by presenting unsignaled presentations of an aversive unconditional stimulus. The present study investigated IU as a predictor of reinstatement effects, such that individuals higher in IU, relative to lower IU, would show larger reinstatement. Sixty-two participants completed the Intolerance of Uncertainty Scale and provided threat expectancy ratings (i.e. certainty of receiving a shock) during a differential threat conditioning and extinction paradigm with reinstatement. Findings suggested a differential increase in threat expectancy ratings to both the threat and safety cue following reinstatement, although this effect was small and did not survive follow-up tests. Nevertheless, IU was a significant predictor of reinstatement to the threat cue but not the safety cue, although this effect was not in the expected direction. Specifically, higher IU was associated with reduced threat expectancy ratings post-reinstatement. These findings provide support for the limited literature demonstrating an important role for IU in reinstatement effects and should be investigated further.

Attenuated transcriptional response to pro-inflammatory cytokines in schizophrenia hiPSC-derived neural progenitor cells

Maternal immune activation (MIA) during prenatal development is an environmental risk factor for psychiatric disorders including schizophrenia (SZ). Converging lines of evidence from human and animal model studies suggest that elevated cytokine levels in the maternal and fetal compartments are an important indication of the mechanisms driving this association. However, there is variability in susceptibility to the psychiatric risk conferred by MIA, likely influenced by genetic factors. How MIA interacts with a genetic profile susceptible to SZ is challenging to test in animal models. To address this gap, we examined whether differential gene expression responses occur in forebrain-lineage neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (hiPSC) generated from three individuals with a diagnosis of schizophrenia and three healthy controls. Following acute (24 h) treatment with either interferon-gamma (IFNγ; 25 ng/μl) or interleukin (IL)-1β (10 ng/μl), we identified, by RNA sequencing, 3380 differentially expressed genes (DEGs) in the IFNγ-treated control lines (compared to untreated controls), and 1980 DEGs in IFNγ-treated SZ lines (compared to untreated SZ lines). Out of 4137 genes that responded significantly to IFNγ across all lines, 1223 were common to both SZ and control lines. The 2914 genes that appeared to respond differentially to IFNγ treatment in SZ lines were subjected to a further test of significance (multiple testing correction applied to the interaction effect between IFNγ treatment and SZ diagnosis), yielding 359 genes that passed the significance threshold. There were no differentially expressed genes in the IL-1β-treatment conditions after Benjamini-Hochberg correction. Gene set enrichment analysis however showed that IL-1β impacts immune function and neuronal differentiation. Overall, our data suggest that a) SZ NPCs show an attenuated transcriptional response to IFNγ treatment compared to controls; b) Due to low IL-1β receptor expression in NPCs, NPC cultures appear to be less responsive to IL-1β than IFNγ; and c) the genes differentially regulated in SZ lines – in the face of a cytokine challenge – are primarily associated with mitochondrial, “loss-of-function”, pre- and post-synaptic gene sets. Our findings particularly highlight the role of early synaptic development in the association between maternal immune activation and schizophrenia risk.

Intimate partner violence, suicidality, and self-harm: a probability sample survey of the general population in England

Intimate partner violence (IPV) is a recognised risk factor for psychiatric disorders. There is little current evidence on IPV and self-harm and suicidality, and we therefore aimed to investigate the associations between experience of lifetime and past-year IPV with suicidal thoughts, suicide attempt, and self-harm in the past year. We analysed the 2014 Adult Psychiatric Morbidity Survey, a cross-sectional survey of 7058 adults (aged ≥16 years) in England, which used a multistage random probability sampling design and involved face-to-face interviews. Participants were asked about experience of physical violence and sexual, economic, and emotional abuse from a current or former partner, and about suicidal thoughts, suicide attempts, and self-harm. Other adversities were recorded through an adapted version of the List of Threatening Experiences. Multivariable logistic regression models quantified associations between different indicators of lifetime and past-year IPV, with past-year non-suicidal self-harm, suicidal thoughts, and suicide attempts. All analyses were weighted. Using weighted percentages, we found that a fifth (21·4%) of 7058 adults reported lifetime experience of IPV, and that 27·2% of women and 15·3% of men had experienced IPV. Among women, 19·6% had ever experienced emotional IPV, 18·7% physical IPV, 8·5% economic IPV, and 3·7% sexual IPV, which was higher than in men (8·6%, 9·3%, 3·6%, and 0·3%, respectively). Findings for ethnicity were unclear. Lifetime prevalence of IPV was higher in those living in rented accommodation or deprived neighbourhoods. Among people who had attempted suicide in the past year, 49·7% had ever experienced IPV and 23·1% had experienced IPV in the past year (including 34·8% of women and 9·4% of men). After adjusting for demographics, socioeconomics, and lifetime experience of adversities, the odds ratio of a past-year suicide attempt were 2·82 (95% CI 1·54-5·17) times higher in those who have ever experienced IPV, compared with those who had not. Fully adjusted odds ratios for past-year self-harm (2·20, 95% CI 1·37-3·53) and suicidal thoughts (1·85, 1·39-2·46) were also raised in those who had ever experienced IPV. IPV is common in England, especially among women, and is strongly associated with self-harm and suicidality. People presenting to services in suicidal distress or after self-harm should be asked about IPV. Interventions designed to reduce the prevalence and duration of IPV might protect and improve the lives of people at risk of self-harm and suicide. UK Prevention Research Partnership.

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.