Genomewide Association Scan of Suicidal Thoughts and Behaviour in Major Depression

Background Suicidal behaviour can be conceptualised as a continuum from suicidal ideation, to suicidal attempts to completed suicide. In this study we identify genes contributing to suicidal behaviour in the depression study RADIANT. Methodology/Principal Findings A quantitative suicidality score was composed of two items from the SCAN interview. In addition, the 251 depression cases with a history of serious suicide attempts were classified to form a discrete trait. The quantitative trait was correlated with younger onset of depression and number of episodes of depression, but not with gender. A genome-wide association study of 2,023 depression cases was performed to identify genes that may contribute to suicidal behaviour. Two Munich depression studies were used as replication cohorts to test the most strongly associated SNPs. No SNP was associated at genome-wide significance level. For the quantitative trait, evidence of association was detected at GFRA1, a receptor for the neurotrophin GDRA (p = 2e-06). For the discrete trait of suicide attempt, SNPs in KIAA1244 and RGS18 attained p-values of <5e-6. None of these SNPs showed evidence for replication in the additional cohorts tested. Candidate gene analysis provided some support for a polymorphism in NTRK2, which was previously associated with suicidality. Conclusions/Significance This study provides a genome-wide assessment of possible genetic contribution to suicidal behaviour in depression but indicates a genetic architecture of multiple genes with small effects. Large cohorts will be required to dissect this further

Attachment and coping in psychosis in relation to spiritual figures

Background: Studies have found higher levels of insecure attachment in individuals with schizophrenia. Attachment theory provides a framework necessary for conceptualizing the development of interpersonal functioning. Some aspects of the attachment of the believer to his/her spiritual figure are similar to those between the child and his/her parents. The correspondence hypothesis suggests that early child-parent interactions correspond to a person's relation to a spiritual figure. The compensation hypothesis suggests that an insecure attachment history would lead to a strong religiousness/spirituality as a compensation for the lack of felt security. The aim of this study is to explore attachment models in psychosis vs. healthy controls, the relationships between attachment and psychopathology and the attachment processes related to spiritual figures. Methods: Attachment models were measured in 30 patients with psychosis and 18 controls with the AAI (Adult Attachment interview) in relationship with psychopathology. Beliefs and practices related to a spiritual figure were investigated by qualitative and quantitative analyses. Results: Patients with psychosis showed a high prevalence of insecure avoidant attachment. Spiritual entities functioned like attachment figures in two thirds of cases. Interviews revealed the transformation of internal working models within relation to a spiritual figure: a compensation process was found in 7 of the 32 subjects who showed a significant attachment to a spiritual figure. Conclusions: Attachment theory allows us to highlight one of the underlying dimensions of spiritual coping in patients with psychosis

Suicidal ideation during treatment of depression with escitalopram and nortriptyline in Genome-Based Therapeutic Drugs for Depression (GENDEP): a clinical trial

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Functional Variant in Complement C3 Gene Promoter and Genetic Susceptibility to Temporal Lobe Epilepsy and Febrile Seizures

BACKGROUND: Human mesial temporal lobe epilepsies (MTLE) represent the most frequent form of partial epilepsies and are frequently preceded by febrile seizures (FS) in infancy and early childhood. Genetic associations of several complement genes including its central component C3 with disorders of the central nervous system, and the existence of C3 dysregulation in the epilepsies and in the MTLE particularly, make it the C3 gene a good candidate for human MTLE. METHODOLOGY/PRINCIPAL FINDINGS: A case-control association study of the C3 gene was performed in a first series of 122 patients with MTLE and 196 controls. Four haplotypes (HAP1 to 4) comprising GF100472, a newly discovered dinucleotide repeat polymorphism [(CA)8 to (CA)15] in the C3 promoter region showed significant association after Bonferroni correction, in the subgroup of MTLE patients having a personal history of FS (MTLE-FS+). Replication analysis in independent patients and controls confirmed that the rare HAP4 haplotype comprising the minimal length allele of GF100472 [(CA)8], protected against MTLE-FS+. A fifth haplotype (HAP5) with medium-size (CA)11 allele of GF100472 displayed four times higher frequency in controls than in the first cohort of MTLE-FS+ and showed a protective effect against FS through a high statistical significance in an independent population of 97 pure FS. Consistently, (CA)11 allele by its own protected against pure FS in a second group of 148 FS patients. Reporter gene assays showed that GF100472 significantly influenced C3 promoter activity (the higher the number of repeats, the lower the transcriptional activity). Taken together, the consistent genetic data and the functional analysis presented here indicate that a newly-identified and functional polymorphism in the promoter of the complement C3 gene might participate in the genetic susceptibility to human MTLE with a history of FS, and to pure FS. CONCLUSIONS/SIGNIFICANCE: The present study provides important data suggesting for the first time the involvement of the complement system in the genetic susceptibility to epileptic seizures and to epilepsy

Diagnostic du trouble de personnalité borderline à l’adolescence : revue francophone

Le trouble de personnalité borderline (TPB) est une pathologie fréquente, sévère et encore majoritairement diagnostiquée chez l’adulte bien que sa présence à l’adolescence soit aujourd’hui attestée. En effet, plusieurs obstacles semblent s’opposer à ce diagnostic avant l’âge de 18 ans. Mis à part la difficulté pouvant exister pour différencier une crise d’adolescence transitoire des traits de personnalité borderline, il existe aussi une certaine réserve émanant des professionnels de la santé à stigmatiser leurs plus jeunes patients avec cette étiquette en particulier. Pourtant, être en mesure de pouvoir identifier et traiter cette pathologie durant cette période développementale permettrait de réduire nombre de conséquences négatives associées à ce trouble à long terme. Pour parvenir à cette identification précoce, il est nécessaire de créer des outils fiables et valides capables d’évaluer ce trouble chez les adolescents. L’objet de cet article est de présenter les études actuelles portant sur les difficultés liées au diagnostic de TPB à l’adolescence mais aussi de mettre en avant les solutions envisageables. Nous détaillerons donc les caractéristiques principales du TPB ainsi que sa présentation à l’adolescence. Puis enfin nous aborderons les différents outils existant actuellement pour diagnostiquer et évaluer cette pathologie chez les adolescents.Borderline personality disorder (BPD) is a frequent and severe pathology. Although BPD is mostly diagnosed in adults, evidence shows that it can also be adequately diagnosed in adolescents. However, several obstacles seem to prevent this diagnosis from being made on patients younger than 18. Aside from the fact that drawing a line between borderline personality features and the transitional adolescent turmoil could be complicated, some health professionals are reluctant to make a diagnosis that stigmatizes their patients, especially the youngest ones. However, being able to identify and treat BPD during this developmental stage would reduce many adverse outcomes in the long run. Achieving early detection requires reliable and valid tools to screen and diagnose BPD in adolescents. The aim of this article is not only to review studies reporting on difficulties to diagnose BPD in adolescents but also to highlight some realistic solutions. We explain in detail how BPD symptoms manifest during adolescence. We also present the tools currently available to assess and diagnose this pathology in adolescents

Practical considerations for the evaluation and management of Attention Deficit Hyperactivity Disorder (ADHD) in adults

Attention deficit with or without hyperactivity disorder (ADHD) is one of the most frequent neuropsychiatric disorders, and affects 2-4% of adults. In contrast with many European countries, the identification and management of adult ADHD remains underdeveloped in France, and a subject of controversy. This review provides a practical update on current knowledge about ADHD in adults for French-speaking professionals who have to detect or manage adult patients with ADHD. ADHD is classified as a neurodevelopmental disorder in the recent update of the international diagnostic classification. While symptoms and impairment due to ADHD are frequently severe during childhood, they often evolve as children grow older, with frequent persistent disabilities in adulthood. In adulthood, the clinical presentation, as in childhood, involves the symptom triad of inattention, hyperactivity and impulsivity. However, differences are noted: hyperactivity is more often internalized, symptoms of inattention may be masked by anxiety symptoms or obsessive-like compensation strategies. ADHD is often diagnosed during childhood, but it is not rare for the diagnosis to be made later. Failure to recognise symptoms resulting in misdiagnosis, or alternatively well-developed compensation factors could be two underlying reasons for the long delay until diagnosis. Other symptoms, such as emotional deregulation or executive function-related symptoms are also usually observed in adults. In addition, in adults, ADHD is often associated with other psychiatric disorders (in 80% of cases); this makes the diagnosis even more difficult. These disorders encompass a broad spectrum, from mood disorders (unipolar or bipolar), to anxiety disorders, and other neurodevelopmental disorders and personality disorders, especially borderline and antisocial personality disorder. Substance-use disorders are very common, either as a consequence of impulsivity and emotional dysregulation or as an attempt at self-treatment. Sleep disorders, especially restless leg syndrome and hypersomnolence, could share common pathophysiological mechanisms with ADHD. ADHD and comorbidity-related symptoms are responsible for serious functional impairment, in various domains, leading to academic, social, vocational, and familial consequences. The impact on other psychiatric disorders as an aggravating factor should also be considered. The considerable disability and the poorer quality of life among adults with ADHD warrant optimal evaluation and management. The diagnostic procedure for ADHD among adults should be systematic. Once the positive diagnosis is made, the evaluation enables characterisation of the levels of severity and impairment at individual level. A full examination should also assess medical conditions associated with ADHD, to provide personalized care. In recent years, a growing number of assessment tools have been translated and validated in French providing a wide range of structured interviews and standardized self-report questionnaires for the evaluation of core and associated ADHD symptoms, comorbidities and functional impairment. The treatment of ADHD in adults is multimodal, and aims to relieve the symptoms, limit the burden of the disease, and manage comorbidities. The most relevant and validated psychological approaches are psycho-education, cognitive-behavioural therapy and "third wave therapies" with a specific focus on emotional regulation. Cognitive remediation and neurofeedback are promising strategies still under evaluation. Medications, especially psychostimulants, are effective for alleviating ADHD symptoms with a large effect size. Their safety and tolerance are satisfactory, although their long-term clinical benefit is still under discussion. In France, methylphenidate is the only stimulant available for the treatment of ADHD. Unfortunately, there is no authorization for its use among adults except in continuation after adolescence. Hence the prescription, which is subject to the regulations on narcotics, is off-label in France. This article aims to provide practical considerations for the management of ADHD and associated disorders in adults, in this particular French context

Association of AKT1 gene variants and protein expression in both schizophrenia and bipolar disorder

The AKT1 gene has been associated with the genetic aetiology of schizophrenia. Following the overlap model of bipolar disorder and schizophrenia, we aimed to investigate AKT1 genetic variants and protein expression in both diseases. A total of 679 subjects with European ancestry were included: 384 with schizophrenia, 130 with bipolar disorder and 165 controls. Six single nucleotide polymorphisms (SNPs) were investigated for association with the diseases using single- and multi-locus analyses. AKT1 and AKT2 protein levels were measured in post-mortem brain tissues from ante-mortem diagnosed schizophrenia (n = 30) and bipolar disorder subjects (n = 12) and matched controls. The analysis identified a significant global distortion in schizophrenia (P = 0.0026) and a weak association in bipolar disorder (P = 0.046). A sliding window procedure showed a five-SNP haplotype (TCGAG) to be associated with schizophrenia (P = 1.22 x 10(-4)) and bipolar disorder (P = 0.0041) and a four-SNP haplotype (TCGA) with the combined sample (1.73 x 10(-5)). On the basis of selected genotypes, a significant difference in protein expression emerged between subjects (P < 0.02). In conclusion, our findings, by showing the involvement of the AKT1 gene in both schizophrenia and bipolar disorder, support the role of AKT1 in the genetics of both disorders and add support to the view that there is some genetic overlap between them

Addition of methylphenidate to intensive dialectical behaviour therapy for patients suffering from comorbid borderline personality disorder and ADHD: a naturalistic study

Attention deficit hyperactivity disorder (ADHD) is frequently comorbid with borderline personality disorder (BPD). However, few studies have examined how comorbid BPD-ADHD patients, treated or not with methylphenidate (MPH), respond to psychotherapy compared to non-comorbid BPD patients. In this perspective, we used a naturalistic study to compare, during a month-long intensive dialectical behaviour therapy (DBT), the clinical course of BPD patients and comorbid BPD-ADHD patients who were treated or untreated with MPH. Out of the 158 BPD patients recruited, 59 had adult ADHD as a comorbidity; among these, 29 underwent a treatment with MPH or des-methylphenidate, while the 30 others did not. MPH treatment was given non-randomly and only when ADHD was considered to be hampering the capacity of the subjects to follow the therapy. Patients completed the following forms upon admission and after 1 month of treatment: the adult ADHD Self-Report Scale (ASRS v.1.1), the Barratt Impulsiveness Scale (BIS-10), the State-Trait Anger Expression (STAXI), the Beck Depression Inventory II (BDI-II), and the Beck Hopelessness Scale. At baseline, comorbid BPD-ADHD patients showed significantly higher impulsiveness than BPD patients. In the entire sample, there was a significant decrease in all dimensions ranging from small to large effect sizes during the 4-week intensive DBT. BPD-ADHD patients who were undergoing MPH treatment showed a significantly improved response to DBT treatment for Trait-State Anger scores, motor impulsiveness, depression severity, and ADHD severity, when compared to those without stimulant medication. This study outlines the importance of systematically screening BPD patients for ADHD, since a MPH-based treatment will improve the symptoms of patients who are comorbid for BPD and ADHD. Due to the non-random allocation of subjects, more severely affected patients were more readily placed on MPH; this suggests that the more severe the ADHD symptoms, the greater the chance for the patient of being treated