Characterisation of age and polarity at onset in bipolar disorder

Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses

Profile of vortioxetine in the treatment of major depressive disorder: an overview of the primary and secondary literature

Marc Kelliny, Paul E Croarkin, Katherine M Moore, William V Bobo Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA Abstract: This article reviews the pharmacological profile and available efficacy and tolerability/safety data for vortioxetine, one of the most recent antidepressant drugs to be approved in the USA for the treatment of major depressive disorder (MDD) in adults. The efficacy of vortioxetine for treating MDD in adults is supported by eight positive short-term (6- to 12-weeks) randomized, placebo-controlled trials, and one positive randomized, double-blind, 52-week relapse prevention trial. Based on pooled data from short-term randomized trials and from longer-term studies, vortioxetine appears to be well tolerated and to have a low incidence of adverse effects on sexual functioning. Vortioxetine also appears to be effective for treating symptoms of MDD in the elderly based on the results of one randomized trial for which recruitment was focused on this specific population. Nevertheless, effectiveness studies that directly compare the clinical effects of vortioxetine with other established antidepressant drugs are lacking, and there is no evidence as yet that vortioxetine is more clinically effective than other types of antidepressants. Some preliminary suggestions concerning the place of vortioxetine among the broad range of pharmacological treatments for adults with MDD are provided. Keywords: vortioxetine, Lu AA21004, pharmacological profile, pharmacokinetics, drug interactions, adverse effects/side effects/safety, depression, major depressio

Preliminary Evidence for Anhedonia as a Marker of Sexual Trauma in Female Adolescents

Ayse Irem Sonmez,1,2 Charles P Lewis,1 Arjun P Athreya,3 Julia Shekunov,2 Paul E Croarkin2 1Department of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, Minneapolis, MN, USA; 2Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA; 3Department of Molecular Pharmacology &Experimental Therapeutics, Mayo Clinic, Rochester, MN, USACorrespondence: Ayse Irem SonmezDepartment of Psychiatry and Behavioral Sciences, University of Minnesota Medical School, 2312 S 6th St, Minneapolis, MN, 55454, USATel +1 612-273-8383Email [email protected]: Major depressive disorder (MDD) is a common condition with heterogeneous presentations that often include predominant anhedonia. Previous studies have revealed that childhood trauma is a potent risk factor for the development of MDD; however, the clinical implications of this finding are not fully understood.Methods: Participants were adolescents (age 13– 21 years) with a diagnosis of moderate-to-severe major depressive disorder and healthy controls. We used generalized linear models to assess the relationship between anhedonia severity and trauma severity in a cross-sectional dataset.Results: This cross-sectional analysis of an adolescent sample that underwent clinical evaluations and a trauma assessment, suggested that anhedonia was associated with historical trauma severity. The association between anhedonia and sexual abuse was greater in female participants compared to male participants.Discussion: Our results were partially in line with the reported literature in adult samples. Future studies aiming to characterize the trauma–anhedonia relationship in adolescents should utilize scales designed specifically to measure these constructs in young populations, and scales that assess specific subtypes of anhedonia.Keywords: adolescent, anhedonia, emotional abus

N-acetylaspartate normalization in bipolar depression after lamotrigine treatment

Objectives: The aim of the present study was to examine N-acetylaspartate (NAA), a general marker of neuronal viability, and total NAA (tNAA), the combined signal of NAA and N-acetylaspartylglutamate, in bipolar depression before and after lamotrigine treatment. Given that NAA is synthesized through direct acetylation of aspartate by acetyl-coenzyme A-l-aspartate-N-acetyltransferase, we hypothesized that treatment with lamotrigine would be associated with an increase in NAA level. Methods: Patients with bipolar depression underwent two-dimensional proton magnetic resonance spectroscopy of the anterior cingulate at baseline (n = 15) and after 12 weeks of lamotrigine treatment (n = 10). A group of age-matched healthy controls (n = 9) underwent scanning at baseline for comparison. Results: At baseline, patients with bipolar depression had significantly lower NAA [mean standard deviation (SD) = 1.13 (0.21); p = 0.02] than controls [mean (SD) = 1.37 (0.27)]. Significant increases in NAA [mean (SD) = 1.39 (0.21); p = 0.01] and tNAA [mean (SD) = 1.61 (0.25); p = 0.02] levels were found after 12 weeks of lamotrigine treatment. Conclusions: These data suggest an NAA deficit in bipolar depression that is normalized after lamotrigine treatment. Future research is warranted to evaluate whether baseline NAA level is a potential biomarker for identifying lamotrigine response patterns and whether this functional brain change has an associated clinical response

N-acetylaspartate normalization in bipolar depression after lamotrigine treatment

Objectives: The aim of the present study was to examine N-acetylaspartate (NAA), a general marker of neuronal viability, and total NAA (tNAA), the combined signal of NAA and N-acetylaspartylglutamate, in bipolar depression before and after lamotrigine treatment. Given that NAA is synthesized through direct acetylation of aspartate by acetyl-coenzyme A-l-aspartate-N-acetyltransferase, we hypothesized that treatment with lamotrigine would be associated with an increase in NAA level. Methods: Patients with bipolar depression underwent two-dimensional proton magnetic resonance spectroscopy of the anterior cingulate at baseline (n = 15) and after 12 weeks of lamotrigine treatment (n = 10). A group of age-matched healthy controls (n = 9) underwent scanning at baseline for comparison. Results: At baseline, patients with bipolar depression had significantly lower NAA [mean standard deviation (SD) = 1.13 (0.21); p = 0.02] than controls [mean (SD) = 1.37 (0.27)]. Significant increases in NAA [mean (SD) = 1.39 (0.21); p = 0.01] and tNAA [mean (SD) = 1.61 (0.25); p = 0.02] levels were found after 12 weeks of lamotrigine treatment. Conclusions: These data suggest an NAA deficit in bipolar depression that is normalized after lamotrigine treatment. Future research is warranted to evaluate whether baseline NAA level is a potential biomarker for identifying lamotrigine response patterns and whether this functional brain change has an associated clinical response

Methodological issues in defining aggression for content analyses of sexually explicit material

There exists an important tradition of content analyses of aggression in sexually explicit material. The majority of these analyses use a definition of aggression that excludes consent. This article identifies three problems with this approach. First, it does not distinguish between aggression and some positive acts. Second, it excludes a key element of healthy sexuality. Third, it can lead to heteronormative definitions of healthy sexuality. It would be better to use a definition of aggression such as Baron and Richardson's (1994) in our content analyses, that includes a consideration of consent. A number of difficulties have been identified with attending to consent but this article offers solutions to each of these