•Baseline cortisol levels are generally low in hair.•A standardized analytical method for hair cortisol measurement is needed.•Hair cortisol is age dependent and influenced by sex and hair ...color.•Age-dependent normative baseline cortisol levels are highly recommended.
The measurement of hair cortisol is increasingly used to measure long-term cumulative cortisol levels and investigate its role as an important stress mediator. In this study a comparative statistical analysis of five independent studies (all analyzed in our laboratory) was performed to investigate baseline ranges of cortisol values in hair and evaluate potential influences of sex, age and hair color. Cortisol concentrations in hair of 554 subjects were measured and a comparative statistical analysis was performed. The analysis showed that cortisol levels significantly differ depending on age. The toddler group (7 months (0.6 years) to 3 years) showed significantly higher values (median 10pg/mg, p-value<0.0001, d=0.78) than the adolescent group. The adolescent groups showed significantly lower (p-value<0.0001, d=0.58 and p<0.0001, d=0.13) values (median 2.4pg/mg and 2.8pg/mg) than the adult group (median 5.8pg/mg).
Furthermore, in the adult group men showed significantly higher cortisol values than women (p-value<0.05, d=0.17). This effect could not be seen in the adolescent group. Black hair showed higher cortisol concentrations than blond hair (p-value<0.0001, d=1.3). In addition, two rounds of interlaboratory comparisons for hair cortisol samples between four laboratories revealed very consistent results.
Our results demonstrate that baseline cortisol levels are generally low in hair thus making a standardized and well-elaborated analytical method indispensable for accurate determination. Age-dependent normative baseline cortisol levels (toddlers, adolescents and adults) are highly recommended based on the comparative analysis comprising five independent studies.
The genetic basis of bipolar disorder has long been thought to be complex, with the potential involvement of multiple genes, but methods to analyze populations with respect to this complexity have ...only recently become available. We have carried out a genome-wide association study of bipolar disorder by genotyping over 550,000 single-nucleotide polymorphisms (SNPs) in two independent case-control samples of European origin. The initial association screen was performed using pooled DNA, and selected SNPs were confirmed by individual genotyping. While DNA pooling reduces power to detect genetic associations, there is a substantial cost saving and gain in efficiency. A total of 88 SNPs, representing 80 different genes, met the prior criteria for replication in both samples. Effect sizes were modest: no single SNP of large effect was detected. Of 37 SNPs selected for individual genotyping, the strongest association signal was detected at a marker within the first intron of diacylglycerol kinase eta (DGKH; P=1.5 x 10(-8), experiment-wide P<0.01, OR=1.59). This gene encodes DGKH, a key protein in the lithium-sensitive phosphatidyl inositol pathway. This first genome-wide association study of bipolar disorder shows that several genes, each of modest effect, reproducibly influence disease risk. Bipolar disorder may be a polygenic disease.
The oxytocin system is involved in human social behavior and social cognition such as attachment, emotion recognition and mentalizing (i.e. the ability to represent mental states of oneself and ...others). It is shaped by social experiences in early life, especially by parent–infant interactions. The single nucleotid polymorphism rs53576 in the oxytocin receptor (OXTR) gene has been linked to social behavioral phenotypes.
In 195 adult healthy subjects we investigated the interaction of OXTR rs53576 and childhood attachment security (CAS) on the personality traits “adult attachment style” and “alexithymia” (i.e. emotional self-awareness), on brain structure (voxel-based morphometry) and neural activation (fMRI) during an interactive mentalizing paradigm (prisoner's dilemma game; subgroup: n=163).
We found that in GG-homozygotes, but not in A-allele carriers, insecure childhood attachment is - in adulthood - associated with a) higher attachment-related anxiety and alexithymia, b) higher brain gray matter volume of left amygdala and lower volumes in right superior parietal lobule (SPL), left temporal pole (TP), and bilateral frontal regions, and c) higher mentalizing-related neural activity in bilateral TP and precunei, and right middle and superior frontal gyri. Interaction effects of genotype and CAS on brain volume and/or function were associated with individual differences in alexithymia and attachment-related anxiety. Interactive effects were in part sexually dimorphic.
The interaction of OXTR genotype and CAS modulates adult personality as well as brain structure and function of areas implicated in salience processing and mentalizing. Rs53576 GG-homozygotes are partially more susceptible to childhood attachment experiences than A-allele carriers.
•A gene-by-environment interaction was investigated in healthy adults (n=195).•Rs53576 and childhood attachment security (CAS) jointly modulated alexithymia.•Interaction of rs53576 and CAS was sexually dimorphic for attachment-related anxiety.•Interaction modulated structure and function of brain areas related to mentalizing.•GG-homozygotes of rs53576 were partly more susceptible to CAS than A-allele carriers.
Recent genetic data on schizophrenia (SCZ) have suggested that proteins of the postsynaptic density of excitatory synapses have a role in its etiology. Mutations in the three SHANK genes encoding for ...postsynaptic scaffolding proteins have been shown to represent risk factors for autism spectrum disorders and other neurodevelopmental disorders. To address if SHANK2 variants are associated with SCZ, we sequenced SHANK2 in 481 patients and 659 unaffected individuals. We identified a significant increase in the number of rare (minor allele frequency<1%) SHANK2 missense variants in SCZ individuals (6.9%) compared with controls (3.9%, P=0.039). Four out of fifteen non-synonymous variants identified in the SCZ cohort (S610Y, R958S, P1119T and A1731S) were selected for functional analysis. Overexpression and knockdown-rescue experiments were carried out in cultured primary hippocampal neurons with a major focus on the analysis of morphological changes. Furthermore, the effect on actin polymerization in fibroblast cell lines was investigated. All four variants revealed functional impairment to various degrees, as a consequence of alterations in spine volume and clustering at synapses and an overall loss of presynaptic contacts. The A1731S variant was identified in four unrelated SCZ patients (0.83%) but not in any of the sequenced controls and public databases (P=4.6 × 10(-5)). Patients with the A1731S variant share an early prodromal phase with an insidious onset of psychiatric symptoms. A1731S overexpression strongly decreased the SHANK2-Bassoon-positive synapse number and diminished the F/G-actin ratio. Our results strongly suggest a causative role of rare SHANK2 variants in SCZ and underline the contribution of SHANK2 gene mutations in a variety of neuropsychiatric disorders.
Symptom dimensions have not yet been comprehensively tested as predictors of the substantial heterogeneity in outcomes of antidepressant treatment in major depressive disorder.
We tested nine symptom ...dimensions derived from a previously published factor analysis of depression rating scales as predictors of outcome in 811 adults with moderate to severe depression treated with flexibly dosed escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP). The effects of symptom dimensions were tested in mixed-effect regression models that controlled for overall initial depression severity, age, sex and recruitment centre. Significant results were tested for replicability in 3637 adult out-patients with non-psychotic major depression treated with citalopram in level I of Sequenced Treatment Alternatives to Relieve Depression (STAR*D).
The interest-activity symptom dimension (reflecting low interest, reduced activity, indecisiveness and lack of enjoyment) at baseline strongly predicted poor treatment outcome in GENDEP, irrespective of overall depression severity, antidepressant type and outcome measure used. The prediction of poor treatment outcome by the interest-activity dimension was robustly replicated in STAR*D, independent of a comprehensive list of baseline covariates.
Loss of interest, diminished activity and inability to make decisions predict poor outcome of antidepressant treatment even after adjustment for overall depression severity and other clinical covariates. The prominence of such symptoms may require additional treatment strategies and should be accounted for in future investigations of antidepressant response.
Introduction
Research of COVID-19-Pandemic mental health impact focus on three groups: the general population, (2) so called vulnerable groups (e.g. individuals with mental disorders) and (3) ...individuals suffering COVID-19 including Long-COVID syndromes.
Objectives
We investigate whether individuals with a history of depression in the past, react to the COVID-19 pandemic with increased depressive symptoms.
Methods
Longitudinal Data stem from the NAKO-Baseline-Assessment (2014-2019, 18 study centers in Germany, representative sampled individuals from 20 to 74 years) and the subsequent NAKO-COVID-Assessment (5-11/2020). The sample for analysis comprises 115.519 individuals. History of psychiatric disorder was operationalized as lifetime self-report for physician-diagnosed depression. Depressive symptoms were measured with the PHQ 9.
Results
Mean age of the sample at baseline was 49.95 (SD 12.53). It comprised 51.70 women; 14 % of the individuals had a history of
physician-diagnosed depression. Considering a PHQ-Score with cut-off 10 as a clinical relevant depression, 3.65 % of the individuals without history of depression and 24.19 % of those with a history of depression were depressed at baseline. The NAKO-COVID-Assessment revealed 6.53 % depressed individuals without any history of depression and a similar rate of 23.29 % in those with history of depression.
Conclusions
In contrast to that what we expected, individuals with a history of a physician-diagnosed depression, did not react with increasing depressiveness during the first phase of the pandemic in Germany. Several reasons could be discussed. Whether there medium and long-term impact remains open.
Disclosure
No significant relationships.
Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk ...genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.
How to do genetic counseling in psychiatry? Johansson Soller, M.; Moldovan, R.; Ingvoldstad Malmgren, C. ...
EUROPEAN PSYCHIATRY,
04/2021, Letnik:
64, Številka:
S1
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Genetic counselling has been defined as the process of helping people “understand and adapt to medical, psychosocial, and familial aspects of genetic conditions.” It can also help patients and ...families deal with stigma and understand the significance of possible genetic findings. Psychiatric genetic counselling (PGC) is an emerging field aimed to help people with a personal or family history of psychiatric illnesses such as schizophrenia, bipolar disorder, or neuropsychiatric conditions, to understand genetic etiological mechanisms as a critical component. Counselling strategies are used to identify and adapt to psychological and familial consequences of the conditions and to reduce stigma surrounding the psychiatric illness. A recent survey showed that PGC is still not routinely offered and usually only discussed at the initiative of the patient, e.g. if they ask about the possibility of “hereditary" illness, or if a caregiver during a session for another indication, identifies the family history. If a monogenetic or chromosomal cause is identified, the genetic counselling follows a more traditional path, but if, on the other hand, the cause is complex, the counselling will not be as clearcut. It will then focus on explaining risk for disease with quite uncertain riskscores as no causative genetic change is identified. Although genetic testing most often cannot be offered and individual risk scores based on genetic markers cannot be given, there is still great value for patients and their relatives in PGC. Studies have shown that the effect of PGC is an increase of empowerment and a reduction of stigma.
Disclosure
No significant relationships.
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