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1.
Int J Bipolar Disord ; 9(1): 12, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797645

RESUMO

BACKGROUND: Impaired working memory is a core cognitive deficit in both bipolar disorder and schizophrenia. Its study might yield crucial insights into the underpinnings of both disorders on the cognitive and neurophysiological level. Visual working memory capacity is a particularly promising construct for such translational studies. However, it has not yet been investigated across the full spectrum of both disorders. The aim of our study was to compare the degree of reductions of visual working memory capacity in patients with bipolar disorder (PBD) and patients with schizophrenia (PSZ) using a paradigm well established in cognitive neuroscience. METHODS: 62 PBD, 64 PSZ, and 70 healthy controls (HC) completed a canonical visual change detection task. Participants had to encode the color of four circles and indicate after a short delay whether the color of one of the circles had changed or not. We estimated working memory capacity using Pashler's K. RESULTS: Working memory capacity was significantly reduced in both PBD and PSZ compared to HC. We observed a small effect size (r = .202) for the difference between HC and PBD and a medium effect size (r = .370) for the difference between HC and PSZ. Working memory capacity in PSZ was also significantly reduced compared to PBD with a small effect size (r = .201). Thus, PBD showed an intermediate level of impairment. CONCLUSIONS: These findings provide evidence for a gradient of reduced working memory capacity in bipolar disorder and schizophrenia, with PSZ showing the strongest degree of impairment. This underscores the importance of disturbed information processing for both bipolar disorder and schizophrenia. Our results are compatible with the cognitive manifestation of a neurodevelopmental gradient affecting bipolar disorder to a lesser degree than schizophrenia. They also highlight the relevance of visual working memory capacity for the development of both behavior- and brain-based transdiagnostic biomarkers.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33756033

RESUMO

A library of glycoforms of human interleukin 6 (IL-6) comprising complex and mannosidic N-glycans was generated by semisynthesis. The three segments were connected by sequential native chemical ligation followed by two-step refolding. The central glycopeptide segments were assembled by pseudoproline-assisted Lansbury aspartylation and subsequent enzymatic elongation of complex N-glycans. Nine IL-6 glycoforms were synthesized, 7 of which were evaluated for in vivo plasma clearance in rats and compared to non-glycosylated recombinant IL-6 from E. coli. Each IL-6 glycoform was tested in three animals and reproducibly showed individual serum clearances depending on the structure of the N-glycan. The clearance rates were atypical, since the 2,6-sialylated glycoforms of IL-6 cleared faster than the corresponding asialo IL-6 with terminal galactoses. Compared to non-glycosylated IL-6 the plasma clearance of IL-6 glycoforms was delayed in the presence of larger and multibranched N-glycans in most cases.

4.
Neurobiol Dis ; 154: 105337, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33753289

RESUMO

TOR1A is the most common inherited form of dystonia with still unclear pathophysiology and reduced penetrance of 30-40%. ∆ETorA rats mimic the TOR1A disease by expression of the human TOR1A mutation without presenting a dystonic phenotype. We aimed to induce dystonia-like symptoms in male ∆ETorA rats by peripheral nerve injury and to identify central mechanism of dystonia development. Dystonia-like movements (DLM) were assessed using the tail suspension test and implementing a pipeline of deep learning applications. Neuron numbers of striatal parvalbumin+, nNOS+, calretinin+, ChAT+ interneurons and Nissl+ cells were estimated by unbiased stereology. Striatal dopaminergic metabolism was analyzed via in vivo microdialysis, qPCR and western blot. Local field potentials (LFP) were recorded from the central motor network. Deep brain stimulation (DBS) of the entopeduncular nucleus (EP) was performed. Nerve-injured ∆ETorA rats developed long-lasting DLM over 12 weeks. No changes in striatal structure were observed. Dystonic-like ∆ETorA rats presented a higher striatal dopaminergic turnover and stimulus-induced elevation of dopamine efflux compared to the control groups. Higher LFP theta power in the EP of dystonic-like ∆ETorA compared to wt rats was recorded. Chronic EP-DBS over 3 weeks led to improvement of DLM. Our data emphasizes the role of environmental factors in TOR1A symptomatogenesis. LFP analyses indicate that the pathologically enhanced theta power is a physiomarker of DLM. This TOR1A model replicates key features of the human TOR1A pathology on multiple biological levels and is therefore suited for further analysis of dystonia pathomechanism.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33541809

RESUMO

This narrative review summarizes and discusses the implications of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and the upcoming International Classification of Diseases (ICD)-11 classification systems on the prevalence of bipolar disorder and on the validity of the DSM-5 diagnosis of bipolar disorder according to the Robin and Guze criteria of diagnostic validity. Here we review and discuss current data on the prevalence of bipolar disorder diagnosed according to DSM-5 versus DSM-IV, and data on characteristics of bipolar disorder in the two diagnostic systems in relation to extended Robin and Guze criteria: 1) clinical presentation, 2) associations with para-clinical data such as brain imaging and blood-based biomarkers, 3) delimitation from other disorders, 4) associations with family history / genetics, 5) prognosis and long-term follow-up, and 6) treatment effects. The review highlights that few studies have investigated consequences for the prevalence of the diagnosis of bipolar disorder and for the validity of the diagnosis. Findings from these studies suggest a substantial decrease in the point prevalence of a diagnosis of bipolar with DSM-5 compared with DSM-IV, ranging from 30-50%, but a smaller decrease in the prevalence during lifetime, corresponding to a 6% reduction. It is concluded that it is likely that the use of DSM-5 and ICD-11 will result in diagnostic delay and delayed early intervention in bipolar disorder. Finally, we recommend areas for future research.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33637837

RESUMO

Depressed patients often do not respond to the first antidepressant prescribed, resulting in sequential trials of different medications. Personalised medicine offers a means of reducing this delay; however, the clinical effectiveness of personalised approaches to antidepressant treatment has not previously been tested. We assessed the clinical effectiveness of using a predictive algorithm, based on behavioural tests of affective cognition and subjective symptoms, to guide antidepressant treatment. We conducted a multicentre, open-label, randomised controlled trial in 913 medication-free depressed patients. Patients were randomly assigned to have their antidepressant treatment guided by a predictive algorithm or treatment as usual (TaU). The primary outcome was the response of depression symptoms, defined as a 50% or greater reduction in baseline score of the QIDS-SR-16 scale, at week 8. Additional prespecified outcomes included symptoms of anxiety at week 8, and symptoms of depression and functional outcome at weeks 8, 24 and 48. The response rate of depressive symptoms at week 8 in the PReDicT (55.9%) and TaU (51.8%) arms did not differ significantly (odds ratio: 1.18 (95% CI: 0.89-1.56), P = 0.25). However, there was a significantly greater reduction of anxiety in week 8 and a greater improvement in functional outcome at week 24 in the PReDicT arm. Use of the PReDicT test did not increase the rate of response to antidepressant treatment estimated by depressive symptoms but did improve symptoms of anxiety at week 8 and functional outcome at week 24. Our findings indicate that personalisation of antidepressant treatment may improve outcomes in depressed patients.

7.
Neurosci Biobehav Rev ; 125: 582-591, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33582234

RESUMO

Studies have demonstrated an increased risk of accidents and injuries in children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). However, little is known about how accident risk may alter over the lifespan. Additionally, it would be important to know if the most common types of accidents and injuries differ in ADHD patients over different age groups. Furthermore, there is increasing evidence of an ameliorating effect of ADHD medication on accident risk. Lastly, the underlying risk factors and causal mechanisms behind increased accident risk remain unclear. We therefore conducted a systematic review focusing on the above described research questions. Our results suggested that accident/injury type and overall risk changes in ADHD patients over the lifespan. ADHD medication appeared to be similarly effective at reducing accident risk in all age groups. However, studies with direct comparisons of accident/injuries and effects of medication at different age groups or in old age are still missing. Finally, comorbidities associated with ADHD such as substance abuse appear to further increase the accident/injury risk.

8.
Lancet ; 397(10277): 914-927, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33581801

RESUMO

Anxiety disorders form the most common group of mental disorders and generally start before or in early adulthood. Core features include excessive fear and anxiety or avoidance of perceived threats that are persistent and impairing. Anxiety disorders involve dysfunction in brain circuits that respond to danger. Risk for anxiety disorders is influenced by genetic factors, environmental factors, and their epigenetic relations. Anxiety disorders are often comorbid with one another and with other mental disorders, especially depression, as well as with somatic disorders. Such comorbidity generally signifies more severe symptoms, greater clinical burden, and greater treatment difficulty. Reducing the large burden of disease from anxiety disorders in individuals and worldwide can be best achieved by timely, accurate disease detection and adequate treatment administration, scaling up of treatments when needed. Evidence-based psychotherapy (particularly cognitive behavioural therapy) and psychoactive medications (particularly serotonergic compounds) are both effective, facilitating patients' choices in therapeutic decisions. Although promising, no enduring preventive measures are available, and, along with frequent therapy resistance, clinical needs remain unaddressed. Ongoing research efforts tackle these problems, and future efforts should seek individualised, more effective approaches for treatment with precision medicine.

9.
Sci Rep ; 11(1): 1155, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441847

RESUMO

Predicting lithium response prior to treatment could both expedite therapy and avoid exposure to side effects. Since lithium responsiveness may be heritable, its predictability based on genomic data is of interest. We thus evaluate the degree to which lithium response can be predicted with a machine learning (ML) approach using genomic data. Using the largest existing genomic dataset in the lithium response literature (n = 2210 across 14 international sites; 29% responders), we evaluated the degree to which lithium response could be predicted based on 47,465 genotyped single nucleotide polymorphisms using a supervised ML approach. Under appropriate cross-validation procedures, lithium response could be predicted to above-chance levels in two constituent sites (Halifax, Cohen's kappa 0.15, 95% confidence interval, CI [0.07, 0.24]; and Würzburg, kappa 0.2 [0.1, 0.3]). Variants with shared importance in these models showed over-representation of postsynaptic membrane related genes. Lithium response was not predictable in the pooled dataset (kappa 0.02 [- 0.01, 0.04]), although non-trivial performance was achieved within a restricted dataset including only those patients followed prospectively (kappa 0.09 [0.04, 0.14]). Genomic classification of lithium response remains a promising but difficult task. Classification performance could potentially be improved by further harmonization of data collection procedures.

10.
Acta Neuropsychiatr ; : 1-7, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33478614

RESUMO

BACKGROUND: Dietary lipids (omega-3 polyunsaturated fatty acids (n-3) PUFAs) and saturated fatty acids (SFA) seem to play an important role in brain health. (n-3) PUFAs have been shown to improve cerebral perfusion and to promote synaptogenesis. In this study, we investigated the relationship between dietary fat composition, cognitive performance and brain morphology in cognitively healthy individuals. METHODS: A total of 101 cognitively healthy participants (age: 42.3 ± 21.3 years, 62 females) were included in this study. Verbal memory was assessed using the California Verbal Learning Test (CVLT). Intake of (n-3) PUFA and SFA was calculated from food-frequency questionnaire-derived data (EPIC-FFQ). Magnetic resonance imaging (MRI) data were obtained (Siemens Trio 3T scanner) and grey matter volumes (GMV) were assessed by voxel-based morphometry (VBM/SPM8). We examined the association of SFA/(n-3) PUFA ratio and memory performance as well as GMV using regression models adjusted for age, sex, education, body mass index, apolipoprotein E (APOE) status and alcohol consumption. For VBM data, a multiple regression analysis was performed using the same covariates as mentioned before with intracranial volume as an additional covariate. RESULTS: A high SFA/(n-3) PUFA ratio was significantly (p < 0.05) correlated with poorer verbal memory performance and with lower GMV in areas of the left prefrontal cortex that support memory processes. CONCLUSIONS: These findings suggest that a diet rich in PUFAs is likely to exert favourable effects on brain morphology in brain areas important for memory and executive functions. This could constitute a possible mechanism for maintaining cognitive health in older age.

11.
Eur Neuropsychopharmacol ; 43: 116-128, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33388218

RESUMO

EEG studies have shown that adult ADHD patients have less stable brain arousal regulation than age and gender matched controls. Psychostimulants have brain arousal stabilising properties evident in EEG patterns. The aim of this study was to investigate whether the stability of brain arousal regulation has prognostic value in predicting response to methylphenidate therapy in adult ADHD patients. In an open-label, single-arm, multi-centre, confirmatory trial, 121 adult ADHD patients were recruited and 112 qualified for the full analysis set. All participants received an initial dose of 20 mg extended release methylphenidate at baseline. After a titration phase of up to 4 weeks, patients remained on a weight-based target dose of extended release methylphenidate for 4 weeks. Using the Vigilance Algorithm Leipzig (VIGALL 2.1), we assessed brain arousal regulation before the treatment with methylphenidate, based on a 15-min EEG at quiet rest recorded at baseline. Using automatic stage-classification of 1 s segments, we computed the mean EEG-vigilance (indexing arousal level) and an arousal stability score (indexing arousal regulation). The primary endpoint was the association between successful therapy, defined by a 30% reduction in CAARS, and stable/unstable brain arousal. 52 patients (46%) showed an unstable brain arousal regulation of which 23% had therapy success. In the stable group, 35% had therapy success, implying an absolute difference of 12 percentage points (95% CI -5 to 29, p = 0.17) in the direction opposite to the hypothesized one. There were no new findings regarding the tolerability and safety of extended release methylphenidate therapy.

12.
Eur Neuropsychopharmacol ; 44: 105-120, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33483252

RESUMO

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.

13.
Neurosci Biobehav Rev ; 124: 100-123, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33515607

RESUMO

Attention-deficit / hyperactivity disorder (ADHD) and Bipolar Disorder (BD) are common mental disorders with a high degree of comorbidity. However, no systematic review with meta-analysis has aimed to quantify the degree of comorbidity between both disorders. To this end we performed a systematic search of the literature in October 2020. In a meta-analysis of 71 studies with 646,766 participants from 18 countries, it was found that about one in thirteen adults with ADHD was also diagnosed with BD (7.95 %; 95 % CI: 5.31-11.06), and nearly one in six adults with BD had ADHD (17.11 %; 95 % CI: 13.05-21.59 %). Substantial heterogeneity of comorbidity rates was present, highlighting the importance of contextual factors: Heterogeneity could partially be explained by diagnostic system, sample size and geographical location. Age of BD onset occurred earlier in patients with comorbid ADHD (3.96 years; 95 % CI: 2.65-5.26, p < 0.001). Cultural and methodological differences deserve attention for evaluating diagnostic criteria and clinicians should be aware of the high comorbidity rates to prevent misdiagnosis and provide optimal care for both disorders.

14.
Neurosci Biobehav Rev ; 124: 63-77, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33516734

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders worldwide, and in the majority of patients persists into adulthood. However, it remains unclear how maternal ADHD could affect pregnancy and birth as well as early mother-(father)-child interaction. There are several studies investigating the effect of depressed or anxious parents on parent-child-interactions in early infancy, but data about the influence of parental ADHD is lacking although it is a common mental disorder in parents. Additionally, the prescription of stimulant and other ADHD medication for adult ADHD patients is rising due to improved diagnostic procedures and a greater awareness of this disorder in adulthood among psychiatrists and psychologists. However, this leads to increased numbers of treated ADHD women that wish to have children or experience unplanned pregnancies while taking stimulant medication. In our systematic review we aimed at analysing the current evidence for the association of maternal ADHD with pregnancy and birth outcomes, pregnancy risks and health behaviour in pregnancy, as well as the association of parental ADHD with early parent-child interaction and early child development in the first 3 years. Furthermore, we reviewed recent evidence on the risks of stimulant and non-stimulant treatment for ADHD in pregnancy and lactation.

16.
Neurosci Biobehav Rev ; 121: 307-345, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33359622

RESUMO

The risk for major depressive disorder (MDD) is considerably increased in young adults with attention-deficit/hyperactivity disorder (ADHD) but underlying mechanisms are poorly understood. This review explores ADHD-specific neurocognitive impairments as possible underlying mechanisms for ADHD-depression comorbidity. Two systematic literature searches were conducted in EBSCOhost, PubMED, and Cochrane Reviews databases according to PRISMA guidelines. The first search identified 18 meta-analyses of cross-sectional and longitudinal studies on cognitive dysfunctions in MDD across the lifespan. The second search identified six original studies on reaction time variability in MDD. During acute depression, children and adults showed cognitive deficits that overlapped with some of the ADHD-related impairments. Findings from remitted patients, high-risk individuals, and few prospective studies suggest that a subset of these shared impairments, specifically executive dysfunctions (selective attention, verbal fluency, working memory) and long-term memory problems, are candidate pre-existing risk markers of depression. We discuss if and how these specific neurocognitive mechanisms may mediate developmental pathways from ADHD to depression. If replicated by longitudinal studies, these findings may guide future prevention strategies.

17.
Scand J Med Sci Sports ; 31(4): 903-913, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33341993

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent disorder in childhood and identifying risk factors associated with developing ADHD during childhood and adolescence is relevant from a clinical and epidemiological point of view. This work examines (a) whether overweight/obesity and low cardiorespiratory fitness (CRF) are associated with increased ADHD symptoms in childhood (cross-sectional analysis), and (b) whether overweight/obesity and low CRF levels during childhood predict increased ADHD symptoms in adolescence (longitudinal analysis). Data were examined from a longitudinal study of Estonian inhabitants who took part in the European Youth Heart Study (EYHS) in 1998 and 1999 (baseline age 9 years), who were re-evaluated 6 years later as part of the longitudinal Estonian Children Personality Behaviour and Health Study (ECPBHS). CRF was determined via an incremental maximal cycle-ergometer test, overweight/obesity was based on body mass index (BMI), and the 7-point af Klinteberg Hyperactivity Scale was used to assess ADHD symptoms at both time points. In the cross-sectional analysis, children with overweight/obesity were at greater risk of ADHD symptoms compared to underweight/normal weight children, as were those unfit compared to fit children (OR = 1.92 and 95%CI = 1.02-3.55, and OR = 1.84 and 95%CI = 1.13-2.98, respectively). The cross-sectional association between BMI and ADHD symptoms was mediated by CRF (z = 2.116, 42.9%; P = .034). The longitudinal analysis showed being unfit in childhood was associated with a greater risk of increased ADHD symptoms 6 years later in adolescence (OR = 2.26 and 95%CI = 1.14-4.47), even after adjusting for baseline ADHD symptoms and BMI. Our result suggests that being unfit is an additional risk factor for increased ADHD symptoms during childhood and adolescence. The association between BMI and ADHD symptoms was mediated by CRF in the cross-sectional analysis, and no association was seen between overweight/obesity and increased ADHD symptoms.

18.
BMJ Open ; 10(12): e040119, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262189

RESUMO

INTRODUCTION: Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%-60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity. METHODS AND ANALYSIS: This is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score <10), mean change in patients' self-reported Beck Depression Inventory (BDI-II) and mean change in high-density lipoprotein, low-density lipoprotein and total cholesterol from baseline to week 12. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226-EK 11) and by the relevant federal authority (Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences. TRIAL REGISTRATION NUMBERS: NCT04301271, DRKS00021119, EudraCT 2018-002947-27.

19.
Front Psychiatry ; 11: 536112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33250788

RESUMO

Background: Behavioral tasks focusing on different subdomains of reward processing may provide more objective and quantifiable measures of anhedonia and impaired motivation compared with clinical scales. Typically, single tasks are used in relatively small studies to compare cases and controls in one indication, but they are rarely included in larger multisite trials. This is due to limited systematic standardization as well as the challenges of deployment in international studies and stringent adherence to the high regulatory requirements for data integrity. The Reward Task Optimization Consortium (RTOC) was formed to facilitate operational implementation of reward processing tasks, making them suitable for use in future large-scale, international, multisite drug development studies across multiple indications. The RTOC clinical study aims to conduct initial optimization of a set of tasks in patients with major depressive disorder (MDD) or schizophrenia (SZ). Methods: We will conduct a multicenter study across four EU countries. Participants (MDD = 37, SZ = 37, with ≤80 age- and gender-matched healthy volunteers) will attend a study visit comprising screening, self-report and clinically rated assessments of anhedonia and symptom severity, and three reward processing tasks; specifically, the Grip Strength Effort task, the Doors task, and the Reinforcement Learning Working Memory task. The Grip Strength Effort and Doors tasks include simultaneous electroencephalography/event-related potential recordings. Outcomes will be compared using a two-way group design of MDD and SZ with matched controls, respectively. Further analyses will include anhedonia assessment scores as covariates. Planned analyses will assess whether our findings replicate previously published data, and multisite deployment will be evaluated through assessments of quality and conduct. A subset of participants will complete a second visit, to assess test-retest reliability of the task battery. Discussion: This study will evaluate the operational deployment of three reward processing tasks to the regulatory standards required for use in drug development trials. We will explore the potential of these tasks to differentiate patients from controls and to provide a quantitative marker of anhedonia and/or impaired motivation, establishing their usefulness as endpoints in multisite clinical trials. This study should demonstrate where multifaceted reward deficits are similar or divergent across patient populations. Registration: ClinicalTrials.gov (NCT04024371).

20.
Front Psychiatry ; 11: 552532, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33192665

RESUMO

Objective: Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how such genetic risk manifests in young, high-risk adults. We postulated that BD-PRS would be associated with risk factors for BD. Methods: A final sample of 185 young, high-risk German adults (aged 18-35 years) were grouped into three risk groups and compared to a healthy control group (n = 1,100). The risk groups comprised 117 cases with attention deficit hyperactivity disorder (ADHD), 45 with major depressive disorder (MDD), and 23 help-seeking adults with early recognition symptoms [ER: positive family history for BD, (sub)threshold affective symptomatology and/or mood swings, sleeping disorder]. BD-PRS was computed for each participant. Logistic regression models (controlling for sex, age, and the first five ancestry principal components) were used to assess associations of BD-PRS and the high-risk phenotypes. Results: We observed an association between BD-PRS and combined risk group status (OR = 1.48, p < 0.001), ADHD diagnosis (OR = 1.32, p = 0.009), MDD diagnosis (OR = 1.96, p < 0.001), and ER group status (OR = 1.7, p = 0.025; not significant after correction for multiple testing) compared to healthy controls. Conclusions: In the present study, increased genetic risk for BD was a significant predictor for MDD and ADHD status, but not for ER. These findings support an underlying shared risk for both MDD and BD as well as ADHD and BD. Improving our understanding of the underlying genetic architecture of these phenotypes may aid in early identification and risk stratification.

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