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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.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
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.
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.
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.
Fluoroquinolones (FQs) and extended-spectrum cephalosporins (ESCs) are associated with higher risk of Clostridioides difficile infection (CDI). Decreasing the unnecessary use of FQs and ESCs is a goal of antimicrobial stewardship. Understanding how prescribers perceive the risks and benefits of FQs and ESCs is needed.
We conducted interviews with clinicians from 4 hospitals. Interviews elicited respondent perceptions about the risk of ESCs, FQs, and CDI. Interviews were audio recorded, transcribed, and analyzed using a flexible coding approach.
Interviews were conducted with 64 respondents (38 physicians, 7 nurses, 6 advance practice providers, and 13 pharmacists). ESCs and FQs were perceived to have many benefits, including infrequent dosing, breadth of coverage, and greater patient adherence after hospital discharge. Prescribers stated that it was easy to make decisions about these drugs, so they were especially appealing to use in the context of time pressures. They described having difficulty discontinuing these drugs when prescribed by others due to inertia and fear. Prescribers were skeptical about targeting specific drugs as a stewardship approach and felt that the risk of a negative outcome from under treatment of a suspected bacterial infection was a higher priority than the prevention of CDI.
Prescribers in this study perceived many advantages to using ESCs and FQs, especially under conditions of time pressure and uncertainty. In making decisions about these drugs, prescribers balance risk and benefit, and they believed that the risk of CDI was acceptable in compared with the risk of undertreatment.
Behavioral addictions, like computergame addiction respectively internet addiction, have become a growing concern in research. Currently similarities between behavioral addictions and substance dependency are discussed in the scientific community controversially. Unfortunately a mismatch exists between high rates of treatment seeking people and low rates of scientific studies on computergame-addiction, especially concerning risk factors and their contribution to the etiology of computergame addiction.
The aim of this contribution is to shed light on possible etiological factors of computergame addiction concerning personality and vulnerability to stress in clients of the “Ambulanz für Spielsucht”, a specialized outpatient clinic at the University of Mainz.
131 clients were testet with several psychometric measures including ACA-S (Scale for the Assessment of Computergame-Addiction), SCL-90R (Symptom Checklist 90R), NEO-FFI (NEO Five-Factory-Inventory) and Brief-COPE.
69.4% (91 clients) fulfilled criteria for computergame addiction, 30.6% (40 persons) showed no psychopathology. The examination unveilled several caracteristics in addicted computergamers: They revealed higher levels concerning Global Severity Index (GSI), with increased subscales of depression and social insecurity. They showed significantly higher scores in the personality factor “Neuroticism” and decreased scores in the factors “Extraversion” and “Conscientiousness”. Addicted computergamers stand out from normal gamers in respect of nature of coping strategies, making predominantly use of avoiding ones.
The results contribute to a better understanding of underlying mechanisms leading to and sustaining addictive computergame behavior. The role of maladaptive coping strategies and social insecurity points out the necessity to add appropriate elements to psychotherapeutic intervention strategies.
Accumulating evidence suggests that deficits of visual selective attention may already occur at early stages of Alzheimer's disease (AD) like the prodromal phase of mild cognitive impairment (MCI).
Our study investigated visual selective attention in amnestic MCI and probable AD patients compared to healthy elderly controls. Groups were matched for age, gender and education. In combination with Bundesen's ‘theory of visual attention’, two mathematically independent and quantitative parameter estimates were derived from a partial report of briefly presented letter arrays: top-down control of attentional selection, representing task-related attentional weighting for prioritizing relevant visual objects, and spatial distribution of attentional weights across the left and right hemifield.
Compared to controls, MCI patients showed significantly reduced top-down controlled selection which further deteriorated in AD subjects. Moreover, attentional weighting was significantly unbalanced across hemifields in MCI and tended to be more lateralized in AD. The majority of patients was biased to the left. Across MCI and AD patients, carriers of the apolipoprotein E ɛ4 allele (ApoE4) revealed a leftward spatial bias. The leftward bias was the more pronounced the younger the ApoE4-positive patients and the earlier disease onset. ApoE4-negative subjects showed balanced attentional weighting.
These results indicate that impaired top-down control may be linked to early dysfunction of fronto-parietal cortico-cortical networks. Accompanying, an early interhemispheric asymmetry in temporo-parietal cortical interactions might cause a pathological spatial bias. As the inheritance of ApoE4 is associated with asymmetric parietal metabolism, a pathological spatial bias may function as early cognitive marker for detecting probable AD subjects.
In order to systematically specify the affected and preserved attentional components in adults with ADHD, we used an assessment tool (Finke et al, 2006) based on Bundesen's ‘theory-of-visual-attention’ (TVA) to compare two groups of adults with ADHD (medicated and unmedicated) and a matched healthy control group. TVA provides four quantitative, mathematically independent parameter estimates: visual perceptual processing speed (elements/s), working memory (WM) storage capacity (number of elements), spatial distribution of attentional weights, and top-down control. All parameters are assessed with highly similar stimuli (letters) and response requirements (verbal report), imposing comparable demands on perceptual and motor skills. Performance is assessed in terms of accuracy at certain exposure durations instead of response latency, avoiding confoundation with motor dysfunction (e.g. hyperactivity). The WM storage capacity was reduced in unmedicated ADHD patients, was significantly higher in medicated patients but was still significantly worse compared to normal controls. The spatial distribution of attentional weights is altered in that unmedicated ADHD patients did not show the normal preference for the left visual hemi-field (‘pseudoneglect'). Perceptual processing speed and top-down control of attention were comparable across groups. In conclusion, the attentional core deficit in ADHD seems to consist of a reduction in WM storage capacity, i.e. in the amount of information that can be maintained in parallel. Since no deficits in speed and top-down control have been found, slow and variable performance in response-based task might rather reflect impairments in the initiation, execution and inhibition of motor responses than impairments on the level of perceptual processing.
Until now, no studies have been published about the prevalence and needs of children with a mentally ill parent nor about interventions for this vulnerable group in the federal state of Saxony, Germany.
Therefore, the multi-centre study HELP-S for Children was initiated by the University of Leipzig in cooperation with the Technical University of Dresden. The aim of HELP-S for Children is to identifiy the prevalence and specific needs of children with a mentally ill parent.
All psychiatric outpatients of Leipzig and Dresden at an appointed date will be asked to participate in the study. Patients with minor children will be asked to fill out a detailed questionnaire about the perceived needs of their children and the existing and lacking support possibilities. Because there is no adequate instrument to assess the needs of the children with a mentally ill parent, we will develop a standardized questionnaire by using expert interviews and a pre-test with mentally ill parents.
The standardized questionnaire, which we will develop for this study, will be useable in other studies about needs of children with a mentally ill parent. Furthermore, we will gather information about the prevalence of children of mentally ill parents who are outpatients and about the specific needs of these children in the age of 0 to 18. These results will be presented and discussed during an expert workshop at the end of the project to explore ways to improve the situation of children with a mentally ill parent.
In recent years the amount of adults claiming to have a neuropsychological disorder increased dramatically, raising the suspicion that some of them may malinger symptoms for secondary gain, such as receiving compensation or drugs. Hence, valid diagnostic tools in the assessment of neuropsychiatric conditions are of great interest. In our experiment, we investigated whether adults feigning symptoms of Attention-deficit/hyperactivity disorder (ADHD) can be successfully detected by an assessment based on the ‘theory of visual attention’, namely TVA
[Bundesen, C. (1990). A theory of visual attention. Psychological Review 97, 523-547]. Therefore, we provided healthy adults with information about ADHD (available on the internet) and instructed them to feign symptoms on self-report scales, as well as on the whole report of TVA, which provides an quantitative, parametric measure of the affected and preserved attentional functions of ADHD adults. Our results show that malingerers were indeed able to feign symptoms on the conventional questionnaires, but not capable of imitating the specific response pattern on the whole report of TVA that ADHD patients show. We found a sensitivity of 80 % and a specificity of 93 % for the whole report of TVA. Beyond the detection of adults malingering ADHD, TVA may also help to identify adults feigning symptoms of other neuropsychological disorders.
At present, limited quantitative data about computer addiction of young people are available. The study was designed to obtain the prevalence rate of computer addiction of children. A further objective was to increase the know-how about cyber-related addictions and their comorbidity of mental disorders.
Survey among children/young people and their parents using questionnaires CBCL, YSR, CSVK, OSV and View. The children answered the questions of CSVK and OSV, adolescents over the age of 11 further filled in YSR. The parents were interviewed using CBCL and View.
Data collection was in the paediatric psychiatry in Munich, data analysis in the University of Mainz.
100 patients between 8 and 18 years of age, who asked for an outpatient or inpatient treatment of various mental disorders, filled in the questionnaires from July to November 2009 (63% male and 37% female).
The prevalence of computer addiction was 3%. The prevalence of computer abuse was 7%.
The study exhibited a significant difference in gender: boys showed to be mainly addicted, girls mainly improper users.
It was further observed that the young cyber junkies use games, chats, emails and communities more frequently than average users.
In accordance with other studies it was determined that possible comorbidities are depression, anxiety disorders and aggressive behaviour.
In addition to other mental disorders, 3-6% of the patients in a German psychiatry were found to be computer addicted. It is important to do research for a better diagnostic and therapeutic treatment or implementation of preventive interventions.
Cognitive behavioural therapy (CBT) is an important treatment in conjunction with psychopharmacotherapy in schizophrenia. However, there is only very little research on the effects of such interventions on brain function.
Recent studies have suggested that jumping to conclusions and a specific attributional bias is a predominant cognitive style in patients which might lead to the development of delusions. In this multi-centre fMRI trial, we investigated the effect of nine months of CBT on neural correlates of “jumping to conclusions” and the “attributional style” in patients with psychosis. Eighty patients and 80 control subjects were recruited in six centres and measured with 3-Tesla functional magnetic imaging (fMRI) before and after CBT.
It could be shown that CBT ameliorates differences in brain activations between patients and controls after nine months.
These results support the feasibility of fMRI multicenter trials and sheds further light into the mechanisms relating psychotherapy to brain function in Schizophrenia.
Structural and functional deviations in schizophrenic patients with formal thought disorder (FTD) point towards a dysfunction within left sided language network.
Independent component analysis (ICA), a new approach to fMRI analysis, enables to target the question of a network dysfunction directly. Using this method in healthy controls it was possible to identify the language networks separately for the left and the right hemispheres In the present study we use ICA analysis to examine changes of the language network separate for each hemisphere in relation to the severity of FTD.
We hypothesize increasing disintegration with increasing severity of FTD only in the left sided language network while the right language network should remain unaffected.
We investigated 16 schizophrenic patients with different severity of FTD and matched healthy controls using ICA decomposition of the BOLD signal. The spatial similarity of the individual language networks was correlated to the severity of FTD.
The integrity of the left language network decrease with increasing severity of FTD (r = -0.79, p < 0.01), while the integrity of the right language network show no significant correlation to the severity of FTD.
For the first time the isolated breakdown of the left sided language network was linked specifically to schizophrenic FTD. This result unites older manly left hemispheric findings of structural and functional abnormalities in schizophrenic FTD.
In the treatment of MDD, insufficient treatment outcome and the delayed onset of action still remain major problems.
Measuring plasma concentrations, i.e. TDM is a possible option to improve therapeutic outcomes.
The aim of this prospective and naturalistic study was to evaluate the economic and clinical benefit of TDM for depressed inpatients treated with citalopram.
Inpatients with MDD according to ICD-10 were included and treated with citalopram. Psychopathology was assessed by the 17-item Hamilton Depression (HAMD-17) rating scale in weekly intervals for five weeks. In parallel, serum concentrations of citalopram were measured.
55 patients were included (27f). 84% of the patients with citalopram plasma concentrations below 50 ng/ml (n = 36) were non-responders in week five. Among patients who achieved plasma concentrations ≥50 ng/ml (n = 19) on day 7, 47% became responder at week five (p = 0.025). Patients with plasma levels ≥50 ng/ml had a significantly shorter duration of hospitalization (49 ± 20) than patients below 50 ng/ml (72 ± 37; p = 0.033).
Our results show that citalopram plasma levels above 50 ng/ml are predictive for later treatment outcome and that TDM is cost effective due to reduced duration of hospitalization.
The influence of repetitive transcranial magnetic stimulation (rTMS) on mood in healthy people is uncertain, as former studies show divergent results. Previous studies in healthy volunteers focused exclusively on the immediate effect of a single session of rTMS on mood.
The aim of this study was to analyse the influence on mood of a series of 9 High Frequency (HF) rTMS stimulations of the left dorsolateral prefrontal cortex (DLPFC).
44 young healthy male volunteers were randomly assigned to receive 9 sessions of active HF-rTMS (n = 22) or sham rTMS (n = 22) over the left DLPFC. Each session in the active group consisted of 15 trains of 25 Hz starting with 100% of motor threshold. Sham stimulation was performed following the same protocol, but using a sham coil. The variables of interest were the Beck Depression Inventory (BDI) and Visual Analogue Scales (VAS) which quantified “mood”, “enjoyment” and “energy”.
We found a significant reduction of the BDI score in the active group (GLM, p < 0.001) whereas no significant changes of the BDI score were caused by sham stimulation (GLM, p = 0.109). We did not find significant differences caused by active or sham stimulation in VAS scales except for the VAS labelled lively/gloomy immediately after stimulation. The active group was found to be more “gloomy” (p = 0.001).
Our data support the hypothesis that a 9-day long series of HF-rTMS of the left DLPFC improves mood, analysed by BDI in healthy young men.
A significant part computer game players and internet users show clinical features of abuse and addiction (loss of control, withdrawal symptoms, tolerance, continuation of game play even with increasing negative consequence in social and academic life). Similar mechanisms are suggested to underlie the pathogenesis and maintenance of internet and computer game addiction and substance-related addictions.
Neuroscientific research on internet and computer game addiction is sparse, yet emerging. To review previous studies is the objective of the present project.
We aim to identify common findings regarding the neurophysiological processes underlying internet and computer game addiction. This could be helpful for establishing a sound model for these emerging disorders.
Neuroscientific studies on internet and computer game addiction were systematically searched in “Pubmed”, “Google scholar” and “PsychInfo”. Titles were examined first to screen potential articles, followed by abstracts, and then manuscripts were downloaded. The reference sections of downloaded manuscripts were examined for additional references not located in the searches.
Neuroscientific research on internet and computer game addiction is mainly located in the Asian area, probably due to a higher regional prevalence. Methodologies range from ERP, resting state EEG, resting state fMRI, VBM to PET, investigating very different concepts of addiction, including impulsivity, craving, reward processing and cue-reactivity.
Addicted internet and computer game users are overall suggested to have altered brain mechanisms similar to individuals with substance addictions. However, a sound model on the neurophysiologic alterations has not been established yet.