Publications by authors named "Stefan Borgwardt"

300 Publications

The societal cost of treatment-seeking patients with borderline personality disorder in Germany.

Eur Arch Psychiatry Clin Neurosci 2021 Oct 4. Epub 2021 Oct 4.

Department of Psychiatry and Psychotherapy, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.

According to previous research, borderline personality disorder (BPD) is associated with high cost-of-illness. However, there is still a shortage of cost-of-illness-studies assessing costs from a broad societal perspective, including direct and indirect costs. Further, there are considerable differences in the results among the existing studies. In the present study, 167 German men and women seeking specialized outpatient treatment for BPD were included. We assessed societal cost-of-illness bottom-up through structured face-to-face interviews and encompassed a wide range of cost components. All costs were calculated for the 2015 price level. Cost-of-illness amounted to € 31,130 per patient and year preceding disorder-specific outpatient treatment. € 17,044 (54.8%) were direct costs that were mostly related to hospital treatment. Indirect costs amounted to € 14,086 (45.2%). Within indirect costs, costs related to work disability were the most crucial cost driver. The present study underlines the tremendous economic burden of BPD. According to the present study, both the direct and indirect costs are of significant importance for the societal costs associated with BPD. Besides the need for more disorder-specific treatment facilities for men and women with BPD, we assume that education and employment are topics that should be specifically targeted and individually supported at an early stage of treatment.Trial Registration: German Clinical Trial Registration, DRKS00011534, Date of Registration: 11/01/2017, retrospectively registered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00406-021-01332-1DOI Listing
October 2021

Risk and Protective Factors for Personality Disorders: An Umbrella Review of Published Meta-Analyses of Case-Control and Cohort Studies.

Front Psychiatry 2021 6;12:679379. Epub 2021 Sep 6.

Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology, London, United Kingdom.

The putative risk/protective factors for several personality disorders remain unclear. The vast majority of published studies has assessed personality characteristics/traits rather than disorders. Thus, the current umbrella review of meta-analyses (MAs) aims to systematically assess risk or protective factors associated with personality disorders. We searched PubMed-MEDLINE/PsycInfo databases, up to August 31, 2020. Quality of MAs was assessed with AMSTAR-2, while the credibility of evidence for each association was assessed through standard quantitative criteria. Out of 571 initial references, five meta-analyses met inclusion criteria, encompassing 56 associations of 26 potential environmental factors for antisocial, dependent, borderline personality disorder, with a median of five studies per association, and median 214 cases per association. Overall, 35 (62.5%) of the associations were nominally significant. Six associations met class II (i.e., highly suggestive) evidence for borderline personality disorder, with large effect sizes involving childhood emotional abuse (OR = 28.15, 95% CI 14.76-53.68), childhood emotional neglect (OR = 22.86, 95% CI 11.55-45.22), childhood any adversities (OR = 14.32, 95% CI 10.80-18.98), childhood physical abuse (OR = 9.30, 95% CI 6.57-13.17), childhood sexual abuse (OR = 7.95, 95% CI 6.21-10.17), and childhood physical neglect (OR = 5.73, 95% CI 3.21-10.21), plus 16 further associations supported by class IV evidence. No risk factor for antisocial or dependent personality disorder was supported by class I, II, and III, but six and seven met class IV evidence, respectively. Quality of included meta-analyses was rated as moderate in two, critically low in three. The large effect sizes found for a broad range of childhood adversities suggest that prevention of personality disorders should target childhood-related risk factors. However, larger cohort studies assessing multidimensional risk factors are needed in the field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.679379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450571PMC
September 2021

[PsyYoung: A transcantonal project for facilitating access to care for young people at risk for psychotic disorders].

Rev Med Suisse 2021 Sep;17(751):1597-1601

Service de psychiatrie générale, Département de psychiatrie, CHUV et Université de Lausanne, 1011 Lausanne.

Approximately 2% of adolescents and young adults display symptoms indicating a high risk for psychotic disorders. Apart from a risk of 20-35% of developing a psychotic disorder, these individuals show high rates of persisting mental health problems and functional impairment, even in the absence of a psychotic transition. Treatment in specialized centers can improve outcomes in these patients, but the need to provide timely access to care needs to be balanced against the risks of premature psychiatrization, stigmatization and unnecessary medication treatment. The transcantonal project PsyYoung aims to optimize early detection in young people, while at the same time minimizing unnecessary psychiatrization. This will be achieved through improved networking across the entire care chain and a stepped-care intervention approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2021

Neural mapping of anhedonia across psychiatric diagnoses: A transdiagnostic neuroimaging analysis.

Neuroimage Clin 2021 Sep 16;32:102825. Epub 2021 Sep 16.

University of Basel, Department of Psychiatry (UPK), Basel, Switzerland. Electronic address:

Anhedonia has been associated with abnormal reward-related striatal dopamine functioning in patients with different psychiatric disorders. Here, we tested whether anhedonia expression mapped onto striatal volume across several psychiatric diagnoses. T1-weighted images from 313 participants including 89 healthy controls (HC), 22 patients with opioid use disorder (OUD), 50 patients with major depressive disorder (MDD), 45 patients with borderline personality disorder (BPD), 49 patients with first-episode psychosis (FEP), 43 patients with cocaine use disorder (CUD) and 15 patients with schizophrenia (SZ) were included. Anhedonia was assessed with subscores of the Beck Depression Inventory (BDI) and/or the Scale for the Assessment of Negative Symptoms (SANS). Voxel-based morphometry (VBM) was conducted for identifying dimensional symptom-structure associations using region of interest (ROI, dorsal and ventral striatum) and whole-brain analyses, as well as for group comparisons of striatal volume. ROI analyses revealed significant negative relationships between putamen volume and BDI and SANS anhedonia scores across OUD, MDD, BPD, CUD and SZ patients (n = 175) and MDD, FEP and SZ patients (n = 114), respectively. Whole-brain VBM analyses confirmed these associations and further showed negative relationships between anhedonia severity and volume of the bilateral cerebellum. There were group differences in right accumbens volume, which however were not related to anhedonia expression across the different diagnoses. Our findings indicate volumetric abnormalities in the putamen and cerebellum as a common neural substrate of anhedonia severity that cut across psychiatric entities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nicl.2021.102825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455863PMC
September 2021

The clinical relevance of formal thought disorder in the early stages of psychosis: results from the PRONIA study.

Eur Arch Psychiatry Clin Neurosci 2021 Sep 17. Epub 2021 Sep 17.

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University Munich, Nussbaumstr. 7, 80336, Munich, Germany.

Background: Formal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This study aimed to identify stable and generalizable FTD-subgroups of patients with recent-onset psychosis (ROP) by applying a comprehensive data-driven clustering approach and to test the validity of these subgroups by assessing associations between this FTD-related stratification, social and occupational functioning, and neurocognition.

Methods: 279 patients with ROP were recruited as part of the multi-site European PRONIA study (Personalised Prognostic Tools for Early Psychosis Management; www.pronia.eu). Five FTD-related symptoms (conceptual disorganization, poverty of content of speech, difficulty in abstract thinking, increased latency of response and poverty of speech) were assessed with Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS).

Results: The results with two patient subgroups showing different levels of FTD were the most stable and generalizable clustering solution (predicted clustering strength value = 0.86). FTD-High subgroup had lower scores in social (p < 0.001) and role (p < 0.001) functioning, as well as worse neurocognitive performance in semantic (p < 0.001) and phonological verbal fluency (p < 0.001), short-term verbal memory (p = 0.002) and abstract thinking (p = 0.010), in comparison to FTD-Low group.

Conclusions: Clustering techniques allowed us to identify patients with more pronounced FTD showing more severe deficits in functioning and neurocognition, thus suggesting that FTD may be a relevant marker of illness severity in the early psychosis pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00406-021-01327-yDOI Listing
September 2021

Editorial: Trajectories of Brain Abnormalities in Early Schizophrenia.

Front Psychiatry 2021 31;12:744471. Epub 2021 Aug 31.

Department of Psychiatry, University of Basel, Basel, Switzerland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.744471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439355PMC
August 2021

Novel Gyrification Networks Reveal Links with Psychiatric Risk Factors in Early Illness.

Cereb Cortex 2021 Sep 14. Epub 2021 Sep 14.

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, 80336, Germany.

Adult gyrification provides a window into coordinated early neurodevelopment when disruptions predispose individuals to psychiatric illness. We hypothesized that the echoes of such disruptions should be observed within structural gyrification networks in early psychiatric illness that would demonstrate associations with developmentally relevant variables rather than specific psychiatric symptoms. We employed a new data-driven method (Orthogonal Projective Non-Negative Matrix Factorization) to delineate novel gyrification-based networks of structural covariance in 308 healthy controls. Gyrification within the networks was then compared to 713 patients with recent onset psychosis or depression, and at clinical high-risk. Associations with diagnosis, symptoms, cognition, and functioning were investigated using linear models. Results demonstrated 18 novel gyrification networks in controls as verified by internal and external validation. Gyrification was reduced in patients in temporal-insular, lateral occipital, and lateral fronto-parietal networks (pFDR < 0.01) and was not moderated by illness group. Higher gyrification was associated with better cognitive performance and lifetime role functioning, but not with symptoms. The findings demonstrated that gyrification can be parsed into novel brain networks that highlight generalized illness effects linked to developmental vulnerability. When combined, our study widens the window into the etiology of psychiatric risk and its expression in adulthood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhab288DOI Listing
September 2021

A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium.

Hum Brain Mapp 2021 Sep 8. Epub 2021 Sep 8.

Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) [Georgia State University, Georgia Institute of Technology], Emory University, Atlanta, Georgia, USA.

Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25625DOI Listing
September 2021

Effectiveness and safety of the adjunctive use of an internet-based self-management intervention for borderline personality disorder in addition to care as usual: results from a randomised controlled trial.

BMJ Open 2021 09 8;11(9):e047771. Epub 2021 Sep 8.

Gaia AG, Hamburg, Germany.

Importance: Borderline personality disorder (BPD) is a severe mental disorder that is often inadequately treated.

Objective: To determine if adding a self-management intervention to care as usual (CAU) is effective and safe.

Design: Randomised, controlled, rater-blind trial. Duration of treatment and assessments: 12 months.

Setting: Secondary care, recruited mainly via the internet.

Participants: Patients with BPD and BPD Severity Index (BPDSI) of at least 15.

Interventions: CAU by treating psychiatrist and/or psychotherapist alone or adjunctive use of an internet-based self-management intervention that is based on schema therapy (priovi).

Main Outcome Measure: Outcomes were assessed by trained raters. The primary outcome was change in BPDSI. The safety outcome was the number of serious adverse events (SAEs). The primary outcome time point was 12 months after randomisation.

Results: Of 383 participants assessed for eligibility, 204 were included (91.7% female, mean age: 32.4 years; 74% were in psychotherapy and 26% were in psychiatric treatment). The slope of BPDSI change did not differ significantly between groups from baseline to 12 months (F= 1.857, p=0.14). At 12 months, the within-group effect sizes were d=1.38 (95% CI 1.07 to 1.68) for the intervention group and d=1.02 (95% CI 0.73 to 1.31) for the control group. The between-group effect size was d=0.27 (95% CI 0.00 to 0.55) in the intention-to-treat sample and d=0.39 (95% CI 0.09 to 0.68) for those who used the intervention for at least 3 hours (per-protocol sample). We found no significant differences in SAEs.

Conclusions: We have not found a significant effect in favour of the intervention. This might be due to the unexpectedly large effect in the group receiving CAU by a psychiatrist and/or psychotherapist alone.

Trial Registration: NCT03418142.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-047771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438831PMC
September 2021

Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats.

Sci Rep 2021 Sep 7;11(1):17747. Epub 2021 Sep 7.

Department of Molecular Biology and Endocrinology, "VINČA", Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.

Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Tianeptine (Tian) has been used as antidepressant with anxiolytic properties and recently as a nootropic to improve cognitive performance, but its mechanism of action is unknown. We conducted a proteomic study on the hippocampal synaptosomal fractions of adult male Wistar rats exposed to chronic social isolation (CSIS, 6 weeks), an animal model of depression and after chronic Tian treatment in controls (nootropic effect) and CSIS-exposed rats (lasting 3 weeks of 6-week CSIS) (therapeutic effect). Increased expression of Syn1 and Camk2-related neurotransmission, vesicle transport and energy processes in Tian-treated controls were found. CSIS led to upregulation of proteins associated with actin cytoskeleton, signaling transduction and glucose metabolism. In CSIS rats, Tian up-regulated proteins involved in mitochondrial energy production, mitochondrial transport and dynamics, antioxidative defense and glutamate clearance, while attenuating the CSIS-increased glycolytic pathway and cytoskeleton organization proteins expression and decreased the expression of proteins involved in V-ATPase and vesicle endocytosis. Our overall findings revealed that synaptic vesicle dynamics, specifically exocytosis, and mitochondria-related energy processes might be key biological pathways modulated by the effective nootropic and antidepressant treatment with Tian and be a potential target for therapeutic efficacy of the stress-related mood disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-97186-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423821PMC
September 2021

Change in Interpersonal and Metacognitive Skills During Treatment With Cognitive Behavioral Analysis System of Psychotherapy and Metacognitive Therapy: Results From an Observational Study.

Front Psychiatry 2021 16;12:619674. Epub 2021 Aug 16.

Department of Psychiatry, Psychosomatics and Psychotherapy, University of Lübeck, Lübeck, Germany.

Interpersonal skills deficits and dysfunctional metacognitive beliefs have been implicated in the etiology and maintenance of depression. This study aimed to investigate the association between changes in these skills deficits and change in depressive symptoms over the course of treatment with Cognitive Behavioral Analysis System of Psychotherapy (CBASP) and Metacognitive Therapy (MCT). In this prospective, parallel group observational study, data was collected at baseline and after 8 weeks of an intensive day clinic psychotherapy program. Based on a shared decision between patients and clinicians, patients received either CBASP or MCT. Ninety patients were included in the analyses (CBASP: age = 38.7, 40.5% female, MCT: age = 44.7, 43.3% female). Interpersonal deficits were assessed with the short-form of the Luebeck Questionnaire for Recording Preoperational Thinking (LQPT-SF) and the Impact Message Inventory (IMI-R). Metacognitive beliefs were assessed with the Metacognition Questionnaire-30 (MCQ-30). The Quick Inventory of Depressive Symptomatology (QIDS-SR16) was utilized to assess depressive symptoms. A regression analysis was conducted to assess variables associated with outcome. ANCOVAs were utilized to investigate whether improvement in skills deficits is dependent on type of treatment received. Improvements in preoperational thinking and increases in friendly-dominant behavior were associated with change in depressive symptoms. There was no association between reductions in dysfunctional metacognitive beliefs and a decrease in depressive symptoms. While both treatment groups showed significant improvements in interpersonal and metacognitive skills, there was no significant between-group difference in the change scores for either of these skills. Our findings suggest that changes in interpersonal skills seem to be of particular relevance in the treatment of depression. These results have to be replicated in a randomized-controlled design before firm conclusions can be drawn.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.619674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415348PMC
August 2021

Toward Generalizable and Transdiagnostic Tools for Psychosis Prediction: An Independent Validation and Improvement of the NAPLS-2 Risk Calculator in the Multisite PRONIA Cohort.

Biol Psychiatry 2021 Nov 6;90(9):632-642. Epub 2021 Jul 6.

Institute of Mental Health, University of Birmingham, Birmingham, United Kingdom; School of Psychology, University of Birmingham, Birmingham, United Kingdom.

Background: Transition to psychosis is among the most adverse outcomes of clinical high-risk (CHR) syndromes encompassing ultra-high risk (UHR) and basic symptom states. Clinical risk calculators may facilitate an early and individualized interception of psychosis, but their real-world implementation requires thorough validation across diverse risk populations, including young patients with depressive syndromes.

Methods: We validated the previously described NAPLS-2 (North American Prodrome Longitudinal Study 2) calculator in 334 patients (26 with transition to psychosis) with CHR or recent-onset depression (ROD) drawn from the multisite European PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Patients were categorized into three risk enrichment levels, ranging from UHR, over CHR, to a broad-risk population comprising patients with CHR or ROD (CHR|ROD). We assessed how risk enrichment and different predictive algorithms influenced prognostic performance using reciprocal external validation.

Results: After calibration, the NAPLS-2 model predicted psychosis with a balanced accuracy (BAC) (sensitivity, specificity) of 68% (73%, 63%) in the PRONIA-UHR cohort, 67% (74%, 60%) in the CHR cohort, and 70% (73%, 66%) in patients with CHR|ROD. Multiple model derivation in PRONIA-CHR|ROD and validation in NAPLS-2-UHR patients confirmed that broader risk definitions produced more accurate risk calculators (CHR|ROD-based vs. UHR-based performance: 67% [68%, 66%] vs. 58% [61%, 56%]). Support vector machines were superior in CHR|ROD (BAC = 71%), while ridge logistic regression and support vector machines performed similarly in CHR (BAC = 67%) and UHR cohorts (BAC = 65%). Attenuated psychotic symptoms predicted psychosis across risk levels, while younger age and reduced processing speed became increasingly relevant for broader risk cohorts.

Conclusions: Clinical-neurocognitive machine learning models operating in young patients with affective and CHR syndromes facilitate a more precise and generalizable prediction of psychosis. Future studies should investigate their therapeutic utility in large-scale clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopsych.2021.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500930PMC
November 2021

The mediating effect of difficulties in emotion regulation on the association between childhood maltreatment and borderline personality disorder.

Eur J Psychotraumatol 2021;12(1):1934300. Epub 2021 Aug 13.

Department of Psychiatry and Psychotherapy, University of Lübeck, LübeckGermany.

Background: Childhood maltreatment and difficulties in emotion regulation are common in patients with Borderline Personality Disorder (BPD) and Depressive Disorders (DD).

Objective: This study examines differences between patients with BPD and patients with DD, regarding childhood maltreatment and difficulties in emotion regulation as well as the mediating effect of different aspects of emotion regulation deficits on the association between childhood maltreatment and BPD-symptoms.

Method: A total of 305 participants, 177 with BPD and 128 with DD completed an assessment including the Childhood Trauma Questionnaire (CTQ), the Emotion Regulation Scale (DERS), the Brief Symptom Inventory (BSI), and the Structured Clinical Interview for DSM-IV (SCID). Data was analyzed using multiple analyses of variances and mediation analyses.

Results: Patients with BPD reported more childhood maltreatment and more difficulties in emotion regulation than patients with DD. When general symptom severity, age, and gender were included in the analysis as covariates only group differences regarding 'impulse control difficulties' ((1,299) = 38.97, < .001, η = .115), 'limited access to emotion regulation strategies' ((1,299) = 4.66, = .032, η = .015), and 'lack of emotional clarity' ((1,299) = 9.38, = .002, η = .030) remained statistically significant. A mediation analysis, including above-mentioned covariates, indicated an association between emotional abuse and BPD-symptoms, which was mediated by difficulties in emotion regulation (indirect effect = .012, 95% [.001; .031], R = .429). Subscale analyses revealed 'impulse control difficulties' as the aspect of difficulties in emotion regulation that has the greatest impact on this association ( = .021, 95% [.003; .045]).

Conclusions: Patients with BPD display more childhood maltreatment and difficulties in emotion regulation than patients with DD. Difficulties in emotion regulation, especially difficulties in impulse control, seem to play an important role in the association between childhood emotional abuse and BPD-symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/20008198.2021.1934300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366657PMC
August 2021

Primary prevention of depression: An umbrella review of controlled interventions.

J Affect Disord 2021 Nov 31;294:957-970. Epub 2021 Jul 31.

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK; OASIS service, South London and Maudsley NHS Foundation Trust, London, UK; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. Electronic address:

Background: Primary prevention has the potential to modify the course of depression, but the consistency and magnitude of this effect are currently undetermined.

Methods: PRISMA and RIGHT compliant (PROSPERO:CRD42020179659) systematic meta-review, PubMed/Web of Science, up to June 2020. Meta-analyses of controlled interventions for the primary prevention of depressive symptoms [effect measures: standardized mean difference (SMD)] or depressive disorders [effect measure: relative risk (RR)] were carried out. Results were stratified by: (i) age range; (ii) target population (general and/or at-risk); (iii) intervention type. Quality (assessed with AMSTAR/AMSTAR-PLUS content) and credibility (graded as high/moderate/low) were assessed. USPSTF grading system was used for recommendations.

Results: Forty-six meta-analyses (k=928 individual studies, n=286,429 individuals, mean age=22.4 years, 81.1% female) were included. Effect sizes were: SMD=0.08-0.53; for depressive symptoms; RR=0.90-0.28 for depressive disorders. Sensitivity analyses including only RCTs did not impact the findings. AMSTAR median=9 (IQR=8-9); AMSTAR-PLUS content median=4.25 (IQR=4-5). Credibility of the evidence was insufficient/low in 43 (93.5%) meta-analyses, moderate in two (4.3%), and high in one (2.2%): reduction of depressive symptoms using psychosocial interventions for young adults only, and a combination of psychological and educational interventions in primary care had moderate credibility; preventive administration of selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in individuals with a stroke had high credibility.

Limitations: Intervention heterogeneity and lack of long-term efficacy evaluation.

Conclusions: Primary preventive interventions for depression might be effective. Among them, clinicians may offer SSRIs post-stroke to prevent depressive disorders, and psychosocial interventions for children/adolescents/young adults with risk factors or during the prenatal/perinatal period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2021.07.101DOI Listing
November 2021

Case Report: CBD Cigarettes for Harm Reduction and Adjunctive Therapy in a Patient With Schizophrenia and Substance Use Disorder.

Front Psychiatry 2021 22;12:712110. Epub 2021 Jul 22.

Department of Psychiatry (Universitäre Psychiatrische Kliniken), University of Basel, Basel, Switzerland.

The treatment of patients with schizophrenia and substance use disorder poses a challenge for clinicians. Continued use of cannabis and cocaine can exacerbate psychotic symptoms and worsen the course of disease. To date, no pharmacotherapy is available for patients with cannabis use disorder (CUD). Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the main active constituents in , with the latter being linked to an increased risk of psychosis. We describe a clinical case of a male patient diagnosed with schizophrenia, combined personality disorder, CUD and cocaine use disorder. Over the course of 8 years, he was hospitalized 30 times due to psychotic relapses and continued substance use. Consequently, CBD cigarettes with a low THC content (<1%) were used as adjunctive therapy. Additionally, we established off-label treatment with methylphenidate to support abstinence. The patient reported to feel significantly less need to consume illegal cannabis with a high THC content. He stopped to use cocaine, for the time being, and has not been hospitalized since. This case report demonstrates the potential of smoked CBD as a substitute for severe and chronic CUD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.712110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339295PMC
July 2021

The non-specific nature of mental health and structural brain outcomes following childhood trauma.

Psychol Med 2021 Jul 6:1-10. Epub 2021 Jul 6.

Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany.

Background: Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure.

Methods: We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry.

Results: (i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains 'emotional neglect' and 'emotional abuse' were most predictive for CHR and ROP, while in ROD 'physical abuse' and 'sexual abuse' were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found.

Conclusions: These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0033291721002439DOI Listing
July 2021

Lower cholinergic basal forebrain volumes link with cognitive difficulties in schizophrenia.

Neuropsychopharmacology 2021 Jun 29. Epub 2021 Jun 29.

TUM-NIC Neuroimaging Center, Technical University of Munich, School of Medicine, Munich, 81675, Germany.

A potential pathophysiological mechanism of cognitive difficulties in schizophrenia is a dysregulated cholinergic system. Particularly, the cholinergic basal forebrain nuclei (BFCN), the source of cortical cholinergic innervation, support multiple cognitive functions, ranging from attention to decision-making. We hypothesized that BFCN structural integrity is altered in schizophrenia and associated with patients' attentional deficits. We assessed gray matter (GM) integrity of cytoarchitectonically defined BFCN region-of-interest in 72 patients with schizophrenia and 73 healthy controls, matched for age and gender, from the COBRE open-source database, via structural magnetic resonance imaging (MRI)-based volumetry. MRI-derived measures of GM integrity (i.e., volumes) were linked with performance on a symbol coding task (SCT), a paper-pencil-based metric that assesses attention, by correlation and mediation analysis. To assess the replicability of findings, we repeated the analyses in an independent dataset comprising 26 patients with schizophrenia and 24 matched healthy controls. BFCN volumes were lower in patients (t(139)=2.51, p = 0.01) and significantly associated with impaired SCT performance (r = 0.31, p = 0.01). Furthermore, lower BFCN volumes mediated the group difference in SCT performance. When including global GM volumes, which were lower in patients, as covariates-of-no-interest, these findings disappeared, indicating that schizophrenia did not have a specific effect on BFCN relative to other regional volume changes. We replicated these findings in the independent cohort, e.g., BFCN volumes were lower in patients and mediated patients' impaired SCT performance. Results demonstrate lower BFCN volumes in schizophrenia, which link with patients' attentional deficits. Data suggest that a dysregulated cholinergic system might contribute to cognitive difficulties in schizophrenia via impaired BFCN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41386-021-01070-xDOI Listing
June 2021

How do patients with borderline personality disorder experience Distress Tolerance Skills in the context of dialectical behavioral therapy?-A qualitative study.

PLoS One 2021 15;16(6):e0252403. Epub 2021 Jun 15.

Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany.

Distress Tolerance Skills (DTS) are an important component of Dialectical Behavioral Therapy (DBT), a therapy method frequently used for treating patients with Borderline Personality Disorder (BPD). However, little is known about how DTS-training is experienced by individuals with BPD. The aim of this study was to explore BPD patients' experiences with receiving DTS-training. Qualitative data were collected through semi-structured interviews with 24 individuals (87.5% females) with a primary diagnosis of BPD who received DTS-training in the context of 18 months of DBT treatment. Interview data were analyzed following the procedures of qualitative content analysis. Participants reported various effects of DTS including an immediate reduction of tension. Patients perceived DTS as a tool to cope with difficult interpersonal situations and emergencies and stated that this helped them to feel stable, safe and self-confident. Patients reported difficulties during the initial engagement, the learning process and the application of DTS as well as various facilitating factors. Implications of the findings for further research and for optimizing DTS-training in clinical practice are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252403PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205175PMC
June 2021

Functional brain network dysfunctions in subjects at high-risk for psychosis: A meta-analysis of resting-state functional connectivity.

Neurosci Biobehav Rev 2021 09 10;128:90-101. Epub 2021 Jun 10.

Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Electronic address:

Although emerging evidence suggests that altered functional connectivity (FC) of large-scale neural networks is associated with disturbances in individuals at high-risk for psychosis, the findings are still far to be conclusive. We conducted a meta-analysis of seed-based resting-state functional magnetic resonance imaging studies that compared individuals at clinical high-risk for psychosis (CHR), first-degree relatives of patients with schizophrenia, or subjects who reported psychotic-like experiences with healthy controls. Twenty-nine studies met the inclusion criteria. The MetaNSUE method was used to analyze connectivity comparisons and symptom correlations. Our results showed a significant hypo-connectivity within the salience network (p = 0.012, uncorrected) in the sample of CHR individuals (n = 810). Additionally, we found a positive correlation between negative symptom severity and FC between the default mode network and both the salience network (p < 0.001, r = 0.298) and the central executive network (p = 0.003, r = 0.23) in the CHR group. This meta-analysis lends support for the hypothesis that large-scale network dysfunctions represent a core neural deficit underlying psychosis development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neubiorev.2021.06.020DOI Listing
September 2021

Multimodal prognosis of negative symptom severity in individuals at increased risk of developing psychosis.

Transl Psychiatry 2021 05 24;11(1):312. Epub 2021 May 24.

Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.

Negative symptoms occur frequently in individuals at clinical high risk (CHR) for psychosis and contribute to functional impairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive models either included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes (SIPS-N), whole-brain gyrification, or both to forecast negative symptoms of at least moderate severity in 94 CHR. We also conducted sequential risk stratification to stratify CHR into different risk groups based on the SIPS-N and gyrification model. Additionally, we assessed the models' ability to predict functional outcomes in CHR and their transdiagnostic generalizability to predict negative symptoms in 96 patients with recent-onset psychosis (ROP) and 97 patients with recent-onset depression (ROD). Baseline SIPS-N and gyrification predicted moderate/severe negative symptoms with significant balanced accuracies of 68 and 62%, while the combined model achieved 73% accuracy. Sequential risk stratification stratified CHR into a high (83%), medium (40-64%), and low (19%) risk group regarding their risk of having moderate/severe negative symptoms at 9 months follow-up. The baseline SIPS-N model was also able to predict social (61%), but not role functioning (59%) at above-chance accuracies, whereas the gyrification model achieved significant accuracies in predicting both social (76%) and role (74%) functioning in CHR. Finally, only the baseline SIPS-N model showed transdiagnostic generalization to ROP (63%). This study delivers a multimodal prognostic model to identify those CHR with a clinically relevant negative symptom severity and functional impairments, potentially requiring further therapeutic consideration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-021-01409-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144430PMC
May 2021

Regular Caffeine Intake Delays REM Sleep Promotion and Attenuates Sleep Quality in Healthy Men.

J Biol Rhythms 2021 08 23;36(4):384-394. Epub 2021 May 23.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

Acute caffeine intake can attenuate homeostatic sleep pressure and worsen sleep quality. Caffeine intake-particularly in high doses and close to bedtime-may also affect circadian-regulated rapid eye movement (REM) sleep promotion, an important determinant of subjective sleep quality. However, it is not known whether such changes persist under chronic caffeine consumption during daytime. Twenty male caffeine consumers (26.4 ± 4 years old, habitual caffeine intake 478.1 ± 102.8 mg/day) participated in a double-blind crossover study. Each volunteer completed a caffeine (3 × 150 mg caffeine daily for 10 days), a withdrawal (3 × 150 mg caffeine for 8 days then placebo), and a placebo condition. After 10 days of controlled intake and a fixed sleep-wake cycle, we recorded electroencephalography for 8 h starting 5 h after habitual bedtime (i.e., start on average at 04:22 h which is around the peak of circadian REM sleep promotion). A 60-min evening nap preceded each sleep episode and reduced high sleep pressure levels. While total sleep time and sleep architecture did not significantly differ between the three conditions, REM sleep latency was longer after daily caffeine intake compared with both placebo and withdrawal. Moreover, the accumulation of REM sleep proportion was delayed, and volunteers reported more difficulties with awakening after sleep and feeling more tired upon wake-up in the caffeine condition compared with placebo. Our data indicate that besides acute intake, also regular daytime caffeine intake affects REM sleep regulation in men, such that it delays circadian REM sleep promotion when compared with placebo. Moreover, the observed caffeine-induced deterioration in the quality of awakening may suggest a potential motive to reinstate caffeine intake after sleep.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/07487304211013995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276335PMC
August 2021

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis.

JAMA Psychiatry 2021 Jul;78(7):753-766

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.

Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.

Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).

Design, Setting, And Participants: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.

Main Outcomes And Measures: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).

Results: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001).

Conclusions And Relevance: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapsychiatry.2021.0638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100913PMC
July 2021

Risk and protective factors for cannabis, cocaine, and opioid use disorders: An umbrella review of meta-analyses of observational studies.

Neurosci Biobehav Rev 2021 07 15;126:243-251. Epub 2021 Mar 15.

Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology, London, UK; Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Outreach and Support in South London (OASIS) Service, South London and Maudsley NHS Foundation Trust, London, UK.

Several meta-analyses of observational studies have addressed the association between risk and protective factors and cannabis/cocaine/opioid use disorders, but results are conflicting. No umbrella review has ever graded the credibility of this evidence (not significant/weak/suggestive/highly suggestive/convincing). We searched Pubmed-MEDLINE/PsycInfo, last search September 21, 2020. We assessed the quality of meta-analyses with the AMSTAR-2 tool. Out of 3,072 initial references, five were included, providing 19 associations between 12 putative risk/protective factors and cannabis/cocaine/opioid use disorders (cases: 4539; N = 1,118,872,721). While 84 % of the associations were statistically significant, none was convincing. One risk factor (smoking) had highly suggestive evidence for association with nonmedical use of prescription opioid medicines (OR = 3.07, 95 %CI:2.27 to 4.14). Convincing evidence emerged in sensitivity analyses on antisocial behavior and cannabis use disoder (OR 3.34, 95 %CI 2.53-4.41). Remaining associations had weak evidence. The quality of meta-analyses was rated as moderate in two (40 %), low in one (20 %), and critically low in two (40 %). Future research is needed to better profile risk/protective factors for cannabis/cocaine/opioid use disorders disorders informing preventive approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neubiorev.2021.03.014DOI Listing
July 2021

Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?

Neuropsychopharmacology 2021 07 15;46(8):1475-1483. Epub 2021 Mar 15.

University of Cologne, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany.

In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (N = 40, N = 13). Impaired patients showed significantly increased negative symptomatology (p = 0.003), reduced cognitive performance (p < 0.001) and general functioning (p < 0.035) in comparison to spared patients. Neurocognitive deficits of the impaired subgroup persist in both discovery and validation sample across several domains, including verbal memory and processing speed. A GMV pattern (balanced accuracy = 60.1%, p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41386-021-00963-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209013PMC
July 2021

Association between age of cannabis initiation and gray matter covariance networks in recent onset psychosis.

Neuropsychopharmacology 2021 07 3;46(8):1484-1493. Epub 2021 Mar 3.

Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany.

Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41386-021-00977-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209059PMC
July 2021

Towards clinical application of prediction models for transition to psychosis: A systematic review and external validation study in the PRONIA sample.

Neurosci Biobehav Rev 2021 06 23;125:478-492. Epub 2021 Feb 23.

Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital of Cologne, Cologne, Germany. Electronic address:

A multitude of prediction models for a first psychotic episode in individuals at clinical high-risk (CHR) for psychosis have been proposed, but only rarely validated. We identified transition models based on clinical and neuropsychological data through a registered systematic literature search and evaluated their external validity in 173 CHRs from the Personalised Prognostic Tools for Early Psychosis Management (PRONIA) study. Discrimination performance was assessed with the area under the receiver operating characteristic curve (AUC), and compared to the prediction of clinical raters. External discrimination performance varied considerably across the 22 identified models (AUC 0.40-0.76), with two models showing good discrimination performance. None of the tested models significantly outperformed clinical raters (AUC = 0.75). Combining predictions of clinical raters and the best model descriptively improved discrimination performance (AUC = 0.84). Results show that personalized prediction of transition in CHR is potentially feasible on a global scale. For implementation in clinical practice, further rounds of external validation, impact studies, and development of an ethical framework is necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neubiorev.2021.02.032DOI Listing
June 2021

The impact of daily caffeine intake on nighttime sleep in young adult men.

Sci Rep 2021 Feb 25;11(1):4668. Epub 2021 Feb 25.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

Acute caffeine intake can delay sleep initiation and reduce sleep intensity, particularly when consumed in the evening. However, it is not clear whether these sleep disturbances disappear when caffeine is continuously consumed during daytime, which is common for most coffee drinkers. To address this question, we investigated the sleep of twenty male young habitual caffeine consumers during a double-blind, randomized, crossover study including three 10-day conditions: caffeine (3 × 150 mg caffeine daily), withdrawal (3 × 150 mg caffeine for 8 days, then switch to placebo), and placebo (3 × placebo daily). After 9 days of continuous treatment, electroencephalographically (EEG)-derived sleep structure and intensity were recorded during a scheduled 8-h nighttime sleep episode starting 8 (caffeine condition) and 15 h (withdrawal condition) after the last caffeine intake. Upon scheduled wake-up time, subjective sleep quality and caffeine withdrawal symptoms were assessed. Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions. Nevertheless, EEG power density in the sigma frequencies (12-16 Hz) during non-rapid eye movement sleep was reduced in both caffeine and withdrawal conditions when compared to placebo. These results indicate that daily caffeine intake in the morning and afternoon hours does not strongly impair nighttime sleep structure nor subjective sleep quality in healthy good sleepers who regularly consume caffeine. The reduced EEG power density in the sigma range might represent early signs of overnight withdrawal from the continuous presence of the stimulant during the day.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-84088-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907384PMC
February 2021

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 17. Epub 2021 Feb 17.

Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25364DOI Listing
February 2021

Daily Caffeine Intake Induces Concentration-Dependent Medial Temporal Plasticity in Humans: A Multimodal Double-Blind Randomized Controlled Trial.

Cereb Cortex 2021 05;31(6):3096-3106

Centre for Chronobiology, University Psychiatric Clinics, University of Basel, 4002 Basel, Switzerland.

Caffeine is commonly used to combat high sleep pressure on a daily basis. However, interference with sleep-wake regulation could disturb neural homeostasis and insufficient sleep could lead to alterations in human gray matter. Hence, in this double-blind, randomized, cross-over study, we examined the impact of 10-day caffeine (3 × 150 mg/day) on human gray matter volumes (GMVs) and cerebral blood flow (CBF) by fMRI MP-RAGE and arterial spin-labeling sequences in 20 habitual caffeine consumers, compared with 10-day placebo (3 × 150 mg/day). Sleep pressure was quantified by electroencephalographic slow-wave activity (SWA) in the previous nighttime sleep. Nonparametric voxel-based analyses revealed a significant reduction in GMV in the medial temporal lobe (mTL) after 10 days of caffeine intake compared with 10 days of placebo, voxel-wisely adjusted for CBF considering the decreased perfusion after caffeine intake compared with placebo. Larger GMV reductions were associated with higher individual concentrations of caffeine and paraxanthine. Sleep SWA was, however, neither different between conditions nor associated with caffeine-induced GMV reductions. Therefore, the data do not suggest a link between sleep depth during daily caffeine intake and changes in brain morphology. In conclusion, daily caffeine intake might induce neural plasticity in the mTL depending on individual metabolic processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhab005DOI Listing
May 2021

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 11. Epub 2021 Feb 11.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25320DOI Listing
February 2021
-->