Theta burst stimulation add on to dialectical behavioral therapy in borderline-personality-disorder: methods and design of a randomized, single-blind, placebo-controlled pilot trial.

Specialized psychotherapeutic treatments like dialectical behavioral therapy (DBT) are recommended as first treatment for borderline personality disorder (BPD). In recent years, studies have emerged that focus on repetitive transcranial magnetic stimulation (rTMS) in BPD. Both have independently demonstrated efficacy in the treatment of BPD. Intermitted theta burst stimulation (iTBS), a modified design of rTMS, is thought to increase the excitability of neurons and could be a supplement to psychotherapy in addition to being a standalone treatment. However, no studies to date have investigated the combination of DBT and rTMS/iTBS. This study protocol describes the methods and design of a randomized, single-blinded, sham-controlled clinical pilot study in which BPD patients will be randomly assigned to either iTBS or sham during four consecutive weeks (20 sessions in total) in addition to standardized DBT treatment. The stimulation will focus on the unilateral stimulation of the left dorsolateral prefrontal cortex (DLPFC), which plays an important role in the control of impulsivity and risk-taking. Primary outcome is the difference in borderline symptomatology, while secondary target criteria are depressive symptoms, general functional level, impulsivity and self-compassion. Statistical analysis of therapy response will be conducted by Mixed Model Repeated Measurement using a 2 × 2-factorial between-subjects design with the between-subject factor stimulation (TMS vs. Sham) and the within-subject factor time (T0 vs. T1). Furthermore, structural magnetic resonance imaging (MRI) will be conducted and analyzed. The study will provide evidence and insight on whether iTBS has an enhancing effect as add-on to DBT in BPD.Trial registration: drks.de (DRKS00020413) registered 13/01/2020.

The somatic care of patients with comorbid mental disorders: protocol of a mixed-methods study aiming to identify barriers to and enablers of utilization of somatic healthcare (SoKo).

BACKGROUND: Healthcare for people with somatic and comorbid mental diseases can pose a challenge to the healthcare system. The aim of the SoKo study (the Somatic care of patients with mental Comorbidity) is to assess the current state of care and the facilitators and barriers of somatic care of people with somatic disorders and comorbidity of a mental disorder. METHODS: The study is conducted as a mixed-methods approach and will include (a) descriptive and inferential analysis of secondary claims data of persons insured by a German statutory health insurance company in North Rhine-Westphalia (Techniker Krankenkasse, TK-NRW), (b) qualitative individual interviews and group discussions, and (c) based on (a) and (b), quantitative surveys of both patients and physicians. We intend to analyse a sample of claims data of about 2.6 million persons insured by TK-NRW (group comparisons between TK-NRW insured persons with a diagnosis of a prevalent somatic disease [ICD-10-GM E01-E07, E11, E66, I10-I15, I20-I25, I60-I64] with and without comorbidity of a mental disorder [F00-F99]), in order to assess the uptake of somatic care by people with mental and somatic comorbidity. In addition, primary data from patients with the aforementioned somatic illnesses and a mental comorbidity as well as primary data from physicians (general practitioners and medical specialists) will be collected. The focus here will be on support factors and barriers in the somatic care of people with mental comorbidity. DISCUSSION: Up to now, there have been no published results of a systematic collection of both secondary and primary data on the utilisation of different care services of somatically ill patients with mental comorbidity for Germany. The present mixed-methods study aims to address this gap. TRIAL REGISTRATION: The trial is registered with the German Clinical Trials Register DRKS: DRKS00030513. The trial was registered on 3rd February 2023.

Treatment of hypertension and obstructive sleep apnea counteracts cognitive decline in common neurocognitive disorders in diagnosis-related patterns.

The aim of this study was to investigate the effect of arterial hypertension (AH) and of obstructive sleep apnea (OSA) on cognitive course in the neurocognitive disorder (NCD) cohort RIFADE which enrolled patients with NCD due to Alzheimer's disease (AD), vascular NCD (vNCD), and mixed NCD (AD + vNCD = mNCD). Multiple risk factors (RF), including AH and OSA, that contribute to the development of various kinds of dementia have been identified in previous studies. Studies that observed AH lacked investigation of long-term effects and did not isolate it from other RF. Studies involving OSA as a risk factor did not include participants with all stages of NCD. 126 subjects were screened for AH and OSA. Repeated cognitive measurements were performed with the DemTect as primary outcome and the clock drawing test as secondary outcome measure. 90 patients had AH (71.4%) and 40 patients had OSA (31.7%). RF-status had a significant effect on cognitive outcome in models with RF as single factors (AH p = 0.027, OSA p < 0.001), a 2-factor analysis with AH × OSA (AH as main factor p = 0.027) as well as a model including the 3 factors AH × OSA × diagnosis (p = 0.038). Similarly, a 3-factor model was significant for the clock-drawing test, whereas single factor-models remained insignificant. AH and OSA appear to be risk factors in common NCD and cognitive decline can be mitigated by treatment of these RF.

The neurocognitive disorder cohort RIFADE: Aims, methods, first results showing cognitive improvement in a subgroup.

BACKGROUND: The NCD cohort study RIFADE (RIsk FActors of DEmentia) investigates the interaction of risk factors and neurocognitive disorders (NCDs) due to Alzheimer's disease (NCD-AD) and NCD of vascular type (NCD-vascular). Retrospective recruitment referred to a period from 2007 to 2018 in a single centre. In addition to the baseline visit, follow-up visits took place at 3, 6, 12 months followed by yearly visits. Visit times varied in part depending on adherence. The study also comprises an EEG bank and a bank with cerebral MRI (c-MRI). METHODS: Inclusion criteria were broad in order to cover a wide range of patterns of NCD. At baseline, patients underwent a large panel of assessments, e.g. including clinical history, diagnostic evaluation for NCD according to DSM-IV and NINDS AIREN criteria, a cognitive test battery including the DemTect, the clock drawing test and the Instrumental-Activities-of-Daily-Living-scale of Lawton and Brodie, EEG and c-MRI. At each follow-up visit, cognitive tests were repeated, in most cases also EEGs and in some cases c-MRIs. Numerous risk factors (RF) including vascular RF, atrial fibrillation, heart failure, sleep apnoea and lifestyle factors such as sedentary lifestyle, low cognitive style and smoking were evaluated for presence and for correction status at each visit, and modulation of uncorrected RF was initiated. RESULTS: Overall, 126 subjects with a clinical diagnosis of NCD were included (52% female, mean age 71 ± 10.6 years (range 35e86)), number of follow-up visits per subject 2.9 ± 2.4, observation time per subject 3.4 ± 2.8 years). Of these, 55/28/17% presented with the clinical stages subjective cognitive decline (SCD)/mild cognitive impairment (MCI)/dementia (major NCD). Clinical diagnoses, retrospectively re-evaluated according to DSM-5, were 5/21/68/6% Alzheimer´s disease (NCD-AD)/vascular NCD (NCD-vascular) / mixed NCD (NCD-AD + NCD-vascular)/unspecified NCD. First longitudinal results revealed a mean DemTect score at baseline 12.6 ± 4.2 vs last visit 12.0 ± 4.8 (p = 0.08) and a clock drawing test score at baseline 1.9 ± 1.3 vs last visit 2.3 ± 1.5 (p < 0.0001). Of all subjects with MCI or major NCD (n = 57), 19 improved in the clinical stage from baseline to last visit (33.3%). Sixteen subjects progressed from SCD or MCI (n = 104) to major NCD (15.4%). CONCLUSION: The German NCD cohort RIFADE comprises patients with all clinical stages of NCD. A considerable subgroup improved in clinical stage. Further analysis is needed to answer the question of whether modulation of multiple risk factors provides a favourable effect on cognitive outcome in NCD.

Predicting the role of coping factors on pandemic-related anxiety.

The year 2020 saw the emergence of a worldwide pandemic caused by the novel coronavirus COVID-19. Measures against further spread of the virus were taken nearly everywhere in the world. Many countries also imposed social distancing rules and lockdowns on their population. This situation has caused a lot of fear and insecurity, along with reactance and even unrest in some countries. In this study, we measured the psychological concepts of resilience, reactance, positive schemas, social solidarity, and anxiety among psychiatric patients and in how far these factors influence their psychopathological anxiety during the pandemic. The aim was to better understand in what ways these factors influence pandemic anxiety to be able to reduce its negative psychological effects. Findings show a significant effect of positive schemas and social solidarity on the level of pandemic anxiety in a sample of psychiatric patients, but no correlation between resilience or reactance and pandemic anxiety. Based on these insights, the inclusion of positive schemas and social solidarity for therapy should be considered. Looking deeper into the relation between positive schemas and pandemic anxiety could provide insight into the different ways that schemas influence people's anxiety and determine whether some of them are particularly important.

Inpatient Suicides in Late Life: A Retrospective Analysis of a Hospital Group with Nine Psychiatric Clinics.

OBJECTIVE: Inpatient suicides are rare incidents; however, the impacts of such events on associated families and hospital staff are severe. Therefore, preventive strategies need to focus on risk factors. Clinical management in a hospital setting must integrate the home environment and social life of patients. Nevertheless, home leaves require careful preparation. METHODS: Suicides were reported systematically from all psychiatric departments of the Landschaftsverband Rheinland (an assembly of municipalities) using a structured form during two periods (1995-2004, 2005-2014). From these reports we extracted data on suicide methods and sociodemographic and clinical variables. Only patients 65 years and older were included. RESULTS: From a total of 551 reports on suicides in the period of 1995-2014, 103 patients 65 years and older (60 women, 43 men) died by suicide. In contrast to the general trend in Germany during this period, no decline in overall suicide rates was found. Most patients were treated because of depression (73.8%); schizophrenic psychosis was diagnosed in 11.7%; and dementia was only diagnosed in 1.9%. The most frequent suicide method was hanging (40%). All suicides within the hospital were hangings. The majority of suicides occurred outside the hospital during approved home leaves. Only 7% of suicides occurred when patients left the hospital without permission. Almost half of the patients (n = 44) died by suicide during the first month of treatment. With longer duration of hospitalization, the risk of suicide decreased. There were no significant trends with regard to suicide methods between the two periods. CONCLUSIONS: In the first weeks of hospitalizations the patients are most endangered to die by suicide. Therefore, home leaves need careful consideration.

Mental disorders of geriatric inpatients: symptom characteristics and treatment outcome.

OBJECTIVES: The aim of this study was to describe neuropsychiatric disorders of geriatric inpatients, to investigate associations of psychopathological symptomatology with clinical variables and to determine its impact on treatment outcome. METHODS: From January to April 2018, treatment data of geriatric inpatient records were collected retrospectively. Clinical diagnoses of neuropsychiatric disorders, that is, depression, dementia, and delirium, were identified. Clinical correlations were calculated by χ2-tests and t-tests. Confounding variables for determined correlations were ascertained by analyses of variance. Functional measurements (Barthel Index, Timed Up and Go, Tinetti Test, and De Morton Immobility Index) were assessed at start and end of geriatric inpatient treatment. RESULTS: The mean age of the included 280 inpatients was 84 years, 71% were female, and the mean duration of treatment was 19.5 days. Twenty-nine percent of cases suffered from dementia, 27% from depression, and 15% from delirium at the time of geriatric treatment onset. Mentally ill inpatients, in addition, presented with a significantly higher number of comorbidities, compared to the group of mentally healthy inpatients. In contrast to the dementia and the delirium group of inpatients, prescription of analgetics was highest among the mentally healthy inpatients and inpatients with depression. Improvement was observed in each of the defined groups, and significant functional differences between all groups were found. CONCLUSION: Neuropsychiatric disorders occur quite often in a geriatric hospital department, especially depression and dementia. Clinical correlations determined in this study suggest a close relationship of mental and somatic disorders in geriatric inpatients. This study further demonstrates that neuropsychiatric disorders in multimorbid, elderly patients do not prevent functional improvement.

Psychopathological and demographic characteristics of hallucinating patients with schizophrenia and schizoaffective disorder: an analysis based on AMDP data.

Hallucinations are at the core of the diagnosis of schizophrenia and schizoaffective disorders, and many neuroscience studies focus on hallucinations. However, there is a lack of data on prevalence, subtyping, and clinical correlates of hallucinations as well as on the comparison of hallucinating schizophrenia versus hallucinating schizoaffective patients. Analysis of all psychopathology evaluations is based on the AMDP scale in a German psychiatric university hospital between 2007 and 2013 regarding patients with schizophrenia or schizoaffective disorder (diagnosed according to ICD-10). Hallucinating versus non-hallucinating patients and age- and gender-matched hallucinating schizophrenic versus schizoaffective patients were compared with regard to key psychopathological and demographic characteristics. Relative to patients with schizoaffective disorder, patients with schizophrenia more often hallucinated at admission (36.6 vs. 16.2 %, RR: 2.3, p < 0.001). By subtype, frequency of hallucinations ranked auditory verbal > other auditory > visual > somatic/tactile > olfactory/gustatory. Hallucinating patients of either disorder were more often affected with respect to delusions (83 vs. 62 % and 81 vs. 48 % among patients with schizophrenia and schizoaffective disorder, respectively [both p < 0.0001]) and anxiety. Hallucinating patients with schizoaffective disorder did not differ from hallucinating patients with schizophrenia. This is one of the few studies providing data on hallucinations in a routine clinical care setting. Hallucinations are a sign and likely a cause of greater illness severity. Patients with schizoaffective disorder less often experience hallucinations than patients with schizophrenia, but if they do, they seem to resemble patients with schizophrenia with regard to illness severity.

Estrogen receptor beta polymorphisms and cognitive performance in women: associations and modifications by genetic and environmental influences.

Genetic and environmental risk factors contribute to the pathogenesis of Alzheimer's dementia. Besides known genetic risk factors like the apolipoprotein (APO) Eε4 allele, single nuclear polymorphisms (SNPs) of the estrogen receptors (ESRs) are candidate genetic risk factors, while air pollution represents an environmental risk factor for dementia. Effects of these risk factors and their interaction were investigated in the SALIA cohort of 834 non-demented elderly women. Cognitive function was assessed by the CERAD-plus test battery. Air pollution was estimated by land use regression (LUR) models. Genotyping was carried out for nine ESR1 and ESR2 SNPs and two ApoE SNPs. Carriers of minor ESR2 alleles showed significantly reduced cognitive performance in the CERAD total score with most pronounced deficits in semantic memory (rs1256062, rs10144225, and rs2274705) and executive function (rs1256062). The minor allele effects of ESR2 were stronger in carriers of APOEε4 for the cognitive domain 'executive function' (p value of interaction 0.023 for rs1256062). The investigated ESR1 SNPs were not associated with cognition. Furthermore, we found a significant gene-environment interaction between the ESR2 SNP rs1256062 and air pollution on cognition. Carriers of two major alleles of rs1256062 were more susceptible for an air pollution-induced decrease in performance of 'figure copying' than carriers of minor alleles (p value of interaction, e.g., 0.031 for PM2.5). In conclusion, ESR2 but not ESR1 minor alleles were associated with lower cognitive performance in elderly women with an indication of a gene-gene interaction with APOEε4. We also found indications for gene-environment interactions of ESR2 with traffic-related air pollution exposure on cognitive performance.

The effects of combined acamprosate and integrative behaviour therapy in the outpatient treatment of alcohol dependence: a randomized controlled trial.

AIMS: The aim of this randomized, controlled, multisite trial was to evaluate the efficacy of combined treatment with integrative behaviour therapy (IBT) and acamprosate on drinking behaviour in detoxified alcohol-dependent patients. METHODS: A total of 371 patients were randomized to one of the three treatment conditions: IBT plus acamprosate, IBT plus placebo, or supportive counselling ('treatment as usual', TAU) plus acamprosate. The main outcome was success rate, i.e., rate of abstinence plus improvement according to the criteria of Feuerlein and Küfner (1989), at the end of the six-month treatment phase and at the subsequent six-month follow-up. Drinking status was validated by blood parameters (CDT, GGT, and MCV). Data were analyzed by an intent-to-treat model and missing data were classified as relapse. RESULTS: The success rates at the end of treatment under both TAU plus acamprosate (37.7%) and IBT plus placebo (48%) almost reached the levels derived from the literature. However, adding acamprosate to IBT did not result in the expected increase in success rate (IBT plus acamprosate: 47.6%), and success rates did not differ significantly between groups. Similarly, there was no significant difference between treatment success rates at follow-up. CONCLUSION: The results suggest that the combination of acamprosate and IBT is not more effective than treatment with either IBT or acamprosate alone. However, the two acamprosate conditions differed in success rate by about 10%, which might constitute a clinically relevant though statistically non-significant effect.

The relation of regional cerebral perfusion and atrophy in mild cognitive impairment (MCI) and early Alzheimer's dementia.

The spatial and temporal relations between regional cerebral blood flow (rCBF) and brain volume (rVOL) changes in incipient and early Alzheimer's dementia (AD) are not fully understood. The participants comprised 30 subjects with mild cognitive impairment (MCI) and 15 with mild AD who were examined using structural and perfusion-weighted magnetic resonance imaging (MRI) at 1.5 Tesla. Hippocampus and amygdala volumes were measured by manual volumetry. A region-of-interest co-localisation method was used to calculate rCBF values. DNA samples were genotyped for apolipoprotein E (APO E). In comparisons of AD with MCI, rCBF was reduced in the posterior cingulum only, while profound rVOL reductions occurred in both right and left amygdala and in the right hippocampus, and as a trend, in the left hippocampus. Brain volumes of the hippocampus and the amygdala were uncorrelated with the respective rCBF variables in both MCI and AD. Hippocampal but not amygdalar volumes were associated with presence of one or two APOE epsilon4 alleles in MCI and mild AD, while there was no association of APOE epsilon4 allele with rCBF. These data support earlier indications that rCBF and rVOL changes are at least partly dissociated in the early pathogenesis of AD and heterogeneously associated with the APOE risk allele. The data also support the concept of functional compensatory brain activation and the diaschisis hypothesis as relevant in incipient and early AD.

Blood biomarkers of osteoporosis in mild cognitive impairment and Alzheimer's disease.

Previous studies revealed some comorbidity of Alzheimer's disease and osteoporosis not only for advanced disease, but also for the incipient conditions cognitive decline and decline of bone mineral density. To detect comorbidity with osteoporosis at a subclinical level, we studied concentrations of biochemical osteoporosis markers in blood plasma of subjects with mild cognitive impairment and mild Alzheimer's disease compared to subjects with primary osteoporosis and age-matched cognitively normal controls in an explorative approach. Regarding disease-spanning molecular pathology we also studied osteoprotegerin, a decoy receptor of RANKL and TRAIL. Equally increased C-terminal collagen fragments, marking bone catabolism, were seen in osteoporosis and Alzheimer's disease (+68%) versus controls. Osteocalcin, marking bone remodelling and anabolism, was concomitantly increased in osteoporosis (+63%), as a trend, and significantly in Alzheimer's disease (+76%). Osteoprotegerin was unchanged between patient groups and controls. 25 (OH) vitamin D plasma levels were low normal and of equal amount in all groups except for the osteoporosis group. These results point to increased bone catabolism and concomitant remodelling/anabolism unrelated to vitamin D state in mild Alzheimer's disease, but not in mild cognitive impairment. This corroborates previous findings of comorbidity of Alzheimer's disease with osteoporosis in the early disease course at the level of biochemical blood markers. Regarding osteoprotegerin, previously reported plasma level increases in Alzheimer's disease were not observed in this study, which does not rule out subtle changes to be detected in larger samples or the possibility that other components of osteoprotegerin pathways are affected in Alzheimer's disease.

Detection of changed regional cerebral blood flow in mild cognitive impairment and early Alzheimer's dementia by perfusion-weighted magnetic resonance imaging.

The utility of perfusion-weighted magnetic resonance imaging (PW-MRI) for detecting changes in regional cerebral blood flow (rCBF) in patients with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) was evaluated. Thirteen cognitively normal (CN) elderly subjects, 35 mostly amnestic MCI subjects and 20 subjects with mild probable AD were enrolled. During i.v. injection of gadopentetate dimeglumine, a dynamic T2*-weighted single-shot EPI sequence was conducted using a 1.5-T scanner. Frontobasal (FROB), temporoparietal (TPAR), mesiotemporal (MTMP), anterior and posterior cingular (ACING, PCING), amygdala (AMYG), thalamus and cerebellar brain regions were studied. rCBF was computed from regional cerebral blood volume and arterial input function and normalised to white matter. Images were analysed by manually placed regions of interest using anatomical coregistration. Significant decreases of rCBF were detected in MCI vs. CN in MTMP (-23%), AMYG (-20%) and ACING (-15%) with no further decline in mild AD. In PCING hypoperfusion (-10%) was confined to AD. These hypoperfusional changes are a possible correlate of localised impairment of CNS function. In FROB no perfusion changes were observed between diagnostic groups, but hyperperfusion was observed in mild dementia stages, possibly reflecting functional compensatory mechanisms. These data suggest that PW-MRI detects specific changes in rCBF not only in AD, but also in amnestic MCI, a disorder suggested to largely represent a pre-dementia stage of AD. This method may thus be useful in both research and clinical applications to detect early functional brain changes in the pathogenesis of dementias.

First vs multiple episode schizophrenia: two-year outcome of intermittent and maintenance medication strategies.

Results of studies on intermittent neuroleptic treatment strategies in first episode (FE) schizophrenia have not been published. Aims of the present study were to elucidate the comparative efficacy of prodrome-based neuroleptic intervention in first vs multiple episode (ME) schizophrenia. As to the methods, three randomly assigned open neuroleptic treatment strategies were compared over 2 years in 363 schizophrenic outpatients (115 FE, 248 ME; ICD-9, RDC): maintenance medication vs two intermittent medication strategies (prodrome-based intervention and crisis intervention). Concerning relapse prevention, the results demonstrate that ME patients seemed to profit most from maintenance medication compared to both intermittent treatments, whereas FE patients did equally well under maintenance medication and prodrome-based intervention treatment. Psychopathology, social adjustment, subjective well-being, and side-effects after two years did not differ significantly between the FE and ME patients irrespective of treatment strategy. Concerning treatment adherence, FE patients complied better with prodrome-based intervention than with maintenance medication. Cumulative neuroleptic dosage was lowest in FE patients under intermittent treatment. In conclusion, maintenance medication is the best strategy for relapse prevention in ME patients. In FE patients, prodrome-based intermittent intervention seems to be equivalent or even better with respect to compliance and dosage applied.