Cerebrospinal Fluid Homer-3 Autoantibodies in a Patient with Amnestic Mild Cognitive Impairment.

(1) Background: Homer-3 antibodies are associated with cerebellar disease ranging from subacute degeneration to cerebellitis. However, cognitive impairment associated with Homer-3 autoantibodies has not been reported until now. (2) Methods: in retrospect, we systematically studied clinical, cranial magnetic resonance imaging (cMRI), electroencephalography (EEG) and lumbar puncture data, including neural autoantibodies of a clinical case. (3) Results: we describe the case of a 56-year-old woman presenting with amnestic mild cognitive impairment in association with serum and CSF detection of Homer-3 autoantibodies and a depressive syndrome. cMRI revealed cerebellar atrophy. CSF analysis showed elevated ptau181 protein. Applying the criteria for an autoimmune psychiatric syndrome revealed a plausible autoimmune basis for the mild cognitive impairment. (4) Discussions: our case report demonstrates an amnestic mild cognitive impairment and depressive symptoms associated with Homer-3 autoantibodies as a novel feature of Homer-3 antibody-related disease. We also propose that cognitive dysfunction might result from impaired AMPAR signaling in the hippocampus induced by Homer-3 antibodies, which will have to be verified in further research.

Establishment of a teaching hospital-based dementia consultation service for rurally-based regional district general hospitals.

Objective: The treatment of patients with dementia poses a considerable challenge to regional district general hospitals, particularly in rural areas. Here we report the establishment and initial evaluation of a dementia-specific consultation service provided by a teaching hospital-based Psychiatry Department to regional district general hospitals in surrounding smaller towns. Methods: The consultation service was provided to patients with pre-existing or newly suspected dementia, who were in acute hospital care for concurrent conditions. An evaluation of 61 consultations - 49 on-site and 12 via telemedicine - was performed to assess the needs of the participating hospitals and the specific nature of the referrals to the consultation service. Results: Suspected dementia or cognitive dysfunction was the primary reason for consultation requests (>50% of cases). Other common requests concerned suspected delirium, behavioral symptoms, and therapeutic recommendations. During the consultations, a diagnosis of dementia was reached in 52.5% of cases, with other common diagnoses including delirium and depression. Recommendations related to pharmacotherapy were given in 54.1% of consultations. Other recommendations included referral for outpatient neurological or psychiatric follow-up, further diagnostic assessment, or assessment in a memory clinic. Geriatric psychiatric inpatient treatment was recommended in only seven cases (11.5 %). Conclusion: Our initial evaluation demonstrates the feasibility of providing a dementia-specific consultation service in rural areas. The service has the potential to reduce acute transfers to inpatient geriatric psychiatry and enables older patients with dementia or delirium to be treated locally by helping and empowering rurally-based regional hospitals to manage these problems and associated complications.

Evolution of psychosocial burden and psychiatric symptoms in patients with psychiatric disorders during the Covid-19 pandemic.

The Covid-19 pandemic highly impacts mental health worldwide. Patients with psychiatric disorders are a vulnerable risk population for worsening of their condition and relapse of symptoms. This study investigates the pandemic-related course of psychosocial burden in patients with pre-existing mental disorders. With the newly developed Goettingen psychosocial Burden and Symptom Inventory (Goe-BSI) psychosocial burden has been traced retrospectively (1) before the pandemic (beginning of 2020), (2) at its beginning under maximum lockdown conditions (March 2020), and (3) for the current state after maximum lockdown conditions (April/May 2020). The Goe-BSI also integrates the Adjustment Disorder New Module (ADNM-20), assesses general psychiatric symptoms, and resilience. A total of 213 patients covering all major psychiatric disorders (ICD-10 F0-F9) were interviewed once in the time range from April, 24th until May 11th, 2020. Across all diagnoses patients exhibited a distinct pattern with an initial rise followed by a decline of psychosocial burden (p < 0.001, partial η2 = 0.09; Bonferroni-corrected pairwise comparisons between all three time-points: p < 0.05 to 0.001). Female gender and high ADNM-20 scores were identified as risk factors for higher levels and an unfavorable course of psychosocial burden over time. Most psychiatric symptoms remained unchanged. Trajectories of psychosocial burden vary in parallel to local lockdown restrictions and seem to reflect an adaptive stress response. For female patients with pre-existing mental disorders and patients with high-stress responses, timely and specific treatment should be scheduled. With the continuation of the pandemic, monitoring of long-term effects is of major importance, especially when long incubation times for the development of mental health issues are considered.

Medium-term and peri-lockdown course of psychosocial burden during the ongoing COVID-19 pandemic: a longitudinal study on patients with pre-existing mental disorders.

While the COVID-19 pandemic continues, patients with pre-existing mental disorders are increasingly recognized as a risk group for adverse outcomes. However, data are conflicting and cover only short time spans so far. Here, we investigate the medium-term and peri-lockdown-related changes of mental health outcomes in such patients in a longitudinal study. A cohort of 159 patients comprising all major mental disorders (ICD-10 F0-F9) were interviewed twice with the Goettingen psychosocial Burden and Symptom Inventory (Goe-BSI) to evaluate psychosocial burden, psychiatric symptoms and resilience at the end of the first (April/May 2020) and the second lockdown in Germany (November/December 2020). For the primary outcome "psychosocial burden" ratings also comprised retrospective pre-pandemic (early 2020) and very early states during the pandemic (March 2020). For all diagnostic groups, psychosocial burden varied significantly over time (p < 0.001) with an increase from the pre-pandemic to the initial phase (p < 0.001), followed by a steady decrease across both lockdowns, normalizing in November/December 2020. Female gender, high adjustment disorder symptom load at baseline and psychiatric comorbidities were risk factors for higher levels and an unfavorable course of psychosocial burden. Most psychiatric symptoms changed minimally, while resilience decreased over time (p = 0.044 and p = 0.037). The longitudinal course of psychosocial burden indicates an initial stress response, followed by a return to pre-pandemic levels even under recurrent lockdown conditions, mimicking symptoms of an adjustment disorder. Strategies for proactive, specific and continuous treatment have to address resilience capacities before their depletion in the pandemic aftermath, especially for patients with additional risk factors.

Current clinical practice of electroconvulsive therapy and repetitive transcranial magnetic stimulation in psychiatry, a German sample.

The purpose of the study was to evaluate the current clinical practice of Electroconvulsive Therapy and Repetitive Transcranial Magnetic Stimulation in German psychiatry. Case-based data (> 1.000.000 cases) were collected according to §21 of the German hospital remuneration law from January 2015 to December 2017. The study cohort comprises approximately 35-40% of the annual psychiatric cases and hospitals in Germany. Frequency of ECT and rTMS cases were investigated considering main diagnoses according to ICD-10 and treatment settings (inpatient vs. day-care). ECT cases with short-term hospitalization (≤ 4 days) were supposed to be maintenance ECT cases. A linear regression analysis was conducted to estimate trends in the use of ECT and rTMS. Different groups were compared using Chi-square tests. ECT and rTMS cases appear to increase in total during the observation period possibly due to facilities newly introducing ECT and rTMS but also to increased frequency of treatments. Both treatments were rarely performed in day-care settings (0.89% and 11.25%). ECT was performed in 1.72% of all cases with affective disorders and in 1.48% with major depressions, respectively. Age ≥ 65 years, females, severe and psychotic depression were significantly associated with a higher rate of ECT cases. > 40% of all ECT cases were possibly maintenance ECT cases. Only 0.60% of these were performed in day- care settings. rTMS was primarily performed in major depression (86,7% of all rTMS cases). This study suggests a growing demand for ECT and rTMS. Nevertheless, the use of ECT is still low compared to the high prevalence of treatment resistant depression. The use of rTMS is even lower and seems to be restricted to specialized institutions. Maintenance ECT is frequently carried out in an inpatient setting. Limitations of this study are the case- and group-based analysis, missing data on outpatient services and treatment sessions per case. Therefore, the database is not necessarily representative for the entire German healthcare system. Further studies are needed to verify the presented findings and should address the feasibility of ambulatory and day-care ECT services.

Motivations for people with cognitive impairment to complete an advance research directive - a qualitative interview study.

BACKGROUND: Research with persons with dementia is important to better understand the causes of dementia and to develop more effective diagnostics, therapies, and preventive measures. Advance Research Directives (ARDs) have been suggested as a possible solution to include persons with dementia in research in an ethically sound way. Little is known about how people, especially those affected by cognitive impairment, understand and regard the use of ARDs, as empirical studies are mainly conducted with healthy, non-cognitively impaired, participants. METHODS: This qualitative study, a sub-study of a larger study on the evaluation of ARDs in the context of dementia research in Germany, consists of semi-structured in-depth interviews with 24 persons with cognitive impairment. RESULTS: Our results indicate that most participants consider ARDs a valuable tool for allowing them to make their own decisions. Many would prefer to draft an ARD when they are still healthy or soon after the diagnosis of cognitive impairment. Participants suggested that the completion of ARDs can be advanced with the provision of practical support and increased dissemination of information on ARDs in society. CONCLUSION: Persons with subjective or mild cognitive impairment (SCI/MCI) suggested several motivating factors and concerns for completing an ARD. Clinicians need to be trained to accommodate patients' needs for sufficient and adequate information. Furthermore, a standardised, partly pre-formulated template could be helpful for drafting an ARD. As such tested templates are currently not yet available, this addresses the urgent need for more translational and implementation research for the use of ARDs.

Case Report: Association of a Variant of Unknown Significance in the FIG4 Gene With Frontotemporal Dementia and Slowly Progressing Motoneuron Disease: A Case Report Depicting Common Challenges in Clinical and Genetic Diagnostics of Rare Neuropsychiatric and Neurologic Disorders.

BACKGROUND: Modern genetics have in many ways revolutionized clinical routine and have, for instance, shown that formerly distinct disease entities relate to common pathogenic mutations. One such example is the connection between dementia and amyotrophic lateral sclerosis (ALS) in a continuous disease spectrum affirmed by the discovery of shared mutations. CASE REPORT: We describe a new variant in the FIG4 gene in a patient with slowly progressing frontotemporal dementia (FTD) and probable primary lateral sclerosis (PLS). The patient initially showed depressive symptoms and global cognitive deficits. Severe difficulties with language and hallucinations became clearer as the disease progressed. Nuclear medicine imaging and cerebrospinal fluid (CSF) biomarkers were not specific for defined categories of dementia, but neuropsychological testing and clinical features finally led to an allocation of the syndrome to the non-fluent variant of primary progressive aphasia (nfv PPA). Because of increasing limb weakness and bulbar symptoms, motoneuron disease in the form of PLS was diagnosed, strongly supported by elevated CSF neurofilament and electrophysiologic assessments. The detected variant in the FIG4 gene is described as pathogenic or likely pathogenic in common databases and reported once in the literature. While the phenotype of our patient fits the description of FIG4-associated disease in literature, we consider the present variant as VUS in this case. CONCLUSION: We describe a variant in the FIG4 gene in a patient with slowly progressing FTD and PLS. Mutations in the FIG4 gene have been associated with ALS and PLS; however, this exact mutation was not reported in ALS or PLS patients before. The case illustrates generic diagnostic challenges in patients presenting with genetic variants that offer an explanation for otherwise uncommon symptom combinations but yet are of unknown significance.

Nuclear medical imaging as part of dementia diagnostics in psychiatric day-care clinics and inpatient care settings.

BACKGROUND: Current guidelines support the use of nuclear medical imaging (NMI) techniques for differential diagnostics of certain cases of dementia. AIMS: We aimed at studying the association between using NMI and the accuracy of dementia diagnoses. Additionally, we evaluated the effect of conducting NMI on the duration of hospital treatment. METHODS: This study was based on data collected according to §21 of the German hospital remuneration law, including relevant diagnostic and procedural codes for NMI in dementia patients. In total, more than 7.2 million cases treated in German psychiatric and somatic hospitals between 2015 and 2017 were included. Associations between the frequency of NMI and the accuracy of dementia diagnoses in terms of specific vs. unspecific diagnostic codes were analyzed using Fischer's exact test. RESULTS: In total, 351,106 cases with a dementia diagnosis were encoded during the study period. NMI was performed in 1.03% or 0.15% of all patients with dementia in psychiatric or somatic clinics, respectively. In psychiatric clinics, the proportion of unspecific dementia diagnoses decreased from 20.86% in 2015 to 17.73% in 2017. NMI was mainly performed within psychiatric day-care settings. Interestingly, patients receiving NMI stayed shorter within day-care settings (8.1 ± 16.0 days) compared to inpatient settings (38.3 ± 44.7 days). CONCLUSIONS: Nuclear medical imaging is often performed in psychiatric day-care settings. Further studies are warranted to understand the predictive diagnostic value of NMI in dementia diagnosis compared with clinical, CSF and structural imaging in different healthcare settings.

Family load impacts orbitofrontal volume in first-episode schizophrenia.

In schizophrenia, reduced orbitofrontal cortex (OFC) volume is inconsistently reported. To investigate the impact of genetic load on OFC volume, manual MRI-tracing in 23 first-episode schizophrenia patients (FE-SZ) and 23 controls was performed. FE-SZ with genetic load showed a decrease in OFC volume compared to FE-SZ without load and controls.

Joint crisis plans and psychiatric advance directives in German psychiatric practice.

This study explores the attitude of German psychiatrists in leading positions towards joint crisis plans and psychiatric advance directives. This topic was examined by contacting 473 medical directors of German psychiatric hospitals and departments. They were asked to complete a questionnaire developed by us. That form contained questions about the incidence and acceptance of joint crisis plans and psychiatric advance directives and previous experiences with them. 108 medical directors of psychiatric hospitals and departments responded (response rate: 22.8%). Their answers demonstrate that in their hospitals these documents are rarely used. Among the respondents, joint crisis plans are more accepted than psychiatric advance directives. There is a certain uncertainty when dealing with these instruments. Our main conclusion is that German psychiatry needs an intensified discussion on the use of instruments for patients to constitute procedures for future critical psychiatric events. For this purpose it will be helpful to collect more empirical data. Furthermore, the proposal of joint crisis plans in psychiatric hospitals and departments should be discussed as well as the possibility of consulting an expert during the preparation of a psychiatric advance directive.

Cholinergic blockade under working memory demands encountered by increased rehearsal strategies: evidence from fMRI in healthy subjects.

The connection between cholinergic transmission and cognitive performance has been established in behavioural studies. The specific contribution of the muscarinic receptor system on cognitive performance and brain activation, however, has not been evaluated satisfyingly. To investigate the specific contribution of the muscarinic transmission on neural correlates of working memory, we examined the effects of scopolamine, an antagonist of the muscarinic receptors, using functional magnetic resonance imaging (fMRI). Fifteen healthy male, non-smoking subjects performed a fMRI scanning session following the application of scopolamine (0.4 mg, i.v.) or saline in a placebo-controlled, repeated measure, pseudo-randomized, single-blind design. Working memory was probed using an n-back task. Compared to placebo, challenging the cholinergic transmission with scopolamine resulted in hypoactivations in parietal, occipital and cerebellar areas and hyperactivations in frontal and prefrontal areas. These alterations are interpreted as compensatory strategies used to account for downregulation due to muscarinic acetylcholine blockade in parietal and cerebral storage systems by increased activation in frontal and prefrontal areas related to working memory rehearsal. Our results further underline the importance of cholinergic transmission to working memory performance and determine the specific contribution of muscarinic transmission on cerebral activation associated with executive functioning.

Thalamic volumes in patients with bipolar disorder.

There are several hypotheses on functional neuronal networks that modulate mood states and which might form the neuroanatomical basis of bipolar disorder. The thalamus has been reported to be a key structure within the circuits that modulate mood states and might thus play an important role within the aetiology of the bipolar affective disorder. Nevertheless, structural brain imaging studies on the thalamus volume of bipolar patients have shown heterogeneous results. Using structural MRI scanning, we compared the thalamus volume of 41 euthymic bipolar patients to the thalamus volume of 41 well-matched healthy controls. Taking the concomitant medication as a co-variable within the patient group, the analysis of variance revealed a significantly smaller relative volume of the right thalamus in patients not treated with lithium when compared with healthy controls. In contrast, there are no significant differences concerning the thalamus volume between all euthymic bipolar patients and healthy controls. The study only shows findings of a transverse section. No longitudinal analysis was performed. More detailed information on patients' pharmacological histories could not be obtained. In conclusion, this result may be interpreted as an indication of the impact of the thalamus in the pathogenesis of the bipolar I disorder and emphasises the need for further longitudinal studies in bipolar patients with special attention paid to the concomitant medication, in particular to the role of lithium.

Muscarinic antagonist effects on executive control of attention.

Acetylcholine plays a major role in mediating attention processes. We investigated the muscarinic antagonist effect of scopolamine on functional neuro-anatomy of attention and cognition. We assessed 12 healthy volunteers while performing the Attention Network Task on 0.4 mg scopolamine and placebo in a single-blind randomized trial in a 1.5 T magnetic resonance scanner. Neurocognitive measures included verbal learning, verbal memory, verbal fluency, trail making, digit span, a continuous performance task and a planning task (Tower of London). When compared to placebo, scopolamine increased reaction times for conflicting stimulus processing, together with decreasing brain activation in the anterior cingulate cortex (a brain region involved in conflict processing) suggestive of a muscarinic antagonist effect on executive control of attention. Contrary to the notion of a predominantly right-hemispheric lateralization of cognitive processes associated with orienting attention, scopolamine reduced brain activity in left superior and left middle frontal brain areas. Our neuropsychological test data revealed a selective effect of scopolamine on verbal learning and memory while other cognitive domains, such as planning and working memory, were unaffected. These findings are consistent with muscarinic modulation of dopaminergic neurotransmission in frontal attention networks when processing conflicting information.

Nicotinic antagonist effects on functional attention networks.

Cholinergic neurotransmission has been implicated in memory and attention. We investigated the effect of the non-competitive nicotinic antagonist mecamylamine on three components of attention processes (i.e. alerting, orienting and executive control) in 12 healthy male subjects whilst performing the Attention Network Task (ANT) in a magnetic resonance imaging (MRI) scanner. Participants received 15 mg mecamylamine in a single blind and placebo- controlled randomized procedure 90 min prior to obtaining functional MRI data. Our results confirm previous reports of beneficial effects of cueing (alerting and orienting) and detrimental effects of conflict (executive control) on reaction times when performing the ANT. The functional MRI data confirmed distinct neural networks associated with each of the three attention components. Alerting was associated with increased left temporal lobe activation while orienting increased bilateral prefrontal, right precuneus and left caudate activation. Executive control activated anterior cingulate and precuneus. Mecamylamine slowed overall response time and down-regulated brain activation associated with orienting and to some extent brain activation associated with executive control when compared to placebo. These findings are consistent with nicotinic modulation of orienting attention by cueing and executive control when responding to conflicting information. The latter nicotine antagonist effect may be mediated via cholinergic modulation of dopamine neurotransmission in mesolimbic pathways.