Neuromodulators regulate circuits throughout the nervous system, and revealing the cell types and stimulus conditions controlling their release is vital to understanding their function. The effects ...of the neuromodulator nitric oxide (NO) have been studied in many circuits, including in the vertebrate retina, where it regulates synaptic release, gap junction coupling, and blood vessel dilation, but little is known about the cells that release NO. We show that a single type of amacrine cell (AC) controls NO release in the inner retina, and we report its light responses, electrical properties, and calcium dynamics. We discover that this AC forms a dense gap junction network and that the strength of electrical coupling in the network is regulated by light through NO. A model of the network offers insights into the biophysical specializations leading to auto-regulation of NO release within the network.
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•nNOS-2 amacrine cells are the main source of nitric oxide (NO) in the inner retina•These cells release NO rapidly upon light-induced depolarization•nNOS-2 amacrine cells are electrically coupled in the dark and decouple with NO•This network demonstrates a new auto-regulation mechanism for NO release
Jacoby et al. show that a single amacrine cell type, the nNOS-2 AC, controls nitric oxide (NO) release in the retina. nNOS-2 ACs are electrically coupled in the dark and decouple in the light by sensing their own NO release.
Abstract
We study experimentally the optical dipole trapping of a cloud of cold atoms in a high-finesse cavity in the parameter regime where the atomic back-action on the cavity mode is significant. ...Back-action based effects lead to state selective optical manipulation schemes. We identify a parameter range where the collective back action of the atoms is needed for the trapping, i.e. a single atom would not be trapped under the same laser drive conditions. The collective self-trapping is demonstrated by the observation of a significant increase of the trapping time as a function of the atom number. The atomic back action on the cavity field gives rise to a simultaneous real-time monitoring of the number of trapped atoms. This is used to show a non-exponential collapse of the atom trap.
Objectives
More than half of patients with major depression who do not respond to initial antidepressants become treatment resistant (TRD), and while electroconvulsive therapy (ECT) is effective, it ...involves anesthesia and other medical risks that are of concern in geriatric patients. Past studies have suggested that theta cordance (TC), a correlate of cerebral metabolism measured by electroencephalography, could guide treatment decisions related to patient selection and engagement of the therapeutic target.
Methods/Design
Eight patients with late‐life treatment resistant depression (LL‐TRD) underwent magnetoencephalography (MEG) at baseline and following seven sessions of ECT. We tested whether the mean and regional frontal cortex TC were able to differentiate early responders from nonresponders.
Results
Five patients whose depression severity decreased by >30% after seven sessions were considered early responders. We found no baseline differences in mean frontal TC between early responders compared with nonresponders, but early responders exhibited a significant increase in TC following ECT. Further, we found that compared with nonresponders, early responders exhibited a greater change in TC specifically within the right prefrontal cortex.
Conclusions
These results support the hypothesis that increases in frontal TC are associated with antidepressant response. We expand on previous findings by showing that this change is specific to the right prefrontal cortex. Validation of this neural marker could contribute to improved ECT outcomes, by informing early clinical decisions about the acute efficacy of this treatment.
Introduction
Major Depressive Disorder (MDD) is one of the most common mental illnesses worldwide and is strongly associated with suicidality. Commonly used treatments for MDD with suicidality ...include crisis intervention, oral antidepressants (although risk of suicidal behavior is high among non-responders and during the first 10-14 days of the treatment) benzodiazepines and lithium. Although several interventions addressing suicidality exist, only few studies have characterized in detail patients with MDD and suicidality, including treatment, clinical course and outcomes. Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D)-study is an investigator-initiated trial funded by Janssen-Cilag
GmbH.
Objectives
For population 1 out of 3 OASIS-D populations, to assess the sub-population of patients with suicidality and its correlates in hospitalized individuals with MDD.
Methods
The ongoing OASIS-D study consecutively examines hospitalized patients at 8 German psychiatric university hospitals treated as part of routine clinical care. A sub-group of patients with persistent suicidality after >48 hours post-hospitalization are assessed in detail and a sub-group of those are followed for 6 months to assess course and treatment of suicidality associated with MDD. The present analysis focuses on a preplanned interim analysis of the overall hospitalized population with MDD.
Results
Of 2,049 inpatients (age=42.5±15.9 years, females=53.2%), 68.0% had severe MDD without psychosis and 21.2% had moderately severe MDD, with 16.7% having treatment-resistant MDD. Most inpatients referred themselves (49.4%), followed by referrals by outpatient care providers (14.6%), inpatient care providers (9.0%), family/friends (8.5%), and ambulance (6.8%). Of these admissions, 43.1% represented a psychiatric emergency, with suicidality being the reason in 35.9%. Altogether, 72.4% had at least current passive suicidal ideation (SI, lifetime=87.2%), including passive SI (25.1%), active SI without plan (15.5%), active SI with plan (14.2%), and active SI with plan+intent (14.1%), while 11.5% had attempted suicide ≤2 weeks before admission (lifetime=28.7%). Drug-induced mental and behavioral disorders (19.6%) were the most frequent comorbid disorders, followed by personality disorders (8.2%). Upon admission, 64.5% were receiving psychiatric medications, including antidepressants (46.7%), second-generation antipsychotics (23.0%), anxiolytics (11.4%) antiepileptics (6.0%), and lithium (2.8%). Altogether, 9.8% reported nonadherence to medications within 6 months of admission.
Conclusions
In adults admitted for MDD, suicidality was common, representing a psychiatric emergency in 35.9% of patients. Usual-care treatments and outcomes of suicidality in hospitalized adults with MDD require further study.
Disclosure of Interest
None Declared
As physical activity may modify the effect of the apolipoprotein E (APOE) ε4 allele on the risk of dementia and Alzheimer's disease (AD) dementia, we tested for such a gene-environment interaction in ...a sample of general practice patients aged ⩾75 years.
Data were derived from follow-up waves I-IV of the longitudinal German study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). The Kaplan-Meier survival method was used to estimate dementia- and AD-free survival times. Multivariable Cox regression was used to assess individual associations of APOE ε4 and physical activity with risk for dementia and AD, controlling for covariates. We tested for gene-environment interaction by calculating three indices of additive interaction.
Among the randomly selected sample of 6619 patients, 3327 (50.3%) individuals participated in the study at baseline and 2810 (42.5%) at follow-up I. Of the 2492 patients without dementia included at follow-up I, 278 developed dementia (184 AD) over the subsequent follow-up interval of 4.5 years. The presence of the APOE ε4 allele significantly increased and higher physical activity significantly decreased risk for dementia and AD. The co-presence of APOE ε4 with low physical activity was associated with higher risk for dementia and AD and shorter dementia- and AD-free survival time than the presence of APOE ε4 or low physical activity alone. Indices of interaction indicated no significant interaction between low physical activity and the APOE ε4 allele for general dementia risk, but a possible additive interaction for AD risk.
Physical activity even in late life may be effective in reducing conversion to dementia and AD or in delaying the onset of clinical manifestations. APOE ε4 carriers may particularly benefit from increasing physical activity with regard to their risk for AD.
Objectives
To investigate time-dependent predictors of frailty in old age longitudinally.
Design
Population-based prospective cohort study.
Setting
Elderly individuals were recruited via GP offices ...at six study centers in Germany. The course of frailty was observed over 1.5 years (follow up wave 4 and follow up wave 5).
Participants
1,602 individuals aged 80 years and older (mean age 85.4 years SD 3.2, with mean CSHA CFS 3.5 SD 1.6) at follow up wave 4.
Measurements
Frailty was assessed by using the Canadian Study of Health and Aging Clinical Frailty Scale (CSHA CFS), ranging from 1 (very fit) to 7 (severely frail).
Results
Fixed effects regressions revealed that frailty increased significantly with increasing age (ß=.2) as well as the occurrence of depression (ß=.5) and dementia (ß=.8) in the total sample. Changes in marital status and comorbidity did not affect frailty. While the effects of depression and dementia were significant in women, these effects did not achieve statistical significance in men.
Conclusion
Our findings highlight the role of aging as well as the occurrence of dementia and depression for frailty. Specifically, in order to delay frailty in old age, developing interventional strategies to prevent depression might be a fruitful approach.
Objective
In this study, we aimed to analyze the association between new—incident—subjective memory complaints (SMC) and risk of subsequent dementia in a general population sample aged 75+ years.
...Method
Data were derived from follow‐up (FUP) waves I‐V of the population‐based Leipzig Longitudinal Study of the Aged (LEILA75+). We used the Kaplan–Meier survival method to estimate dementia‐free survival times of individuals with and without incident SMC and multivariable Cox proportional hazards regression to assess the association between incident SMC and risk of subsequent dementia, controlled for covariates.
Results
Of 443 non‐demented individuals, 58 (13.1%) developed dementia during a subsequent 5.4‐year follow‐up period. Participants with incident SMC showed a significantly higher progression to dementia (18.5% vs. 10.0%; P = 0.010) and a significantly shorter mean dementia‐free survival time than those without (6.2 vs. 6.8 years; P = 0.008). The association between incident SMC and risk of subsequent dementia remained significant in the multivariable Cox analysis (adjusted hazard ratio = 1.8; P = 0.028).
Conclusion
Our findings suggest higher progression to dementia and shorter dementia‐free survival in older individuals with incident SMC. These findings support the notion that such subjective complaints should be taken seriously in clinical practice as possible early indicators of incipient dementia.
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