Cell-type specific inhibitory plasticity in subicular pyramidal cells.

The balance between excitation and inhibition is essential to the proper function of cortical circuits. To maintain this balance during dynamic network activity, modulation of the strength of inhibitory synapses is a central requirement. In this study, we aimed to characterize perisomatic inhibition and its plasticity onto pyramidal cells (PCs) in the subiculum, the main output region of the hippocampus. We performed whole-cell patch-clamp recordings from the two main functional PC types, burst (BS) and regular spiking (RS) neurons in acute rat hippocampal slices and applied two different extracellular high-frequency stimulation paradigms: non-associative (presynaptic stimulation only) and associative stimulation (concurrent pre-and postsynaptic stimulation) to induce plasticity. Our results revealed cell type-specific differences in the expression of inhibitory plasticity depending on the induction paradigm: While associative stimulation caused robust inhibitory plasticity in both cell types, non-associative stimulation produced long-term potentiation in RS, but not in BS PCs. Analysis of paired-pulse ratio, variance of IPSPs, and postsynaptic Ca2+ buffering indicated a dominant postsynaptic calcium-dependent signaling and expression of inhibitory plasticity in both PC types. This divergence in inhibitory plasticity complements a stronger inhibition and a higher intrinsic excitability in RS as compared to BS neurons, suggesting differential involvement of the two PC types during network activation and information processing in the subiculum.

[Support for families with a mentally ill parent : Which forms of help do mentally ill parents utilize and which would they like to have?] / Unterstützung für Familien mit einem psychisch erkrankten Elternteil : Welche Hilfen nehmen psychisch erkrankte Eltern in Anspruch und welche wünschen sie sich?

BACKGROUND: In Germany different offers of social support are available for families that are provided by different sectors, e.g., the youth welfare and the healthcare systems. OBJECTIVE: Documentation of the utilized help, child-related factors that are associated with the utilization and the parental desires for support. MATERIAL AND METHODS: Survey of 160 parents undergoing (partial) inpatient treatment in psychiatric hospitals via an oral interview using standardized and semi-standardized instruments. RESULTS: The results show that nonprofessional help by family and friends as well as support offers provided by the healthcare system are used most frequently. Families that perceived their children as more burdened receive more help than families with children judged as being less burdened. There are regional differences especially in the utilization of high-threshold help by the healthcare system. DISCUSSION: Support offers seem to reach families with mental illnesses, especially those that are particularly burdened; however, there are regional differences regarding the utilization of support as well as the wishes for specific support offers.

The psychological burden of COVID-19 on the desire for parenthood in minoritized sexual identities: a study on depressive symptoms and family planning in Germany.

BACKGROUND: The COVID-19 pandemic continues to spread across the globe and is associated with significant clinical and humanitarian burden. The desire for parenthood has been described to be positively correlated with psychological well-being: An unfulfilled wish for parenthood is associated with impaired mental health, and the wish for parenthood is a predictor for the development of depressive symptoms. While higher rates of anxiety and depression have been reported in individuals with minoritized sexual identities (compared to heterosexual individuals) during the COVID-19 pandemic, the specific impact of the pandemic and its social restriction measures on this population is poorly understood. METHODS: From April to July 2020, we conducted an anonymous cross-sectional survey online among N = 2463 adults living in Germany. We screened for depressive symptoms (Patient Health Questionnaire-4; PHQ-4) and assessed individuals' desire for parenthood during the pandemic, and motives for or against the desire for parenthood (Leipzig questionnaire on motives for having a child, Version 20; LKM-20), with the aim of identifying differences between individuals with minoritized sexual identities and heterosexual individuals. RESULTS: Compared to heterosexual individuals (n = 1304), individuals with minoritized sexual identities (n = 831) indicated higher levels of depressive symptoms. In our study sample the majority of all participants (81.9%) reported no change in the desire for parenthood since the COVID-19 pandemic. CONCLUSION: The findings underline the unmet need for social, psychological and medical support in regard to family-planning and the desire for parenthood during a pandemic. Furthermore, future research should explore COVID-19-related psychological consequences on individuals' desire for parenthood and building a family.

Acute effects of lithium augmentation on the kidney in geriatric compared with non-geriatric patients with treatment-resistant depression.

INTRODUCTION: Lithium augmentation (LA) of antidepressants is a first-line therapy option for treatment-resistant depression (TRD). Nevertheless, it is rarely used in geriatric patients mostly because of the fear of kidney toxicity. The purpose of this study is to investigate estimated glomerular filtration rate (eGFR) changes and number of acute kidney injuries (AKI) using LA in geriatric compared with non-geriatric patients. METHODS: In a prospective multicenter cohort study, eGFR changes were measured in 201 patients with unipolar depression (nage≥65years  = 29; nage<65years  = 172) at baseline and over 2-6 weeks of LA. We used linear mixed models to investigate changes in eGFR upon LA and assessed the number of AKIs, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. RESULTS: Both age groups showed a significant eGFR decline over the course of treatment with lower eGFR in geriatric patients. The lithium serum level (interpretable as "effect of LA") had a significant effect on eGFR decline. Both effects (age group and lithium serum level) on eGFR decline did not influence each other, meaning the effect of LA on eGFR decline did not differ between age groups. Two AKIs were observed in the geriatric age group when serum lithium levels exceeded the therapeutic range of >0.8 mmol/L. CONCLUSION: This is the first study investigating eGFR change and AKI upon LA for TRD in geriatric compared with non-geriatric patients. Our data suggest that LA, as an effective treatment option in geriatric patients, should be closely monitored to avoid AKIs.

Hippocampal Dysfunction in Schizophrenia and Aberrant Hippocampal Synaptic Plasticity in Rodent Model Psychosis: a Selective Review.

Schizophrenia is a complex, heterogeneous psychiatric disorder that affects about 1% of the global population. Hippocampal dysfunction has been linked to both cognitive deficits and positive symptoms in schizophrenia. Here, we briefly review current findings on disrupted hippocampal processing from a clinical perspective before concentrating on preclinical studies of aberrant hippocampal synaptic plasticity using the N-methyl-D-aspartate receptor hypofunction model of psychosis and related findings from genetic models. Taken together, the results put the case for maladaptive hippocampal synaptic plasticity and its extrinsic connections as mechanistic underpinnings of cognitive impairments in schizophrenia.

Depression in primary care and the role of evidence-based guidelines: cross-sectional data from primary care physicians in Germany.

BACKGROUND: Depression is the most common mental health burden worldwide. Primary care physicians (PCPs) play a key role in the care provision for people with depression. The first objective of the present study was to examine the health care situation of depression in primary care, focusing on the cooperation between PCPs and mental health specialists. Secondly, we aimed at examining the role of the German S3 Guideline for Unipolar Depression in the primary care provision. METHODS: Data of N = 75 PCPs were analysed from a cross-sectional online survey. Analysis of descriptive information on the current status of primary health care and depression was conducted. Further, to examine factors that are related to the usage of guidelines, multiple regression was performed. RESULTS: Only 22.1% of PCPs described the quality of cooperation with ambulatory mental health specialist as good. The most frequent problems in the cooperation were of structural nature (49.3%, long waiting list, few therapy units, as well as barriers in the communication and the information exchange). With regard to the role of the guideline, 65% of PCPs reported never or seldom using the guideline and 31.7% of PCPs perceived the guideline as not useful at all. In addition, perceived usefulness of the S3 guideline was positively associated with the usage of the guideline. Results of the logistic regression revealed a significant association between the usage of the German S3 Guideline for Unipolar Depression and rating of perceived usefulness of the guideline (OR: 4.771; 95% CI: 2.15-10.59; p < 0.001). CONCLUSION: This study highlights the central role of PCPs and demonstrates major barriers in the outpatient health care provision of depression. Present findings suggest a strong need for collaborative health care models to resolve obstacles resulting from fragmented mental health care systems. Finally, reported perceived barriers in the implementation of the German S3 Guideline for Unipolar Depression indicate the urge to involve PCPs in the development of evidence-based guidelines, in order to ensure a successful implementation and usage of guidelines in clinical practice.

The Impact of the COVID-19 Pandemic on Sexual Health in Cis Women Living in Germany.

BACKGROUND: Preliminary research shows a substantial impact of the COVID-19 pandemic on women's sexual health, whereby empirical work on sexual well-being of minoritized sexual identities is still rare. AIM: The objective of this study was to explore sexual health in heterosexual, lesbian and bisexual cis women during the first wave of COVID-19 pandemic in Germany. METHODS: An anonymous nationwide online survey was conducted among cis women during the first nationwide lockdown in Germany from April 20th to July 20th, 2020. The questionnaire was distributed via e-mail, online chats and social-media platforms. OUTCOMES: Demographic variables and self-report measures from the Sexual Behavior Questionnaire (SBQ-G) "before the pandemic" and "since the pandemic" were collected. RESULTS: A total of 1,368 cis women participants were included: heterosexual women (n = 844), lesbian women (n = 293), bisexual women (n = 231). Results indicate overall decrease in frequency of sexual contacts and masturbation during the COVID-19 pandemic. Regarding differences before and during the pandemic lesbian women showed significant changes in sexual arousal whereas heterosexual women showed significant changes in all dimensions except capability to enjoy sexual intercourse. The data of bisexual women showed significant changes in almost all dimensions except for frequency of sexual intercourse and sexual arousal. Results of the multiple regression analysis revealed that being younger than 36 years-old, and being in a relationship as well as being heterosexual (compared with being lesbian) is positively associated with general satisfaction with sexual life during the pandemic. CLINICAL IMPLICATIONS: The findings suggest that during a pandemic sexual and mental health care for (cis) women should be provided and address the specific needs of sexual minority groups. STRENGTHS & LIMITATIONS: This is the first study to describe sexual behavior in heterosexual, lesbian and bisexual women during the COVID-19 pandemic in Germany. Limitations, however, include the fact that the data described were obtained at only one time point so there is a possibility of recall bias, and that the results cannot be generalized because of the underrepresentation of women over age 46. CONCLUSION: This study examined the impact of the COVID-19 pandemic and resulting social constraints on the sexual health of particular groups of lesbian and bisexual women, which may improve preparedness for future public health and policy crises. Batz F, Lermer E, Hatzler L, et al. The Impact of the COVID-19 Pandemic on Sexual Health in Cis Women Living in Germany. J Sex Med 2022;19:907-922.

Changes in Electric Brain Response to Affective Stimuli in the First Week of Antidepressant Treatment: An Exploratory Study.

INTRODUCTION: Asymmetrical alpha and frontal theta activity have been discussed as neurobiological markers for antidepressant treatment response. While most studies focus on resting-state EEG, there is evidence that task-related activity assessed at multiple time points might be superior in detecting subtle early differences. METHODS: This was a naturalistic study design assessing participants in a psychiatric in- and outpatient hospital setting. We investigated stimulus-related EEG asymmetry (frontal and occipital alpha-1 and alpha-2) and power (frontal midline theta) assessed at baseline and 1 week after initiation of pharmacological depression treatment while presenting affective stimuli. We then compared week 4 responders and nonresponders to antidepressant treatment. RESULTS: Follow-up analyses of a significant group × emotion × time interaction (p < 0.04) for alpha-1 asymmetry showed that responders differed significantly at baseline in their asymmetry scores in response to sad compared to happy faces with a change in this pattern 1 week later. Nonresponders did not show this pattern. No significant results were found for alpha-2, occipital alpha-1, and occipital alpha-2 asymmetry or frontal midline theta power. DISCUSSION: Our study addresses the gap in comparisons of task-related EEG activity changes measured at two time points and supports the potential value of this approach in detecting early differences in responders versus nonresponders to pharmacological treatment. Important limitations include the small sample size and the noncontrolled study design.

Electrocardiographic Changes During Initiation of Lithium Augmentation of Antidepressant Pharmacotherapy.

PURPOSE/BACKGROUND: Lithium augmentation of antidepressants represents a common strategy to overcome treatment resistance in patients with major depressive disorder. The use of lithium has been associated with cardiovascular adverse effects such as QTc prolongation and tachyarrhythmia. Although the previous studies investigated monotherapy with lithium, the aim of this study was to investigate electrocardiographic changes in LA. METHODS/PROCEDURES: A 12-lead surface electrocardiogram (ECG) was obtained from 38 patients with major depressive disorder before and during LA. Changes in heart rate, PQ, QRS and QTc interval, QT dispersion, ST segment, and T- and U-wave alterations were analyzed using a linear mixed model. FINDINGS/RESULTS: The ECG readings of 33 patients were evaluated. Lithium augmentation was not significantly associated with changes in heart rate, QTc, PQ, or QRS interval. We found a significant decrease in QT dispersion. These results were independent of sex, age, stable comedication, and comorbidities. During LA, we observed 9 cases of T-wave alterations and 2 cases of new U waves. CONCLUSIONS: Our data provide no evidence for serious ECG abnormalities at therapeutic serum lithium levels in patients treated with LA. In particular, we did not find evidence for QTc time lengthening or tachyarrhythmia, such as torsades des pointes. The recommended intervals for ECG checks should be considered to detect long-term effects of LA.

Faster speed of onset of the depressive episode is associated with lower cytokine serum levels (IL-2, -4, -6, -10, TNF-α and IFN-γ) in patients with major depression.

INTRODUCTION: Cytokines might play a key role in the pathophysiology of major depressive disorder (MDD). The speed of onset of depressive episodes has been discussed as an important clinical parameter in MDD. The aim of this study was to investigate a potential influence of the speed of onset of the depressive episode on cytokine serum levels. METHOD: Serum level of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) granulocyte and monocyte colony stimulating factor (GM-CSF) were measured in a total of 92 patients with MDD that did not respond to at least one previous antidepressant treatment. Patients were retrospectively divided in two groups: Faster (≤4 weeks) and slower (>4 weeks) onset of the depressive episode defined as the time passing from the first depressive symptoms to a full-blown depressive episode by using information from a clinical interview. RESULTS: We found significantly lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with a faster onset compared to patients with a slower onset of the depressive episodes. Furthermore, lower cytokine serum levels of IL-2, IL-8, IL-10 and IFN-γ were found in patients with a shorter duration (less than 6 months) compared to a longer duration (6-24 months) of the current depressive episode. This effect on cytokines was independent from the effect of the speed of onset of the depressive episode. CONCLUSIONS: Patients with faster onset of the depressive episode might represent a biological subtype of MDD with lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ.

Well-being during COVID-19 pandemic: A comparison of individuals with minoritized sexual and gender identities and cis-heterosexual individuals.

BACKGROUND: Preliminary empirical data indicates a substantial impact of the COVID-19 pandemic on well-being and mental health. Individuals with minoritized sexual and gender identities are at a higher risk of experiencing such negative changes in their well-being. The objective of this study was to compare levels of well-being among cis-heterosexual individuals and individuals with minoritized sexual and gender identities during the COVID-19 pandemic. METHODS: Using data obtained in a cross-sectional online survey between April 20 to July 20, 2020 (N = 2332), we compared levels of well-being (WHO-5) across subgroups (cis-individuals with minoritized sexual identities, individuals with minoritized gender identities and cis-heterosexual individuals) applying univariate (two-sample t-test) and multivariate analysis (multivariate linear regression). RESULTS: Results indicate overall lower levels of well-being as well as lower levels of well-being in minoritized sexual or gender identities compared to cis-heterosexual individuals. Further, multivariate analyses revealed that living in urban communities as well as being in a relationship were positively associated with higher levels of well-being. Furthermore, a moderation analysis showed that being in a relationship reduces the difference between groups in terms of well-being. CONCLUSION: Access to mental healthcare for individuals with minoritized sexual and gender identities as well as access to gender-affirming resources should be strengthened during COVID-19 pandemic. Healthcare services with low barriers of access such as telehealth and online peer support groups should be made available, especially for vulnerable groups.

Stress-Induced Enhanced Long-Term Potentiation and Reduced Threshold for N-Methyl-D-Aspartate Receptor- and ß-Adrenergic Receptor-Mediated Synaptic Plasticity in Rodent Ventral Subiculum.

Stress is a biologically relevant signal and can modulate hippocampal synaptic plasticity. The subiculum is the major output station of the hippocampus and serves as a critical hub in the stress response network. However, stress-associated synaptic plasticity in the ventral subiculum has not been adequately addressed. Therefore, we investigated the impact of a single exposure to an inherently stressful two-way active avoidance conditioning on the induction of long-term potentiation (LTP) at CA1-subiculum synapses in ventral hippocampal slices from young adult rats 1 day after stressor exposure. We found that acute stress enhanced LTP and lowered the induction threshold for a late-onset LTP at excitatory CA1 to subicular burst-spiking neuron synapses. This late-onset LTP was dependent on the activation of ß-adrenergic and glutamatergic N-methyl-D-aspartate receptors and independent of D1/D5 dopamine receptor activation. Thereby, we present a cellular mechanism that might contribute to behavioral stress adaptation after acute stressor exposure.

Neurocan genome-wide psychiatric risk variant affects explicit memory performance and hippocampal function in healthy humans.

Alterations of the brain extracellular matrix (ECM) can perturb the structure and function of brain networks like the hippocampus, a key region in human memory that is commonly affected in psychiatric disorders. Here, we investigated the potential effects of a genome-wide psychiatric risk variant in the NCAN gene encoding the ECM proteoglycan neurocan (rs1064395) on memory performance, hippocampal function and cortical morphology in young, healthy volunteers. We assessed verbal memory performance in two cohorts (N = 572, 302) and found reduced recall performance in risk allele (A) carriers across both cohorts. In 117 participants, we performed functional magnetic resonance imaging using a novelty-encoding task with visual scenes. Risk allele carriers showed higher false alarm rates during recognition, accompanied by inefficiently increased left hippocampal activation. To assess effects of rs1064395 on brain morphology, we performed voxel-based morphometry in 420 participants from four independent cohorts and found lower grey matter density in the ventrolateral and rostral prefrontal cortex of risk allele carriers. In silico eQTL analysis revealed that rs1064395 SNP is linked not only to increased prefrontal expression of the NCAN gene itself, but also of the neighbouring HAPLN4 gene, suggesting a more complex effect of the SNP on ECM composition. Our results suggest that the NCAN rs1064395 A allele is associated with lower hippocampus-dependent memory function, variation of prefrontal cortex structure and ECM composition. Considering the well-documented hippocampal and prefrontal dysfunction in bipolar disorder and schizophrenia, our results may reflect an intermediate phenotype by which NCAN rs1064395 contributes to disease risk.

Loss of Long-Term Potentiation at Hippocampal Output Synapses in Experimental Temporal Lobe Epilepsy.

Patients suffering from temporal lobe epilepsy (TLE) show severe problems in hippocampus dependent memory consolidation. Memory consolidation strongly depends on an intact dialog between the hippocampus and neocortical structures. Deficits in hippocampal signal transmission are known to provoke disturbances in memory formation. In the present study, we investigate changes of synaptic plasticity at hippocampal output structures in an experimental animal model of TLE. In pilocarpine-treated rats, we found suppressed long-term potentiation (LTP) in hippocampal and parahippocampal regions such as the subiculum and the entorhinal cortex (EC). Subsequently we focused on the subiculum, serving as the major relay station between the hippocampus proper and downstream structures. In control animals, subicular pyramidal cells express different forms of LTP depending on their intrinsic firing pattern. In line with our extracellular recordings, we could show that LTP could only be induced in a minority of subicular pyramidal neurons. We demonstrate that a well-characterized cAMP-dependent signaling pathway involved in presynaptic forms of LTP is perturbed in pilocarpine-treated animals. Our findings suggest that in TLE, disturbances of synaptic plasticity may influence the information flow between the hippocampus and the neocortex.

EEG Frontal Asymmetry and Theta Power in Unipolar and Bipolar Depression.

BACKGROUND: Distinguishing between unipolar and bipolar depression is of high clinical relevance. However, there is sparse research directly comparing these groups in terms of EEG activity. METHOD: We investigated 87 participants' left and right EEG frontal alpha-1, alpha-2, and theta activity related to happy and sad face stimuli in unipolar (UD, n=33) and bipolar (BD, n=22) depressed participants, and controls without depression (HC, n=32). RESULTS: Post-hoc analysis of an observed hemisphere x group interaction (p< .037) showed significant differences in alpha-1 asymmetry only for the comparison of UD and HC (p< .006). Further analysis of a significant emotion x group interaction (p= .001) revealed a differential impact of stimulus valence on theta power between the groups (p< .001). The valence dependent theta power of the BD differed from that of the UD (p< .0002) and the HC (p< .004). Alpha-1 asymmetry classified HC and both depressed groups with an accuracy of .69. Valence-related theta classified BD from UD with an accuracy of .83. Leave-one-out cross validation resulted in slightly reduced accuracy. LIMITATIONS: Important limitations were the small sample size and that subjects were not medication-free. CONCLUSIONS: Our results demonstrate the value of simple, task related EEG activity for differentiating not only healthy individuals from those with depression, but also individuals with unipolar depression from those with bipolar depression.

Psychosis in German prisoners: Comparison of the clinical appearance of psychotic disorder of an imprisoned population with a not detained community group.

Surveys confirm risk factors for the incarceration of patients with psychosis including homelessness and comorbidity. There is also agreement that severe psychosis can lead to violence. Data describing prisoners with psychosis in Germany are scarce. We aimed to compare patients with psychosis in a prison hospital and patients with psychosis in a community hospital. Demographic data were collected, as well as comorbidity in the form of substance dependence and a psychiatric assessment using the German version of the 18-item Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS). In the prison hospital group more patients were homeless (17 versus 2%) and non-German (36 versus 4%). There were also more patients with substance dependence or abuse in the prison hospital group. The total scores of BPRS and PANSS were lower in the prison hospital group (BPRS, 43.8 versus 51.2; PANSS, 71.5 versus 83.7). We assume that social disintegration for mentally disturbed offenders prior to incarceration hindered effective treatment. To avoid further social disintegration and possible further deterioration of mental health status of released offenders, which may lead to reoffending after imprisonment, discharge management after release from prison should be improved.