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Late-life depression is associated with significant cognitive impairment. Meta-analyses showed that depression is associated with an increased risk for Alzheimer's disease (AD) and it might be an etiological factor for AD. Since late-life depression is often connected with cognitive impairment and dementia is usually associated with depressive symptoms, a simple diagnostic approach to distinguish between the disorders is challenging. Several overlapping pathophysiological substrates might explain the comorbidity of both syndromes. Firstly, a stress syndrome, i.e., elevated cortisol levels, has been observed in up to 70% of depressed patients and also in AD pathology. Stress conditions can cause hippocampal neuronal damage as well as cognitive impairment. Secondly, the development of a depression and dementia after the onset of vascular diseases, the profile of cerebrovascular risk factors in both disorders and the impairments depending on the location of cerebrovascular lesions, speak in favor of a vascular hypothesis as a common factor for both disorders. Thirdly, neuroinflammatory processes play a key role in the etiology of depression as well as in dementia. Increased activation of microglia, changes in Transforming-Growth-Factor beta1 (TGF-beta1) signaling, production of pro-inflammatory cytokines as well as reduction of anti-inflammatory molecules are examples of common pathways impaired in dementia and depression. Fourthly, the neurotrophin BDNF is highly expressed in the central nervous system, especially in the hippocampus, where it plays a key role in the proliferation, differentiation and the maintenance of neuronal integrity throughout lifespan. It has been associated not only with antidepressant properties but also a reduction of cognitive impairment and therefore could be involved also in AD. Another etiologic factor is amyloid accumulation, as plasma amyloid beta-42 independently predicts both late-onset depression and AD. Higher plasma amyloid beta-42 predicts the development of late onset depression and conversion to possible AD. However, clinical trials with antibodies against beta amyloid recently failed, i.e., Solanezumab, Aducanumab, and Crenezumab. An overproduction of amyloid-beta might simply reflect a form of synaptic plasticity to compensate for neuronal dysfunction in different kind of neurological and psychiatric diseases of multiple etiologies. The tau hypothesis, sex/gender specific differences, epigenetics and the gut microbiota-brain axis imply other potential common pathways connecting late-life depression and dementia. In conclusion, different potential pathophysiological links between dementia and depression highlight several specific synergistic and multifaceted treatment possibilities, depending on the individual risk profile of the patient.

Depressive disorders pose significant challenges to global public health, necessitating effective prevention and management strategies. Notably, the occurrence of suicide frequently coincides with depressive episodes. Suicide is as a paramount global health concern that demands efficacious preventive strategies. Current psychiatric approaches heavily rely on pharmacological interventions but have had limited success in addressing the global burden of mental health issues. Suboptimal nutrition, with its impact on the neuroendocrine system, has been implicated in the underlying pathology of depressive disorders. Folate, a group of water-soluble compounds, plays a crucial role in various central nervous system functions. Depressed individuals often exhibit low levels of serum and red blood cell folate. Multiple studies and systematic reviews have investigated the efficacy of folic acid and its derivative, L-methylfolate, which can cross the blood–brain barrier, as stand-alone or adjunct therapies for depression. Although findings have been mixed, the available evidence generally supports the use of these compounds in depressed individuals. Recent studies have established links between the one-carbon cycle, folate–homocysteine balance, immune system function, glutamate excitation via NMDA (N-methyl-D-aspartate) receptors, and gut microbiome eubiosis in mood regulation. These findings provide insights into the complex neurobiological mechanisms underlying the effects of folate and related compounds in depression. Through a comprehensive review of the existing literature, this study aims to advance our understanding of the therapeutic potential of folic acid and related compounds in depression treatment. It also seeks to explore their role in addressing suicidal tendencies and shed light on the neurobiological mechanisms involved, leveraging the latest discoveries in depression research.

A promising new treatment approach for major depressive disorder (MDD) targets the microbiota-gut-brain (MGB) axis, which is linked to physiological and behavioral functions affected in MDD. This is the first randomized controlled trial to determine whether short-term, high-dose probiotic supplementation reduces depressive symptoms along with gut microbial and neural changes in depressed patients. Patients with current depressive episodes took either a multi-strain probiotic supplement or placebo over 31 days additionally to treatment-as-usual. Assessments took place before, immediately after and again four weeks after the intervention. The Hamilton Depression Rating Sale (HAM-D) was assessed as primary outcome. Quantitative microbiome profiling and neuroimaging was used to detect changes along the MGB axis. In the sample that completed the intervention (probiotics N  = 21, placebo N  = 26), HAM-D scores decreased over time and interactions between time and group indicated a stronger decrease in the probiotics relative to the placebo group. Probiotics maintained microbial diversity and increased the abundance of the genus Lactobacillus , indicating the effectivity of the probiotics to increase specific taxa. The increase of the Lactobacillus was associated with decreased depressive symptoms in the probiotics group. Finally, putamen activation in response to neutral faces was significantly decreased after the probiotic intervention. Our data imply that an add-on probiotic treatment ameliorates depressive symptoms (HAM-D) along with changes in the gut microbiota and brain, which highlights the role of the MGB axis in MDD and emphasizes the potential of microbiota-related treatment approaches as accessible, pragmatic, and non-stigmatizing therapies in MDD. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591.

High utilizers (HU) are patients with an above-average use of psychiatric inpatient treatment. A precise characterization of this patient group is important when tailoring specific treatment approaches for them. While the current literature reports evidence of sociodemographic, and socio-clinical characteristics of HU, knowledge regarding their psychological characteristics is sparse. This study aimed to investigate the association between patients’ psychological characteristics and their utilization of psychiatric inpatient treatment. Patients from the University Psychiatric Clinics (UPK) Basel diagnosed with schizophrenia spectrum or bipolar affective disorders participated in a survey at the end of their inpatient treatment stay. The survey included assessments of psychological characteristics such as quality of life, self-esteem, self-stigma, subjective experience and meaning of psychoses, insight into the disease, and patients’ utilization of psychiatric inpatient treatment in the last 30 months. The outcome variables were two indicators of utilization of psychiatric inpatient treatment, viz. “utilization pattern” (defined as HU vs. Non-HU [NHU]) and “length of stay” (number of inpatient treatment days in the last 30 months). Statistical analyses included multiple regression models, the least absolute shrinkage and selection operator (lasso) method, and the random forest model. We included 112 inpatients, of which 50 were classified as HU and 62 as NHU. The low performance of all statistical models used after cross-validation suggests that none of the estimated psychological variables showed predictive accuracy and hence clinical relevance regarding these two outcomes. Results indicate no link between psychological characteristics and inpatient treatment utilization in patients diagnosed with schizophrenia spectrum or bipolar affective disorders. Thus, in this study, the examined psychological variables do not seem to play an important role in patients’ use of psychiatric inpatient treatment; this highlights the need for additional research to further examine underlying mechanisms of high utilization of psychiatric inpatient treatment.

There has been little research exploring the relationship between personality traits, self-esteem, and stigmatizing attitudes toward those with mental disorders. Furthermore, the mechanisms through which the beholder’s personality influence mental illness stigma have not been tested. The aim of this study is to examine the relationship between Big Five personality traits, self-esteem, familiarity, being a healthcare professional, and stigmatization. Moreover, this study aims to explore the mediating effect of perceived dangerousness on the relationship between personality traits and desire for social distance. We conducted a vignette-based representative population survey ( N  = 2207) in the canton of Basel-Stadt, Switzerland. Multiple regression analyses were employed to examine the associations between personality traits, self-esteem, familiarity, and being a healthcare professional with the desire for social distance and perceived dangerousness. The mediation analyses were performed using the PROCESS macro by Hayes. Analyses showed associations between personality traits and stigmatization towards mental illness. Those who scored higher on openness to experience ( β  = − 0.13, p  < 0.001), ( β  = − 0.14, p  < 0.001), and those who scored higher on agreeableness ( β  = − 0.15, p  < 0.001), ( β  = − 0.12, p  < 0.001) showed a lower desire for social distance and lower perceived dangerousness, respectively. Neuroticism ( β  = − 0.06, p  = 0.012) was inversely associated with perceived dangerousness. Additionally, high self-esteem was associated with increased stigmatization. Personal contact or familiarity with people having mental disorders was associated with decreased stigmatization. Contrarily, healthcare professionals showed higher perceived dangerousness ( β  = 0.04, p  = 0.040). Finally, perceived dangerousness partially mediated the association between openness to experience (indirect effect = −  .57, 95% CI [− .71, − 0.43]) as well as agreeableness (indirect effect = − 0.57, 95% CI [− 0.74, − 0.39]) and desire for social distance. Although the explained variance in all analyses is < 10%, the current findings highlight the role of personality traits and self-esteem in areas of stigma. Therefore, future stigma research and anti-stigma campaigns should take individual differences into consideration. Moreover, the current study suggests that perceived dangerousness mediates the relationship between personality traits and desire for social distance. Further studies are needed to explore the underlying mechanisms of such relationship. Finally, our results once more underline the necessity of increasing familiarity with mentally ill people and of improving the attitude of healthcare professionals towards persons with mental disorders.

Circadian desynchronizations are associated with psychiatric disorders as well as with higher suicidal risk. Brown adipose tissue (BAT) is important in the regulation of body temperature and contributes to the homeostasis of the metabolic, cardiovascular, skeletal muscle or central nervous system. BAT is under neuronal, hormonal and immune control and secrets batokines: i.e., autocrine, paracrine and endocrine active substances. Moreover, BAT is involved in circadian system. Light, ambient temperature as well as exogen substances interact with BAT. Thus, a dysregulation of BAT can indirectly worsen psychiatric conditions and the risk of suicide, as one of previously suggested explanations for the seasonality of suicide rate. Furthermore, overactivation of BAT is associated with lower body weight and lower level of blood lipids. Reduced body mass index (BMI) or decrease in BMI respectively, as well as lower triglyceride concentrations were found to correlate with higher risk of suicide, however the findings are inconclusive. Hyperactivation or dysregulation of BAT in relation to the circadian system as a possible common factor is discussed. Interestingly, substances with proven efficacy in reducing suicidal risk, like clozapine or lithium, interact with BAT. The effects of clozapine on fat tissue are stronger and might differ qualitatively from other antipsychotics; however, the significance remains unclear. We suggest that BAT is involved in the brain/environment homeostasis and deserves attention from a psychiatric point of view. Better understanding of circadian disruptions and its mechanisms can contribute to personalized diagnostic and therapy as well as better assessment of suicide risk.

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABAA receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. GABA is readily available and approved as a food supplement in many countries. Although there is substantial evidence indicating that orally ingested GABA may affect GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that oral GABA intake may exert beneficial effects on the brain and psyche through the gut–brain axis. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

In major depressive disorder (MDD), cognitive dysfunctions strongly contribute to functional impairments but are barely addressed in current therapies. Novel treatment strategies addressing cognitive symptoms in depression are needed. As the gut microbiota-brain axis is linked to depression and cognition, we investigated the effect of a 4-week high-dose probiotic supplementation on cognitive symptoms in depression. This randomized controlled trial included 60 patients with MDD, of whom 43 entered modified intention-to-treat analysis. A probiotic supplement or indistinguishable placebo containing maltose was administered over 31 days in addition to treatment as usual for depression. Participant scores on the Verbal Learning Memory Test (VLMT), Corsi Block Tapping Test, and both Trail Making Test versions as well as brain-derived neurotrophic factor levels were assessed at 3 different time points: before, immediately after and 4 weeks after intervention. Additionally, brain activation changes during working memory processing were investigated before and immediately after intervention. We found a significantly improved immediate recall in the VLMT in the probiotic group immediately after intervention, and a trend for a time × group interaction considering all time points. Furthermore, we found a time × group interaction in hippocampus activation during working memory processing, revealing a remediated hippocampus function in the probiotic group. Other measures did not reveal significant changes. The modest sample size resulting from our exclusion of low-compliant cases should be considered. Additional probiotic supplementation enhances verbal episodic memory and affects neural mechanisms underlying impaired cognition in MDD. The present findings support the importance of the gut microbiota-brain axis in MDD and emphasize the potential of microbiota-related regimens to treat cognitive symptoms in depression. clinicaltrials.gov identifier NCT02957591.

Often, after an inpatient stay, early readmission occurs, which is detrimental to the patient. University Psychiatric Clinics Basel developed a 3-month transitional intervention program to bridge inpatient and community treatment by supporting people after their discharge from the psychiatric hospital. In line with international guidelines, this transitional intervention was delivered as assertive community treatment in the homes of people who wished to participate. Data from the 3-year pilot project starting in 2019 have been collected to analyze the success of its implementation and treatment effectiveness in reducing follow-up inpatient treatment days when comparing people choosing to participate in the transitional program and receiving treatment ( n cases  = 456) versus people declining participation ( n cases  = 104). Results indicate that within 3 years, a multidisciplinary team could be assembled that was able to work with a caseload of up to 66 persons per month. Receipt of treatment was descriptively associated with lower numbers of inpatient treatment days, stays, and involuntary admissions 6 months after discharge; however, this difference did not reach statistical significance. Program participants further reported very high levels of satisfaction. These findings provide an outlook on the program’s feasibility and potential benefits.

Open-door policies in psychiatric wards are increasingly recommended as a means to reduce coercion and enhance patient autonomy. However, evidence that integrates patient perspectives on ward openness and related safety measures remains limited. Traditional qualitative approaches often lack the breadth to fully capture the complexity of these views. We hypothesized that patients would prefer open-door treatment and hold a critical view of locked-ward environments, emphasizing autonomy and dignity in care. This study aims to systematically explore psychiatric patients' perspectives on open-door versus locked-ward treatment, identifying key themes and quantifying preferences within a large clinical sample. A hybrid questionnaire survey was conducted in September 2023 at the University Psychiatric Clinics (UPK) Basel. The survey examined psychiatric service usage and integrated key factors from a meta-review, including ward relationships, environment, autonomy, legal status, coercion, care entitlement, and expectations at admission and discharge. The final sample comprised 604 patients (response rate 19.1%) drawn from an initial pool of 3212 former inpatients. A text mining approach using latent Dirichlet allocation, a Bayesian topic modeling technique, was applied to analyze open-ended responses and identify latent thematic structures. The majority of respondents (347/544, 63.8%) rated open-door treatment as \"very important\" (10 out of 10 on a Likert scale). In contrast, only 21.0% (127/552) of participants were willing to accept voluntary treatment in locked wards, with 70.4% (425/552) explicitly rejecting this option. Logistic regression indicated that younger patients were significantly more likely to accept locked ward treatment (β=-.18, P=.04), while patients diagnosed with mood disorders (ICD-10 [International Statistical Classification of Diseases and Related Health Problems, Tenth Revision] F3) showed a trend toward lower acceptance (β=-.42, P=.08). Gender and other diagnoses were not significant predictors. Latent Dirichlet allocation identified 5 key topics within patient narratives, which hierarchical clustering grouped into 2 overarching themes: Restriction and Institutionalization, characterized by terms indicating confinement, loss of control, and social isolation; and Autonomy and Self-Determination, which emphasizes patients' desire for freedom, control over daily life, and access to nature and outdoor spaces. This study provides robust evidence that psychiatric patients overwhelmingly prioritize open-door policies, linking them to enhanced autonomy, trust, and therapeutic engagement. The thematic analysis highlights the psychological and social costs of locked wards and the critical need for flexible, patient-centered care models. Younger age and diagnostic category influence willingness to accept locked settings, suggesting the need for tailored approaches. Institutions aiming to implement open-door policies should consider these preferences alongside adequate staffing, therapeutic programming, and environmental modifications to foster autonomy while maintaining safety. Integrating patient perspectives in policy design may enhance treatment satisfaction and clinical outcomes.