Purpose Fetal alcohol spectrum disorders (FASD) are a group of neurodevelopmental disorders caused by intrauterine alcohol exposure. The disorder is associated with a variety of neurocognitive deficits and reduced everyday functioning. FASD is also associated with an increased risk of substance use and substance-related disorders. Methods Data were collected in a special diagnostic service for adults with FASD at a university linked psychiatric hospital. The Diagnostic Interview for Mental Disorders (Mini DIPS-OA) and parts of the European Addiction Severity Index (EUROP-ASI-R) were used for the structured diagnosis of differential and comorbidity diagnoses as well as substance use. Results The sample comprised 238 individuals (48.7% female). The 30-day prevalence for alcohol was 54.3% for men and 36.1% for women. The 12-month prevalence for cannabis use was 31.3% for men and 17.9% for women. A diagnosis of substance-related disorder was confirmed in 7.1% (men: 4.6%, women 2.5%). Alcohol-related disorders were present in 2.1% of men and 0.8% of women. Cannabis-related disorders were present in 0.8% of women and 1.7% of men. Conclusion Adults living with FASD reported consuming alcohol less frequently than the general German population. The prevalence of alcohol-related disorders was lower in the FASD sample than in the general German population. However, adults living with FASD are a vulnerable group when it comes to cannabis use. This could lead to a deterioration in cognitive abilities that are already impaired due to FASD. Comorbid substance-related disorders were diagnosed in less than one in ten people, which is significantly lower than the rates described in the literature to date.

Introduction:Esketamine nasal spray (EN) has been approved in Germany since 2021 for the treatment of treatment-resistant depression (TRD). Historically, the development of EN resulted from the positive results of randomized clinical trials on the off-label use of subnarcotic ketamine infusions (SKI) for TRD. How effective, tolerable, and safe is off-label SKI compared to EN? Methods:Narrativ review. Selective literature search in PubMed for clinical studies comparing SKI and EN for TRD. International guidelines for depression and the cost-effectiveness of SKI and EN in inpatient treatment were also considered. Results:Randomized direct comparative studies between EN and SKI are currently lacking. There is solid circumstantial evidence for the equivalence of acute treatment of TRD with SKI (usually 0.5 mg/kg body weight intravenously over 40-45 minutes) or EN (usually 56 or 84 mg per dose) in terms of effectiveness, safety, and tolerability: 9 meta-analyses (2 network meta-analyses) and 7 real-world studies (1 prospective, 6 retrospective comparative studies). SKI and subanesthetic esketamine infusions were also equivalent. A similar picture is emerging for serial treatment. Favorable tolerability and safety data have been available for EN for over 5 years (for serial SKI no such long-term observations). The USA and Canada have included off-label SKI as an alternative to approved EN in their guidelines for add-on treatment of TRD. For the German healthcare system, inpatient add-on treatment with SKI is about 2.3 to 3.8 times cheaper than with EN. Discussion and Conclusion:Based on the above evidence, we estimate that there is currently low to moderate confidence according to GRADE for assuming the equivalence in effectiveness, tolerability, and safety of add-on treatment of TRD with SKI or EN. A more accurate assessment will be possible in 2030 at the earliest, when the results of an ongoing direct comparative clinical study are available. When updating the guidelines, we recommend checking whether the off-label add-on SKI can be provisionally placed at the same level as the add-on EN in the TRD treatment algorithm, as is the case in the USA and Canada. We hereby also encourage (i) health insurance companies to cover the costs of add-on SKI and (ii) the German authorities to review the off-label prescribability of SKI for TRD by the Joint Federal Committee (GB-A).

Fetal alcohol spectrum disorders (FASD) are a group of neurodevelopmental disorders caused by alcohol exposure during pregnancy. FASD is associated with various neurocognitive disorders over the entire lifespan. Comorbid mental health disorders seem to be highly prevalent. Suicide attempts and substance use as well as substance use disorders are also associated with FASD in adults. However, previous studies report small or very selective samples. Little is known about gender differences in larger samples of adults with FASD. Structured clinical interviews based on DSM-5 diagnostic criteria were administered for the diagnosis of mental health disorders, suicidality, and substance use including substance-related disorders. Data was analyzed separately for men and women to identify gender differences. The sample consisted of 238 adults (51.3

Abstract Given the large numbers of stimulant NPS having recently been identified from web crawler activities, this chapter comments on the pharmacological, clinical pharmacological, toxicity, and acute/chronic treatment/management issues pertaining to a range of novel stimulants, including psychedelic phenethylamines, novel amphetamine-like molecules, synthetic cathinones, synthetic cocaine analogues, and methylphenidate-like new psychoactive substances (NPS). The online market of NPS is developing much more rapidly than academic research, and a range of novel molecules are consistently offered to vulnerable customers. One of the main issues that has emerged relates to the possibility of intense, acute and chronic, medical and psychopathological consequences of ingesting NPS stimulants. Future NPS-related tutoring activities will allow clinicians to better understand the complex pharmacological and toxicological issues related to the ingestion of these molecules, which in turn would reduce the negative social impact of NPS misuse, unnecessary hospital admissions, and avoidable deaths.

Abstract Cerebrospinal fluid amyloid beta 42, total tau, and phosphorylated tau 181 are well accepted markers of Alzheimer’s disease. These biomarkers better reflect disease pathogenesis compared to clinical diagnosis. Here, we perform a genome wide association study meta-analysis including 18,948 individuals of European ancestry and identify 12 genome-wide significant loci across all three biomarkers, eight of them novel. We replicate the association of biomarkers with APOE , CR1 , GMNC/CCDC50 and C16orf95/MAP1LC3B . Novel loci include BIN1 for amyloid beta and GNA12, MS4A6A, SLCO1A2 with both total tau and phosphorylated tau 181, as well as additional loci on chr. 8, near ANGPT1 and chr. 9 near SMARCA2 . We also demonstrate that these variants have significant association with Alzheimer’s disease risk, disease progression and/or brain amyloidosis. The associated genes are implicated in lipid metabolism independent of APOE , coupled with autophagy and brain volume regulation driven by total tau and phosphorylated tau 181 dysregulation.

ABSTRACT Background and Aims The increase in the use of gabapentinoids in the treatment of patients with chronic non‐cancer pain (CNCP) has drawn attention to the possibility of substance use disorder (SUD) due to gabapentinoids. Systematic literature reviews have provided evidence of the risk of SUD due to gabapentinoids within substance‐using populations. Despite concerns, prescription rates of gabapentinoids continue to increase in many countries, such as the USA, the UK, and Germany. Gabapentinoids are frequently prescribed off‐label for chronic pain regardless of neuropathic pain diagnosis, increasing the risk for problematic use. A recent literature review suggests that there is a potential for SUDs in CNCP, but robust data focusing specifically on this population is lacking. The present study aims to address this by investigating SUD due to gabapentinoids in a cohort of patients with CNCP. Methods This study employs an anonymous, self‐reported questionnaire‐based cross‐sectional design. It was conducted among CNCP patients in n = 11 general practitioner practices across two regions of Germany. A total of 93 adult patients with CNCPs who were treated with gabapentinoids were included in the final analysis. The questionnaire utilized was based on validated and established diagnostic instruments, including questions aligned with the DSM‐5. Results The data revealed a prevalence of 26.9% (n = 25) for at least a mild SUD in the sample, including 5.4% with severe SUD. Logistic regression with sociodemographic, pain‐related, and psychological variables revealed that male sex was a statistically significant predictor of SUD due to gabapentoids (Exp(B) = 3.97, p < 0.05; CI: 1.40–11.26). This analysis is limited by sample size and self reported data. Conclusion The results suggest a relevant risk for SUDs due to gabapentinoids in CNCP patients. Special care should be taken when prescribing gabapentinoids to patients with CNCP. Male sex as a predictor of SUD due to gabapentinoids should be further investigated.

While the somatic effects of obesity are increasingly well understood, growing evidence indicates that there is a cognitive effect such as a decline in episodic memory. Studies in animals revealed an association between obesity, memory impairment and neurotransmitters such as γ-aminobutyric acid (GABA) and glutamate. In the present study we aimed to assess the relation of body mass index (BMI) as indicator of overwight/obesity, memory and GABA / glutamate concentrations in the medial prefrontal cortex (mPFC) and precuneus in human subjects aged 19 to 41 years. We found that memory performance is predicted by mPFC GABA concentration in individuals with a low and a moderate BMI, but not in individuals with a high BMI (> 26) indicating overweight/obesity. MPFC glutamate and precuneus GABA/ glutamate levels appeared to be not related to the association between BMI and memory performance. Our findings suggest that clinically relevant overweight/obesity affects GABAergic processes in the frontal cortex and is related to lower memory performance in a group of young and middle-aged human subjects.

Background: Sexualized substance use (SSU) describes the use of psychotropic substances in the context of sexual activity. Less is known about the role of sexualized substance use among individuals with substance use disorders (SUD) and its effect on the course of the disorder, e.g., regarding relapses after abstinence. Methods: A convenience sample of individuals undergoing SUD rehabilitation in Germany was surveyed. A questionnaire asked about SSU, sex as a risk factor for relapse, and the importance of sexuality in treatment. Results: N = 490 (30.1% female) participated; 55% of men and 63% of women reported SSU, and 56.5% of heterosexual and 82.9% of homosexual men reported SSU (p < 0.017; r = 0.20). Stimulant users are more likely to report SSU than alcohol (p < 0.001) and sedative users (p < 0.001; r = 0.296 and r = 0.261). Furthermore, 15% of women and 18% of men consider sexual activity a risk factor for relapse; homosexual men (65%) consider it significantly more often than heterosexual men (14%), while 41.2% of heterosexual women and 55% of homosexual women consider it a factor. Additionally, 27.4% of heterosexual and 69.4% identified sexuality as an important topic for therapy, while 19.8% of heterosexual women, 30% of homosexual women, 13.5% of heterosexual men, and 47.2% of homosexual men reported that sexuality had been addressed in their therapy. Conclusions: SSU was reported by individuals with a SUD who were undergoing rehabilitation treatment. Furthermore, patients consider sexual activity as a potential risk factor for relapse, with this being particularly the case for stimulant users. The topic of sexuality is highly important for patients and should, therefore, be given greater consideration in therapy in the future.

Neuroinflammation is a central feature of Alzheimer's disease (AD), yet the mechanisms linking inflammatory protease systems to disease pathology remain incompletely understood. The kallikrein-kinin system (KKS), a major source of bradykinin, has been associated with AD mainly at the peripheral level, but its regulation within the human brain remains largely unexplored. Here, we investigated KKS activity in human AD tissue and a transgenic mouse model, with a particular focus on serine protease kallikrein-8 (KLK8). We observed that both bradykinin and bradykinin B1 receptor levels are increased in the hippocampus of AD patients, with a pronounced upregulation in females. In the TgCRND8 mouse model of AD, hippocampal bradykinin levels were also elevated, while heterozygous KLK8 knockout ameliorated this pathological effect, supporting a functional contribution of KLK8. Analysis of kallikrein expression revealed a selective increase in KLK8 in the AD hippocampus, whereas the canonical kinin-generating proteases, tissue kallikrein (KLK1) and plasma kallikrein (KLKB1), remained unchanged. In vitro cleavage assays demonstrated that recombinant human KLK8 can process both low- and high-molecular-weight kininogens, and functional assays confirmed that KLK8 increases bradykinin levels in human hippocampal tissue and plasma, an effect that was blocked by a KLK8-neutralizing antibody. Together, these findings identify KLK8 as a previously unrecognized modulator of the KKS in the AD brain. Our data support a model in which elevated KLK8 contributes to dysregulated bradykinin production and B1R signaling, providing a mechanistic link between KLK8 activity and neuroinflammation in Alzheimer's disease.

Background: Child abuse (CA) is a well-established risk factor for suicidal ideation (SI) and suicidal behaviour (SB). However, only few studies have investigated the impact of CA on the persistence of SI over time. Those existing studies have used varying operationalizations to measure the persistence of SI, leading to inconsistent findings.Objective: The aim of this study is to examine the persistence of SI by integrating prospective ecological momentary assessments (EMAs) with retrospective structured interviews within one clinical sample.Method: Patients admitted to psychiatric hospitals following an acute suicidal crisis (n = 75) or recent suicide attempt (n = 107) were assessed shortly after admission and then, after discharge, engaged in a 3-week EMA (EMA phase 1), followed by a 6-month EMA period (EMA phase 2). SI was measured using the Self-Injurious Thoughts and Behaviors Interview at baseline and via EMA prompts during both phases. Persistence was indicated by the number of episodes and repeated reports of SI. Multiple regression analyses were conducted to examine the influence of CA on the persistence of SI.Results: Retrospective interview data showed that CA predicted the persistence of SI over the year before a suicidal crisis or suicide attempt (β = .22, t = 2.67, p = .008). Prospective EMA data indicated that CA was associated with greater persistence of passive SI during EMA phase 1 (β = .20, t = 2.19, p = .030) and with higher persistence of active SI in EMA phase 2 (β = .21, t = 1,99, p = .050).Conclusions: This study shows that CA is linked to greater persistence of SI across different methods and time points. It also highlights the importance of distinguishing between passive and active SI when examining persistence.

Zusammenfassung Unregulierte Substanzen unterliegen bei Herstellung und Verkauf keiner nachvollziehbaren Qualitätskontrolle. Für Konsumierende bestehen daher erhebliche Unsicherheiten hinsichtlich der Herkunft der erworbenen Substanzen, deren Wirkstoff sowie die Konzentration und Beimengungen, die ihrerseits psychoaktive und/oder toxische Wirkungen haben können. Dies bedingt ein erhöhtes Risiko für gesundheitliche Beschwerden, Vergiftungen und Todesfälle. Drug Checking fungiert als schadensminimierender Ansatz und ermöglicht es Nutzer*innen, Substanzen auf Qualität und Zusammensetzung testen zu lassen und eine informierte Entscheidung bezüglich ihres Konsums zu treffen. In zahlreichen Ländern haben sich inzwischen Drug Checking Angebote etabliert. Der Bundesgesetzgeber hat im Jahr 2023 den Bundesländern ermöglicht, Modellvorhaben zum Drug Checking zu implementieren. Voraussetzung hierfür sind entsprechende Landesverordnungen. Im Rahmen dieser Übersichtsarbeit soll der Stand der internationalen Versorgungspraxis und die Evidenz des Drug Checkings dargestellt werden.

Introduction:The fundamental association between unemployment and health problems has long been recognized. This raises questions about the most common illnesses among unemployed people and any resulting loss of productivity. The aim of the study is to present the 20 most common illnesses among unemployed people examined by the Medical Service (ÄD) of the Federal Employment Agency (BA) and to analyze any resulting loss of productivity for the (general) labor market and other associated factors. Methods:For this multi-year cross-sectional study study (2016-2021), the 20 most common diseases/ diagnoses from all (n=4,249,028) social medical assessments conducted by the Medical Service (ÄD) of the Federal Employment Agency were analyzed, along with the respective primary and secondary diagnoses based on ICD-10 codes and associated factors (gender, age, performance profile) from the ÄD databases. For data analyses descriptive statistics and binary logistic regression were used. Results:Of the approximately 500,000 social medical assessments carried out by the MS each year, nearly all clients (2016: 90.1%; 2021: 99.5%) received a diagnosis. Depressive episodes (n=416,531; 10.2%), recurrent depressive disorders (n=415,651; 10.1%) and (other) anxiety disorders (n=169,112; 4.6%) belong to the most frequent diagnoses. Among the non-psychiatric disorders, back pain (n=243,389; 6.6%), (primary) hypertension (n=146,316; 4.0%) and (other) disc damage (n=91,861; 2.2%) occupy the top three places. Age and gender differed significantly depending on the disease. Overall, 33.9% of all assessed clients were classified as incapacitated (<3 hours/day), with mental illnesses being the most common reason for this, with schizophrenia being the most common at 63.6%). Discussion:Mental disorders are particularly common among people who are unemployed. This should be taken into account in medical care and labor market integration to overcome both: unemployment and (psychiatric) illness. Keywords: Unemployment, illnesses, epidemiology, inability to work, long term unemployment.

BACKGROUND:Patients with Major Depressive Disorder (MDD) exhibit biased information processing. This study investigates the clinical and neural efficacy of a cognitive bias modification (CBM) training in patients and healthy control (HCS), fostering processing of positive emotion stimuli. METHODS:In a single-blind randomised controlled trial (DRKS00029756), MDD outpatients and HCS, aged 18-60 years, were randomised to positivity training (PT) or control training (CT). Randomisation was carried out by study assistants, blinding researchers. Participants underwent 10 tablet-based dot-probe sessions over 14 days. PT implicitly redirected attention toward positive stimuli to improve depressive symptoms. Primary outcome was pre and post-training EEG-derived Early Posterior Negativity (EPN), investigating neural sensitivity towards positive stimuli. Secondary clinical outcomes included changes in depression symptoms. FINDINGS:From February 2023 to October 2024, 240 participants were included (119 MDD; 121 HCS). 62 MDD and 61 HCS underwent PT; 57 MDD and 60 HCS received CT. In MDD, EPN to positive high arousal stimuli revealed an interaction between time (pre/post) and training (PT/CT), F(1,97) = 5.017, p < 0.028, η2 = 0.049. The between-treatment difference was 1.65 μV, 95% CI [0.19, 3.11]. EPN amplitudes shifted towards negativity in PT and positivity in CT. Depression symptom decreased from pre to post and from pre to follow-up. With respect to adverse events, one patient in the control training was regularly admitted to hospital. INTERPRETATION:CBM positivity training was associated with neural changes in MDD, supporting its potential to target pre-attentive positive emotion processing. Further EEG follow-up and higher stimulus contrasts in the training conditions may clarify clinical relevance. FUNDING:Funded by DFG (ID: 507720021).

Objective In this study, the success of inpatient qualified withdrawal treatment in an age-specific setting was compared with that in a mixed-age setting. Methods 175 patients (137 male, average age 59.4 years) with different substance-related disorders were examined. Treatment success was defined as the regular termination of treatment. Results During the observation period significantly more elderly patients were admitted to the age-specific setting than to the mixed-age setting. Regardless of the treatment setting, more than 80% of patients completed withdrawal treatment regularly. For the overall group as well as for the subgroup of opioid dependent persons in maintenance treatment, withdrawal treatment was significantly more successful in an age-specific setting. Conclusion The demographic development and these results speak in favor of the implementation of age-specific services for older patients with substance-related disorders.

BACKGROUND:The use of psychoactive substances is associated with the risk of somatic complications requiring treatment. Psychiatric consultations can be requested in this context. AIM:Description of physical and psychological complications of acute and chronic use of various drugs (except alcohol and benzodiazepines), and the procedure for consultations. MATERIALS:Narrative literature review. RESULTS:Severe physical and psychological complications of drug use can also occur with sporadic use. New psychoactive substances (NPS) in particular are known to have severe side effects compared to plant-based drugs with similar effects. Sporadic drug use, harmful use, and dependence must be differentiated diagnostically. Somatic complications of chronic use usually occur with dependent use, especially with intravenous drug administration. Depending on the individual case, recommendations for abstinence, safer use, or motivational interventions to take up a subsequent support program should be made. This requires precise knowledge of the local treatment network for drug users. Medication is used to alleviate withdrawal symptoms symptomatically. Potential complications must be taken into account during withdrawal treatment, e.g. withdrawal delirium and seizures in the case of GABA-ergic drugs. Maintenance treatment is the therapy of choice for opioid addicts. CONCLUSION:Addiction psychiatry consultations should not only offer help in the management of current clinical problems, but should also show those affected the possibilities of further care and treatment.

BACKGROUND/OBJECTIVES:According to a diathesis-stress model for the development of mental illness, it is assumed that, in addition to pre-existing individual vulnerability, the occurrence of acute strains is an etiological factor. The SARS-CoV-2 pandemic was a collective massive stressor, which could predispose to a first manifestation of a mental disorder or the exacerbation of a pre-existing mental disorder. The aim of this study was to investigate the effects of the pandemic on the cohort of patients admitted to hospital during the first year of the pandemic. METHODS:Patients admitted to inpatient treatment in a university psychiatric hospital in an urban region from April 2020 to March 2021 were interviewed using a systematic questionnaire assessing individual stress factors in the context of the pandemic. On the basis of the interview, clinical practitioners rated the influence of the pandemic on the admission. RESULTS:Six hundred and forty-five patients were interviewed. Only 6.4% showed a strong influence of the pandemic on inpatient admission. This group was characterized by a comparatively high level of socioeconomic functioning. Additionally, the majority of this group had a pre-existing mental disorder. CONCLUSIONS:For the majority of patients, the pandemic had only a minor influence on their hospitalization; only for 6.4% was a high impact of the pandemic reported. We hypothesize that this group's higher socioeconomic functioning in addition to a pre-existing mental disorder made them vulnerable to pandemic-associated limitations. These data confirm a complex diathesis-stress model for the development of mental illness in the context of an acute collective stressor.

AIM:From a public health perspective, the provision of information on low-risk consumption is highly relevant for behavior with addictive potential and negative health, psychological or social consequences. This article provides an overview of the effectiveness and benefits of such recommendations for alcohol, cannabis, gambling and gaming. METHODS:An overview based on a narrative review. RESULTS:The recommendation for alcohol consumption limits can no longer be upheld on the basis of current evidence. Instead, abstinence is recommended. In the case of cannabis, it is currently not possible to determine thresholds for the frequency and quantity of use with regard to consequential harms. Current recommendations, therefore, relate to "safer use". With respect to gambling, initial but not yet reliable empirical data are available. Thresholds of varying consumption dimensions, such as the involvement in different forms of gambling, the regularity or duration of gambling as well as the amount of money spent, must be taken into account. There are no evidence-based consumption recommendations for gaming. Furthermore, a consideration of the media content that goes beyond pure usage time is essential before any recommendations can be derived. Overall, the effectiveness of recommendations depends on the perception and acceptance of the population. CONCLUSION:Recommendations for consumption are based on the available evidence and must be continuously reviewed and adapted, as can be seen from the example of alcohol consumption. Behavioral recommendations must be communicated in a suitable form so that they are understood without bias and are accepted by the general population.

As 700,000 people per year commit suicide worldwide, improvements in suicide prevention and the prediction of suicide attempts or suicide in clinical care are mandatory. This systematic review aims to examine heart rate (HR) and heart rate variability (HRV) as risk factors for the development of suicidal thoughts and behaviour in clinical and non-clinical populations. The systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA). We will retrieve relevant literatures across the following databases: PubMed, PsycINFO, Cochrane Library and Web of Science. Additionally, we will manually search the reference lists of all relevant articles. If studies are published or translated in English and measure HRV or HR and suicidal thoughts or behaviour, they will be included. Two reviewers will independently complete the article selection, data extraction and risk of bias ratings. A third reviewer will resolve disagreements. Tabular and narrative synthesis will be done accordingly and a risk of bias assessment will be conducted by the QUIPS (Quality In Prognosis) tool. This systematic review will present evidence from which conclusions can be made regarding the relationship between HRV and HR and suicidal thoughts and behaviour. By identifying risk factors associated with suicidality and differentiating between factors for suicidal thoughts versus behaviour, this review will potentially contribute theoretically to our understanding of the causal factors involved in influencing increasing levels of suicidality. This is a systematic review of published literature and thereby ethical approval was not sought. Results will be disseminated through conferences and publications in relevant peer-reviewed journals. The results will have important implications for risk prediction for suicidal thoughts and behaviour. The protocol follows the PRISMA guidelines (Page et al.,BMJ 372:n71,2021). Thus, two reviewers will perform data extraction and risk of bias evaluation separately. We will exclude non-English translated or published studies, which might be a limitation and bias against non-English-speaking countries. PROSPERO registration number: CRD42023460068

Non-pharmacological interventions are increasingly recognized as first-line therapies for managing dementia symptoms alongside pharmacologic strategies. Among these, therapy gardens and horticultural interventions have emerged as promising adjunctive approaches. This pilot study aimed to evaluate the effects of a six-month dementia-friendly therapy garden intervention on psychological well-being, specifically depression levels, and to determine whether baseline dementia severity predicts treatment success. The study was conducted in a real-world setting, with a final sample of 28 dementia patients. Unlike previous studies, this intervention incorporated multimodal stimulation, including sensory, motor, and cognitive elements. Results indicated a significant reduction in depression, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) after six months of intervention (p <.05). However, depression scores assessed using the Hamilton Depression Rating Scale (HAM-D) showed only a trend toward improvement but did not reach statistical significance. No improvements were observed at the three-month mark, suggesting that sustained engagement is necessary for measurable benefits. Cognitive function, as assessed by dementia severity, did not show significant improvement, and dementia severity at baseline was not a significant predictor of treatment response. These findings underscore the potential of dementia-friendly therapy gardens to provide meaningful psychological benefits by significantly reducing depression over time. Notably, even individuals with more advanced dementia benefited, challenging the prevailing notion that non-pharmacological interventions are primarily effective in early disease stages. These results highlight the need for further research on the long-term effects and mechanisms underlying garden-based interventions in dementia care.