Depressive symptoms remaining after antidepressant treatment increase the risk of relapse and recurrence. We aimed to analyze the distribution and main drivers of remaining symptoms in patients with a major depressive episode.

Two independent samples of 8,229 and 5,926 patients from two large naturalistic studies were retrospectively analyzed. DSM-IV criteria for major depressive episodes were assessed during two face-to-face visits with clinicians: before the prescription of a new antidepressant, and after 6 weeks of treatment. The Hospital Anxiety and Depression Scale (HADS) was used to assess baseline severity of anxiety and depression.

In both samples, two clusters of remaining symptoms were observed. The first cluster encompassed symptoms related to a negative emotional and cognitive bias and was specifically driven by the baseline severity of depression. The second cluster encompassed neurovegetative symptoms and was specifically driven by the baseline severity of anxiety.

The baseline anxiety-depressive balance of patients could be considered to adapt the treatment, focusing on emotional and cognitive symptoms with patients with high baseline severity of depression, and neurovegetative symptoms with patients with high baseline anxiety severity.

Electroconvulsive therapy (ECT) is a safe and effective treatment for several major psychiatric conditions, including treatment-resistant depression, mania, and schizophrenia; nevertheless, its use remains controversial. Despite its availability in some European countries, ECT is still rarely used in others. This study aims to investigate the experiences and attitudes of early career psychiatrists (ECPs) across Europe towards ECT and to examine how their exposure to ECT influences their perceptions.

In Europe, a cross-sectional survey was conducted among ECPs, including psychiatric trainees and recently fully qualified psychiatrists.

A total of 573 participants from 30 European countries were included in the study, of whom more than half (N = 312; 54.5%) received ECT training. Overall, ECPs had a positive attitude towards ECT, with the vast majority agreeing or strongly agreeing that ECT is an effective (N = 509; 88.8%) and safe (N = 464; 81.0%) treatment and disagreeing or strongly disagreeing that ECT was used as a form of control or punishment (N = 545; 95.1%). Those who had received ECT training during their psychiatry training were more likely to recommend ECT to their patients (p < 0.001, r = 0.34), and held more positive views on its safety (p < 0.001, r = 0.31) and effectiveness (p < 0.001, r = 0.33). Interest in further education about ECT was moderately high (modal rating on Likert scale: 4, agree), irrespective of prior training exposure.

ECT training is associated with more favorable perceptions of its safety and effectiveness among ECPs. There is a general willingness among ECPs to expand their knowledge and training on ECT, which could enhance patients’ access to this treatment.

Postpartum anxiety (PPA) symptoms have harmful effects on child development and mother–infant interactions. Accordingly, in-depth knowledge of associated risk factors is crucial for prevention policies. This study aimed to estimate PPA symptom prevalence at 2 months and to identify associated risk factors in a representative sample of all women who gave birth in France in 2021, and in two subgroups: women with no postpartum depression (PPD) symptoms, and those with no history of mental health care.

Among the 12,723 women included in the representative French national perinatal survey 2021ENP, 7,133 completed the Edinburgh Postnatal Depression Scale (EPDS) self-administered questionnaire – including three anxiety-specific items (EPDS-3A) – at 2 months postpartum. We estimated the adjusted prevalence ratios (aPR) of PPA symptoms using Poisson regression models with robust variance.

PPA symptom prevalence at 2 months was 27.6% (95% CI [26.5–28.8]). Associated risk factors were: age ≤ 34 years (maximum aPR = 1.38 [1.22–1.58] obtained for persons aged 25–29 years vs. 35–39 years), poorer health literacy (1.15 [1.07–1.23]), a history of medical termination of pregnancy (1.32 [1.05–1.68]), psychological (1.31 [1.17–1.47]) or psychiatric (1.42 [1.24–1.63]) care history since adolescence, nulliparity (1.23 [1.12–1.35]), no weight gain or loss (1.29 [1.03–1.61] vs. 9–15 kg gain) or gain ≥23 kg (1.20 [1.00–1.43]) during pregnancy, ≥3 pregnancy-related emergency consultations (1.16 [1.03–1.31] vs. none), poor/good support during pregnancy, (1.16 [1.00–1.34] and 1.15 [1.05–1.26], respectively, vs. very good), sadness (1.52 [1.36–1.69]), anhedonia (1.48 [1.27–1.72]), or both (1.99 [1.79–2.21]) during pregnancy, not at all/not very satisfied with pain management during childbirth (1.16 [1.01–1.32] vs. quite/very satisfied). Similar risk factors were found in the ‘no PPD symptoms’ and ‘no history of mental health care’ subgroups.

Estimated PPA symptom prevalence at 2 months in our study sample was 27.6%. The risk factors we identified may guide future prevention policies.

Functional impairment is a major concern among those presenting to youth mental health services and can have a profound impact on long-term outcomes. Early recognition and prevention for those at risk of functional impairment is essential to guide effective youth mental health care. Yet, identifying those at risk is challenging and impacts the appropriate allocation of indicated prevention and early intervention strategies.

We developed a prognostic model to predict a young person’s social and occupational functional impairment trajectory over 3 months. The sample included 718 young people (12–25 years) engaged in youth mental health care. A Bayesian random effects model was designed using demographic and clinical factors and model performance was evaluated on held-out test data via 5-fold cross-validation.

Eight factors were identified as the optimal set for prediction: employment, education, or training status; self-harm; psychotic-like experiences; physical health comorbidity; childhood-onset syndrome; illness type; clinical stage; and circadian disturbances. The model had an acceptable area under the curve (AUC) of 0.70 (95% CI, 0.56–0.81) overall, indicating its utility for predicting functional impairment over 3 months. For those with good baseline functioning, it showed excellent performance (AUC = 0.80, 0.67–0.79) for identifying individuals at risk of deterioration.

We developed and validated a prognostic model for youth mental health services to predict functional impairment trajectories over a 3-month period. This model serves as a foundation for further tool development and demonstrates its potential to guide indicated prevention and early intervention for enhancing functional outcomes or preventing functional decline.

While omega-3 polyunsaturated fatty acids (PUFAs) have shown promise as an adjunctive treatment for schizophrenia and other psychotic disorders, the overall consensus about their efficacy across studies is still lacking and findings to date are inconclusive. No clinical trials or systematic reviews have yet examined if omega-3 PUFAs are associated with differential levels of efficacy at various stages of psychosis.

A systematic bibliographic search of randomized double-blind placebo-controlled trials (RCTs) examining the effect of omega-3 PUFAs as a monotherapy or adjunctive therapy versus a control group in adults and children at ultra-high risk (UHR) for psychosis, experiencing a first-episode psychosis (FEP), or diagnosed with an established psychotic disorder was conducted. Participants’ clinical symptoms were evaluated using total and subscale scores on validated psychometric scales.

No beneficial effect of omega-3 PUFAs treatment was found in comparison with that of placebo (G = −0.26, 95% CI −0.55 to 0.03, p = 0.08). Treatment of omega-3 PUFAs did not prove any significant improvement in psychopathology in UHR (G = −0.09, 95% CI −0.45 to 0.27, p = 0.63), FEP (G = −1.20, 95% CI −5.63 to 3.22, p = 0.59), or schizophrenia patients (G = −0.17, 95% CI −0.38 to −0.03, p = 0.10).

These findings confirm previous evidence that disputes the original reported findings of the beneficial effect of omega-3 PUFAs in schizophrenia. Furthermore, accumulative evidence of the use of omega-3 as a preventive treatment option in UHR is not supported, suggesting that the need for future studies in this line of research should not be promoted.

Substance use may be associated with the onset of psychotic symptoms, necessitating treatment for individuals with comorbid mental health and substance use disorders (MHD/SUD). COVID-19 significantly impacted individuals with MHD/SUD, reducing access to appropriate care and treatment. Changes in drug availability and prices during the pandemic may have influenced drug consumption. This study aimed to determine the frequency of substance-induced psychosis (SIP) during COVID-19 among individuals with MHD/SUD and to explore substance fidelity by following patterns of SIP over time.

In this retrospective cohort study, we analyzed data from all individuals with MHD/SUD registered in 2019–2021 in the Norwegian Patient Register. We used graphical approaches, descriptives, and Poisson regression to study occurrence and risk of SIP episodes in the three-year observation period. Sankey diagrams were used to examine trajectories of psychotic episodes induced by various substances.

Despite a decrease in individuals diagnosed with SIP during COVID-19, SIP episodes increased overall. We observed a decline in cannabis-induced psychosis, but a rise in SIP episodes involving amphetamines and multiple substances. Among individuals with recurrent SIP episodes, the psychosis was more often induced by different substances during COVID-19 (2020: RR, 1.50 [95% CI, 1.34–1.67]; 2021: RR, 1.30 [95% CI, 1.16–1.46]) than in 2019.

During COVID-19, fewer individuals were hospitalized with SIP, but those patients experienced more episodes. There were fewer cannabis-induced psychotic episodes, but more SIP hospitalizations caused by central stimulants and more SIP diagnoses caused by different substances, possibly reflecting changes in drug availability and pricing.

Emerging evidence suggests a potential association between “leaky gut syndrome” and low-grade systemic inflammation in individuals with psychiatric disorders, such as schizophrenia. Gut dysbiosis could increase intestinal permeability, allowing the passage of toxins and bacteria into the systemic circulation, subsequently triggering immune-reactive responses. This study delves into understanding the relationship between plasma markers of intestinal permeability and symptom severity in schizophrenia. Furthermore, the influence of lifestyle habits on these intestinal permeability markers was determined.

Biomarkers of intestinal permeability, namely lipopolysaccharide-binding protein (LBP), lipopolysaccharides (LPS), and intestinal fatty acid binding protein (I-FABP), were analyzed in 242 adult schizophrenia patients enrolled in an observational, cross-sectional, multicenter study from four centers in Spain (PI17/00246). Sociodemographic and clinical data were collected, including psychoactive drug use, lifestyle habits, the Positive and Negative Syndrome Scale to evaluate schizophrenia symptom severity, and the Screen for Cognitive Impairment in Psychiatry to assess cognitive performance.

Results revealed elevated levels of LBP and LPS in a significant proportion of patients with schizophrenia (62% and 25.6%, respectively). However, no statistically significant correlation was observed between these biomarkers and the overall clinical severity of psychotic symptoms or cognitive performance, once confounding variables were controlled for. Interestingly, adherence to a Mediterranean diet was negatively correlated with I-FABP levels (beta = −0.186, t = −2.325, p = 0.021), suggesting a potential positive influence on intestinal barrier function.

These findings underscore the importance of addressing dietary habits and promoting a healthy lifestyle in individuals with schizophrenia, with potential implications for both physical and psychopathological aspects of the disorder.

Cognitive impairment is a core feature of psychosis, which adversely affects global functioning and quality of life and has been consistently reported from the early stages of illness. Patients with first-episode psychosis (FEP) exhibit deficits in processing speed, short-term memory, attention, working memory, and executive functioning, which respond poorly to psychotropic drugs. Among non-pharmacological approaches, physical activity has shown promise in improving cognitive functioning in schizophrenia spectrum disorders. However, current evidence lacks specific data on individuals with FEP. In this review, we aim to explore the potential role of physical activity-based interventions in ameliorating the cognitive functions of people with FEP.

The literature search was conducted on PubMed, PsycINFO, and Web of Science in March 2024, identifying 127 de-duplicated records. One additional article was identified by screening the reference lists of the included studies. A total of six studies fulfilled the inclusion criteria and were reviewed. They all analyzed the effect of structured physical activity interventions on the cognitive functioning of patients with FEP.

Preliminary findings suggest that physical activity interventions enhance memory, attention, and executive functions of patients with FEP but not social cognition and motor function.

Study differences in sample characteristics, design, and intervention protocols prevent firm conclusions about the cognitive-boosting effects of the interventions in FEP. Further studies using more rigorous methodologies are needed to understand the durability of these effects and the underlying mechanisms.

The prevalence of mental health disorders has significantly increased in recent years, posing substantial challenges to healthcare systems worldwide, particularly primary care (PC) settings. This study examines trends in mental health diagnoses in PC settings in Catalonia from 2010 to 2019 and identifies associated sociodemographic, clinical characteristics, psychopharmacological treatments, and resource utilization patterns.

Data from 947,698 individuals without prior severe mental illness, derived from the Data Analytics Program for Health Research and Innovation (PADRIS), were analyzed for this study. Sociodemographic data, diagnoses, and resource utilization were extracted from electronic health records. Descriptive statistics, chi-square tests, Mann–Whitney tests, and a multivariate binary logistic regression were employed to analyze the data.

Over the study period, 172,112 individuals (18.2%) received at least one mental health diagnosis in PC, with unspecified anxiety disorder (40.5%), insomnia (15.7%) and unspecified depressive disorder (10.2%) being the most prevalent. The prevalence of these diagnoses increased steadily until 2015 and stabilized thereafter. Significant associations were found between mental health diagnoses, female sex, lower socioeconomic status, higher BMI, and smoking status in a multivariate binary logistic regression.

This study highlights a growing burden of stress-related mental health diagnoses in PC in Catalonia, driven by demographic and socioeconomic factors. These findings may be indicative of broader trends across Europe and globally. Addressing this rising prevalence requires innovative approaches and collaborative strategies that extend beyond traditional healthcare resources. Engaging stakeholders is essential for implementing effective, sustainable solutions that promote mental health in Catalonia and potentially inform similar initiatives worldwide.

Theoretical and empirical contributions have identified insula as key in addiction. However, anatomical modifications of the insula in addictive states, and their variations across substance use disorders (SUDs), remain to be specifically explored. We therefore explored the specificities and commonalities of insula gray matter (GM) alterations in severe alcohol use disorder (sAUD) and severe cocaine use disorder (sCUD).

We explored insula GM volume through a refined parcellation in 12 subregions (six bilateral): anterior inferior cortex (AIC), anterior short gyrus, middle short gyrus, posterior short gyrus, anterior long gyrus (ALG), and posterior long gyrus (PLG). Using a linear mixed model analysis, we explored the insula volume profiles of 50 patients with sAUD, 61 patients with sCUD, and 36 healthy controls (HCs).

In both sAUD and sCUD, we showed overall insular lower volume with a right-sided lateralization effect, and a major volume deficit in bilateral ALG. Moreover, differences emerged across groups, with higher left AIC and PLG volume deficits in sCUD compared to sAUD and HC.

We offered the first joint exploration of GM insular volumes in two SUD through refined parcellation, thus unveiling the similarities and dissimilarities in volume deficit profiles. Our results bring evidence complementing prior ones suggesting the core role of the right and posterior insula in craving and interoception, two crucial processes in addiction. Left AIC and PLG group differences also show that, while insula is a region of interest in SUD, sCUD and sAUD generate distinct insular profiles, which might parallel clinical differences across SUD.

A large increase in the rate of hospitalizations for adolescents and children with anorexia nervosa (AN) was observed during the coronavirus disease (COVID-19) pandemic. It is still not clear whether this was a temporary effect or whether the increased admission rates persist.

Data were retrieved from the largest health insurance in Germany comprising 2.5 million children between 9 and 19 y. All patients of this age group with a discharge diagnosis of typical (AN) and atypical AN (AAN) according to the International Classification of Diseases, Tenth Revision (ICD-10), were included. Admission rates per 10,000 person-years were computed separately by sex, age and type of AN for entire years from 2019 to 2022 and the first half of 2023 in relation to the entire number of insured persons of the same sex and age per year.

Two years after the final lockdown admission rates were still significantly higher in adolescent and childhood AN than in the pre-COVID-19 time. While admission rates declined for adolescents in 2023, those for children remained high, with an increase for girls of more than 40% compared with the rate before the pandemic (1.42 (CI 1.26, 1.60); p < 0.0001). The highest admission risk for AAN relative to the pre-COVID-19 period was observed in adolescents in the first half of 2023 (1.6; CI 1.34; 1.90; p < 0.0001).

Children appear to be especially vulnerable to the pandemic-associated disruptions. Clinicians should try to determine the ongoing effects of the pandemic and support early detection and treatment of AN to prevent its often lifelong consequences.

Since its introduction in the diagnostic manuals DSM-5 and ICD-11, the construct of personality functioning has gained increasing attention. However, it remains unclear which factors might predict improvement in personality functioning.

We examined a sample of 648 completed psychodynamic psychotherapies conducted by 172 therapists at the Heidelberg Institute for Psychotherapy. A machine learning approach was used to filter for variables that are relevant for the prediction of the improvement of personality functioning from a broad data set of variables collected at the beginning of each psychodynamic psychotherapy.

On average, we found an improvement of 0.24 (SD = 0.48) in the OPD-SQ. This corresponds to a medium effect in the improvement of personality functioning. Patients with initially high impairment experienced particularly large improvements. Overall, we found a large number of variables that proved to be predictive for the improvement of personality functioning. Limitations in social activity due to physical and emotional problems proved to be one of the most important predictors of improvement. Most of the effect sizes were small.

Overall, the improvement in personality functioning during psychotherapy is determined more by the sum of a large number of small effects than by individual variables. In particular, variables that capture social areas of life proved to be robust predictors.

Quality of life is decreased in bipolar disorders (BD) and contributes to poor prognosis. However, little is known about the causal pathways that may affect it. This study aimed to explore health-related QoL (HRQoL) in BD and investigate its relationship with cognition and psychosocial functioning.

This multicenter cross-sectional study used a neuropsychological battery to assess five cognition domains. Functioning was evaluated using global and domain-based tools, and health-related HRQoL was assessed using the EQ-5D-3L. Structural equation modeling was used to test whether the association between cognition and HRQoL would be mediated by functioning in BD while controlling for covariates such as residual depression, anxiety, antipsychotic medication, and psychotic features.

We included 1 190 adults with euthymic BD. The model provided a good fit for the data. In this model, the direct effect of cognition on HRQoL was not significant (β = − 0.03, z = −0.78, p = 0.433). The total effect of cognition on HRQoL was weak, albeit significant (β = 0.05, z = 3.6, p < 0.001), thus suggesting that cognition affected HRQoL only indirectly through functioning. Anxiety was associated with decreased functioning (β = −0.27, z = −7.4, p < 0.001) and QoL (β = −0.39, z = −11.8, p < 0.001).

These findings suggest that improving cognition may not directly lead to a higher HRQoL. Cognitive remediation is expected to improve HRQoL only through functioning enhancement. They also reveal the potential importance of functional remediation and reduction of comorbid anxiety symptoms in improving HRQoL in BD.

The “suicidal transition” from ideation to an act has become a specific topic of research. However, rates in the general population, variations across time and risk factors are unclear.

Data were collected from the phone survey Baromètre Santé among 18–75-year-olds in France. Seven independent samples interviewed between 2000 and 2021 (total N = 133,827 people; 51.3% females) were questioned about suicidal ideation and attempts over the previous 12 months. Transition was calculated as the weighted ratio of attempt on ideation 12-month rates.

Mean 12-month rates of suicidal ideation, attempts and transition were 4.7% (95% Confidence Interval (CI) (4.6–4.8)), 0.5% (95% CI (0.4–0.5)) and 7.7% (95% CI (6.8–8.6)), respectively. Transition rates varied between 4.5 and 11.9% across surveys. In multivariable analyses, higher transitions rates were associated with a previous suicide attempt (adjusted Odds Ratio (aOR) = 11.1 95% CI (7.9–15.6)); 18–25 vs 26–55-year-olds (1.8 95% CI (1.2–2.8)); lower vs higher income (1.7 95% CI (1.0–2.7); and lower vs higher professional categories (aOR around 1.9). No significant association was found with gender, education level, employment status, living alone, urbanicity, current major depression, daily smoking, weekly heavy drinking, cannabis use, and body mass index.

Most people with suicidal ideation do not attempt suicide. These findings emphasize the need to avoid generic terms such as “suicidality”, and to increase research on suicidal transition to improve prevention and prediction. They may also inform the organization of suicide prevention in the general population.

Clinical decision support systems (CDSS) based on machine-learning (ML) models are emerging within psychiatry. If patients do not trust this technology, its implementation may disrupt the patient-clinician relationship. Therefore, the aim was to examine whether receiving basic information about ML-based CDSS increased trust in them.

We conducted an online randomized survey experiment in the Psychiatric Services of the Central Denmark Region. The participating patients were randomized into one of three arms: Intervention = information on clinical decision-making supported by an ML model; Active control = information on a standard clinical decision process, and Blank control = no information. The participants were unaware of the experiment. Subsequently, participants were asked about different aspects of trust and distrust regarding ML-based CDSS. The effect of the intervention was assessed by comparing scores of trust and distrust between the allocation arms.

Out of 5800 invitees, 992 completed the survey experiment. The intervention increased trust in ML-based CDSS when compared to the active control (mean increase in trust: 5% [95% CI: 1%; 9%], p = 0.0096) and the blank control arm (mean increase in trust: 4% [1%; 8%], p = 0.015). Similarly, the intervention reduced distrust in ML-based CDSS when compared to the active control (mean decrease in distrust: −3%[−1%; −5%], p = 0.021) and the blank control arm (mean decrease in distrust: −4% [−1%; −8%], p = 0.022). No statistically significant differences were observed between the active and the blank control arms.

Receiving basic information on ML-based CDSS in hospital psychiatry may increase patient trust in such systems.

Suicidal behavior constitutes a multi-cause phenomenon that may also be present in people without a mental disorder. This study aims to analyze suicidal behavior outcomes in a sample of attempters, from a symptom-based approach.

The sample comprised 673 patients (72% female; M = 40.9 years) who attended a hospital emergency department due to a suicide attempt. A wide range of clinical factors (e.g., psychopathology symptoms, psychiatric diagnoses, impulsivity, acquired capability), was administered within 15 days after the index attempt. Nine psychopathology domains were explored to identify the profile of symptoms, using latent profile analysis. The relationship between the profile membership and suicide outcome (i.e., intensity of suicidal ideation, number of suicide behaviors, and medical injury derived from index attempt) was also studied, using linear and logistic regression.

Three psychopathology profiles were identified: high-symptom profile (45.02% of participants), moderate-symptom profile (42.50%), and low-symptom profile (12.48%). High-symptom profile members were more likely to show higher risk of non-suicidal self-injury, acquired capability for suicide, and more severe suicide behavior and ideation. On the other hand, a more severe physical injury was associated with low-symptom profile membership in comparison to membership from the other profiles (OR < 0.45, p < .05).

A symptom-based approach may be useful to monitor patients and determine the risk of attempt repetition in the future and potential medical injury, and to optimize prevention and intervention strategies.

Nearly two-thirds of individuals with a mental disorder start experiencing symptoms during adolescence or early adulthood, and the onset of a mental disorder during this critical life stage strongly predicts adverse socioeconomic and health outcomes. Subthreshold manifestations of autism spectrum disorders (ASDs), also called autistic traits (ATs), are known to be associated with a higher vulnerability to the development of other psychiatric disorders. This study aimed to assess the presence of ATs in a population of young adults seeking specialist assistance and to evaluate the study population across various psychopathological domains in order to determine their links with ATs.

We recruited a sample of 263 adolescents and young adults referring to a specialized outpatient clinic, and we administered them several self-report questionnaires for the evaluation of various psychopathological domains. We conducted a cluster analysis based on the prevalence of ATs, empathy, and sensory sensitivity scores.

The cluster analysis identified three distinct groups in the sample: an AT cluster (22.43%), an intermediate cluster (45.25%), and a no-AT cluster (32.32%). Moreover, subjects with higher ATs exhibited greater symptomatology across multiple domains, including mood, anxiety, eating disorder severity, psychotic symptoms, and personality traits such as detachment and vulnerable narcissism.

This study highlights the importance of identifying ATs in young individuals struggling with mental health concerns. Additionally, our findings underscore the necessity of adopting a dimensional approach to psychopathology to better understand the complex interplay of symptoms and facilitate tailored interventions.

This study investigates the effects of accelerated high-frequency repetitive transcranial magnetic stimulation (aHF-rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC), on locus coeruleus (LC) functional connectivity in the treatment of refractory medication-resistant major depression (MRD).

We studied 12 antidepressant-free refractory MRD patients, focusing on how aHF-rTMS affects the LC, a central component of the brain’s noradrenergic system and key to mood regulation and stress response.

A stronger decrease in LC functional connectivity following aHF-rTMS treatment resulted in better clinical improvement. We observed such LC functional connectivity decreases with several brain regions, including the superior frontal gyrus, precentral gyrus, middle occipital gyrus, and cerebellum. Moreover, our exploratory analyses hint at a possible role for E-field modeling in forecasting clinical outcomes. Additional analyses suggest potential genetic and dopaminergic factors influencing changes in LC functional connectivity in relation to clinical response.

The findings of this study underscore the pivotal role of the LC in orchestrating higher cognitive functions through its extensive connections with the prefrontal cortices, facilitating decision-making, influencing attention, and addressing depressive rumination. Additionally, the observed enhancement in LC-(posterior) cerebellar connectivity not only highlights the cerebellum’s role in moderating clinical outcomes through noradrenergic system modulation but also suggests its potential as a predictive marker for aHF-rTMS efficacy. These results reveal new insights into the neural mechanisms of refractory depression and suggest therapeutic targets for enhancing noradrenergic activity, thereby addressing both cognitive and psychomotor symptoms associated with the disorder.