Investigating brain structure and tDCS response in obsessive-compulsive disorder.

Obsessive-Compulsive Disorder (OCD) is characterized by intrusive thoughts and repetitive behaviors, with associated brain abnormalities in various regions. This study explores the correlation between neural biomarkers and the response to transcranial Direct Current Stimulation (tDCS) in OCD patients. Using structural MRI data from two tDCS trials involving 55 OCD patients and 28 controls, cortical thickness, and gray matter morphometry was analyzed. Findings revealed thicker precentral and paracentral areas in OCD patients, compared to control (p < 0.001). Correlations between cortical thickness and treatment response indicated a significant association between a thinner precentral area and reduced Yale-Brown Obsessive Compulsive Scale (YBOCS) scores (p = 0.02). While results highlight the complexity of treatment response predictors, this study sheds light on potential neural markers for tDCS response in OCD patients. Further investigations with larger datasets are warranted to better understand the underpinnings of these biomarkers and their implications for personalized treatment approaches.

Testing an Imagery Rescripting Exercise Targeting Fear of Self.

A feared possible self refers to the unwanted characteristics that a person may possess or develop. We tested an experimental paradigm to target fear of possible self using imagery rescripting. A student sample (n = 91), with moderate obsessive-compulsive disorder symptoms, engaged in written and audio-guided exercises to evoke episodic future mental imagery that represented their feared possible self. Participants were then randomized between imagery rescripting or neutral imagery control tasks. The results revealed no difference between conditions in fear of self or general obsessional beliefs following the manipulation. State anxiety and the urge to neutralize the imagery reduced more in the control condition than in the rescripting condition. These findings suggest that the current paradigm is emotionally engaging but not effective at addressing fear of self as measured. Methodological improvements such as removing a written component of the rescripting task and idiosyncratic measuring of fear of self are proposed.

Scoping Review of Acceptance and Commitment Therapy for Obsessive-Compulsive Disorder in Iran.

Acceptance and commitment therapy (ACT) for obsessive-compulsive disorder (OCD) has been found efficacious in randomized clinical trials (RCTs), but the two widely known RCTs were conducted within the United States with predominantly White samples. Research that evaluates treatments like ACT for OCD outside the typical Western cultures is needed. The current scoping review summarizes the key characteristics and findings from 18 RCTs that evaluated ACT for OCD in Iran. These RCTs are largely unknown in the broader scientific literature despite representing the vast majority of ACT for OCD trials, in part because the majority are published in Persian. The preponderance of RCTs treated participants in groups, and most protocols did not include exposure exercises. Of 18 trials, 5 were single sex. Use of selective serotonin reuptake inhibitors (SSRIs) was common with all participants on stable doses at pretreatment in many of the trials. Methodological quality was low to medium. ACT was inconsistent against nontraditional comparison conditions, slightly favorable to empirically validated treatments, and favorable compared with the waitlist and SSRIs. The process of change data indicated that ACT increased the psychological flexibility more than cognitive behavior therapy or SSRIs. These results highlight that findings on ACT for OCD from Western populations replicate and generalize to individuals in Iran. These findings also offer insights gained from studying ACT in Iran and significantly expand the literature based on ACT for OCD that can be integrated into scholarship by all researchers.

Investigating an Acceptance and Commitment Therapy-Based Exposure Therapy Intervention in Treatment-Refractory OCD and Related Disorders: Changes in Psychological Flexibility, Treatment Engagement, and Treatment Perceptions.

While exposure therapy is the most effective psychological treatment for obsessive-compulsive disorder (OCD), anxiety, and traumatic stress-related disorders, it is not universally effective, indicating a need for further treatment optimization. This study investigated a shift in approach to exposure therapy with 29 treatment-refractory adults in an OCD clinic not responding to standard treatment, comprising habituation-based exposure therapy. Participants completed standard exposure as a continuation of standard clinic treatment, followed by an acceptance and commitment therapy (ACT) consultation session to assess psychological inflexibility processes interfering with treatment progress, and then an ACT-based exposure targeting behavior change through increasing psychological flexibility. After each exposure, participants and independent raters reported levels of psychological flexibility, rituals, distress, treatment engagement, and treatment perceptions. We observed that the shift to ACT-based exposure was associated with greater psychological flexibility, treatment engagement, treatment acceptability, and treatment preference. These findings suggest that there may be situations where ACT-based exposure has particular utility.

Neurobiology of Obsessive-Compulsive Disorder from Genes to Circuits: Insights from Animal Models.

Obsessive-compulsive disorder (OCD) is a chronic, severe psychiatric disorder that has been ranked by the World Health Organization as one of the leading causes of illness-related disability, and first-line interventions are limited in efficacy and have side-effect issues. However, the exact pathophysiology underlying this complex, heterogeneous disorder remains unknown. This scenario is now rapidly changing due to the advancement of powerful technologies that can be used to verify the function of the specific gene and dissect the neural circuits underlying the neurobiology of OCD in rodents. Genetic and circuit-specific manipulation in rodents has provided important insights into the neurobiology of OCD by identifying the molecular, cellular, and circuit events that induce OCD-like behaviors. This review will highlight recent progress specifically toward classic genetic animal models and advanced neural circuit findings, which provide theoretical evidence for targeted intervention on specific molecular, cellular, and neural circuit events.

Early maladaptive schemas in autogenous and reactive subtypes of obsessive-compulsive disorder.

AIMS: The aim of this study is to identify early maladaptive schemas in patients with obsessive-compulsive disorder (OCD) and to determine the use of these schemas in OCD autogenous and reactive subtypes. METHODS: The study population included 40 healthy volunteers, and 90 patients diagnosed with OCD. The Yale-Brown Obsession-Compulsion Scale (Y-BOCS) was administered to the OCD group to determine the severity of the disorder, and the Y-BOCS Symptom Checklist was applied to determine the patients with autogenous (n = 37) and reactive (n = 53) subtypes of OCD. Young Schema Questionnaire-Short Form 3 (YSQ-SF3) scales were applied to all participants. RESULTS: When autogenous and reactive subtype groups of OCD were compared with each other, the schema domains of disconnection (p = 0.004), high standards (p = 0.008), other-directedness (p < 0.001) and the schema dimensions of failure (p < 0.001), emotional deprivation (p < 0.001), defectiveness (p = 0.007), approval seeking (p = 0.007) and punishment (p = 0.001) were found to be more dominant in the autogenous group. CONCLUSIONS: The findings of the study support that there are differences between autogenous and reactive subtypes of OCD in terms of dominant schemas. Therefore, its thought that the use of Schema Therapy methods in which schemas appropriate for subtypes are investigated in the treatment of OCD patients will contribute favorably to the treatment response.

Identifying subgroups of urge suppression in Obsessive-Compulsive Disorder using machine learning.

Obsessive-compulsive disorder (OCD) is phenomenologically heterogeneous. While predominant models suggest fear and harm prevention drive compulsions, many patients also experience uncomfortable sensory-based urges ("sensory phenomena") that may be associated with heightened interoceptive sensitivity. Using an urge-to-blink eyeblink suppression paradigm to model sensory-based urges, we previously found that OCD patients as a group had more eyeblink suppression failures and greater activation of sensorimotor-interoceptive regions than controls. However, conventional approaches assuming OCD homogeneity may obscure important within-group variability, impeding precision treatment development. This study investigated the heterogeneity of urge suppression failure in OCD and examined relationships with clinical characteristics and neural activation. Eighty-two patients with OCD and 38 controls underwent an fMRI task presenting 60-s blocks of eyeblink suppression alternating with free-blinking blocks. Latent profile analysis identified OCD subgroups based on number of erroneous blinks during suppression. Subgroups were compared on behavior, clinical characteristics, and brain activation during task. Three patient subgroups were identified. Despite similar overall OCD severity, the subgroup with the most erroneous eyeblinks had the highest sensory phenomena severity, interoceptive sensitivity, and subjective urge intensity. Compared to other subgroups, this subgroup exhibited more neural activity in somatosensory and interoceptive regions during the early phase (first 30 s) of blink suppression and reduced activity in the middle frontal gyrus during the late phase (second 30 s) as the suppression period elapsed. Heterogeneity of urge suppression in OCD was associated with clinical characteristics and brain function. Our results reveal potential treatment targets that could inform personalized medicine.

Serum Erythropoietin and Ischemic-Modified Albumin Levels in Adolescents with Obsessive-Compulsive Disorder.

Erythropoietin (EPO) has neuroprotective effects by increasing oxidative stress resistance and stabilizing redox balance. Ischemic-modified albumin (IMA) is a product of protein oxidation, and recent evidence suggests that IMA can be used as an indicator of oxidative damage. This study aimed to investigate serum EPO and IMA levels in obsessive-compulsive disorder (OCD) patients and to investigate the relationship between EPO and IMA levels and clinical variables such as disease duration and disease severity. A total of 68 adolescents (11-18 years old), including 35 OCD patients (18 males/17 females) and 33 healthy controls (14 males/19 females) without comorbid disorders matched for age, gender, and BMI, were included in the study. The enzyme-amplified chemiluminescence technique determined serum EPO levels, and serum IMA levels were determined by the spectrophotometric method. Serum EPO levels were lower in OCD patients compared to healthy controls (p = 0.002; Z = - 3.123), and serum IMA levels (ABSU) were significantly higher in the OCD group (p = 0.005). A significant positive correlation was found between IMA levels and the duration of OCD symptoms (p = 0.015, r = 0.409). The study's findings contribute to the growing body of evidence implicating inflammatory and oxidative processes in the pathogenesis of OCD. The potential of EPO and IMA levels as diagnostic biomarkers for OCD aligns with the ongoing efforts to identify reliable biological markers for the disorder. The positive correlation of IMA levels with the duration of OCD shows the importance of early detection of oxidative damage.

Does responsibility for potential harm attenuate the effects of repeated checking on metamemory and automatization?

BACKGROUND AND OBJECTIVES: Repeated checking results in large reductions in metamemory variables (confidence, details, and vividness). It has been suggested that the underlying mechanism is gradual automatization. At the same time, individuals with obsessive-compulsive disorder (OCD) are reluctant to automatize routine processes. The aim was to investigate whether high responsibility for potential harm, typical of OCD, would attenuate the effects of repeated checking on metamemory variables and automatization. METHODS: One hundred seventy-five participants were initially provided with a cover story that put the subsequent virtual checking task in a context of potential harm for not checking properly. Participants were randomly allocated to four experimental groups (varying high and low responsibility, relevant and irrelevant checking) and performed a virtual checking task repeatedly, using either identical stimuli (relevant checking) or different stimuli (irrelevant checking) between the first and final checking trial. Metamemory variables were rated on visual analogue scales, and response latencies were assessed to establish automatization. RESULTS: Larger reductions in metamemory variables following relevant checking compared to irrelevant checking replicated previous findings. High responsibility did not affect these results. Large reductions in response latencies across the checking trials (automatization) were also independent of the perceived responsibility. LIMITATIONS: We did not include individuals with OCD. CONCLUSIONS: Since responsibility did not influence the effects of repeated checking on metamemory variables, findings are consistent with the idea that automatization remains a plausible explanation of the effects of repeated checking on metamemory variables in individuals with OCD.

Effect of maternal obsessive-compulsive disorder (OCD) on feto-maternal outcomes: A systematic review and meta-analysis.

BACKGROUND: Mental health disorders in pregnant women have been related to unfavorable obstetric and neonatal outcomes. Obsessive-compulsive disorder (OCD) significantly distresses mothers and affects the maternal-infant bond. OBJECTIVES: The present meta-analysis and systematic review aimed to assess the association of maternal OCD with adverse feto-maternal outcomes. SEARCH STRATEGY: A systematic search was undertaken in the five databases-Cochrane, Embase, ProQuest, Web of Science, and PubMed-on September 5, 2023. SELECTION CRITERIA: Studies that included pregnant women with OCD in whom the feto-maternal outcomes were reported were included in the systematic review. DATA COLLECTION AND ANALYSIS: Two pass screening ("title-abstract screening" followed by "full-text review"), and data extraction by two authors independently using the Nested-Knowledge Auto living semi-automated systematic review platform was carried out. The decision for selected studies was reviewed by a third author. Of the 360 studies identified, eight were included for the meta-analysis. Meta-analysis was conducted using R software. MAIN RESULTS: Of the 24 maternal and neonatal adverse outcomes assessed, 11 were found to be associated with maternal OCD, notably pre-eclampsia (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.19-1.57), antepartum hemorrhage or placental abruption (OR 1.32, 95% CI 1.13-1.54), postpartum hemporrhage (OR 1.19, 95% CI 1.08-1.31), cesarean section delivery (OR 1.32, 95% CI 1.23-1.41), emergency cesarean section (OR 1.22, 95% CI 1.15-1.30), preterm birth (OR 1.41, 95% CI 1.21-1.64), low birth weight (OR 1.41, 95% CI 1.28-1.54), low Apgar score at 5 min (OR 2.37, 95% CI 1.32-4.27), neonatal hypoglycemia (OR 1.37, 95% CI 1.23-1.53), neonatal respiratory distress (OR 1.77, 95% CI 1.44-2.16), and major congenital malformations (OR 1.37, 95% CI 1.08-1.74). CONCLUSION: OCD in pregnant women might be associated with multiple adverse feto-maternal outcomes.

Deontological Guilt Mediates the Effects of Personality on the Symptoms of Romantic Relationship Obsessive Compulsive Disorder (ROCD).

Objective: Relationship obsessive-compulsive disorder (ROCD), a clinical variant of OCD, is associated with personality traits and guilt sensitivity. Previous studies have not investigated whether the guilt associated with ROCD stems from deontological or altruistic morality. The main aim of the present study was to explore the differentiated impact of deontological and altruistic guilt on ROCD symptoms in romantic relationships. The study also aimed to test the mediating role of guilt in the relationships between personality traits and ROCD symptoms. Method: Through linear regressions and path analysis, we examined the results of an online survey administered to 659 emerging adults, assessing the Big-5 personality traits, ROCD symptoms, and the moral orientation of guilt feelings (deontological/altruistic). Results: Results revealed the negative influence of agreeableness and emotionality on ROCD symptoms. Moral dirtiness, as a facet of deontological moral orientation, was found to mediate the effects of personality predictors on relationship-centred but not on partner-focused ROCD symptoms, providing support for differential diagnosis. Conclusions: These findings provide a clearer understanding of the cognitive determinants that sustain ROCD symptoms and offer evidence on associated personality traits. These results may represent a valuable source of knowledge for researchers as well as clinical therapists dealing with ROCD symptoms, couple disorders, and sexual dysfunction.

Drug repurposing for obsessive-compulsive disorder using deep learning-based binding affinity prediction models.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disease in which patients suffer from obsessions compelling them to engage in specific rituals as a temporary measure to alleviate stress. In this study, deep learning-based methods were used to build three models which predict the likelihood of a molecule interacting with three biological targets relevant to OCD, SERT, D2, and NMDA. Then, an ensemble model based on those models was created which underwent external validation on a large drug database using random sampling. Finally, case studies of molecules exhibiting high scores underwent bibliographic validation showcasing that good performance in the ensemble model can indicate connection with OCD pathophysiology, suggesting that it can be used to screen molecule databases for drug-repurposing purposes.

The impact of illness duration on brain activity in goal-directed and habit-learning systems in obsessive-compulsive disorder progression: A resting-state functional imaging study.

It is increasingly evident that structural and functional changes in brain regions associated with obsessive-compulsive disorder (OCD) are often related to the development of the disease. However, limited research has been conducted on how the progression of OCD may lead to an imbalance between goal-directed and habit-learning systems. This study employs resting-state functional imaging to examine the relationship between illness duration and abnormal brain function in goal-directed/habitual-learning systems. Demographic, clinical, and multimodal fMRI data were collected from participants. Our findings suggest that, compared to healthy controls, individuals with OCD exhibit abnormal brain functional indicators in both goal-directed and habit-learning brain regions, with a more pronounced reduction observed in the goal-directed regions. Additionally, abnormal brain activity is associated with illness duration, and the abnormalities observed in goal-directed regions are more effective in distinguishing different courses of OCD patients. Patients with different durations of OCD have functional abnormalities in the goal-directed and habitual-learning brain regions. There are differences in the degree of abnormality in different brain regions, and these abnormalities may disrupt the balance between goal-directed and habitual-learning systems, leading to increasing reliance on repetitive behaviors.

Relationships between obsessive-compulsive disorder and the big five personality traits: A meta-analysis.

Although several studies have examined the relationships between obsessive-compulsive disorder (OCD) and the Big Five personality traits (i.e., neuroticism, extraversion, openness, agreeableness, and conscientiousness), the results have been inconsistent. Therefore, this meta-analysis comprehensively examined the relationships between OCD and these traits. In total, 23 studies (29 independent datasets) with 30,138 participants were analyzed. The pooled effect size was 0.34 (95% confidence interval [CI]: 0.28, 0.40) for neuroticism, -0.14 (95% CI: -0.18, -0.10) for extraversion, -0.04 (95% CI: -0.09, 0.02) for openness, -0.10 (95% CI: -0.16, -0.04) for agreeableness, and -0.03 (95% CI: -0.11, 0.05) for conscientiousness, indicating that OCD was associated with higher scores for neuroticism and lower scores for extraversion and agreeableness. Meta-regression and subgroup analyses indicated that heterogeneity was mainly due to differences in sample types and OCD measurement instruments. Sensitivity analysis showed that the results of the meta-analysis were robust. Overall, neuroticism was a maladaptive trait, whereas extraversion and agreeableness were adaptive traits for OCD. Although the results could be sample- and instrument-specific, our findings may inform preventions and interventions for OCD symptoms.

Characteristics of Patients With Intractable Obsessive-Compulsive Disorder With High/Low Responsiveness to Gamma Knife Surgery.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a psychiatric condition that causes significant distress and social costs and often follows a chronic course with frequent relapses. Approximately 20% of patients do not respond to medication or cognitive behavioral therapy; gamma knife surgery (GKS) has been proposed as a treatment option for these patients. However, research on GKS for OCD patients is rare. METHODS: In this study, 10 patients with treatment-resistant OCD underwent GKS, and the treatment response and side effects were assessed. The improvement in patients' obsessive-compulsive symptoms was evaluated using the Yale-Brown Obsessive Compulsive Scale (YBOCS) scores following GKS. Additionally, the characteristics distinguishing the groups with favorable responses to GKS from those with less favorable responses were examined. RESULTS: GKS was well tolerated, and patients demonstrated a statistically significant reduction in YBOCS scores before and after GKS (p=0.016). Patients that responded to GKS exhibited distinct characteristics from those who did not respond. Patients who responded poorly tended to present an earlier age of onset, a longer duration of illness, more frequent hospitalizations, poorer social functioning, and a greater incidence of suicide attempts/thoughts. CONCLUSION: This study not only demonstrated that GKS is a safe and effective treatment method for intractable OCD but also revealed characteristics distinguishing patients who respond well to GKS from those who do not. These results may aid in the selection of patients for future application of GKS.

The Relationship of Rumination, Worry and OCD Symptoms During Technology Supported Mindfulness Therapy for OCD.

BACKGROUND: In this study, we re-examined data from a previous randomized controlled trial investigating 'technology supported mindfulness' (TSM)-an 8-week treatment intervention for individuals experiencing OCD. The current analysis involves an examination of the longitudinal relationships between rumination, worry and OCD symptom changes during mindfulness treatment, in comparison to a waitlist control. METHODS: Participants experiencing OCD (n = 71) were randomly assigned to 8 weeks of (1) TSM or (2) waitlist control. We tested the extent to which rumination (using the Ruminative Response Scale) and worry (using the Penn State Worry Questionnaire) are associated with OCD symptom changes during the acute phase of treatment, concurrently (i.e., within the same longitudinal model). RESULTS: Generalized linear model (GLM) results indicated a significant time (week 1 vs. week 8) by condition interaction involving decreased rumination in the TSM condition: F(1, 61) = 13.37, p = 0.001, partial η2 = 0.18 and observed power = 0.94. A second GLM demonstrated decreased worry in the TSM condition: F(1, 69) = 37.34, p = 0.001, partial η2 = 0.35 and observed power = 0.83. Longitudinal 'latent difference' structural equation analyses demonstrated a cross-lagged association between worry (but not rumination) and OCD symptom changes. CONCLUSIONS: Individuals in the TSM condition experienced greater reductions in rumination and worry during 8 weeks of TSM treatment compared to the waitlist control, and reduced worry predicted subsequent OCD symptom reduction.

Neurocognitive performance in the context of acute symptom reduction in OCD: Treatment effects and the impact of BDNF.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with neurocognitive impairments. The present study examined the effect of treatment on neurocognitive performance in OCD and the relationship between neurocognitive change and symptom change. The present study also examined polymorphisms influencing brain derived neurotrophic factor (BDNF) as predictors of neurocognitive change. METHOD: Treatment-seeking participants with OCD (N = 125) were assigned to cognitive behavioural therapy (CBT) alone, CBT combined with regular physical exercise, exercise alone, or a waitlist control group. Measures of OCD symptom severity and a neuropsychological battery were completed pre- and post-treatment. Blood or saliva samples were used to genotype the BDNF Val66Met polymorphism. RESULTS: OCD symptom severity was not cross-sectionally associated with neurocognitive performance. Several neurocognitive measures improved over treatment. The BDNF Val66Met polymorphism was significantly associated with worse performance on the Stroop test but did not significantly predict change in neurocognitive performance over time. LIMITATIONS: Limitations include lack of a healthy control group. CONCLUSION: Improvement in neurocognitive performance corresponded to symptomatic improvement and was independent of the BDNF Val66Met genotype.

When Dhat Syndrome is Delusional: A Case Series.

The Dhat syndrome is a culture-bound syndrome associated with anxiety and somatic and mood symptoms related to semen loss. It sometimes occurs in women, in whom it comes with vaginal discharge. Only a single case has been reported whereby Dhat delusion was associated with schizophrenia. In this case report, we dwell on two individuals suffering from a somatic-type delusional disorder with Dhat-like symptoms who had initially presented classical symptoms of the Dhat syndrome. Further studies are needed to explore the intersections of Dhat syndrome and psychoses, as well as the risk factors involved in mutual predisposition.

Transcranial direct current stimulation as early augmentation in adolescent obsessive compulsive disorder: A pilot proof-of-concept randomized control trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is proven to be safe in treating various neurological conditions in children and adolescents. It is also an effective method in the treatment of OCD in adults. AIM: To assess the safety and efficacy of tDCS as an add-on therapy in drug-naive adolescents with OCD. METHODS: We studied drug-naïve adolescents with OCD, using a Children's Yale-Brown obsessive-compulsive scale (CY-BOCS) scale to assess their condition. Both active and sham groups were given fluoxetine, and we applied cathode and anode over the supplementary motor area and deltoid for 20 min in 10 sessions. Reassessment occurred at 2, 6, and 12 wk using CY-BOCS. RESULTS: Eighteen adolescents completed the study (10-active, 8-sham group). CY-BOCS scores from baseline to 12 wk reduced significantly in both groups but change at baseline to 2 wk was significant in the active group only. The mean change at 2 wk was more in the active group (11.8 ± 7.77 vs 5.25 ± 2.22, P = 0.056). Adverse effects between the groups were comparable. CONCLUSION: tDCS is safe and well tolerated for the treatment of OCD in adolescents. However, there is a need for further studies with a larger sample population to confirm the effectiveness of tDCS as early augmentation in OCD in this population.

The risk of Alzheimer's disease and cognitive impairment characteristics in eight mental disorders: A UK Biobank observational study and Mendelian randomization analysis.

INTRODUCTION: The cognitive impairment patterns and the association with Alzheimer's disease (AD) in mental disorders remain poorly understood. METHODS: We analyzed data from 486,297 UK Biobank participants, categorizing them by mental disorder history to identify the risk of AD and the cognitive impairment characteristics. Causation was further assessed using Mendelian randomization (MR). RESULTS: AD risk was higher in individuals with bipolar disorder (BD; hazard ratio [HR] = 2.37, P < 0.01) and major depressive disorder (MDD; HR = 1.63, P < 0.001). MR confirmed a causal link between BD and AD (ORIVW = 1.098), as well as obsessive-compulsive disorder (OCD) and AD (ORIVW = 1.050). Cognitive impairments varied, with BD and schizophrenia showing widespread deficits, and OCD affecting complex task performance. DISCUSSION: Observational study and MR provide consistent evidence that mental disorders are independent risk factors for AD. Mental disorders exhibit distinct cognitive impairment prior to dementia, indicating the potential different mechanisms in AD pathogenesis. Early detection of these impairments in mental disorders is crucial for AD prevention. HIGHLIGHTS: This is the most comprehensive study that investigates the risk and causal relationships between a history of mental disorders and the development of Alzheimer's disease (AD), alongside exploring the cognitive impairment characteristics associated with different mental disorders. Individuals with bipolar disorder (BD) exhibited the highest risk of developing AD (hazard ratio [HR] = 2.37, P < 0.01), followed by those with major depressive disorder (MDD; HR = 1.63, P < 0.001). Individuals with schizophrenia (SCZ) showed a borderline higher risk of AD (HR = 2.36, P = 0.056). Two-sample Mendelian randomization (MR) confirmed a causal association between BD and AD (ORIVW = 1.098, P < 0.05), as well as AD family history (proxy-AD, ORIVW = 1.098, P < 0.001), and kept significant after false discovery rate correction. MR also identified a nominal significant causal relationship between the obsessive-compulsive disorder (OCD) spectrum and AD (ORIVW = 1.050, P < 0.05). Individuals with SCZ, BD, and MDD exhibited impairments in multiple cognitive domains with distinct patterns, whereas those with OCD showed only slight declines in complex tasks.