Klüver-Bucy syndrome (KBS) is a neuropsychiatric condition characterized by hypersexuality, hyperorality, hyperphagia, visual agnosia, hypermetamorphosis, and emotional changes such as placidity and loss of fear. Distinc...Klüver-Bucy syndrome (KBS) is a neuropsychiatric condition characterized by hypersexuality, hyperorality, hyperphagia, visual agnosia, hypermetamorphosis, and emotional changes such as placidity and loss of fear. Distinct diagnostic criteria are used to define both complete and partial KBS, but clinicians often face challenges due to symptom variability and unvalidated criteria. In this systematic review, the authors searched the PubMed, Embase, PsycNet, Latin America and the Caribbean Literature on Health Sciences, and OpenGrey literature databases from their inception to January 24, 2025, focusing on KBS case reports and series. Inclusion criteria required patients to meet at least three of the six classic KBS features (partial KBS) or all six features (complete KBS). Studies involving orbitofrontal syndrome were excluded. Data were independently extracted and summarized. In total, 141 articles describing 157 cases that met the inclusion criteria were included. Hypersexuality (84%), hyperorality (84%), and hyperphagia (73%) were most common in KBS, whereas hypermetamorphosis (52%) and visual agnosia (47%) were less frequent. Cognitive changes, such as attentional and memory disturbances, were also common. Neuroimaging showed bilateral temporal lobe lesions in 73% of KBS cases. Major KBS causes included central nervous system infections (27%), traumatic brain injuries (14%), and autoimmune conditions (12%). Most reports lacked standardized symptom assessment, risking underreporting of features such as visual agnosia and hypermetamorphosis. This review highlights variability in KBS and its neuropsychiatric features. A new diagnostic framework with defined certainty levels is proposed. Future research should validate these criteria and explore targeted therapies to improve the understanding and management of this syndrome.
OBJECTIVE: The capacity to complete financial tasks accurately and efficiently is fundamental to financial independence; however, early declines in the progression of Alzheimer's disease may contribute to personal financ...OBJECTIVE: The capacity to complete financial tasks accurately and efficiently is fundamental to financial independence; however, early declines in the progression of Alzheimer's disease may contribute to personal financial loss, risk for elder abuse, and increased caregiver burden. Slower performance on measures of financial capacity may reflect early disease-related changes, foreshadowing subsequent cognitive decline. The authors investigated the relationship between the time needed to complete financial tasks and white matter tract diffusion characteristics among older individuals with or without mild cognitive impairment (MCI). METHODS: Fifteen participants with MCI and 15 healthy control participants completed diffusion MRI scans, a neuropsychological assessment, and the Financial Capacity Instrument-Short Form (FCI-SF). In analyses of data adjusted for demographic characteristics, Geriatric Depression Scale scores, and FCI-SF total score, the authors used diffusion tensor imaging to investigate correlations between the time needed to complete financial tasks and diffusion characteristics of white matter tracts terminating in the angular and fusiform gyri. RESULTS: FCI-SF completion times were significantly prolonged among participants with MCI compared with healthy control participants. The two groups did not significantly differ in diffusion metrics across the selected white matter tracts. FCI-SF total completion time was significantly correlated with multiple diffusion metrics in the arcuate, vertical occipital, and inferior longitudinal fasciculi of individuals with MCI. CONCLUSIONS: Completion time measures of the FCI-SF may reflect early disease-related changes in white matter tracts implicated in reading and arithmetic performance.
OBJECTIVE: The authors evaluated changes associated with a 3-week interdisciplinary intensive outpatient program that delivers integrated neuropsychiatric rehabilitation for veterans and first responders with persistent...OBJECTIVE: The authors evaluated changes associated with a 3-week interdisciplinary intensive outpatient program that delivers integrated neuropsychiatric rehabilitation for veterans and first responders with persistent postconcussive and co-occurring symptoms after remote traumatic brain injury. METHODS: In this retrospective cohort study, 128 patients completed patient-reported measures, including the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist for DSM-5 (PCL-5), and Life Satisfaction Questionnaire-11 (LiSat-11), and objective assessments, comprising Addenbrooke's Cognitive Examination-III (ACE-III), gait speed, computerized dynamic posturography (for conducting the Sensory Organization Test [SOT]), and Modified Clinical Test of Sensory Interaction in Balance (mCTSIB). Paired t tests were used to compare intake with discharge measures, and a linear mixed-effects model was used to examine NSI scores over time with covariate adjustment. RESULTS: The NSI total score decreased by 15.6 points (41%, Cohen's d=1.11); ACE-III scores improved by 6.8 points (Cohen's d=1.41); and forward and backward gait speeds, SOT composite scores, and mCTSIB condition 4 scores showed significant improvements (Cohen's d=0.68-0.87). The proportion of patients screening at or above a common PTSD threshold on the PCL-5 declined from 51% at intake to 20% at discharge, and higher baseline PCL-5 scores were associated with higher NSI scores across time points (p<0.001). CONCLUSIONS: These findings are consistent with multidomain benefits of intensive, interdisciplinary neuropsychiatric rehabilitation in this population. These results support the potential of integrated care models to reduce symptom burden and improve cognitive, mobility, vestibular, and life satisfaction outcomes over 3 weeks, while underscoring the close linkage between posttraumatic stress severity and neurobehavioral symptom burden.
OBJECTIVE: Persistent cognitive, emotional, and somatic symptoms after mild traumatic brain injury (mTBI) and co-occurring health conditions require multimodal treatment approaches. In this study, the authors assessed th...OBJECTIVE: Persistent cognitive, emotional, and somatic symptoms after mild traumatic brain injury (mTBI) and co-occurring health conditions require multimodal treatment approaches. In this study, the authors assessed the efficacy of an integrated practice unit (IPU) approach to treat veterans with chronic post-mTBI symptoms and co-occurring conditions. METHODS: Patient-reported outcomes were retrospectively assessed with scores on the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist for DSM-5 (PCL-5), Life Satisfaction Questionnaire-11 (LiSaT-11), Participation of Recombined Tools-objective (PART-O), and Patient Global Impression of Change (PGIC) instruments during and after participation in an intensive outpatient program. Unadjusted analyses were conducted with paired t tests between time points, and linear mixed models that were controlled for demographic factors were used to evaluate changes in NSI and PCL-5 scores between time points. RESULTS: Records from 219 participants (88% men), mean±SD age=45.8±9.6 years, were included. Total NSI, PCL-5, and LiSaT-11 scores improved from admission to discharge and to 1 month after discharge; observed effect sizes were medium to very large. Average PART-O total scores did not significantly improve between admission and 1 month postdischarge. The observed improvements in total NSI and PCL-5 scores remained statistically significant after analyses were adjusted for demographic factors. Responder analyses indicated clinically meaningful improvements in mTBI and posttraumatic stress symptoms. Nearly all participants endorsed positive PGIC statements at discharge and 1 month postdischarge. CONCLUSIONS: The IPU approach to the evaluation and management of persistent post-mTBI symptoms and co-occurring conditions suggests significant symptom reduction and improvement in wellness in a veteran population.
OBJECTIVE: The relationship between hydrocephalus and comorbid psychiatric conditions among adults remains unclear. The authors characterized the prevalence of psychiatric conditions among adult patients with hydrocephal...OBJECTIVE: The relationship between hydrocephalus and comorbid psychiatric conditions among adults remains unclear. The authors characterized the prevalence of psychiatric conditions among adult patients with hydrocephalus and compared the rates of these conditions among hydrocephalus subtypes. METHODS: A retrospective study of patients ages ≥18 years from a tertiary hydrocephalus specialty center was conducted by reviewing electronic health record data. Participants (N=2,668) were required to have an diagnosis of hydrocephalus (G91) or congenital hydrocephalus (Q03) in their active problem list. Hierarchical logistic regression analysis was performed to compare psychiatric outcomes among hydrocephalus subtypes after analyses had been adjusted for age at the last visit, gender, and number of hydrocephalus center encounters. RESULTS: Overall, 31% of the study participants had at least one comorbid psychiatric condition, most commonly depression (15%), anxiety disorder (10%), dementia (7%), or a substance use disorder (5%). Female gender was significantly associated with depression and anxiety disorder. Older age was linked to increased odds of dementia and a history of psychiatric encounters, and younger age was associated with anxiety disorders, substance use disorders, intellectual disability, developmental disorders, and childhood-onset behavioral and emotional disorders. Congenital hydrocephalus was associated with higher odds of intellectual disability, and no significant difference in psychiatric outcomes was detected between communicating and obstructive hydrocephalus. CONCLUSIONS: Comorbid psychiatric conditions affect a substantial proportion of adult patients with hydrocephalus. Age and gender differences in psychiatric diagnoses resemble trends in the general population. These findings highlight a need to improve psychiatric screening among adult patients with hydrocephalus.
Kamal S, Kennel N, Li AM
… +12 more, Gale S, Hennessey EL, Rodriguez BN, Feany MB, Stern AM, Ganesh VS, Schildkrout B, Daffner K, Silbersweig DA, Singhal T, Kletenik I, Miller MB
Examining risk factors for the development of dementia, a devastating condition, is of increasing importance in clinical research. Adverse childhood experiences (ACEs) represent one set of potentially modifiable dementia...Examining risk factors for the development of dementia, a devastating condition, is of increasing importance in clinical research. Adverse childhood experiences (ACEs) represent one set of potentially modifiable dementia risk factors with known impacts on neurodevelopment and health. Refining approaches used in previous reviews, the authors of this review and meta-analysis sought to answer the question, What is the strength of the association between ACEs and dementia in later life? The authors searched PubMed, EMBASE, and Web of Science, including peer-reviewed studies involving adults exposed to ACEs and a comparison group of unexposed adults. The outcome of interest was dementia of any etiology, and study quality was assessed. Separate meta-analyses were performed with odds ratios and hazard ratios (HRs). The literature search yielded 2,032 articles, of which 13 were included for analysis. ACE exposure (OR=1.54, 95% CI=1.38-1.71, p<0.001; HR=1.51, 95% CI=1.24-1.84, p<0.001) and exposure to parental death in childhood (OR=1.42, 95% CI=1.16-1.74, p<0.001) were associated with increased odds of or risk for developing dementia, respectively. This meta-analytic review is the most extensive examination of the ACE-dementia relationship to date, and its findings suggest that several ACEs are associated with increased dementia odds and risk. Although the number of studies reviewed was small and the studies were mostly of fair quality, necessitating caution in interpretation, nearly all of their results supported the association between ACE and dementia. High-quality prospective cohort studies incorporating biomarkers to measure ACE outcomes will be essential.
OBJECTIVE: The authors conducted a systematic review and meta-analysis of clinical trials testing rehabilitation therapies for treating functional neurological disorder (FND). METHODS: The authors searched databases for...OBJECTIVE: The authors conducted a systematic review and meta-analysis of clinical trials testing rehabilitation therapies for treating functional neurological disorder (FND). METHODS: The authors searched databases for clinical trials of patients with FND who received rehabilitation therapies. Some trials included a mental health intervention, but psychotherapy-only trials were excluded. Study quality was assessed by using a modified version of the NIH quality assessment tool for a before-after (pre-post) study with no control group. RESULTS: In total, 8,162 studies were screened for eligibility. Among these, 30 articles (N=1,581 participants) were included. Results of a meta-analysis of proportions revealed that 74% of the participants in FND rehabilitation trials had clinical improvement, but effect sizes varied significantly across studies. Twenty-three studies provided sufficient data to calculate pre-post rehabilitation effect sizes, which were uniformly positive for FND symptoms and physical function. Meta-analysis of seven available randomized controlled trials (RCTs) indicated a significant treatment effect on FND symptoms and that effects on physical function, fatigue, and mental health were not statistically significant. The generalizability of these findings was limited by heterogeneity across studies, attributed to differences in populations, treatment protocols, study designs, and outcome measures. CONCLUSIONS: Rehabilitation therapies are a promising approach for improving FND symptoms, and calculated estimates indicate that >70% of patients experience clinical improvement after rehabilitative treatment. However, additional high-quality RCTs are needed to clarify the overall efficacy of rehabilitation for FND and to identify which aspects of clinical improvement are most responsive to rehabilitation interventions.
Maziero MP, Lee EA, Colpo GD
… +11 more, Couture L, Merrill LC, Baskin L, Cahuiche AE, Petway A, Fan H, Reese E, Anderson KM, McCullough LD, Schulz PE, Ortiz GJ
J Neuropsychiatry Clin Neurosci
· 2026 Apr · PMID 41943185
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OBJECTIVE: Neurological symptoms are commonly reported among individuals with postacute sequelae of COVID-19 (PASC), with cognitive impairment being the most common feature, but cognitive trajectories in PASC have not be...OBJECTIVE: Neurological symptoms are commonly reported among individuals with postacute sequelae of COVID-19 (PASC), with cognitive impairment being the most common feature, but cognitive trajectories in PASC have not been clearly defined. The authors determined long-term cognitive changes in a cohort of individuals hospitalized with COVID-19, characterized their distinct cognitive trajectories, and identified factors associated with each trajectory at 36 months posthospitalization. METHODS: The sample comprised 630 patients who were hospitalized with severe COVID-19 symptoms; 214 patients returned for at least one follow-up assessment over a 36-month period. Cognitive function, including attention, cognitive flexibility, processing speed, and memory, was evaluated by using BrainCheck, a validated digital platform, at 3-6, 12, 24, and 36 months posthospitalization. Longitudinal changes in cognitive performance and their associations with demographic factors, medical history, and neuropsychiatric symptoms were analyzed with linear mixed-effects models. RESULTS: Four distinct cognitive trajectories over 36 months were identified and characterized. Group 1 (N=103, 48%) exhibited consistent normal cognitive function, group 2 (N=14, 7%) transitioned from unimpaired to impaired, group 3 (N=29, 14%) changed from impaired to unimpaired, and group 4 (N=68, 32%) showed persistent impairment across all domains. Poorer cognitive outcomes were associated with Hispanic ethnicity, although effects varied across domains. CONCLUSIONS: As with many viral encephalitides, some patients showed stable normal or abnormal cognition or improved cognition over time. Surprisingly, however, a fourth subset exhibited delayed cognitive decline. This observation suggests that PASC-associated mechanisms, perhaps including chronic cerebral inflammation, may cause progressive cognitive impairment well after the initial infection clears.
Vassilaki M, Syrjanen JA, Krell-Roesch J
… +9 more, Graff-Radford J, Vemuri P, Fields JA, Kremers WK, Jack CR, Knopman DS, Lyketsos CG, Petersen RC, Geda YE
J Neuropsychiatry Clin Neurosci
· 2026 · PMID 41837745
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OBJECTIVE: The authors conducted a population-based investigation of mild behavioral impairment (MBI) in the Mayo Clinic Study of Aging setting. MBI refers to new onset of neuropsychiatric symptoms (NPS) among adults age...OBJECTIVE: The authors conducted a population-based investigation of mild behavioral impairment (MBI) in the Mayo Clinic Study of Aging setting. MBI refers to new onset of neuropsychiatric symptoms (NPS) among adults ages ≥50 that is not due to a psychiatric disorder and that may be a precursor of cognitive decline or dementia. METHODS: The Neuropsychiatric Inventory Questionnaire was used in a cross-sectional study of participants ≥50 years without dementia to assess for NPS. Linear and logistic regression models were estimated and adjusted for age, sex, and education. RESULTS: The study sample comprised 2,713 participants (mean±SD age=74.6±9.5 years, 47% women). Overall, 11% of the participants had MBI at the first follow-up; 2,498 were cognitively unimpaired (10% of whom had MBI), and 215 had mild cognitive impairment (MCI; 29% of whom had MBI). Having MBI was associated with significantly higher odds of MCI (OR=3.47, 95% CI=2.46-4.84) and lower cognitive scores. Severe MBI was associated with even higher MCI odds (OR=5.15, 95% CI=2.73-9.37) and lower cognitive scores. CONCLUSIONS: In this study of older adults, participants with MCI were almost three times more likely than cognitively unimpaired participants to have MBI. Having MBI was associated with increased odds of having MCI and lower cognitive scores.
OBJECTIVE: Severe psychiatric symptoms beginning in late life warrant evaluation for secondary causes, including neurodegenerative disorders. When neurodegenerative disorders manifest initially with isolated psychiatric...OBJECTIVE: Severe psychiatric symptoms beginning in late life warrant evaluation for secondary causes, including neurodegenerative disorders. When neurodegenerative disorders manifest initially with isolated psychiatric features, they may be clinically indistinguishable from primary psychiatric illnesses such as late-onset schizophrenia. Accurate diagnosis is critical, especially for patients with underlying dementia with Lewy bodies (DLB), a synucleinopathy marked by early psychiatric symptoms, in particular psychosis, and extreme sensitivity to antipsychotic medications. Although clinically available biomarker tests are used in neurology to support the diagnosis of synucleinopathy, they have not been systematically applied in psychiatric populations. METHODS: This case series describes five consecutive psychiatric inpatients (four with psychosis) who, over a 3-month period, received testing with a clinically approved skin biopsy to detect phosphorylated alpha-synuclein in cutaneous nerves as part of neurological and neuropsychiatric evaluations for late-onset severe psychiatric symptoms. RESULTS: Two of the four patients with psychosis tested positive for synucleinopathy, and a third had multiple DLB features but tested negative. None of the patients met proposed clinical criteria for prodromal DLB, underscoring the need for updated criteria. CONCLUSIONS: DLB may underlie a substantial proportion of late-onset psychosis. Clinically available biomarker tests, routinely used in neurology to diagnose DLB and other neurodegenerative disorders with motor or cognitive symptoms, can also identify these disorders when they begin with psychiatric symptoms. Prospective biomarker-based research is essential to improve recognition of psychiatric-onset DLB, refine diagnostic criteria, and guide appropriate treatment.
OBJECTIVE: The authors examined the associations among depression, pain, motor function, and cognitive performance in Parkinson's disease (PD) to determine whether these relationships differ between the tremor-dominant (...OBJECTIVE: The authors examined the associations among depression, pain, motor function, and cognitive performance in Parkinson's disease (PD) to determine whether these relationships differ between the tremor-dominant (TD) and postural instability and gait difficulty (PIGD) motor subtypes of PD. METHODS: Cognitive performance was assessed with a broad neuropsychological test battery. Pain was measured with the King's Parkinson's Disease Pain Scale, Numeric Rating Scale, Color Analog Scale, and Douleur Neuropathique 4; motor function with the Movement Disorder Society Unified Parkinson's Disease Rating Scale (Part III and selected Part II items); and mood with the Hospital Anxiety and Depression Scale. Composite scores were derived via factor analysis. Mediation analyses (hierarchical regression and Sobel test) were performed with data from the full sample and stratified by motor subtype. RESULTS: Motor function significantly mediated the relationship between depression and cognitive performance in the full sample and in the PIGD group, but not in the TD group. Pain was not significantly associated with cognition. Patients with the PIGD subtype had greater motor impairment, higher depression scores, and lower cognitive performance than those with the TD subtype. CONCLUSIONS: Motor dysfunction may represent a significant pathway that links depressive symptoms and cognitive performance in PD, particularly in the PIGD subtype. Pain lacked a significant association with cognition. These findings underscore the clinical relevance of jointly assessing motor and nonmotor symptoms in PD, particularly among patients with the PIGD subtype.
Troyer EA, Meng W, Cheng M
… +10 more, Delfel EL, Vaida F, Yang X, Jacobus J, Dennis EL, Wilde EA, Abildskov T, Hesselink JR, Bigler ED, Max JE
J Neuropsychiatry Clin Neurosci
· 2026 Mar · PMID 41833964
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OBJECTIVE: Pediatric mild traumatic brain injury (mTBI) is a major public health concern. New psychiatric disorders (NPDs) can arise after mTBI, yet postinjury NPDs in nonclinical samples remain poorly understood. METHOD...OBJECTIVE: Pediatric mild traumatic brain injury (mTBI) is a major public health concern. New psychiatric disorders (NPDs) can arise after mTBI, yet postinjury NPDs in nonclinical samples remain poorly understood. METHODS: NPDs were prospectively characterized for youths ages 9-11 years who experienced an mTBI in their first year of participation in the Adolescent Brain Cognitive Development study, compared with control groups of orthopedically injured and noninjured individuals; a broad set of preinjury factors was accounted for in analyses. RESULTS: Between baseline (ages 9-10) and year 1 (ages 10-11), 135 youths had an mTBI, with 110 incurring a first lifetime mTBI. The prevalence of NPDs at the year-1 study visit was comparable among the injury groups, and mTBI did not predict NPDs at year 1. Preinjury psychiatric diagnoses significantly predicted NPDs (NPD-current [NPD-C] group: OR=2.18, 95% CI=1.30-3.61, p=0.003; NPD-any [NPD-A] group: OR=1.70, 95% CI=1.16-2.52, p=0.006), and self-reported Hispanic ethnicity was associated with lower odds of NPDs at year 1 (NPD-C group: OR=0.19, 95% CI=0.03-0.78, p=0.018; NPD-A group: OR=0.57, 95% CI=0.31-0.98, p=0.043). CONCLUSIONS: These results suggest that for nonclinically selected youths with mTBI, in the first year after late childhood injury, mTBI is not associated with differential odds of NPDs. Preinjury psychiatric history predicted NPDs, and self-reported Hispanic ethnicity predicted lower odds of NPDs at year 1. Future studies are needed to further characterize psychiatric sequelae after pediatric mTBI across adolescence to identify risk and protective factors for targeted prevention and intervention strategies.
OBJECTIVE: Impulse control disorders (ICDs) are a complication of Parkinson's disease (PD) treatment, but whether deep brain stimulation (DBS) affects ICDs remains unknown. Studies have focused on de novo ICDs among indi...OBJECTIVE: Impulse control disorders (ICDs) are a complication of Parkinson's disease (PD) treatment, but whether deep brain stimulation (DBS) affects ICDs remains unknown. Studies have focused on de novo ICDs among individuals receiving subthalamic nucleus DBS (STN-DBS), but the effects of DBS of the globus pallidus pars internus (GPi-DBS) are less understood. Rates and severities of ICDs among individuals receiving GPi-DBS or STN-DBS were compared. METHODS: Twenty-seven individuals with PD receiving bilateral DBS (17 STN, 10 GPi-DBS) were prospectively enrolled. Before surgery, participants had a neurological and neuropsychological evaluation. At 12-18 months post-DBS, the participants completed an abbreviated battery and an ICD rating scale. Volume of tissue activated (VTA), the intersection of each participant's stimulation volume with atlas-defined subregions of the DBS target, was explored in a sample subset. RESULTS: GPi-DBS participants had significantly higher post-DBS ICD severity scores compared with STN-DBS participants (p=0.040, Cohen's d=0.73), despite lower presurgical scores. A significant interaction between DBS target and time point (p=0.015, η²=0.26) indicated increased ICD symptoms in the GPi group postsurgery. Post-DBS, 80% and 35% of the GPi-DBS and STN-DBS participants met ICD criteria, respectively. Differences in ICDs persisted in analyses controlled for levodopa-equivalent daily dose. ICD improvements post-DBS were linked to greater VTA overlap in STN limbic regions, with no significant VTA associations with GPi-DBS. CONCLUSIONS: GPi-DBS may increase the risk for de novo ICDs. This observation should be interpreted with caution because of the small sample size and low statistical significance. Additional research may clarify the relationships between DBS targets and ICD outcomes.