The Journal Of Neuropsychiatry And Clinical Neurosciences[JOURNAL]
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200 papers
Altered Neural Processing of Interoception in Patients With Functional Neurological Disorder: A Task-Based fMRI Study.
Sojka P, Serranová T, Khalsa SS … +2 more , Perez DL, Diez I
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39558709 · Publisher ↗
OBJECTIVE: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing...
OBJECTIVE: Research suggests that disrupted interoception contributes to the development and maintenance of functional neurological disorder (FND); however, no functional neuroimaging studies have examined the processing of interoceptive signals in patients with FND. METHODS: The authors examined univariate and multivariate functional MRI neural responses of 38 patients with mixed FND and 38 healthy control individuals (HCs) during a task exploring goal-directed attention to cardiac interoception-versus-control (exteroception or rest) conditions. The relationships between interoception-related neural responses, heartbeat-counting accuracy, and interoceptive trait prediction error (ITPE) were also investigated for FND patients. RESULTS: When attention was directed to heartbeat signals versus exteroception or rest tasks, FND patients showed decreased neural activations (and reduced coactivations) in the right anterior insula and bilateral dorsal anterior cingulate cortices (among other areas), compared with HCs. For FND patients, heartbeat-counting accuracy was positively correlated with right anterior insula and ventromedial prefrontal activations during interoception versus rest. Cardiac interoceptive accuracy was also correlated with bilateral dorsal anterior cingulate activations in the interoception-versus-exteroception contrast, and neural activations were correlated with ITPE scores, showing inverse relationships to those observed for heartbeat-counting accuracy. CONCLUSIONS: This study identified state and trait interoceptive disruptions in FND patients. Convergent between- and within-group findings contextualize the pathophysiological role of cingulo-insular (salience network) areas across the spectrum of functional seizures and functional movement disorder. These findings provide a starting point for the future development of comprehensive neurophysiological assessments of interoception for FND patients, features that also warrant research as potential prognostic and monitoring biomarkers.
Neuropsychiatric Vulnerabilities and Sequelae of Human Trafficking in the United States.
Gordon M, Evenstad J, Nathani K … +2 more , Coverdale J, Nguyen P
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39558708 · Publisher ↗
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Primary Polydipsia in a Case of Genetic Behavioral Variant Frontotemporal Dementia.
Cantu Y, White T, Austgen G … +3 more , Rizk C, Okusaga OO, Jones MB
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39558707 · Full text
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Apathy and Functional Status in Early-Stage Huntington's Disease.
Gibson JS, Hay KR, Claassen DO … +5 more , McDonell KE, Brown AE, Wynn A, Jiang J, Isaacs DA
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39558706 · Full text
OBJECTIVE: Apathy is common in Huntington's disease (HD) and difficult to treat. Multiple recent calls have been made to increase understanding of apathy across the spectrum of HD severity. Functional status is an import...
OBJECTIVE: Apathy is common in Huntington's disease (HD) and difficult to treat. Multiple recent calls have been made to increase understanding of apathy across the spectrum of HD severity. Functional status is an important outcome in HD trials; however, no consensus currently exists regarding the impact of apathy on functional status in HD. The authors aimed to identify correlates of apathy and effects on functional status in a primarily early-stage HD sample. METHODS: This study included secondary analyses of data from a study of neuropsychiatric symptoms in a clinical HD sample. Spearman correlation analyses were used to assess the relationships between apathy (with the Frontal Systems Behavior Scale-Apathy [FrSBe-Apathy] subscore), clinical variables, and patient-reported outcomes. To assess the association of apathy with functional status, two multiple regression analyses were performed, with a different functional status measure (Adult Functional Adaptive Behavior [AFAB] scale or Total Functional Capacity [TFC] scale) as the dependent variable in each analysis. RESULTS: Statistically significant correlates of apathy included the Quality of Life in Neurological Disorders (Neuro-QoL) Satisfaction With Social Roles and Activities and Neuro-QoL Positive Affect and Well-Being scores (N=70 patients). Univariate correlation analyses also revealed statistically significant associations of FrSBe-Apathy scores with both functional status measures. In the multiple regression analyses, apathy significantly contributed to variability in functional status as measured by both the AFAB (N=49 patients) and TFC (N=56 patients) scales. CONCLUSIONS: These results underscore the need to address apathy as a target for improving functional status, social satisfaction, and well-being in HD, even for individuals with early-stage HD.
The Vagus Nerve and the Brain-Gut Axis: Implications for Neuropsychiatric Disorders.
López-Ojeda W, Hurley RA
J Neuropsychiatry Clin Neurosci · 2024 · PMID 39402936 · Publisher ↗
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Cognition and Ventral Attention Network Connectivity: Associations With Treatment Response in Posttraumatic Stress Disorder.
Chou T, Dougherty DD, Sorg SF … +2 more , Pitman RK, Tanev KS
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39385577 · Full text
OBJECTIVE: Posttraumatic stress disorder (PTSD) is a highly heterogeneous disorder, which makes it difficult to link clinical phenotypes with biomarkers to improve treatment outcomes. Findings from previous studies sugge...
OBJECTIVE: Posttraumatic stress disorder (PTSD) is a highly heterogeneous disorder, which makes it difficult to link clinical phenotypes with biomarkers to improve treatment outcomes. Findings from previous studies suggest that cognitive measures such as verbal memory or attention paired with within-ventral attention network (VAN) or salience network resting-state functional connectivity may predict treatment response among individuals with PTSD. METHODS: In a sample comprising 20 individuals with PTSD and 10 healthy control group individuals, the investigators subtyped individuals by using both discriminant function analysis and standardized norms for a single measure of memory and neuropsychological batteries of memory, attention, and executive functioning; attempted to replicate previous findings of lower within-VAN connectivity among individuals with cognitive impairment; and explored whether within-VAN connectivity paired with cognitive impairment predicted treatment outcomes. RESULTS: PTSD patients with cognitive impairment (defined by using a discriminant function analysis with verbal memory performance) had greater within-VAN resting-state functional connectivity compared with control group individuals and cognitively intact PTSD patients at a level that fell short of statistical significance (F=3.41; df=2, 21; η=0.237). The interaction between verbal memory performance and within-VAN connectivity also predicted treatment-related change in PTSD symptoms at a level that also fell short of statistical significance (β=-0.442). CONCLUSIONS: These findings somewhat support the clinical utility of identifying cognitive phenotypes within PTSD (by using discriminant function analysis and verbal memory performance) to predict treatment outcomes.
The Neuroconnective Endophenotype, a New Approach Toward Typing Functional Neurological Disorder: A Case-Control Study.
Bulbena-Vilarrasa A, Martínez-García M, Pintor Pérez L … +5 more , Camara M, Arbelo-Cabrera N, Bulbena-Cabré A, Pérez-Sola V, Baeza-Velasco C
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39385576 · Publisher ↗
OBJECTIVE: Functional neurological disorder (FND) is a core neuropsychiatric condition that includes both physical and mental symptoms. Recently, a validated clinical phenotype termed neuroconnective endophenotype (NEP),...
OBJECTIVE: Functional neurological disorder (FND) is a core neuropsychiatric condition that includes both physical and mental symptoms. Recently, a validated clinical phenotype termed neuroconnective endophenotype (NEP), which includes several physical and psychological characteristics together with joint hypermobility (hypermobility spectrum disorders), was found at a significantly higher frequency among patients with anxiety. The purpose of the present study was to examine the presence of the NEP among patients with FND. METHODS: The authors conducted a multicenter case-control study comprising 27 FND patients and 27 healthy control participants (matched by sex and age) ages 13 to 58 years. Eight questionnaires were administered. Proportional differences were examined with Student's t tests, one-way analyses of variance, and chi-square tests. RESULTS: Differences between FND patients and control participants were observed. FND patients had higher sensory sensitivity, increased prevalence of hypermobility features (including relevant physical signs and symptoms), greater frequency of polarized behaviors, a greater number of both psychiatric and physical comorbidities, and an increase in the characteristics and sensations typical of anxiety. Particularly striking was the presence of the hypermobility spectrum in more than 75% of FND patients compared with 15% among control participants. CONCLUSIONS: FND patients presented higher scores in all five dimensions included in the NEP. Thus, this phenotype, solidifying the original association between anxiety and the hypermobility spectrum, could help to identify an FND subtype when evaluating and managing FND patients, because it provides a new global view of patients' physical and mental symptoms.
Refining Research Diagnostic Criteria for Catatonia Among Delirium, Medical, Affective, and Psychosis Patient Groups.
Trzepacz PT, Franco JG, Chakrabarti S … +4 more , Ghosh A, Sahoo S, Chakravarty R, Grover S
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39385575 · Publisher ↗
OBJECTIVE: The authors proposed catatonia diagnostic criteria that require the presence of three neuropsychiatric symptom clusters, rated over 24 hours; this system differs from other symptom clustering proposals and is...
OBJECTIVE: The authors proposed catatonia diagnostic criteria that require the presence of three neuropsychiatric symptom clusters, rated over 24 hours; this system differs from other symptom clustering proposals and is intended to increase diagnostic rigor over Bush-Francis Catatonia Rating Scale (BFCRS) or DSM-5 criteria. METHODS: By applying new BFCRS item score thresholds, symptoms were clustered into three categories to comprise the Research Diagnostic Criteria for Catatonia (RDCC): akinesia (criterion A), unusual motor signs (criterion B), and behavioral signs (criterion C). RDCC symptom clusters were analyzed in four prospectively evaluated patient groups (delirium, medical, affective, and psychosis) (N=341). RESULTS: Use of the RDCC, compared with the DSM-5-TR and BFCRS, resulted in far fewer diagnoses of catatonia in the four patient groups: medical, N=1 out of 42 (2%); affective, N=1 out of 45 (2%); psychosis, N=3 out of 53 (6%); and delirium, N=0 out of 201. Permutations of the RDCC with more relaxed criteria were assessed, requiring either symptom thresholds or numbers of symptoms to meet criteria, resulting in catatonia rate gradations between those obtained with the RDCC and those obtained with current systems. The Cochrane Q test found that the DSM-5-TR was not dissimilar to the RDCC, if fulfilling numerical thresholds for criteria A-C, although any level of symptom severity was allowed. Confirmatory factor analysis with three goodness-of-fit indexes validated the RDCC. CONCLUSIONS: The RDCC requires akinetic symptoms on the basis of literature demonstrating their high BFCRS prevalence and exploratory factor analysis co-loadings, plus symptoms from unusual motor and behavioral signs. Compared with current lenient diagnostic approaches, having the symptoms required by the RDCC produced lower catatonia rates in the psychosis, affective, and medical groups and revealed no patients with catatonia in the delirium group. Subdividing DSM-5-TR symptoms into several different criteria may improve diagnosis. RDCC symptom clusters are both research data-based and amenable to further research for validation.
Characterizing the Effects of Concussion and Head Impact Exposure: Design, Methods, and Participant Traits of the CARE 2.0 Study.
McAllister TW, Broglio SP, Perkins SM … +4 more , Katz BP, Pasquina PF, McCrea MA, CARE Consortium Investigators
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39385574 · Publisher ↗
OBJECTIVE: This article describes the design, methods, and participant characteristics of the second phase of the Concussion Assessment, Research, and Education (CARE) Consortium study ("CARE 2.0") of the effects of conc...
OBJECTIVE: This article describes the design, methods, and participant characteristics of the second phase of the Concussion Assessment, Research, and Education (CARE) Consortium study ("CARE 2.0") of the effects of concussion and repetitive head impact exposure on neuropsychiatric health. METHODS: The authors conducted a prospective multisite observational study of male and female collegiate athletes and military service academy cadets and midshipmen participating in the CARE study. Participants were assessed at three time points: undergraduate baseline (UB), before departure from university or service academy (exit), and up to 6 years following graduation (postgrad) via an online battery of brain health assessments. Participant characteristics were compared across the three time points and four levels of head impact exposure. RESULTS: A total of 4,643 participants completed the exit assessment, and 3,981 completed the postgrad assessment. Relative to the UB assessment cohort, the exit and postgrad assessment cohorts differed with respect to the percentage of women, baseline Wechsler Test of Adult Reading scores, National Collegiate Athletic Association division category, sport contact level, and number of previous concussions. The median standardized difference across balancing variables, assessment time points, and degree of head impact exposure was 0.12 (with 90% of effect sizes ≤0.29). CONCLUSIONS: Although there were some statistically significant differences between participants across assessments, the effect sizes were modest, and overall the data suggest that the exit and postgrad cohorts reflect the characteristics of the baseline cohort. The CARE study design and its large, richly characterized sample provide an opportunity to answer important questions about cumulative and persistent effects of concussion and repetitive head impact exposure on neuropsychiatric health.
Race-Ethnicity, Rurality, and Age in Prospective Preferences and Concerns Regarding Closed-Loop Implanted Neural Devices.
Chen BB, Haeusermann T, Dada A … +5 more , Hamilton RH, James JE, Fong KC, Dohan D, Chiong W
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39169740 · Full text
OBJECTIVE: Responsive and human-centered neurotechnology development requires attention to public perceptions, particularly among groups underserved by existing treatments. METHODS: The authors conducted a preregistered...
OBJECTIVE: Responsive and human-centered neurotechnology development requires attention to public perceptions, particularly among groups underserved by existing treatments. METHODS: The authors conducted a preregistered nationally representative survey (https://osf.io/ej9h2) using the NORC at the University of Chicago AmeriSpeak panel. One vignette compared an implanted neural device with surgical resection in a scenario involving epilepsy, and another compared an implanted neural device with medications in a scenario involving mood disorders. The survey also contained questions about respondents' confidence that a device would be available if needed and confidence that enough research has been conducted among people like themselves. Responses were entered into nested survey-weighted logistic regression models, including a base demographic model (to test the overall effect of demographic factors) and an adjusted model that also included socioeconomic, religious and political, and health care access predictors. RESULTS: A total of 1,047 adults responded to the survey, which oversampled Black non-Hispanic (N=214), Hispanic (N=210), and rural (N=219) Americans. In the base demographic model, older Americans were more likely to prefer an implanted device in the two scenarios, and non-Hispanic Black Americans were less likely than non-Hispanic White Americans to prefer a device; rural Americans were less confident than urban or suburban Americans in having access, and non-Hispanic Black and rural Americans were less confident that enough research has been conducted among people like themselves. In adjusted models, income was a key mediator, partially explaining the effect of age and the contrast between Black and White non-Hispanic respondents on preferences for a device in the epilepsy scenario and fully explaining the effect of rurality on confidence in access. CONCLUSIONS: Demographic differences in prospective preferences and concerns highlight the importance of including members of underserved communities in neurotechnology development.
An 11-Fold Higher Risk of Incident Mild Cognitive Impairment With Hispanic Ethnicity and Baseline Neuropsychiatric Symptoms.
Salazar R, Dwivedi AK, Alvarado LA … +2 more , Escamilla M, Texas Alzheimer’s Research and Care Consortium
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39169739 · Publisher ↗
OBJECTIVE: Neuropsychiatric symptoms (NPSs) have been linked to cognitive decline. This study explored ethnic differences and the effects of baseline NPSs on incident mild cognitive impairment (MCI) among 386 Hispanic an...
OBJECTIVE: Neuropsychiatric symptoms (NPSs) have been linked to cognitive decline. This study explored ethnic differences and the effects of baseline NPSs on incident mild cognitive impairment (MCI) among 386 Hispanic and non-Hispanic participants from the Texas Harris Alzheimer's Research Study. METHODS: Data on NPSs from the Neuropsychiatric Inventory Questionnaire were available for all participants. Cox proportional hazards regression models were used to estimate the effect of ≥1 NPS at baseline and Hispanic ethnicity on incident MCI over a 7-year follow-up period. RESULTS: NPSs at baseline were associated with incident MCI for Hispanic participants but not non-Hispanic participants. Being Hispanic with at least one NPS at baseline had an 11-times higher risk of incident MCI. CONCLUSIONS: The Hispanic participants converted to MCI to a greater extent than the non-Hispanic participants. Only depressive symptoms increased the risk of MCI among non-Hispanics. Being of Hispanic ethnicity and having NPSs appeared to jointly increase the risk of progressing to MCI. To better understand the Alzheimer's disease continuum, further studies should explore other cultural, genetic, and medical risk factors influencing disease progression. Our findings strongly suggest the need to incorporate NPSs as outcomes of disease progression in future clinical trials involving Hispanic participants.
Relationship Between Posttraumatic Headache and Depression After Mild Traumatic Brain Injury.
Beal ML, Psoter KJ, Bechtold KT … +7 more , Nagpaul V, Peters ME, Rao V, Van Meter TE, Falk H, Korley FK, Roy D
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39113495 · Publisher ↗
OBJECTIVE: Mild traumatic brain injury (mTBI) can lead to psychiatric and somatic symptoms for some patients, including posttraumatic headache (PTH) and depression. This study attempted to further establish the relations...
OBJECTIVE: Mild traumatic brain injury (mTBI) can lead to psychiatric and somatic symptoms for some patients, including posttraumatic headache (PTH) and depression. This study attempted to further establish the relationship between PTH and depression following mTBI and investigate whether the presence of PTH immediately following injury can identify patients at risk for developing depressive symptoms up to 6 months later. METHODS: This study was a secondary analysis of data from Head Injury Serum Markers for Assessing Response to Trauma (HeadSMART), a prospective study of adult patients in the emergency department with head injury. Participants included 265 patients who met criteria for mTBI and completed the Rivermead Post-Concussion Symptoms Questionnaire, to identify PTH within 24 hours after injury, and the Patient Health Questionnaire-9, to assess depressive symptoms during follow-up. Measures were completed at the initial visit immediately after the injury in the emergency department and at 1-, 3-, and 6-month follow-up visits. RESULTS: Patients with acute PTH (aPTH) at time of injury were more likely to report PTH at 1, 3, and 6 months. They also had more severe depressive symptoms and a greater likelihood of clinically significant depression at all time points. CONCLUSIONS: Patients with aPTH within 24 hours after injury were more likely to report continued symptoms of PTH and clinically significant depression at 1, 3, and 6 months. These findings provide support for using the presence of aPTH in the emergency department following mTBI as an indicator for monitoring persistent PTH and depressive symptoms in the postacute recovery period.
Cognitive Performance of Latino and White Non-Latino Individuals With Parkinson's Disease.
Valenzuela Y, Luna K, Uribe-Kirby R … +6 more , Pawlak A, Pitman L, Cuellar-Rocha P, Lucatero GR, Santos MM, Jones JD
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39113494 · Full text
OBJECTIVE: Cognitive impairment is a common nonmotor symptom in Parkinson's disease (PD). Individuals of Latino background are traditionally underrepresented in research on PD. Despite the fact that Latinos comprise 18%...
OBJECTIVE: Cognitive impairment is a common nonmotor symptom in Parkinson's disease (PD). Individuals of Latino background are traditionally underrepresented in research on PD. Despite the fact that Latinos comprise 18% of the U.S. population, they commonly make up less than 5% of samples in studies of PD. Emerging evidence suggests that Latino individuals with PD may experience disparities relative to White non-Latinos in terms of having more severe motor symptoms, more severe depressive symptoms, and worse health-related quality of life. The purpose of the present study was to investigate differences in cognitive performance between Latino and White non-Latino individuals with PD and examine correlates of cognitive performance. METHODS: Data were obtained from the Parkinson's Progression Markers Initiative. Participants included 60 Latino individuals with PD and 1,009 White non-Latino individuals with PD, all of whom were followed annually for up to 5 years. Participants completed neuropsychological tests of attention and working memory, processing speed, visuospatial functioning, verbal fluency, and immediate and delayed memory and recall. RESULTS: Relative to White non-Latino individuals with PD, Latino individuals with PD had significantly lower scores on the global measure of cognitive functioning, a test of processing speed, and tests of working memory and attention. Years of education was the strongest correlate of performance in these three cognitive domains among individuals in the Latino group. CONCLUSIONS: These findings provide initial evidence of disparities in cognitive functioning among Latino individuals with PD. Educational disadvantages may be one potential driver of these disparities.
Psychiatric Manifestations in Early to Middle Stages of Fragile X-Associated Tremor-Ataxia Syndrome (FXTAS).
Chi MH, Bourgeois JA, Santos E … +7 more , Kim K, Ponzini MD, Mendoza G, Schneider A, Hessl D, Tassone F, Hagerman RJ
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39113493 · Full text
OBJECTIVE: The purpose of the present study was to assess the psychiatric manifestations of early to middle stages of fragile X-associated tremor-ataxia syndrome (FXTAS) and their relationship with executive function and...
OBJECTIVE: The purpose of the present study was to assess the psychiatric manifestations of early to middle stages of fragile X-associated tremor-ataxia syndrome (FXTAS) and their relationship with executive function and cytosine-guanine-guanine (CGG) repeat numbers across genders. METHODS: Cross-sectional data from 100 participants (62 men, 38 women; mean±SD age=67.11±7.90 years) with FXTAS stage 1, 2, or 3 were analyzed, including demographic information, cognitive measures, psychiatric assessments (Symptom Checklist-90-Revised and Behavioral Dyscontrol Scale-II [BDS-II]), and CGG repeat number. RESULTS: Participants with FXTAS stage 3 exhibited significantly worse psychiatric outcomes compared with participants with either stage 1 or 2, with distinct gender-related differences. Men showed differences in anxiety and hostility between stage 3 and combined stages 1 and 2, whereas women exhibited differences in anxiety, depression, interpersonal sensitivity, obsessive-compulsive symptoms, and somatization, as well as in the Global Severity Index, the Positive Symptom Distress Index, and the Positive Symptom Total. Among male participants, negative correlations were observed between BDS-II total scores and obsessive-compulsive symptoms, as well as between anxiety and CGG repeat number. CONCLUSIONS: These findings suggest that even at early FXTAS stages, patients have significant cognitive and other psychiatric symptoms, with notable gender-specific differences. This study underscores the clinical and prognostic relevance of comorbid psychiatric conditions in FXTAS, highlighting the need for early intervention and targeted support for individuals with relatively mild motor deficits.
Quetiapine, Clozapine, and Pimavanserin Treatment Response in Monogenic Parkinson's Disease Psychosis: A Systematic Review.
Colijn MA
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39034670 · Publisher ↗
Psychotic symptoms frequently occur in idiopathic Parkinson's disease (PD) and often require treatment with antipsychotic therapy. Most antipsychotics have the potential to worsen the motor symptoms of PD; quetiapine, cl...
Psychotic symptoms frequently occur in idiopathic Parkinson's disease (PD) and often require treatment with antipsychotic therapy. Most antipsychotics have the potential to worsen the motor symptoms of PD; quetiapine, clozapine, and pimavanserin are commonly used for the treatment of idiopathic PD because these medications tend to be comparatively well tolerated. Although psychotic symptoms may also occur in monogenic forms of PD, no reviews have focused on the use of antipsychotic medications in this context. The objective of the present systematic review was to characterize the effectiveness and tolerability of quetiapine, clozapine, and pimavanserin in monogenic PD-associated psychosis. A literature search was performed with PubMed, Scopus, and Embase. The search yielded 24 eligible articles describing 30 individuals, although treatment response with respect to psychotic symptoms was described in only 11 cases; of these, six individuals experienced symptomatic improvement or remission (four with clozapine and two with quetiapine), two exhibited a poor therapeutic response (one to clozapine and one to quetiapine), and the other three responded initially to antipsychotic therapy before experiencing a recurrence of symptoms. The use of quetiapine and clozapine in variant-associated PD is briefly reviewed separately. Notably, no reports of pimavanserin therapy were identified. In keeping with the idiopathic PD literature, relatively low doses of medication were used in most cases. Lastly, side effects were rarely reported. Although quetiapine and particularly clozapine may be effective and well tolerated in the treatment of monogenic PD psychosis, this review highlights the paucity of available evidence to guide clinical decision making in this context.
Characterizing Neurobehavioral Dysregulation Among Former American Football Players: Findings From the DIAGNOSE CTE Research Project.
Pulukuri SV, Fagle TR, Trujillo-Rodriguez D … +16 more , van Amerongen S, Bernick C, Geda YE, Wethe JV, Peskind ER, Katz DI, Alosco ML, Palmisano JN, Tripodis Y, Adler CH, Balcer LJ, Reiman EM, Shenton ME, Cummings JL, Stern RA, DIAGNOSE CTE Research Project
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39034669 · Full text
OBJECTIVE: Neurobehavioral dysregulation (NBD), a core clinical feature of traumatic encephalopathy syndrome, encompasses neuropsychiatric symptoms reported among individuals with a history of repetitive head impact expo...
OBJECTIVE: Neurobehavioral dysregulation (NBD), a core clinical feature of traumatic encephalopathy syndrome, encompasses neuropsychiatric symptoms reported among individuals with a history of repetitive head impact exposure, including contact sport athletes. The objective of this study was to examine the construct and subconstructs of NBD through a series of factor and cluster analyses. METHODS: Six clinician-scientists selected self-report questionnaire items relevant to NBD from seven available neuropsychiatric scales through a blinded voting process. These items were subjected to confirmatory factor analyses in a sample of 178 former college and professional American football players and 60 asymptomatic individuals without a history of repetitive head impact exposure. All participants were enrolled in the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy Research Project. Factor scores were generated on the basis of the optimal expert-informed model for NBD. Construct validity was assessed with neuropsychiatric scales not included in generation of the factor scores. Cluster analyses with NBD factor scores were used to examine symptom profiles. RESULTS: Factor analyses confirmed that NBD was composed of four subconstructs: explosivity, emotional dyscontrol, impulsivity, and affective lability. Cluster analyses indicated four distinct symptom profiles of NBD in this group of former football players: asymptomatic (N=80, 45%), short fuse (N=33, 19%), high affective lability (N=34, 19%), and high NBD (N=31, 17%). CONCLUSIONS: These findings characterize NBD as a multifaceted clinical construct with a heterogeneous presentation, providing a foundation for empirical work on the diagnostic criteria for traumatic encephalopathy syndrome and research on the neurobiological underpinnings of NBD.
Functional Neurological Disorders Among Patients With Tremor.
Baizabal-Carvallo JF, Alonso-Juarez M, Jankovic J
J Neuropsychiatry Clin Neurosci · 2025 · PMID 39034668 · Publisher ↗
OBJECTIVE: Functional neurological disorders (FNDs) are increasingly recognized in the general population and neurology clinics, and there is evidence that patients with neurological disorders are more likely to have a F...
OBJECTIVE: Functional neurological disorders (FNDs) are increasingly recognized in the general population and neurology clinics, and there is evidence that patients with neurological disorders are more likely to have a FND. This study was designed to identify the clinical features of FNDs among patients with movement disorders when the two disorders coexist. METHODS: The clinical histories and video recordings of 150 consecutive patients with tremors were examined: the types of tremor included essential tremor; essential tremor plus; dystonic tremor; tremor associated with dystonia; and drug-induced, myoclonic, orthostatic, task-specific, parkinsonian, Holmes, and unclassified tremor. Using criteria for "possible" and "probable" coexistent FND, clinical features that helped differentiate between functional and other neurological tremors were identified. RESULTS: There were 27 (18%) patients with functional manifestations, and 17 (11% of full sample) of these patients had signs suggestive of comorbid functional tremor. Patients with comorbid functional manifestations were younger at presentation, and these patients had greater severity of tremor, particularly upper limb postural tremor. Functional manifestations were not more commonly observed among patients with any particular type of tremor, except for patients with Holmes tremor, who were more likely to have comorbid functional neurological manifestations. CONCLUSIONS: About 18% of patients with diverse types of tremors also had comorbid functional neurological manifestations. Of the coexistent FNDs, functional tremor was the most common. Patients with co-occurring functional and other neurological tremors presented for evaluation at a younger age and had greater severity of arm tremor than those without comorbid functional neurological manifestations.
APOE×BDNF Interaction and Poorer Cognitive Outcomes Among Veterans With Mild Traumatic Brain Injury: An Exploratory Study.
Ton Loy AF, Adler JS, Merritt VC … +3 more , Sorg SF, Bondi MW, Delano-Wood L
J Neuropsychiatry Clin Neurosci · 2024 · PMID 38988190 · Publisher ↗
OBJECTIVE: The authors examined the interaction between apolipoprotein E (APOE) ε4 and brain-derived neurotrophic factor (BDNF) Val66Met alleles on neuropsychological functioning among veterans with histories of mild tra...
OBJECTIVE: The authors examined the interaction between apolipoprotein E (APOE) ε4 and brain-derived neurotrophic factor (BDNF) Val66Met alleles on neuropsychological functioning among veterans with histories of mild traumatic brain injury (mTBI). METHODS: Participants were 78 veterans with mTBI (85% males; mean±SD age=32.95±7.00 years; mean time since injury=67.97±34.98 months) who completed a structured clinical interview and underwent a comprehensive neuropsychological assessment. Participants also provided a buccal swab for determination of their APOE and BDNF genotypes. Three cognitive composite scores were calculated from the neuropsychological assessment, reflecting visuospatial speed (seven variables), executive functioning (10 variables), and memory (eight variables). Two-way analyses of covariance (ANCOVAs) adjusted for age, sex, and race-ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning. RESULTS: ANCOVAs revealed no significant main effects of APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE-by-BDNF genotype interaction for all three cognitive composite measures (visuospatial speed: η=0.055; executive functioning: η=0.064; and memory: η=0.068). Specifically, the ε4+/Met+ (N=8) subgroup demonstrated the poorest cognitive functioning relative to all other allele subgroups (ε4+/Met-: N=12, ε4-/Met+: N=23, and ε4-/Met-: N=35). CONCLUSIONS: This exploratory study is the first to show that, compared with other allele subgroups assessed, veterans with both ε4 and Met alleles demonstrated the poorest cognitive functioning across several cognitive domains known to be negatively affected in the context of mTBI. Further research with larger sample sizes is needed to replicate these findings.
Socioemotional Dysfunction From Temporal Lobe Involvement in Frontotemporal Dementia: A Preliminary Report.
Holiday KA, Sheppard A, Khattab YI … +3 more , Chavez D, Melrose RJ, Mendez MF
J Neuropsychiatry Clin Neurosci · 2024 · PMID 38988189 · Publisher ↗
OBJECTIVE: Socioemotional changes, rather than cognitive impairments, are the feature that defines behavioral variant frontotemporal dementia (bvFTD). Investigators have attributed the socioemotional changes in bvFTD and...
OBJECTIVE: Socioemotional changes, rather than cognitive impairments, are the feature that defines behavioral variant frontotemporal dementia (bvFTD). Investigators have attributed the socioemotional changes in bvFTD and other dementias to frontal lobe dysfunction; however, recent work implies a further contribution from right anterior temporal disease. The authors evaluated relationships between regional brain atrophy and socioemotional changes in both bvFTD and early-onset Alzheimer's disease (EOAD). METHODS: This study explored the neuroanatomical correlations of performance on the Socioemotional Dysfunction Scale (SDS), an instrument previously shown to document socioemotional changes in bvFTD, among 13 patients with bvFTD not preselected for anterior temporal involvement and 16 age-matched patients with early-onset Alzheimer's disease (EOAD). SDS scores were correlated with volumes of regions of interest assessed with tensor-based morphometric analysis of MRI images. RESULTS: As expected, the bvFTD group had significantly higher SDS scores overall and smaller frontal regions compared with the EOAD group, which in turn had smaller volumes in temporoparietal regions. SDS scores significantly correlated with lateral anterior temporal lobe (ATL) atrophy, and a regression analysis that controlled for diagnosis indicated that SDS scores predicted lateral ATL volume. Within the bvFTD group, higher SDS scores were associated with smaller lateral and right ATL regions, as well as a smaller orbitofrontal cortex. Within the EOAD group, higher SDS scores were associated with a smaller right parietal cortex. CONCLUSIONS: This study confirms that, in addition to orbitofrontal disease, there is a prominent right and lateral ATL origin of socioemotional changes in bvFTD and further suggests that right parietal involvement contributes to socioemotional changes in EOAD.
Loneliness and Resting-State Functional Brain Connectivity Among Older Adults: A Proportional Correlation.
Imai A, Matsuoka T, Ueno D … +1 more , Narumoto J
J Neuropsychiatry Clin Neurosci · 2025 · PMID 38988188 · Publisher ↗
OBJECTIVE: Loneliness reportedly increases the risk of dementia, especially Alzheimer's disease (AD). The authors' previous study demonstrated associations between loneliness and structural abnormalities observed in earl...
OBJECTIVE: Loneliness reportedly increases the risk of dementia, especially Alzheimer's disease (AD). The authors' previous study demonstrated associations between loneliness and structural abnormalities observed in early-stage AD. The present study examined associations between the brain's functional characteristics and loneliness among older adults with concerns about cognitive decline. METHODS: This single-center study included 43 participants (13 with amnestic mild cognitive impairment and 30 with normal cognition). Participants were assessed with the revised University of California Los Angeles (UCLA) Loneliness Scale and underwent resting-state functional MRI. Functional images were preprocessed with the CONN toolbox. The selected seeds were within brain regions reportedly associated with loneliness. One-sample general linear model analysis was performed to examine regressions of UCLA Loneliness Scale scores and functional connectivity between the seeds and regions of interest. RESULTS: The revised UCLA Loneliness Scale scores were positively correlated with functional connectivity between the right hippocampus and left lateral parietal lobe and were negatively correlated with functional connectivity between the left amygdala and left frontal operculum and between the left amygdala and right supramarginal gyrus. Analyses were adjusted for age, sex, and education and scores on the Mini-Mental State Examination and Clinical Dementia Rating scale. CONCLUSIONS: Loneliness was associated with abnormal function of the hippocampus, parts of the parietal lobe and frontal cortex, and the amygdala. These findings may suggest a possible correlation between loneliness and neurological changes associated with dementia.
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