White Matter Hyperintensities and Mild TBI in Post-9/11 Veterans and Service Members.

INTRODUCTION: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. MATERIALS AND METHODS: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median postinjury interval of 8 years) or negative mTBI history (n = 198), were examined. RESULTS: White matter hyperintensities were present in both mTBI and comparison groups at similar rates (39% and 37%, respectively). There was an age-by-diagnostic group interaction, such that older Veterans and Service Members with a history of mTBI demonstrated a significant increase in the number of WMHs present compared to those without a history of mTBI. Additional associations between an increase in the number of WMHs and service-connected disability, insulin-like growth factor-1 levels, and worse performance on tests of episodic memory and executive functioning-processing speed were found. CONCLUSIONS: Subtle but important clinical relationships are identified when larger samples of mTBI participants are used to examine the relationship between history of head injury and radiological findings. Future studies should use follow-up magnetic resonance imaging and longitudinal neurobehavioral assessments to evaluate the long-term implications of WMHs following mTBI.

Cenozoic seeds of Vitaceae reveal a deep history of extinction and dispersal in the Neotropics.

The remarkably diverse plant communities of the Neotropics are the result of diversification driven by multiple biotic (for example, speciation, extinction and dispersal) and abiotic (for example, climatic and tectonic) processes. However, in the absence of a well-preserved, thoroughly sampled and critically assessed fossil record, the associated processes of dispersal and extinction are poorly understood. We report an exceptional case study documenting patterns of extinction in the grape family (Vitaceae Juss.) on the basis of fossil seeds discovered in four Neotropical palaeofloras dated between 60 and 19 Ma. These include a new species that provides the earliest evidence of Vitaceae in the Western Hemisphere. Eight additional species reveal the former presence of major clades of the family that are currently absent from the Neotropics and elucidate previously unknown dispersal events. Our results indicate that regional extinction and dispersal have substantially impacted the evolutionary history of Vitaceae in the Neotropics. They also suggest that while the Neotropics have been dynamic centres of diversification through the Cenozoic, extant Neotropical botanical diversity has also been shaped by extensive extinction over the past 66 million years.

Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders-ENIGMA study in people with bipolar disorders and obesity.

Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.

Looking beyond psychosocial adversity and sex: Clinical factors associated with ADHD and other psychiatric disorders in a non-Caucasian sample of high-risk siblings.

This study examined the association of clinical factors, independent of sex and high psychosocial adversity (HPAd), with the presence of ADHD or other mental disorders, specifically within a middle-income country with a non-Caucasian population. A multi-centric cross-sectional study was conducted in three sites in Colombia. Our study recruited trios of an ADHD proband, one sibling, and one parent. We used valid instruments for assessing parents and siblings. The sample included 223 siblings, an average age of 12.3 (SD 3.9), and 51.1% Females. The ADHD recurrence risk ratio (λ) was 12. The clinical factors mainly associated with the presence of ADHD, independent of sex and HPAd, were 1) Pregnancy and childbirth complications, 2) Delayed psychomotor development, 3) Temperament, and 4) Sleep disturbances. Our research showed that, independently of HPAd and the male sex, there were other clinical factors associated with ADHD and other psychiatric disorders in this population. These findings need to be replicated in similar populations globally.

Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.

BACKGROUND: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. METHODS: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. RESULTS: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. CONCLUSIONS: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.

Geospatial investigations in Colombia reveal variations in the distribution of mood and psychotic disorders.

BACKGROUND: Geographical variations in mood and psychotic disorders have been found in upper-income countries. We looked for geographic variation in these disorders in Colombia, a middle-income country. We analyzed electronic health records from the Clínica San Juan de Dios Manizales (CSJDM), which provides comprehensive mental healthcare for the one million inhabitants of Caldas. METHODS: We constructed a friction surface map of Caldas and used it to calculate the travel-time to the CSJDM for 16,295 patients who had received an initial diagnosis of mood or psychotic disorder. Using a zero-inflated negative binomial regression model, we determined the relationship between travel-time and incidence, stratified by disease severity. We employed spatial scan statistics to look for patient clusters. RESULTS: We show that travel-times (for driving) to the CSJDM are less than 1 h for ~50% of the population and more than 4 h for ~10%. We find a distance-decay relationship for outpatients, but not for inpatients: for every hour increase in travel-time, the number of expected outpatient cases decreases by 20% (RR = 0.80, 95% confidence interval [0.71, 0.89], p = 5.67E-05). We find nine clusters/hotspots of inpatients. CONCLUSIONS: Our results reveal inequities in access to healthcare: many individuals requiring only outpatient treatment may live too far from the CSJDM to access healthcare. Targeting of resources to comprehensively identify severely ill individuals living in the observed hotspots could further address treatment inequities and enable investigations to determine factors generating these hotspots.

The frequencies of mental disorders vary by geographic region. Investigating such variations may lead to more equitable access to mental healthcare and to scientific discoveries that reveal specific localized factors that contribute to the causes of mental illness. This study examined the frequency of three disorders with a major impact on public health ­ schizophrenia, bipolar disorder, and major depressive disorder ­ by analyzing electronic health records from a hospital providing comprehensive mental health care for a large region in Colombia. We show that individuals receiving outpatient care mainly live relatively near the facility. Those receiving inpatient care live throughout the region, but cluster in a few scattered locations. Future research could lead to strategies for more equitable provision of mental healthcare in Colombia and identify environmental or genetic factors that affect the likelihood that someone will develop one of these disorders.

The origin and speciation of orchids.

Orchids constitute one of the most spectacular radiations of flowering plants. However, their origin, spread across the globe, and hotspots of speciation remain uncertain due to the lack of an up-to-date phylogeographic analysis. We present a new Orchidaceae phylogeny based on combined high-throughput and Sanger sequencing data, covering all five subfamilies, 17/22 tribes, 40/49 subtribes, 285/736 genera, and c. 7% (1921) of the 29 524 accepted species, and use it to infer geographic range evolution, diversity, and speciation patterns by adding curated geographical distributions from the World Checklist of Vascular Plants. The orchids' most recent common ancestor is inferred to have lived in Late Cretaceous Laurasia. The modern range of Apostasioideae, which comprises two genera with 16 species from India to northern Australia, is interpreted as relictual, similar to that of numerous other groups that went extinct at higher latitudes following the global climate cooling during the Oligocene. Despite their ancient origin, modern orchid species diversity mainly originated over the last 5 Ma, with the highest speciation rates in Panama and Costa Rica. These results alter our understanding of the geographic origin of orchids, previously proposed as Australian, and pinpoint Central America as a region of recent, explosive speciation.

Comparison of the neurocognitive profile of the children of parents with bipolar disorder and controls: A transnational cross-sectional study.

INTRODUCTION: Studies that have compared the cognitive alterations of the children of parents with bipolar disorder (CPBD) versus the children of control parents (CCP), present heterogeneous results due to the studies' methodological differences, the age of the population studied, and the lack of standardisation of the measures used for the different neurocognitive domains. The objective was to compare the neurocognitive profile of CPBD versus CCP to observe if there are differences that could be proposed as possible endophenotypes of BD. RESULTS: A total of 107 individuals (51 CPBD, and 56 CCP) with ages between 6 and 16 (mean, 12.2±2.80) years of age were evaluated. Seventy-four point five percent of the CPBD group had some disorder compared to 67.9% of the CCP group. Tests such as letter-F phonemic verbal fluency, letter-S phonemic verbal fluency, overall F-A-S phonemic verbal fluency, story recall and retrieval, and Wisconsin perseverative errors showed a difference with a small effect size, but with a high degree of uncertainty. CONCLUSIONS: The CPBD did not have differences in their neurocognitive profile in comparison with CCP. Both groups have a high prevalence of psychopathology, which is a factor that could explain the lack of differences in neurocognitive performance.

Psychopathological Risk in Siblings of Subjects with Attention-Deficit/Hyperactivity Disorder: A cross-Sectional Study.

OBJECTIVE: We aim to determine the prevalence of mental disorders in siblings of children with attention deficit hyperactivity disorder (ADHD), and to determine how psychosocial adversity factors relate to this psychopathology, in a low-middle income country (Colombia). METHODS: We evaluated subjects with ADHD diagnosed according to the DSM-5 criteria, one of their parents and one of their siblings (ages 8-19). We used the ADHD rating scale and a set of instruments to assess the presence of mental disorders as well as psychosocial adversity. RESULTS: We evaluated 74 trios formed by the index case with ADHD, one sibling and one of the parents. We found that 24.3% of the participating siblings also met the criteria for ADHD and another 24.3% for other psychiatric disorders. The risk of these siblings having ADHD increased further when one of the parents reported a history of ADHD. We also found that 28.3% of the families faced high levels of psychosocial adversity as per their scores in the Rutter Adversity Index. CONCLUSIONS: Siblings of subjects with ADHD showed a significant risk for ADHD and other mental disorders. That risk increased if a parent reported a history of ADHD and also when two or more psychosocial adversity factors were present. This study supports the importance of early detection in efforts to decrease the risk for other siblings.

Predicting diagnostic conversion from major depressive disorder to bipolar disorder: an EHR based study from Colombia.

Bipolar Disorder (BD) is a severe and chronic disorder characterized by recurrent episodes of depression, mania, and/or hypomania. Most BD patients initially present with depressive symptoms, resulting in a delayed diagnosis of BD and poor clinical outcomes. This study leverages electronic health record (EHR) data from the Clínica San Juan de Dios Manizales in Colombia to identify features predictive of the transition from Major Depressive Disorder (MDD) to BD. Analyzing EHR data from 13,607 patients diagnosed with MDD over 15 years, we identified 1,610 cases of conversion to BD. Using a multivariate Cox regression model, we identified severity of the initial MDD episode, the presence of psychosis and hospitalization at first episode, family history of mood or psychotic disorders, female gender to be predictive of the conversion to BD. Additionally, we observed associations with medication classes (prescriptions of mood stabilizers, antipsychotics, and antidepressants) and clinical features (delusions, suicide attempt, suicidal ideation, use of marijuana and alcohol use/abuse) derived from natural language processing (NLP) of clinical notes. Together, these risk factors predicted BD conversion within five years of the initial MDD diagnosis, with a recall of 72% and a precision of 38%. Our study confirms many previously identified risk factors identified through registry-based studies (such as female gender and psychotic depression at the index MDD episode), and identifies novel ones (specifically, suicidal ideation and suicide attempt extracted from clinical notes). These results simultaneously demonstrate the validity of using EHR data for predicting BD conversion as well as underscore its potential for the identification of novel risk factors and improving early diagnosis.

Psychopathological Risk in Siblings of Subjects with Attention-Deficit/Hyperactivity Disorder: A cross-Sectional Study

Objective: We aim to determine the prevalence of mental disorders in siblings of children with attention deficit hyperactivity disorder (ADHD), and to determine how psychosocial adversity factors relate to this psychopathology, in a low-middle income country (Colombia). Methods: We evaluated subjects with ADHD diagnosed according to the DSM-5 criteria, one of their parents and one of their siblings (ages 8-19). We used the ADHD rating scale and a set of instruments to assess the presence of mental disorders as well as psychosocial adversity. Results: We evaluated 74 trios formed by the index case with ADHD, one sibling and one of the parents. We found that 24.3% of the participating siblings also met the criteria for ADHD and another 24.3% for other psychiatric disorders. The risk of these siblings having ADHD increased further when one of the parents reported a history of ADHD. We also found that 28.3% of the families faced high levels of psychosocial adversity as per their scores in the Rutter Adversity Index. Conclusions: Siblings of subjects with ADHD showed a significant risk for ADHD and other mental disorders. That risk increased if a parent reported a history of ADHD and also when two or more psychosocial adversity factors were present. This study supports the importance of early detection in efforts to decrease the risk for other siblings.

Objetivo: Nuestro objetivo es determinar la prevalencia de trastornos mentales en hermanos de casos con TDAH y cómo los factores de adversidad psicosocial se relacionan con esta psicopatología en un país de ingresos bajos-medios (Colombia). Métodos: Se evaluó a sujetos con TDAH diagnosticado según los criterios del DSM-5, uno de sus padres y uno de sus hermanos (edades, 8-19 anos). Mediante la escala de calificación del TDAH y un conjunto de otros instrumentos se evaluó la presencia de trastornos mentales y adversidad psicosocial. Resultados: Se evaluó a 74 tríos formados por el caso índice con TDAH, un hermano y uno de los padres. Se halló que un 24,3% de los hermanos participantes también cumplían los criterios de TDAH y otro 24,3%, otros trastornos psiquiátricos. El riesgo de que estos hermanos tuvieran TDAH aumentó aún más cuando uno de los padres informó antecedentes de TDAH. También, que el 28,3% de las familias se enfrentaron a altos niveles de adversidad psicosocial según sus puntuaciones en el Índice de Adversidad de Rutter. Conclusiones: Los hermanos de sujetos con TDAH mostraron un significativo riesgo de TDAH y otros trastornos mentales. Ese riesgo aumenta si uno de los padres reporta antecedentes de TDAH y también cuando se presentan 2 o más factores de adversidad psicosocial. Este estudio respalda la importancia de la detección temprana con el fin de disminuir el riesgo para otros hermanos.

Bridging two oceans: small toothed cetaceans (Odontoceti) from the Late Miocene Chagres Formation, eastern Caribbean (Colon, Panama).

Fossil cetaceans are often found in Miocene marine outcrops across the globe. However, because this record is not homogeneous, the dissimilar increase in occurrences, along with the sampling bias has created regions with extensive records and others with great scarcity. Among these, the Caribbean has remained enigmatic due to the lack of well-preserved cetacean fossils. Here, we report new Caribbean fossil cetaceans from the Upper Miocene Chagres Formation exposed along Piña beach, Eastern Panama, including a scaphokogiine kogiid, an Acrophyseter-like physeteroid and the phocoenid Piscolithax. Along with previous records of the iniid Isthminia panamensis and the kogiine Nanokogia isthmia, the Chagres cetacean fauna shows some similarities with other Late Miocene cetacean communities such as the Californias in the North Pacific, although their closest affinities lie with the eastern South Pacific Pisco Formation, Peru. Such findings indicate that though deep and intermediate Caribbean-Pacific water interchange was reduced by the Middle Miocene due to the shallowing of the Central American Seaway, shallow waters marine connection that persisted until the Pliocene might have facilitated the dispersal of coastal species across both sides of the Isthmus.

Country-level gender inequality is associated with structural differences in the brains of women and men.

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.

The evolution of extant South American tropical biomes.

This review explores the evolution of extant South American tropical biomes, focusing on when and why they developed. Tropical vegetation experienced a radical transformation from being dominated by non-angiosperms at the onset of the Cretaceous to full angiosperm dominance nowadays. Cretaceous tropical biomes do not have extant equivalents; lowland forests, dominated mainly by gymnosperms and ferns, lacked a closed canopy. This condition was radically transformed following the massive extinction event at the Cretaceous-Paleogene boundary. The extant lowland tropical rainforests first developed at the onset of the Cenozoic with a multistratified forest, an angiosperm-dominated closed canopy, and the dominance of the main families of the tropics including legumes. Cenozoic rainforest diversity has increased during global warming and decreased during global cooling. Tropical dry forests emerged at least by the late Eocene, whereas other Neotropical biomes including tropical savannas, montane forests, páramo/puna, and xerophytic forest are much younger, greatly expanding during the late Neogene, probably at the onset of the Quaternary, at the expense of the rainforest.

Chemical Composition, Enantiomeric Distribution and Biological Activity of Essential Oil from Morella pubescens (Humb. & Bonpl. ex Willd.) Wilbur.

The species Morella pubescens, commonly known as wax laurel, is a tree belonging to the Myricaceae family that can be found from Costa Rica to Bolivia. In this study, the chemical composition, enantiomeric distribution, and biological activity of essential oil isolated from the leaves of this species was determined. Hydrodistillation was used to isolate the essential oil (EO). Gas chromatography coupled with mass spectrometry was used to determine the qualitative composition, gas chromatography equipped with a flame ionization detector was used to determine quantitative composition, and gas chromatography on an enantioselective column was used to determine enantiomeric distribution. The broth microdilution method was employed to assess the antibacterial capacity of the essential oil against seven opportunistic microorganisms, including three Gram-positive cocci bacteria, a Gram-positive bacilli bacterium and three Gram-negative bacilli bacteria. 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid radical cation and 2,2-diphenyl-1-picrylhydryl free radical were used as reagents to determine the antioxidant activity of essential oil. The spectrophotometric method was used to analyze the acetylcholinesterase inhibitory effect of the essential oil. The extraction method afforded a low yield of around 0.076 ± 0.008% (v/w). Fifty-eight chemical compounds, which represent 97.9% of the total composition, were identified in the essential oil. Sesquiterpene hydrocarbons were the most representative group with 24 compounds (67.8%). The principal constituents were (E)-caryophyllene (27.5 ± 1.3%), limonene (11.8 ± 0.6%), δ-selinene (9.1 ± 0.2%), ß-selinene (8.0 ± 0.2%), selina-3,7(11)-diene (5.3 ± 0.2%) and germacrene B (5.0 ± 0.5%). Three pairs of enantiomers were identified in the essential oil of Morella pubescens. Essential oil presented strong activity against the bacterium Enterococcus faecium (ATCC 27270) with an MIC of 250 µg/mL. The antioxidant activity of essential oil was very strong in the ABTS method with an SC50 of 46.4 ± 1.0 µg/mL and was strong in the DPPH method with an SC50 of 237.1 ± 1.8 µg/mL. Additionally, the essential oil reported strong anticholinesterase activity with an IC50 of 133.5 ± 1.06 µg/mL.

Ancestry component as a major predictor of lithium response in the treatment of bipolar disorder.

BACKGROUND: Bipolar Disorder (BD) represents the seventh major cause of disability life-years-adjusted. Lithium remains as a first-line treatment, but clinical improvement occurs only in 30 % of treated patients. Studies suggest that genetics plays a major role in shaping the individual response of BD patients to lithium. METHODS: We used machine-learning techniques (Advance Recursive Partitioned Analysis, ARPA) to build a personalized prediction framework of BD lithium response using biological, clinical, and demographical data. Using the Alda scale, we classified 172 BD I-II patients as responders or non-responders to lithium treatment. ARPA methods were used to build individual prediction frameworks and to define variable importance. Two predictive models were evaluated: 1) demographic and clinical data, and 2) demographic, clinical and ancestry data. Model performance was assessed using Receiver Operating Characteristic (ROC) curves. RESULTS: The predictive model including ancestry yield the best performance (sensibility = 84.6 %, specificity = 93.8 % and AUC = 89.2 %) compared to the model without ancestry (sensibility = 50 %, Specificity = 94.5 %, and AUC = 72.2 %). This ancestry component best predicted lithium individual response. Clinical variables such as disease duration, the number of depressive episodes, the total number of affective episodes, and the number of manic episodes were also important predictors. CONCLUSION: Ancestry component is a major predictor and significantly improves the definition of individual Lithium response in BD patients. We provide classification trees with potential bench application in the clinical setting. While this prediction framework might be applied in specific populations, the used methodology might be of general use in precision and translational medicine.

Mechanisms of change in posttraumatic headache-related disability: A mediation model.

OBJECTIVE: To explore whether the association between change in headache management self-efficacy and posttraumatic headache-related disability is partially mediated by a change in anxiety symptom severity. BACKGROUND: Many cognitive-behavioral therapy treatments for headache emphasize stress management, which includes anxiety management strategies; however, little is currently known about mechanisms of change in posttraumatic headache-related disability. Increasing our understanding of mechanisms could lead to improvements in treatments for these debilitating headaches. METHODS: This study is a secondary analysis of veterans (N = 193) recruited to participate in a randomized clinical trial of cognitive-behavioral therapy, cognitive processing therapy, or treatment as usual for persistent posttraumatic headache. The direct relationship between headache management self-efficacy and headache-related disability, along with partial mediation through change in anxiety symptoms was tested. RESULTS: The mediated latent change direct, mediated, and total pathways were statistically significant. The path analysis supported a significant direct pathway between headache management self-efficacy and headache-related disability (b = -0.45, p < 0.001; 95% confidence interval [CI: -0.58, -0.33]). The total effect of change of headache management self-efficacy scores on change in Headache Impact Test-6 scores was significant with a moderate-to-strong effect (b = -0.57, p = 0.001; 95% CI [-0.73, -0.41]). There was also an indirect effect through anxiety symptom severity change (b = -0.12, p = 0.003; 95% CI [-0.20, -0.04]). CONCLUSIONS: In this study, most of the improvements in headache-related disability were related to increased headache management self-efficacy with mediation occurring through change in anxiety. This indicates that headache management self-efficacy is a likely mechanism of change of posttraumatic headache-related disability with decreases in anxiety explaining part of the improvement in headache-related disability.

Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.

BACKGROUND: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. METHODS: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. RESULTS: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. CONCLUSIONS: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.