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.

Correlation between cognitive performance and structural neuroanatomy in patients with type I bipolar affective disorder treated with and without lithium.

INTRODUCTION: Lithium treatment of bipolar disorder (BD) has been associated with less cognitive impairment and fewer changes in structural brain anatomy compared to other treatments. However, the studies are heterogeneous and few assess whether these effects are related. The objective of this study was to evaluate and relate cognitive performance and structural neuroanatomy in patients treated with and without lithium. METHODS: Cross-sectional study that included 48 subjects with BD-I, of which 22 were treated with lithium and 26 without lithium. Performance was assessed on Wechsler III (WAIS III), TMT A and B (Trial Making Test) neuropsychological tests, California verbal learning test (CVLT), Rey complex figure test and Wisconsin card sorting test. Brain structures obtained by magnetic resonance imaging (MRI) were evaluated. The standardised mean difference (SMD) between both groups was calculated, adjusted for confounding variables using a propensity score, and the Spearman correlation coefficient (ρ) was used to assess the relationship between cognitive performance and neuroanatomical regions. RESULTS: Compared to the group without lithium, the group with lithium had fewer perseverative errors in the Wisconsin test (SMD = -0.69) and greater left and right cortical areas (SMD = 0.85; SMD = 0.92); greater surface area in the left anterior cingulate (SMD = 1.32), right medial orbitofrontal cortex (SMD = 1.17), right superior frontal gyrus (SMD = 0.82), and right and left precentral gyrus (SMD = 1.33; SMD = 0.98); greater volume of the right amygdala (SMD = 0.57), right hippocampus (SMD = 0.66), right putamen (SMD = 0.87) and right thalamus (SMD = .67). In the lithium group, a correlation was found with these errors and the thickness of the left precentral gyrus (ρ = -0.78), the volume of the right thalamus (ρ = -0.44), and the right amygdala (ρ = 0.6). CONCLUSIONS: The lithium group had better cognitive flexibility and greater dimension in some frontal and subcortical cortical regions. Furthermore, there was a moderate to high correlation between performance in this executive function and the thickness of the right precentral gyrus, and the volumes of the thalamus and the right amygdala. These findings could suggest a neuroprotective effect of lithium.

Correlación entre el desempeño cognitivo y la neuroanatomía estructural en pacientes con trastorno afectivo bipolar tipo I tratados con y sin litio / Correlation Between Cognitive Performance and Structural Neuroanatomy in Patients with Type I Bipolar Affective Disorder Treated with and Without Lithium

RESUMEN Introducción: El tratamiento del trastorno afectivo bipolar (TAB) con litio se ha relacionado con menos deterioro cognitivo y menores cambios en la anatomía estructural cerebral comparado con otros tratamientos. Sin embargo, los estudios son heterogéneos y son pocos los que evalúan si estos efectos están relacionados. El objetivo de este estudio es evaluar y relacionar el desempeno cognitivo y la neuroanatomía estructural en pacientes tratados con y sin litio. Métodos: Estudio de corte trasversal que incluyó a 48 sujetos con TAB I: 22 tratados con litio y 26 sin litio. Se evaluó el desempeno en las pruebas neuropsicológicas Wechsler III (WAIS III), TMTAyB (Trial Making Test), prueba de aprendizaje verbal de California (TAVEC), prueba de Figura compleja de Rey y prueba de clasificación de tarjetas de Wisconsin. Se evaluaron estructuras cerebrales obtenidas por resonancia magnétiva (RM) cerebral. Se calculó la diferencia de medias estandarizada (DME) entre ambos grupos, con ajuste por variables de confusión mediante puntuación de propensión, y se empleó el coeficiente de correlación de Spearman (p) para evaluar la relación existente entre el desempeno cognitivo y las regiones neuroanatómicas. Resultados: Respecto al grupo sin litio, el grupo con litio tuvo menos errores perseverativos en el Wisconsin (DME = -0,69) y mayores áreas corticales derecha e izquierda (DME = 0,85 y DME = 0,92); mayor superficie en el cíngulo anterior izquierdo (DME = 1,32), la corteza orbi-tofrontal medial derecha (DME = 1,17), el giro frontal superior derecho (DME = 0,82), los giros precentrales derecho e izquierdo (DME = 1,33 y DME = 0,98); mayor volumen de la amígdala derecha (DME = 0,57), el hipocampo derecho (DME = 0,66), el putamen derecho (DME = 0,87) y el tálamo derecho (DME = 0,67). En el grupo con litio, se encontró una correlación con dichos errores y el espesor del giro precentral izquierdo (p = -0,78), el volumen del tálamo derecho (p = -0,44) y la amígdala derecha (p = 0,6). Conclusiones: El grupo con litio tuvo mejor flexibilidad cognitiva y mayor dimensión en algunas regiones corticales frontales y subcorticales. Además, hubo correlación moderada a alta entre el desempeno en esta función ejecutiva y el espesor del giro precentral derecho, y los volúmenes del tálamo y la amígdala derecha. Estos hallazgos podrían indicar un efecto neuroprotector del litio

ABSTRACT Introduction: Lithium treatment of bipolar disorder (BD) has been associated with less impairment and fewer changes in structural brain anatomy compared to other treatments. However, the studies are heterogeneous and few assess whether these effects are related. The objective of this study was to evaluate and relate cognitive performance and structural neuroanatomy in patients treated with and without lithium. Methods: Cross-sectional study that included 48 subjects with BD-I, of which 22 were treated with lithium and 26 without lithium. Performance was assessed on Wechsler III (WAIS III), TMT A and B (Trial Making Test) neuropsychological tests, California verbal learning test (CVLT), Rey complex figure test and Wisconsin card sorting test. Brain structures obtained by magnetic resonance imaging (MRI) were evaluated. The standardised mean difference (SMD) between both groups was calculated, adjusted for confounding variables using a propen-sity score, and the Spearman correlation coefficient (p) was used to assess the relationship between cognitive performance and neuroanatomical regions. Results: Compared to the group without lithium, the group with lithium had fewer perse-verative errors in the Wisconsin test (SMD = -0.69) and greater left and right cortical areas (SMD = 0.85; SMD = 0.92); greater surface area in the left anterior cingulate (SMD = 1.32), right medial orbitofrontal cortex (SMD = 1.17), right superior frontal gyrus (SMD = 0.82), and right and left precentral gyrus (SMD = 1.33; SMD = 0.98); greater volume of the right amyg-dala (SMD = 0.57), right hippocampus (SMD = 0.66), right putamen (SMD = 0.87) and right thalamus (SMD=.67). In the lithium group, a correlation was found with these errors and the thickness of the left precentral gyrus (p = -0.78), the volume of the right thalamus (p =-0.44), and the right amygdala (p = 0.6). Conclusions: Thelithium group had better cognitive flexibility and greater dimension in some frontal and subcortical cortical regions. Furthermore, there was a moderate to high correlation between performance in this executive function and the thickness of the right precentral gyrus, and the volumes of the thalamus and the right amygdala. These findings could suggest a neuroprotective effect of lithium.

Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals.

AIMS: Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry. METHODS: We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14 sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles. RESULTS: We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex. CONCLUSIONS: We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.

Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles  and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.

Correlation Between Cognitive Performance and Structural Neuroanatomy in Patients with Type I Bipolar Affective Disorder Treated with and Without Lithium. / Correlación entre el desempeño cognitivo y la neuroanatomía estructural en pacientes con trastorno afectivo bipolar tipo I tratados con y sin litio.

INTRODUCTION: Lithium treatment of bipolar disorder (BD) has been associated with less cognitive impairment and fewer changes in structural brain anatomy compared to other treatments. However, the studies are heterogeneous and few assess whether these effects are related. The objective of this study was to evaluate and relate cognitive performance and structural neuroanatomy in patients treated with and without lithium. METHODS: Cross-sectional study that included 48 subjects with BD-I, of which 22 were treated with lithium and 26 without lithium. Performance was assessed on Wechsler III (WAIS III), TMT A and B (Trial Making Test) neuropsychological tests, California verbal learning test (CVLT), Rey complex figure test and Wisconsin card sorting test. Brain structures obtained by magnetic resonance imaging (MRI) were evaluated. The standardised mean difference (SMD) between both groups was calculated, adjusted for confounding variables using a propensity score, and the Spearman correlation coefficient (ρ) was used to assess the relationship between cognitive performance and neuroanatomical regions. RESULTS: Compared to the group without lithium, the group with lithium had fewer perseverative errors in the Wisconsin test (SMD = -0.69) and greater left and right cortical areas (SMD = 0.85; SMD = 0.92); greater surface area in the left anterior cingulate (SMD = 1.32), right medial orbitofrontal cortex (SMD = 1.17), right superior frontal gyrus (SMD = 0.82), and right and left precentral gyrus (SMD = 1.33; SMD = 0.98); greater volume of the right amygdala (SMD = 0.57), right hippocampus (SMD = 0.66), right putamen (SMD = 0.87) and right thalamus (SMD=.67). In the lithium group, a correlation was found with these errors and the thickness of the left precentral gyrus (ρ = -0.78), the volume of the right thalamus (ρ =-0.44), and the right amygdala (ρ = 0.6). CONCLUSIONS: The lithium group had better cognitive flexibility and greater dimension in some frontal and subcortical cortical regions. Furthermore, there was a moderate to high correlation between performance in this executive function and the thickness of the right precentral gyrus, and the volumes of the thalamus and the right amygdala. These findings could suggest a neuroprotective effect of lithium.

Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities.

BACKGROUND: Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear. AIMS: We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed. METHOD: This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model. RESULTS: A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (P = 0.006). Controls showed a positive correlation between total grey matter volume and income (R = 0.14, P = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (R = -0.076, P = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure. CONCLUSIONS: Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.

Rostral Middle Frontal Volumetric Differences in Bipolar Offspring versus Community Controls Offspring.

Neuroanatomical findings in the anterior limbic network in bipolar disorder (BD) adults have not been replicated in other populations such as bipolar offspring (BO). The aim of this study was to compare some brain areas volumes between BO with and without a lifetime affective disorder (AD) to a group of community control offspring (CCO). Methods: A descriptive observational cross-sectional study was carried out, with multiple comparison groups. Seven subjects (11-17 years old) from the BO with AD group were compared to seven subjects from the BO without AD group and seven subjects from the CCO group (match by age, gender and Tanner stage). Magnetic resonance imaging was performed with a Philips 3 Teslas device and volumetric segmentation was performed with the Freesurfer image analysis suite. Results: A larger size was found in the right middle frontal rostral region in the BO with AD group compared to the other two groups (p = 0.041). A higher volume was also found in BO with AD group in the left pars opercularis (Cohen d = 0.63) and in the right cingulate isthmus (d = 0.53) when compared with BO without AD group, and in the right hippocampus (d = 0.53) when compared to CCO group. A smaller volume was found in the BO without AD group versus CCO group in the left anterior caudate (d = 0.6). The BO groups (with and without AD) compared to CCO have a higher volume in the right frontal pole (d = 0.52). These volumetric differences can be attributed to the condition of BO with AD.

Los hallazgos neuroanatómicos en la red límbica anterior en el trastorno bipolar (TB) en adultos no se han replicado en otras poblaciones, como en los hijos de pacientes con trastorno bipolar (HPTB). El objetivo de este estudio fue comparar los volúmenes de áreas del cerebro entre HPTB, con y sin algún trastorno afectivo (TA) a lo largo de la vida, con un grupo de hijos de padres control de la comunidad (HPC). Métodos: Se realizó un estudio observacional, descriptivo y transversal, con múltiples grupos de comparación. Siete sujetos (11-17 años) del grupo HPTB con TA se compararon con siete sujetos del grupo HPTB sin TA y siete sujetos del grupo HPC (pareados por edad, sexo y estadio Tanner). La resonancia magnética nuclear se realizó con un resonador Philips 3 Teslas y la segmentación volumétrica se realizó con el conjunto de análisis de imagen Freesurfer. Resultados: Se encontró un tamaño mayor en la región frontal rostral medial derecha en el grupo HPTB con TA en comparación con los otros dos grupos (p = 0.041). También se encontró un mayor volumen en el grupo HPTB con TA en el opérculo frontal izquierdo (Cohen d = 0, 63) y en el istmo del giro del cíngulo derecho (d = 0, 53) cuando se comparó con el grupo sin TA, y en el hipocampo derecho (d = 0, 53) en comparación con el grupo HPC. Se encontró un volumen más pequeño en el grupo HPTB sin TA versus grupo HPC en el caudado anterior izquierdo (d = 0, 6). Los grupos HPTB (con y sin TA) en comparación con HPC tienen un volumen mayor en el polo frontal derecho (d = 0.52). Estas diferencias volumétricas pueden atribuirse a la condición de HPTB con TA.

Imaging Social and Environmental Factors as Modulators of Brain Dysfunction: Time to Focus on Developing Non-Western Societies.

Social and environmental factors are known risk factors and modulators of mental health disorders. We here conducted a nonsystematic review of the neuroimaging literature studying the effects of poverty, urbanicity, and community violence, highlighting the opportunities of studying non-Western developing societies such as those in Latin America. Social and environmental factors in these communities are widespread and have a large magnitude, as well as an unequal distribution, providing a good opportunity for their characterization. Studying the effect of poverty in these settings could help to explore the brain effect of economic improvements, disentangle the effect of absolute and relative poverty, and characterize the modulating impact of poverty on the underlying biology of mental health disorders. Exploring urbanicity effects in highly unequal cities could help identify the specific factors that modulate this effect as well as examine a possible dose-response effect by studying megacities. Studying brain changes in those living among violence, which is particularly high in places such as Latin America, could help to characterize the interplay between brain predisposition and exposure to violence. Furthermore, exploring the brain in an adverse environment should shed light on the mechanisms underlying resilience. We finally provide examples of two methodological approaches that could contribute to this field, namely a big cohort study in the developing world and a consortium-based meta-analytic approach, and argue about the potential translational value of this research on the development of effective social policies and successful personalized medicine in disadvantaged societies.

Evaluación de estructuras cerebrales por resonancia magnética en personas infectadas con el virus de la inmunodeficiencia humana (VIH) y adherentes al tratamiento antirretroviral / Evaluation by MRI of brain structures of HIV subjects with adherence to antiretroviral therapy

Introducción: los cambios estructurales del cerebro se pueden observar en fases tempranas de la infección por VIH y acelerarse en estadios avanzados, aunque queda por profundizar con más estudios clínicos la relación que pueda existir entre la adherencia al tratamiento antirretroviral y los cambios en los volúmenes de las estructuras cerebrales. Objetivo: identificar los cambios en estructurascerebrales de personas infectadas con VIH por medio de la resonancia magnética y explorar su relación con el tratamiento antirretroviral. Materiales y métodos: se eligieron 2 grupos, cada uno con 16 individuos; el primero conformado por personas infectadas con VIH y tratamiento adherente y el segundo con individuos no infectados (grupo control). Los volúmenes de las estructuras corticales, subcorticales, las regiones superficiales de la sustancia blanca y gris fueron calculados para los dos hemisferios, en los cuales se utilizaron algoritmos automáticos de la plataforma de análisis de imágenesFreeSurfer. Los datos anatómicos de los individuos fueron adquiridos en un equipo de resonancia magnética 3T en el Instituto de Alta Tecnología Médica (IATM), Medellín, Colombia. Resultados: el análisis de las estructuras corticales y subcorticales no arrojó diferencias significativas entre las volumetríasdel grupo control y los individuos infectados con VIH/adherentes al tratamiento. Conclusión: los hallazgos muestran que el cerebro puede estar posiblemente sin alteraciones en sus estructuras corticales y subcorticales en los individuos con VIH adherentes al tratamiento, en primera o segunda línea de tratamiento antirretroviral, y, a la vez, estos resultados pueden aportar nuevas estrategias de neuroprotección ante el autocuidado frente al esquema de tratamento.

Introduction: structural brain changes can be detected in early stages of HIV infection and may be accelerated in advanced stages, however it still important to have more clinic studies for analyze the relationship between the adherence to antiretroviral therapy and changes in the volume of brain structures. Objective: To identify changes in brain structures from HIV subjects by using Magnetic Resonance Imaging (MRI) and to correlate the findings with the antiretroviral treatment. Materials and methods: Two groups with 16 subjects were chosen: a HIV group of subjects with medication adherence and healthy subjects (control group). By using the automatic segmentation software for brain Freesurfer, cortical and subcortical structures volumes as well as grey and white matter surface area were calculated for both brain hemispheres. Data were acquired through 3T MRI scanner in the Instituto de Alta Tecnología Médica (IATM) from Medellin (Colombia). Results: There were not statistically significant differences in cortical and subcortical structures between control group and subjects HIV infected with adherence to treatment. Conclusion: These findings show that subjects infectedwith VIH in first or second line of antiretroviral treatment probably do not have any change on the brain cortical and subcortical structures. In addition, this allows developing new neuroprotection and self-care strategies during the current treatment plans.