Cortical thickness patterns as state biomarker of anorexia nervosa.

OBJECTIVE: Only few studies have investigated cortical thickness in anorexia nervosa (AN), and it is unclear whether patterns of altered cortical thickness can be identified as biomarkers for AN. METHOD: Cortical thickness was measured in 19 adult women with restricting-type AN, 24 individuals recovered from restricting-type AN (REC-AN) and 24 healthy controls. Those individuals with current or recovered from AN had previously shown altered regional cortical volumes across orbitofrontal cortex and insula. A linear relevance vector machine-learning algorithm estimated patterns of regional thickness across 24 subdivisions of those regions. RESULTS: Region-based analysis showed higher cortical thickness in AN and REC-AN, compared to controls, in the right medial orbital (olfactory) sulcus, and greater cortical thickness for short insular gyri in REC-AN versus controls bilaterally. The machine-learning algorithm identified a pattern of relatively higher right orbital, right insular and left middle frontal cortical thickness, but lower left orbital, right middle and inferior frontal, and bilateral superior frontal cortical thickness specific to AN versus controls (74% specificity and 74% sensitivity, χ2 p < .004); predicted probabilities differed significantly between AN and controls (p < .023). No pattern significantly distinguished the REC-AN group from controls. CONCLUSIONS: Higher cortical thickness in medial orbitofrontal cortex and insula probably contributes to higher gray matter volume in AN in those regions. The machine-learning algorithm identified a mixed pattern of mostly higher orbital and insular, but relatively lower superior frontal cortical thickness in individuals with current AN. These novel results suggest that regional cortical thickness patterns could be state markers for AN.

Brain correlates of alexithymia in eating disorders: A voxel-based morphometry study.

AIMS: Alexithymia is a personality trait that consists of difficulty in identifying and acknowledging one's own and others' feelings. Recent studies reported that alexithymia is present in both anorexia (AN) and bulimia nervosa (BN). Brain morphological studies on healthy subjects showed that alexithymia correlates with several brain regions involved in emotions processing. The aim of this study was to investigate the anatomical correlates of alexithymia in AN and BN. METHODS: We performed a voxel-based morphometry study on 21 patients with AN and 18 with BN. Seventeen healthy subjects were used as a control group. Alexithymia, depression and anxiety were assessed with self-administered questionnaires and correlated to gray matter (GM) density in each group. RESULTS: In BN, alexithymia was correlated with the GM of the parietal lobe, in particular of the right angular gyrus. The correlation was predominantly linked with Difficulty Describing Feelings. In AN, we did not find correlations between GM and alexithymia. CONCLUSIONS: In BN, our results support the hypothesis that this trait may represent a relevant pathogenic or maintenance factor that contributes to relational difficulties, present in this pathology. In AN, the lack of correlation between GM volume and alexithymia may be influenced by atrophy in several brain regions that in turn can be, as previously reported, a consequence of caloric restriction. Also, the nature of alexithymia may be different from that of BN and controls and this trait could be secondary to a psychopathologic process specific to AN.

An exploratory study to subtype obese binge eaters by personality traits.

BACKGROUND: Obesity and binge eating disorder (BED) are prevalent conditions that severely affect the quality of life of many people in developed countries, but an effective treatment remains elusive. Personality traits have been studied extensively in this population, leading to different, and at times conflicting, results. Subtyping BED people along these features could add to our knowledge of the disorder. METHODS: We applied a two-step cluster analysis, followed by bootstrapping validation, to the Temperament and Character Inventory scores of 462 subjects affected by obesity and BED or subthreshold BED. RESULTS: We found two clusters of subjects; however, the categorization in clusters 1 and 2 did not appear to strictly overlap with the distinction between BED and subthreshold BED. The first cluster showed higher harm avoidance and a lower self-directedness. Cluster 1 patients had higher depression, higher eating impulsivity, greater problems with their body image and poorer quality of life than cluster 2 patients. CONCLUSIONS: Our results seem to confirm the heterogeneity of the binge eater population and suggest the importance of harm avoidance and self-directedness to subtype these subjects. These results could generate exploratory works regarding personality in obese people with BED to discover more targeted treatments.

Urinary cortisol and psychopathology in obese binge eating subjects.

BACKGROUND: Investigations on the relationship between obesity, binge eating and the function of hypothalamic-pituitary-adrenal (HPA) axis have led to inconsistent results. General psychopathology affects HPA axis function. The present study aims to examine correlations between binge eating, general psychopathology and HPA axis function in obese binge eaters. METHODS: Twenty-four hour urinary free cortisol (UFC/24 h) was measured in 71 obese binge eating women. The patients were administered psychometric tests investigating binge eating, psychopathology and clinical variables. The relationship between binge eating, psychopathology and urinary cortisol was investigated, controlling for age and BMI. RESULTS: We found an inverse correlation between UFC/24 h and binge eating, depression, obsessive-compusive symptoms, somatization and sensitivity. In a regression model a significant inverse correlation between urinary cortisol and psychopathology was confirmed. CONCLUSIONS: Urinary cortisol levels in obese patients with binge eating disorder show an inverse correlation with several dimensions of psychopathology which are considered to be typical of a cluster of psychiatric disorders characterized by low HPA axis function, and are very common in obese binge eating patients. If these results are confirmed, UFC/24 h might be considered a biomarker of psychopathology in obese binge eaters.

Inpatient Early Intervention for Serious Mental Illnesses Is Associated With Fewer Rehospitalizations Compared With Treatment as Usual in a High-volume Public Psychiatric Hospital Setting.

OBJECTIVE: High-acuity publicly funded inpatient psychiatric settings usually feature short lengths of stay and high readmission rates. This study examined the influence of an early intervention program for serious mental illnesses (SMI) on readmissions at 6 and 12 months postdischarge at a high-volume, urban public inpatient psychiatric hospital. METHODS: The Early Onset Treatment Program (EOTP) is a cost-free, 90-day inpatient multidisciplinary service intervention program for uninsured patients who are within 5 years of SMI onset, funded as a pilot program by the Texas state legislature. Rehospitalization rates at 6 and 12 months were extracted from electronic medical records for EOTP participants (n=165) and comparison patients matched on demographics and diagnosis (n=155). The comparison group received treatment as usual at the same psychiatric hospital. Group re-admission rates were compared using logistic and Poisson regression analyses. RESULTS: Group membership was a significant predictor of rehospitalization (P<0.0001) at both 6 and 12 months. Expressed as 1/odds ratio (OR), the EOTP group was less likely to readmit once and more than once at 6 months postdischarge (1/OR=3.82 and 4.74, respectively) compared with the non-EOTP group. The EOTP group was also less likely to readmit once and more than once at 12 months postdischarge (1/OR=2.96 and 3.51, respectively). CONCLUSIONS: The results suggest that participation in the EOTP service in this high-acuity setting was significantly related to reduced likelihood of rehospitalization at 6 and 12 months. Several variables may account for this observation, including length of stay, longer medication adherence, environmental stability, and more individualized and extensive psychotherapy treatment.

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group.

BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

Risk factors for metabolic and cardiovascular disease in inpatients with severe mental illness.

Patients with severe mental illness (SMI) have increased burden of somatic illnesses, especially cardiovascular disease. Characterizing the cardiovascular risk profile of patients with SMI is therefore crucial to understanding how to decrease morbidity and mortality in these vulnerable populations. In this observational study, entropy balancing (a form of propensity score matching) was used to compare cardiometabolic health in a sample of the general population from the National Health and Nutrition Examination Survey (NHANES) datasets to inpatients hospitalized in a large, urban, academic psychiatric hospital in Harris County, Texas. Data were analyzed using independent linear regression models for blood pressure, blood glucose, TG:HDL ratio, total cholesterol, and body mass index as outcome variables. Systolic blood pressure (F=34•75, p<0•0001), diastolic blood pressure (F=90•53, p<0•0001), blood glucose (F=12•89, p<0•0001), and the TG:HDL ratio (F=3•16, p<0•0001) were all elevated in the psychiatric inpatient sample vs. the NHANES sample. Contrary to expectations, total cholesterol (F=32•18, p<0•0001) and BMI (F=15•05, p<0•0001) were lower in this sample vs. the NHANES sample. Patients hospitalized with SMI show a cardiometabolic profile which confers greater risk of diabetes- and hypertension-related mortality. Approaches should be developed to target indicators of cardiometabolic health in this population to reduce long-term mortality.

Customizing Early Intervention Treatment for Psychosis in the UTHealth - Harris County Psychiatric Center.

High-need, high-cost patients include those with diagnosed serious mental illnesses (e.g., schizophrenia; SMI). They often delay or fail to seek treatment. If they receive treatment, care is often sought from generalist settings (e.g., primary care or emergency medicine) or is suboptimal due to the provision of limited, non-evidence-based intervention and lack of communication, integration, and coordination among providers. This results in high aggregate costs and poor outcomes. Value-based health care requires care coordination to address the medical and social needs of this population. We describe a unique early intervention program for SMI that emanates from an inpatient setting: The Early Onset Treatment Program (EOTP) at the University of Texas Health Science Center at Houston-Harris County Psychiatric Center. The EOTP offers free, phase-specific, multidisciplinary treatment to young adults without health insurance with the aim of improving their long-term outcomes and reducing the rate of rehospitalization. An evaluation of the EOTP indicates program participants were significantly less likely to be rehospitalized at six months (4.73 times less likely) and at 12 months (3.5 times less likely) than a comparison group (p <.001), and participants' scores of symptomatology and disability significantly decreased following treatment.

Inpatient early intervention for serious mental illnesses and post-discharge criminal involvement in a high-volume psychiatric hospital setting.

Individuals with serious mental illness (SMI) are at increased risk for arrest and incarceration relative to the same-community population without SMI. Publicly-funded inpatient psychiatric hospitals usually feature short lengths of stay and limited opportunities for extended services that might impact criminal justice involvement after discharge. This study examined the influence of an early intervention program for SMI at a high-volume public psychiatric hospital on involvement in the criminal justice system post-discharge. The Early Onset Treatment Program (EOTP) is an extended service intervention program for uninsured patients who are within 5 years of SMI onset. Criminal justice records (number of arrests with conviction, days of incarceration) were obtained for EOTP participants (n = 164) and comparison patients (n = 164) matched on demographics, diagnosis, and discharge date via propensity score matching. Data were zero-inflated and analyzed using hurdle models, controlling for prior arrests. The EOTP group was less likely to be convicted of at least one crime post-discharge (0 arrests vs. > 0, p < .001), and spent fewer days incarcerated (if incarcerated ≥1 day, p < .03). Participation in the EOTP service was linked to reduced likelihood of post-discharge arrest and days incarcerated. Several alternative variables may contribute to this preliminary observation, including length of stay, medication adherence, longer environmental stability, and individual patient characteristics.

Emotional imagination of negative situations: Functional neuroimaging in anorexia and bulimia.

AIM: The present study aims to extend the knowledge of the neural correlates of emotion processing in first episode subjects affected by anorexia nervosa (AN) or bulimia nervosa (BN). We applied an emotional distress paradigm targeting negative emotions thought to be relevant for interpersonal difficulties and therapeutic resistance mechanisms. METHODS: The current study applied to 44 female participants with newly diagnosed AN or BN and 20 matched controls a neuroimaging paradigm eliciting affective responses. The measurements also included an extensive assessment comprising clinical scales, neuropsychological tests, measures of emotion processing and empathy. RESULTS: AN and BN did not differ from controls in terms of emotional response, emotion matching, self-reported empathy and cognitive performance. However, eating disorder and psychopathological clinical scores, as well as alexithymia levels, were increased in AN and BN. On a neural level, no significant group differences emerged, even when focusing on a region of interest selected a priori: the amygdala. Some interesting findings put in relation the hippocampal activity with the level of Body Dissatisfaction of the participants, the relative importance of the key nodes for the common network in the decoding of different emotions (BN = right amygdala, AN = anterior cingulate area), and the qualitative profile of the deactivations. CONCLUSIONS: Our data do not support the hypothesis that participants with AN or BN display reduced emotional responsiveness. However, peculiar characteristics in emotion processing could be associated to the three different groups. Therefore, relational difficulties in eating disorders, as well as therapeutic resistance, could be not secondary to a simple difficulty in feeling and identifying basic negative emotions in AN and BN participants.

Higher Prevalence of Metabolic Syndrome in Child-adolescent Patients with Bipolar Disorder.

OBJECTIVE: Previous studies have indicated a convergent and bidirectional relationship between metabolic syndrome (MetS) and bipolar disorder (BD). As most of these studies focused mainly on adults diagnosed with BD, our study aims to investigate and characterize metabolic disturbances in child-adolescents diagnosed with BD. METHODS: We retrospectively examined the medical records of psychiatric hospitalizations with admitting diagnosis of BD in child-adolescents (age ＜ 18 years). Body mass index (BMI), lipid profile, fasting blood glucose, and blood pressure were primary variables. National Cholesterol Education Program criteria were used to define MetS. Reference group data was obtained from the National Health and Nutrition Examination Survey study. Statistical analyses included t tests, chi-square tests, and Fisher's exact tests. RESULTS: We identified 140 child-adolescent patients with BD (mean age = 15.12 ± 1.70 years, 53% male). MetS was significantly more common in BD compared to the reference group: 14% (95% confidence interval [95% CI] 8-20) vs. 6.7% (95% CI 4.1-9.2), p = 0.001 with no significant difference by sex. MetS components were higher in the BD group, particularly BMI ≥ 95% (25% vs. 11.8%, p ＜ 0.001) and high blood pressure (17% vs. 8%, p = 0.05). Moreover, female patients had lower odds of high blood pressure (odds ratio = 0.24 [95% CI 0.08-0.69], p = 0.005). CONCLUSION: Compared with the general child-adolescent population, the prevalence of MetS was significantly higher in patients with BD of same age. This reiterates the notion of an increased risk of MetS in patients diagnosed with BD; and thus, further exploration is warranted.

The role of anger in adherence to highly active antiretroviral treatment in patients infected with HIV.

BACKGROUND: Adherence to highly active antiretroviral treatment (HAART) is critical to long-term treatment success in patients infected with human immunodeficiency virus (HIV). However, the relationship between psychological variables and medication adherence is still poorly understood. The aim of this study was to investigate how anger dimensions in subjects with HIV affect adherence to antiretroviral drugs. METHODS: One hundred and thirty outpatients with HIV who were nondepressed and receiving HAART were administered the State-Trait Anger Inventory and a compliance self-report questionnaire. They also underwent clinical laboratory tests aimed at investigating immune function and disease stage. RESULTS: Forty-three patients (33%) reported suboptimal adherence. Full compliance with HAART was related to higher age, lower HIV RNA level, lower trait anger, lower outside-directed anger and greater anger control. In a multiple regression analysis, low trait anger (p = 0.02) and high anger control (p = 0.03) were significantly associated with full adherence to HAART. CONCLUSIONS: Anger dimensions are linked with, and may affect, adherence to HAART. A better understanding of the psychological determinants of compliance might allow for the identification of patients who are at higher risk of nonadherence. To sustain adherence to HAART, these patients may benefit from increased clinical attention or intervention.

Duloxetine in obese binge eater outpatients: preliminary results from a 12-week open trial.

OBJECTIVE: Attempts have been made to find appropriate drug regimens to treat binge eating disorder (BED). Several reports have examined the use of selective serotonin reuptake inhibitors (SSRIs) or mood stabilizers; both serotonin and noradrenalin reuptake inhibitors (SNRIs) have been reported to be useful for binge eating, but the available data are limited. We evaluated the efficacy of duloxetine, an SNRI, in 45 obese patients who reported binge eating. METHODS: Forty-five patients with BED or binge eating with sub-threshold symptoms (s-BED) with high eating impulsivity, received duloxetine 60-120 mg/day for 12 weeks. RESULTS: A significant reduction in number of binges/week was observed in BED patients; statistical analyses performed on the whole sample revealed significant reductions in scores on the binge eating scale (BES) and the Beck depression inventory (BDI), weight, body mass index (BMI), clinical global impression, and the bulimia scale of the eating disorder inventory-2. The reduction in BES and BDI scores was not statistically different between BED and s-BED subjects. CONCLUSIONS: Although preliminary, results from this open trial suggest that duloxetine may be a successful option to reduce binge eating and depressive symptoms in both obese BED and s-BED outpatients.

A randomized, double-blind trial comparing sertraline and fluoxetine 6-month treatment in obese patients with Binge Eating Disorder.

Previous studies support the use of selective serotonin reuptake inhibitors (SSRIs), in overweight patients with Binge Eating Disorder (BED), but results are far from conclusive. Sertraline has been studied less extensively, and there have been a few studies concerning SSRIs that report follow-up data at more than 12 weeks of follow-up. The present study assesses the effectiveness of sertraline and fluoxetine over a period of 24 weeks in obese patients with BED (DSM-IV-TR). Forty-two obese outpatients were randomized and assigned to one of two different drug treatments: 22 were treated with sertraline (dose range: 100-200 mg/day) and 20 with fluoxetine (dose range: 40-80 mg/day). Subjects were assessed at baseline and at 8, 12, and 24 weeks of treatment for binge frequency, weight loss, and severity of psychopathology. No significant differences were found between the two treatments. After 8 weeks of treatment a significant improvement in the Binge Eating Scale score and a significant weight loss emerged. These results were maintained by responders (weigh loss of at least 5% of baseline weight) over 24 weeks. The results suggest that a 6-month treatment with SSRI may be an effective option to treat patients with BED.

Oxcarbazepine for the treatment of binge eating disorder: a case series.

We present a case series of nine obese outpatients with a diagnosis of binge eating disorder who were treated with a flexible dose of the anticonvulsant oxcarbazepine. The drug has not previously been used to treat this disorder. Five patients dropped out at various points of the study, giving only fragmented data. Where data were available, all patients reported side effects (n=7) and some showed a reduction (n=4) or no change (n=3) in binge episode frequency. Some patients lost weight over the study period (n=3; range, 3-5 kg); others showed no change (n=2) or an increase in weight (n=3; range, 1.8-2.9 kg). Our results were inconsistent, but the drug was effective for some patients who showed marked impulsivity in eating behaviours and depressive symptoms.

Liraglutide for psychiatric disorders: clinical evidence and challenges.

Obesity and diabetes are both risk factors and consequences of psychiatric disorders. Glucagon like peptide 1 (GLP-1) receptor agonists such as liraglutide are widely used in the treatment of diabetes and obesity. There are considerable amounts of preclinical studies showing the effects of liraglutide on promotion of neurogenesis, while preventing apoptosis and oxidation. Preliminary clinical evidence has suggested that liraglutide could decrease weight gain, improve cognition and prevent cognitive decline. Accordingly, liraglutide has been regarded as a potential candidate for the management of psychiatric disorders. Herein, we will discuss the association between obesity/diabetes and psychiatric disorders, and the emerging use of liraglutide in psychiatry.

Childhood emotional abuse and neglect in obese patients with and without binge eating disorder: Personality and psychopathology correlates in adulthood.

The link between childhood traumatic experiences such as sexual and physical abuse and EDs in adulthood has been widely demonstrated. To date, however, little research focused on the association between emotional abuse and neglect in childhood and Binge Eating Disorder (BED) and obesity in adulthood. We enrolled 127 patients [84 with BED and 43 obese] and 45 healthy controls (HCs). All participants were administered the same battery of psychometric tests. Between-group differences were explored and the relationship between emotional abuse and neglect in childhood and personality and psychopathology in adulthood was tested. Obese patients showed higher scores in emotional abuse and neglect and sexual abuse when compared to HCs. Within obese participants, those with BED reported higher emotional abuse and emotional neglect than obese without BED and HCs; the BED group differed in physical and sexual abuse from obese participants. The association between traumatic experiences in childhood and obesity in adulthood has been confirmed independently of the type of trauma. Therapists should take into account the traumatic etiology of BED, in particular psychological abuse, even in those patients who do not recall physical or sexual abuses. Specific techniques to approach traumatic experiences could be applied to BED or non-BED patients.

Inhibitory control in obesity and binge eating disorder: A systematic review and meta-analysis of neurocognitive and neuroimaging studies.

The ability to exercise appropriate inhibitory control is critical in the regulation of body weight, but the exact mechanisms are not known. In this systematic review, we identified 37 studies that used specific neuropsychological tasks relevant to inhibitory control performance in obese participants with and without binge eating disorder (BED). We performed a meta-analysis of the studies that used the stop signal task (N=8). We further examined studies on the delay discounting task, the go/no-go task and the Stroop task in a narrative review. We found that inhibitory control is significantly impaired in obese adults and children compared to individuals with body weight within a healthy range (Standardized Mean Difference (SMD): 0.30; CI=0.00, 0.59, p=0.007). The presence of BED in obese individuals did not impact on task performance (SMD: 0.05; CI: -0.22, 0.32, p=0.419). Neuroimaging studies in obesity suggest that lower prefrontal cortex activity affects inhibitory control and BMI. In summary, impairment in inhibitory control is a critical feature associated with obesity and a potential target for clinical interventions.

Reduced Inhibitory Control Mediates the Relationship Between Cortical Thickness in the Right Superior Frontal Gyrus and Body Mass Index.

Unhealthy eating behaviors often develop in the setting of inadequate inhibitory control, a function broadly ascribed to the prefrontal cortex (PFC). Regulation of inhibitory control by the PFC and its anatomical components and their contribution to increasing body mass index (BMI) are poorly understood. To study the role of PFC in the regulation of inhibitory control and body weight, we examined measures of cortical thickness in PFC sub-regions, inhibitory control (color-word interference task (CWIT)), and BMI in 91 healthy volunteers. We tested the predictive effect of PFC sub-regional cortical thickness on BMI and mediation by inhibitory control measured with CWIT. Measures of depression (BDI-II), anxiety (STAI-T) and trauma-related symptoms (TSC-40) were collected; the disinhibition scale of the three-factor eating questionnaire (TFEQ) was used to assess disinhibited eating. We then tested the relationship between BD-II, STAI-T, TSC-40, TFEQ, CWIT, and BMI with correlation analyses. Right superior frontal gyrus cortical thickness significantly predicted BMI (ß=-0.91; t=-3.2; p=0.002). Mediation analysis showed a significant indirect effect of cortical thickness on BMI mediated by inhibitory control (95% CI=-6.1, -0.67). BMI was unrelated to BDI-II, STAI-T, TSC-40, or TFEQ scores. We found an inverse relationship between cortical thickness in the right-superior frontal gyrus and BMI, which was fully mediated by inhibitory control neurocognitive performance. Our results suggest possible targets for neuromodulation in obesity (ie superior frontal gyrus) and a quantifiable mediator of their effects (ie inhibitory control).

Individualized Prediction and Clinical Staging of Bipolar Disorders using Neuroanatomical Biomarkers.

BACKGROUND: Neuroanatomical abnormalities in Bipolar disorder (BD) have previously been reported. However, the utility of these abnormalities in distinguishing individual BD patients from Healthy controls and stratify patients based on overall illness burden has not been investigated in a large cohort. METHODS: In this study, we examined whether structural neuroimaging scans coupled with a machine learning algorithm are able to distinguish individual BD patients from Healthy controls in a large cohort of 256 subjects. Additionally, we investigated the relationship between machine learning predicted probability scores and subjects' clinical characteristics such as illness duration and clinical stages. Neuroimaging scans were acquired from 128 BD patients and 128 Healthy controls. Gray and white matter density maps were obtained and used to 'train' a relevance vector machine (RVM) learning algorithm which was used to distinguish individual patients from Healthy controls. RESULTS: The RVM algorithm distinguished patients from Healthy controls with 70.3 % accuracy (74.2 % specificity, 66.4 % sensitivity, chi-square p<0.005) using white matter density data and 64.9 % accuracy (71.1 % specificity, 58.6 % sensitivity, chi-square p<0.005) with gray matter density. Multiple brain regions - largely covering the fronto - limbic system were identified as 'most relevant' in distinguishing both groups. Patients identified by the algorithm with high certainty (a high probability score) - belonged to a subgroup with more than ten total lifetime manic episodes including hospitalizations (late stage). CONCLUSIONS: These results indicate the presence of widespread structural brain abnormalities in BD which are associated with higher illness burden - which points to neuroprogression.