Luca Lavagnino

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.

Treatment of obese patients with binge eating disorder using topiramate: a review

Topiramate is an anticonvulsant drug used for the treatment of epilepsy and prophylaxis of migraine. Some authors have proposed its use as a mood stabilizer and have reported its efficacy in reducing impulsiveness and improving mood regulation, possibly via its antagonism to glutamatergic transmission in the lateral hypothalamus, although this indication is still controversial. Weight loss is a side effect consistently reported in the medical literature in patients treated with topiramate. Given its potential role in stabilizing mood and reducing impulse control problems and weight, topiramate has been proposed as a treatment for obese patients with binge eating disorder (BED). The aim of this paper is to review published data on the efficacy and safety of topiramate for the treatment of obese subjects with BED. Although the evidence is preliminary, topiramate appears to be a relatively safe and effective treatment for obese subjects with BED. Limitations of the studies and future directions for research are discussed.

Changes in the corpus callosum in women with late-stage bipolar disorder.

This study investigated the differences in corpus callosum (CC) volumes between women with early‐stage and late‐stage bipolar I (BP I) disorder using the criteria previously described in the literature.

Reduced hippocampus volume and memory performance in bipolar disorder patients carrying the BDNF val66met met allele

BACKGROUND Previous studies investigated the impact of brain-derived neurotrophic factor (BDNF) val66met (rs6265) on hippocampus volumes and neurocognition in bipolar disorders (BD), but the results were not consistent. This study aimed to investigate the effect of BDNF polymorphism on hippocampus volumes and memory performance in well-characterized adult populations diagnosed with type I BD (BD-I) and major depressive disorder (MDD) compared with healthy controls (HC). METHODS 48 BD-I patients, 33 MDD patients and 60 HC were genotyped for BDNF rs6265 using DNA isolated from white blood cells. Individuals with val/met and met/met genotypes were grouped as met carriers and compared to those with the val/val. Brain segmentations were obtained from structural magnetic resonance imaging (MRI) using the Freesurfer. Memory performance was assessed with the California Verbal Learning Task (CVLT). RESULTS We found a significant diagnosis effect and marginal interaction between diagnosis and BDNF genotype group for both hippocampus volumes and memory performance. BDNF met allele carrier BD patients had smaller hippocampus volumes and reduced performance on multiple CVLT scores compared to MDD patients and HC. CONCLUSIONS We provide strong evidence for the BDNF val66met polymorphism as a putative biological signature for the neuroanatomical and cognitive abnormalities commonly observed in BD patients.

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

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.

Reduced Resting-State Functional Connectivity of the Somatosensory Cortex Predicts Psychopathological Symptoms in Women with Bulimia Nervosa

Background: Alterations in the resting-state functional connectivity (rs-FC) of several brain networks have been demonstrated in eating disorders. However, very few studies are currently available on brain network dysfunctions in bulimia nervosa (BN). The somatosensory network is central in processing body-related stimuli and it may be altered in BN. The present study therefore aimed to investigate rs-FC in the somatosensory network in bulimic women. Methods: Sixteen medication-free women with BN (age = 23 ± 5 years) and 18 matched controls (age = 23 ± 3 years) underwent a functional magnetic resonance resting-state scan and assessment of eating disorder symptoms. Within-network and seed-based functional connectivity analyses were conducted to assess rs-FC within the somatosensory network and to other areas of the brain. Results: Bulimia nervosa patients showed a decreased rs-FC both within the somatosensory network (t = 9.0, df = 1, P = 0.005) and with posterior cingulate cortex and two visual areas (the right middle occipital gyrus and the right cuneus) (P = 0.05 corrected for multiple comparison). The rs-FC of the left paracentral lobule with the right middle occipital gyrus correlated with psychopathology measures like bulimia (r = −0.4; P = 0.02) and interoceptive awareness (r = −0.4; P = 0.01). Analyses were conducted using age, BMI (body mass index), and depressive symptoms as covariates. Conclusion: Our findings show a specific alteration of the rs-FC of the somatosensory cortex in BN patients, which correlates with eating disorder symptoms. The region in the right middle occipital gyrus is implicated in body processing and is known as extrastriate body area (EBA). The connectivity between the somatosensory cortex and the EBA might be related to dysfunctions in body image processing. The results should be considered preliminary due to the small sample size.

Individualized identification of euthymic bipolar disorder using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and machine learning

BACKGROUND Previous studies have reported that patients with bipolar disorder (BD) present with cognitive impairments during mood episodes as well as euthymic phase. However, it is still unknown whether reported neurocognitive abnormalities can objectively identify individual BD patients from healthy controls (HC). METHODS A total of 21 euthymic BD patients and 21 demographically matched HC were included in the current study. Participants performed the computerized Cambridge Neurocognitive Test Automated Battery (CANTAB) to assess cognitive performance. The least absolute shrinkage selection operator (LASSO) machine learning algorithm was implemented to identify neurocognitive signatures to distinguish individual BD patients from HC. RESULTS The LASSO machine learning algorithm identified individual BD patients from HC with an accuracy of 71%, area under receiver operating characteristic curve of 0.7143 and significant at p=0.0053. The LASSO algorithm assigned individual subjects with a probability score (0-healthy, 1-patient). Patients with rapid cycling (RC) were assigned increased probability scores as compared to patients without RC. A multivariate pattern of neurocognitive abnormalities comprising of affective Go/No-go and the Cambridge gambling task was relevant in distinguishing individual patients from HC. LIMITATIONS Our study sample was small as we only considered euthymic BD patients and demographically matched HC. CONCLUSION Neurocognitive abnormalities can distinguish individual euthymic BD patients from HC with relatively high accuracy. In addition, patients with RC had more cognitive impairments compared to patients without RC. The predictive neurocognitive signature identified in the current study can potentially be used to provide individualized clinical inferences on BD patients.

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.

The relationship between cortical thickness and body mass index differs between women with anorexia nervosa and healthy controls.

Anorexia nervosa (AN) is a severe psychiatric disorder characterized by extreme underweight. Studies conducted with structural MRI found reductions in brain volumes in several areas, but results are mixed. Cortical thickness has shown in other samples specific correlations with BMI in different BMI ranges. In this study, we applied a well validated procedure implemented in Freesurfer software toolkit to investigate cortical thickness in a sample of 21 patients with AN and 18 healthy controls, focusing on group differences and on the relationship between BMI and cortical thickness. Cortical thickness was reduced in patients with AN, but group differences did not survive correction for multiple comparisons. The relationship between BMI and cortical thickness was significantly different in patients with AN compared to controls in the left superior parietal/occipital cortex and left post central cortex. These findings suggest that the relationship between cortical thickness and BMI in patients with AN with less than two years of illness duration significantly differs from that in controls and possible biological mechanisms that may explain this relationship are discussed.

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 (β=-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).