Damien Ringuenet

Influence of prefrontal target region on the efficacy of repetitive transcranial magnetic stimulation in patients with medication-resistant depression: a [18F]-fluorodeoxyglucose PET and MRI study

It is currently unknown whether the antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) depends on specific characteristics of the stimulated frontal area, such as metabolic changes. We investigated the effect of high-frequency rTMS, administered over the most hypometabolic prefrontal area in depressed patients in a two-site, double-blind, randomized placebo-controlled add-on study. Forty-eight patients with medication-resistant major depression underwent magnetic resonance imaging and [(18)F]-fluorodeoxyglucose positron emission tomography (PET) in order to determine a target area for rTMS. After randomization to PET-guided (n = 16), standard (n = 18), or sham rTMS (n = 14) conditions, the patients received 10 sessions of 10-Hz rTMS (1600 pulses/session) at 90% motor threshold. Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores did not differ between PET-guided, standard and sham groups at 2-wk end-point. Exploratory comparison of left PET-guided (n = 9), right PET-guided, standard, and sham rTMS revealed significant effects. The highest improvement in MADRS scores was observed with left PET-guided (60 + or - 31%), significantly superior to sham (30 + or - 37%, p = 0.01) and right-guided (31 + or - 33%, p = 0.02) stimulation. Comparison between left PET-guided and standard rTMS (49 + or - 28%) was not significant (p = 0.12). Comparison between stimulation over dorsolateral prefrontal cortex (BA 9-46), stimulation of other areas, and sham rTMS was statistically significant. Stimulation over BA 9-46 region (n = 15) was superior to sham rTMS (p = 0.02). The results do not support the general hypothesis of increased antidepressant effects of high-frequency rTMS with prefrontal hypometabolism-related PET guidance. Nonetheless, whether metabolism and anatomy characteristics of left frontal area underneath the coil might account for an increase or speeding up of rTMS effects needs further investigation.

Cortical folding difference between patients with early-onset and patients with intermediate-onset bipolar disorder

OBJECTIVES Cerebral abnormalities have been detected in patients with bipolar disorder (BD). In comparison to BD with a later onset, early-onset BD has been found to have a poorer outcome. However, it is yet unknown whether neuroanatomical abnormalities differ between age-at-onset subgroups of the illness. We searched for cortical folding differences between early-onset (before 25 years) and intermediate-onset (between 25 and 45 years) BD patients. METHODS Magnetic resonance images of 22 early-onset BD patients, 14 intermediate-onset BD patients, and 50 healthy participants were analyzed using a fully automated method to extract, label, and measure the sulcal area in the whole cortex. Cortical folding was assessed by computing global sulcal indices (the ratio between total sulcal area and total outer cortex area) for each hemisphere, and local sulcal indices for 12 predefined regions in both hemispheres. RESULTS Intermediate-onset BD patients had a significantly reduced local sulcal index in the right dorsolateral prefrontal cortex in comparison to both early-onset BD patients and healthy subjects, and lower global sulcal indices in both hemispheres in comparison to healthy subjects (p < 0.05, Bonferroni corrected). Brain tissue volumes did not differ between groups. CONCLUSIONS This study provided the first evidence of a neuroanatomic difference between intermediate-onset and early-onset BD, which lends further support to the existence of different age-at-onset subgroups of BD.

Baseline Brain Metabolism in Resistant Depression and Response to Transcranial Magnetic Stimulation

Neuroimaging studies of patients with treatment-resistant depression (TRD) have reported abnormalities in the frontal and temporal regions. We sought to determine whether metabolism in these regions might be related to response to repetitive transcranial magnetic stimulation (TMS) in patients with TRD. Magnetic resonance images and baseline resting-state cerebral glucose uptake index (gluMI) obtained using 18F-fluorodeoxyglucose positron emission tomography were analyzed in TRD patients who had participated in a double-blind, randomized, sham-controlled trial of prefrontal 10 Hz TMS. Among the patients randomized to active TMS, 17 responders, defined as having 50% depression score decrease, and 14 nonresponders were investigated for prestimulation glucose metabolism and compared with 39 healthy subjects using a voxel-based analysis. In nonresponders relative to responders, gluMI was lower in left lateral orbitofrontal cortex (OFC), and higher in left amygdala and uncinate fasciculus. OFC and amygdala gluMI negatively correlated in nonresponders, positively correlated in responders, and did not correlate in healthy subjects. Relative to healthy subjects, both responders and nonresponders displayed lower gluMI in right dorsolateral prefrontal (DLPFC), right anterior cingulate (ACC), and left ventrolateral prefrontal cortices. Additionally, nonresponders had lower gluMI in left DLPFC, ACC, left and right insula, and higher gluMI in left amygdala and uncus. Hypometabolisms were partly explained by gray matter reductions, whereas hypermetabolisms were unrelated to structural changes. The findings suggest that different patterns of frontal–temporal–limbic abnormalities may distinguish responders and nonresponders to prefrontal magnetic stimulation. Both preserved OFC volume and amygdala metabolism might precondition response to TMS.

Levels of autistic traits in anorexia nervosa: a comparative psychometric study

BackgroundA number of characteristics associated with Autism Spectrum Disorders (ASD) are over-represented among patients with Anorexia Nervosa (AN) as well as among relatives of these patients. Yet the co-occurrence of autistic traits in AN has not been fully explored and no previous study has directly compared self-reported evaluations of cognitive and socio-affective skills in AN and ASD.MethodsWe aimed to determine the degree of overlap between AN and ASD from scores on questionnaires classically used to measure ASD impairments. Fifteen AN participants, 15 ASD participants and two groups of matched controls completed a battery of self-reports measuring: autistic traits (Autism-Spectrum Quotient), empathy (Empathy Quotient-short and Interpersonal Reactivity Index), systemizing (Systemizing Quotient-short) and alexithymia (Bermond-Vorst Alexithymia Questionnaire-B). Univariate comparisons of mean totalled scores were performed on each measure (patients vs. controls, and AN vs. ASD), and a Principal Component Analysis was used to study subject proximities in a reduced-factor space constructed from AQ, BVAQ-B and IRI subscales.ResultsThese analyses revealed similarities in a few cognitive domains (Attention Switching, Perspective Taking and Fantasy, lack of emotional introspection) and in some nonspecific affective dimensions (depression and feelings of distress), but also marked dissimilarities in social skills (the ability to communicate emotions to others, empathizing).ConclusionThe AN and ASD participants reported similar needs for sameness, and similar difficulties understanding their emotions and taking the perspective of another, but contrasting abilities to feel concerned in interpersonal situations. Our mixed findings encourage further exploration of transdiagnostic similarities and associations between these disorders.

Underweight patients with anorexia nervosa: Comparison of bioelectrical impedance analysis using five equations to dual X-ray absorptiometry

BACKGROUND & AIMS Body weight changes do not reflect the respective changes of body compartments, namely fat-free mass (FFM) and fat mass (FM). Both bioelectrical Impedance Analysis (BIA) and the Dual X-ray absorptiometry (DXA) measure FFM and FM. This study in underweight patients with anorexia nervosa (AN) aims to compare measurements of FM and FFM done by DXA and BIA using 5 different BIA equations already validated in healthy population and to identify the most suitable BIA equation for AN patients. METHODS Fifty female patients with AN (BMI=14.3 ± 1.49, age=19.98 ± 5.68yrs) were included in the study. Body composition was measured by DXA (Delphi W, Hologic, Bedford, MA) and by 50 kHz BIA (FORANA, Helios) using 5 different BIA equations validated in healthy population (Sun, Geneva, Kushner, Deurenberg and Roubenoff equations). Comparison between the DXA and the 5 BIA equations was done using the sum of the squares of differences and Bland-Altman plots. RESULTS The Deurenberg equation gave the best estimates of FFM when compared to the measurements by DXA (FFM(dxa)=35.80 kg versus FFM(deurenberg)=36.36 kg) and very close estimates of FM (FM(dxa)=9.16 kg and FM(deurenberg)=9.57 kg) The Kushner equation showed slightly better estimates for FM (FM(kushner)=9. 0kg) when compared to the DXA, but not for FFM. Sun equation gave the broadest differences for FM and FFM when compared with DXA. CONCLUSION The best available BIA equation to calculate the FFM and the FM in patients with AN is the Deurenberg equation. It takes into account the weight, height and age and is applicable in adults and adolescents AN patients with BMI of 12.8-21.0, and for ages between 13.4 and up to 36.9 years.

Amygdala and regional volumes in treatment-resistant versus nontreatment-resistant depression patients

Although treatment‐resistant and nontreatment‐resistant depressed patients show structural brain anomalies relative to healthy controls, the difference in regional volumetry between these two groups remains undocumented.

Anorexia nervosa hyperactivity-induced ischemic colitis (ANHIC): a new cause of anaemia.

Anorexia nervosa (AN) is a complex and multifactorial psychiatric pathologywith frequent acute or chronic somatic repercussions. It is classically considered that not only malnutrition, metabolic variations and numerous deficiencies in the restrictive sub-type of AN but also digestive lesions associated with other eating disorders sub-type (binge/purging AN, bulimia nervosa, rumination disorder, PICA) can lead to haematological changes [1]. In the literature, anaemia is more specifically and frequently described in AN and mainly as a result of medullary hypometabolism [2]. Despite common representations, cases of anaemia described in restrictive-type AN are not rare and are mostly transient andmoderately severe [3]. In contrast, the detection of some atypical biological stigmata such as a severe microcytic anaemia should raise the question of a differential diagnosis, or at least the co-occurrence of an organic pathology, such as inflammatory colopathy or coeliac disease [4]. Other cases of severe and profound anaemia, often developing very suddenly, can be observed in situations of extreme malnutrition with very low body weights and/or very rapid weight loss. The mechanism implicated is gelatinous degeneration of the bone marrow usually affecting the three cell lines, with a risk of multi-organ failure that is life threatening in the short term [5]. Finally, cases of severe anaemia have been described in Lasthénie de Ferjol syndrome, where the eating disorder is associated with severe psychiatric comorbidity [6]. We report the case of a female adolescent patient with AN presenting severe, recurrent episodes of red blood cell depletion, which did not fit the previously described situations, and could be related to a new and underdiagnosed clinical entity we called anorexia nervosa hyperactivity-induced ischemic colitis (ANHIC).