Associations of harsh, unpredictable environment, amygdala connectivity and overeating for children.

OBJECTIVE: In harsh and unpredictable environments, individuals tend to engage in activities that yield immediate rewards as delayed benefits can be unavailable. Substantial evidence suggests that a harsh and unpredictable childhood environment is associated with overeating. However, the neuromechanisms underlying this association remain unclear. This study aimed to investigate amygdala connectivity in relation to environmental harshness and unpredictability (EHU) from an evolutionary perspective and examine their relationship with overeating in children. METHODS: Eighty-five children aged 8 to 12 years were scanned using a magnetic resonance imaging machine to assess resting-state functional connectivity (RSFC) of the two subregions of the amygdala (i.e., centromedial amygdala [CMA]; basolateral amygdala [BLA]). Self-reports of EHU and parental reports of overeating, including food responsiveness and enjoyment of food, were obtained cross-sectionally. Furthermore, findings indicated that children completed high- and low-calorie food portion choice tasks in the absence of hunger at 12 months of follow-up. RESULTS: EHU was positively associated with parental reports of overeating, including food responsiveness and enjoyment, as well as children's selection of high-calorie food portion sizes. Moreover, static RSFC analyses revealed that EHU was negatively associated with bilateral BLA-left inferior frontal gyrus (IFG) connectivity, while dynamic RSFC analyses found that EHU was negatively associated with right CMA, left inferior parietal lobule, and right CMA-right precuneus connectivity. Particularly, the left BLA-left IFG connectivity mediated the association between EHU and parental reports of food responsiveness. CONCLUSION: EHU was negatively associated with amygdala connectivity, which is implicated in the intrinsic processing of emotional regulation. Furthermore, deficits in emotional regulation resulted in increased energy intake. These insights provide a new perspective for understanding the developmental neuromechanisms underlying obesity.

Uncontrolled eating: a unifying heritable trait linked with obesity, overeating, personality and the brain.

Many eating-related psychological constructs have been proposed to explain obesity and overeating. However, these constructs, including food addiction, disinhibition, hedonic hunger, emotional eating, binge eating and the like all have similar definitions, emphasizing loss of control over intake. As questionnaires measuring the constructs correlate strongly (r > 0.5) with each other, we propose that these constructs should be reconsidered to be part of a single broad phenotype: uncontrolled eating. Such an approach enables reviewing and meta-analysing evidence obtained with each individual questionnaire. Here, we describe robust associations between uncontrolled eating, body mass index (BMI), food intake, personality traits and brain systems. Reviewing cross-sectional and longitudinal data, we show that uncontrolled eating is phenotypically and genetically intertwined with BMI and food intake. We also review evidence on how three psychological constructs are linked with uncontrolled eating: lower cognitive control, higher negative affect and a curvilinear association with reward sensitivity. Uncontrolled eating mediates all three constructs' associations with BMI and food intake. Finally, we review and meta-analyse brain systems possibly subserving uncontrolled eating: namely, (i) the dopamine mesolimbic circuit associated with reward sensitivity, (ii) frontal cognitive networks sustaining dietary self-control and (iii) the hypothalamus-pituitary-adrenal axis, amygdala and hippocampus supporting stress reactivity. While there are limits to the explanatory and predictive power of the uncontrolled eating phenotype, we conclude that treating different eating-related constructs as a single concept, uncontrolled eating, enables drawing robust conclusions on the relationship between food intake and BMI, psychological variables and brain structure and function.

Is brain response to food rewards related to overeating? A test of the reward surfeit model of overeating in children.

The reward surfeit model of overeating suggests that heightened brain response to rewards contributes to overeating and subsequent weight gain. However, previous studies have not tested whether brain response to reward is associated with food intake, particularly during childhood, a period of dynamic development in reward and inhibitory control neurocircuitry. We conducted functional magnetic resonance imaging (fMRI) with 7-11-year-old children (n = 59; healthy weight, n = 31; overweight, n = 28; 54% female) while they played a modified card-guessing paradigm to examine blood-oxygen-level-dependent (BOLD) response to anticipating and winning rewards (food, money, neutral). Food intake was assessed at three separate meals that measured different facets of eating behavior: 1) typical consumption (baseline), 2) overindulgence (palatable buffet), and 3) eating in the absence of hunger (EAH). A priori regions of interest included regions implicated in both reward processing and inhibitory control. Multiple stepwise regressions were conducted to examine the relationship between intake and BOLD response to rewards. Corrected results showed that a greater BOLD response in the medial prefrontal cortex for anticipating food compared to money positively correlated with how much children ate at the baseline and palatable buffet meals. BOLD response in the dorsolateral prefrontal cortex for winning food compared to money was positively correlated with intake at the palatable buffet meal and EAH. All aforementioned relationships were independent of child weight status. Findings support the reward surfeit model by showing that increased brain response to food compared to money rewards positively correlates with laboratory measures of food intake in children.

Fine morphological evaluation of hypothalamus in patients with hyperphagia.

BACKGROUND: Various metabolic diseases induced by eating disorders are some of the most serious and difficult problems for modern public healthcare. However, little is known about hyperphagia, partly because of the lack of a clear definition. Several basic studies have analyzed eating habits using endocrinological or neurophysiological approaches, which have suggested a controlled balance between the hunger and satiety centers in the central nervous system. However, more detailed neuro-radiologic evaluations have not been achieved for the hypothalamus, and evaluations were limited only to the floor of the third ventricles. METHODS: Fine structures of hypothalamic morphology were investigated using high-resolution magnetic resonance imaging in seven patients with hypothalamo-pituitary tumors, who suffered from preoperative hyperphagia-induced severe obesity and metabolic disorders. Body mass index (BMI) varied from 22.4 to 40.5 kg/m2 (mean 32.8 kg/m2). Clinical data were compared with the data of nine patients without hyperphagia and seven healthy volunteers. RESULTS: Morphological evaluation was possible in all patients and control subjects, and patients with hyperphagia had significantly shortened maximum distances between the ependymal layers of the lateral wall of the third ventricle and fornixes (hyperphagia group right side 0.30 mm, left side 0.23 mm vs. patients without hyperphagia group right side 1.60, left side 1.53 vs. healthy group right side 1.73 mm, left side 1.85 mm) (p < 0.01). Two patients achieved postoperative improvement in both clinical and neuro-radiological findings. CONCLUSION: Eating and metabolic disorders are related to strong dysfunction of the medial nuclei of the hypothalamus in patients with hypothalamo-pituitary tumors. We report the first case of dynamic improvement from hyperphagia, with both symptomatic and neuro-radiological findings.

Elevated monoamine oxidase a binding during major depressive episodes is associated with greater severity and reversed neurovegetative symptoms.

Inadequate treatment response occurs in approximately 40% of major depressive episodes (MDEs), and one approach to solve this is careful matching of treatment to the specific pathologies of MDE. One such biological abnormality is elevated monoamine oxidase A (MAO-A) levels, which occurs in the prefrontal and anterior cingulate cortex (PFC and ACC) during MDE; however, the subtypes for which this abnormality is most prominent are unknown. We hypothesized that MAO-A levels in the PFC and ACC are most elevated in MDE with greater severity and reversed neurovegetative symptoms (hypersomnia and either hyperphagia or weight gain). MAO-A VT (an index of MAO-A density) was measured using [(11)C]harmine positron emission tomography (PET) in 42 subjects with MDEs secondary to major depressive disorder and 37 healthy controls. The effect of severity and reversed neurovegetative symptoms on MAO-A VT in the PFC and ACC was analyzed using a multivariate analysis of variance (MANOVA). Greater severity and reversed neurovegetative symptoms were associated with elevated MAO-A VT in the PFC and ACC (MANOVA, severity: F(2,38)=5.44, p=0.008; reversed neurovegetative symptoms: F(2,38)=5.13, p=0.01). Increased MAO-A level, when greater severity and reversed neurovegetative symptoms are present, may explain the association of these clinical features with a preferential response to MAO inhibitors, which is especially well-evidenced for reversed neurovegetative symptoms in MDE. As MAO-A creates oxidative stress, facilitates apoptosis, and metabolizes monoamines, therapeutics opposing these processes are predicted to best treat MDE with greater severity and reversed neurovegetative symptoms.

Hypothalamic obesity syndrome: rare presentation of CNS+ B-cell lymphoblastic lymphoma.

Hypothalamic obesity syndrome can affect brain tumor patients following surgical intervention and irradiation. This syndrome is rare at diagnosis in childhood cancer, but has been reported with relapse of acute lymphoblastic leukemia. Here we present a case of hypothalamic obesity syndrome as the primary presentation of a toddler found to have CNS+ B-cell lymphoblastic lymphoma. Cytogenetic studies on diagnostic cerebrospinal fluid revealed MLL gene rearrangement (11q23). Hyperphagia and obesity dramatically improved following induction and consolidation chemotherapy. We describe a novel presentation of hypothalamic obesity syndrome in CNS B-cell lymphoblastic lymphoma, responsive to chemotherapy.