Yuri Okamoto

Attenuated Left Prefrontal Activation during a Verbal Fluency Task in Patients with Depression

Functional neuroimaging studies on patients with depression have found abnormal activity in the left prefrontal and anterior cingulate cortex compared with healthy controls. Other studies have shown that these regions become active in healthy subjects during verbal fluency tasks, while patients with depression show impaired performance on such tasks. We used functional magnetic resonance imaging to investigate changes in cerebral blood oxygenation associated with a verbal fluency task in depressed patients and healthy volunteers. In contrast to 10 age- and sex-matched healthy control subjects who activated the left prefrontal cortex and the anterior cingulate cortex during word generation, 10 depressed subjects showed attenuated activation in the left prefrontal cortex and did not show significant activation in the anterior cingulate cortex. These findings suggest that impaired performance during verbal fluency task in depressed patients is associated with abnormal neural responses within these regions.

Neural processing of negative word stimuli concerning body image in patients with eating disorders: An fMRI study

Eating disorders (EDs) are associated with abnormalities of body image perception. The aim of the present study was to investigate the functional abnormalities in brain systems during processing of negative words concerning body images in patients with EDs. Brain responses to negative words concerning body images (task condition) and neutral words (control condition) were measured using functional magnetic resonance imaging in 36 patients with EDs (12 with the restricting type anorexia nervosa; AN-R, 12 with the binging-purging type anorexia nervosa; AN-BP, and 12 with bulimia nervosa; BN) and 12 healthy young women. Participants were instructed to select the most negative word from each negative body-image word set and to select the most neutral word from each neutral word set. In the task relative to the control condition, the right amygdala was activated both in patients with AN-R and in patients with AN-BP. The left medial prefrontal cortex (mPFC) was activated both in patients with BN and in patients with AN-BP. It is suggested that these brain activations may be associated with abnormalities of body image perception. Amygdala activation may be involved in fearful emotional processing of negative words concerning body image and strong fears of gaining weight. One possible interpretation of the finding of mPFC activation is that it may reflect an attempt to regulate the emotion invoked by the stimuli. These abnormal brain functions may help provide better accounts of the psychopathological mechanisms underlying EDs.

Brain activation during the perception of stressful word stimuli concerning interpersonal relationships in anorexia nervosa patients with high degrees of alexithymia in an fMRI paradigm

Several studies have reported that anorexia nervosa (AN) patients have high levels of alexithymia. However, relatively little is known about the underlying neurobiological relationships between alexithymia and AN. We used functional magnetic resonance imaging to examine the brain responses in 30 AN patients and 20 healthy women during the processing of negative words concerning interpersonal relationships. We investigated the relationship between alexithymia levels and brain activation in AN. AN patients showed significant activation of the orbitofrontal cortex, dorsolateral prefrontal cortex and medial prefrontal cortex while processing negative words concerning interpersonal relationships, as compared to the processing of neutral words. Moreover, the subjective rating of unpleasantness with negative words and neural activities in the amygdala, posterior cingulate cortex (PCC) and anterior cingulate cortex (ACC) negatively correlated with the level of alexithymia in AN. Our neuroimaging results suggest that AN patients tend to cognitively process negative words concerning interpersonal relationships, resulting in activation of the prefrontal cortex. Lower activation of the amygdala, PCC and ACC in response to these words may contribute to the impairments of emotional processing that are hallmarks of alexithymia. Functional abnormalities associated with alexithymia may be involved in the emotional processing impairments in AN patients.

Psychological and weight-related characteristics of patients with anorexia nervosa-restricting type who later develop bulimia nervosa.

BackgroundPatients with anorexia nervosa-restricting type (AN-R) sometimes develop accompanying bulimic symptoms or the full syndrome of bulimia nervosa (BN). If clinicians could predict who might change into the bulimic sub-type or BN, preventative steps could be taken. Therefore, we investigated anthropometric and psychological factors possibly associated with such changes.MethodAll participants were from a study by the Japanese Genetic Research Group for Eating Disorders. Of 80 patients initially diagnosed with AN-R, 22 changed to the AN-Binge Eating/Purging Type (AN-BP) and 14 to BN for some period of time. The remaining 44 patients remained AN-R only from the onset to the investigation period. Variables compared by ANOVA included anthropometric measures, personality traits such as Multiple Perfectionism Scale scores and Temperament and Character Inventory scores, and Beck Depression Inventory-II scores.ResultsIn comparison with AN-R only patients, those who developed BN had significantly higher current BMI (p < 0.05) and maximum BMI in the past (p < 0.05). They also scored significantly higher for the psychological characteristic of parental criticism (p < 0.05) and lower in self-directedness (p < 0.05), which confirms previous reports, but these differences disappeared when the depression score was used as a co-variant. No significant differences were obtained for personality traits or depression among the AN-R only patients irrespective of their duration of illness.ConclusionThe present findings suggest a tendency toward obesity among patients who cross over from AN-R to BN. Low self-directedness and high parental criticism may be associated with the development of BN by patients with AN-R, although the differences may also be associated with depression.

Single or repeated treatment with electroconvulsive shock increases number of serotonin uptake binding sites in the frontal cortex

The effects of a single or repeated treatment with electroconvulsive shock (ECS) or imipramine on the central serotonin (5-HT) uptake binding sites were studied in the rat frontal cortex and hippocampus. The selective 5-HT uptake inhibitor citalopram and clomipramine potently inhibited the binding for [3H]paroxetine (5-HT uptake binding sites) in the frontal cortex. The antidepressant drugs imipramine and desipramine inhibited the binding moderately, but the 5-HT-related agents, 5-HT, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), mianserin and ketanserin inhibited it weakly. A single ECS increased the density of [3H]paroxetine binding sites, but did not alter the affinity, after 1 or 24 h, in the frontal cortex. Repeated treatment with ECS, but not with imipramine, increased the density of [3H]paroxetine binding sites in the same region. The hippocampal [3H]paroxetine binding did not change after any of these treatments. These results suggest that a single treatment with ECS causes a rapid increase in the neuronal 5-HT transporter complex and the increase lasts for 14 days in the frontal cortex.

Temporomesial activation in young females associated with unpleasant words concerning body image

Previous behavioral studies suggest that people who have an abnormal eating behavior may perceive information concerning body image distortion more aversively than others. We performed a functional magnetic resonance imaging (fMRI) study on 15 young women, using an emotional decision task including unpleasant words concerning body image and neutral words. The left amygdala and right parahippocampal gyrus were activated by unpleasant words concerning body image relative to neutral words. In addition, activation of the right parahippocampal gyrus was negatively correlated with the severity of psychological and behavioral problems assessed by the Eating Disorder Inventory-2. This activation also positively correlated with the subjects’ rating of pleasantness of words concerning body image. These results demonstrated that the temporomesial area plays an important role in the perception of unpleasant words concerning body image. In particular, it is suggested that the right parahippocampal gyrus may be associated with subjective sensitivity to unpleasant information concerning body image.

A ghrelin gene variant may predict crossover rate from restricting-type anorexia nervosa to other phenotypes of eating disorders: a retrospective survival analysis.

Background Patients with anorexia nervosa restricting type (AN-R) often develop bulimic symptoms and crossover to AN-binge eating/purging type (AN-BP), or to bulimia nervosa (BN). We have reported earlier that genetic variants of an orexigenic peptide ghrelin are associated with BN. Here, the relationship between a ghrelin gene variant and the rate of change from AN-R to other phenotypes of eating disorders (EDs) was investigated. Methods Participants were 165 patients with ED, initially diagnosed as AN-R. The dates of their AN-R onset and changes in diagnosis to other subtypes of ED were investigated retrospectively. Ghrelin gene 3056 T→C SNP (single nucleotide polymorphism) was genotyped. Probability and hazard ratios were analyzed using life table analysis and Coxs proportional hazard regression model, in which the starting point was the time of AN-R onset and the outcome events were the time of (i) onset of binge eating, that is, when patients changed to binge eating AN and BN and (ii) recovery of normal weight, that is, when patients changed to BN or remission. Results Patients with the TT genotype at 3056 T→C had a higher probability and hazard ratio for recovery of normal weight. The ghrelin SNP was not related with the onset of binge eating. Conclusion The 3056 T→C SNP of the ghrelin gene is related to the probability and the rate of recovery of normal body weight from restricting-type AN.

No association of brain‐derived neurotrophic factor Val66Met polymorphism with anorexia nervosa in Japanese

The Met66 allele of the Val66Met polymorphism in the brain‐derived neurotrophic factor (BDNF) gene has been reported to be associated with anorexia nervosa (AN), and also lower minimum body mass index (BMI) and higher harm avoidance in AN. We genotyped the Val66Met polymorphism (rs6265) in 689 AN cases and 573 control subjects. There were no significant differences in the genotype or allele frequencies of the Val66Met between AN and control subjects (allele wise, odds ratio = 0.920, 95% CI 0.785–1.079, P = 0.305). No difference was found in minimum BMIs related to Val66Met in AN (one‐way ANOVA, P > 0.05). Harm avoidance scores on the Temperament and Character Inventory were lower in the Met66 allele carriers (P = 0.0074) contrary to the previous report. Thus we were unable to replicate the previous findings that the Met66 allele of the BDNF is associated with AN and that the minimum BMI is lower or the harm avoidance score is higher in AN patients with the Met66 allele.

Effects of behavioural activation on the neural basis of other perspective self-referential processing in subthreshold depression: a functional magnetic resonance imaging study

Background It has been demonstrated that negatively distorted self-referential processing, in which individuals evaluate ones own self, is a pathogenic mechanism in subthreshold depression that has a considerable impact on the quality of life and carries an elevated risk of developing major depression. Behavioural activation (BA) is an effective intervention for depression, including subthreshold depression. However, brain mechanisms underlying BA are not fully understood. We sought to examine the effect of BA on neural activation during other perspective self-referential processing in subthreshold depression. Method A total of 56 subjects underwent functional magnetic resonance imaging scans during a self-referential task with two viewpoints (self/other) and two emotional valences (positive/negative) on two occasions. Between scans, while the intervention group (n = 27) received BA therapy, the control group (n = 29) did not. Results The intervention group showed improvement in depressive symptoms, increased activation in the dorsal medial prefrontal cortex (dmPFC), and increased reaction times during other perspective self-referential processing for positive words after the intervention. Also, there was a positive correlation between increased activation in the dmPFC and improvement of depressive symptoms. Additionally, there was a positive correlation between improvement of depressive symptoms and increased reaction times. Conclusions BA increased dmPFC activation during other perspective self-referential processing with improvement of depressive symptoms and increased reaction times which were associated with improvement of self-monitoring function. Our results suggest that BA improved depressive symptoms and objective monitoring function for subthreshold depression.

Detailed course of depressive symptoms and risk for developing depression in late adolescents with subthreshold depression: a cohort study

Purpose Despite its clinical importance, adolescent subthreshold depression remains a largely neglected topic. The aims of this study were to accurately identify the natural course of depressive symptoms and the risk for developing major depressive episode (MDE) in late adolescents with subthreshold depression over 1 year. Patients and methods One hundred and seventy-two participants <20 years of age (mean age: 18.32 years, standard deviation: 0.50), who did not meet the full criteria for an MDE, were selected from 2,494 screened freshmen based on the Beck Depression Inventory, 2nd edition (BDI-II). We conducted a cohort study of three groups (low-, middle-, and high-symptom groups) divided based on BDI-II scores, over a 1 year period with the use of bimonthly assessments. Temporal changes of depressive symptoms were analyzed using linear mixed modeling and growth mixture modeling. Results First, we found that late adolescents with subthreshold depression (high depressive symptoms) were split between the increasing and decreasing depressive symptoms groups, whereas the majority of the less-symptoms group remained stable during 1 year. Second, in comparison with late adolescents with less depressive symptoms, those with subthreshold depression had an elevated risk of later depression. Conclusion Some late adolescents with subthreshold depression had increased depressive symptoms and developed an MDE during 1 year. Therefore, it is necessary for us to rigorously assess the changes in subthreshold depressive symptoms over time in late adolescents.