Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization.

Previous studies reported decreased glutamate levels in the anterior cingulate cortex (ACC) in non-treatment-resistant schizophrenia and first-episode psychosis. However, ACC glutamatergic changes in subjects at high-risk for psychosis, and the effects of commonly experienced environmental emotional/social stressors on glutamatergic function in adolescents remain unclear. In this study, adolescents recruited from the general population underwent proton magnetic resonance spectroscopy (MRS) of the pregenual ACC using a 3-Tesla scanner. We explored longitudinal data on the association of combined glutamate-glutamine (Glx) levels, measured by MRS, with subclinical psychotic experiences. Moreover, we investigated associations of bullying victimization, a risk factor for subclinical psychotic experiences, and help-seeking intentions, a coping strategy against stressors including bullying victimization, with Glx levels. Finally, path analyses were conducted to explore multivariate associations. For a contrast analysis, gamma-aminobutyric acid plus macromolecule (GABA+) levels were also analyzed. Negative associations were found between Glx levels and subclinical psychotic experiences at both Times 1 (n = 219, mean age 11.5 y) and 2 (n = 211, mean age 13.6 y), as well as for over-time changes (n = 157, mean interval 2.0 y). Moreover, effects of bullying victimization and bullying victimization × help-seeking intention interaction effects on Glx levels were found (n = 156). Specifically, bullying victimization decreased Glx levels, whereas help-seeking intention increased Glx levels only in bullied adolescents. Finally, associations among bullying victimization, help-seeking intention, Glx levels, and subclinical psychotic experiences were revealed. GABA+ analysis revealed no significant results. This is the first adolescent study to reveal longitudinal trajectories of the association between glutamatergic function and subclinical psychotic experiences and to elucidate the effect of commonly experienced environmental emotional/social stressors on glutamatergic function. Our findings may deepen the understanding of how environmental emotional/social stressors induce impaired glutamatergic neurotransmission that could be the underpinning of liability for psychotic experiences in early adolescence.

Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

Cerebral cortical structural alteration patterns across four major psychiatric disorders in 5549 individuals.

According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the disorders. We hypothesized that there are also similarities and differences in cortical structural neuroimaging features among these psychiatric disorders. T1-weighted magnetic resonance imaging scans were performed for 5,549 subjects recruited from 14 sites. Effect sizes were determined using a linear regression model within each protocol, and these effect sizes were meta-analyzed. The similarity of the differences in cortical thickness and surface area of each disorder group was calculated using cosine similarity, which was calculated from the effect sizes of each cortical regions. The thinnest cortex was found in SZ, followed by BD and MDD. The cosine similarity values between disorders were 0.943 for SZ and BD, 0.959 for SZ and MDD, and 0.943 for BD and MDD, which indicated that a common pattern of cortical thickness alterations was found among SZ, BD, and MDD. Additionally, a generally smaller cortical surface area was found in SZ and MDD than in BD, and the effect was larger in SZ. The cosine similarity values between disorders were 0.945 for SZ and MDD, 0.867 for SZ and ASD, and 0.811 for MDD and ASD, which indicated a common pattern of cortical surface area alterations among SZ, MDD, and ASD. Patterns of alterations in cortical thickness and surface area were revealed in the four major psychiatric disorders. To our knowledge, this is the first report of a cross-disorder analysis conducted on four major psychiatric disorders. Cross-disorder brain imaging research can help to advance our understanding of the pathogenesis of psychiatric disorders and common symptoms.

Longitudinal change in mismatch negativity (MMN) but not in gamma-band auditory steady-state response (ASSR) is associated with psychological difficulties in adolescence.

Adolescence is a critical period for psychological difficulties. Auditory mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are representative electrophysiological indices that mature during adolescence. However, the longitudinal association between MMN/ASSR and psychological difficulties among adolescents remains unclear. We measured MMN amplitude for duration and frequency changes and ASSR twice in a subsample (n = 67, mean age 13.4 and 16.1 years, respectively) from a large-scale population-based cohort. No significant longitudinal changes were observed in any of the electroencephalography indices. Changes in SDQ-TD were significantly associated with changes in duration MMN, but not frequency MMN and ASSR. Furthermore, the subgroup with higher SDQ-TD at follow-up showed a significant duration MMN decrease over time, whereas the subgroup with lower SDQ-TD did not. The results of our population neuroscience study suggest that insufficient changes in electroencephalography indices may have been because of the short follow-up period or non-monotonic change during adolescence, and indicated that the longitudinal association with psychological difficulties was specific to the duration MMN. These findings provide new insights that electrophysiological change may underlie the development of psychosocial difficulties emerging in adolescence.

Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment.

Antipsychotic drugs are the mainstay in the treatment of schizophrenia. However, one-third of patients do not show adequate improvement in positive symptoms with non-clozapine antipsychotics. Additionally, approximately half of them show poor response to clozapine, electroconvulsive therapy, or other augmentation strategies. However, the development of novel treatment for these conditions is difficult due to the complex and heterogenous pathophysiology of treatment-resistant schizophrenia (TRS). Therefore, this review provides key findings, potential treatments, and a roadmap for future research in this area. First, we review the neurobiological pathophysiology of TRS, particularly the dopaminergic, glutamatergic, and GABAergic pathways. Next, the limitations of existing and promising treatments are presented. Specifically, this article focuses on the therapeutic potential of neuromodulation, including electroconvulsive therapy, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation. Finally, we propose multivariate analyses that integrate various perspectives of the pathogenesis, such as dopaminergic dysfunction and excitatory/inhibitory imbalance, thereby elucidating the heterogeneity of TRS that could not be obtained by conventional statistics. These analyses can in turn lead to a precision medicine approach with closed-loop neuromodulation targeting the detected pathophysiology of TRS.

Daily fat intake is associated with basolateral amygdala response to high-calorie food cues and appetite for high-calorie food.

OBJECTIVES: Animal studies have indicated that fat intake mediates amygdala activation, which in turn promotes fat intake, while amygdala activation increases the preference for fat and leads to increased fat intake. However, the association among fat intake, amygdala activation, and appetite for high-calorie foods in humans remains unclear. Thus, to examine this association, we conducted a functional magnetic resonance imaging (fMRI) experiment. METHODS: Fifty healthy-weight adults (18 females; mean age: 22.9 ± 3.02 years) were included. Participants were shown images of high-calorie and low-calorie foods and were instructed to rate their desire to eat the food items during fMRI. All participants provided information on their daily fat intake using a self-reported questionnaire. Associations among fat intake, the desire to eat high-calorie or low-calorie food items, and amygdala responses to food items were examined. RESULTS: The basolateral amygdala (BLA) response was positively associated with fat intake ([x, y, z] = [24, -6, -16], z = 3.91, pFWE-corrected = 0.007) and the desire to eat high-calorie food items ([26, -4, -16], z = 3.75, pFWE-corrected = 0.010). Structural equation modeling showed that the desire for high-calorie food items was predicted by BLA response to high-calorie food items (p = 0.013, ß = 3.176), and BLA response was predicted by fat intake (p < 0.001, ß = 0.026). DISCUSSION: Fat intake influences BLA response to high-fat food, which in turn increases the desire to eat palatable high-fat food. This may lead to additional fat intake and increase the risk of weight gain.

Data-mining analysis of media frame effects on social perception of schizophrenia renaming in Korea.

BACKGROUND: In 2011, Korean Neuropsychiatric Association renamed schizophrenia from 'mind split disorder' ('Jungshinbunyeolbyung' in Korean) to 'attunement disorder' ('Johyeonbyung' in Korean), in a strategic way to reduce social stigma toward people with schizophrenia. However, there remains an elusive consensus that how the renaming effort has contributed to changes in the social perception of schizophrenia in Korea. METHODS: With this regard, we explored whether media frames alter the social perception, in ways of respecting or disrespecting schizophrenia patients before and after the renaming. This study extensively investigated media keywords related to schizophrenia across the time by applying both language and epidemiologic analyses. RESULTS: In results, the media keywords have been negatively described for schizophrenia patients both before and after the renaming. Further, from an analysis using the regression model, a significant correlation was observed between the frequency of negative keywords and the hospitalization frequency of schizophrenia patients. CONCLUSIONS: These findings suggest that the social perception of schizophrenia has been scarcely changed, but rather remained negatively biased against schizophrenia patients, in spite of the renaming effort. Notably, the biased media frames have been demonstrated to negatively impact on the social perception, and even on the medical use patterns of general schizophrenia patients. In conclusion, we suggest that the unbiased media frames along with the renaming effort may collectively help reduce the negative social perception of schizophrenia. TRIAL REGISTRATION: This study was approved from the Institute of Review Board (IRB) of the Yoing-In Mental Hospital (IRB No. YIMH-IRB-2019-02).

Distinctive alterations in the mesocorticolimbic circuits in various psychiatric disorders.

AIM: Increasing evidence suggests that psychiatric disorders are linked to alterations in the mesocorticolimbic dopamine-related circuits. However, the common and disease-specific alterations remain to be examined in schizophrenia (SCZ), major depressive disorder (MDD), and autism spectrum disorder (ASD). Thus, this study aimed to examine common and disease-specific features related to mesocorticolimbic circuits. METHODS: This study included 555 participants from four institutes with five scanners: 140 individuals with SCZ (45.0% female), 127 individuals with MDD (44.9%), 119 individuals with ASD (15.1%), and 169 healthy controls (HC) (34.9%). All participants underwent resting-state functional magnetic resonance imaging. A parametric empirical Bayes approach was adopted to compare estimated effective connectivity among groups. Intrinsic effective connectivity focusing on the mesocorticolimbic dopamine-related circuits including the ventral tegmental area (VTA), shell and core parts of the nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) were examined using a dynamic causal modeling analysis across these psychiatric disorders. RESULTS: The excitatory shell-to-core connectivity was greater in all patients than in the HC group. The inhibitory shell-to-VTA and shell-to-mPFC connectivities were greater in the ASD group than in the HC, MDD, and SCZ groups. Furthermore, the VTA-to-core and VTA-to-shell connectivities were excitatory in the ASD group, while those connections were inhibitory in the HC, MDD, and SCZ groups. CONCLUSION: Impaired signaling in the mesocorticolimbic dopamine-related circuits could be an underlying neuropathogenesis of various psychiatric disorders. These findings will improve the understanding of unique neural alternations of each disorder and will facilitate identification of effective therapeutic targets.

The effect of acquisition duration on cerebral blood flow-based resting-state functional connectivity.

Resting-state functional connectivity (rs-FC) is widely used to examine the functional architecture of the brain, and the blood-oxygenation-level-dependent (BOLD) signal is often utilized for determining rs-FC. However, the BOLD signal is susceptible to various factors that have less influence on the cerebral blood flow (CBF). Therefore, CBF could comprise an alternative for determining rs-FC. Since acquisition duration is one of the essential parameters for obtaining reliable rs-FC, we investigated the effect of acquisition duration on CBF-based rs-FC to examine the reliability of CBF-based rs-FC. Nineteen participants underwent CBF scanning for a total duration of 50 min. Variance of CBF-based rs-FC within the whole brain and 13 large-scale brain networks at various acquisition durations was compared to that with a 50-min duration using the Levene's test. Variance of CBF-based rs-FC at any durations did not differ from that at a 50-min duration (p > .05). Regarding variance of rs-FC within each large-scale brain network, the acquisition duration required to obtain reliable estimates of CBF-based rs-FC was shorter than 10 min and varied across large-scale brain networks. Altogether, an acquisition duration of at least 10 min is required to obtain reliable CBF-based rs-FC. These results indicate that CBF-based resting-state functional magnetic resonance imaging (rs-fMRI) with more than 10 min of total acquisition duration could be an alternative method to BOLD-based rs-fMRI to obtain reliable rs-FC.

Shared functional impairment in the prefrontal cortex affects symptom severity across psychiatric disorders.

BACKGROUND: The prefrontal deficits in psychiatric disorders have been investigated using functional neuroimaging tools; however, no studies have tested the related characteristics across psychiatric disorders considering various demographic and clinical confounders. METHODS: We analyzed 1558 functional brain measurements using a functional near-infrared spectroscopy during a verbal fluency task from 1200 participants with three disease spectra [196 schizophrenia, 189 bipolar disorder (BPD), and 394 major depressive disorder (MDD)] and 369 healthy controls along with demographic characteristics (age, gender, premorbid IQ, and handedness), task performance during the measurements, clinical assessments, and medication equivalent doses (chlorpromazine, diazepam, biperiden, and imipramine) in a consistent manner. The association between brain functions and demographic and clinical variables was tested using a general linear mixed model (GLMM). Then, the direction of relationship between brain activity and symptom severity, controlling for any other associations, was estimated using a model comparison of structural equation models (SEMs). RESULTS: The GLMM showed a shared functional deficit of brain activity and a schizophrenia-specific delayed activity timing in the prefrontal cortex (false discovery rate-corrected p < 0.05). Comparison of SEMs showed that brain activity was associated with the global assessment of functioning scores in the left inferior frontal gyrus opercularis (IFGOp) in BPD group and the bilateral superior temporal gyrus and middle temporal gyrus, and the left superior frontal gyrus, inferior frontal gyrus triangularis, and IFGOp in MDD group. CONCLUSION: This cross-disease large-sample neuroimaging study with high-quality clinical data reveals a robust relationship between prefrontal function and behavioral outcomes across three major psychiatric disorders.

Reduced signal propagation elicited by frontal transcranial magnetic stimulation is associated with oligodendrocyte abnormalities in treatment-resistant depression.

BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (dlPFC) has been established in patients with treatment-resistant depression (TRD), suggesting that alterations in signal propagation from the left dlPFC to other brain regions may be linked to the pathophysiology of TRD. Alterations at the cellular level, including dysfunction of oligodendrocytes, may contribute to these network abnormalities. The objectives of the present study were to compare signal propagation from the left dlPFC to other neural networks in patients with TRD and healthy controls. We used TMS combined with electroencephalography to explore links between cell-specific gene expression and signal propagation in TRD using a virtual-histology approach. METHODS: We examined source-level estimated signal propagation from the left dlPFC to the 7 neural networks in 60 patients with TRD and 30 healthy controls. We also calculated correlations between the interregional profiles of altered signal propagation and gene expression for 9 neural cell types derived from the Allen Human Brain Atlas data set. RESULTS: Signal propagation from the left dlPFC to the salience network was reduced in the θ and α bands in patients with TRD (p = 0.0055). Furthermore, this decreased signal propagation was correlated with cellspecific gene expression of oligodendrocytes (p < 0.000001). LIMITATIONS: These results show only part of the pathophysiology of TRD, because stimulation was limited to the left dlPFC. CONCLUSION: Reduced signal propagation from the left dlPFC to the salience network may represent a pathophysiological endophenotype of TRD; this finding may be associated with reduced expression of oligodendrocytes.

Nutrient infusion evoked magnetic resonance imaging signal in the human hypothalamus.

BACKGROUND: The hypothalamus receives ingested nutrient information via ascending gut-related projections and plays a significant role in the regulation of food intake. Human neuroimaging studies have observed changes in the activity or connectivity of the hypothalamus in response to nutrient ingestion. However, previous neuroimaging studies have not yet assessed differences in temporal changes of hypothalamic responses to various nutrients in humans. Thus a repeated measures functional magnetic resonance imaging (fMRI) study using 30-min scans was designed to examine differences in hypothalamic responses to various nutrients. METHODS: In this study, 18 healthy adults (mean age, 22.4 years; standard deviation, 4.8; age range, 19-39 years; 11 males and seven females) underwent fMRI sessions. On the day of each session, one of the four solutions (200 ml of monosodium glutamate, glucose, safflower oil emulsion, or saline) was administered to participants while fMRI scanning. RESULTS: Infused amino acid and glucose, but not lipid emulsion, increased lateral hypothalamic responses as compared to a saline infusion ([x, y, z] = [4, -4, -10], z = 2.96). In addition, only hypothalamic responses to saline, but not those to the infusion of other nutrients, elicited a subjective sensation of hunger. CONCLUSION: These findings suggest that lateral hypothalamic responses to ingested nutrients may mediate homeostatic sensations in humans.

The association between clinical symptoms and later subjective quality of life in individuals with ultra-high risk for psychosis and recent-onset psychotic disorder: A longitudinal investigation.

AIM: Subjective quality of life is a clinically relevant outcome that is strongly associated with the severity of clinical symptoms in individuals with ultra-high risk for psychosis and patients with recent-onset psychotic disorder. Our objective was to examine whether longitudinal changes in clinical symptoms are associated with quality of life in ultra-high risk individuals and patients with recent-onset psychotic disorder. METHODS: Individuals with ultra-high risk and patients with recent-onset psychosis disorder were recruited in the same clinical settings at baseline and were followed up with more than 6 months and less than 5 years later. We assessed five factors of clinical symptoms using the positive and negative syndrome scale, and quality of life using the World Health Organization quality of life questionnaire-short form. We used multiple regression to examine the relationships between clinical symptoms and quality of life while controlling for diagnosis, follow-up period, age, and sex. RESULTS: Data were collected from 22 individuals with ultra-high risk and 27 patients with recent-onset psychosis disorder. The multiple regression analysis results indicated that the more severe anxiety/depression was at baseline, the poorer the quality of life at follow-up. Further, improvement of anxiety/depression and disorganized thoughts were associated with improvement in quality of life. The difference in diagnosis did not affect the association between clinical symptoms and quality of life. CONCLUSION: These findings suggest that the improvement of anxiety/depression and disorganized thoughts is important in the early stages of psychosis before it becomes severe, affecting the quality of life.

Cross-scanner reproducibility and harmonization of a diffusion MRI structural brain network: A traveling subject study of multi-b acquisition.

Characterization of brain networks by diffusion MRI (dMRI) has rapidly evolved, and there are ongoing movements toward data sharing and multi-center studies. To extract meaningful information from multi-center data, methods to correct for the bias caused by scanner differences, that is, harmonization, are urgently needed. In this work, we report the cross-scanner differences in structural network analyses using data from nine traveling subjects (four males and five females, 21-49 years-old) who underwent scanning using four 3T scanners (public database available from the Brain/MINDS Beyond Human Brain MRI project (http://mriportal.umin.jp/)). The reliability and reproducibility were compared to those of data from another set of four subjects (all males, 29-42 years-old) who underwent scan-rescan (interval, 105-147 days) with the same scanner as well as scan-rescan data from the Human Connectome Project database. The results demonstrated that the reliability of the edge weights and graph theory metrics was lower for data including different scanners, compared to the scan-rescan with the same scanner. Besides, systematic differences between scanners were observed, indicating the risk of bias in comparing networks obtained from different scanners directly. We further demonstrate that it is feasible to reduce inter-scanner variabilities while preserving the inter-subject differences among healthy individuals by modeling the scanner effects at the level of network matrices, when traveling-subject data are available for calibration between scanners. The present data and results are expected to serve as a basis for developing and evaluating novel harmonization methods.

Comparison of traveling-subject and ComBat harmonization methods for assessing structural brain characteristics.

Multisite magnetic resonance imaging (MRI) is increasingly used in clinical research and development. Measurement biases-caused by site differences in scanner/image-acquisition protocols-negatively influence the reliability and reproducibility of image-analysis methods. Harmonization can reduce bias and improve the reproducibility of multisite datasets. Herein, a traveling-subject (TS) dataset including 56 T1-weighted MRI scans of 20 healthy participants in three different MRI procedures-20, 19, and 17 subjects in Procedures 1, 2, and 3, respectively-was considered to compare the reproducibility of TS-GLM, ComBat, and TS-ComBat harmonization methods. The minimum participant count required for harmonization was determined, and the Cohen's d between different MRI procedures was evaluated as a measurement-bias indicator. The measurement-bias reduction realized with different methods was evaluated by comparing test-retest scans for 20 healthy participants. Moreover, the minimum subject count for harmonization was determined by comparing test-retest datasets. The results revealed that TS-GLM and TS-ComBat reduced measurement bias by up to 85 and 81.3%, respectively. Meanwhile, ComBat showed a reduction of only 59.0%. At least 6 TSs were required to harmonize data obtained from different MRI scanners, complying with the imaging protocol predetermined for multisite investigations and operated with similar scan parameters. The results indicate that TS-based harmonization outperforms ComBat for measurement-bias reduction and is optimal for MRI data in well-prepared multisite investigations. One drawback is the small sample size used, potentially limiting the applicability of ComBat. Investigation on the number of subjects needed for a large-scale study is an interesting future problem.

Dietary Restraint Related to Body Weight Maintenance and Neural Processing in Value-Coding Areas in Adolescents.

BACKGROUND: There is an alarming increase in the obesity prevalence among children in an environment of increasing availability of preprocessed high-calorie foods. However, some people maintain a healthy weight even in such obesogenic environments. This difference in body weight management could be attributed to individual differences in dietary restraint; however, its underlying neurocognitive mechanisms in adolescents remain unclear. OBJECTIVES: This study aimed to elucidate these neurocognitive mechanisms in adolescents by examining the relationships between dietary restraint and the food-related value-coding region located in the ventromedial prefrontal cortex (vmPFC). METHODS: The association between dietary restraint and BMI was tested using a multilinear regression analysis in a large early adolescent cohort (n = 2554; age, 12.2 ± 0.3 years; BMI, 17.9 ± 2.5 kg/m2; 1354 boys). Further, an fMRI experiment was designed to assess the association between the vmPFC response to food images and dietary restraint in 30 adolescents (age, 17.6 ± 1.9 years; BMI, 20.7 ± 2.2 kg/m2; 13 boys). Additionally, using 54 individuals from the cohort (age, 14.5 ± 0.6 years; BMI, 18.8 ± 2.6 kg/m2; 31 boys), we assessed the association between dietary restraint and intrinsic vmPFC-related functional connectivity. RESULTS: In the cohort, adolescents with increased dietary restraint showed a lower BMI (ß = -0.38; P < 0.001; B = -0.06; SE = 0.003). The fMRI results showed a decreased vmPFC response to high-calorie food were correlated with greater dietary restraint. Moreover, there was an association of attenuated intrinsic vmPFC-related functional connectivity in the superior and middle frontal gyrus and the middle temporal gyrus with greater dietary restraint. CONCLUSIONS: Our findings suggest that dietary restraint in adolescents could be a preventive factor for weight gain; its effect involves modulating the vmPFC, which is associated with food value coding.

Associations between plasma testosterone levels and season, nutritional status, age, and body size in free-ranging male Asian black bears (Ursus thibetanus) in central Honshu, Japan.

Testosterone is an important regulator of male reproduction in terms of spermatogenesis and physiological changes in the accessory reproductive organs. Despite the important role of the testosterone level in male reproduction, testosterone levels vary among male bears even during the breeding season, and the causative underlying factors remain unknown. We postulated that testosterone levels are higher during the breeding season than during other seasons in free-ranging male bears, and that testosterone levels increase with advancing age, larger body size, and better nutritional status. We assessed potential factors (season, time of sampling, body condition index, head circumference, and age) associated with the testosterone level in 80 blood samples collected from free-ranging Asian black bears (Ursus thibetanus) captured in barrel traps in the Ashio-Nikko Mountains and Okutama Mountains in central Honshu Island, Japan. The plasma testosterone level was higher during the breeding season (May-July) than during the non-breeding season (August-November). The body condition index was significantly and positively associated with the plasma testosterone level. None of the other factors were significantly associated with the plasma testosterone level. Therefore, the body condition index may be essential for maintaining high plasma testosterone levels. These findings imply that testosterone secretion might be activated in free-ranging males during the breeding season, and animals with good nutritional status may be able to maintain high plasma testosterone levels. This study uncovered an association between nutritional conditions and reproductive activity in male bears.

Volumetric differences in gray and white matter of cerebellar Crus I/II across the different clinical stages of schizophrenia.

AIM: Schizophrenia is considered to be a disorder of progressive structural brain abnormalities. Previous studies have indicated that the cerebellar Crus I/II plays a critical role in schizophrenia. We aimed to investigate how specific morphological features in the Crus I/II at different critical stages of the schizophrenia spectrum contribute to the disease. METHODS: The study involved 73 participants on the schizophrenia spectrum (28 with ultra-high risk for psychosis [UHR], 17 with first-episode schizophrenia [FES], and 28 with chronic schizophrenia) and 79 healthy controls. We undertook a detailed investigation into differences in Crus I/II volume using a semiautomated segmentation method optimized for the cerebellum. We analyzed the effects of group and sex, as well as their interaction, on Crus I/II volume in gray matter (GM) and white matter (WM). RESULTS: Significant group × sex interactions were found in WM volumes of the bilateral Crus I/II; the males with UHR demonstrated significantly larger WM volumes compared with the other male groups, whereas no significant group differences were found in the female groups. Additionally, WM and GM volumes of the Crus I/II had positive associations with symptom severity in the UHR group, whereas, in contrast, GM volumes in the FES group were negatively associated with symptom severity. CONCLUSIONS: The present findings provide evidence that the morphology of Crus I/II is involved in schizophrenia in a sex- and disease stage-dependent manner. Additionally, alterations of WM volumes of Crus I/II may have potential as a biological marker of early detection and treatment for individuals with UHR.

Functional connectomes linking child-parent relationships with psychological problems in adolescence.

The child-parent relationship is a significant factor in an adolescent's well-being and functional outcomes. Epidemiological evidence indicates that relationships with the father and mother are differentially associated with specific psychobehavioral problems that manifest differentially between boys and girls. Neuroimaging is expected to bridge the gap in understanding such a complicated mapping between the child-parent relationships and adolescents' problems. However, possible differences in the effects of child-father and child-mother relationships on sexual dimorphism in children's brains and psychobehavioral problems have not been examined yet. This study used a dataset of 10- to 13-year-old children (N â€‹= â€‹93) to reveal the triad of associations among child-parent relationship, brain, and psychobehavioral problems by separately estimating the respective effects of child-father and child-mother relationships on boys and girls. We first fitted general linear models to identify the effects of paternal and maternal relationships in largely different sets of children's resting-state functional connectivity, which we term paternal and maternal functional brain connectomes (FBCs). We then performed connectome-based predictive modeling (CPM) to predict children's externalizing and internalizing problems from these parental FBCs. The models significantly predicted a range of girls' internalizing problems, whereas the prediction of boys' aggression was also significant using a more liberal uncorrected threshold. A series of control analyses confirmed that CPMs using FBCs associated with peer relationship or family socioeconomic status failed to make significant predictions of psychobehavioral problems. Lastly, a causal discovery method identified causal paths from daughter-mother relationship to maternal FBC, and then to daughter's internalizing problems. These observations indicate sex-dependent mechanisms linking child-parent relationship, brain, and psychobehavioral problems in the development of early adolescence.

Association between duration of breastfeeding based on maternal reports and dorsal and ventral striatum and medial orbital gyrus volumes in early adolescence.

Maternal breastfeeding has an impact on motor and emotional development in children of the next generation. Elucidating how breastfeeding during infancy affects brain regional structural development in early adolescence will be helpful for promoting healthy development. However, previous studies that have shown relationships between breastfeeding during infancy and cortical brain regions in adolescence are usually based on maternal retrospective recall of breastfeeding, and the accuracy of the data is unclear. In this study, we investigated the association between breastfeeding duration and brain regional volume in a population-neuroimaging study of early adolescents in Japan (N â€‹= â€‹207; 10.5-13.4 years) using voxel-based morphometry, which enabled us to analyze the whole brain. We evaluated breastfeeding duration as indexed by maternal and child health handbook records during infancy. The results showed a significant positive correlation between the duration of breastfeeding and gray matter volume in the dorsal and ventral striatum and the medial orbital gyrus. Post hoc exploratory analyses revealed that the duration of breastfeeding was significantly correlated with emotional behavior. Additionally, the volume in the medial orbital gyrus mediated an association between breastfeeding duration and emotional behavior. This is the first study to evaluate the effect of breastfeeding during infancy on regional brain volumes in early adolescence based on maternal and child health handbook records. Our findings shed light upon the importance of maternal breastfeeding for brain development related to emotional and motivational processing in early adolescence.