Multivariate sharp-wave ripples in schizophrenia during awake state.

AIMS: Schizophrenia (SZ) is a brain disorder characterized by psychotic symptoms and cognitive dysfunction. Recently, irregularities in sharp-wave ripples (SPW-Rs) have been reported in SZ. As SPW-Rs play a critical role in memory, their irregularities can cause psychotic symptoms and cognitive dysfunction in patients with SZ. In this study, we investigated the SPW-Rs in human SZ. METHODS: We measured whole-brain activity using magnetoencephalography (MEG) in patients with SZ (n = 20) and sex- and age-matched healthy participants (n = 20) during open-eye rest. We identified SPW-Rs and analyzed their occurrence and time-frequency traits. Furthermore, we developed a novel multivariate analysis method, termed "ripple-gedMEG" to extract the global features of SPW-Rs. We also examined the association between SPW-Rs and brain state transitions. The outcomes of these analyses were modeled to predict the positive and negative syndrome scale (PANSS) scores of SZ. RESULTS: We found that SPW-Rs in the SZ (1) occurred more frequently, (2) the delay of the coupling phase (3) appeared in different brain areas, (4) consisted of a less organized spatiotemporal pattern, and (5) were less involved in brain state transitions. Finally, some of the neural features associated with the SPW-Rs were found to be PANSS-positive, a pathological indicator of SZ. These results suggest that widespread but disorganized SPW-Rs underlies the symptoms of SZ. CONCLUSION: We identified irregularities in SPW-Rs in SZ and confirmed that their alternations were strongly associated with SZ neuropathology. These results suggest a new direction for human SZ research.

Disrupted local beta band networks in schizophrenia revealed through graph analysis: A magnetoencephalography study.

AIMS: Schizophrenia (SZ) is characterized by psychotic symptoms and cognitive impairment, and is hypothesized to be a 'dysconnection' syndrome due to abnormal neural network formation. Although numerous studies have helped elucidate the pathophysiology of SZ, many aspects of the mechanism underlying psychotic symptoms remain unknown. This study used graph theory analysis to evaluate the characteristics of the resting-state network (RSN) in terms of microscale and macroscale indices, and to identify candidates as potential biomarkers of SZ. Specifically, we discriminated topological characteristics in the frequency domain and investigated them in the context of psychotic symptoms in patients with SZ. METHODS: We performed graph theory analysis of electrophysiological RSN data using magnetoencephalography to compare topological characteristics represented by microscale (degree centrality and clustering coefficient) and macroscale (global efficiency, local efficiency, and small-worldness) indices in 29 patients with SZ and 38 healthy controls. In addition, we investigated the aberrant topological characteristics of the RSN in patients with SZ and their relationship with SZ symptoms. RESULTS: SZ was associated with a decreased clustering coefficient, local efficiency, and small-worldness, especially in the high beta band. In addition, macroscale changes in the low beta band are closely associated with negative symptoms. CONCLUSIONS: The local networks of patients with SZ may disintegrate at both the microscale and macroscale levels, mainly in the beta band. Adopting an electrophysiological perspective of SZ as a failure to form local networks in the beta band will provide deeper insights into the pathophysiology of SZ as a 'dysconnection' syndrome.

Glutamine + glutamate level predicts the magnitude of microstructural organization in the gray matter in the healthy elderly.

BACKGROUND: Diffusion tensor imaging (DTI), which is a technique for measuring the degree and direction of movement of water molecules in tissue, has been widely used to noninvasively assess white matter (WM) or gray matter (GM) microstructures in vivo. Mean diffusivity (MD), which is the average diffusion across all directions, has been considered as a marker of WM tract degeneration or extracellular space enlargement in GM. Recent lines of evidence suggest that cortical MD can better identify early-stage Alzheimer's disease than structural morphometric parameters in magnetic resonance imaging. However, knowledge of the relationships between cortical MD and other biological factors in the same cortical region, e.g. metabolites, is still limited. METHODS: Thirty-three healthy elderly individuals [aged 50-77 years (mean, 63.8±7.4 years); 11 males and 22 females] were enrolled. We estimated the associations between cortical MD and neurotransmitter levels. Specifically, we measured levels of γ-aminobutyric acid (GABA) and glutamate + glutamine (Glx), which are inhibitory and excitatory neurotransmitters, respectively, in medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) using MEGA-PRESS magnetic resonance spectroscopy, and we measured regional cortical MD using DTI. RESULTS: Cortical MD was significantly negatively associated with Glx levels in both mPFC and PCC. No significant association was observed between cortical MD and GABA levels in either GM region. CONCLUSION: Our findings suggest that degeneration of microstructural organization in GM, as determined on the basis of cortical MD measured by DTI, is accompanied by the decline of Glx metabolism within the same GM region.

Characterization of the signature of peripheral innate immunity in women with later-life major depressive disorder.

The prevalence of depression in later life is higher in women than in men. However, the sex difference in the pathophysiology of depression in elderly patients is not fully understood. Here, we performed gene expression profiling in leukocytes of middle-aged and elderly patients with major depressive disorder, termed later-life depression (LLD) in this context, and we characterized the sex-dependent pathophysiology of LLD. A microarray dataset obtained from leukocytes of patients (aged ≥50 years) with LLD (32 males and 39 females) and age-matched healthy individuals (20 males and 24 females) was used. Differentially expressed probes were determined by comparing the expression levels between patients and healthy individuals, and then functional annotation analyses (Ingenuity Pathway Analysis, Reactome pathway analysis, and cell-type enrichment analysis) were performed. A total of 1656 probes were differentially expressed in LLD females, but only 3 genes were differentially expressed in LLD males. The differentially expressed genes in LLD females were relevant to leukocyte extravasation signaling, Tec kinase signaling and the innate immune response. The upregulated genes were relevant to myeloid lineage cells such as CD14+ monocytes. In contrast, the downregulated genes were relevant to CD4+ and CD8+ T cells. Remarkable innate immune signatures are present in the leukocytes of LLD females but not males. Because inflammation is involved in the pathophysiology of depression, the altered inflammatory activity may be involved in the pathophysiology of LLD in women. In contrast, abnormal inflammation may be an uncommon feature in LLD males.

Is Utena's Brief Objective Measures (UBOM) useful in real-world behavioral assessment of functioning? Validity and utility testing in patients with schizophrenia.

AIM: Utena's Brief Objective Measures (UBOM) was developed to assess psychophysiological functions proximal to real-world functioning in individuals with psychiatric disorders, including schizophrenia (SCZ), to facilitate shared decision-making. However, the validity of UBOM has not been fully examined. METHODS: We conducted a cross-sectional observational study to evaluate the validity of each of the three tests in UBOM: UBOM-Pulse, UBOM-Ruler, and UBOM-Random. We investigated associations: (i) between UBOM and existing cognitive- and autonomic-function tests; and (ii) between UBOM and daily social functioning. The participants included SCZ individuals and healthy controls. We evaluated the cognitive and autonomic function using UBOM, the heart rate variability test, the simple reaction time test, and the Brief Assessment of Cognition in Schizophrenia, Japanese version. We also assessed the daily social functioning using the WHO Disability Assessment Schedule 2.0 and the modified Global Assessment of Functioning, Japanese version. RESULTS: Thirty-one SCZ individuals and 35 healthy control individuals participated in this study. In the SCZ group, UBOM-Ruler was significantly associated with the Cognition and Getting Along domains of WHO Disability Assessment Schedule 2.0. UBOM-Random was significantly associated with the Brief Assessment of Cognition in Schizophrenia's Working Memory, Verbal Fluency and Attention domains, and the modified Global Assessment of Functioning in the SCZ group. CONCLUSION: The validity of the current version of UBOM is imperfect and further improvements will be necessary to attain the originally intended goal of developing a brief assessment tool for real-world functioning in SCZ.

γ-Aminobutyric acid type A receptor binding affinity in the right inferior frontal gyrus at resting state predicts the performance of healthy elderly people in the visual sustained attention test.

ABSTRACTBackground:Although recent studies have suggested that the γ-aminobutyric acid type A (GABAA) receptor binding affinity can be a more sensitive marker of age-related neuronal loss than regional gray matter (GM) volume, knowledge about the relationship between decreased GABAA receptor binding affinity and cognitive decline during normal aging is still limited. METHODS: Thirty-seven healthy elderly individuals (aged 50-77 years (mean, 64.5 ± 7.3 years); 15 males and 22 females) were enrolled in this study. We investigated the association of the performance of the healthy elderly in the attentional function test with regional GM volume, regional cerebral bold flow (rCBF), and GABAA receptor binding affinity in the resting state by structural magnetic resonance imaging (MRI), arterial spin labeling (ASL), and 123I-iomazenil (IMZ) SPECT, with the analysis focusing on the bilateral inferior frontal gyri. RESULTS: The score of the rapid visual information processing (RVP) test, which is used to assess visual sustained attention, showed a positive correlation with GABAA receptor binding affinity in the right inferior frontal gyrus. No significant correlation was found between RVP test score and regional GM volume or rCBF. CONCLUSION: The findings of 123I-IMZ SPECT, but not those of structural MRI or ASL, suggest that a decreased GABAA receptor binding affinity can be a sensitive marker of cognitive impairment.

The inhibition/excitation ratio related to task-induced oscillatory modulations during a working memory task: A multtimodal-imaging study using MEG and MRS.

Detailed studies on the association between neural oscillations and the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate have been performed in vitro. In addition, recent functional magnetic resonance imaging studies have characterized these neurotransmitters in task-induced deactivation processes during a working memory (WM) task. However, few studies have investigated the relationship between these neurotransmitters and task-induced oscillatory changes in the human brain. Here, using combined magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS), we investigated the modulation of GABA and glutamate + glutamine (Glx) concentrations related to task-induced oscillations in neural activity during a WM task. We first acquired resting-state MRS and MEG data from 20 healthy male volunteers using the n-back task. Time-frequency analysis was employed to determine the power induced during the encoding and retention phases in perigenual anterior cingulate cortex (pg-ACC), mid-ACC, and occipital cortex (OC). Statistical analysis showed that increased WM load was associated with task-induced oscillatory modulations (TIOMs) of the theta-gamma band relative to the zero-back condition (TIOM0B) in each volume of interest during the encoding phase of the n-back task. The task-induced oscillatory modulations in the two-back condition relative to the zero-back condition (TIOM2B-0B) were negatively correlated with the percent rate change of the correct hit rate for 2B-0B, but positively correlated with GABA/Glx. The positive correlation between TIOM2B-0B and GABA/Glx during the WM task indicates the importance of the inhibition/excitation ratio. In particular, a low inhibition/excitation ratio is essential for the efficient inhibition of irrelevant neural activity, thus producing precise task performance.

Intact neural activity during a Go/No-go task is associated with high global functioning in schizophrenia.

AIM: Go/No-go derived event-related potential (ERP) signals have been widely used in schizophrenia research to monitor self-control deficits in this disorder. However, no study to date has associated Go/No-go-related ERP with global functioning. METHODS: Participants consisted of 21 patients with schizophrenia and 22 healthy controls. We used a visual Go/No-go paradigm to measure Go/No-go-related N2/P3 ERP components by means of a 64-electrode cap for electroencephalogram recording. We used the Global Assessment of Functioning to evaluate global functioning and analyzed the correlation between ERP indices and global functioning scores. RESULTS: N2 amplitudes were reduced in patients with schizophrenia, but not influenced by either of the Go/No-go conditions. P3 amplitudes were influenced by the Go/No-go conditions, but not reduced in patients with schizophrenia. Global functioning was correlated with the No-go P3 amplitudes, but not N2 amplitudes, in patients with schizophrenia. CONCLUSION: These results indicate that global functioning is associated with intact neural activity rather than impaired neural activity during Go/No-go response inhibition tasks in patients with schizophrenia.

Magnetoencephalography study of the effect of attention modulation on somatosensory processing in patients with major depressive disorder.

AIMS: Although affective and/or attention modulation of somatosensory processing has been well studied, the biological bases of somatic symptoms in patients with major depressive disorder (MDD) have rarely been examined. To elucidate changes in somatosensory processing underlying somatic symptoms in patients with MDD, we conducted a magnetoencephalography study of patients with MDD and healthy controls. METHODS: After median nerve stimulation, somatosensory evoked fields (SEF) were recorded in 10 patients with MDD and 10 sex-, age-, and height-matched healthy volunteers under somatosensory attending, visually attending, and non-attending conditions. The latencies and magnitudes of N20m and P60m SEF were examined. RESULTS: In the MDD group, P60m latency was significantly prolonged, irrespective of attention modulation, whereas N20m latency and root mean squares N20m and P60m amplitudes remained unchanged. Prolonged P60m latency negatively correlated with the somatosensory threshold, which was relatively high in the MDD group. Prolonged P60m latency also negatively correlated with a state of anxiety during the examination, but not with depressive symptoms or psychotropic medication. CONCLUSIONS: These results suggested that patients with MDD experience dysfunction in somatosensory information processing, approximately 60 ms after stimuli, irrespective of attentional conditions.

Relationship of γ-aminobutyric acid and glutamate+glutamine concentrations in the perigenual anterior cingulate cortex with performance of Cambridge Gambling Task.

The anterior cingulate cortex (ACC), consisting of the perigenual ACC (pgACC) and mid-ACC (i.e., affective and cognitive areas, respectively), plays a significant role in the performance of gambling tasks, which are used to measure decision-making behavior under conditions of risk. Although recent neuroimaging studies have suggested that the γ-aminobutyric acid (GABA) concentration in the pgACC is associated with decision-making behavior, knowledge regarding the relationship of GABA concentrations in subdivisions of the ACC with gambling task performance is still limited. The aim of our magnetic resonance spectroscopy study is to investigate in 20 healthy males the relationship of concentrations of GABA and glutamate+glutamine (Glx) in the pgACC, mid-ACC, and occipital cortex (OC) with multiple indexes of decision-making behavior under conditions of risk, using the Cambridge Gambling Task (CGT). The GABA/creatine (Cr) ratio in the pgACC negatively correlated with delay aversion score, which corresponds to the impulsivity index. The Glx/Cr ratio in the pgACC negatively correlated with risk adjustment score, which is reported to reflect the ability to change the amount of the bet depending on the probability of winning or losing. The scores of CGT did not significantly correlate with the GABA/Cr or Glx/Cr ratio in the mid-ACC or OC. Results of this study suggest that in the pgACC, but not in the mid-ACC or OC, GABA and Glx concentrations play a distinct role in regulating impulsiveness and risk probability during decision-making behavior under conditions of risk, respectively.

[Optical Topography as an Auxiliary Laboratory Test for Differential Diagnosis of Depressive State: Clinical Application of Near-infrared Spectroscopy (NIRS) as the First Trial for Approved Laboratory Tests in Psychiatry].

The lack of clinical laboratory tests is a major obstacle in the reliable diagnosis and quantitative treatment assessment and prevention of psychiatric disorders and in the development of patient-centric psychiatric practices. Optical topography has been approved as an insurance-covered auxiliary laboratory test for differential diagnosis of depressive state by Ministry of Health, Labour and Welfare in Japan since 2014. Near-infrared spectroscopy (NIRS), theoretical basis of optical topography, is one of functional neuroimaging techniques that has been increasingly employed in psychology and psychiatry. Because NIRS can detect only cerebral cortex reactivities with low spatial resolution and may suffer from contaminating signals from skin and skull, its data should be interpreted as a global index of cerebral cortex reactivities. Within these limitations, the advantages of NIRS over fMRI such as complete non-invasiveness, small measurement apparatus, high time resolution, and natural examination setting lead it to one of the preferred methods in studies of brain substrates of psychiatric disorders. Two-thirds of the original articles on NIRS application in psychiatry have been published by Japanese researchers. NIRS examination of major depressive disorder, bipolar disorder, and schizophrenia using a verbal fluency task of only three minutes demonstrated diagnosis-specific characteristics of frontal lobe function. These characteristics have been established as suggesting potential diagnosis of bipolar disorder or schizophrenia in clinically diagnosed major depressive disorder. In order to establish the application of NIRS as clinically useful laboratory tests in psychiatry, auxiliary nature of NIRS examination for differential diagnosis should be properly recognized both by patients and psychiatrists.

[Democratizing the Privileges of Psychiatrists].

Psychiatrists are endowed with many privileges in their clinical practices. These include privileges to engage with personally and socially important disorders, those stemming from the role of psychiatrists as medical professionals, and those given by their situation in the context of a social psychiatric system. These privileges allow psychiatrists to attain profound insight into the significance and value of life. Psychiatrists must inculcate a mission to be aware of and to make use of these privileges for advances in psychiatry and clinical practices. One of the most important privileges of psychiatrists is to share their feeling of self-respect obtained by devoting themselves to "the most important medicine for humans" with their patients, families, and colleagues.

Functional abnormalities in the left ventrolateral prefrontal cortex during a semantic fluency task, and their association with thought disorder in patients with schizophrenia.

Thought disorder is one of the primary symptoms in schizophrenia, yet the neural correlates and related semantic processing abnormalities remain unclear. We aimed to investigate the relationship between functional prefrontal abnormalities and thought disorder in schizophrenia using 2 types of verbal fluency tasks: the letter fluency task (LFT) and the category fluency task (CFT). Fifty-six adult patients with schizophrenia and 56 healthy controls matched for age, gender, and IQ participated in the study. During completion of the 2 types of verbal fluency tasks, we measured oxy- and deoxy-hemoglobin concentration ([oxy-Hb] and [deoxy-Hb]) signal changes over a wide area of the bilateral prefrontal cortex, using a 52-channel near-infrared spectroscopy (NIRS) system. Thought disorder scores were evaluated using the positive and negative syndrome scale. CFT performance was significantly higher than LFT performance in both groups, while there was no significant difference in any prefrontal NIRS signal changes between the 2 tasks in either group. In both versions of verbal fluency task, healthy controls exhibited a significantly greater NIRS signal change than did patients with schizophrenia. On the CFT only, left ventrolateral prefrontal NIRS [deoxy-Hb] signals were significantly associated with thought disorder scores in patients with schizophrenia. Our results suggest that left ventrolateral prefrontal abnormalities in category fluency might be related to thought disorder in schizophrenia. This could lead to an improved understanding of the neural mechanisms within the left ventrolateral prefrontal cortex involved in mediating semantic processing, as well as the relationship between semantic processing abnormalities and thought disorder in schizophrenia.

Neuroimaging-aided differential diagnosis of the depressive state.

A serious problem in psychiatric practice is the lack of specific, objective biomarker-based assessments to guide diagnosis and treatment. The use of such biomarkers could assist clinicians in establishing differential diagnosis, which may improve specific individualised treatment. This multi-site study sought to develop a clinically suitable neuroimaging-guided diagnostic support system for differential diagnosis at the single-subject level among multiple psychiatric disorders with depressive symptoms using near-infrared spectroscopy, which is a compact and portable neuroimaging method. We conducted a multi-site, case-control replication study using two cohorts, which included seven hospitals in Japan. The study included 673 patients (women/men: 315/358) with psychiatric disorders (major depressive disorder, bipolar disorder, or schizophrenia) who manifested depressive symptoms, and 1007 healthy volunteers (530/477). We measured the accuracy of the single-subject classification in differential diagnosis among major psychiatric disorders, based on spatiotemporal characteristics of fronto-temporal cortical haemodynamic response patterns induced by a brief (<3 min) verbal fluency task. Data from the initial site were used to determine an optimal threshold, based on receiver-operator characteristics analysis, and to generate the simplest and most significant algorithm, which was validated using data from the remaining six sites. The frontal haemodynamic patterns detected by the near-infrared spectroscopy method accurately distinguished between patients with major depressive disorder (74.6%) and those with the two other disorders (85.5%; bipolar disorder or schizophrenia) that presented with depressive symptoms. These results suggest that neuroimaging-guided differential diagnosis of major psychiatric disorders developed using the near-infrared spectroscopy method can be a promising biomarker that should aid in personalised care in real clinical settings. Potential confounding effects of clinical (e.g., age, sex) and systemic (e.g., autonomic nervous system indices) variables on brain signals will need to be clarified to improve classification accuracy.

A NIRS-fMRI investigation of prefrontal cortex activity during a working memory task.

Near-infrared spectroscopy (NIRS) is commonly used for studying human brain function. However, several studies have shown that superficial hemodynamic changes such as skin blood flow can affect the prefrontal NIRS hemoglobin (Hb) signals. To examine the criterion-related validity of prefrontal NIRS-Hb signals, we focused on the functional signals during a working memory (WM) task and investigated their similarity with blood-oxygen-level-dependent (BOLD) signals simultaneously measured by functional magnetic resonance imaging (fMRI). We also measured the skin blood flow with a laser Doppler flowmeter (LDF) at the same time to examine the effect of superficial hemodynamic changes on the NIRS-Hb signals. Correlation analysis demonstrated that temporal changes in the prefrontal NIRS-Hb signals in the activation area were significantly correlated with the BOLD signals in the gray matter rather than those in the soft tissue or the LDF signals. While care must be taken when comparing the NIRS-Hb signal with the extracranial BOLD or LDF signals, these results suggest that the NIRS-Hb signal mainly reflects hemodynamic changes in the gray matter. Moreover, the amplitudes of the task-related responses of the NIRS-Hb signals were significantly correlated with the BOLD signals in the gray matter across participants, which means participants with a stronger NIRS-Hb response showed a stronger BOLD response. These results thus provide supportive evidence that NIRS can be used to measure hemodynamic signals originating from prefrontal cortex activation.

A novel factor FLOURY ENDOSPERM2 is involved in regulation of rice grain size and starch quality.

Rice (Oryza sativa) endosperm accumulates a massive amount of storage starch and storage proteins during seed development. However, little is known about the regulatory system involved in the production of storage substances. The rice flo2 mutation resulted in reduced grain size and starch quality. Map-based cloning identified FLOURY ENDOSPERM2 (FLO2), a member of a novel gene family conserved in plants, as the gene responsible for the rice flo2 mutation. FLO2 harbors a tetratricopeptide repeat motif, considered to mediate a protein-protein interactions. FLO2 was abundantly expressed in developing seeds coincident with production of storage starch and protein, as well as in leaves, while abundant expression of its homologs was observed only in leaves. The flo2 mutation decreased expression of genes involved in production of storage starch and storage proteins in the endosperm. Differences between cultivars in their responsiveness of FLO2 expression during high-temperature stress indicated that FLO2 may be involved in heat tolerance during seed development. Overexpression of FLO2 enlarged the size of grains significantly. These results suggest that FLO2 plays a pivotal regulatory role in rice grain size and starch quality by affecting storage substance accumulation in the endosperm.

[Pathophysiology of psychiatric disorders revealed by clinical neurophysiology].

Clinical neurophysiological finidngs in schizophrenia can be categoraized into three groups: abnormalities of P50 and prepulse inhibition in the risk stage, those of P300 and N100 in the onset stage, and those of MMN in the chronic stage. These findings correspond to the pathophysiological development of schizophrenia through the clinical stages, respectively: filtering dysfunction as a predisposition, sensory dysfunction around the first psychotic episode, and higher cognitive dysfunction during the chronic course. Such brain dysfunctions can also be demonstrated by near-infrared spectroscopy (NIRS) examination in clinical settings. Establishing biomarkers as a clinical laboratory test for the diagnosis and treatment of psychiatric disorders and sharing the obtained results among patients and medical professionals are expected to facilitate patient-centered psychiatric practice.

The Characteristics of Power Spectral Density in Bipolar Disorder at the Resting State.

Bipolar disorder (BD) is a common psychiatric disorder, but its pathophysiology is not fully elucidated. The current study focused on its electrophysiological characteristics, especially power spectral density (PSD). Resting state with eyes opened magnetoencephalography data were collected from 21 patients with BD and 22 healthy controls. The whole brain's PSD was calculated from source reconstructed waveforms at each frequency band (delta: 1-3 Hz, theta: 4-7 Hz, alpha: 8-12 Hz, low beta: 13-19 Hz, high beta: 20-29 Hz, and gamma: 30-80 Hz). We compared PSD values on the marked vertices at each frequency band between healthy and patient groups using a Mann-Whitney rank test to examine the relationship between significantly different PSD and clinical measures. The PSD in patients with BD was significantly decreased in lower frequency bands, mainly in the default mode network (DMN) areas (bilateral medial prefrontal cortex, bilateral precuneus, left inferior parietal lobe, and right temporal cortex in the alpha band) and salience network areas (SAL; left anterior insula [AI] at the delta band, anterior cingulate cortex at the theta band, and right AI at the alpha band). No significant differences in PSD were observed at low beta and high beta. PSD was not correlated with age or other clinical scales. Altered PSDs of the DMN and SAL were observed in the delta, theta, and alpha bands. These alterations contribute to the vulnerability of BD through the disturbance of self-referential mental activity and switching between the default mode and frontoparietal networks.

Corrigendum: Being praised for prosocial behaviors longitudinally reduces depressive symptoms in early adolescents: a population-based cohort study.

[This corrects the article DOI: 10.3389/fpsyt.2022.865907.].

Associations among parenting experiences during childhood and adolescence, hypothalamus-pituitary-adrenal axis hypoactivity, and hippocampal gray matter volume reduction in young adults.

Recent human studies have indicated that adverse parenting experiences during childhood and adolescence are associated with adulthood hypothalamus-pituitary-adrenal (HPA) axis hypoactivity. Chronic HPA axis hypoactivity inhibits hippocampal gray matter (GM) development, as shown by animal studies. However, associations among adverse parenting experiences during childhood and adolescence, HPA axis activity, and brain development, particularly hippocampal development, are insufficiently investigated in humans. In this voxel-based structural magnetic resonance imaging study, using a cross-sectional design, we examined the associations among the scores of parental bonding instrument (PBI; a self-report scale to rate the attitudes of parents during the first 16 years), cortisol response determined by the dexamethasone/corticotropin-releasing hormone test, and regional or total hippocampal GM volume in forty healthy young adults with the following features: aged between 18 and 35 years, no cortisol hypersecretion in response to the dexamethasone test, no history of traumatic events, or no past or current conditions of significant medical illness or neuropsychiatric disorders. As a result, parental overprotection scores significantly negatively correlated with cortisol response. Additionally, a significant positive association was found between cortisol response and total or regional hippocampal GM volume. No significant association was observed between PBI scores and total or regional hippocampal GM volume. In conclusion, statistical associations were found between parental overprotection during childhood and adolescence and adulthood HPA axis hypoactivity, and between HPA axis hypoactivity and hippocampal GM volume reduction in healthy young adults, but no significant relationship was observed between any PBI scores and adulthood hippocampal GM volume.