Dual-MEG interbrain synchronization during turn-taking verbal interactions between mothers and children.

Verbal interaction and imitation are essential for language learning and development in young children. However, it is unclear how mother-child dyads synchronize oscillatory neural activity at the cortical level in turn-based speech interactions. Our study investigated interbrain synchrony in mother-child pairs during a turn-taking paradigm of verbal imitation. A dual-MEG (magnetoencephalography) setup was used to measure brain activity from interactive mother-child pairs simultaneously. Interpersonal neural synchronization was compared between socially interactive and noninteractive tasks (passive listening to pure tones). Interbrain networks showed increased synchronization during the socially interactive compared to noninteractive conditions in the theta and alpha bands. Enhanced interpersonal brain synchrony was observed in the right angular gyrus, right triangular, and left opercular parts of the inferior frontal gyrus. Moreover, these parietal and frontal regions appear to be the cortical hubs exhibiting a high number of interbrain connections. These cortical areas could serve as a neural marker for the interactive component in verbal social communication. The present study is the first to investigate mother-child interbrain neural synchronization during verbal social interactions using a dual-MEG setup. Our results advance our understanding of turn-taking during verbal interaction between mother-child dyads and suggest a role for social "gating" in language learning.

Discharge to home from a palliative care unit: impact on survival and factors associated with home death after the discharge: a cohort study.

BACKGROUND: Staying at home during the dying process is important for many patients; and palliative care units (PCUs) can help facilitate home death. This study compared patient survival between those who were discharged to home from a palliative care unit and those who were not, and aimed to identify the factors associated with home death after the discharge. METHODS: This retrospective cohort study used a database of patients admitted to a palliative care unit at Kouseiren Takaoka Hospital in Japan. All consecutive patients admitted to the hospital's PCU between October 2016 and March 2020 were enrolled. Patient survival and factors potentially associated with survival and place of death were obtained. A total of 443 patients with cancer were analyzed, and 167 patients were discharged to home and 276 were not. RESULTS: Propensity score matching analyses revealed that median survival time was significantly longer in patients who were discharged to home than those who were not (57 vs. 27 days, P < 0.001). Multiple logistic regression analysis identified that worse Palliative Prognostic Index (odds ratio [OR] = 1.21, 95% confidence interval [CI] = 1.03-1.44, p = 0.025) and family members' desire for home death (OR = 6.30, 95% CI = 2.32-17.1, p < 0.001) were significantly associated with home death after their discharge. CONCLUSIONS: Discharge to home from palliative care units might have some positive impacts on patient survival.

Expression of Transcripts Selective for GABA Neuron Subpopulations across the Cortical Visuospatial Working Memory Network in the Healthy State and Schizophrenia.

Visuospatial working memory (WM), which is impaired in schizophrenia, depends on a distributed network including visual, posterior parietal, and dorsolateral prefrontal cortical regions. Within each region, information processing is differentially regulated by subsets of γ-aminobutyric acid (GABA) neurons that express parvalbumin (PV), somatostatin (SST), or vasoactive intestinal peptide (VIP). In schizophrenia, WM impairments have been associated with alterations of PV and SST neurons in the dorsolateral prefrontal cortex. Here, we quantified transcripts selectively expressed in GABA neuron subsets across four cortical regions in the WM network from comparison and schizophrenia subjects. In comparison subjects, PV mRNA levels declined and SST mRNA levels increased from posterior to anterior regions, whereas VIP mRNA levels were comparable across regions except for the primary visual cortex (V1). In schizophrenia subjects, each transcript in PV and SST neurons exhibited similar alterations across all regions, whereas transcripts in VIP neurons were unaltered in any region except for V1. These findings suggest that the contribution of each GABA neuron subset to inhibitory regulation of local circuitry normally differs across cortical regions of the visuospatial WM network and that in schizophrenia alterations of PV and SST neurons are a shared feature across these regions, whereas VIP neurons are affected only in V1.

Auditory steady-state response at 20 Hz and 40 Hz in young typically developing children and children with autism spectrum disorder.

AIM: The early detection of autistic tendencies in children is essential for providing proper care and education. The auditory steady-state response (ASSR) provides a passive, non-invasive technique for assessing neural synchrony at specific response frequencies in many mental disorders, including autism spectrum disorder (ASD), but few studies have investigated its use in young children. This study investigated the ASSR at 20 Hz and 40 Hz in typically developing (TD) children and children with ASD aged 5-7 years. METHODS: The participants were 23 children with ASD and 32 TD children aged 5-7 years. Using a custom-made magnetoencephalography device, we measured ASSR at 20 Hz and 40 Hz, compared the results between groups, and evaluated the association with intellectual function as measured by Kaufmann Assessment Battery for Children. RESULTS: Responses to 20 Hz and 40 Hz were clearly detected in both groups with no significant difference identified. Consistent with previous findings, right dominance of the 40-Hz ASSR was observed in both groups. In the TD children, the right-side 40-Hz ASSR was correlated with age. The Kaufmann Assessment Battery for Children score was correlated with the left-side 40-Hz ASSR in both groups. CONCLUSION: Right-dominant ASSR was successfully detected in young TD children and children with ASD. No difference in ASSR was observed between the children with ASD and the TD children, although the right-side 40-Hz ASSR increased with age only in the TD children. Left-side 40-Hz ASSR was associated with intelligence score in both groups.

Altered Gamma Oscillations during Motor Control in Children with Autism Spectrum Disorder.

Autism is hypothesized to result in a cortical excitatory and inhibitory imbalance driven by inhibitory interneuron dysfunction, which is associated with the generation of gamma oscillations. On the other hand, impaired motor control has been widely reported in autism. However, no study has focused on the gamma oscillations during motor control in autism. In the present study, we investigated the motor-related gamma oscillations in autism using magnetoencephalography. Magnetoencephalographic signals were recorded from 14 right-handed human children with autism (5 female), aged 5-7 years, and age- and IQ-matched 15 typically developing children during a motor task using their right index finger. Consistent with previous studies, the autism group showed a significantly longer button response time and reduced amplitude of motor-evoked magnetic fields. We observed that the autism group exhibited a low peak frequency of motor-related gamma oscillations from the contralateral primary motor cortex, and these were associated with the severity of autism symptoms. The autism group showed a reduced power of motor-related gamma oscillations in the bilateral primary motor cortex. A linear discriminant analysis using the button response time and gamma oscillations showed a high classification performance (86.2% accuracy). The alterations of the gamma oscillations in autism might reflect the cortical excitatory and inhibitory imbalance. Our findings provide an important clue into the behavioral and neurophysiological alterations in autism and a potential biomarker for autism.SIGNIFICANCE STATEMENT Currently, the diagnosis of autism has been based on behavioral assessments, and a crucial issue in the diagnosis of autism is to identify objective and quantifiable clinical biomarkers. A key hypothesis of the neurophysiology of autism is an excitatory and inhibitory imbalance in the brain, which is associated with the generation of gamma oscillations. On the other hand, motor deficits have also been widely reported in autism. This is the first study to demonstrate low motor performance and altered motor-related gamma oscillations in autism, reflecting a brain excitatory and inhibitory imbalance. Using these behavioral and neurophysiological parameters, we classified autism and control group with good accuracy. This work provides important information on behavioral and neurophysiological alterations in patients with autism.

Enrichment of deleterious variants of mitochondrial DNA polymerase gene (POLG1) in bipolar disorder.

AIM: Rare missense variants, which likely account for a substantial portion of the genetic 'dark matter' for a common complex disease, are challenging because the impacts of variants on disease development are difficult to substantiate. This study aimed to examine the impacts of amino acid substitution variants in the POLG1 found in bipolar disorder, as an example and proof of concept, in three different modalities of assessment: in silico predictions, in vitro biochemical assays, and clinical evaluation. We then tested whether deleterious variants in POLG1 contributed to the genetics of bipolar disorder. METHODS: We searched for variants in the POLG1 gene in 796 Japanese patients with bipolar disorder and 767 controls and comprehensively investigated all 23 identified variants in the three modalities of assessment. POLG1 encodes mitochondrial DNA polymerase and is one of the causative genes for a Mendelian-inheritance mitochondrial disease, which is occasionally accompanied by mood disorders. The healthy control data from the Tohoku Medical Megabank Organization were also employed. RESULTS: Although the frequency of carriers of deleterious variants varied from one method to another, every assessment achieved the same conclusion that deleterious POLG1 variants were significantly enriched in the variants identified in patients with bipolar disorder compared to those in controls. CONCLUSION: Together with mitochondrial dysfunction in bipolar disorder, the present results suggested deleterious POLG1 variants as a credible risk for the multifactorial disease.

Enhanced brain signal variability in children with autism spectrum disorder during early childhood.

Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age-related increase of brain signal variability in a specific timescale in TD children, whereas atypical age-related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region-specifically and timescale-specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical-developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales.

Magnetoencephalography in the study of children with autism spectrum disorder.

Magnetoencephalography (MEG) is a non-invasive neuroimaging technique that provides a measure of cortical neural activity on a millisecond timescale with high spatial resolution. MEG has been clinically applied to various neurological diseases, including epilepsy and cognitive dysfunction. In the past decade, MEG has also emerged as an important investigatory tool in neurodevelopmental studies. It is therefore an opportune time to review how MEG is able to contribute to the study of atypical brain development. We limit this review to autism spectrum disorder (ASD). The relevant published work for children was accessed using PubMed on 5 January 2015. Case reports, case series, and papers on epilepsy were excluded. Owing to their accurate separation of brain activity in the right and left hemispheres and the higher accuracy of source localization, MEG studies have added new information related to auditory-evoked brain responses to findings from previous electroencephalography studies of children with ASD. In addition, evidence of atypical brain connectivity in children with ASD has accumulated over the past decade. MEG is well suited for the study of neural activity with high time resolution even in young children. Although further studies are still necessary, the detailed findings provided by neuroimaging methods may aid clinical diagnosis and even contribute to the refinement of diagnostic categories for neurodevelopmental disorders in the future.

[Study of Somatosensory Event-Related Potential in Mood Disorder].

There have been a number of inconsistent previous reports indicating that mood disorder patients are relatively sensitive or conversely insensitive to physical pain. However, there have been few such studies examining pain using neurophysiological techniques. The present study was performed to investigate the differences in tactile sense recognition between mood disorder patients and control subjects using a tactile sense recognition P300 measuring system. Tactile stimuli were delivered to the index finger as frequent stimuli and to the ring finger as infrequent stimuli. Subjects were requested to press a button promptly and accurately in response to infrequent stimuli. N140 and P300 were measured in the event-related potential to infrequent stimulus paradigm. The subjects evaluated stimuli on a visual analog scale (VAS). The amplitudes of P300 were smaller for the mood disorder patients than for control subjects. The VAS scores of mood disorder patients were significantly higher than those of control subjects. In mood disorder patients, the amplitude of P300 was negatively correlated with the HAM-D score. These results suggest dysfunction of tactile sense recognition in mood disorder patients. In addition, the amplitude of P300 may be useful as a biological marker for psychological conditions in mood disorder patients.

[The Possible Role of Oxytocin in Autism Spectrum Disorder].

The core symptoms of autism spectrum disorder (ASD) comprise impairments of social communication and social interactions as well as restricted and repetitive patterns of interests and activities. No definitive treatments for these core symptoms currently exist. Oxytocin, a highly conserved peptide, has been suggested to moderate inter-individual relationships based on the results of many vertebrate studies. Recently, oxytocin has received a great deal of attention as a promising candidate for the treatment of ASD. Here, we review studies on the role of oxytocin in ASD. Numerous randomized controlled trials (RCTs) have shown single- dose oxytocin administration to have significantly favorable effects compared with placebo for both neuro-typical individuals and individuals with ASD. Furthermore, extended administra- tion of oxytocin was associated with effects that significantly exceeded those of a placebo in three of five published RCTs for ASD. Moreover, approximately 20 RCTs investigating whether oxytocin is favorable for ASD participants are in progress, according to clinical trial registries certified by the World Health Organization. The results of these RCTs may elucidate the issues regarding favorable and adverse effects, appropriate doses and treatment durations, participant selection, and specifically how to assess the changes in impairments of social com- munication and social interactions. In addition, it is necessary to consider which version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) is used for the diagnosis of ASD in each RCT because the range of individuals diagnosed with ASD has become gradually nar- rower with each DSM revision, i. e., the Fourth Edition, the Fourth Edition Text Revision, and the Fifth Edition.

Unusual developmental pattern of brain lateralization in young boys with autism spectrum disorder: Power analysis with child-sized magnetoencephalography.

AIMS: Autism spectrum disorder (ASD) is often described as comprising an unusual brain growth pattern and aberrant brain lateralization. Although it is important to study the pathophysiology of the developing ASD cortex, examples of physiological brain lateralization in young children with ASD have yet to be well examined. METHODS: Thirty-eight boys with ASD (aged 3-7 years) and 38 typically developing (TD) boys (aged 3-8 years) concentrated on video programs and their brain activities were measured non-invasively. We employed a customized child-sized magnetoencephalography system in which the sensors were located as close to the brain as possible for optimal recording in young children. To produce a credible laterality index of the brain oscillations, we defined two clusters of sensors corresponding to the right and left hemispheres. We focused on the laterality index ([left - right]/[left+right]) of the relative power band in seven frequency bands. RESULTS: The TD group displayed significantly rightward lateralized brain oscillations in the theta-1 frequency bands compared to the ASD group. CONCLUSIONS: This is the first study to demonstrate unusual brain lateralization of brain oscillations measured by magnetoencephalography in young children with ASD.

Broader autism phenotype in mothers predicts social responsiveness in young children with autism spectrum disorders.

AIMS: The aim of this study was to identify phenotypes in mothers and fathers that are specifically associated with disturbances in reciprocal social interactions and communication in their young children with autism spectrum disorder (ASD) in a Japanese sample. METHODS: Autistic traits in parents were evaluated using the Autism-spectrum Quotient (AQ), the Empathy Quotient (EQ) and the Systemizing Quotient (SQ) in 88 parents (44 mothers and corresponding fathers) of children with ASD and in 60 parents (30 mothers and corresponding fathers) of typically developing (TD) children. For the measurement of autistic traits in children, we employed the Social Responsiveness Scale (SRS). RESULTS: In two of the five AQ subscales (social skills and communication), the parents of ASD children scored significantly higher than did the parents of TD children, regardless of whether the parent was a mother or a father. In addition, in mothers of ASD children, there were significant positive correlations between two of the five AQ subscales (attention-switching and communication) and the SRS T-score in their children. CONCLUSIONS: This is the first study to demonstrate that the social skills and communication subscales in the AQ are more sensitive as autism traits in a Japanese sample and to demonstrate that some autistic traits in mothers are specifically associated with disturbances in the social ability of their young children with ASD, as measured by the SRS score. Further study is necessary to determine whether these results were caused by genetic or environmental factors.

A longitudinal study of auditory evoked field and language development in young children.

The relationship between language development in early childhood and the maturation of brain functions related to the human voice remains unclear. Because the development of the auditory system likely correlates with language development in young children, we investigated the relationship between the auditory evoked field (AEF) and language development using non-invasive child-customized magnetoencephalography (MEG) in a longitudinal design. Twenty typically developing children were recruited (aged 36-75 months old at the first measurement). These children were re-investigated 11-25 months after the first measurement. The AEF component P1m was examined to investigate the developmental changes in each participant's neural brain response to vocal stimuli. In addition, we examined the relationships between brain responses and language performance. P1m peak amplitude in response to vocal stimuli significantly increased in both hemispheres in the second measurement compared to the first measurement. However, no differences were observed in P1m latency. Notably, our results reveal that children with greater increases in P1m amplitude in the left hemisphere performed better on linguistic tests. Thus, our results indicate that P1m evoked by vocal stimuli is a neurophysiological marker for language development in young children. Additionally, MEG is a technique that can be used to investigate the maturation of the auditory cortex based on auditory evoked fields in young children. This study is the first to demonstrate a significant relationship between the development of the auditory processing system and the development of language abilities in young children.

Relationship between brain network pattern and cognitive performance of children revealed by MEG signals during free viewing of video.

Application of graph theory to analysis of functional networks in the brain is an important research trend. Extensive research on the resting state has shown a "small-world" organization of the brain network as a whole. However, the small-worldness of children's brain networks in a working state has not yet been well characterized. In this paper, we used a custom-made, child-sized magnetoencephalography (MEG) device to collect data from children while they were watching cartoon videos. Network structures were analyzed and compared with scores on the Kaufman Assessment Battery for Children (K-ABC). The results of network analysis showed that (1) the small-world scalar showed a negative correlation with the simultaneous processing raw score, a measure of visual processing (Gv) ability, and (2) the children with higher simultaneous processing raw scores possessed network structures that can be more efficient for local information processing than children with lower scores. These results were compatible with previous studies on the adult working state. Additional results obtained from further analysis of the frontal and occipital lobes indicated that high cognitive performance could represent better local efficiency in task-related sub-networks. Under free viewing of cartoon videos, brain networks were no longer confined to their strongest small-world states; connections became clustered in local areas such as the frontal and occipital lobes, which might be a more useful configuration for handling visual processing tasks.

Effects of brain amyloid deposition and reduced glucose metabolism on the default mode of brain function in normal aging.

Brain ß-amyloid (Aß) deposition during normal aging is highlighted as an initial pathogenetic event in the development of Alzheimer's disease. Many recent brain imaging studies have focused on areas deactivated during cognitive tasks [the default mode network (DMN), i.e., medial frontal gyrus/anterior cingulate cortex and precuneus/posterior cingulate cortex], where the strength of functional coordination was more or less affected by cerebral Aß deposits. In the present positron emission tomography study, to investigate whether regional glucose metabolic alterations and Aß deposits seen in nondemented elderly human subjects (n = 22) are of pathophysiological importance in changes of brain hemodynamic coordination in DMN during normal aging, we measured cerebral glucose metabolism with [(18)F]FDG, Aß deposits with [(11)C]PIB, and regional cerebral blood flow during control and working memory tasks by H(2)(15)O on the same day. Data were analyzed using both region of interest and statistical parametric mapping. Our results indicated that the amount of Aß deposits was negatively correlated with hemodynamic similarity between medial frontal and medial posterior regions, and the lower similarity was associated with poorer working memory performance. In contrast, brain glucose metabolism was not related to this medial hemodynamic similarity. These findings suggest that traceable Aß deposition, but not glucose hypometabolism, in the brain plays an important role in occurrence of neuronal discoordination in DMN along with poor working memory in healthy elderly people.

Lateralized theta wave connectivity and language performance in 2- to 5-year-old children.

Recent neuroimaging studies support the view that a left-lateralized brain network is crucial for language development in children. However, no previous studies have demonstrated a clear link between lateralized brain functional network and language performance in preschool children. Magnetoencephalography (MEG) is a noninvasive brain imaging technique and is a practical neuroimaging method for use in young children. MEG produces a reference-free signal, and is therefore an ideal tool to compute coherence between two distant cortical rhythms. In the present study, using a custom child-sized MEG system, we investigated brain networks while 78 right-handed preschool human children (32-64 months; 96% were 3-4 years old) listened to stories with moving images. The results indicated that left dominance of parietotemporal coherence in theta band activity (6-8 Hz) was specifically correlated with higher performance of language-related tasks, whereas this laterality was not correlated with nonverbal cognitive performance, chronological age, or head circumference. Power analyses did not reveal any specific frequencies that contributed to higher language performance. Our results suggest that it is not the left dominance in theta oscillation per se, but the left-dominant phase-locked connectivity via theta oscillation that contributes to the development of language ability in young children.

Language performance and auditory evoked fields in 2- to 5-year-old children.

Language development progresses at a dramatic rate in preschool children. As rapid temporal processing of speech signals is important in daily colloquial environments, we performed magnetoencephalography (MEG) to investigate the linkage between speech-evoked responses during rapid-rate stimulus presentation (interstimulus interval < 1 s) and language performance in 2- to 5-year-old children (n = 59). Our results indicated that syllables with this short stimulus interval evoked detectable P50m, but not N100m, in most participants, indicating a marked influence of longer neuronal refractory period for stimulation. The results of equivalent dipole estimation showed that the intensity of the P50m component in the left hemisphere was positively correlated with language performance (conceptual inference ability). The observed positive correlations were suggested to reflect the maturation of synaptic organisation or axonal maturation and myelination underlying the acquisition of linguistic abilities. The present study is among the first to use MEG to study brain maturation pertaining to language abilities in preschool children.

Neuroprotective and ameliorative actions of polyunsaturated fatty acids against neuronal diseases: implication of fatty acid-binding proteins (FABP) and G protein-coupled receptor 40 (GPR40) in adult neurogenesis.

Adult neurogenesis in the mammalian brain is well-known to occur in the subgranular zone of the hippocampus. As the hippocampus is related to learning, memory, and emotions, adult hippocampal neurogenesis possibly contributes to these functions. Adult neurogenesis is modulated by polyunsaturated fatty acids (PUFA) such as docosahexaenoic and arachidonic acids that are essential for normal brain development, maintenance, and function. They are reported to improve spatial learning and memory in rodents and cognitive functions in humans. However, detailed mechanisms of PUFA effects still remain obscure. PUFA are functionally linked with chaperons called fatty acid-binding proteins (FABP). FABP uptake and transport PUFA to different intracellular organelles. Intriguingly, PUFA were determined as ligands for G protein-coupled receptor 40 (GPR40), a cell membrane receptor abundantly expressed in the brain and the pancreas of primates. While the role of GPR40 in pancreatic ß-cells is associated with insulin secretion, its role in the brain is not yet clarified presumably because of its absence in the rodent brain. The purpose of this review is to discuss the role of PUFA in adult neurogenesis, considering the role of GPR40 and FABP in the hippocampal neurogenic niche. Here, the authors would like to introduce a PUFA-GPR40 signaling pathway that is specific for the primate brain.

CD38 gene knockout juvenile mice: a model of oxytocin signal defects in autism.

Oxytocin (OXT) in the hypothalamus is the biological basis of social recognition, trust, and bonding. We showed that CD38, a leukaemia cell marker, plays an important role in the hypothalamus in the process of OXT release in adult mice. Disruption of Cd38 (Cd38(-/-)) produced impairment of maternal behavior and male social recognition in mice, similar to the behavior observed in Oxt and OXT receptor (Oxtr) gene knockout (Oxt(-/-) and Oxtr(-/-), respectively) mice. Locomotor activity induced by separation from the dam was higher and the number of ultrasonic vocalization (USV) calls was lower in Cd38(-/-) than Cd38(+/+) pups. These phenotypes seemed to be caused by the high plasma OXT levels during development from neonates to 3-week-old juvenile mice. ADP-ribosyl cyclase activity was markedly lower in the knockout mice from birth, suggesting that weaning for mice is a critical time window of differentiating plasma OXT. Contribution by breastfeeding was an important exogenous source for regulating plasma OXT before weaning by the presence of OXT in milk and the dam's mammary glands. The dissimilarity of Cd38(-/-) infant behaviour to Oxt(-/-) or Oxtr(-/-) mice can be explained partly by this exogenous source of OXT. These results suggest that secretion of OXT into the brain in a CD38-dependent manner may play an important role in the development of social behavior, and mice with OXT signalling deficiency, including Cd38(-/-), Oxt(-/-) and Oxtr(-/-) mice are good animal models for developmental disorders, such as autism.

Platelet-derived growth factor BB: A potential diagnostic blood biomarker for differentiating bipolar disorder from major depressive disorder.

Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) due to overlapping depressive symptoms. This study investigated whether serum platelet-derived growth factor BB (PDGF-BB) is a differential diagnostic biomarker for BD and MDD. An initial SOMAscan proteomics assay of 1311 proteins in small samples from patients with BD and MDD and healthy controls (HCs) suggested that serum levels of PDGF-BB differed between BD and MDD. We then conducted a two-step, exploratory, cross-sectional, case-control study at our institute and five sites that included a total of 549 participants (157 with BD, 144 with MDD, and 248 HCs). Clinical symptoms were assessed using the Hamilton Depression Rating Scale and the Young Mania Rating Scale. In the initial analysis at our institute, serum PDGF-BB levels in the MDD group (n = 36) were significantly lower than those in the BD (n = 39) and HC groups (n = 36). In the multicenter study, serum PDGF-BB levels in the MDD group were again significantly lower than those in the BD and HC groups, with no significant difference between the BD and HC groups. Treatment with sodium valproate was associated with significantly lower serum PDGF-BB levels in patients with BD. After controlling for confounding factors (sex, age, body mass index, clinical severity, and valproate medication), serum PDGF-BB levels were lower in the MDD group than in the BD group regardless of mood state. Our findings suggest that serum PDGF-BB may be a potential biomarker to differentiate BD and MDD.