Automatic Depression Detection Using Smartphone-Based Text-Dependent Speech Signals: Deep Convolutional Neural Network Approach.

BACKGROUND: Automatic diagnosis of depression based on speech can complement mental health treatment methods in the future. Previous studies have reported that acoustic properties can be used to identify depression. However, few studies have attempted a large-scale differential diagnosis of patients with depressive disorders using acoustic characteristics of non-English speakers. OBJECTIVE: This study proposes a framework for automatic depression detection using large-scale acoustic characteristics based on the Korean language. METHODS: We recruited 153 patients who met the criteria for major depressive disorder and 165 healthy controls without current or past mental illness. Participants' voices were recorded on a smartphone while performing the task of reading predefined text-based sentences. Three approaches were evaluated and compared to detect depression using data sets with text-dependent read speech tasks: conventional machine learning models based on acoustic features, a proposed model that trains and classifies log-Mel spectrograms by applying a deep convolutional neural network (CNN) with a relatively small number of parameters, and models that train and classify log-Mel spectrograms by applying well-known pretrained networks. RESULTS: The acoustic characteristics of the predefined text-based sentence reading automatically detected depression using the proposed CNN model. The highest accuracy achieved with the proposed CNN on the speech data was 78.14%. Our results show that the deep-learned acoustic characteristics lead to better performance than those obtained using the conventional approach and pretrained models. CONCLUSIONS: Checking the mood of patients with major depressive disorder and detecting the consistency of objective descriptions are very important research topics. This study suggests that the analysis of speech data recorded while reading text-dependent sentences could help predict depression status automatically by capturing the characteristics of depression. Our method is smartphone based, is easily accessible, and can contribute to the automatic identification of depressive states.

BAF53b, a Neuron-Specific Nucleosome Remodeling Factor, Is Induced after Learning and Facilitates Long-Term Memory Consolidation.

Although epigenetic mechanisms of gene expression regulation have recently been implicated in memory consolidation and persistence, the role of nucleosome-remodeling is largely unexplored. Recent studies show that the functional loss of BAF53b, a postmitotic neuron-specific subunit of the BAF nucleosome-remodeling complex, results in the deficit of consolidation of hippocampus-dependent memory and cocaine-associated memory in the rodent brain. However, it is unclear whether BAF53b expression is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain site for fear memory encoding and storage. To address these questions, we used viral vector approaches to either decrease or increase BAF53b function specifically in the lateral amygdala of adult mice in auditory fear conditioning paradigm. Knockdown of Baf53b before training disrupted long-term memory formation with no effect on short-term memory, basal synaptic transmission, and spine structures. We observed in our qPCR analysis that BAF53b was induced in the lateral amygdala neurons at the late consolidation phase after fear conditioning. Moreover, transient BAF53b overexpression led to persistently enhanced memory formation, which was accompanied by increase in thin-type spine density. Together, our results provide the evidence that BAF53b is induced after learning, and show that such increase of BAF53b level facilitates memory consolidation likely by regulating learning-related spine structural plasticity.SIGNIFICANCE STATEMENT Recent works in the rodent brain begin to link nucleosome remodeling-dependent epigenetic mechanism to memory consolidation. Here we show that BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced in the lateral amygdala neurons at the late phase of consolidation after fear conditioning. Using specific gene knockdown or overexpression approaches, we identify the critical role of BAF53b in the lateral amygdala neurons for memory consolidation during long-term memory formation. Our results thus provide an idea about how nucleosome remodeling can be regulated during long-term memory formation and contributes to the permanent storage of associative fear memory in the lateral amygdala, which is relevant to fear and anxiety-related mental disorders.

Potential effectiveness of digital therapeutics specialized in executive functions as adjunctive treatment for clinical symptoms of attention-deficit/hyperactivity disorder: a feasibility study.

Introduction: The role of digital therapeutics (DTx) in the effective management of attention deficit/hyperactivity disorder (ADHD) is beginning to gain clinical attention. Therefore, it is essential to verify their potential efficacy. Method: We aimed to investigate the improvement in the clinical symptoms of ADHD by using DTx AimDT01 (NUROW) (AIMMED Co., Ltd., Seoul, Korea) specialized in executive functions. NUROW, which consists of Go/No-go Task- and N-Back/Updating-based training modules and a personalized adaptive algorithm system that adjusts the difficulty level according to the user's performance, was implemented on 30 Korean children with ADHD aged 6 to 12 years. The children were instructed to use the DTx for 15 min daily for 4 weeks. The Comprehensive attention test (CAT) and Childhood Behavior Checklist (CBCL) were used to assess the children at baseline and endpoint. In contrast, the ADHD-Rating Scale (ARS) and PsyToolkit were used weekly and followed up at 1 month, for any sustained effect. Repeated measures ANOVA was used to identify differences between the participants during visits, while t-tests and Wilcoxon signed-rank tests were used to identify changes before and after the DTx. Results: We included 27 participants with ADHD in this analysis. The ARS inattention (F = 4.080, p = 0.010), hyperactivity (F = 5.998. p < 0.001), and sum (F = 5.902, p < 0.001) significantly improved. After applying NUROW, internalized (t = -3.557, p = 0.001, 95% CI = -3.682--0.985), other (Z = -3.434, p = 0.001, effect size = -0.661), and sum scores (t = -3.081, p = 0.005, 95% CI = -10.126--2.022) were significantly changed in the CBCL. The overall effect was confirmed in the ARS sustained effect analysis even after 1 month of discontinuing the DTx intervention. Discussion: According to caregivers, the findings indicate that DTx holds potential effect as an adjunctive treatment in children with ADHD, especially in subjective clinical symptoms. Future studies will require detailed development and application targeting specific clinical domains using DTx with sufficient sample sizes.Clinical trial registration: KCT0007579.

Valproate Adjuvant Cognitive Behavioral Therapy in Panic Disorder Patients With Comorbid Bipolar Disorder: Case Series and Review of the Literature.

Anxiety disorders are the most common comorbid psychiatric disorders in patients with bipolar disorder. Managing anxiety symptoms in comorbid conditions is challenging and has received little research interest. The findings from preclinical research on fear conditioning, an animal model of anxiety disorder, have suggested that memory reconsolidation updating (exposure-based therapy) combined with valproate might facilitate the amelioration of fear memories. Here, three cases of successful amelioration of agoraphobia and panic symptoms through valproate adjuvant therapy for cognitive behavioral therapy in patients who failed to respond to two to three consecutive standard pharmacotherapy trials over several years are described. To the best of the author's knowledge, this is the first attempt to combine CBT with valproate in patients with panic disorder, agoraphobia, and comorbid bipolar disorder. Additionally, the background preclinical research on this combination therapy based on the reconsolidation-updating mechanism, the inhibition of histone deacetylase 2, and critical period reopening, off-label use of valproate in panic disorder, plasticity-augmented psychotherapy, and how to combine valproate with CBT is discussed.

Design and Methods of a Prospective Smartphone App-Based Study for Digital Phenotyping of Mood and Anxiety Symptoms Mixed With Centralized and Decentralized Research Form: The Search Your Mind (S.Y.M., ) Project.

In this study, the Search Your Mind (S.Y.M., ) project aimed to collect prospective digital phenotypic data centered on mood and anxiety symptoms across psychiatric disorders through a smartphone application (app) platform while using both centralized and decentralized research designs: the centralized research design is a hybrid of a general prospective observational study and a digital platform-based study, and it includes face-to-face research such as informed written consent, clinical evaluation, and blood sampling. It also includes digital phenotypic assessment through an application-based platform using wearable devices. Meanwhile, the decentralized research design is a non-face-to-face study in which anonymous participants agree to electronic informed consent forms on the app. It also exclusively uses an application-based platform to acquire individualized digital phenotypic data. We expect to collect clinical, biological, and digital phenotypic data centered on mood and anxiety symptoms, and we propose a possible model of centralized and decentralized research design.

Association between the IL10 rs1800896 Polymorphism and Tardive Dyskinesia in Schizophrenia.

OBJECTIVE: Interleukin-10 (IL-10) is a major immunoregulatory cytokine and its gene plays a fundamental role in anti-inflammatory and immunosuppressive activity. This study aimed to examine the association between the IL10 gene promoter -1082G/A polymorphism (rs1800896) and tardive dyskinesia (TD) in schizophrenia. METHODS: Two hundred and eighty unrelated Korean schizophrenic patients participated in this study (105 TD and 175 non-TD patients). TD was diagnosed using the Research Diagnostic Criteria for TD and Abnormal Involuntary Movement Scale (AIMS). Genotyping was performed by RT-PCR and high-resolution melting curve analysis. RESULTS: The distributions of genotypic frequencies did not differ between patients with and without TD (χ2=4.33, p=0.115). However, allelic frequencies of the two groups were different (χ2=4.45, p=0.035); the A allele frequency was higher in TD. The total AIMS scores of the three genotypes were not different (F=1.33, p=0.266). However, the total AIMS scores of the A allele carrier and the A allele non-carrier were significantly different (t=5.79, p<0.001). Logistic regression analaysis showed that IL10 -1082G/A genotype significantly predicts presence of TD (p=0.045) after adjusting for covariates such as age and treatment duration. CONCLUSION: This finding suggests that the A allele of rs1800896 may be associated with TD development following a low IL-10 function.

Efficacy and safety of oral SOCG in treatment of major depressive disorder: A protocol for a phase II, randomized, double-blind, placebo controlled, parallel-groups, dose finding exploratory study.

INTRODUCTION: Major depressive disorder (MDD) is a common condition worldwide, and leads to degradation in quality of life and large socioeconomic costs. There has been increasing demand for new therapies with fewer side effects. SOCG (SOCG tablet) is a modified prescription of So-ochim-tang, which is widely used in Traditional Korean Medicine to treat MDD. We aim to evaluate the efficacy of SOCG in treating MDD, and identify the optimum dose. DESIGN: The protocol we are following is that of a Phase II clinical trial with a randomized, double blinded, placebo controlled, and parallel design. One hundred forty-eight participants will be randomly divided into 4 groups and treated for 8 weeks. OUTCOME MEASURES: The primary outcome will be the score in the Korean Version of the Hamilton Depression Rating Scale. Scores in the Korean version of the Beck Depression Inventory-II Korean Symptom Check List-95 (KSCL-95), State Trait Anxiety Inventory-Korean version, State- Trait Anger Expression Inventory- Korean version (STAXI-K), Insomnia Severity Index (ISI), and the EuroQol-5 Dimension (EQ-5D) will be considered as secondary outcomes. DISCUSSION AND CONCLUSIONS: Demonstration of human safety and efficacy of SOCG in the present trial and identification of the appropriate dose will justify a New Drug Application and a phase III clinical trial. Further, we expect that this new antidepressant will be able to increase cure rates, and alleviate the burden of medical expenses. TRIAL REGISTRATION NUMBER: Clinical Research Information Service, Republic of Korea (KCT0002763).

Predicting neurocognitive function with hippocampal volumes and DTI metrics in patients with Alzheimer's dementia and mild cognitive impairment.

INTRODUCTION: Cognitive performance in patients with Alzheimer's dementia (AD) and mild cognitive impairment (MCI) has been reported to be related to hippocampal atrophy and microstructural changes in white matter (WM). We aimed to predict the neurocognitive functions of patients with MCI or AD using hippocampal volumes and diffusion tensor imaging (DTI) metrics via partial least squares regression (PLSR). METHODS: A total of 148 elderly female subjects were included: AD (n = 49), MCI (n = 66), and healthy controls (n = 33). Twenty-four hippocampal subfield volumes and the average values for fractional anisotropy (FA) and mean diffusivity (MD) of 48 WM tracts were used as predictors, CERAD-K total scores, scores of CERAD-K 7 cognitive subdomains and K-GDS were used as dependent variables in PLSR. RESULTS: Regarding MCI patients, DTI metrics such as the MD values of the left retrolenticular part of the internal capsule and left fornix (cres)/stria terminalis were significant predictors, while hippocampal subfield volumes, like the left CA1 and hippocampal tail, were main contributors to cognitive function in AD patients, although global FA/MD values were also strong predictors. The 10-fold cross-validation and stricter 300-iteration tests proved that global cognition measured by the CERAD-K total scores and the scores of several CERAD-K subdomains can be reliably predicted using the PLSR models. CONCLUSIONS: Our findings indicate different structural contributions to cognitive function in MCI and AD patients, implying that diffuse WM microstructural changes may precede hippocampal atrophy during the AD neurodegenerative process.

Dehydroepiandrosterone Sulfate Level Varies Nonlinearly with Symptom Severity in Major Depressive Disorder.

OBJECTIVE: The pathophysiology of major depressive disorder (MDD) is still not well understood. Conflicting results for surrogate.biomarkers in MDD have been reported, which might be a consequence of the heterogeneity of MDD patients. Therefore, we aim to investigate how the severity of depression and various symptom domains are related to the levels of dehydroepiandrosterone sulfate (DHEA-s) in MDD patients. METHODS: We recruited 117 subjects from a general practice. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Depressive symptoms were divided into three subdomains according to BDI items; somatic symptoms, guilt and failure, and mood and inhibition. RESULTS: In subjects with very-mild-to-moderate depression, the DHEA-s level increased as BDI score did. However, the DHEA-s levels in the subjects with severe depression were significantly lower than in subjects with moderate depression (p=0.003). DHEA-s level was correlated with the BDI subscore for guilt and failure in very-mild-to-moderate depression (r=0.365, p=0.006). CONCLUSION: The DHEA-s level appears to be indicative of MDD severity with respect to depressive symptoms, especially regarding guilt and failure. Our findings suggest that the upregulation of DHEA-s may be a part of a compensatory process in very-mild-to-moderate depression, and the failure of this compensation mechanism may underlie the development of severe depression.

Plasticity-augmented psychotherapy for refractory depressive and anxiety disorders.

Psychotherapy and pharmacotherapy have been the mainstays of treatment for depression and anxiety disorders during the last century. However, treatment response has not improved in the last few decades, with only half of all patients responding satisfactorily to typical antidepressants. To fulfill the needs of the remaining patients, new treatments with better efficacy are in demand. The addition of psychotherapy to antidepressant treatment has been shown to be superior to pharmacotherapy alone. However, the time costs of psychotherapy limit its use for clinicians and patients. Advancements in neuroscience have contributed to an improved understanding of the pathogenesis of depressive and anxiety disorders. In particular, recent advances in the field of fear conditioning have provided valuable insight into the treatment of refractory depressive and anxiety disorders. In this review, we studied the reconsolidation-updating paradigm and the concept of epigenetic modification, which has been shown to permanently attenuate remote fear memory. This has implications for drug-augmented, e.g. antidepressant and valproic acid, psychotherapy. Future research on more sophisticated psychotherapy techniques will increase the desirability of this treatment modality for both clinicians and patients.

Toward understanding the role of the neuron-specific BAF chromatin remodeling complex in memory formation.

The long-term storage of memory requires the finely tuned coordination of intracellular signaling with the transcriptional, translational and epigenetic regulations of gene expression. Among the epigenetic mechanisms, however, we know relatively little about the involvement of chromatin remodeling-dependent control of gene expression in cognitive brain functions, compared with our knowledge of other such mechanisms (for example, histone modifications and DNA methylation). A few recent studies have implicated the Brm/Brg-associated factor (BAF) chromatin-remodeling complex, a mammalian homolog of the yeast Swi/Snf complex, in neuronal structural/functional plasticity and memory formation. The BAF complex was previously known to have a critical role in neurodevelopment, but these recent findings indicate that it also contributes to both cognitive functions in the adult brain and human mental disorders characterized by intellectual disability. In this review, we provide a brief overview of the BAF complexes, introduce recent research findings that link their functions to memory formation, and speculate on the yet-unknown molecular mechanisms that may be relevant to these processes.

Association between Serotonin-Related Polymorphisms in 5HT2A, TPH1, TPH2 Genes and Bipolar Disorder in Korean Population.

OBJECTIVE: The aim of the present study was to examine the association between serotonin-related gene polymorphisms and bipolar disorder in the Korean population. In addition, we sought to explore the relationship between the clinical characteristics of bipolar patients and serotonin-related gene polymorphisms. METHODS: Inpatients with bipolar disorder (n=103) and control subjects (n=86) were genotyped for 5HT2A 1438A/G, tryptophan hydroxylase 1 (TPH1) 218 A/C, and TPH2 703G/T. We divided patients with bipolar disorder into two groups according to the presence of psychotic symptoms. The severity of their symptoms was measured using the Young Mania Rating Scale (YMRS) and the Brief Psychiatric Rating Scale (BPRS). RESULTS: There were no significant differences in the genotype distributions or allelic frequencies in the three serotonergic polymorphisms between patients with bipolar disorder and normal controls. There were significant differences in genotype distributions and allele frequencies of the 5-HT2A -1438A/G polymorphism between the psychotic mania group and the non-psychotic mania group (genotype: chi(2)=7.50, p=0.024; allele: chi(2)=5.92, p=0.015). However, after Bonferroni correction this signifact difference disappeared. We did not find significant differences in the genotype distributions or allelic frequencies in the TPH1 218 A/C and TPH2 703G/T polymorphisms between the psychotic mania group and non-psychotic mania group. CONCLUSION: We failed to found the statistically significant association between three polymorphisms and bipolar disorder. However, there was a trend towards association between 5-HT2A -1438A/G polymorphism and psychotic symptom in bipolar disorder. Future research should seek to clarify this association.