Development of an innovative approach using portable eye tracking to assist ADHD screening: a machine learning study.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) affects a significant proportion of the pediatric population, making early detection crucial for effective intervention. Eye movements are controlled by brain regions associated with neuropsychological functions, such as selective attention, response inhibition, and working memory, and their deficits are related to the core characteristics of ADHD. Herein, we aimed to develop a screening model for ADHD using machine learning (ML) and eye-tracking features from tasks that reflect neuropsychological deficits in ADHD. Methods: Fifty-six children (mean age 8.38 ± 1.58, 45 males) diagnosed with ADHD based on the Diagnostic and Statistical Manual of Mental Disorders, fifth edition were recruited along with seventy-nine typically developing children (TDC) (mean age 8.80 ± 1.82, 33 males). Eye-tracking data were collected using a digital device during the performance of five behavioral tasks measuring selective attention, working memory, and response inhibition (pro-saccade task, anti-saccade task, memory-guided saccade task, change detection task, and Stroop task). ML was employed to select relevant eye-tracking features for ADHD, and to subsequently construct an optimal model classifying ADHD from TDC. Results: We identified 33 eye-tracking features in the five tasks with the potential to distinguish children with ADHD from TDC. Participants with ADHD showed increased saccade latency and degree, and shorter fixation time in eye-tracking tasks. A soft voting model integrating extra tree and random forest classifiers demonstrated high accuracy (76.3%) at identifying ADHD using eye-tracking features alone. A comparison of the model using only eye-tracking features with models using the Advanced Test of Attention or Stroop test showed no significant difference in the area under the curve (AUC) (p = 0.419 and p=0.235, respectively). Combining demographic, behavioral, and clinical data with eye-tracking features improved accuracy, but did not significantly alter the AUC (p=0.208). Discussion: Our study suggests that eye-tracking features hold promise as ADHD screening tools, even when obtained using a simple digital device. The current findings emphasize that eye-tracking features could be reliable indicators of impaired neurobiological functioning in individuals with ADHD. To enhance utility as a screening tool, future research should be conducted with a larger sample of participants with a more balanced gender ratio.

Depression and posttraumatic stress disorder in adolescents with nonsuicidal self-injury: comparisons of the psychological correlates and suicidal presentations across diagnostic subgroups.

BACKGROUND: Nonsuicidal self-injury (NSSI) combined with suicide ideation increases the risk of suicidal behaviors. Depression and posttraumatic stress disorder (PTSD) are comorbidities of NSSI compounding this relationship. The present study compared diagnostic subgroups of NSSI based on current depression and PTSD on psychological correlates (i.e., vulnerabilities and impairment) and suicidal presentations (i.e., suicidal cognitions and behaviors) in a psychiatric sample of adolescents. METHODS: Eighty-seven adolescents meeting DSM-5 criteria for NSSI and 104 age-range-matched nonclinical controls (NC) participated. Participants completed self-report measures on psychological vulnerabilities and impairment (e.g., emotion regulation difficulties, negative cognitions). Adolescents with NSSI also completed clinical interviews on psychiatric diagnoses and a recent self-injurious behavior (SIB). Scores on the psychological correlates of NSSI were compared between adolescents with NSSI and NC, and across three diagnostic subgroups of NSSI (A: NSSI+/depression-/PTSD-, n = 14; B: NSSI+/depression+/PTSD-, n = 57; C: NSSI+/depression+/PTSD+, n = 14). Differences between NSSI diagnostic subgroups were tested on the motives for SIB and accompanying suicidal presentations (e.g., desire, intent, motive, lethality). RESULTS: Common comorbidities of NSSI included depression, panic disorder, generalized anxiety disorder, and PTSD. The NSSI subgroup classification was significantly associated with panic disorder, which was controlled for in the subsequent group comparisons. Overall, adolescents who engage in NSSI with vs. without depression reported more psychological vulnerabilities and impairment and a greater degree of suicidal thoughts/desire in SIB (i.e., groups B, C >A), which remained significant after controlling for panic disorder. An increased odds of the suicidal motive for SIB was found in adolescents with all three conditions (i.e., group C: NSSI+/depression+/PTSD+) compared to those with NSSI but neither depression nor PTSD (i.e., group A: NSSI+/depression-/PTSD-); however, this was not significant after controlling for panic disorder. CONCLUSIONS: Psychological underpinnings of adolescent NSSI in clinical contexts may be largely associated with concurrent depression. Suicidal motives in adolescents who engage in NSSI in the presence of depression and PTSD may be confounded by the co-occurrence of panic disorder. This study warrants the importance of attending to the comorbid depression with NSSI in adolescents as it is related to an increase in suicidal desire accompanying SIB.

A Survey on the Journal of the Korean Academy of Child and Adolescent Psychiatry: Implications for Growth and Development.

Objectives: This study aimed to assess the status of the Journal of the Korean Academy of Child and Adolescent Psychiatry (JKACAP) and propose measures for its growth and development. Methods: The study was conducted using a questionnaire survey targeting members of the Korean Academy of Child and Adolescent Psychiatry. The six key elements analyzed were Access to the journal, Convenience following conversion to English, Recognition as an international journal and institutional achievements, Author perspectives on manuscript submission,Transition to an online-only journal, and Content and identity of the journal. Results: The survey revealed that email notification was highly effective for Journal Accessibility, with the website and search engines also frequently being used by members. Conversion to English in 2018 initially impacted readability and submission rates, but these concerns have decreased over time. However, the Recognition of JKACAP as an international academic journal was still not on par with SCIE journals, highlighting the need for further efforts towards SCIE inclusion. Despite these challenges and limited research opportunities, there was an active intention among members to submit manuscripts. Respondents showed a notable preference for the Transition to an online-only journal. Regarding content and identity of the JKACAP, members predominantly favored review articles and perceived the journal as a research and communication platform for Korean child and adolescent psychiatrists. Conclusion: The results indicate the need for JKACAP to enhance its digital accessibility, provide more support for domestic and international authors, and actively seek SCIE indexing. Addressing the varied content preferences of its members, improving the submission process, and transitioning to an online-only format could further its growth and solidify its position as an internationally recognized academic journal in the field of child and adolescent psychiatry.

Measures of Connectivity and Dorsolateral Prefrontal Cortex Volumes and Depressive Symptoms Following Treatment With Selective Serotonin Reuptake Inhibitors in Adolescents.

Importance: Selective serotonin reuptake inhibitors (SSRIs) are considered a first-line pharmacological treatment for adolescent depression with moderate or higher levels of symptom severity. Thus, it is important to understand neurobiological changes related to SSRIs during the course of treatment for adolescents with depression. Objective: To examine neurobiological changes associated with SSRI treatment in adolescents with major depressive disorder (MDD) by measuring longitudinal changes in volume and resting-state functional connectivity (rsFC) in the dorsolateral prefrontal cortex (DLPFC), a core region of cognitive control. Design, Setting, and Participants: This cohort study was conducted with an open-label design. Adolescents with MDD and healthy controls were recruited at the Seoul National University Hospital (Seoul, South Korea). Adolescents with MDD were treated with escitalopram for 8 weeks. Data analysis was conducted between April 2021 and February 2022. Main Outcomes and Measures: Depressive symptoms were assessed using the Children's Depression Rating Scale-Revised. The outcome measure was defined as the change in Children's Depression Rating Scale-Revised scores from week 0 (before treatment) to week 8 (after treatment) or upon termination. Participants completed structural and resting-state functional magnetic resonance imaging (rsfMRI) assessments before (week 0) and after (week 8) SSRI treatment. Repeated measures analysis of variance and liner mixed model analyses were used to examine the longitudinal associations of SSRI treatment with DLPFC volume and rsFC between responders who showed at least a 40% decrease in depressive symptoms and nonresponders who did not. Results: Ninety-five adolescents with MDD and 57 healthy controls were initially recruited. The final analyses of volume included 36 responders (mean [SD] age, 15.0 [1.6] years; 25 girls [69.4%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). Analyses of rsFC included 33 responders (mean [SD] age, 15.2 [1.5] years; 21 girls [63.6%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). The longitudinal associations of SSRI treatment were more evident in responders than in nonresponders. Responders showed significantly increased right DLPFC volume, decreased bilateral DLPFC rsFC with the superior frontal gyri, and decreased left DLPFC rsFC with the ventromedial PFC after treatment compared with before treatment. Furthermore, increased right DLPFC volume was correlated with decreased rsFC between the right DLPFC and superior frontal gyri after SSRI treatment. Conclusions and Relevance: The preliminary results of this cohort study suggest that the DLPFC volumetric and rsFC changes may serve as potential neurobiological treatment markers that are associated with symptom improvement in adolescents with MDD.

Effects of Parental Verbal Abuse Experience on the Glutamate Response to Swear Words in the Ventromedial Prefrontal Cortex: A Functional 1H-magnetic Resonance Spectroscopy Study.

Objective: Several lines of evidence indicate verbal abuse (VA) critically impacts the developing brain; however, whether VA results in changes in brain neurochemistry has not been established. Here, we hypothesized that exposure to recurrent parental VA elicits heightened glutamate (Glu) responses during the presentation of swear words, which can be measured with functional magnetic resonance spectroscopy (fMRS). Methods: During an emotional Stroop task consisting of blocks of color and swear words, metabolite concentration changes were measured in the ventromedial prefrontal cortex (vmPFC) and the left amygdalohippocampal region (AMHC) of healthy adults (14 F/27 M, 23 ± 4 years old) using fMRS. The dynamic changes in Glu and their associations with the emotional state of the participants were finally evaluated based on 36 datasets from the vmPFC and 30 from the AMHC. Results: A repeated-measures analysis of covariance revealed a modest effect of parental VA severity on Glu changes in the vmPFC. The total score on the Verbal Abuse Questionnaire by parents (pVAQ) was associated with the Glu response to swear words (ΔGluSwe). The interaction term of ΔGluSwe and baseline N-acetyl aspartate (NAA) level in the vmPFC could be used to predict state-trait anxiety level and depressive mood. We could not find any significant associations between ΔGluSwe in the AMHC and either pVAQ or emotional states. Conclusion: Parental VA exposure in individuals is associated with a greater Glu response towards VA-related stimuli in the vmPFC and that the accompanying low NAA level may be associated with anxiety level or depressive mood.

Outcomes After Endovascular Treatment of Direct Carotid Cavernous Fistulas: Systematic Review and Meta-Analysis.

BACKGROUND: Direct carotid cavernous fistulas (dCCF) involve pathologic shunting from the internal carotid artery into the cavernous sinus. We systematically reviewed the methods and outcomes of endovascular therapy for dCCF. METHODS: PubMed, Scopus, and EMBASE were used to identify studies that reported outcomes for patients undergoing embolization of dCCF. Outcomes included rates of occlusion, complications, symptom improvement, and recurrence. Pooled rates for each outcome were obtained with random effects models. The influence of embolization method on outcomes was assessed with meta-regressions. RESULTS: There were 16 studies comprising 270 patients. The mean age was 39.6 years, there were 36.3% females, and the mean follow-up was 19.7 months. Coils were the most common method of embolization (69.3%), followed by Onyx (31.1%), covered stent (22.2%), N-butyl cyanoacrylate (6.7%), and flow diversion (4.8%). The pooled overall occlusion rate was 92.1% (95% confidence interval [CI], 86.3-95.6; I2 = 29.2%). The pooled complication rate was 10.9% (95% CI, 7.3-16; I2 = 0%). Use of coils were associated with a slightly lower odds of overall complications (odds ratio, 0.98; 95% CI, 0.97-0.99) and cranial nerve palsy (odds ratio, 0.98; 95% CI, 0.97-0.99). The pooled fistula recurrence rate was 8.3% (95% CI, 4.3-15.4; I2 = 30.9%). CONCLUSIONS: Endovascular therapy for dCCF is associated with high occlusion and low complication rates. Recurrence is not uncommon, highlighting the need for close follow-up.

Alteration of cortical functional networks in mood disorders with resting-state electroencephalography.

Studies comparing bipolar disorder (BD) and major depressive disorder (MDD) are scarce, and the neuropathology of these disorders is poorly understood. This study investigated source-level cortical functional networks using resting-state electroencephalography (EEG) in patients with BD and MDD. EEG was recorded in 35 patients with BD, 39 patients with MDD, and 42 healthy controls (HCs). Graph theory-based source-level weighted functional networks were assessed via strength, clustering coefficient (CC), and path length (PL) in six frequency bands. At the global level, patients with BD and MDD showed higher strength and CC, and lower PL in the high beta band, compared to HCs. At the nodal level, compared to HCs, patients with BD showed higher high beta band nodal CCs in the right precuneus, left isthmus cingulate, bilateral paracentral, and left superior frontal; however, patients with MDD showed higher nodal CC only in the right precuneus compared to HCs. Although both MDD and BD patients had similar global level network changes, they had different nodal level network changes compared to HCs. Our findings might suggest more altered cortical functional network in patients with BD than in those with MDD.

Development and validation of the Self-Harm Screening Inventory (SHSI) for adolescents.

Despite the rapidly increasing rate of non-suicidal self-injury (NSSI) among adolescents, there is a dearth of culturally appropriate psychological measures screening for NSSI among the adolescents in the Asian countries. This study aimed to develop and validate the Self-Harm Screening Inventory (SHSI), a culturally sensitive and suitable scale for screening adolescents for NSSI. In total, 514 Korean adolescents (aged 12-16 years) were recruited nationwide. All participants gave informed consent and completed the online self-report measures on NSSI, depression, anxiety, and self-esteem. Thereafter, preliminary items were developed through a series of steps: literature review, ratings of experts on self-harm and suicide, and statistical analyses. Ten of the 20 preliminary items were eliminated after exploratory factor analysis due to low endorsement and factor loading (less than .70). The final version of the SHSI comprised 10 binary items relating to self-harm behaviors within the past year (e.g., cut my body with sharp objects, hit my body). A confirmatory factor analysis supported a one-factor structure, as hypothesized. The one-factor model had a good model fit (x2(35) = 84.958, p < .001, RMSEA = .053, CFI = .981, TLI = .975, SRMR = .124). The SHSI also had good internal consistency (Cronbach's alpha = .795) and 4-week test-retest reliability (r = .786, p < .01). The SHSI had high correlations with another self-harm related scale, the Self-Harm Inventory (r = .773, p < .01), and moderate correlations with the Child Depression Inventory (r = .484, p < .01) and Revised Children's Manifest Anxiety Scale (r = .433, p < .01). Additionally, the SHSI was negatively correlated with the Rosenberg Self-Esteem Scale (r = -.399, p < .01). The findings indicate that the SHSI is a reliable and valid measure for the screening of self-harm behaviors among adolescents.

Reduced Volume of a Brainstem Substructure in Adolescents with Problematic Smartphone Use.

OBJECTIVES: Despite the growing concern regarding the adverse effects related to problematic smartphone use (PSU), little is known about underlying morphologic changes in the brain. The brainstem is a deep brain structure that consists of several important nuclei associated with emotions, sensations, and motor functions. In this study, we sought to examine the difference in the volume of brainstem substructures among adolescents with and without PSU. METHODS: A total of 87 Korean adolescents participated in this study. The PSU group (n=20, age=16.2±1.1, female:male=12:8) was designated if participants reported a total Smartphone Addiction Proneness Scale (SAPS) score of ≥42, whereas the remaining participants were assigned to the control group (n=67, age=15.3±1.7, female:male=19:48). High-resolution T1 magnetic resonance imaging was performed, and the volume of each of the four brainstem substructures [midbrain, pons, medulla, and superior cerebellar peduncle (SCP)] was measured. Analysis of covariance was conducted to reveal group differences after adjusting for effects of age, gender, whole brain-stem volume, depressive symptoms, and impulsivity. RESULTS: The PSU group showed a significantly smaller volume of the SCP than the control group (F=8.273, p=0.005). The volume of the SCP and the SAPS score were negatively correlated (Pearson's r=-0.218, p=0.047). CONCLUSION: The present study is the first to reveal an altered volume of the brainstem substructure among adolescents with PSU. This finding suggests that the altered white matter structure in the brainstem could be one of the neurobiological mechanisms underlying behavioral changes in PSU.

Machine-learning-based diagnosis of drug-naive adult patients with attention-deficit hyperactivity disorder using mismatch negativity.

Relatively little is investigated regarding the neurophysiology of adult attention-deficit/hyperactivity disorder (ADHD). Mismatch negativity (MMN) is an event-related potential component representing pre-attentive auditory processing, which is closely associated with cognitive status. We investigated MMN features as biomarkers to classify drug-naive adult patients with ADHD and healthy controls (HCs). Sensor-level features (amplitude and latency) and source-level features (source activation) of MMN were investigated and compared between the electroencephalograms of 34 patients with ADHD and 45 HCs using a passive auditory oddball paradigm. Correlations between MMN features and ADHD symptoms were analyzed. Finally, we applied machine learning to differentiate the two groups using sensor- and source-level features of MMN. Adult patients with ADHD showed significantly lower MMN amplitudes at the frontocentral electrodes and reduced MMN source activation in the frontal, temporal, and limbic lobes, which were closely associated with MMN generators and ADHD pathophysiology. Source activities were significantly correlated with ADHD symptoms. The best classification performance for adult ADHD patients and HCs showed an 81.01% accuracy, 82.35% sensitivity, and 80.00% specificity based on MMN source activity features. Our results suggest that abnormal MMN reflects the adult ADHD patients' pathophysiological characteristics and might serve clinically as a neuromarker of adult ADHD.

Relationship of Social and Behavioral Characteristics to Suicidality in Community Adolescents With Self-Harm: Considering Contagion and Connection on Social Media.

A close link has been established between self-harm and suicide risk in adolescents, and increasing attention is given to social media as possibly involved in this relationship. It is important to identify indicators of suicidality (i.e., suicide ideation or attempt) including aspects related to contagion in online and offline social networks and explore the role of social media in the relationship between social circumstances and suicidality in young adolescents with self-harm. This study explored characteristics of Korean adolescents with a recent history of self-harm and identified how behavioral and social features explain lifetime suicidality with emphasis on the impact of social media. Data came from a nationwide online survey among sixth- to ninth-graders with self-harm during the past 12 months (n = 906). We used χ2 tests of independence to explore potential concomitants of lifetime suicidality and employed a multivariate logistic regression model to examine the relationship between the explanatory variables and suicidality. Sensitivity analyses were performed with lifetime suicide attempt in place of lifetime suicidality. 33.9% (n = 306) and 71.2% (n = 642) reported to have started self-harm by the time they were fourth- and six-graders, respectively; 44.3% (n = 400) reported that they have friends who self-harm. Having endorsed moderate/severe forms and multiple forms of self-harm (OR 5.36, p < 0.001; OR 3.13, p < 0.001), having engaged in self-harm for two years or more (OR 2.42, p = 0.001), having friends who self-harm (OR 1.92, p = 0.013), and having been bullied at school were associated with an increased odds of lifetime suicidality (OR 2.08, p = 0.004). Notably, having posted content about one's self-harm on social media during the past 12 months was associated with an increased odds of lifetime suicidality (OR 3.15, p < 0.001), whereas having seen related content in the same period was not. Sensitivity analyses yielded similar results with lifetime suicide attempt, supporting our findings from the logistic regression. The current study suggests that self-harm may be prevalent from early adolescence in South Korea with assortative gathering. The relationship of vulnerable adolescents' social circumstances to suicide risk may be compounded by the role of social media. As the role of social media can be linked to both risk (i.e., contagion) and benefit (i.e., social connection and support), pre-existing vulnerabilities alongside SH and what online communication centers on should be a focus of clinical attention.

Caudate nucleus volume mediates the link between glutamatergic neurotransmission and problematic smartphone use in youth.

BACKGROUND AND AIMS: Problematic smartphone use (PSU) is growing rapidly among teens. It has similar presentations as other behavioral addictions in terms of excessive use, impulse control problems, and negative consequences. However, the underlying neurobiological mechanisms remain undiscovered. We hypothesized that structural changes in the striatum might serve as an important link between alteration in glutamate signaling and development of PSU. METHODS: Among 88 participants, twenty (F:M, 12:8; age 16.2 ± 1.1) reported high scores in the smartphone addiction proneness scale (SAPS) with a cut-off score of 42; the other 68 (F:M, 19:49; age 15.3 ± 1.7) comprised the control group. Sociodemographic data and depression, anxiety, and impulsivity traits were measured. Striatal volumes (caudate, putamen, and nucleus accumbens) were estimated from T1 imaging data. Serum glutamate levels were estimated from peripheral blood samples. Group comparisons of each data were performed after controlling for age and gender. Mediation analyses were conducted to test the indirect effects of glutamate level alteration on PSU through striatal volumetric alteration. RESULTS: The PSU group showed a decrease in both caudate volumes than the control group. Left caudate volume was positively correlated with serum glutamate level, and negatively with impulsivity traits and SAPS scores. The mediation model revealed a significant indirect effect of serum glutamate on SAS scores through the reduced left caudate volume. DISCUSSION AND CONCLUSIONS: This study suggests that altered glutamatergic neurotransmission may be associated with PSU among teens, possibly through reduced left caudate volume. Current findings might support neural mechanisms of smartphone addiction.

Altered cortical functional network in drug-naive adult male patients with attention-deficit hyperactivity disorder: A resting-state electroencephalographic study.

Relatively little is known about the neurophysiology of adult Attention-deficit/hyperactivity disorder (ADHD). Brain network analysis can yield important insights into the neuropathology in adult ADHD. The objective of this study was to investigate source-level cortical functional network using resting-state electroencephalography (EEG) in drug-naive adult patients with ADHD. Resting-state EEG was performed for 30 adult male patients with ADHD and 27 male healthy controls. Source-level weighted functional networks based on graph theory were evaluated, including strength, clustering coefficient (CC) and path length (PL) in six frequency bands. At the global level, strength (η2 = 0.167) and CC (η2 = 0.156) were lower while PL (η2 = 0.159) was higher for the high beta band in the ADHD patient group compared to healthy controls. At the nodal level, CCs of the high beta band were lower in the left middle temporal gyrus (η2 = 0.244), right inferior occipital cortex (η2 = 0.214), right posterior transverse collateral sulcus (η2 = 0.237), and right anterior occipital sulcus (η2 = 0.251) for the adult ADHD group. Furthermore, the nodal-level high beta band CCs of the left middle temporal gyrus and right anterior occipital sulcus were significantly negatively correlated with ADHD symptoms. The altered cortical functional network showed inefficient connectivity in the left middle temporal gyrus, belonging to the default mode network, the right inferior occipital cortex, belonging to the extrastriate visual resting state network, the right posterior transverse collateral sulcus, belonging to the visual network, and the anterior occipital sulcus, reflecting visual attention, which might affect the pathophysiology of ADHD. Taken together, these attenuated network inefficiencies in adult patients with ADHD may lead to suboptimal information processing and affect symptoms of ADHD, such as inattention and hyperactivity. Our findings should be further replicated using longitudinal study designs.

The Thirty-First Year Journey, the Journal of the Korean Academy of Child and Adolescent Psychiatry.

OBJECTIVES: The Journal of the Korean Academy of Child and Adolescent Psychiatry (JKACAP) has had a 31 year-long history, sharing research and reviews of children and adolescents' mental health to promote voluntary participation and communication of the members of this society. Here, we have reviewed the detailed history of the journal from the perspective of developmental progression of JKACAP and discussed the direction of further development. METHODS & RESULTS: We reviewed the journey of the journal by focusing on the effort it took to take the journal to a global standard, and discussed the future direction of progress of JKACAP, based on the opinions raised at the Editor-in-Chiefs' reunion. CONCLUSION: JKACAP has just stepped on the path to globalization by being indexed in Emerging Sources Citation Index, PubMed Central, and Scopus. It is time to progress to another dimension, by acknowledging and overcoming more complicated issues, such as augmenting impact of the journal, expanding domains of interdisciplinary collaboration, and more global cooperation.

Mismatch negativity indices and functional outcomes in unipolar and bipolar depression.

The aim of the study was to explore the association between functional outcomes and mismatch negativity (MMN) activity in participants with mood disorders. The study participants were 27 subjects with major depressive disorder (MDD), 29 subjects with bipolar disorder (BD), and 33 healthy controls who performed a passive auditory oddball paradigm while electroencephalography (EEG) was recorded. Peak amplitudes and source activity of the MMN were compared across groups. Mood and anxiety symptoms were evaluated. The functional levels were the lowest in the BD group, followed by the MDD and healthy control groups. The subjects with BD had significantly lower MMN amplitudes at the frontal and frontocentral electrodes than the healthy controls. The source activity of the MMN from the left anterior cingulate cortex, inferior frontal gyrus, and middle frontal gyrus was significantly increased in the BD group compared to the MDD group. Significant correlations were detected between the functional outcomes and MMN amplitudes at frontal and frontocentral sites. The functional outcome was significantly correlated with left frontal regions. In conclusion, MMN activity appears to be a promising candidate as an evaluation tool for functional outcomes in mood disorders.

The indirect effect of peer problems on adolescent depression through nucleus accumbens volume alteration.

Literature suggests that neurobiological factors such as brain structure play an important role in linking social stress with depression in adolescence. We aimed to examine the role of subcortical volumetric alteration in the association between peer problems as one type of social stress and adolescent depression. We hypothesized that there would be indirect effects of peer problems on adolescent depression through subcortical volumetric alteration. Seventy eight adolescents with major depressive disorder (MDD) (age mean [SD] = 14.9 ± 1.5, 56 girls) and 47 healthy controls [14.3 ± 1.4, 26 girls]) participated in this study. High-resolution structural T1 images were collected using the Siemens 3T MR scanner. Subcortical volumes were segmented using the Freesurfer 6.0 package. Peer problems were assessed using the Peer-Victimization Scale and the Bullying-Behavior Scale. There was a significant indirect effect of peer problems on adolescent depression through nucleus accumbens (NAcc) volume alteration, but not through the amygdala and hippocampal volumes. This result supported our model, which stated that peer problems have indirect effects through subcortical volumetric alteration (i.e., increased NAcc volume) on adolescent depression. Our finding suggests that altered NAcc volume may serve as a pathway, through which peer problems as one type of social stressor contribute to adolescent depression.

Increase of orexin A in the peripheral blood of adolescents with Internet gaming disorder.

BACKGROUND AND AIMS: Overindulgence in Internet gaming, which is related to rapid development of the online game industry, can cause a psychiatric disorder known as Internet gaming disorder (IGD). The number of adolescents with IGD is on the rise in countries with developed Internet technologies, such as South Korea. Therefore, it is important to develop biomarkers to detect patients at high risk of IGD. This study investigated expression levels of proteins in the blood of adolescents to provide insight into the development of biomarkers. METHODS: We collected blood samples from 73 subjects [40 healthy adolescents (Internet gaming control, IGC) and 33 adolescents with IGD] between 13:00 and 15:00. We analyzed the expression levels of orexin A, oxytocin, cortisol, melatonin, BDNF, sICAM-1, RANTES, and NCAM using multiplex assay kits. RESULTS: Orexin A was significantly (p = .016) elevated in the IGD group and the expression levels of melatonin tended to be higher (p = .055) in the IGD group. On the other hand, increased Internet gaming time in the IGD group was negatively correlated (p = .041) with expression of BDNF. On the contrary, sICAM-1 associated with inflammation exhibited the tendency of the positive correlation (p = .073) with Internet gaming time in the IGD group. DISCUSSION AND CONCLUSIONS: We identified elevation of orexin A in the peripheral blood of adolescents with IGD and a negative correlation between Internet gaming time and BDNF in adolescents with IGD. Our results provide useful information to understand the pathophysiology of IGD in adolescents.

Exploring characteristic features of attention-deficit/hyperactivity disorder: findings from multi-modal MRI and candidate genetic data.

The current study examined whether machine learning features best distinguishing attention-deficit/hyperactivity disorder (ADHD) from typically developing children (TDC) can explain clinical phenotypes using multi-modal neuroimaging and genetic data. Cortical morphology, diffusivity scalars, resting-state functional connectivity and polygenic risk score (PS) from norepinephrine, dopamine and glutamate genes were extracted from 47 ADHD and 47 matched TDC. Using random forests, classification accuracy was measured for each uni- and multi-modal model. The optimal model was used to explain symptom severity or task performance and its robustness was validated in the independent dataset including 18 ADHD and 18 TDC. The model consisting of cortical thickness and volume features achieved the best accuracy of 85.1%. Morphological changes across insula, sensory/motor, and inferior frontal cortex were also found as key predictors. Those explained 18.0% of ADHD rating scale, while dynamic regional homogeneity within default network explained 6.4% of the omission errors in continuous performance test. Ensemble of PS to optimal model showed minor effect on accuracy. Validation analysis achieved accuracy of 69.4%. Current findings suggest that structural deformities relevant to salience detection, sensory processing, and response inhibition may be robust classifiers and symptom predictors of ADHD. Altered local functional connectivity across default network predicted attentional lapse. However, further investigation is needed to clarify roles of genetic predisposition.

Prediction of sleep side effects following methylphenidate treatment in ADHD youth.

OBJECTIVE: Sleep problems is the most common side effect of methylphenidate (MPH) treatment in ADHD youth and carry potential to negatively impact long-term self-regulatory functioning. This study aimed to examine whether applying machine learning approaches to pre-treatment demographic, clinical questionnaire, environmental, neuropsychological, genetic, and neuroimaging features can predict sleep side effects following MPH administration. METHOD: The present study included 83 ADHD subjects as a training dataset. The participants were enrolled in an 8-week, open-label trial of MPH. The Barkley Stimulant Side Effects Rating Scale was used to determine the presence/absence of sleep problems at the 2nd week of treatment. Prediction of sleep side effects were performed with step-wise addition of variables measured at baseline: demographics (age, gender, IQ, height/weight) and clinical variables (ADHD Rating Scale-IV (ADHD-RS) and Disruptive Behavior Disorder rating scale) at stage 1, neuropsychological test (continuous performance test (CPT), Stroop color word test) and genetic/environmental variables (dopamine and norepinephrine receptor gene (DAT1, DRD4, ADRA2A, and SLC6A2) polymorphisms, blood lead, and urine cotinine level) at stage 2, and structural connectivities of frontostriatal circuits at stage 3. Three different machine learning algorithms ((Logistic Ridge Regression (LR), support vector machine (SVM), J48) were used for data analysis. Robustness of classifier model was validated in the independent dataset of 36 ADHD subjects. RESULTS: Classification accuracy of LR was 95.5% (area under receiver operating characteristic curve (AUC) 0.99), followed by SVM (91.0%, AUC 0.85) and J48 (90.0%, AUC 0.87) at stage 3 for predicting sleep problems. The inattention symptoms of ADHD-RS, CPT response time variability, the DAT1, ADRA2A DraI, and SLC6A2 A-3081T polymorphisms, and the structural connectivities between frontal and striatal brain regions were identified as the most differentiating subset of features. Validation analysis achieved accuracy of 86.1% (AUC 0.92) at stage 3 with J48. CONCLUSIONS: Our results provide preliminary support to the combination of multimodal classifier, in particular, neuroimaging features, as an informative method that can assist in predicting MPH side effects in ADHD.

Anatomical and Neurochemical Correlates of Parental Verbal Abuse: A Combined MRS-Diffusion MRI Study.

Despite the critical impact of parental dialog on children who remain physically and psychologically dependent, most studies have focused on brain alterations in people exposed to moderate-to-high levels of emotional maltreatment with/without psychopathology. We measured metabolites in the pregenual anterior cingulate cortex (pgACC) acquired with single-voxel proton magnetic resonance spectroscopy and anatomical connectivity assessed with probabilistic tractography in 46 healthy young adults who experienced no-to-low level parental verbal abuse (paVA) during their childhood and adolescence. The partial least square regression (PLSR) model showed that individual variance of perceived paVA was associated with chemical properties and structural connectivity of pregenual anterior cingulate cortex (pgACC; prediction R 2 = 0.23). The jackknife test was used to identify features that significantly contributed to the partial least square regression (PLSR) model; a negative association of paVA was found with myo-inositol concentration, anatomical connectivities with the right caudate and with the right transverse temporal gyrus. Of note, positive associations were also found with the left pars triangularis, left cuneus, right inferior temporal cortex, right entorhinal cortex and right amygdala. Our results showing both a negative association of frontal glial function and positive associations of anatomical connectivities in several networks associated with threat detection or visual information processing suggest both anatomical and neurochemical adaptive changes in medial frontolimbic networks to low-level paVA experiences.