Differentiation between suicide attempt and suicidal ideation in patients with major depressive disorder using cortical functional network.

Studies exploring the neurophysiology of suicide are scarce and the neuropathology of related disorders is poorly understood. This study investigated source-level cortical functional networks using resting-state electroencephalography (EEG) in drug-naïve depressed patients with suicide attempt (SA) and suicidal ideation (SI). EEG was recorded in 55 patients with SA and in 54 patients with SI. Particularly, all patients with SA were evaluated using EEG immediately after their SA (within 7 days). Graph-theory-based source-level weighted functional networks were assessed using strength, clustering coefficient (CC), and path length (PL) in seven frequency bands. Finally, we applied machine learning to differentiate between the two groups using source-level network features. At the global level, patients with SA showed lower strength and CC and higher PL in the high alpha band than those with SI. At the nodal level, compared with patients with SI, patients with SA showed lower high alpha band nodal CCs in most brain regions. The best classification performances for SA and SI showed an accuracy of 73.39%, a sensitivity of 76.36%, and a specificity of 70.37% based on high alpha band network features. Our findings suggest that abnormal high alpha band functional network may reflect the pathophysiological characteristics of suicide and serve as a clinical biomarker for suicide.

Preventive effect of aripiprazole once-monthly on relapse into mood episodes in bipolar disorder: A multicenter, one-year, retrospective, mirror image study.

BACKGROUND: We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment. METHODS: Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit. RESULTS: The overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM. LIMITATIONS: The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times. CONCLUSION: The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals.

Prevalence and Comorbidities of Adult Attention-deficit/hyperactivity Disorder in a Community Sample from Korea.

Objective: : Attention-deficit/hyperactivity disorder (ADHD) is prevalent in adults, and psychiatric comorbidities are common in adults with ADHD. We aimed to examine the prevalence of adult ADHD with several common psychiatric conditions in a community sample in Korea and the association between adult ADHD and risk of psychiatric comorbidities. Methods: : This study used a cross-sectional survey design. We provided supplementary and optional self-report questionnaires, including the Korean version of the World Health Organization Adult ADHD Self-Report Scale (ASRS) short screening scale, Patient Health Questionnaire-9 for screening for depression, Alcohol Use Disorders Identification Test alcohol consumption questions, and the Korean version of the Mood Disorders Questionnaire, to Korean adults who visited one of six centers of a large private healthcare company for the National General Health Examination. Results: : A total of 17,799 subjects included in this study, and 430 (2.4%) were positive on the ASRS screen. ADHD was significantly associated with the 19-30-year-old age group (odds ratio [OR] = 3.938), lower income (OR = 1.298), depression (OR = 11.563), and bipolar disorder (OR = 3.162). Conclusion: : Adult ADHD was highly associated with depression and bipolar disorder, suggesting that clinicians should carefully evaluate and treat such psychiatric disorders in adults with ADHD symptoms.

Psychological aftereffects experienced by sexually abused children: Psychopathological characteristics revealed by the K-CBCL.

Children who have been sexually abused may experience various short- and long-term psychological sequelae and behavioral problems. This study assessed the mental health of sexually abused children using the Korean-Child Behavior Checklist (K-CBCL) and examined differences from a control group. The participants were 97 children who had been sexually abused and who visited a local Sunflower Center, and 178 control participants. Data were collected via the K-CBCL and analyzed using SPSS version 25.0. T-tests, cross-tabulation, and logistic regression analyses were performed. Scores from the K-CBCL Problem Behavior Syndrome scale were compared between sexually abused children and the control participants. Significant differences were observed between the 2 groups in all the subscales. Compared to the control group, children who were sexually abused showed statistically significant differences in the total problem behavior, internalization, anxiety/depression, withdrawal/depression (withdrawn), somatic symptoms, externalization, rule-breaking behavior (delinquency), aggressive behavior, social immaturity, thought problems, attention problems, and other subscale scores. Sexual violence hurts the overall mental health of children who are abused, including their emotional, behavioral, and social factors. Our findings suggest that multidisciplinary assessment and treatment are required for children who have experienced sexual abuse.

The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD): Changes in Preferred Treatment Strategies and Medications over 20 Years and Five Editions.

BACKGROUND: The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) is an expert consensus guideline for depressive disorder created in 2002, and since then, four revisions (2006, 2012, 2017, 2021) have been published. In this study, changes in the content of the KMAP-DD survey and recommendations for each period were examined. METHODS: The development process of the KMAP-DD was composed of two stages. First, opinions from experts with abundant clinical experience were gathered through surveys. Next, a final guideline was prepared through discussion within the working committee regarding the suitability of the results with reference to recent clinical studies or other guidelines. RESULTS: In mild depressive symptoms, antidepressant (AD) monotherapy was preferred, but when severe depression or when psychotic features were present, a combination of AD and atypical antipsychotics (AD + AAP) was preferred. AD monotherapy was preferred in most clinical subtypes. AD monotherapy was preferred for mild depressive symptoms, and AD + AAP was preferred for severe depression and depression with psychotic features in children, adolescents, and the elderly. CONCLUSIONS: This study identified the changes in the KMAP-DD treatment strategies and drug preferences in each period over the past 20 years. This work is expected to aid clinicians in establishing effective treatment strategies.

Korean Medication Algorithm Project for Bipolar Disorder 2022: Comparisons with Other Treatment Guidelines.

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) with other recently published guidelines for treating bipolar disorder. We reviewed a total of six recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2022 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy in a same degree for mania. However, the KMAP-BP 2022 recommended MS + AAP combination therapy for psychotic mania, mixed mania and psychotic depression as treatment of choice. Aripiprazole, quetiapine and olanzapine were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Some guideline suggested olanzapine is a second-line options during maintenance treatment, related to concern about long-term tolerability. Most guidelines advocated newer AAPs (asenapine, cariprazine, long-acting injectable risperidone, and aripiprazole once monthly) as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. KMAP-BP 2022 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2022, predominantly in the treatment of psychotic mania, mixed mania and psychotic depression.

Korean Medication Algorithm Project for Bipolar Disorder 2022, Fifth Revision: An Executive Summary.

Objective: We revised the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP), first published in 2002 and revised in 2006, 2010, 2014, and 2018, to reflect recent progress in the treatment of bipolar disorder. Methods: The questionnaires consisted of 56 items for adult patients and 7 items for child/adolescent patients, and were used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of bipolar disorder. The review committee included 87 Korean psychiatrists and 40 child and adolescent psychiatry experts. Results: For treatment of manic episodes, a combination of a mood stabilizer (MS) and atypical antipsychotics (AAP), or monotherapy with MS or AAP were recommended as first-line treatments. Combinations of MS and AAP, or AAP and lamotrigine (LMT) were recommended as first-line treatments for depressive episodes regardless of the severity. Monotherapy with MS, AAP, or LMT were also first-line treatments for mild to moderate depressive episodes. For mixed features, a combination of MS and AAP, or monotherapy with AAP or MS were recommended as first-line treatments, and a combination of AAP and LMT, or MS and LMT were the first-line treatments for depressive mixed state. Conclusion: The recommendations of the KMAP-BP 2022 have changed from the previous version, to reflect the evolution of the social culture and healthcare system in Korea and recent evidence regarding pharmacotherapy of bipolar disorder. The KMAP-BP 2022 provides clinicians with a wealth of information regarding appropriate strategies to treat patients with bipolar disorder.

Corrigendum: Electrophysiological changes between patients with suicidal ideation and suicide attempts: An event-related potential study.

[This corrects the article DOI: 10.3389/fpsyt.2022.900724.].

Electrophysiological Changes Between Patients With Suicidal Ideation and Suicide Attempts: An Event-Related Potential Study.

Introduction: Inhibitory control is regarded as an important ability related to the transition from suicidal ideation to suicide attempts. In event-related potential, patients with dysfunction of inhibitory control demonstrate a reduction in the no-go amplitude. This study aimed to determine the association between the no-go event-related potential component and suicidal behaviors among suicide attempters and ideators who never attempted suicide. Methods: Overall, 150 patients who visited the emergency room by suicide attempts or patients who visited the psychiatric department with suicidal ideation were recruited and instructed to perform a go/no-go task during electroencephalography recording. The Beck Depression Inventory, Beck Anxiety Inventory, Barratt Impulsivity Scale, Difficulties in Emotional Regulation Scale, and Acquired Capability for Suicide Scale were used. Individuals were divided into two groups: those with suicide attempt group) and with suicidal ideation (SI group) without SA. The psychological characteristics and event-related potentials of the two groups were compared. Correlation analyses were conducted to test the association between the clinical characteristics and event-related potentials. Results: The SA group had significantly decreased no-go P3 amplitudes at all electrodes compared to the SI group. In the correlation analysis between the clinical measurements and event-related potentials in all the participants, no-go P3 amplitudes in whole electrode sites were negatively correlated with the scores of the acquired capability for the suicide scale. Conclusions: This study revealed that suicide attempters have dysfunction in controlling inhibition compared to suicide ideators reflected in the no-go P3. Our findings suggested that no-go P3 can be a biomarker associated suicide attempts in suicide ideators.

Impact of Interpersonal Relationships and Acquired Capability for Suicide on Suicide Attempts: A Cross-Sectional Study.

OBJECTIVE: This study examined the path model predicting suicide attempts (SA) by interpersonal need for suicide desire, acquired capability for suicide, the emotion dysregulation, and depression symptoms in people admitted to hospitals for medical treatment. METHODS: A total of 344 participants (200 depressed patients with attempted suicide, 144 depressed patients with suicidal ideation) were enrolled for this study. Depression, anxiety, emotion regulation, interpersonal needs, and acquired capability for suicide were evaluated. A model with pathways from emotion regulation difficulties and interpersonal needs to SA was proposed. Participants were divided into two groups according to the presence of SA or suicidal ideation. RESULTS: Acquired capability for suicide mediated the path from depression to SA. In the path model, difficulties in emotion regulation and interpersonal needs predicted depression significantly. Although depression itself was not significantly related to acquired capability for suicide, depression was significantly related to acquired capability for suicide in suicide attempter group. CONCLUSION: Interventions with two factors affecting SA will clarify the suicide risk and contribute to finding risk factors.

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.

The Korean Medication Algorithm Project for Depressive Disorder 2021: Comparisons with Other Treatment Guidelines.

The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) first was published in 2002, and has been revised four times, in 2006, 2012, 2017, and 2021. In this review, we compared recommendations from the recently revised KMAP-DD 2021 to four global clinical practice guidelines (CPGs) for depression published after 2010. The recommendations from the KMAP-DD 2021 were similar to those from other CPGs, although there were some differences. The KMAP-DD 2021 reflected social culture and the healthcare system in Korea and recent evidence about pharmacotherapy for depression, as did other recently published evidence-based guidelines. Despite some intrinsic limitations as an expert consensus-based guideline, the KMAP-DD 2021 can be helpful for Korean psychiatrists making decisions in clinical settings by complementing previously published evidence-based guidelines, especially for some clinical situations lacking evidence from rigorously designed clinical trials.

Prevalence and Comorbidities of Attention Deficit Hyperactivity Disorder Among Adults and Children/Adolescents in Korea.

OBJECTIVE: This study investigated the prevalence and comorbidities of attention deficit hyperactivity disorder (ADHD) among adults and children/adolescents in Korea. METHODS: This study used data from the Korea Health Insurance Review and Assessment Service collected from 2008 to 2018. Study participants comprised patients with at least one diagnosis of ADHD (International Statistical Classification of Diseases and Related Health Provisions, 10th revision code F90.0). Prevalence rates and psychiatric comorbidities were also analyzed. RESULTS: We identified 878,996 patients diagnosed with ADHD between 2008 and 2018. The overall prevalence rate of diagnosed ADHD increased steeply from 127.1/100,000 in 2008 to 192.9/100,000 in 2018; it increased 1.47 times in children/adolescents (≤ 18 years) and 10.1 times in adults (＞ 18 years) during this period. Among adult and children/ adolescent ADHD patients, 61.84% (95% confidence interval [95% CI] 61.74-61.93) and 78.72% (95% CI 78.53- 78.91) had at least one psychiatric comorbidity, respectively. CONCLUSION: Our results showed that the prevalence rate of diagnosed ADHD has increased in Korea; however, it is lower than the global average. Further studies are required to identify and treat vulnerable populations appropriately.

Comparison between Atomoxetine and OROS Methylphenidate as an Adjunctive to SSRIs in Attention-deficit/Hyperactivity Disorder Adults with Comorbid Partially Responsive Major Depressive Disorder: A Head-to-head, 12-week, Randomized, Rater-blinded Clinical Trial.

OBJECTIVE: This study aimed to compare the efficacy and safety of atomoxetine (ATX) and OROS methylphenidate (MPH) as adjunctive to selective serotonin reuptake inhibitors (SSRIs) in adults with attention-deficit hyperactivity disorder (ADHD) with comorbid partially responsive major depressive disorder (MDD). METHODS: Sixty Korean adults with ADHD and comorbid partially responsive MDD were recruited in a 12-week, randomized, rater-blinded, active-controlled trial and were evenly randomized to ATX or OROS MPH treatment. RESULTS: Depressive symptoms measured using the Hamilton Depression Rating Scale and Clinically Useful Depression Outcome Scale, and ADHD symptoms measured using the Adult ADHD Self-Report Scale, as well as the Clinical Global Impression-Severity, Clinical Global Impression-Improvement, and the Sheehan Disability Scale scores were significantly improved in both groups during the 12 weeks of treatment. The changes in all outcome measures during the 12-week treatment were not significantly different between the two groups (all p > 0.05). No serious adverse events were reported and there were no significant differences in systolic and diastolic blood pressure, pulse rate, weight, or body mass index between the ATX and MPH groups. CONCLUSION: Our findings suggest that ATX and MPH can be used as adjunctive treatments in adults with ADHD and comorbid partially responsive MDD. The efficacy and tolerability of ATX and MPH in adults with ADHD did not differ significantly. Further studies should be conducted to draw a definitive conclusion.

Electrophysiological Changes Related to Childhood Trauma in Patients with Major Depressive Disorder: An Event-related Potential Study.

OBJECTIVE: Childhood trauma is the most important environmental factor for several psychiatric disorders. Depressed patients with childhood trauma appear to have severe symptoms that frequently recur. This study investigated whether depressed patients with childhood trauma showed attenuated Nogo event-related potentials (ERPs) and source activity during response-inhibition tasks. METHODS: Forty-four patients patients with major depressive disorder (MDD) were instructed to perform a Go/Nogo task during electroencephalography. Sensors and source activities of N2 and P3 of the Nogo ERPs were analyzed. The participants' clinical symptoms were assessed using the Childhood Trauma Questionnaire (CTQ), Beck Depression Inventory, State-Trait Anxiety Inventory, Barratt Impulsivity Scale, and Affective Lability Scale. The participants were divided into two groups (low and high), based on their total CTQ scores. RESULTS: MDD subjects with high CTQ scores showed significantly decreased Nogo P3 amplitudes at the frontal, frontocentral, central, and parietal electrodes than those with low CTQ scores (all p < 0.01). In Nogo P3, the source activities of the right cuneus, right posterior cingulate cortex, right precuneus, left supramarginal gyrus, and left lingual gyrus were significantly lower in the high CTQ group than in the low one (all p < 0.01). There were significant negative correlations between the total CTQ scores and the Nogo P3 amplitudes in the frontocentral (p = 0.03) and parietal regions (p = 0.02), which showed lower source activity in the Nogo P3 condition. CONCLUSION: Depressed patients with severe childhood trauma showed different Nogo-ERP characteristics, which might reflect inhibitory failure and dysfunction in related brain regions.

Korean Medication Algorithm for Depressive Disorder 2021, Fourth Revision: An Executive Summary.

OBJECTIVE: In the 19 years since the Korean College of Neuropsychopharmacology and the Korean Society for Affective Disorders developed the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) in 2002, four revisions have been conducted. METHODS: To increase survey efficiency in this revision, to cover the general clinical practice, and to compare the results with previous KMAP-DD series, the overall structure of the questionnaire was maintained. The six sections of the questionnaire were as follows: 1) pharmacological treatment strategies for major depressive disorder (MDD) with/without psychotic features; 2) pharmacological treatment strategies for persistent depressive disorder and other depressive disorder subtypes; 3) consensus for treatment-resistant depression; 4) the choice of an antidepressant in the context of safety, adverse effects, and comorbid physical illnesses; 5) treatment strategies for special populations (children/adolescents, elderly, and women); and 6) non-pharmacological biological therapies. Recommended first-, second-, and third-line strategies were derived statistically. RESULTS: There has been little change in the four years since KMAP-DD 2017 due to the lack of newly introduced drug or treatment strategies. However, shortened waiting time between the initial and subsequent treatments, increased preference for atypical antipsychotics (AAPs), especially aripiprazole, and combination strategies with AAPs yield an active and somewhat aggressive treatment trend in Korea. CONCLUSION: We expect KMAP-DD to provide clinicians with useful information about the specific strategies and medications appropriate for treating patients with MDD by bridging the gap between clinical real practice and the evidence-based world.

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.

What Event-Related Potential Tells Us about Brain Function: Child-Adolescent Psychiatric Perspectives.

Electroencephalography (EEG) measures neural activation due to various cognitive processes. EEG and event-related potentials (ERPs) are widely used in studies investigating psychopathology and neural substrates of psychiatric diseases in children and adolescents. The present study aimed to review recent ERP studies in child and adolescent psychiatry. ERPs are non-invasive methods for studying synaptic functions in the brain. ERP might be a candidate biomarker in child-adolescent psychiatry, considering its ability to reflect cognitive and behavioral functions in humans. For the EEG study of psychiatric diseases in children and adolescents, several ERP components have been used, such as mismatch negativity, P300, error-related negativity (ERN), and reward positivity (RewP). Regarding executive functions and inhibition in patients with attention-deficit/hyperactivity disorder (ADHD), P300 latency, and ERN were significantly different in patients with ADHD compared to those in the healthy population. ERN showed meaningful changes in patients with anxiety disorders, such as generalized anxiety disorder, separation anxiety disorder, and obsessive-compulsive disorder. Patients with depression showed significantly attenuated RewP compared to the healthy population, which was related to the symptoms of anhedonia.

The Relationship between Plasma Erythropoietin Levels and Symptoms of Attention Deficit Hyperactivity Disorder.

OBJECTIVE: There are animal models associating dopamine dysfunction with behavioral impairments that model attention deficit hyperactivity disorder (ADHD). Erythropoietin (EPO) has trophic effects on dopaminergic neurons. The aim of this study was to examine the EPO plasma levels and determine whether there was any correlation between plasma EPO levels and clinical characteristics of ADHD. METHODS: Plasma EPO levels were measured in 78 drug-naïve children with ADHD and in 81 healthy children. The severity of ADHD symptoms was determined by scores on the Korean ADHD Rating Scale (K-ARS) in ADHD children and healthy controls. RESULTS: The difference between median plasma EPO levels in ADHD children and in healthy controls was not statistically significant. Adjusting for age and sex, a linear regression analysis showed that inattention score was significantly higher in the second highest tertile of plasma EPO compared to those in the lowest tertile. Hyperactivity-impulsivity score was significantly higher in the highest tertile of plasma EPO compared to those in the lowest tertile. Moreover, total K-ARS scores were significantly higher in the second highest tertile of plasma EPO compared to those in the lowest tertile. CONCLUSION: These findings suggest that plasma EPO levels were related to some ADHD symptoms, which could be used in the monitoring of the disorder.