Predictive values of pre-treatment brain age models to rTMS effects in neurocognitive disorder with depression: Secondary analysis of a randomised sham-controlled clinical trial.

INTRODUCTION: One major challenge in developing personalised repetitive transcranial magnetic stimulation (rTMS) is that the treatment responses exhibited high inter-individual variations. Brain morphometry might contribute to these variations. This study sought to determine whether individual's brain morphometry could predict the rTMS responders and remitters. METHODS: This was a secondary analysis of data from a randomised clinical trial that included fifty-five patients over the age of 60 with both comorbid depression and neurocognitive disorder. Based on magnetic resonance imaging scans, estimated brain age was calculated with morphometric features using a support vector machine. Brain-predicted age difference (brain-PAD) was computed as the difference between brain age and chronological age. RESULTS: The rTMS responders and remitters had younger brain age. Every additional year of brain-PAD decreased the odds of relieving depressive symptoms by ∼25.7% in responders (Odd ratio [OR] = 0.743, p = .045) and by ∼39.5% in remitters (OR = 0.605, p = .022) in active rTMS group. Using brain-PAD score as a feature, responder-nonresponder classification accuracies of 85% (3rd week) and 84% (12th week), respectively were achieved. CONCLUSION: In elderly patients, younger brain age appears to be associated with better treatment responses to active rTMS. Pre-treatment brain age models informed by morphometry might be used as an indicator to stratify suitable patients for rTMS treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR-IOR-16008191.

Concerto of movement: how expertise shapes the synergistic control of upper limb muscles in complex motor tasks with varying tempo and dynamics.

Objective. This research aims to reveal how the synergistic control of upper limb muscles adapts to varying requirements in complex motor tasks and how expertise shapes the motor modules.Approach. We study the muscle synergies of a complex, highly skilled and flexible task-piano playing-and characterize expertise-related muscle-synergy control that permits the experts to effortlessly execute the same task at different tempo and force levels. Surface EMGs (28 muscles) were recorded from adult novice (N= 10) and expert (N= 10) pianists as they played scales and arpeggios at different tempo-force combinations. Muscle synergies were factorized from EMGs.Main results. We found that experts were able to cover both tempo and dynamic ranges using similar synergy selections and achieved better performance, while novices altered synergy selections more to adapt to the changing tempi and keystroke intensities compared with experts. Both groups relied on fine-tuning the muscle weights within specific synergies to accomplish the different task styles, while the experts could tune the muscles in a greater number of synergies, especially when changing the tempo, and switch tempo over a wider range.Significance. Our study sheds light on the control mechanism underpinning expertise-related motor flexibility in highly skilled motor tasks that require decade-long training. Our results have implications on musical and sports training, as well as motor prosthetic design.

Rectified Latent Variable Model-Based EMG Factorization of Inhibitory Muscle Synergy Components Related to Aging, Expertise and Force-Tempo Variations.

Muscle synergy has been widely acknowledged as a possible strategy of neuromotor control, but current research has ignored the potential inhibitory components in muscle synergies. Our study aims to identify and characterize the inhibitory components within motor modules derived from electromyography (EMG), investigate the impact of aging and motor expertise on these components, and better understand the nervous system's adaptions to varying task demands. We utilized a rectified latent variable model (RLVM) to factorize motor modules with inhibitory components from EMG signals recorded from ten expert pianists when they played scales and pieces at different tempo-force combinations. We found that older participants showed a higher proportion of inhibitory components compared with the younger group. Senior experts had a higher proportion of inhibitory components on the left hand, and most inhibitory components became less negative with increased tempo or decreased force. Our results demonstrated that the inhibitory components in muscle synergies could be shaped by aging and expertise, and also took part in motor control for adapting to different conditions in complex tasks.

Moment-to-moment affective dynamics in schizophrenia and bipolar disorder.

BACKGROUND: Affective disturbances in schizophrenia and bipolar disorder may represent a transdiagnostic etiological process as well as a target of intervention. Hypotheses on similarities and differences in various parameters of affective dynamics (intensity, successive/acute changes, variability, and reactivity to stress) between the two disorders were tested. METHODS: Experience sampling method was used to assess dynamics of positive and negative affect, 10 times a day over 6 consecutive days. Patients with schizophrenia (n = 46) and patients with bipolar disorder (n = 46) were compared against age-matched healthy controls (n = 46). RESULTS: Compared to controls, the schizophrenia group had significantly more intense momentary negative affect, a lower likelihood of acute changes in positive affect, and reduced within-person variability of positive affect. The bipolar disorder group was not significantly different from either the schizophrenia group or the healthy control group on any affect indexes. Within the schizophrenia group, level of depression was associated with weaker reactivity to stress for negative affect. Within the bipolar disorder group, level of depression was associated with lower positive affect. CONCLUSIONS: Patients with schizophrenia endured a more stable and negative affective state than healthy individuals, and were less likely to be uplifted in response to happenings in daily life. There is little evidence that these affective constructs characterize the psychopathology of bipolar disorder; such investigation may have been limited by the heterogeneity within group. Our findings supported the clinical importance of assessing multiple facets of affective dynamics beyond the mean levels of intensity.

Childhood adversities and mental disorders in first-year college students: results from the World Mental Health International College Student Initiative.

BACKGROUND: This study investigates associations of several dimensions of childhood adversities (CAs) with lifetime mental disorders, 12-month disorder persistence, and impairment among incoming college students. METHODS: Data come from the World Mental Health International College Student Initiative (WMH-ICS). Web-based surveys conducted in nine countries (n = 20 427) assessed lifetime and 12-month mental disorders, 12-month role impairment, and seven types of CAs occurring before the age of 18: parental psychopathology, emotional, physical, and sexual abuse, neglect, bullying victimization, and dating violence. Poisson regressions estimated associations using three dimensions of CA exposure: type, number, and frequency. RESULTS: Overall, 75.8% of students reported exposure to at least one CA. In multivariate regression models, lifetime onset and 12-month mood, anxiety, and substance use disorders were all associated with either the type, number, or frequency of CAs. In contrast, none of these associations was significant when predicting disorder persistence. Of the three CA dimensions examined, only frequency was associated with severe role impairment among students with 12-month disorders. Population-attributable risk simulations suggest that 18.7-57.5% of 12-month disorders and 16.3% of severe role impairment among those with disorders were associated with these CAs. CONCLUSION: CAs are associated with an elevated risk of onset and impairment among 12-month cases of diverse mental disorders but are not involved in disorder persistence. Future research on the associations of CAs with psychopathology should include fine-grained assessments of CA exposure and attempt to trace out modifiable intervention targets linked to mechanisms of associations with lifetime psychopathology and burden of 12-month mental disorders.

Dimensional structure of one-year post-COVID-19 neuropsychiatric and somatic sequelae and association with role impairment.

This study examined the latent structure of the broad range of complex neuropsychiatric morbidities occurring 1 year after COVID-19 infection. As part of the CU-COVID19 study, 248 (response rate=39.3%) of 631 adults hospitalized for COVID-19 infection in Hong Kong completed an online survey between March-2021 and January-2022. Disorder prevalence was compared against a random non-infected household sample (n=1834). 248 surveys were received on average 321 days post-infection (Mean age: 48.9, 54% female, moderate/severe/critical infection: 58.2%). 32.4% were screened to have at least one mental disorder, 78.7% of whom had concurrent fatigue/subjective cognitive impairment (SCI). Only PTSD (19.1%) was significantly more common than control (14%, p=0.047). Latent profile analysis classified individuals into P1 (12·4%)-no current neuropsychiatric morbidities, P2 (23.1%)-SCI/fatigue, P3 (45.2%)-anxiety/PTSD, P4 (19.3%)-depression. SCI and fatigue pervaded in all profiles (P2-4) with neuropsychiatric morbidities one-year post-infection. PTSD, anxiety and depressive symptoms were most important in differentiating P2-4. Past mental health and P4 independently predicted functional impairment. Neuropsychiatric morbidity was associated with past mental health, reduced resilience, financial problems, but not COVID-19 severity. Their confluence with depressive and anxiety symptoms predicted impairment and are associated with psychological and environmental factors.

Non-suicidal self-injury among first-year college students and its association with mental disorders: results from the World Mental Health International College Student (WMH-ICS) initiative.

BACKGROUND: Although non-suicidal self-injury (NSSI) is an issue of major concern to colleges worldwide, we lack detailed information about the epidemiology of NSSI among college students. The objectives of this study were to present the first cross-national data on the prevalence of NSSI and NSSI disorder among first-year college students and its association with mental disorders. METHODS: Data come from a survey of the entering class in 24 colleges across nine countries participating in the World Mental Health International College Student (WMH-ICS) initiative assessed in web-based self-report surveys (20 842 first-year students). Using retrospective age-of-onset reports, we investigated time-ordered associations between NSSI and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-IV) mood (major depressive and bipolar disorder), anxiety (generalized anxiety and panic disorder), and substance use disorders (alcohol and drug use disorder). RESULTS: NSSI lifetime and 12-month prevalence were 17.7% and 8.4%. A positive screen of 12-month DSM-5 NSSI disorder was 2.3%. Of those with lifetime NSSI, 59.6% met the criteria for at least one mental disorder. Temporally primary lifetime mental disorders predicted subsequent onset of NSSI [median odds ratio (OR) 2.4], but these primary lifetime disorders did not consistently predict 12-month NSSI among respondents with lifetime NSSI. Conversely, even after controlling for pre-existing mental disorders, NSSI consistently predicted later onset of mental disorders (median OR 1.8) as well as 12-month persistence of mental disorders among students with a generalized anxiety disorder (OR 1.6) and bipolar disorder (OR 4.6). CONCLUSIONS: NSSI is common among first-year college students and is a behavioral marker of various common mental disorders.

Clinical and radiomic features for predicting the treatment response of repetitive transcranial magnetic stimulation in major neurocognitive disorder: Results from a randomized controlled trial.

Image-guided repetitive transcranial magnetic stimulation (rTMS) has shown clinical effectiveness in senior adults with co-occurring depression and cognitive impairment, yet the imaging markers for predicting the treatment response are less investigated. In this clinical trial, we examined the efficacy and sustainability of 10 Hz rTMS for the treatment of depression and cognitive impairment in major neurocognitive disorder (NCD) patients and tested the predictive values of imaging-informed radiomic features in response to rTMS treatment. Fifty-five major NCD patients with depression were randomly assigned to receive a 3-week rTMS treatment of either active 10 Hz rTMS (n = 27) or sham rTMS (n = 28). Left dorsolateral prefrontal cortex (DLPFC) was the predefined treatment target. Based on individual structural magnetic resonance imaging scans, surface-based analysis was conducted to quantitatively measure the baseline radiomic features of left DLPFC. Severity of depression, global cognition and the serum brain-derived neurotrophic factor (BDNF) level were evaluated at baseline, 3-, 6- and 12-week follow-ups. Logistic regression analysis revealed that advanced age, higher baseline cognition and randomized group were associated with the remission of depression. Increased cortical thickness and gyrification in left DLPFC were the significant predictors of clinical remission and cognitive enhancement. A 3-week course of 10 Hz rTMS is an effective adjuvant treatment for rapid ameliorating depressive symptoms and enhancing cognitive function. Pre-treatment radiomic features of the stimulation target can predict the response to rTMS treatment in major NCD. Cortical thickness and folding of treatment target may serve as imaging markers to detect the responders. ChiCTR-IOR-16008191, registered on March 30, 2016.

Cost-effectiveness of internet-supported cognitive behavioral therapy for university students with anxiety symptoms: A Markov-model analysis.

BACKGROUND AND AIM: High prevalence of anxiety symptoms has been reported globally in the university students. Cognitive behavioral therapy (CBT) is the recognized treatment for anxiety and is traditionally conducted face-to-face (f-CBT). The efficacy of internet-based CBT (i-CBT) for anxiety has been extensively studied, yet evidence on its cost-effectiveness is scarce. We aimed to evaluate the cost-effectiveness of guided low-intensity i-CBT for university students with mild anxiety symptoms from the societal perspective of Hong Kong. METHODS: A 5-year Markov model was designed to compare outcomes of guided i-CBT and f-CBT in a hypothetical cohort of university students with mild anxiety symptoms. Model inputs of cost and healthcare resources associated with anxiety were retrospectively collected from a cohort of university students with anxiety symptoms. Clinical and utility model inputs were retrieved from published literature. Model outcome measures were anxiety-related total cost (including direct medical and indirect costs) and quality-adjusted life-year (QALY). Sensitivity analyses were performed to examine the robustness of base-case results. RESULTS: In base-case analysis, i-CBT gained higher QALYs (2.9956 versus 2.9917) at lower total cost (US$6,101 versus US$6,246) than f-CBT. In one-way sensitivity analysis, the QALY gained by i-CBT was sensitive to the relative patient acceptance and adherence to CBT. In probabilistic sensitivity analysis, i-CBT was cost-effective in 90.9% of the time at the willingness-to-pay threshold of 138,210 per QALY (3× GDP per capita in Hong Kong). The probability of i-CBT to be cost-effective was 99.9% at a willingness-to-pay threshold of zero. CONCLUSIONS: Guided i-CBT appears to be cost-saving and effective for management of university students with mild symptoms of anxiety from the societal perspective of Hong Kong. The cost-effectiveness of i-CBT is highly subject to the individual acceptance and adherence of CBT delivered by the internet platform.

Protocol for a prospective open-label clinical trial to investigate the utility of concurrent TBS/fNIRS for antidepressant treatment optimisation.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) with theta burst stimulation (i.e. TBS) of the dorsolateral prefrontal cortex (DLPFC) is an innovative treatment for major depressive disorder (MDD). However, fewer than 50% of patients show sufficient response to this treatment; markers for response prediction are urgently needed. Research shows considerable individual variability in the brain responses to rTMS. However, whether differences in individual DLPFC modulation by rTMS can be used as a predictive marker for treatment response remains to be investigated. Here, we present a research programme that will exploit the combination of functional near-infrared spectroscopy (fNIRS) with brain stimulation. Concurrent TBS/fNIRS will allow us to systematically investigate TBS-induced modulation of blood oxygenation as a proxy for induced brain activity changes. The findings from this study will (1) elucidate the immediate effects of excitatory and inhibitory TBS on prefrontal activity in TBS treatment-naïve patients with MDD and (2) validate the potential utility of TBS-induced brain modulation at baseline for the prediction of antidepressant response to 4 weeks of daily TBS treatment. METHODS AND ANALYSIS: Open-label, parallel-group experiment consisting of two parts. In part 1, 70 patients and 37 healthy controls will be subjected to concurrent TBS/fNIRS. Intermittent TBS (iTBS) and continuous TBS (cTBS) will be applied on the left and right DLPFC, respectively. fNIRS data will be acquired before, during and several minutes after stimulation. In part 2, patients who participated in part 1 will receive a 4 week iTBS treatment of the left DLPFC, performed daily for 5 days per week. Psychometric evaluation will be performed periodically and at 1 month treatment follow-up. Statistical analysis will include a conventional, as well as a machine learning approach. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Institutional Review Board. Findings will be disseminated through scientific journals, conferences and university courses. TRIAL REGISTRATION NUMBER: NCT04526002.

Childhood adversities and suicidal thoughts and behaviors among first-year college students: results from the WMH-ICS initiative.

PURPOSE: To investigate the associations of childhood adversities (CAs) with lifetime onset and transitions across suicidal thoughts and behaviors (STB) among incoming college students. METHODS: Web-based self-report surveys administered to 20,842 incoming college students from nine countries (response rate 45.6%) assessed lifetime suicidal ideation, plans and attempts along with seven CAs: parental psychopathology, three types of abuse (emotional, physical, sexual), neglect, bully victimization, and dating violence. Logistic regression estimated individual- and population-level associations using CA operationalizations for type, number, severity, and frequency. RESULTS: Associations of CAs with lifetime ideation and the transition from ideation to plan were best explained by the exact number of CA types (OR range 1.32-52.30 for exactly two to seven CAs). Associations of CAs with a transition to attempts were best explained by the frequency of specific CA types (scaled 0-4). Attempts among ideators with a plan were significantly associated with all seven CAs (OR range 1.16-1.59) and associations remained significant in adjusted analyses with the frequency of sexual abuse (OR = 1.42), dating violence (OR = 1.29), physical abuse (OR = 1.17) and bully victimization (OR = 1.17). Attempts among ideators without plan were significantly associated with frequency of emotional abuse (OR = 1.29) and bully victimization (OR = 1.36), in both unadjusted and adjusted analyses. Population attributable risk simulations found 63% of ideation and 30-47% of STB transitions associated with CAs. CONCLUSION: Early-life adversities represent a potentially important driver in explaining lifetime STB among incoming college students. Comprehensive intervention strategies that prevent or reduce the negative effects of CAs may reduce subsequent onset of STB.

ADHD Comorbidity Structure and Impairment: Results of the WHO World Mental Health Surveys International College Student Project (WMH-ICS).

OBJECTIVE: To examine the prevalence of ADHD and the association of comorbid disorders, and multivariate disorder classes with role impairment in college students. METHOD: About 15,991 freshmen (24 colleges, 9 countries, WMH-ICS) (response rate = 45.6%) completed online WMH-CIDI-SC surveys for 6-month ADHD and six 12-month DSM-IV disorders. We examined multivariate disorder classes using latent class analysis (LCA) and simulated a population attributable risk proportions (PARPs) of ADHD-related impairment. RESULTS: About 15.9% had ADHD, of which 58.4% had comorbidities. LCA classified ADHD respondents to pure (42.9%), internalizing (36.0%), bipolar comorbidities (11.3%), and externalizing disorder classes (9.8%). ADHD, comorbidities, and multivariate disorder classes independently predicted severe impairment. PARPs: eliminating ADHD hypothetically reduced severe impairment by 19.2%, 10.1% adjusted for comorbidities, 9.5% for multivariate disorder classes. CONCLUSIONS: ADHD and comorbid disorders are common and impairing in college students. Personalized transdiagnostic interventions guided by multivariate disorder classes should be explored.

Antidepressant efficacy of low-frequency repetitive transcranial magnetic stimulation in antidepressant-nonresponding bipolar depression: a single-blind randomized sham-controlled trial.

BACKGROUND: To examine the antidepressant efficacy and response predictors of R-DLPFC-LF rTMS for antidepressant-nonresponding BD. METHODS: We conducted a single-blind randomized sham-controlled trial for 54 (28 sham, 26 active) patients with antidepressant-nonresponding BD (baseline MADRS ≥ 20). Patients received 15 daily sessions of active or sham neuronavigated rTMS (Figure-of-8 coil, five 1 Hz 60 s 110% RMT trains). Outcome measures included depressive response (≥ 50% MADRS reduction, CGI ≤ 2) and remission (MADRS < 7, CGI = 1) rates, treatment emergent hypo/mania (YMRS), depressive and anxiety symptoms (HAM-A). RESULTS: 48 patients (25 sham, 23 active) completed treatment, with 3 drop-outs each in active and sham groups. Active rTMS did not produce superior response or remission rates at endpoint or 6 or 12 weeks (ps > 0.05). There was no significant group * time interaction (ps > 0.05) in a multivariate ANOVA with MADRS, HAMA and YMRS as dependent variables. Exploratory analysis found MADRS improvement to be moderated by baseline anxiety (p = 0.02) and melancholia (p = 0.03) at week 3, and depressive onset at weeks 6 (p = 0.03) and 12 (p = 0.04). In subjects with below-mean anxiety (HAMA < 20.7, n = 24), MADRS improvement from active rTMS was superior to sham at week 3 (ITT, t = 2.49, p = 0.04, Cohen's d = 1.05). No seizures were observed. Groups did not differ in treatment-emergent hypomania (p = 0.1). LIMITATIONS: Larger sample size might be needed to power subgroup analyses. Moderation analyses were exploratory. Single-blind design. Unblinding before follow-up assessments due to ethical reasons. CONCLUSIONS: 1-Hz 110% RMT (5 × 60 s trains) R-DLPFC-LF rTMS was not effective for antidepressant non-responding BD but may be further investigated at increased dosage and/or in BD patients with low anxiety. Trial registration CCRB Clinical Trials Registry, CUHK, CUHK_CCT00440. Registered 04 December 2014, https://www2.ccrb.cuhk.edu.hk/registry/public/279.

Personalized prediction of repetitive transcranial magnetic stimulation clinical response in medication-refractory depression data.

This article describes a dataset that was generated as part of the article: Personalized prediction of transcranial magnetic stimulation clinical response in patients with treatment-refractory depression using neuroimaging biomarkers and machine learning (DOI: 10.1016/j.jad.2021.04.081). We collected resting-state functional Magnetic Resonance Imaging data from 70 medication-refractory depressed subjects before undergoing four weeks of repetitive transcranial magnetic stimulation targeting the left dorsolateral prefrontal cortex. The data presented here include information about the seed-based analyses such as regions of interest, individual/group functional connectivity maps and contrast maps. The contrast maps are controlled for age, gender, duration of the current depressive episode, duration since the first depressive episode, and symptom scores. Demographics, clinical characteristics, and categorical treatment response variables are reported as well. Further, the individual connectivity values of the identified neuroimaging biomarkers of long-term clinical response were used as features in the support vector machine models are presented in combination with the trained classifiers of the support vector machine models. Post hoc analyses that were not published in the original analyses are presented as well. Finally, the R or MATLAB code scripts for all figures published in the co-submitted paper are included.

The Differential Effects of Social Media on Depressive Symptoms and Suicidal Ideation Among the Younger and Older Adult Population in Hong Kong During the COVID-19 Pandemic: Population-Based Cross-sectional Survey Study.

BACKGROUND: Social media has become a ubiquitous part of daily life during the COVID-19 pandemic isolation. However, the role of social media use in depression and suicidal ideation of the general public remains unclear. Related empirical studies were limited and reported inconsistent findings. Little is known about the potential underlying mechanisms that may illustrate the relationship between social media use and depression and suicidal ideation during the COVID-19 pandemic. OBJECTIVE: This study tested the mediation effects of social loneliness and posttraumatic stress disorder (PTSD) symptoms on the relationship between social media use and depressive symptoms and suicidal ideation, as well as the moderation effect of age on the mediation models. METHODS: We administered a population-based random telephone survey in May and June 2020, when infection control measures were being vigorously implemented in Hong Kong. A total of 1070 adults (658 social media users and 412 nonusers) completed the survey. Structural equation modeling (SEM) and multigroup SEM were conducted to test the mediation and moderation effects. RESULTS: The weighted prevalence of probable depression was 11.6%; 1.6% had suicidal ideation in the past 2 weeks. Both moderated mediation models of depressive symptoms (χ262=335.3; P<.05; comparative fit index [CFI]=0.94; nonnormed fit index [NNFI]=0.92; root mean square error of approximation [RMSEA]=0.06) and suicidal ideation (χ234=50.8; P<.05; CFI=0.99; NNFI=0.99; RMSEA=0.02) showed acceptable model fit. There was a significantly negative direct effect of social media use on depressive symptoms among older people (ß=-.07; P=.04) but not among younger people (ß=.04; P=.55). The indirect effect via PTSD symptoms was significantly positive among both younger people (ß=.09; P=.02) and older people (ß=.10; P=.01). The indirect effect via social loneliness was significant among older people (ß=-.01; P=.04) but not among younger people (ß=.01; P=.31). The direct effect of social media use on suicidal ideation was not statistically significant in either age group (P>.05). The indirect effects via PTSD symptoms were statistically significant among younger people (ß=.02; P=.04) and older people (ß=.03; P=.01). Social loneliness was not a significant mediator between social media use and suicidal ideation among either age group (P>.05). CONCLUSIONS: Social media may be a "double-edged sword" for psychosocial well-being during the COVID-19 pandemic, and its roles vary across age groups. The mediators identified in this study can be addressed by psychological interventions to prevent severe mental health problems during and after the COVID-19 pandemic.

White matter integrity in young medication-naïve bipolar II depressed adults.

It is unknown if young medication-naïve bipolar II (BPII) depressed patients have increased white matter (WM) disruptions. 27 each of young (average 23 years) and treatment-naïve BPII depressed, unipolar depressed (UD) patients and age-sex-education matched healthy controls (HC) underwent 3 T MRIs with diffusion tensor imaging. Diagnostic ratings included Structured Clinical Interview for DSM Disorders (SCID), Montgomery-Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Hamilton Anxiety Rating Scale (HAM-A). Patients were clinically depressed (MADRS-BPII: 26.15 [SD9.25], UD: 25.56 [5.24], p = 0.86). Compared to UD, BPII had increased family bipolarity (BPII 13.6% vs UD 2.5%, p = 0.01, φc = 0.28), hypomanic symptoms (YMRS-BPII: 4.22 [4.24], UD: 1.33 [2], p = 0.02, d = 0.87), lifetime number of depressive episodes (BPII: 2.37 [1.23], UD: 1.44 [0.75], p = 0.02, d = 0.91), lifetime and current-year number of episodes (lifetime BPII: 50.85 [95.47], UD: 1.7 [1.03]; current-year BPII: 9.93 [16.29], UD: 1.11 [0.32], ps = 0.04, ds = 0.73-0.77) and longer illness duration (BPII: 4.96 years [3.96], UD: 2.99 [3.33], p = 0.15, d = 0.54). BPII showed no increased WM disruptions vs UD or HC in any of the 15 a priori WM tracts. UD had lower right superior longitudinal fasciculus (SLF) (temporal) axial diffusivity (AD) (1.14 vs 1.17 (BPII), 1.16 (HC); F = 6.93, 95% CI of [Formula: see text]: 0.00073, 5.22, ηp2 = 0.15). Principal component analysis followed by exploratory linear discriminant analysis showed that increased R-SLF (temporal) AD, YMRS and family bipolarity distinguished BPII from UD (81.5% sensitivity, 85.2% specificity) independent of episode number and frequency. Young, medication-naïve adults with BPII depression did not show the WM disruptions distinguishing more chronically ill BP patients from UD. These WM disruptions may therefore be partly attributable to illness chronicity. Longitudinal studies should examine the trajectory of WM changes in BPII and UD and predictive validity of these baseline clinical and imaging parameters.

Efficacy of Phase 1 of Life Goals Programme on symptom reduction and mood stability for bipolar disorder.

BACKGROUND: Life Goals Programme (LGP) was developed as a psychological intervention for bipolar disorder, with its structured 6-session psychoeducation phase (Phase 1) targeting understanding of the disorder, medication adherence, early warning signs, and coping with symptoms and triggers. The present study tested the efficacy of Phase 1 of the LGP on symptom recovery and moment-by-moment mood stability, as well as medication adherence and quality of life. METHODS: Adults with bipolar disorder were randomly allocated to the LGP condition (six weekly group sessions) or the waitlist condition (six weeks of standard care, followed by the same LGP intervention). Participants were assessed before and after treatment, and at 6-month follow up. Waitlist participants were additionally assessed at baseline. Assessment included a clinical interview (SCID, MADRS, YMRS, and HAM-A), self-reported questionnaires, and 6-day experience sampling assessment on a mobile device. RESULTS: 64 out-patients with bipolar disorder (44 Bipolar I and 20 Bipolar II subtypes) participated in this study. LGP was well received and attended. Following LGP, there were significant improvements in knowledge about illness and level of anxiety, which were of large effect sizes and sustained at 6-month follow-up. Experience sampling assessment revealed small but significant improvements in moment-by-moment mood stability. Improvement in medication adherence was significant at 6 months and was of a moderate-to-large effect size. Changes in anxiety and mood stability were significantly greater following LGP than standard care. LIMITATIONS: Our results warrant further testing against active control. CONCLUSIONS: There was a robust improvement in emotional regulation following the 6-week LGP.

Unaltered Brain GABA Concentrations and Resting fMRI Activity in Functional Dyspepsia With and Without Comorbid Depression.

BACKGROUND: GABA-deficit characterizes depression (MDD), which is highly comorbid with Functional Dyspepsia (FD). We examined brain GABA concentrations and resting activities in post-prandial distress subtype FD (FD-PDS) patients with and without MDD. METHODS: 24 female age/education-matched FD-PDS with comorbid MDD (FD-PDS-MDD), non-depressed FD-PDS, and healthy controls each were compared on GABA concentrations, resting fMRI (fALFF) in bilateral pregenual anterior cingulate (pgACC), left dorsolateral prefrontal cortex (DLPFC), insula, and somatosensory cortex (SSC). RESULTS: FD-PDS-MDD patients had mild though elevated depressive symptoms. FD-PDS patients had generally mild dyspeptic symptoms. No significant between-group differences in GABA or fALFF were found. No significant correlations were found between GABA and depressive/dyspeptic symptoms after Bonferroni correction. In patients, GABA correlated positively with left insula fALFF (r = 0.38, Bonferroni-corrected p = .03). CONCLUSION: We did not find altered GABA concentrations or brain resting activity in FD-PDS or its MDD comorbidity. The neurochemical link between MDD and FD remains elusive.

Sources of Stress and Their Associations With Mental Disorders Among College Students: Results of the World Health Organization World Mental Health Surveys International College Student Initiative.

The college years are stressful for many students. Identifying the sources of stress and their relative importance in leading to clinically significant emotional problems may assist in the development of targeted stress management interventions. The current report examines the distribution and associations of perceived stress across major life areas with 12-month prevalence of common mental disorders in a cross-national sample of first-year college students. The 20,842 respondents were from 24 universities in 9 countries that participated in the World Health Organization World Mental Health International College Student Initiative. Logistic regression analysis examined associations of current perceived stress in six life areas (financial situation, health, love life, relationships with family, relationships at work/school, problems experienced by loved ones) with six types of 12-month mental disorders (major depressive disorder, bipolar disorder, generalized anxiety disorder, panic disorder, alcohol use disorder, drug use disorder). Population attributable risk proportions (PARPs) were calculated to estimate the upper-bound potential effects of interventions focused on perceived stress in reducing prevalence of mental disorders. The majority of students (93.7%) reported at least some stress in at least one of the six areas. A significant dose-response association was found between extent of stress in each life area and increased odds of at least one of the six disorders. The multivariable models that included all stress measures were significant for all disorders (F = 20.6-70.6, p < 0.001). Interpretation of PARPs as representing causal effects of stresses on disorders suggests that up to 46.9-80.0% of 12-month disorder prevalence might be eliminated if stress prevention interventions were developed to block the associations of stress with these disorders.

Diagnostic Outcomes of Childhood ADHD in Chinese Adults.

Objective: We examined adulthood diagnostic, functioning, and social outcomes of childhood ADHD in a Hong Kong Chinese clinical sample. Method: We identified from the central registry 499 Chinese adults clinically diagnosed with ADHD aged 6 to 12 in 2002-2005 in four Hong Kong child psychiatric centers. Assessments included ADHD Clinical Diagnostic Scale (ACDS), Structured Clinical Interview for DSM Disorders (SCID), and World Health Organization Disability Assessment Schedule (WHO-DAS). Results: Eligible participants = 499. One hundred forty-five completed assessments, two deceased, six incarcerated, 100 had invalid contact, 83 declined, 34 emigrated, and 129 unable to attend. Mean follow-up duration = 14.9 years. Nonrespondents were slightly younger (19.78 vs. 20.53, p < .001). In all, 83.1% of all participants currently met Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD criteria (36.8% inattentive subtype (IA), 43% combined, 3.3% hyperactive/impulsive subtype (H/I) ). One third of persistent ADHD participants currently received care. ADHD persistence was associated with significantly increased psychiatric comorbidity (49.5% vs. 22.7%, p = .02) and poor academic and social outcomes. ADHD persistence and comorbidity independently predicted impairment. Conclusion: Adulthood-persistence of clinically presented childhood ADHD is common and impairing in Hong Kong Chinese.