Sex differences in cerebral blood flow among adolescents with bipolar disorder.

BACKGROUND: Abnormalities in cerebral blood flow (CBF) are common in bipolar disorder (BD). Despite known differences in CBF between healthy adolescent males and females, sex differences in CBF among adolescents with BD have never been studied. OBJECTIVE: To examine sex differences in CBF among adolescents with BD versus healthy controls (HC). METHODS: CBF images were acquired using arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in 123 adolescents (72 BD: 30M, 42F; 51 HC: 22M, 29F) matched for age (13-20 years). Whole brain voxel-wise analysis was performed in a general linear model with sex and diagnosis as fixed factors, sex-diagnosis interaction effect, and age as a covariate. We tested for main effects of sex, diagnosis, and their interaction. Results were thresholded at cluster forming p = 0.0125, with posthoc Bonferroni correction (p = 0.05/4 groups). RESULTS: A main effect of diagnosis (BD > HC) was observed in the superior longitudinal fasciculus (SLF), underlying the left precentral gyrus (F =10.24 (3), p < 0.0001). A main effect of sex (F > M) on CBF was detected in the precuneus/posterior cingulate cortex (PCC), left frontal and occipital poles, left thalamus, left SLF, and right inferior longitudinal fasciculus (ILF). No regions demonstrated a significant sex-by-diagnosis interaction. Exploratory pairwise testing in regions with a main effect of sex revealed greater CBF in females with BD versus HC in the precuneus/PCC (F = 7.1 (3), p < 0.01). CONCLUSION: Greater CBF in female adolescents with BD versus HC in the precuneus/PCC may reflect the role of this region in the neurobiological sex differences of adolescent-onset BD. Larger studies targeting underlying mechanisms, such as mitochondrial dysfunction or oxidative stress, are warranted.

Changes in Media Reporting Quality and Suicides Following National Media Engagement on Responsible Reporting of Suicide in Canada: Changements de la Qualité des reportages dans les médias sur les suicides suite à l'engagement des médias nationaux à la déclaration responsable du suicide au Canada.

OBJECTIVE: Responsible media reporting is an accepted strategy for preventing suicide. In 2015, suicide prevention experts launched a media engagement initiative aimed at improving suicide-related reporting in Canada; its impact on media reporting quality and suicide deaths is unknown. METHOD: This pre-post observational study examined changes in reporting characteristics in a random sample of suicide-related articles from major publications in the Greater Toronto Area (GTA) media market. Articles (n = 900) included 450 from the 6-year periods prior to and after the initiative began. We also examined changes in suicide counts in the GTA between these epochs. We used chi-square tests to analyse changes in reporting characteristics and time-series analyses to identify changes in suicide counts. Secondary outcomes focused on guidelines developed by media professionals in Canada and how they may have influenced media reporting quality as well as on the overarching narrative of media articles during the most recent years of available data. RESULTS: Across-the-board improvement was observed in suicide-related reporting with substantial reductions in many elements of putatively harmful content and substantial increases in all aspects of putatively protective content. However, overarching article narratives remained potentially harmful with 55.2% of articles telling the story of someone's death and 20.8% presenting an other negative message. Only 3.6% of articles told a story of survival. After controlling for potential confounders, a nonsignificant numeric decrease in suicide counts was identified after initiative implementation (ω = -5.41, SE = 3.43, t = 1.58, p = 0.12). CONCLUSIONS: We found evidence that a strategy to engage media in Canada changed the content of reporting, but there was only a nonsignificant trend towards fewer suicides. A more fundamental change in media narratives to focus on survival rather than death appears warranted.

Sociodemographic Differences in Physician-Based Mental Health and Virtual Care Utilization and Uptake of Virtual Care Among Children and Adolescents During the COVID-19 Pandemic in Ontario, Canada: A Population-Based Study.

OBJECTIVE: We sought to evaluate the relationship between social determinants of health and physician-based mental healthcare utilization and virtual care use among children and adolescents in Ontario, Canada, during the COVID-19 pandemic. METHODS: This population-based repeated cross-sectional study of children and adolescents (3-17 years; N = 2.5 million) used linked health and demographic administrative data in Ontario, Canada (2017-2021). Multivariable Poisson regressions with generalized estimating equations compared rates of outpatient physician-based mental healthcare use during the first year of the COVID-19 pandemic with expected rates based on pre-COVID patterns. Analyses were conducted by socioeconomic status (material deprivation quintiles of the Ontario Marginalization index), urban/rural region of residence, and immigration status. RESULTS: Overall, pediatric physician-based mental healthcare visits were 5% lower than expected (rate ratio [RR] = 0.95, 95% confidence interval [CI], 0.92 to 0.98) among those living in the most deprived areas in the first year of the pandemic, compared with the least deprived with 4% higher than expected rates (RR = 1.04, 95% CI, 1.02 to 1.06). There were no differences in overall observed and expected visit rates by region of residence. Immigrants had 14% to 26% higher visit rates compared with expected from July 2020 to February 2021, whereas refugees had similarly observed and expected rates. Virtual care use was approximately 65% among refugees, compared with 70% for all strata. CONCLUSION: During the first year of the pandemic, pediatric physician-based mental healthcare utilization was higher among immigrants and lower than expected among those with lower socioeconomic status. Refugees had the lowest use of virtual care. Further work is needed to understand whether these differences reflect issues in access to care or the need to help inform ongoing pandemic recovery planning.

Clinical correlates of suicidality and self-injurious behaviour among Canadian adolescents with bipolar disorder.

There is high risk of suicidality in bipolar disorder (BD), particularly in early onset cases. The literature regarding correlates and putative predictors of suicide attempts (SA), non-suicidal self-injury (NSSI) and suicidal ideation (SI) among youth with BD remains sparse. Participants included 197 adolescents with BD, divided into 4 groups: SA (with or without NSSI), NSSI (with or without SI), SI only, and comparison group (CG; no SA/NSSI/SI). Diagnoses, treatment, and suicidality measures were determined via semi-structured interviews, conducted between 2009 and 2017. Univariate analyses were followed by multinomial regression. Overall, 73.6% of participants had history of SA, NSSI, and/or SI. In comparison to CG, SA and NSSI were each associated with BD-II/-NOS (odds ratio [OR] = 15.99, p = 0.002; OR = 16.76, p = 0.003), female sex (OR = 6.89, p = 0.006; OR = 3.76, p = 0.02), and emotion dysregulation (OR = 1.10, p < 0.001; OR = 1.07, p = 0.004). NSSI and SI were each associated with most severe lifetime depression (OR = 1.10, p = 0.01; OR = 1.10, p = 0.01). SA and SI were associated with psychiatric hospitalization (OR = 19.45, p = 0.001; OR = 6.09, p = 0.03). SA was associated with poorer global functioning at most severe episode (OR = 0.88, p = 0.008). NSSI was associated with not living with both natural parents (OR = 0.22, p = 0.009). Study limitations include cross-sectional and retrospective design, stringent cut-offs for SA and NSSI, and recruitment from a tertiary clinical setting. Three quarters of adolescents with BD have had suicidality and/or self-injury. SA and NSSI were most similar to one another, and most different from CG, supporting the broader construct of self-harm. Future research should address the gap in knowledge regarding how sex differences and neurobiology are associated with the observed clinical differences.

Antioxidative Defense Genes and Brain Structure in Youth Bipolar Disorder.

BACKGROUND: Oxidative stress is implicated in the neuropathology of bipolar disorder (BD). We investigated the association of single-nucleotide polymorphisms (SNPs) in the antioxidative genes superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3) with structural neuroimaging phenotypes in youth BD. METHODS: SOD2 rs4880 and GPX3 rs3792797 SNP genotypes, along with structural magnetic resonance imaging, were obtained from 147 youth (BD = 75; healthy controls = 72). Images were processed using FreeSurfer, yielding surface area, volume, and thickness values for regions of interest (prefrontal cortex [PFC], caudal anterior cingulate cortex, hippocampus) and for vertex-wise whole-brain analysis. Analyses controlled for age, sex, race, and intracranial volume for volume, area, and thickness analyses. RESULT: Regions of interest analyses revealed diagnosis-by-SOD2 rs4880 interaction effects for caudal anterior cingulate cortex volume and surface area as well as PFC volume; in each case, there was lower volume/area in the BD GG genotype group vs the healthy controls GG genotype group. There was a significant BD diagnosis × GPX3 rs3793797 interaction effect for PFC surface area, where area was lower in the BD A-allele carrier group vs the other genotype groups. Vertex-wise analyses revealed significant interaction effects in frontal, temporal, and parietal regions related to smaller brain structure in the BD SOD2 rs4880 GG group and BD GPX3 rs3793797 A-allele carrier group. CONCLUSION: We found preliminary evidence that SOD2 rs4880 and GPX3 rs3792797 are differentially associated with brain structures in youth with BD in regions that are relevant to BD. Further studies incorporating additional neuroimaging phenotypes and blood levels of oxidative stress markers are warranted.

Inflammatory markers, brain-derived neurotrophic factor, and the symptomatic course of adolescent bipolar disorder: A prospective repeated-measures study.

BACKGROUND: Numerous studies have found elevated pro-inflammatory markers and reduced brain-derived neurotrophic factor (BDNF) during symptomatic episodes of bipolar disorder (BD) in adults. There is a paucity of research examining these markers in youth with BD, or longitudinally in any BD age group. METHODS: 79 adolescents, ages 13-19 years, were enrolled, including 43 symptomatic adolescents with BD and 36 age-matched healthy controls (HC). Blood samples were collected from all participants at intake, and repeatedly from BD participants at pre-specified intervals over the course of two years. Serum was assayed for levels of pro-inflammatory markers (c-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor alpha [TNF-α]), BDNF and the anti-inflammatory marker, IL-10. Week-by-week severity of mood symptoms was assessed using semi-structured interviews. RESULTS: Adolescents with BD provided an average of 4.6 blood samples, on average every 5.0 months. During the most severe symptomatic interval (i.e., highest sum of mood symptom scores) among BD adolescents, levels of CRP (p = 0.01) and pro- to anti-inflammatory ratios (CRP/IL-10; p < 0.001 and IL-6/IL-10; p = 0.046) were significantly greater, and IL-10 levels (p = 0.004) were significantly lower, vs. HC. There were no differences between BD and HC in IL-6, TNF-α or BDNF. Within BD participants, higher BDNF (p = 0.01) and IL-10 levels (p = 0.001) significantly predicted greater burden of mood symptoms over the subsequent epoch. Moreover, higher CRP levels (p = 0.009) at intake predicted greater time to recovery from the index symptomatic episode. CONCLUSIONS: In the first repeated-measures study on this topic in adolescents with BD, we found evidence that CRP, an inexpensive and ubiquitous blood test, may be useful in predicting the prospective course of BD symptoms. Future larger studies are warranted.

Neurostructural correlates of BDNF rs6265 genotype in youth bipolar disorder.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) rs6265 single-nucleotide polymorphism has been associated with bipolar disorder (BD), and with brain structure among adults with BD. We set out to investigate the association of the BDNF rs6265 Met allele with neurostructural phenotypes in youth BD. METHODS: Caucasian youth (N = 99; 13-20 years; n = 56 BD, n = 43 age and sex-matched healthy controls) underwent 3-Tesla Magnetic Resonance Imaging and genotyping for BDNF rs6265. Region of interest (ROI) analyses of the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), and hippocampus were complemented by vertex-wise analyses examining cortical thickness, surface area (SA) and volume. Multivariable models included the main effects of diagnosis and gene, and a diagnosis-by-genotype interaction term, controlling for age, sex, and intracranial volume. RESULTS: There were no significant gene main effects or diagnosis-by-gene interaction effects in ROI analyses. The vertex-wise analysis yielded a significant gene main effect whereby Met allele carriers had greater middle temporal gyrus SA (p = 0.001) and supramarginal gyrus volume (p = 0.03) than Val/Val individuals. Significant interaction effects were found on lateral occipital lobe SA (p = 0.03), whereby the Met allele was associated with increased SA in BD only. Interaction effects were also found on postcentral gyrus SA (p = 0.049) and supramarginal gyrus SA (p = 0.04), with smaller SA in BD Met carriers versus healthy control Met carriers. CONCLUSION: These findings suggest that BDNF rs6265 is differentially associated with regional SA in youth BD. Further investigation is warranted to evaluate whether BDNF protein levels mediate the observed effects, and to evaluate rs6265-related developmental changes.

Healthcare utilization and costs following non-fatal powdered and non-powdered firearm injuries for children and youth.

Little is known about the healthcare and economic burdens of non-fatal firearm injuries for children/youth beyond the initial admission. This study sought to estimate healthcare utilization and total direct healthcare costs of non-fatal powdered and non-powdered (air gun) firearm injuries 1-year post-injury. Using administrative data from 2003 to 2018 on all children/youth 0-24 years old in Ontario, Canada, a matched 1:2 cohort study was conducted to compare children/youth who experienced powdered and non-powdered firearm injuries with those who did not. Mean and median number of healthcare encounters and costs, and respective 95% confidence intervals (CIs) and interquartile ranges (IQRs), were estimated for both weapon type groups and controls and by intent. Children/youth who experienced a powdered and non-powdered firearm injury had a higher number of healthcare encounters and costs per year than those who did not. Mean 1-year costs for those with powdered and non-powdered firearm injuries were $8825 ($8007-$9643) and $2349 ($2118-$2578), respectively, versus $812 ($567-$1058) and $753 ($594-$911), respectively, for those without. Mean 1-year costs were highest for handgun injuries ($12,875 [95% CI $9941-$15,808]), and for intentional assault-related ($13,498 [$11,843-$15,153]; $3287 [$2213-$4362]), and intentional self-injuries ($14,773 [$6893-$22,652]; $6005 [$2193-$9817]) for both powdered and non-powdered firearm injuries, respectively.   Conclusion: Firearm injuries have substantial healthcare and economic burdens beyond the initial injury-related admission; this should be accounted for when examining the overall impact of firearm injuries. What is Known: • Child/youth firearm injuries have significant health and economic burdens. • However, existing work has mainly examined healthcare utilization and costs of initial admissions and/or have been limited to single-center studies and no studies have provide cost estimates by weapon type and intent. What is New: • Children/youth who suffered powdered firearm injuries had higher mean healthcare utilization and costs than those with non-powdered firearm injuries as well as comparable healthy children/youth. • Mean 1-year costs were highest for handgun injuries ($12,875), and for intentional assault-related ($13,498; $3287), and intentional self-injuries ($14,773; $6005) for powdered and non-powdered firearm injuries, respectively.

Neurostructural Correlates of Cannabis Use in Adolescent Bipolar Disorder.

BACKGROUND: Little is known regarding the association of cannabis use with brain structure in adolescents with bipolar disorder (BD). This subject is timely, given expanded availability of cannabis contemporaneously with increased social acceptance and diminished societal constraints to access. Therefore, we set out to examine this topic in a sample of adolescents with BD and healthy control (HC) adolescents. METHODS: Participants included 144 adolescents (47 BD with cannabis use [BDCB+; including 13 with cannabis use disorder], 34 BD without cannabis use [BDCB-], 63 HC without cannabis use) ages 13-20 years. FreeSurfer-processed 3T MRI with T1-weighted contrast yielded measures of cortical thickness, surface area (SA), and volume. Region of interest (amygdala, hippocampus, ventrolateral prefrontal cortex, ventromedial prefrontal cortex, and anterior cingulate cortex) analyses and exploratory vertex-wise analysis were undertaken. A general linear model tested for between-group differences, accounting for age, sex, and intracranial volume. RESULTS: Vertex-wise analysis revealed significant group effects in frontal and parietal regions. In post-hoc analyses, BDCB+ exhibited larger volume and SA in parietal regions, and smaller thickness in frontal regions, relative to HC and BDCB-. BDCB- had smaller volume, SA, and thickness in parietal and frontal regions relative to HC. There were no significant region of interest findings after correcting for multiple comparisons. CONCLUSION: This study found that cannabis use is associated with differences in regional brain structure among adolescents with BD. Future prospective studies are necessary to determine the direction of the observed association and to assess for dose effects.

Markedly increased prevalence of migraine headaches in adolescents with bipolar disorder.

OBJECTIVE: There is substantial evidence of increased prevalence of migraines, and negative psychiatric correlates of migraines, in adults with bipolar disorder (BD). Given the paucity of data on this topic in youth, we investigated the prevalence and correlates of migraine in a large sample of adolescents with BD. METHOD: The study included 165 adolescents with BD-I, -II, or -not otherwise specified (NOS), diagnosed via the KSADS-PL semi-structured interview, and 89 healthy controls (HCs). Non-migraine headache and migraine headache was evaluated using the validated ID-Migraine 3-item screener. RESULTS: Although the prevalence of non-migraine headaches did not differ between adolescents with BD (24.2%) and HCs (32.6%; P = .15), migraine was significantly more prevalent among adolescents with BD (38.2%) compared to HCs (3.4%; adjusted odds ratio 14.76, 95% confidence interval 4.39-49.57; P < .001). Within BD, migraine was associated with female sex, BD-II/-NOS subtype, less severe worst past functioning, higher past depression severity, higher self-reported affective lability, higher body mass index, and less use of lithium and second-generation antipsychotics. DISCUSSION: Migraine is much more prevalent among adolescents with BD compared to HCs; the magnitude of this association exceeds what has been reported in adult samples. Correlates of migraine in youth BD are similar to those found for adults, including the link with the depressive polarity of BD. Future prospective studies are warranted to evaluate temporal associations between migraine and mood symptoms, and to evaluate neurobiological and cardiovascular underpinnings of these associations.

Clinical and neuroimaging correlates of cardiorespiratory fitness in adolescents with bipolar disorder.

INTRODUCTION: Cardiovascular disease (CVD) is exceedingly prevalent, and occurs prematurely in individuals with bipolar disorder (BD). Cardiorespiratory fitness (CRF), arguably the most important modifiable CVD risk factor, is also associated with brain structure and function. There is a gap in knowledge regarding CRF in BD, particularly in relation to brain structure. METHODS: Adolescents with BD (n = 54) and healthy controls (HC; n = 53) completed semi-structured diagnostic interviews, self-report questionnaires, and 20 minutes of cardiorespiratory exercise at 60-80% of estimated maximum heart rate (HR) on a bicycle ergometer. Average power (watts/kg) within this HR range served as a previously validated proxy for CRF. Brain magnetic resonance imaging (MRI) structural analysis was done using FreeSurfer. Analyses controlled for age and sex. RESULTS: CRF was significantly lower in BD vs HC (0.91 ± 0.32 vs 1.01 ± 0.30, p = 0.03, F = 4.66, df=1, η2 =0.04). Within BD, greater depression symptoms were associated with lower CRF (P = .02), and greater physical activity (PA) was associated with greater CRF (P < .001). In multivariable analyses, there were significant main effects of diagnosis (HC>BD; P = .03) and sex (M > F; P < .001) on power. Significant predictors of power within BD included male sex (P = .02) and PA (P = .002) but not depression symptoms (P = .29). Significant diagnosis by CRF interaction effects was found in frontal, parietal, and occipital cortical regions. CONCLUSION: CRF was reduced among adolescents with BD, particularly women, related in part to depression symptoms and inactivity and was differentially associated with regional brain structure. Studies seeking to improve CRF as a means of reducing psychiatric symptoms of BD are warranted.

Elevated lipids are associated with reduced regional brain structure in youth with bipolar disorder.

OBJECTIVE: Abnormal blood lipid levels are common in bipolar disorder (BD) and correlate with mood symptoms and neurocognition. However, studies have not examined the lipid-brain structure association in BD or youth. METHODS: This study examined low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglycerides, and total cholesterol (TC) levels in relation to brain structure utilizing T1-weighted images, among participants ages 13-20 with BD (n = 55) and healthy controls (HC; n = 47). General linear models investigated group differences in the association of lipids with anterior cingulate cortex (ACC), hippocampus, and inferior parietal lobe structure, controlling for age, sex, body mass index, and intracranial volume. For significant associations, post hoc within-group analyses were undertaken. Exploratory vertex-wise analyses further investigated group differences in the lipid-brain structure association. RESULTS: There were significant group differences in the association of LDL-C (ß = -0.29 p = 0.001), and TC (ß = -0.21 p = 0.016), with hippocampal volume, and triglycerides with ACC volume (ß = -0.25 p = 0.01) and area (ß = -0.26 p = 0.004). Elevated lipids were associated with smaller brain structure to a significantly greater extent in BD vs HC. Post hoc analyses revealed that elevated LDL-C (ß = -0.27 p = 0.007) and reduced HDL-C (ß = 0.24 p = 0.01) were associated with smaller hippocampal volume in the BD group. Exclusion of BD second-generation antipsychotic users did not alter these results. Vertex-wise analyses further showed that elevated lipids were associated with smaller brain structure to a significantly greater extent in BD vs HC, across the cortex. CONCLUSION: Elevated lipids are associated with smaller brain structure in BD. Research evaluating lipid-brain structure associations prospectively and whether lipid optimization has salutary effects on brain structure is necessary.

Clinical correlates of socioeconomic status in adolescent bipolar disorder.

BACKGROUND: Lower socioeconomic status (SES) is associated with symptomatic severity, comorbidity, and functional impairment in adults with bipolar disorder (BD). Little is known about clinical correlates of SES in adolescents with BD. METHODS: Participants included 195 adolescents, 13-20 years old, with BD type I, II or not otherwise specified (NOS). Diagnoses were determined by standardized semi-structured interviews. Based on the Hollingshead scale, participants were divided into "low" (SES 1-3) and the "high" (SES 4-5) SES groups. Demographic and clinical correlates of SES were evaluated in univariate analyses; significant variables were evaluated in a logistic regression model. RESULTS: Compared to participants in the high SES group (n = 150), participants in the low SES group (n = 45) were significantly younger, less likely to be of Caucasian race and living with natural parents. In the logistic regression model, controlling for age and race, the low SES group had higher risk of police contact or arrest (OR = 2.41, 95% CI:1.14-5.11, p = 0.022), less treatment with stimulants(OR = 0.20 95% CI: 0.06-0.67, p = 0.009), and more post-traumatic stress disorder (PTSD) (OR = 4.08, 95% CI:1.33-12.46, p = 0.014) compared to the high SES group. In sensitivity analyses that further controlled for intact family, the finding of higher rates of police contact or arrest was no longer significant. LIMITATIONS: Cross-sectional design; higher-skewed SES sample. CONCLUSIONS: Lower SES in adolescent BD is associated with higher legal risk, increased PTSD, and under-treatment of attention-deficit/hyperactivity disorder (ADHD). Future studies are needed to evaluate the inter-relationships of these correlates, using prospective designs that can evaluate the direction of these associations. Further studies incorporating neurobiological markers are also needed to explore mechanisms underlying SES-related differences in BD.

Sex differences in brain structure among adolescents with bipolar disorder.

OBJECTIVES: Bipolar disorder (BD) is twice as prevalent amongst female as amongst male adolescents. Thus far, little is known regarding the neurostructural substrates underlying this disparity. We therefore examined sex differences in neurostructural magnetic resonane imaging (MRI) phenotypes amongst adolescents with BD. METHODS: T1-weighted structural MRI was acquired from 44 BD (25 female [F] and 19 male [M]) and 58 (28 F and 30 M) healthy control (HC) adolescents (13-21 years old). Whole-brain and region-of-interest (ROI) analyses examined structural volume and cortical thickness using FreeSurfer. ROIs included the ventrolateral prefrontal cortex (vlPFC), anterior cingulate cortex (ACC), amygdala and hippocampus. General linear models evaluated sex-by-diagnosis interactions, controlling for age and intracranial volume. RESULTS: Whole-brain analysis revealed sex-by-diagnosis interactions in the left supramarginal gyrus (SMG) (P = .02, η2  = 0.02) and right inferior parietal lobule (IPL) volumes (P = .04, η2  = 0.01). Sex differences in HCs were found in the SMG (M > F) and IPL (F > M). In BD, sex differences were reversed and of smaller magnitude in the SMG (M < F) and of greater magnitude in the IPL (F > M), driven by trends towards smaller SMG and IPL in BD vs HC male participants (P = .05 and .14). Whole-brain analyses for cortical thickness, and ROI analyses for volume and cortical thickness, were not significant. CONCLUSIONS: Normative sex differences may be disrupted in adolescent BD in the SMG and IPL, heteromodal association network hubs responsible for higher order integration of cognitive and emotional processing. Unexpectedly, these findings may inform our understanding of aberrant brain structure in adolescent BD male patients, rather than female patients. Future work should focus on replication, as well as the impact of puberty status and sex hormones on measures of brain structure and function.

Self-harm presentations to hospital trauma centre emergency departments during the first year of the COVID-19 pandemic.

The COVID-19 pandemic raised concerns regarding increased suicide-related behaviours. We compared characteristics and counts of Emergency Department (ED) presentations for self-harm, an important suicide-related outcome, during versus prior to the pandemic's first year. We included patients presenting with self-harm to the ED of two trauma centres in Toronto, Canada. Time series models compared intra-pandemic (March 2020-February 2021) presentation counts to predictions from pre-pandemic data. The self-harm proportion of ED presentations was compared between the intra-pandemic period and preceding three years. A retrospective chart review of eligible patients seen from March 2019-February 2021 compared pre- vs. intra-pandemic patient and injury characteristics. While monthly intra-pandemic self-harm counts were largely within expected ranges, the self-harm proportion of total presentations increased. Being widowed (OR=9.46; 95 %CI=1.10-81.08), employment/financial stressors (OR=1.65, 95 %CI=1.06-2.58), job loss (OR=3.83; 95 %CI=1.36-10.76), and chest-stabbing self-harm (OR=2.50; 95 %CI=1.16-5.39) were associated with intra-pandemic presentations. Intra-pandemic self-harm was also associated with Intensive Care Unit (ICU) admission (OR=2.18, 95 %CI=1.41-3.38). In summary, while the number of self-harm presentations to these trauma centres did not increase during the early pandemic, their proportion was increased. The association of intra-pandemic self-harm with variables indicating medically severe injury, economic stressors, and being widowed may inform future suicide and self-harm prevention strategies.

The association of social, economic, and health-related variables with suicidal and/or self-harm thoughts in individuals admitted to a psychiatric inpatient unit during the COVID-19 pandemic: An exploratory study.

Individuals with pre-existing psychiatric diagnoses appear to be vulnerable to worsening mental health symptoms during the coronavirus disease 2019 (COVID-19) pandemic. Furthermore, psychiatric hospitalizations during the pandemic may be complicated by increased risk of SARS-Cov-2 infection and limited social engagement due to changes in hospital policies. The objective of our exploratory study was to determine whether social, economic, and health-related variables were associated with thoughts of suicide and/or self-harm since March 2020 in individuals admitted to a psychiatric inpatient unit during the COVID-19 pandemic. Chi-square tests revealed four variables were significantly associated with thoughts of suicide and/or self-harm: 1) difficulty with cancellation of important events, 2) some form of loneliness, 3) decreased time spent in green spaces, and 4) increased time spent using devices with screens. The logistic regression model showed a significant association between suicidal and/or self-harm thoughts and cancellation of important events. Further investigation of the loneliness variable components revealed a significant association between suicidal and/or self-harm thoughts and feeling a lack of companionship, feeling isolated, and feeling alone. These results suggest that social challenges experienced during the pandemic were associated with negative mental health symptoms of individuals admitted to a psychiatric inpatient unit.

Cerebral Blood Flow and Core Mood Symptoms in Youth Bipolar Disorder: Evidence for Region-Symptom Specificity.

OBJECTIVE: Building on prior findings in adults, this study investigated regional cerebral blood flow (CBF) in relation to DSM-5 criterion A symptoms of depression and mania in youth with bipolar disorder (BD). METHOD: The study recruited 81 youths with BD and 75 healthy controls 13-20 years old. CBF was ascertained using pseudocontinuous arterial spin labeling magnetic resonance imaging. Region-of-interest analyses examined the amygdala, anterior cingulate cortex (ACC), middle frontal gyrus, and global gray matter CBF. The association of criterion A depression and mania symptoms with CBF was examined dimensionally in youth with BD in regression analyses with continuous symptom severity scores. Age and sex were included as covariates. False discovery rate (FDR) was used to correct for 28 tests (4 regions by 7 symptoms; α < .0017). CBF for BD and healthy control groups was compared to give context for findings. RESULTS: In youth with BD, depressed mood inversely correlated with ACC (ß = -0.31, puncorrected = .004, pFDR = .056) and global (ß = -0.27, puncorrected = .013, pFDR = .09) CBF. The same pattern was observed for anhedonia (ACC CBF: ß = -0.33, puncorrected = .004, pFDR = .056; global CBF: ß = -0.29, puncorrected = .008, pFDR = .07). There were no significant findings for manic symptoms or in BD vs healthy control contrasts. CONCLUSION: The present findings, while not significant after correction for multiple testing, highlight the potential value of focusing on ACC in relation to depressed mood and anhedonia, and demonstrate that CBF is sensitive to depression symptom severity in youth. Lack of findings regarding manic symptoms may relate to the exclusion of fully manic participants in this outpatient sample.

Acute Care Visits for Eating Disorders Among Children and Adolescents After the Onset of the COVID-19 Pandemic.

PURPOSE: Anecdotal reports suggest a significant increase in acute presentations of eating disorders among children and adolescents. Our objective was to compare the rates of emergency department visits and hospitalizations for pediatric eating disorders before and during the first 10 months of the COVID-19 pandemic. METHODS: Using linked health administrative databases, we conducted a population-based repeated cross-sectional study of emergency department visits and hospitalizations for eating disorders among all children and adolescents aged 3-17 years, residing in Ontario, Canada. We defined the pre-COVID period from January 1, 2017, to February 29, 2020, and the post-COVID period from March 1, 2020, to December 26, 2020. Poisson generalized estimating equations were used to model 3-year pre-COVID trends to predict expected post-COVID trends and estimate the relative change from expected rates. RESULTS: In our population of almost 2.5 million children and adolescents, acute care visits for eating disorders increased immediately after the onset of the pandemic, reaching a 4-week peak annualized rate of 34.6 (emergency department visits) and 43.2 per 100,000 population (hospitalizations) in October 2020. Overall, we observed a 66% (adjusted relative rate: 1.66, 95% confidence interval: 1.41-1.96) and 37% (adjusted relative rate: 1.37, 95% confidence interval: 1.25-1.50) increase in risk for emergency department visit and hospitalization, respectively. CONCLUSIONS: Acute care visits for pediatric eating disorders increased significantly in Ontario after the onset of COVID-19 pandemic and remained well above expected levels during the first 10 months of the pandemic. Further research is needed to understand the social and neurobiological mechanisms underlying the observed changes in health system utilization.

Utilization of Physician-Based Mental Health Care Services Among Children and Adolescents Before and During the COVID-19 Pandemic in Ontario, Canada.

IMPORTANCE: Public health measures to reduce the spread of COVID-19 have heightened distress among children and adolescents and contributed to a shift in delivery of mental health care services. OBJECTIVES: To measure and compare physician-based outpatient mental health care utilization before and during the COVID-19 pandemic and quantify the extent of uptake of virtual care delivery. DESIGN, SETTING, AND PARTICIPANTS: Population-based repeated cross-sectional study using linked health and administrative databases in Ontario, Canada. All individuals aged 3 to 17 years residing in Ontario from January 1, 2017, to February 28, 2021. EXPOSURES: Pre-COVID-19 period from January 1, 2017, to February 29, 2020, and post-COVID-19 onset from March 1, 2020, to February 28, 2021. MAIN OUTCOMES AND MEASURES: Physician-based outpatient weekly visit rates per 1000 population for mental health diagnoses overall and stratified by age group, sex, and mental health diagnostic grouping and proportion of virtual visits. Poisson generalized estimating equations were used to model 3-year pre-COVID-19 trends and forecast expected trends post-COVID-19 onset and estimate the change in visit rates before and after the onset of COVID-19. The weekly proportions of virtual visits were calculated. RESULTS: In a population of almost 2.5 million children and adolescents (48.7% female; mean [SD] age, 10.1 [4.3] years), the weekly rate of mental health outpatient visits was 6.9 per 1000 population. Following the pandemic onset, visit rates declined rapidly to below expected (adjusted relative rate [aRR], 0.81; 95% CI, 0.79-0.82) in April 2020 followed by a growth to above expected (aRR, 1.07; 95% CI, 1.04-1.09) by July 2020 and sustained at 10% to 15% above expected as of February 2021. Adolescent female individuals had the greatest increase in visit rates relative to expected by the end of the study (aRR, 1.26; 95% CI, 1.25-1.28). Virtual care accounted for 5.0 visits per 1000 population (72.5%) of mental health visits over the study period, with a peak of 5.3 visits per 1000 population (90.1%) (April 2020) and leveling off to approximately 70% in the latter months. CONCLUSIONS AND RELEVANCE: Physician-based outpatient mental health care in Ontario increased during the pandemic, accompanied by a large, rapid shift to virtual care. There was a disproportionate increase in use of mental health care services among adolescent female individuals. System-level planning to address the increasing capacity needs and to monitor quality of care with such large shifts is warranted.

Severe anhedonia among adolescents with bipolar disorder is common and associated with increased psychiatric symptom burden.

BACKGROUND: Anhedonia, a deficit in the ability to experience pleasure, is a cardinal symptom of major depressive episodes. In contrast to adolescent major depressive disorder, there is limited research examining anhedonia in the context of depression among adolescents with bipolar disorder (BD). We therefore examined clinical characteristics of anhedonia in a large sample of adolescents with BD. METHODS: Participants were 197 adolescents, aged 13-20 years old, with BD type I, II or not otherwise specified. Diagnoses were determined using a semi-structured interview. Anhedonia severity was rated from one to six on the Depression Rating Scale (DRS). Adolescents were divided into "severe" and "non-severe" anhedonia groups based on the DRS item scoring. The association of anhedonia with clinical and demographic variables was evaluated in univariate analyses followed by logistic regression analyses for variables with p ≤ 0.1. RESULTS: Threshold anhedonia was evident among 90.9% during their most severe depressive episode. Significant factors associated with severe most severe lifetime anhedonia ("lifetime anhedonia") included: female sex, lifetime history of self-injurious behavior, physical abuse, affective lability, higher lifetime depression severity, comorbid anxiety disorders, family history of ADHD, and second-generation antipsychotic use. In regression analyses, severe lifetime anhedonia was independently associated with female sex, comorbid anxiety disorders, most severe lifetime mania severity, and lifetime second-generation antipsychotic use. CONCLUSION: The vast majority of adolescents with BD experience anhedonia. More severe anhedonia is associated with indicators of greater illness severity. Future research is warranted to evaluate the neurobiological underpinnings of anhedonia among adolescents with BD.