Burn Patients and Mental Health: A Matched Cohort Study.

OBJECTIVE: To determine the association between burns and hospitalization for mental health disorders up to three decades later. SUMMARY BACKGROUND DATA: Burns are associated with pain, disability, and scarring, but the long-term impact on mental health is unclear. METHODS: We analyzed a cohort of 23,726 burn patients aged ≥10 years who were matched to 223,626 controls from Quebec, Canada, between 1989 and 2022. The main exposure was admission for a burn. We followed patients during 3,642,206 person-years of follow-up to identify future hospitalizations for psychiatric disorders, substance use disorders, and suicide attempts. We estimated adjusted hazard ratios (HR) with 95% confidence intervals (CI) for the association between burns and subsequent mental health hospitalization using Cox proportional hazards regression. RESULTS: Burn patients had 1.76 times greater risk of mental health hospitalization over time (95% CI 1.72-1.81), compared with controls. Associations were present regardless of burn site, but were greatest for burns covering ≥50% of the body (HR 3.29, 95% CI 2.61-4.15), third degree burns (HR 2.04, 95% CI 1.94-2.14), and burns requiring skin grafts (HR 2.00, 95% CI 1.90-2.10). Compared with controls, burn patients had more than two times the risk of hospitalization for eating disorders (HR 3.14, 95% CI 2.50-3.95), psychoactive substance use disorders (HR 2.27, 95% CI 2.17-2.39), and suicide attempts (HR 2.42, 95% CI 2.23-2.62). Risks were particularly elevated within 5 years of the burn, but persisted throughout follow-up. CONCLUSIONS: Burns are associated with an increased risk of hospitalization for mental health disorders up to 30 years later.

Dysfunction in endocannabinoids, palmitoylethanolamide, and degradation of tryptophan into kynurenine in individuals with depressive symptoms.

BACKGROUND: The endocannabinoid (eCB) system and the serotonin (5-HT) are both implicated in the severity of the depression. 5-HT is synthesized from the amino acid tryptophan (Trp), which is also a precursor for kynurenine (Kyn) whose production is increased at the expense of 5-HT in depressed patients. No clinical studies have investigated the crosstalk between the eCB system and the Trp/5-HT/Kyn pathways. Here, we hypothesized that the eCB system is associated with an enhanced Kyn production in relation to the severity of depressive symptoms. METHODS: Eighty-two subjects (51 patients with a diagnosis of depressive disorder (DSM-5) and 31 healthy volunteers), were assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), Beck Depression Scale, and Global Clinical Impression. Serum concentrations of eCBs (N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG)); structurally related fatty acyl compounds 2-oleoylglycerol (2-OG), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA); Trp, Kyn, Kyn/Trp ratio (an index of Trp degradation into Kyn) and 5-HT were also determined. RESULTS: Following a principal component analysis including the severity of depression, Kyn and the Kyn/Trp ratio appear to be directly associated with 2-AG, AEA, and PEA. Interestingly, these biomarkers also permitted to distinguish the population into two main clusters: one of individuals having mild/severe depressive symptoms and the other with an absence of depressive symptoms. Using parametric analysis, higher serum levels of 2-AG, Kyn, and the ratio Kyn/Trp and lower levels of Trp and 5-HT were found in individuals with mild/severe depressive symptoms than in those without depressive symptoms. While in asymptomatic people, PEA was directly associated to Trp, and OEA indirectly linked to 5-HT, in individuals with depressive symptoms, these correlations were lost, and instead, positive correlations between AEA and 2-AG, PEA and AEA, and PEA vs 2-AG and OEA concentrations were found. CONCLUSIONS: Parametric and non-parametric analyses suggest a possible association between eCBs, tryptophan/kynurenine biomarkers, and severity of depression, confirming a likely interplay among inflammation, stress, and depression. The enhanced relationships among the biomarkers of the 2-AG and AEA pathways and related lipids seen in individuals with depressive symptoms, but not in asymptomatics, suggest an altered metabolism of the eCB system in depression.

Connection between maternal suicide attempt and chronic morbidity in children.

BACKGROUND: Maternal suicide attempts are associated with adverse psychosocial outcomes in children, but the association with chronic morbidity is poorly understood. We examined the relationship between maternal suicide attempt and risk of hospitalization for potentially preventable conditions in offspring. METHODS: We analyzed a longitudinal cohort of 1 032 210 children born in Quebec, Canada between 2006 and 2019. The main exposure measure was maternal suicide attempt before or during pregnancy. Outcomes included child hospitalizations for potentially preventable conditions, including infectious diseases, dental caries, atopy, and injury up to 14 years after birth. We used adjusted Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of maternal suicide attempt with risk of hospitalization for these outcomes. RESULTS: Compared with no suicide attempt, children whose mothers attempted suicide had an increased risk of hospitalization for infectious diseases (HR 1.11, 95% CI 1.06-1.16), dental caries (HR 1.31, 95% CI 1.15-1.48), and injury (HR 1.16, 95% CI 1.03-1.31). Risk of hospitalization for any of these outcomes was greater if mothers attempted suicide by hanging (HR 1.46, 95% CI 1.22-1.75), had their first attempt between the age of 25 and 34 years (HR 1.27, 95% CI 1.13-1.42), and had 3 or more attempts (HR 1.56, 95% CI 1.27-1.91). Maternal suicide attempts were more strongly associated with child hospitalization before 10 years of age. CONCLUSIONS: Children whose mothers have a history of suicide attempt have an elevated risk of hospitalization for potentially preventable conditions.

Shifting age of child eating disorder hospitalizations during the Covid-19 pandemic.

BACKGROUND: We studied the effect of the Covid-19 pandemic on child eating disorder hospitalizations in Quebec, Canada. Quebec had one of the strictest lockdown measures targeting young people in North America. METHODS: We analyzed eating disorder hospitalizations in children aged 10-19 years before and during the pandemic. We used interrupted time series regression to assess trends in the monthly number of hospitalizations for anorexia nervosa, bulimia nervosa, and other eating disorders before the pandemic (April 2006 to February 2020), and during the first (March to August 2020) and second waves (September 2020 to March 2021). We determined the types of eating disorders requiring hospital treatment and identified the age, sex and socioeconomic subgroups that were most affected. RESULTS: Hospitalization rates for eating disorders increased during the first (6.5 per 10,000) and second waves (12.8 per 10,000) compared with the period before the pandemic (5.8 per 10,000). The increase occurred for anorexia nervosa as well as other types of eating disorders. The number of girls and boys aged 10-14 years admitted for eating disorders increased during wave 1. Wave 2 triggered an increase in eating disorder admissions among girls aged 15-19 years. Hospitalization rates increased earlier for advantaged than disadvantaged youth. CONCLUSIONS: The Covid-19 pandemic affected hospitalizations for anorexia nervosa as well as other eating disorders, beginning with girls aged 10-14 years during wave 1, followed by girls aged 15-19 years during wave 2. Boys aged 10-14 years were also affected, as well as both advantaged and disadvantaged youth.

Association of hospitalization for suicide attempts in adolescent girls with subsequent hospitalization for eating disorders.

OBJECTIVE: To determine the association between adolescent hospitalization for suicide attempts and the subsequent risk of eating disorder hospitalization. METHOD: This was a cohort study of 162,398 adolescent girls in Quebec, Canada, including 7741 with suicide attempts before 20 years of age, matched to 154,657 adolescents with no attempt between 1989 and 2019. The main exposure measure was suicide attempt hospitalization. The main outcome measure was hospitalization for an eating disorder up to 31 years later, including anorexia nervosa, bulimia nervosa, and other eating disorders. We used adjusted Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between adolescent suicide attempts and eating disorder hospitalization. RESULTS: Adolescent girls admitted for a suicide attempt had 5.55 times the risk of eating disorder hospitalization over time (95% CI 3.74-8.23), compared with matched controls. Suicide attempt was associated with anorexia nervosa (HR 3.57, 95% CI 1.78-7.17) and bulimia nervosa and other eating disorders (HR 8.55, 95% CI 5.48-13.32). Associations were pronounced in girls with repeated suicide attempts. Girls who attempted suicide through self-poisoning had an elevated risk of anorexia nervosa, whereas girls who used violent methods such as cutting or piercing had a greater risk of bulimia nervosa and other eating disorders. Suicide attempt was strongly associated with eating disorder hospitalization in the year following the attempt, but associations persisted throughout follow-up. DISCUSSION: Suicide attempt admission is associated with the long-term risk of eating disorder hospitalization in adolescent girls. PUBLIC SIGNIFICANCE: This study of adolescent girls suggests that suicide attempt admission is associated with the long-term risk of hospitalization for eating disorders. The risk is greatest in the year after the attempt, but persists over time. Adolescents who present with a suicide attempt may benefit from screening for eating disorders and long-term follow-up to help prevent the exacerbation or development of eating disorders.

Distinct Effects of Antidepressants in Association With Mood Stabilizers and/or Antipsychotics in Unipolar and Bipolar Depression.

PURPOSE/BACKGROUND: There is a dearth of studies comparing the clinical outcomes of patients with treatment-resistant unipolar (TRD) depression and depression in bipolar disorder (BD) despite similar treatment strategies. We aimed to evaluate the effects of the pharmacological combinations (antidepressants [AD], mood stabilizers [MS], and/or antipsychotics [AP]) used for TRD and BD at the McGill University Health Center. METHODS/PROCEDURES: We reviewed health records of 206 patients (76 TRD 130 BD) with TRD and BD treated with similar augmentation strategies including AD with MS (AD+MS) or AP (AD+AP) or combination (AD+AP+MS). Clinical outcomes were determined by comparing changes on the 17-time Hamilton Depression Rating Scale (HAMD-17), Quick Inventory of Depressive Symptomatology, and Clinical Global Impression-Severity of Illness at the beginning (T0) and after 3 months of an unchanged treatment (T3). FINDINGS/RESULTS: Baseline HAMD-17 scores in TRD were higher than in BD (P < 0.001), but TRD patients had a greater improvement at end point (P = 0.003). Antidepressants with AP generated greater reductions in HAMD-17 in TRD compared with BD (P = 0.02). Importantly, in BD patients, the addition of AD compared with other treatment strategies failed to improve the outcome. The limitations of this study include possibly unrepresentative subjects from tertiary care settings, incomplete matching of BD and TRD subjects, nonrandomized treatment with unmatched agents, doses, and times, unknown treatment adherence, and nonblinded retrospective outcome assessments. Nevertheless, the findings may reflect real-world interactions of clinically selected pharmacotherapies. IMPLICATIONS/CONCLUSIONS: Combination of augmentation strategies such as AD+AP and/or MS showed a better clinical improvement in patients with TRD compared with BD suggesting a limited evidence for AD potentiation in BD.

A double-blind, randomized, placebo-controlled pilot trial of atorvastatin for nephrogenic diabetes insipidus in lithium users.

OBJECTIVE: Lithium remains an important treatment for mood disorders but is associated with kidney disease. Nephrogenic diabetes insipidus (NDI) is associated with up to 3-fold risk of incident chronic kidney disease among lithium users. There are limited randomized controlled trials (RCT) for treatments of lithium-induced NDI, and existing therapies can be poorly tolerated. Therefore, novel treatments are needed for lithium-induced NDI. METHOD: We conducted a 12-week double-blind pilot RCT to assess the feasibility and efficacy of 20 mg/d atorvastatin vs placebo in the treatment of NDI in chronic lithium users. Patients, recruited between September 2017 and October 2018, were aged 18 to 85, currently on a stable dose of lithium, and determined to have NDI. RESULTS: Urinary osmolality (UOsm) at 12 weeks adjusted for baseline was not statistically different between groups (+39.6 mOsm/kg [95% CI, -35.3, 114.5] in atorvastatin compared to placebo groups). Secondary outcomes of fluid intake and aquaporin-2 excretions at 12 weeks adjusted for baseline were -0.13 L [95% CI, -0.54, 0.28] and 98.68 [95% CI, -190.34, 387.70], respectively. A moderate effect size was observed for improvements in baseline UOsm by ≥100 mOsm/kg at 12 weeks in patients who received atorvastatin compared to placebo (38.45% (10/26) vs 22.58% (7/31); Cohen's d = 0.66). CONCLUSION: Among lithium users with NDI, atorvastatin 20 mg/d did not significantly improve urinary osmolality compared to placebo over a 12-week period. Larger confirmatory trials with longer follow-up periods may help to further assess the effects of statins on NDI, especially within patients with more severe NDI.

Prenatal cannabis use disorder and future risk of road traffic injuries in Canadian children.

The extent to which child traffic injuries may be attributed to parents who use cannabis before driving is unknown. We investigated whether prenatal cannabis use disorders may predict future road traffic injuries in children. We conducted a cohort study of 792,082 children in Quebec, Canada with 6,280,663 years of follow-up between 2006 and 2019. The main exposure measure was maternal cannabis use disorder before or during pregnancy. The main outcome measure was future hospitalizations for transport-related injuries in children after birth. Using Cox proportional hazards regression models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals (CI) for the association of prenatal cannabis use disorders with transport-related injuries in children. Maternal cannabis use disorders before birth were associated with 5.64 times the risk of hospitalization for future motor vehicle crash injuries in children (95% CI 2.61-12.21). The risk increased with the child's age. Prenatal cocaine, opioid, and other drug use disorders were not associated with pediatric transport-related injuries. Maternal cannabis use disorders before birth may be an early predictor of childhood injuries from motor vehicle crashes.

Maternal Substance Abuse and the Later Risk of Fractures in Offspring: L'abus maternel de substances et le risque ultérieur de fractures chez les enfants.

OBJECTIVE: To assess the association of maternal illicit drug abuse before or during pregnancy with future fractures in offspring. METHODS: We performed a longitudinal cohort study of 792,022 infants born in hospitals of Quebec, Canada, between 2006 and 2016, with 5,457,634 person-years of follow-up. The main exposure was maternal substance abuse before or during pregnancy, including cocaine, opioid, cannabis, and other illicit drugs. The main outcome measure was hospitalization for traumatic fracture in offspring up to 12 years of age. We used adjusted Cox regression models to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of maternal drug abuse with the subsequent risk of fracture in children. RESULTS: The incidence of child fractures was higher for maternal illicit drug abuse than no drug abuse (21.2 vs. 15.4 per 10,000 person-years). Maternal drug abuse before or during pregnancy was associated with 2.35 times the risk of assault-related fractures (95% CI, 1.29 to 4.27) and 2.21 times the risk of transport accident-related fractures (95% CI, 1.34 to 3.66), compared with no drug abuse. Associations were strongest before 6 months of age for assault-related fractures (HR = 2.14; 95% CI, 0.97 to 4.72) and after 6 years for transport-related fractures (HR = 2.86; 95% CI, 1.35 to 6.05). Compared with no drug abuse, associations with assault and transport-related fractures were elevated for all drugs including cocaine, opioids, and cannabis. CONCLUSIONS: Maternal illicit drug abuse is associated with future child fractures due to assault and transport accidents.

Preeclampsia and the longitudinal risk of hospitalization for depression at 28 years.

PURPOSE: The association between pregnancy characteristics and risk of depression in women is poorly understood. We investigated the relationship between preeclampsia and risk of hospitalization for depression over three decades. METHODS: We carried out a longitudinal cohort study of 1,210,963 women who delivered an infant in any hospital in Quebec, Canada, between 1989 and 2016. The exposure was preeclampsia at the first or in subsequent pregnancies, including preeclampsia onset time (early < 34 weeks vs. late ≥ 34 weeks of gestation) and severity (mild, severe, superimposed). The outcome was hospitalization for depression any time after pregnancy. We used Cox proportional hazards regression models adjusted for maternal characteristics to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of preeclampsia with depression hospitalization. RESULTS: Women with preeclampsia had a higher incidence of hospitalization for depression compared with no preeclampsia (1.43 vs. 1.14 per 1000 person-years). Preeclampsia was associated with 1.16 times the risk of depression hospitalization after 28 years of follow-up (95% CI 1.09-1.23). Associations were present for mild (HR 1.15, 95% CI 1.07-1.24), severe (HR 1.16, 95% CI 1.04-1.29) and late onset preeclampsia (HR 1.17, 95% CI 1.10-1.25). Risks were more pronounced after the first year postpartum. CONCLUSION: Preeclampsia appears to be associated with the risk of depression hospitalization several decades after pregnancy. Clinicians who care for women with mental health disorders should be aware that a history of preeclampsia increases the risk of severe depression.

Cannabis use disorder and the future risk of cardiovascular disease in parous women: a longitudinal cohort study.

BACKGROUND: Cannabis use is increasing in women of reproductive age, but whether cannabis use disorders increase the long-term risk of cardiovascular disease in this population is not known. Cannabis may cause tachycardia, hypertension, cerebral vasoconstriction, and other adverse cardiovascular effects and has been associated with acute myocardial infarction and stroke. Data on the long-term effects of cannabis on the cardiovascular system are more limited. We assessed the relationship between cannabis use disorders early in life and the future risk of cardiovascular disease in women. METHODS: We analyzed a longitudinal cohort of 1,247,035 pregnant women in Quebec, Canada, between 1989 and 2019. The main exposure was current or past history of cannabis use disorders at cohort entry. The main outcome measure included future hospital admission for any cardiovascular disorder during 18,998,986 person years of follow-up. We used Cox proportional hazards regression models adjusted for patient characteristics to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of cannabis use disorder with the later risk of cardiovascular hospitalization. RESULTS: Women with cannabis use disorders had a higher incidence of cardiovascular hospitalization than unexposed women (58.4 vs. 33.6 per 10,000 person years). Cannabis use disorder was associated with 1.48 times the risk of cardiovascular hospitalization (95% CI 1.27-1.72), compared with no cannabis use disorder. The association was greater for cannabis with concomitant use of other substances (HR 1.84, 95% CI 1.53-2.21) than for cannabis alone (HR 1.30, 95% CI 0.99-1.72). Cannabis use disorder was strongly associated with hemorrhagic stroke, even with adjustment for other substance use (HR 2.08, CI 1.07-4.05). CONCLUSIONS: Cannabis use disorders may increase the long-term risk of cardiovascular disease in women, particularly hemorrhagic stroke. However, some of the excess risk may be due to concomitant use of other substances.

Maternal Mental Disorders before Delivery and the Risk of Dental Caries in Children.

Prevention of childhood caries is an ongoing public health challenge, but the possibility of an association with maternal mental disorders has received limited attention. We estimated the extent to which maternal mental disorders are associated with an increased risk of hospitalization due to dental caries. We conducted a longitudinal cohort study of 790,758 infants born in Quebec, Canada between 2006 and 2016, with follow-up extending to 2018. We identified women with mental disorders before or during pregnancy and computed the incidence of dental caries in their children. We estimated HR and 95% CI for the association of maternal mental disorders with the risk of dental caries, adjusted for personal characteristics. Infants of women with mental disorders before or during pregnancy had a higher incidence of dental caries compared to children of women with no mental disorder (56.1 vs. 27.2 per 10,000 person-years). Maternal stress and anxiety disorders (HR = 1.73; 95% CI 1.60-1.86), depression (HR = 1.81; 95% CI 1.60-2.03), schizophrenia and delusional disorders (HR = 1.69; 95% CI 1.29-2.22), and personality disorders (HR = 1.89; 95% CI 1.70-2.11) were associated with the risk of dental caries. The associations were present throughout childhood, including after 7 years (HR = 1.65; 95% CI 1.38-1.96). Maternal mental disorders were associated with caries of the enamel, dentin, and cementum and caries that reached the dental pulp. Maternal mental disorders before or during pregnancy, especially stress and anxiety, depression, schizophrenia, and personality disorders, are associated with the risk of childhood caries. Women with a history of mental disorders may benefit from enhanced strategies for prevention of dental caries in their children.

Maternal prepregnancy surgery and risk of neonatal abstinence syndrome in future newborns: a longitudinal cohort study.

BACKGROUND: Neonatal abstinence syndrome is increasingly prevalent, and may be related to opioid use disorders caused by postoperative prescriptions for pain control. We assessed the association of maternal prepregnancy surgery with risk of neonatal abstinence syndrome from opioid use disorders in future pregnancies. METHODS: We conducted a longitudinal retrospective cohort study of 2 182 365 deliveries in Quebec, Canada, between 1989 and 2016. The main exposure was maternal prepregnancy surgery. The main outcome measure was neonatal abstinence syndrome in offspring. We adjusted associations for maternal comorbidity and pregnancy characteristics using log-binomial regression models. RESULTS: The prevalence of neonatal abstinence syndrome in the cohort was 10.7 per 10 000 births. Compared with no surgery, prepregnancy surgery was associated with a risk ratio (RR) of neonatal abstinence syndrome of 1.63 (95% confidence interval [CI] 1.49-1.78). Risk was greater for 3 or more prepregnancy surgeries (RR 2.34, 95% CI 2.07-2.63) and age < 15 years at first surgery (1 surgery: RR 2.08, 95% CI 1.71-2.54; 2 or more surgeries: RR 2.79, 95% CI 2.32-3.37). Nearly all surgical specialties increased the risk of neonatal abstinence syndrome, but associations were strongest for cardiothoracic surgery (RR 4.45, 95% CI 2.87-6.91), neurosurgery (RR 3.00, 95% CI 1.56-5.77) and urologic surgery (RR 3.03, 95% CI 2.16-4.26). INTERPRETATION: Prepregnancy surgery is associated with the risk of neonatal abstinence syndrome in future pregnancies. Prescription opioids for postsurgical pain may result in opioid use disorders during future pregnancies, inadvertently increasing the risk of neonatal abstinence syndrome in offspring.

Residential noise exposure and the longitudinal risk of hospitalization for depression after pregnancy: Postpartum and beyond.

OBJECTIVE: Depression is a major public health concern, but the link with the built environment is unclear. We sought to determine the relationship between residential noise during pregnancy and later risk of severe depression in women. METHODS: We analyzed a population-based cohort of 140,456 women with no documented history of mental illness who were pregnant in Montreal between 2000 and 2016. We obtained residential noise estimates (LAeq. 24 h, Lden, Lnight) from land use regression models, and followed the women over time for up to 18 years after pregnancy to identify subsequent hospitalizations for depression or other mental disorders. We used Cox regression to compute hazard ratios and 95% confidence intervals (CI) adjusted for maternal characteristics. RESULTS: There were 8.0 incident hospitalizations for depression and 16.4 for other mental disorders per 10,000 person-years in women exposed to an LAeq. 24 h of 60-64.9 dB(A). The incidence was lower for noise at < 55 dB(A), with 7.4 hospitalizations for depression and 13.8 for other mental disorders per 10,000 person-years. Compared with 50 dB(A), an LAeq. 24 h of 60 dB(A) was associated with 1.16 times (95% CI 0.84-1.62) the risk of depression hospitalization, and 1.34 times (95% CI 1.04-1.74) the risk of other mental disorders. Associations were more prominent for Lnight, with 1.32 times (95% CI 1.08-1.63) the risk of depression hospitalization at 60 dB(A) and 1.68 times the risk (95% CI 1.05-2.67) at 70 dB(A). CONCLUSIONS: Pregnant women exposed to noise, especially nighttime noise, have a greater risk of hospitalization for depression and other mental disorders later in life. Residential noise may be a risk factor for depression after pregnancy.

Psychopathological and sociodemographic features in treatment-resistant unipolar depression versus bipolar depression: a comparative study.

BACKGROUND: Some authors have hypothesized that Treatment-Resistant Unipolar Depression (TRD-UP) should be considered within the bipolar spectrum disorders and that hidden bipolarity may be a risk factor for TRD-UP. However, there are neither studies comparing clinical and sociodemographic data of patients with TRD-UP versus Bipolar (BP) disorders nor are there any examining differences versus Bipolar type I (BP-I) and Bipolar type II (BP-II). METHODS: Charts analysis was conducted on 194 patients followed at the Mood Disorders Clinic of the McGill University Health Center. Sociodemographic, clinical features and depression scales were collected from patients meeting DSM-IV criteria for TRD-UP (n = 100) and BP (n = 94). Binary logistic regression analysis was conducted to examine clinical predictors independently associated with the two disorders. RESULTS: Compared to BP, TRD-UP patients exhibited greater severity of depression, prevalence of anxiety and panic disorders, melancholic features, Cluster-C personality disorders, later onset of depression and fewer hospitalizations. Binary logistic regression indicated that higher comorbidity with anxiety disorders, higher depression scale scores and lower global assessment of functioning (GAF) scores, and lower number of hospitalizations and psychotherapies differentiated TRD-UP from BP patients. We also found that the rate of unemployment and the number of hospitalizations for depression was higher in BP-I than in BP-II, while the rate of suicide attempts was lower in BP-I than in BP-II depressed patients. CONCLUSIONS: These results suggest that TRD-UP constitutes a distinct psychopathological condition and not necessarily a prodromal state of BP depression.

Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial.

BACKGROUND: Lithium is the gold-standard treatment for bipolar disorder, is highly effective in treating major depressive disorder, and has anti-suicidal properties. However, clinicians are increasingly avoiding lithium largely due to fears of renal toxicity. Nephrogenic Diabetes Insipidus (NDI) occurs in 15-20% of lithium users and predicts a 2-3 times increased risk of chronic kidney disease (CKD). We recently found that use of statins is associated with lower NDI risk in a cross-sectional study. In this current paper, we describe the methodology of a randomized controlled trial (RCT) to treat lithium-induced NDI using atorvastatin. METHODS: We will conduct a 12-week, double-blind placebo-controlled RCT of atorvastatin for lithium-induced NDI at McGill University, Montreal, Canada. We will recruit 60 current lithium users, aged 18-85, who have indicators of NDI, which we defined as urine osmolality (UOsm) < 600 mOsm/kg after 10-h fluid restriction. We will randomize patients to atorvastatin (20 mg/day) or placebo for 12 weeks. We will examine whether this improves measures of NDI: UOsm and aquaporin (AQP2) excretion at 12-week follow-up, adjusted for baseline. RESULTS: Not applicable. CONCLUSION: The aim of this clinical trial is to provide preliminary data about the efficacy of atorvastatin in treating NDI. If successful, lithium could theoretically be used more safely in patients with a reduced subsequent risk of CKD, hypernatremia, and acute kidney injury (AKI). If future definitive trials confirm this, this could potentially allow more patients to benefit from lithium, while minimizing renal risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT02967653 . Registered in February 2017.

Risk of central nervous system defects in offspring of women with and without mental illness.

We sought to determine the relationship between maternal mental illness and the risk of having an infant with a central nervous system defect. We analyzed a cohort of 654,882 women aged less than 20 years between 1989 and 2013 who later delivered a live born infant in any hospital in Quebec, Canada. The primary exposure was mental illness during pregnancy or hospitalization for mental illness before pregnancy. The outcomes were neural and non-neural tube defects of the central nervous system in any offspring. We computed risk ratios (RR) and 95% confidence intervals (CI) for the association between mental disorders and risk of central nervous system defects in log-binomial regression models adjusted for age at delivery, total parity, comorbidity, socioeconomic deprivation, place of residence, and time period. Maternal mental illness was associated with an increased risk of nervous system defects in offspring (RR 1.76, 95% CI 1.64-1.89). Hospitalization for any mental disorder was more strongly associated with non-neural tube (RR 1.84, 95% CI 1.71-1.99) than neural tube defects (RR 1.31, 95% CI 1.08-1.59). Women at greater risk of nervous system defects in offspring tended to be diagnosed with multiple mental disorders, have more than one hospitalization for mental disease, or be 17 or older at first hospitalization. A history of mental illness is associated with central nervous system defects in offspring. Women hospitalized for mental illness may merit counseling at first symptoms to prevent central nervous system defects at pregnancy.

Short-Term Natural Course of Depressive Symptoms and Family-Related Stress in Adolescents After Separation From Father.

OBJECTIVE: To determine if separation from a father is associated with short-term changes in mental health or substance use in adolescents. METHODS: Every 3 months, during a 5-year period, we followed 1160 Grade 7 students participating in the Nicotine Dependence in Teens Study who were living with both parents. Participants who reported not living with their father for 6 or more consecutive months during follow-up were categorized as separated from father. Pooled regressions within the framework of generalized estimating equations were used to model the associations between separation from father and indicators of mental health (depressive symptoms, and worry and [or] stress about family relationships or the family situation) and substance use (alcohol use and cigarette smoking) 4 to 6 and 7 to 9 months postseparation, controlling for age, sex, and baseline level of the outcome variable. RESULTS: Compared with adolescents living with both parents, adolescent offspring separated from their fathers were more likely to report depressive symptoms (ß = 0.17, 95% CI 0.01 to 0.33) 4 to 6 months postseparation, as well as worry and (or) stress about their parents separating or divorcing (OR 2.39, 95% CI 1.29 to 4.43), a new family (OR 4.25, 95% CI 2.33 to 7.76), and the family financial situation (OR 2.35, 95% CI 1.53 to 3.60). Separation from father was also marginally significantly related to worry and (or) stress about their relationship with their father (OR 1.53; 95% CI 0.98 to 2.39). At 7 to 9 months postseparation, separation from father continued to be associated with worry and (or) stress about their parents separating or divorcing, a new family, and the family financial situation. Separation from father was no longer associated with worry and (or) stress about their relationship with their father, but it was associated with worry and (or) stress about their relationship with their mother. Separation from father was not related to use of alcohol or cigarettes. CONCLUSION: Adolescent offspring experienced family-related stress and transient depression symptoms in the 4- to 9-month period following separation from their fathers.

Association Between Childhood Sleep-Disordered Breathing and Disruptive Behavior Disorders in Childhood and Adolescence.

We examined the association between sleep-disordered breathing (SDB) and disruptive behavior disorders in 605 children participating in a population-based cohort study. Nineteen percent of children snored (sometimes or often) and 10% had obstructive sleep apnea (OSA) symptoms. Thirteen percent had an ADHD diagnosis or symptoms and 5-9% had behavioral problems or a conduct disorder. Snoring or OSA symptoms were associated with a twofold difference in the odds of ADHD diagnosis or symptoms. OSA symptoms were associated with a threefold to fourfold difference in the odds of behavioral problems or conduct disorder. Clinicians should consider inquiring about SDB in children with disruptive behavior disorders and should also consider disruptive behavior disorders as potential sequelae of SDB.

Symptoms of depression are longitudinally associated with sedentary behaviors among young men but not among young women.

OBJECTIVE: A habitual sedentary lifestyle is associated with adverse health outcomes; however, the predictors of sedentary behaviors have not been sufficiently explored to inform the development and delivery of effective interventions to reduce sedentary behaviors. This study examined whether reports of symptoms of depression could predict weekly time spent in sedentary behaviors (i.e., television watching, computer use) 4years later. METHOD: Self-reported symptoms of depression were assessed at age 20years (2007-08), and television watching time and computer use were assessed at age 24years (2011-12) in 761 adults (45% men) participating in the Nicotine Dependence in Teens study. Data were analyzed using linear regression analysis, with separate models for men and women. RESULTS: After controlling for past sedentary behavior, symptoms of depression at age 20years predicted more computer use 4years later in men (R(2)=.21, ß=.13, p<.05), but not in women. Symptoms of depression did not predict television watching. CONCLUSIONS: Results highlight the need to distinguish between types of sedentary behaviors as their predictors may differ. Further, they provide support for the hypothesis that psychological factors, in this case symptoms of depression, may relate to select sedentary behaviors in young men.