Attention deficit hyperactivity and oppositional defiant disorder symptoms in adolescence and risk of substance use disorders - a general population-based birth cohort study

BACKGROUND: Externalizing symptoms are associated with risk of future substance use disorder (SUD). Few longitudinal studies exist using general population-based samples which assess the spectrum of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms. AIMS/OBJECTIVES: We aimed to study the associations between adolescent ADHD symptoms and subsequent SUD and additionally examine whether the risk of SUD is influenced by comorbid oppositional defiant disorder (ODD) symptoms. METHODS: The Northern Finland Birth Cohort 1986 was linked to nationwide health care register data for incident SUD diagnoses until age 33 years (n = 6278, 49.5% male). ADHD/ODD-case status at age 16 years was defined using parent-rated ADHD indicated by Strengths and Weaknesses of ADHD symptoms and Normal Behaviors (SWAN) questionnaire with 95% percentile cut-off. To assess the impact of ODD comorbidity on SUD risk, participants were categorized into four groups based on their ADHD/ODD case status. Cox-regression analysis with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to study associations between adolescent ADHD/ODD case statuses and subsequent SUD. RESULTS: In all, 552 participants (8.8%) presented with ADHD case status at the age of 16 years, and 154/6278 (2.5%) were diagnosed with SUD during the follow-up. ADHD case status was associated with SUD during the follow-up (HR = 3.84, 95% CI 2.69-5.50). After adjustments for sex, family structure, and parental psychiatric disorder and early substance use the association with ADHD case status and SUD remained statistically significant (HR = 2.60, 95% CI 1.70-3.98). The risk of SUD remained elevated in individuals with ADHD case status irrespective of ODD symptoms. CONCLUSIONS: ADHD in adolescence was associated with incident SUD in those with and without symptoms of ODD. The association of ADHD and SUD persisted even after adjustment for a wide range of potential confounds. This emphasizes the need to identify preventative strategies for adolescents with ADHD so as to improve health outcomes

Tranexamic acid for acute gastrointestinal bleeding (the HALT-IT trial): statistical analysis plan for an international, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Acute gastrointestinal (GI) bleeding is an important cause of mortality worldwide. Bleeding can occur from the upper or lower GI tract, with upper GI bleeding accounting for most cases. The main causes include peptic ulcer/erosive mucosal disease, oesophageal varices and malignancy. The case fatality rate is around 10% for upper GI bleeding and 3% for lower GI bleeding. Rebleeding affects 5-40% of patients and is associated with a four-fold increased risk of death. Tranexamic acid (TXA) decreases bleeding and the need for blood transfusion in surgery and reduces death due to bleeding in patients with trauma and postpartum haemorrhage. It reduces bleeding by inhibiting the breakdown of fibrin clots by plasmin. Due to the methodological weaknesses and small size of the existing trials, the effectiveness and safety of TXA in GI bleeding is uncertain. The Haemorrhage ALleviation with Tranexamic acid - Intestinal system (HALT-IT) trial aims to provide reliable evidence about the effects of TXA in acute upper and lower GI bleeding. METHODS: The HALT-IT trial is an international, randomised, double-blind, placebo-controlled trial of tranexamic acid in 12,000 adults (increased from 8000) with acute upper or lower GI bleeding. Eligible patients are randomly allocated to receive TXA (1-g loading dose followed by 3-g maintenance dose over 24 h) or matching placebo. The main analysis will compare those randomised to TXA with those randomised to placebo on an intention-to-treat basis, presenting the results as effect estimates (relative risks) and confidence intervals. The primary outcome is death due to bleeding within 5 days of randomisation and secondary outcomes are: rebleeding; all-cause and cause-specific mortality; thromboembolic events; complications; endoscopic, radiological and surgical interventions; blood transfusion requirements; disability (defined by a measure of patient's self-care capacity); and number of days spent in intensive care or high-dependency units. Subgroup analyses for the primary outcome will consider time to treatment, location of bleeding, cause of bleed and clinical Rockall score. DISCUSSION: We present the statistical analysis of the HALT-IT trial. This plan was published before the treatment allocation was unblinded. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN11225767. Registered on 3 July 2012; Clinicaltrials.gov, ID: NCT01658124. Registered on 26 July 2012

Emotional neglect and parents’ adverse childhood events

Abstract Introduction: Emotional neglect means that the child’s emotional and developmental needs are not fulfilled by the parents or other caregivers. Adverse childhood events (ACEs) are a risk factor for mental health problems and impaired parenting skills. The objective here was to examine whether parents’ ACEs increase the child’s risk of experiencing emotional neglect. Methods: The participants in the present study were members of the Northern Finland Birth Cohort 1986 (NFBC1986). Emotional neglect experiences were measured in 190 members of this cohort by means of the Trauma and Distress Scale (TADS), and ACEs in both parents were measured with a specific questionnaire. A linear regression model was used to examine the association between parents’ ACEs and the children’s emotional neglect scores. Results: The children’s mean emotional neglect score was 8.11 on a scale from 5 to 25. There was no significant difference between males (mean 8.01) and females (mean 8.19). Only father’s ACEs were associated with child’s emotional neglect score. In the linear regression model, the children’s emotional neglect scores increased by 0.3 points for father’s ACE. Conclusions: Our findings suggest that father’s ACEs may increase the child’s risk of experiencing emotional neglect. It seems that childhood adversities are transferred from parents to children, but larger samples would be needed to confirm these findings

Military performance of men with attention-deficit/hyperactivity disorder:findings from a follow-up study in the Northern Finland birth cohort 1986

Abstract Purpose: The aim of this study was to assess the military performance of men with adolescent attention-deficit/hyperactivity disorder (ADHD) and men with childhood ADHD (in remission during adolescence) as compared with controls without ADHD. Methods: The study employs the general population-based Northern Finland Birth Cohort 1986 (NFBC1986) together with data received from the Finnish Defence Forces (FDF). A total of 38 men with childhood ADHD and 67 with adolescent ADHD were compared with 160 controls. Results: The men with adolescent ADHD were more often deemed unfit for military service, had more military health care visits, more often committed at least one offence during service, received poorer evaluations for team leadership skills and indulged in more alcohol consumption and smoking than the controls, while those with childhood ADHD did not differ from the controls in their military fitness, but received poorer evaluations for team leadership skills and smoked more than did the controls. Conclusions: The conscripts with adolescent ADHD performed worse on many military parameters, but the men with ADHD in remission did not seem to suffer from such negative effects on military performance. The childhood ADHD group in particular was nevertheless somewhat limited in size, which might have led to a Type II error

CaMKII binding to GluN2B is critical during memory consolidation

Memory is essential for our normal daily lives and our sense of self. Ca(2+) influx through the NMDA-type glutamate receptor (NMDAR) and the ensuing activation of the Ca(2+) and calmodulin-dependent protein kinase (CaMKII) are required for memory formation and its physiological correlate, long-term potentiation (LTP). The Ca(2+) influx induces CaMKII binding to the NMDAR to strategically recruit CaMKII to synapses that are undergoing potentiation. We generated mice with two point mutations that impair CaMKII binding to the NMDAR GluN2B subunit. Ca(2+)-triggered postsynaptic accumulation is largely abrogated for CaMKII and destabilized for TARPs, which anchor AMPA-type glutamate receptors (AMPAR). LTP is reduced by 50% and phosphorylation of the AMPAR GluA1 subunit by CaMKII, which enhances AMPAR conductance, impaired. The mutant mice learn the Morris water maze (MWM) as well as WT but show deficiency in recall during the period of early memory consolidation. Accordingly, the activity-driven interaction of CaMKII with the NMDAR is important for recall of MWM memory as early as 24 h, but not 1–2 h, after training potentially due to impaired consolidation

Depressive symptoms as predictors of visual memory deficits in middle-age

Abstract Background: Depression has been known to affect memory and other cognitive domains. The objective of this longitudinal cohort study was to investigate longitudinal associations between depressive symptoms at age 31 years and visual memory and new learning at the age of 46 years. We investigated whether depressive symptoms at age 31 predicted visual memory deficits at age 46 years, and whether changes in depressive symptoms between 31 and 46 years predicted visual memory at age 46. Methods: Participants were members of the Northern Finland Birth Cohort 1966. Depressive symptoms were assessed with the Symptom Checklist-25 (SCL-25) on both occasions. Visual memory and new learning were assessed using Paired Associative Learning (PAL) test at the age 46 follow-up. PAL total errors adjusted and first trial memory score were used as outcomes and basic educational level, relationship status, physical activity and diet at baseline were considered as confounding factors in linear regression analysis. Results: A total of 5029 (57% female) participants were included in the main analysis. No associations were found between depressive symptoms or change in depressive symptoms and visual memory and new learning scores. The result did not change following cut-offs 1.55 and 1.75 for depression. Limitations: SCL-25 only measures symptoms during the past week. Only one cognitive domain was assessed. Conclusions: Contrary to our hypothesis, neither baseline depressive symptoms nor change in depressive symptoms predicted visual memory scores 15 years later. It appears that sub-clinical depressive symptoms do not effect this cognitive domain in the middle-aged population