Journal of Child and Adolescent Psychopharmacology

To examine whether serotonin (5-HT) related genetic variants moderate the effects of selective serotonin reuptake inhibitors (SSRIs) on skeletal outcomes.

Trabecular bone mineral density (BMD) at the radius, lumbar spine (LS) BMD, total body less head (TBLH) bone mineral content (BMC) and markers of bone metabolism (osteocalcin, C-terminal telopeptide of type I collagen [CTX-1], and bone specific alkaline phosphatase to CTX-1 ratio) were examined in an observational study, enrolling 15- to 20-year-old participants, unmedicated or within a month of SSRI initiation. Variants in HTR1A (rs6295), HTR1B (rs6296), HTR1D (rs6300), HTR2A (rs6311 and rs6314), HTR2B (rs6736017), and the serotonin transporter intron 2 variable number tandem repeat (STin2 VNTR) were genotyped. Linear mixed-effects regression analysis examined associations between SSRI use, genetic variants, and skeletal outcomes.

After adjusting for relevant covariates, rs6295 CC and GC genotypes in 262 participants (60% female, mean ± SD age = 18.9 ± 1.6 years) were significantly associated with higher LS BMD compared to the GG genotype. Rs6311 GG SSRI users had greater LS BMD compared to nonusers (β = 0.18, p = <0.0001). Female SSRI users with the combination of rs6295 CC+GC and rs6311 GG genotypes had greater LS BMD than female SSRI nonusers (β = 0.29, p < 0.0001). SSRI users with the rs6295 GG genotype had higher trabecular BMD compared to nonusers (β = 3.60, p = 0.05). No significant interactions were found for TBLH BMC or bone turnover markers. After correcting for multiple comparisons, none of the results retained significance.

In older adolescents and young adults, HTR1A (rs6295) and HTR2A (rs6311) variants may moderate the effect of SSRIs on BMD. Sex differences may exist and require further examination. Further research with larger sample sizes is needed to confirm our preliminary findings.

clinicaltrials.gov NCT02147184.

This study aimed to examine the association between abnormal readings of metabolic parameters detected during second-generation antipsychotic (SGA) treatment and the likelihood of receiving subsequent adverse drug event interventions.

This was a nested case–control study conducted on patients 1–17 years of age with at least two prescriptions of SGAs between January 2010 and January 2019 using TriNetX EMR data. Following an incident density sampling procedure, patients who received the SGA metabolic adverse event intervention (mAEI) (case) were matched with three nonrecipients (controls). The abnormal readings of metabolic parameters within 30 days before the initiation of mAIEs were further identified. These metabolic parameters include body mass index (BMI) and laboratory parameters such as cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, blood glucose, HbA1c, thyroid hormones, liver enzymes, and prolactin. The association of abnormal metabolic parameters with subsequent mAEIs was assessed using a conditional logistic regression model, after adjusting for demographic and other clinical risk factors.

One thousand eight hundred eighty-four children and adolescents met the inclusion criteria and were prescribed SGA mAEIs. The most common types of mAEIs prescribed were weight management pharmacotherapy (40.6%), switching from a high or medium metabolic risk profile SGA to a low-risk one (30.9%), nonpharmacological treatment (25.4%), and switching from SGA polytherapy to monotherapy (11.7%). The conditional logistic regression analysis on matched mAEI recipients and nonrecipients showed that patients with an abnormal BMI had 43% higher odds of receiving mAEI (odds ratio [95% confidence interval]: 1.43 [1.13–1.79]). However, the presence of an abnormal laboratory reading was not associated with the initiation of mAEIs.

The prescribing of mAEIs were associated with the presence of obesity, but not with abnormal readings of other metabolic parameters, suggesting that additional data are needed to clarify the long-term implication of SGA metabolic adverse events other than weight gain and to inform the appropriate timing for interventions.

Prescription of second-generation antipsychotics (SGAs) in youths is rapidly increasing globally, despite the potential for significant adverse effects and long-term health consequences. A known adverse reaction resulting from SGAs is metabolic syndrome (MS). Youths exposed to antipsychotics are at higher risk than adults for adverse drug reactions, including adverse events such as MS (with weight gain as the most significant adverse outcome) and other long-term endocrinological abnormalities. This study aimed to explore the experiences of young patients on factors impacting barriers to metabolic monitoring of SGAs and the strategies to address those barriers thereby providing further guidance on policy and service delivery.

Semi-structured interviews were conducted with patients (youths who were prescribed SGAs) who attended Child and Youth Mental Health Services. The interviews focused on barriers to monitoring and strategies to enhance rates of monitoring that could be customized across study sites.

Young patients revealed that none of them had any concerns or objections to receiving anthropometric metabolic measurements. However, they seemed concerned to undergo blood tests as part of the metabolic monitoring process. Specifically, youths cited their fear of the needles as barrier to undergo the required blood tests. Youths have also reported that their dislike to healthy foods and exercise being the most common challenge they face while trying to engage in a healthy lifestyle to manage the SGAs resulted weight gain.

Prescribers are recommended to actively engage young patients about the expected SGAs-induced adverse effects, the importance of conducting metabolic monitoring, and how to prevent and minimize the expected adverse effects from the start of initiating SGAs. This could be a vital step toward a successful treatment as the insight of youths into the details of the chosen treatment can play a significant role into treatment adherence and recovery.

Major depressive disorder (MDD) is a primary risk factor for suicide, which is one of the leading causes of death among adolescents worldwide. Understanding the heterogeneity of suicidality in adolescents with MDD is critical for suicide prevention and intervention discovery. Quantitative electroencephalography (EEG) is a promising tool to address the knowledge gaps related to the neurophysiological characteristics of depression and suicidality. This study sought to examine resting-state EEG coherence differences in adolescents with MDD and suicidal ideation (SI)/behaviors (SB) and healthy controls (HC) to assess the utility of coherence as a biomarker of suicide.

Twenty-six adolescents with MDD who were hospitalized for suicidality and 30 HC were recruited. The clinical sample was divided into SI (n = 9) and SB (n = 19) subgroups. Eyes closed resting-state EEG were recorded, and coherence was calculated. Depression severity and suicidality were assessed with the Children's Depression Rating Scale Revised and the Columbia Suicide Severity Rating Scale, respectively.

There were intrahemispheric differences in the right hemisphere across multiple electrode pairs. Delta, alpha, and beta coherence were higher in the SB group over the right prefrontofrontal and left parietooccipital electrode pairs, while alpha coherence was higher in the HC group over the right centroparietal electrode pair. There were no significant differences between HC and SI groups in any electrode pair.

Patients with recent SB showed increased coherence in right frontal regions compared with patients with SI, suggesting altered cognitive states between those with SB and SI. These findings may have implications for suicide prevention in adolescents and could serve as useful biomarkers in clinical settings, but larger studies are needed to confirm the results.