Logistic Regression With Machine Learning Sheds Light on the Problematic Sexual Behavior Phenotype.

OBJECTIVES: There has been a longstanding debate about whether the mechanisms involved in problematic sexual behavior (PSB) are similar to those observed in addictive disorders, or related to impulse control or to compulsivity. The aim of this report was to contribute to this debate by investigating the association between PSB, addictive disorders (internet addiction, compulsive buying), measures associated with the construct known as reward deficiency (RDS), and obsessive-compulsive disorder (OCD). METHODS: A Canadian university Office of the Registrar invited 68,846 eligible students and postdoctoral fellows. Of 4710 expressing interest in participating, 3359 completed online questionnaires, and 1801 completed the Mini-International Neuropsychiatric Interview. PSB was measured by combining those screening positive (score at least 6) on the Sexual Addiction Screening Test-Revised Core with those self-reporting PSB. Current mental health condition(s) and childhood trauma were measured by self-report. OCD was assessed by a combination of self-report and Mini-International Neuropsychiatric Interview data. RESULTS: Of 3341 participants, 407 (12.18%) screened positive on the Sexual Addiction Screening Test-Revised Core. On logistic regression, OCD, attention deficit, internet addiction, a family history of PSB, childhood trauma, compulsive buying, and male gender were associated with PSB. On multiple correspondence analysis, OCD appeared to cluster separately from the other measures, and the pattern of data differed by gender. CONCLUSIONS: In our sample, factors that have previously been associated with RDS and OCD are both associated with increased odds of PSB. The factors associated with RDS appear to contribute to a separate data cluster from OCD and to lie closer to PSB.

Emotional blunting with bupropion and serotonin reuptake inhibitors in three randomized controlled trials for acute major depressive disorder.

BACKGROUND: Emotional blunting is theorized to be an adverse effect of antidepressants, particularly serotonin reuptake inhibitors, but this has not been firmly established. Another possibility is that emotional blunting represents a residual depressive symptom. METHODS: We analyzed data from adult outpatients with acute major depressive disorder who participated in three 8-week randomized controlled trials. Trials 1 and 2 were pooled (venlafaxine, n = 378; bupropion, n = 389; placebo, n = 383) and Trial 3 (escitalopram, n = 254; bupropion, n = 260) was analyzed separately. Emotional blunting was measured with the "inability to feel" item from the Montgomery-Åsberg Depression Rating Scale. RESULTS: Emotional responsiveness improved, on average, in all treatment groups. Only a minority of participants (≤6 %) experienced more emotional blunting post-treatment, compared to baseline, with no significant differences between treatment groups, although roughly 20-25 % continued to report an inability to feel normal emotions at the final assessment. In Trials 1 and 2, emotional blunting was associated with poorer outcomes in terms of depressive symptoms, suicidal ideation, and sexual function, but these correlations were nearly identical in the placebo group. LIMITATIONS: The trials were short and cannot speak to the possibility of emotional blunting from long-term treatment. Emotional blunting was measured with a single item. CONCLUSIONS: The study medications did not significantly decrease emotional responsiveness, and there was no evidence that emotional blunting mediated treatment response. In acute treatment, emotional blunting may be better conceptualized as a residual symptom than as an adverse drug effect.

Medication Gaps and Antipsychotic Polypharmacy in Previously Hospitalized Schizophrenia Patients: An Electronic Cohort Study in Three Canadian Provinces.

Background: Real world evidence about antipsychotics focuses on rehospitalization. Modeling the time course of pharmacotherapy would show patients' adherence to medications and physicians' adherence to medication guidelines. We aimed to calculate the cumulative time spent in second generation antipsychotics (SGAs), gaps, antipsychotic polypharmacy, and clozapine in discharged schizophrenia patients. Methods: Hospitalization and pharmacy dispensing data from 2008-2018 in Manitoba, Saskatchewan, and British Columbia were linked and an electronic cohort (N = 2,997) was created (mean follow-up: 49 months, SD = 38). Cohort members were required to have a minimum of 6 weeks medicated with aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, or ziprasidone. Results: The multistate model predicted that schizophrenia patients accumulated 44 months in SGA monotherapy, 4 months in polypharmacy, 11 months in medication gaps and 17 days in clozapine over a 5-year period. The majority of transitions were between SGA and medication gap. Accumulated time in medication gaps was seven times as much as in clozapine. Each 10% delay in SGA initiation post-discharge was associated with a 2, 1, and 6% higher risk for polypharmacy (95% CI: 1.01-1.02), gap (95% CI: 1.01-1.01), and clozapine (95% CI: 1.04-1.08), respectively. Interpretation: Schizophrenia patients accumulated more time unmedicated and in polypharmacy compared to clozapine. Either treatment guidelines for schizophrenia are not followed, or real-world challenges hamper their implementation.

Understanding the inverse relationship between age and psychotic symptoms: The role of borderline personality traits.

OBJECTIVE: There is a well-established inverse relationship between age and positive psychotic symptoms, both in patients with psychotic disorders and in general population samples with psychotic experiences. The reason for this inverse relationship is unclear. We hypothesized that life-course developmental changes in borderline personality traits, which also typically decline with age, might explain the inverse relationship between age and positive psychotic symptoms. METHODS: We tested this hypothesis with data from 19,980 adults who completed 2000, 2007, and 2014 UK Adult Psychiatric Morbidity Survey studies. Hallucinations and delusions were assessed with the Psychosis Screening Questionnaire. Borderline features were assessed with the Structured Clinical Interview for DSM-IV Axis II Personality Disorders Screening Questionnaire. Logistic regression models with effect decompositions were used to conduct the analyses. RESULTS: As expected, age was negatively associated with hallucinations and delusions. These effects were wholly or mostly reduced after controlling for borderline features. Similar results were found in a subgroup of participants with a probable psychotic disorder. Repeating the analysis with a broad index of psychopathology severity instead of borderline features did not produce comparable results. Borderline factor scores reflecting identity/relationship disturbance, mood instability/anger, and self-harm/suicidality were created, all of which appeared to explain part of the inverse relationship between age and psychotic experiences. CONCLUSION: Declining borderline traits throughout adulthood may account for the reduced prevalence of positive psychotic symptoms in both clinical and non-clinical populations. Future research might evaluate the impact of treatments that target borderline traits on positive psychotic symptoms.

The feasibility and acceptability of mobile application-based assessment of suicidality using self-report components of a novel tool, the Suicide Ideation and Behavior Assessment Tool (SIBAT).

The aim of this study was to assess the validity of a mobile application-based self-report questionnaire in the assessment of suicidality. We developed a program for the administration of self-report components of the Suicide Ideation and Behavior Assessment Tool (SIBAT). We invited university students and trainees enrolled in a study of addictions to complete this component of the SIBAT using the program on their mobile devices or personal computer. 196 participants completed all required modules of the SIBAT, with 97 using their mobile device and 99 using their personal computer. Rates of completed questionnaires between the two groups were compared, as were the responses to the items and the total scores. There was a significant difference between proportions of scale completion in both groups, with a greater number of participants who used a personal computer to complete the scale not responding to all questions compared to participants who used a mobile device to complete the scale. Data collected via mobile device showed good concurrent validity with data collected via personal computer. A trend toward greater disclosure of suicidality was observed in the mobile device group however, replication of these findings using larger sample sizes is needed.

Internal consistency and concurrent validity of self-report components of a new instrument for the assessment of suicidality, the Suicide Ideation and Behavior Assessment Tool (SIBAT).

This study aimed to assess the internal consistency of self-report components of the Suicide Ideation and Behavior Assessment Tool (SIBAT) and validate it with relevant elements of the Mini International Neuropsychiatric Interview (MINI). The SIBAT is a newly developed instrument for the evaluation of suicidality. In this study, we invited university students and trainees participating in a study of addictions to complete the self-report component of the SIBAT as an add-on study. We evaluated the internal consistency of the self-report component of the SIBAT and validated it against the suicidality component of the MINI. Data were analysed using both complete case analysis and multiple imputation. SIBAT data were collected for 394 participants, 314 of whom had also completed the MINI. The internal consistency of modules 2, 3, and 5 of the SIBAT was high. Each item from module 5 had a statistically significant association with the corresponding item from the MINI. The sum of scores from modules 2 and 3 had a moderate correlation with the assessment of suicide risk determined by the MINI, and a strong correlation with the total score of SIBAT module 5. The completion median time of modules 2, 3 and 5 was 14.3 min.

Lamotrigine for acute bipolar depression: An exploratory item-level analysis.

OBJECTIVES: Lamotrigine is used to treat bipolar depression despite inconsistent evidence. Here we present the results of an exploratory item-level analysis of pooled data from five randomized placebo-controlled trials of lamotrigine for acute bipolar depression. The goal was to determine if certain depression scale items were more responsive to lamotrigine treatment. METHODS: The pooled sample contained 1072 adult outpatients treated for up to 7-10 weeks. Depressive symptoms were measured with the Hamilton Depression Rating Scale and the Montgomery-Åsberg Depression Rating Scale. Change scores on individual scale items were compared between treatment groups. RESULTS: There were statistically significant effects on items assessing depressed mood/sadness, lack of interest/anhedonia, pessimism/guilt, and anergia/fatigue, on both scales. However, there was marked variation in the baseline symptom prevalence, and items with higher scores at baseline tended to have larger and statistically significant treatment effects. CONCLUSIONS: The results suggested a significant treatment effect on core symptoms of depression. A floor effect appeared to limit the sensitivity of other scale items. Given the exploratory nature of the analysis, firm conclusions cannot be drawn, although the results were consistent with past research. Relying on total depression scale sum scores over targeted assessments of core depressive symptoms may have impeded signal detection in the original trials.

Trend level gene-gender interaction effect for the BDNF rs6265 variant on age of onset of psychosis.

A BDNF rs6265 [A/A] by gender by cannabis use interaction has been associated with age of onset of psychosis (AoP). We examined the gender and cannabis use-adjusted association between BDNF rs6265 [G>A] and AKT1 rs2494732 [T>C] and AoP. Data from 167 Caucasians on AoP and age at first regular cannabis use were collected. Kaplan-Meier and Cox regression analyses were conducted. A trend level gene-gender interaction effect was observed for the BDNF rs6265 A/A genotype, controlling for age at first regular cannabis use. Larger collaborative research projects are required to further investigate this effect.

Associations between the LEP -2548G/A Promoter and Baseline Weight and between LEPR Gln223Arg and Lys656Asn Variants and Change in BMI z Scores in Arab Children and Adolescents Treated with Risperidone.

Data on baseline (antipsychotics-naïve) age, weight, and height, and change in these at 3 subsequent follow-up time points up to 313.6 days (95% CI 303.5-323.7) were collected from 181 risperidone-treated children and adolescents (mean age 12.58 years, SD 4.99, range 2.17-17.7) attending a pediatric neurology clinic in Saudi Arabia. Owing to differences in genotypic distributions in the subsamples, results are reported for the white Arab population (n = 144). Age- and gender-normed body mass index (BMI)-standardized z scores (BMI z) were calculated (LMSgrowth program). Linear regression was performed for baseline weight and BMI z, while change in BMI z was assessed using random effects ordered logistic regression. The following single nucleotide polymorphisms (SNPs) were analyzed: rs7799039 in the LEP promoter, rs1805094 (previously rs8179183), rs1137100 and rs1137101 in the LEPR, and rs1414334 in HTR2C. We found a nominally significant association between rs7799309 and baseline weight, adjusting for height, age, gender, and diagnosis (A/G, p = 0.035, ß = -3.62 vs. G/G). The rs1137101 (G/G, p = 0.018, odds ratio [OR] = 4.13 vs. A/A) and rs1805094 C allele carriers (p = 0.019, OR = 0.51) showed nominally significant associations with change in BMI z categories. Our data support and replicate previous relevant associations for these variants (including with weight gain when on risperidone), whilst being the first report of such associations in patients of Arab ethnicity.

Investigation of the COMT Val158Met variant association with age of onset of psychosis, adjusting for cannabis use.

Objective: COMT rs4680 (Val158Met) genotype moderates the effect of cannabis on the age of onset of psychosis (AoP). We investigated the association between rs4680 and AoP, after adjusting for relevant covariates, in a Canadian Caucasian sample. Methods: One hundred and sixty-nine subjects with psychosis were recruited. AoP, defined as age of DSM-IV diagnosis was established using the Structured Clinical Interview for DSM-IV. Cannabis use data were collected using a self-report computerized questionnaire. DNA was extracted from saliva and genotyping of the COMT Val158Met polymorphism was done by SNaPshot and TaqMan assays. Kaplan-Meier analysis results are reported. Results: In those who had used cannabis before 20 years of age, rs4680 had a trend level effect on AoP (median AoP: Val/Val < Val/Met < Met/Met 19.37, 20.95, 21.24 years, respectively; log-rank test p = .051). Conclusion: Our data are indicative of the need to further investigate the association between the COMT rs4680 variant and AoP in the context of adolescent cannabis use.

Changes in biomarkers of bone turnover in an aripiprazole add-on or switching study.

BACKGROUND: The association between mental illness and osteoporosis and fractures is particularly pronounced in psychotic disorders. Antipsychotic use has previously been described to affect bone density. METHOD: A 52-week follow-up of patients switched to aripiprazole or with aripiprazole added on, conducting a specific analysis of markers of bone turnover: urinary NTX (a biomarker of bone resorption) and serum BSAP (a biomarker of bone formation). Baseline and serial measurements of bone markers NTX, BSAP and of hormones prolactin, oestrogen and testosterone were done at weeks 0 and 1, 2, 6, 12, 26 and 52, respectively. RESULTS: NTX concentration reduced over time but this did not reach significance in the whole group (log-NTX: ß=-0.0012, p=0.142). For BSAP the addition of or replacement with aripiprazole produced a significant reduction (log-BSAP: ß=-0.00039, p=0.002). Analysis with prolactin similarly showed a significant reduction (log-prolactin: ß=-0.0024, p<0.001); other hormones did not change significantly. Sensitivity analysis to compare the switchers to aripiprazole versus the "add-on" showed that the former group had a significant reduction in NTX. CONCLUSIONS: We found that switching to aripiprazole was associated with changes in molecular biomarkers of bone resorption, indicating a more favourable profile for bone health.