Individuals who have recovered from the acute stage of SARS-CoV-2 infection may be at risk of developing post-COVID-19 condition (PCC), characterised by a spectrum of persisting, non-specific, and functionally impairing symptoms across multiple organ systems. Obesity has been implicated as a risk factor for PCC, mediated by chronic systemic inflammation. The foregoing has also been separately reported to mediate cognitive dysfunction in PCC.

This is a post-hoc analysis of a randomised, double-blinded, placebo-controlled clinical trial evaluating vortioxetine treatment for cognitive impairments in persons with PCC who received vortioxetine or placebo for eight weeks. This analysis comprises baseline data, examining the impact of BMI on cognitive functioning measured by the Digit Symbol Substitution Test (DSST) and Trails Making Tests (TMT)-A/B, as well as inflammation, via serum c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).

Complete data from 70 participants were statistically analysed and adjusted for age and sex. BMI was negatively correlated with performance on the DSST (β = −0.003, p = 0.047), TMT-A (β = −0.006, p = 0.025), and TMT-B (β = −0.006, p = 0.002). BMI was positively correlated with serum CRP (unstandardized β = 0.193, standardized β = 0.612, p < 0.001) and ESR (β = 0.039, p < 0.001) levels.

We observed a significant negative correlation between BMI and cognitive functioning, and a significant positive correlation between BMI and inflammation in persons with PCC, suggesting a bidirectional interplay between BMI, PCC, and cognitive function; individuals with an elevated BMI may be at a greater risk of developing PCC and/or presenting with greater cognitive deficits mediated by chronic systemic inflammation.

Life engagement represents a holistic concept that encompasses outcomes reflecting life-fulfilment, well-being and participation in valued and meaningful activities, which is recently gaining attention and scientific interest. Despite its conceptual importance and its relevance, life engagement represents a largely unexplored domain in schizophrenia. The aims of the present study were to independently assess correlates and predictors of patient life engagement in a large and well-characterized sample of schizophrenia patients.

To assess the impact of different demographic, clinical, cognitive and functional parameters on life engagement in a large sample of patients with schizophrenia, data from the social cognition psychometric evaluation project were analyzed.

Overall schizophrenia and depressive symptom severity, premorbid IQ, neurocognitive performance, social cognition performance both in the emotion processing and theory of mind domains, functional capacity, social skills performance and real-world functioning in different areas all emerged as correlates of patient life engagement. Greater symptom severity and greater impairment in real-world interpersonal relationships, social skills, functional capacity and work outcomes emerged as individual predictors of greater limitations in life engagement.

Life engagement in people living with schizophrenia represents a holistic and complex construct, with several different clinical, cognitive and functional correlates. These features represent potential treatment targets to improve the clinical condition and also facilitate the process of recovery and the overall well-being of people living with schizophrenia.

To investigate the effect of cariprazine on cognitive symptom change across bipolar I disorder and schizophrenia.

Post hoc analyses of 3- to 8-week pivotal studies in bipolar I depression and mania were conducted; one schizophrenia trial including the Cognitive Drug Research System attention battery was also analyzed. Outcomes of interest: Montgomery-Åsberg Depression Rating Scale [MADRS], Functioning Assessment Short Test [FAST], Positive and Negative Syndrome Scale [PANSS]). LSMDs in change from baseline to end of study were reported in the overall intent-to-treat population and in patient subsets with specified levels of baseline cognitive symptoms or performance.

In patients with bipolar depression and at least mild cognitive symptoms, LSMDs were statistically significant for cariprazine vs placebo on MADRS item 6 (3 studies; 1.5 mg=−0.5 [P<.001]; 3 mg/d=−0.2 [P<.05]) and on the FAST Cognitive subscale (1 study; 1.5 mg/d=−1.4; P=.0039). In patients with bipolar mania and at least mild cognitive symptoms, the LSMD in PANSS Cognitive subscale score was statistically significant for cariprazine vs placebo (3 studies; −2.1; P=.001). In patients with schizophrenia and high cognitive impairment, improvement in power of attention was observed for cariprazine 3 mg/d vs placebo (P=.0080), but not for cariprazine 6 mg/d; improvement in continuity of attention was observed for cariprazine 3 mg/d (P=.0012) and 6 mg/d (P=.0073).

These post hoc analyses provide preliminary evidence of greater improvements for cariprazine vs placebo across cognitive measures in patients with bipolar I depression and mania, and schizophrenia, suggesting potential benefits for cariprazine in treating cognitive symptoms.

More than 50% patients with major depressive disorder (MDD) have severe functional impairment. The restoration of patient functioning is a critical therapeutic goal among patients with MDD. We conducted a systematic review and network meta-analysis to evaluate the efficacy of pharmacological treatments on self-rated functional outcomes using the Sheehan Disability Scale in adults with MDD in randomized clinical trials.

PubMed, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched from inception to December 10, 2019. Summary statistics are reported as weighted mean differences with 95% confidence intervals. Interventions were ranked using the surface under the cumulative ranking probabilities.

We included 42 randomized controlled trials (RCTs) (n = 18 998) evaluating the efficacy of 13 different pharmacological treatments on functional outcomes, as measured by the Sheehan Disability Scale (SDS). Duloxetine was the most effective pharmacological agent on functional outcomes, followed by (ranked by efficacy): paroxetine, levomilnacipran, venlafaxine, quetiapine, desvenlafaxine, agomelatine, escitalopram, amitriptyline, bupropion, sertraline, vortioxetine, and fluoxetine. Serotonin and norepinephrine reuptake inhibitors were more effective than other drug classes. Additionally, the comparison-adjusted funnel plot suggested the publication bias between small and large studies was relatively low.

Our results indicate that there may be differences across antidepressant agents and classes with respect to self-reported functional outcomes. Validation and replication of these findings in large-scale RCTs are warranted. Our research results will be clinically useful for guiding psychiatrists in treating patients with MDD and functional impairment. PROSPERO registration number CRD42018116663.

Benzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD prescription.

Cross-sectional study using data from the Florida Medicaid Managed Medical Assistance Program from January 1, 2018 to December 31, 2018. Eligible recipients ages 18 to 64, inclusive, enrolled in the Florida Medicaid plan for at least 1 day, and were dually eligible. Recipients either had a serious mental illness (SMI), or non-SMI and anxiety.

Total 125 463 cases were identified (i.e., received BZD or non-BZD prescription). Main effect of patient and prescriber gender was significant F(1, 125 459) = 0.105, P = 0 .745, partial η2 < 0.001. Relative risk (RR) of male prescribers prescribing a BZD compared to female prescribers was 1.540, 95% confidence intervals (CI) [1.513, 1.567], whereas the RR of male patients being prescribed a BZD compared to female patients was 1.16, 95% CI [1.14, 1.18]. Main effects of patient and prescriber gender were statistically significant F(1, 125 459) = 188.232, P < 0.001, partial η2 = 0.001 and F(1, 125 459) = 349.704, P < 0.001, partial η2 = 0.013, respectively.

Male prescribers are more likely to prescribe BZDs, and male patients are more likely to receive BZDs. Further studies are required to characterize factors that influence this gender-by-gender interaction.

Patients unsuccessfully treated by neurostimulation may represent a highly intractable subgroup of depression. While the efficacy of intravenous (IV) ketamine has been established in patients with treatment-resistant depression (TRD), there is an interest to evaluate its effectiveness in a subpopulation with a history of neurostimulation.

This retrospective, posthoc analysis compared the effects of four infusions of IV ketamine in 135 (x̄ = 44 ± 15.4 years of age) neurostimulation-naïve patients to 103 (x̄ = 47 ± 13.9 years of age) patients with a history of neurostimulation. The primary outcome evaluated changes in depression severity, measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16). Secondary outcomes evaluated suicidal ideation (SI), anxiety severity, measured by the Generalized Anxiety Disorder 7-Item (GAD-7), and consummatory anhedonia, measured by the Snaith–Hamilton Pleasure Scale (SHAPS).

Following four infusions, both cohorts reported a significant reduction in QIDS-SR16 Total Score (F (4, 648) = 73.4, P < .001), SI (F (4, 642) = 28.6, P < .001), GAD-7 (F (2, 265) = 53.8, P < .001), and SHAPS (F (2, 302) = 45.9, P < .001). No between-group differences emerged. Overall, the neurostimulation-naïve group had a mean reduction in QIDS-SR16 Total Score of 6.4 (standard deviation [SD] = 5.3), whereas the history of neurostimulation patients reported a 4.3 (SD = 5.3) point reduction.

IV ketamine was effective in reducing symptoms of depression, SI, anxiety, and anhedonia in both cohorts in this large, well-characterized community-based sample of adults with TRD.

Higher body mass index (BMI) has been found to predict greater antidepressant response to intravenous (IV) ketamine treatment. We evaluated the association between BMI and response to repeat-dose IV ketamine in patients with treatment-resistant depression (TRD).

Adults (N = 230) with TRD received four infusions of IV ketamine at a community-based clinic. Changes in symptoms of depression (ie, Quick Inventory for Depressive Symptomatology-Self-Report 16; QIDS-SR16), suicidal ideation (SI; ie, QIDS-SR16 SI item), anxiety (ie, Generalized Anxiety Disorder-7 Scale), anhedonic severity (ie, Snaith–Hamilton Pleasure Scale), and functioning (ie, Sheehan Disability Scale) following infusions were evaluated. Participants were stratified by BMI as normal (18.0-24.9 kg/m2; n = 72), overweight (25-29.9 kg/m2; n = 76), obese I (30-34.9 kg/m2; n = 47), or obese II (≥35.0 kg/m2; n = 35).

Similar antidepressant effects with repeat-dose ketamine were reported between BMI groups (P = .261). In addition, categorical partial response (P = .149), response (P = .526), and remission (P = .232) rates were similar between the four BMI groups.

The findings are limited by the observational, open-label design of this retrospective analysis. Pretreatment BMI did not predict response to IV ketamine, which was effective regardless of BMI.

Fibromyalgia and major depressive disorder (MDD) frequently co-occur. Quetiapine XR has demonstrated efficacy in the treatment of MDD and has recently been shown effective in patients with fibromyalgia.

To evaluate the efficacy and safety of quetiapine XR in patients with MDD and comorbid fibromyalgia.

To report on the antidepressant and analgesic effects of quetiapine XR in a sample of dually diagnosed patients.

An 8-week double-blind, randomized controlled trial in 120 non-psychotic adult outpatients with a confirmed diagnosis of MDD and fibromyalgia. Quetiapine XR was administered once daily in the evening at a starting dose of 50 mg/d for 2 days then 150 mg/d for 2 weeks and up to 300 mg/d if needed. The primary efficacy endpoint was mean change from baseline to week 8 on the HAM-D17 total score. Secondary endpoints included other measures of depression, anxiety, pain, quality of life, global functioning and adverse events.

At week 8, mean change in HAM-D17 score from baseline was significantly greater in the quetiapine XR arm than placebo (-10.0 vs. -5.8, p=0.001). Improvements in the Fibromyalgia Impact Questionaire (FIQ total -11.1 vs. -3.9, p=0.022) and Brief Pain Inventory (BPI-Total -2.1 vs. -1.6, p=0.007) was significantly greater in the quetiapine XR arm versus placebo. Improvements in all secondary outcomes were significantly greater in the quetiapine XR with the exception of the Sheehan Disability Scale total score.

Quetiapine XR demonstrated significant antidepressive and analgesic effects in this population of patients with MDD and fibromyalgia.

Individuals with bipolar disorder (BD) are differentially affected by insulin resistance. Individuals without history of mental disorder with insulin resistance usually have high peripheral concentrations of phenylalanine (PHE) and tyrosine (TYR) together. Catecholamine dysfunction is described to be a state-dependend phenomen in patients suffering from BD. Catecholamines are synthesized from essential amino acids PHE and TYR which are biotransformed to dopamine and subsequently converted to nor/adrenaline. Amino acid dysregulation may be a possible mediator of insulin resistance in BD.

Peripheral PHE and TYR concentrations were investigated in euthymic adults with BD. Amino acid differences between normal and overweight individuals with BD were evaluated and outcomes were correlated with the measures of glucose homeostasis.

Mean plasma PHE to TYR ratio (PHE/TYR) was at the upper limit of the normal range in the whole sample. Enrolled subjects with PHE/TYR beyond the limits of normal exhibited the highest number of prior affective episodes. Sex-specific differences were noted as overweight BD females showed different profiles than normal-weight women. In the overweight females, PHE and TYR concentrations were significantly higher compared to normal-weight women. Significant correlations were noticed between PHE, TYR and PHE/TYR with insulin/Homeostasis Model of Assessment (HOMA)-IR in the whole sample and the subgroup of BD women.

These significant differences in gender, amino acid pathways and in correlations with immune marker as well as insulin function have not been reported previously. Taken together, increased levels of PHE in BD should be considered when adjudicating diabetes risk especially in women.

Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.

Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.

Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.

This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.