Diet and depression: A systematic review of whole dietary interventions as treatment in patients with depression.

BACKGROUND & RATIONALE: Depression is a common mental illness that afflicts over 300 million individuals worldwide. Despite a variety of therapeutic options available, a significant number of depressed patients fail to respond to treatment. Current guidelines for treating depression suggest that supplementation of essential nutrients may be an appropriate adjunctive to treatment, but research investigating full dietary interventions for depressed patients is scarce. STUDY OBJECTIVE: The primary aim of this study was to systematically review published scientific literature investigating full dietary interventions as treatment for individuals with a diagnosis of depression. In doing so, we assessed existing evidence for recommendation of a dietary intervention and reviewed theory of how diet may be important in this context. METHODS: A systematic search was conducted using OVID to search Medline, PsychINFO, and EMBASE, and PubMed for relevant publications. Only studies including full dietary interventions for patients with Major Depressive Episode, Major Depressive Disorder, Persistent Depressive Disorder, Seasonal Affective Disorder, or Dysthymia, as diagnosed using criteria defined in the chapter of "Depressive Disorders" in the DSM, were included. RESULTS: Only five studies met the inclusion criteria for this review. All five studies included in this review reported improvements in mood following dietary intervention as compared to the comparison group. However, heterogeneity in both the dietary intervention and the outcome(s) measured made it difficult to compare these studies against each other and to generalize them to larger populations. CONCLUSION: The findings of this review provide preliminary evidence for the positive impact of dietary interventions in the treatment of depressed patients. However, the mechanism by which particular diets induce positive changes in mood, be it through anti-inflammatory mechanisms or via weight loss in overweight patients, is unclear. Future research investigating the impact of dietary interventions on a large-scale is warranted and needed.

Low-dose ketamine does not improve the speed of recovery from depression in electroconvulsive therapy: a randomized controlled trial

Objective: Electroconvulsive therapy (ECT) is a well-established therapeutic intervention for major depressive disorder. Recent literature has shown that the anesthetic agent ketamine has some antidepressant properties at low doses and may be an alternative therapy for treatment-resistant major depressive disorder. We hypothesized that the use of low-dose ketamine as an anesthetic adjunct in ECT would more rapidly improve depression while maintaining hemodynamic stability than ECT with propofol alone. Methods: Institutional ethics approval was obtained, and the use of ketamine in this study was approved by Health Canada. This is a randomized, double-blinded, placebo-controlled trial that involved ketamine administration at 0.5 mg/kg IV in addition to propofol anesthesia for ECT. The primary outcome was the number of ECT treatments required to achieve a 50% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included the number of ECT treatments required to achieve a 25% reduction in MADRS score, as well as any differences in the Clinical Global Impression Scale for Severity, hemodynamic variables, and seizure duration. Adverse events were recorded for safety assessment. Results: A total of 45 patients completed the study. No difference was found between groups with respect to the primary or secondary outcomes. The ketamine group showed a trend towards a decreased dose of propofol required to achieve adequate anesthesia. No adverse events were reported. Conclusion: Low-dose ketamine does not improve psychiatric outcomes in the setting of propofol-based anesthesia for ECT. Specifically, ketamine did not reduce the number of ECT sessions necessary to achieve a 50 or 25% reduction in MADRS scores. Reassuringly, the fact that no differences in hemodynamic variables or unexpected adverse events occurred suggests that low-dose ketamine may be safely used in this setting should clinical indications warrant its use. Clinical trial registration: ClinicalTrials.gov, NCT02579642

Low-dose ketamine does not improve the speed of recovery from depression in electroconvulsive therapy: a randomized controlled trial.

OBJECTIVE: Electroconvulsive therapy (ECT) is a well-established therapeutic intervention for major depressive disorder. Recent literature has shown that the anesthetic agent ketamine has some antidepressant properties at low doses and may be an alternative therapy for treatment-resistant major depressive disorder. We hypothesized that the use of low-dose ketamine as an anesthetic adjunct in ECT would more rapidly improve depression while maintaining hemodynamic stability than ECT with propofol alone. METHODS: Institutional ethics approval was obtained, and the use of ketamine in this study was approved by Health Canada. This is a randomized, double-blinded, placebo-controlled trial that involved ketamine administration at 0.5 mg/kg IV in addition to propofol anesthesia for ECT. The primary outcome was the number of ECT treatments required to achieve a 50% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included the number of ECT treatments required to achieve a 25% reduction in MADRS score, as well as any differences in the Clinical Global Impression Scale for Severity, hemodynamic variables, and seizure duration. Adverse events were recorded for safety assessment. RESULTS: A total of 45 patients completed the study. No difference was found between groups with respect to the primary or secondary outcomes. The ketamine group showed a trend towards a decreased dose of propofol required to achieve adequate anesthesia. No adverse events were reported. CONCLUSION: Low-dose ketamine does not improve psychiatric outcomes in the setting of propofol-based anesthesia for ECT. Specifically, ketamine did not reduce the number of ECT sessions necessary to achieve a 50 or 25% reduction in MADRS scores. Reassuringly, the fact that no differences in hemodynamic variables or unexpected adverse events occurred suggests that low-dose ketamine may be safely used in this setting should clinical indications warrant its use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02579642.

Methodology for clinical genotyping of CYP2D6 and CYP2C19.

Many antidepressants, atomoxetine, and several antipsychotics are metabolized by the cytochrome P450 enzymes CYP2D6 and CYP2C19, and guidelines for prescribers based on genetic variants exist. Although some laboratories offer such testing, there is no consensus regarding validated methodology for clinical genotyping of CYP2D6 and CYP2C19. The aim of this paper was to cross-validate multiple technologies for genotyping CYP2D6 and CYP2C19 against each other, and to contribute to feasibility for clinical implementation by providing an enhanced range of assay options, customizable automated translation of data into haplotypes, and a workflow algorithm. AmpliChip CYP450 and some TaqMan single nucleotide variant (SNV) and copy number variant (CNV) data in the Genome-based therapeutic drugs for depression (GENDEP) study were used to select 95 samples (out of 853) to represent as broad a range of CYP2D6 and CYP2C19 genotypes as possible. These 95 included a larger range of CYP2D6 hybrid configurations than have previously been reported using inter-technology data. Genotyping techniques employed were: further TaqMan CNV and SNV assays, xTAGv3 Luminex CYP2D6 and CYP2C19, PharmacoScan, the Ion AmpliSeq Pharmacogenomics Panel, and, for samples with CYP2D6 hybrid configurations, long-range polymerase chain reactions (L-PCRs) with Sanger sequencing and Luminex. Agena MassARRAY was also used for CYP2C19. This study has led to the development of a broader range of TaqMan SNV assays, haplotype phasing methodology with TaqMan adaptable for other technologies, a multiplex genotyping method for efficient identification of some hybrid haplotypes, a customizable automated translation of SNV and CNV data into haplotypes, and a clinical workflow algorithm.

Mobile App-Based Self-Report Questionnaires for the Assessment and Monitoring of Bipolar Disorder: Systematic Review.

BACKGROUND: Bipolar disorder is a chronic, progressive illness characterized by recurrent episodes of mania and depression. Self-report scales have historically played a significant role in the monitoring of bipolar symptoms. However, these tools rely on episodic memory, which can be unreliable and do not allow the clinician to monitor brief episodic symptoms or the course of symptoms over shorter periods of time. Mobile app-based questionnaires have been suggested as a tool to improve monitoring of patients with bipolar disorder. OBJECTIVE: This paper aims to determine the feasibility and validity of mobile app-based self-report questionnaires. METHODS: We performed a systematic review of the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, PsycInfo, Web of Science, Ovid MEDLINE, and EMBASE databases were searched for papers published in English that assessed adherence to and the validity of mobile app-based self-report questionnaires. Relevant studies published from database creation to May 22, 2020, were identified, and results examining the validity of and rates of adherence to app-based self-report questionnaires are reported. RESULTS: A total of 13 records were identified for inclusion in this review. Of these studies, 4 assessed the concurrent validity of mobile app-based self-report tools, with the majority of findings indicating significant associations between data collected using these tools and the Young Mania Rating Scale, Hamilton Depression Rating Scale-17, or Montgomery-Åsberg Depression Rating Scale (P<.001 to P=.24). Three studies comparing the variability or range of symptoms between patients with bipolar disorder and healthy controls suggested that these data are capable of differentiating between known groups. Two studies demonstrated statistically significant associations between data collected via mobile app-based self-report tools and instruments assessing other clinically important factors. Adherence rates varied across the studies examined. However, good adherence rates (>70%) were observed in all but 1 study using a once-daily assessment. There was a wide range of adherence rates observed in studies using twice-daily assessments (42%-95%). CONCLUSIONS: These findings suggest that mobile app-based self-report tools are valid in the assessment of symptoms of mania and depression in euthymic patients with bipolar disorder. Data collected using these tools appear to differ between patients with bipolar disorder and healthy controls and are significantly associated with other clinically important measures. It is unclear at this time whether these tools can be used to detect acute episodes of mania or depression in patients with bipolar disorder. Adherence data indicate that patients with bipolar disorder show good adherence to self-report assessments administered daily for the duration of the study periods evaluated.

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.

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.