OBJECTIVES:The prevalence and effects of anxiety on health-related quality of life and clinical outcomes in cirrhosis are not well understood. This is increasingly relevant during COVID-19. Our aim was to use the Mini-International Neuropsychiatric Interview (MINI) to determine the prevalence of anxiety, its association with clinical outcomes in cirrhosis and to develop a rapid cirrhosis-specific anxiety screening nomogram. METHODS:Adults with a diagnosis of cirrhosis were prospectively recruited as outpatients at three tertiary care hospitals across Alberta and followed for up to 6 months to determine the association with unplanned hospitalization/death. The Hospital Anxiety and Depression scale (HADS) was used as a screening tool as it is free of influence from somatic symptoms. Anxiety was diagnosed using the MINI. RESULTS:Of 304 patients, 17% of patients had anxiety by the MINI and 32% by the HADS. Anxious patients had lower health-related quality of life as assessed by the chronic liver disease questionnaire (P < 0.001) and EuroQol Visual Analogue Scale (P < 0.001), and also had higher levels of frailty using the Clinical Frailty score (P = 0.004). Multivariable analysis revealed smoking and three HADS subcomponents as independent predictors of anxiety. These were used to develop a rapid screening nomogram. CONCLUSION:A formal diagnosis of anxiety was made in approximately one in five patients with cirrhosis, and it was associated with worse HrQoL and frailty. The use of a 4-question nonsomatic symptom-based nomogram requires validation but is promising as a rapid screen for anxiety in cirrhosis.

Background: The substantial female hormone fluctuations associated with pregnancy and postpartum have been linked to a greater risk of developing depressive symptoms, particularly in high-risk women (HRW), i.e. those with histories of mood sensitivity to female hormone fluctuations. We have shown that glutamate (Glu) levels in the medial prefrontal cortex (MPFC) decrease during perimenopause, a period of increased risk of developing a major depressive episode. Our team has also demonstrated that percentage gray matter (%GM), another neural correlate of maternal brain health, decreases in the MPFC during pregnancy. Objective: To investigate MPFC Glu levels and %GM from late pregnancy up to 7 weeks postpartum in HRW and healthy pregnant women (HPW). Methods: Single-voxel spectra were acquired from the MPFC of 41 HPW and 22 HRW using 3- Tesla in vivo proton magnetic resonance spectroscopy at five different time points. Results: We observed a statistically significant interaction between time and group for the metabolite Glu, with Glu levels being lower for HRW during pregnancy and early postpartum (p<0.05). MPFC %GM was initially lower during pregnancy and then significantly increased over time in both groups (p<0.01). Conclusion: This investigation suggests that the vulnerability towards PPD is associated with unique fluctuations of MPFC Glu levels during pregnancy and early postpartum period. Our results also suggest that the decline in MPFC %GM associated with pregnancy seems to progressively recover over time. Further investigations are needed to determine the specific role that female hormones play on the physiological changes in %GM during pregnancy and postpartum.

Very little is known about maternal cerebral changes during pregnancy. Since there is an increased risk for major depression during pregnancy and postpartum, it is important to understand the structural and neurochemical changes that occur in the brain during pregnancy. Using proton magnetic resonance spectroscopy (H-1-MRS) (3 T field strength), glutamate (Glu) levels were measured in the medial prefrontal cortex (MPFC) of 21 healthy gravid subjects 2-3 weeks before their due date (6.74 +/- 1.39), and in 14 non-pregnant healthy controls during their follicular phase (8.53 +/- 1.55). Water quantified MPFC Glu levels were decreased in pregnant women (p < 0.01). We also observed a 13.9% decrease in percentage grey matter (%GM) (p < 0.01) in our MPFC voxel. As Glu is mostly found in GM, we repeated the statistical analysis after adjustment for %GM and found that the difference in Glu levels was no longer statistically significant when adjusted for %GM (p = 0.10). This investigation is the only systematic direct investigation of brain tissue composition and Glu levels in pregnant women. The main finding of this investigation is the decreased %GM in healthy pregnant women compared to non-pregnant women. These findings of decreased %GM in pregnancy may be responsible for the frequent complaints by pregnant women of cognitive difficulties also described as pregnesia.

OBJECTIVES:Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale - depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence. METHODS:We searched Medline, Medline In-Process & Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated. RESULTS:6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was -21.1% to 19.5%. CONCLUSIONS:HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview.

Estimates of depression prevalence in pregnancy and postpartum are based on the Edinburgh Postnatal Depression Scale (EPDS) more than on any other method. We aimed to determine if any EPDS cutoff can accurately and consistently estimate depression prevalence in individual studies.

OBJECTIVE:The Maternal Mental Health in Canada, 2018/2019, survey reported that 18% of 7,085 mothers who recently gave birth reported "feelings consistent with postpartum depression" based on scores ≥7 on a 5-item version of the Edinburgh Postpartum Depression Scale (EPDS-5). The EPDS-5 was designed as a screening questionnaire, not to classify disorders or estimate prevalence; the extent to which EPDS-5 results reflect depression prevalence is unknown. We investigated EPDS-5 ≥7 performance relative to major depression prevalence based on a validated diagnostic interview, the Structured Clinical Interview for DSM (SCID). METHODS:We searched Medline, Medline In-Process & Other Non-Indexed Citations, PsycINFO, and the Web of Science Core Collection through June 2016 for studies with data sets with item response data to calculate EPDS-5 scores and that used the SCID to ascertain depression status. We conducted an individual participant data meta-analysis to estimate pooled percentage of EPDS-5 ≥7, pooled SCID major depression prevalence, and the pooled difference in prevalence. RESULTS:A total of 3,958 participants from 19 primary studies were included. Pooled prevalence of SCID major depression was 9.2% (95% confidence interval [CI] 6.0% to 13.7%), pooled percentage of participants with EPDS-5 ≥7 was 16.2% (95% CI 10.7% to 23.8%), and pooled difference was 8.0% (95% CI 2.9% to 13.2%). In the 19 included studies, mean and median ratios of EPDS-5 to SCID prevalence were 2.1 and 1.4 times. CONCLUSIONS:Prevalence estimated based on EPDS-5 ≥7 appears to be substantially higher than the prevalence of major depression. Validated diagnostic interviews should be used to establish prevalence.

OBJECTIVES:A previous individual participant data meta-analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire-9. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum. METHODS:Data accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics. RESULTS:Among fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased. CONCLUSION:Different interviews may not classify major depression equivalently.

D-Serine is a potent co-agonist at the NMDA glutamate receptor and has been the object of many preclinical studies to ascertain the nature of its metabolism, its regional and cellular distribution in the brain, its physiological functions and its possible clinical relevance. The enzymes involved in its formation and catabolism are serine racemase (SR) and D-amino acid oxidase (DAAO), respectively, and manipulations of the activity of those enzymes have been useful in developing animal models of schizophrenia and in providing clues to the development of potential new antipsychotic strategies. Clinical studies have been conducted in schizophrenia patients to evaluate body fluid levels of D-serine and/or to use D-serine alone or in combination with antipsychotics to determine its effectiveness as a therapeutic agent. D-serine has also been used in combination with DAAO inhibitors in preclinical investigations, and interesting results have been obtained. Genetic studies and postmortem brain studies have also been conducted on D-serine and the enzymes involved in its metabolism. It is also of considerable interest that in recent years clinical and preclinical investigations have suggested that D-serine may also have antidepressant properties. Clinical studies have also shown that D-serine may be a biomarker for antidepressant response to ketamine. Relevant to both schizophrenia and depression, preclinical and clinical studies with D-serine indicate that it may be effective in reducing cognitive dysfunction.

Importance:A population-based study using validated algorithms to estimate the costs of treating people with chronic disease with and without mental health disorders is needed. Objective:To determine the association of mental health disorders with health care costs among people with chronic diseases. Design, Setting, and Participants:This population-based cohort study in the Canadian province of Alberta collected data from April 1, 2012, to March 31, 2015, among 991 445 adults 18 years and older with a chronic disease (ie, asthma, congestive heart failure, myocardial infarction, diabetes, epilepsy, hypertension, chronic pulmonary disease, or chronic kidney disease). Data analysis was conducted from October 2017 to August 2018. Exposures:Mental health disorder (ie, depression, schizophrenia, alcohol use disorder, or drug use disorder). Main Outcomes and Measures:Resource use, mean total unadjusted and adjusted 3-year health care costs, and mean total unadjusted 3-year costs for hospitalization and emergency department visits for ambulatory care-sensitive conditions. Results:Among 991 445 participants, 156 296 (15.8%) had a mental health disorder. Those with no mental health disorder were older (mean [SD] age, 58.1 [17.6] years vs 55.4 [17.0] years; P < .001) and less likely to be women (50.4% [95% CI, 50.3%-50.5%] vs 57.7% [95% CI, 57.4%-58.0%]; P < .001) than those with mental health disorders. For those with a mental health disorder, mean total 3-year adjusted costs were $38 250 (95% CI, $36 476-$39 935), and for those without a mental health disorder, mean total 3-year adjusted costs were $22 280 (95% CI, $21 780-$22 760). Having a mental health disorder was associated with significantly higher resource use, including hospitalization and emergency department visit rates, length of stay, and hospitalization for ambulatory care-sensitive conditions. Higher resource use by patients with mental health disorders was not associated with health care presentations owing to chronic diseases compared with patients without a mental health disorder (chronic disease hospitalization rate per 1000 patient days, 0.11 [95% CI, 0.11-0.12] vs 0.06 [95% CI, 0.06-0.06]; P < .001; overall hospitalization rate per 1000 patient days, 0.88 [95% CI, 0.87-0.88] vs 0.43 [95% CI, 0.43-0.43]; P < .001). Conclusions and Relevance:This study suggests that mental health disorders are associated with substantially higher resource utilization and health care costs among patients with chronic diseases. These findings have clinical and health policy implications.

OBJECTIVE:Two previous individual participant data meta-analyses (IPDMAs) found that different diagnostic interviews classify different proportions of people as having major depression overall or by symptom levels. We compared the odds of major depression classification across diagnostic interviews among studies that administered the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). METHODS:Data accrued for an IPDMA on HADS-D diagnostic accuracy were analysed. We fit binomial generalized linear mixed models to compare odds of major depression classification for the Structured Clinical Interview for DSM (SCID), Composite International Diagnostic Interview (CIDI), and Mini International Neuropsychiatric Interview (MINI), controlling for HADS-D scores and participant characteristics with and without an interaction term between interview and HADS-D scores. RESULTS:There were 15,856 participants (1942 [12%] with major depression) from 73 studies, including 15,335 (97%) non-psychiatric medical patients, 164 (1%) partners of medical patients, and 357 (2%) healthy adults. The MINI (27 studies, 7345 participants, 1066 major depression cases) classified participants as having major depression more often than the CIDI (10 studies, 3023 participants, 269 cases) (adjusted odds ratio [aOR] = 1.70 (0.84, 3.43)) and the semi-structured SCID (36 studies, 5488 participants, 607 cases) (aOR = 1.52 (1.01, 2.30)). The odds ratio for major depression classification with the CIDI was less likely to increase as HADS-D scores increased than for the SCID (interaction aOR = 0.92 (0.88, 0.96)). CONCLUSION:Compared to the SCID, the MINI may diagnose more participants as having major depression, and the CIDI may be less responsive to symptom severity.

Introduction The 30-item Geriatric Depression Scale (GDS-30) and the shorter GDS-15, GDS-5 and GDS-4 are recommended as depression screening tools for elderly individuals. Existing meta-analyses on the diagnostic accuracy of the GDS have not been able to conduct subgroup analyses, have included patients already identified as depressed who would not be screened in practice and have not accounted for possible bias due to selective reporting of results from only better-performing cut-offs in primary studies. Individual participant data meta-analysis (IPDMA), which involves a standard systematic review, then a synthesis of individual participant data, rather than summary results, could address these limitations. The objective of our IPDMA is to generate accuracy estimates to detect major depression for all possible cut-offs of each version of the GDS among studies using different reference standards, separately and among participant subgroups based on age, sex, dementia diagnosis and care settings. In addition, we will use a modelling approach to generate individual participant probabilities for major depression based on GDS scores (rather than a dichotomous cut-off) and participant characteristics (eg, sex, age, dementia status, care setting). Methods and analysis Individual participant data comparing GDS scores to a major depression diagnosis based on a validated structured or semistructured diagnostic interview will be sought via a systematic review. Data sources will include Medline, Medline In-Process & Other Non-Indexed Citations, PsycINFO and Web of Science. Bivariate random-effects models will be used to estimate diagnostic accuracy parameters for each cut-off of the different versions of the GDS. Prespecified subgroup analyses will be conducted. Risk of bias will be assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Ethics and dissemination The findings of this study will be of interest to stakeholders involved in research, clinical practice and policy. PROSPERO registration number CRD42018104329.

Summary Background Depression is associated with substantial morbidity and mortality in cirrhosis, but is underdiagnosed and undertreated. Aims Using the Mini International Neuropsychiatric Interview (MINI) as a gold‐standard, to determine prevalence, predictors, and outcomes of depression, and to develop a screening nomogram for use in cirrhosis patients. Methods Cirrhotic outpatients 18‐80 years of age, not on anti‐depressants, were consecutively recruited from liver clinics at three tertiary care hospitals. Baseline health‐related quality of life (HRQoL) and frailty were determined by the chronic liver disease questionnaire, EQ‐VAS, Clinical Frailty Scale and Fried Frailty Criteria. Depression was identified using the MINI and participants were followed up to 6 months to determine unplanned hospitalization/death. Results Of 305 patients, 62% were male; mean age 55(10) years; mean MELD 12.5(5), 61% Child Pugh B/C. Prevalence of depression 18% by MINI. Patients with depression had lower baseline HRQoL and higher frailty scores. Five independently predictive factors were used to develop a clinical nomogram for the diagnosis of clinical depression. These included three Hospital Anxiety and Depression Screening tool variables: “I have lost interest in my appearance” (adjusted odds ratio [aOR] 2.2, P = 0.006), “I look forward with enjoyment to things” (aOR 2.0, P = 0.02), “I feel cheerful” (aOR 2.8, P = 0.002), and two demographic variables: younger age (aOR 0.92, P = 0.001) and not being married or in a common‐law relationship (aOR 0.30, P = 0.008). Conclusions Depression is common in patients with cirrhosis. It has a significant impact on HRQoL and functional status. The developed clinical nomogram is promising for the rapid screening of depression in patients with cirrhosis.

The aim of this work was to study whether the dietary supplementation with arginine (Arg) and glutamine (Gln) or the combination of both influence the digestibility, body composition, and reproductive performance of rabbit does during the first three parturitions. A Control diet containing 29.8 g nitrogen (N), 313 g aNDFom per kg DM and 1.85 g digestible N/MJ digestible energy (DN/DE) was formulated, and another 3 diets were obtained by adding (g/kg) 4 Arg, 4 Gln and a mixture of 4 Arg and 4 of Gln to the Control diet. Eighty nulliparous rabbit does were randomly assigned to the diets (20/diet) before the first insemination. After each parturition litter size were homogenized within each treatment and does inseminated 11 d later. Chemical composition and energy content of rabbit does and their performance, litter growth and milk production were measured between birth and weaning (25 d) along three parturitions. Amino acid supplementation increased the DN content (P = 0.015) and tended to increase the DN/DE ratio compared to Control group (P = 0.077) leading to an increase of digestible N intake during lactation (P = 0.004). In this period, Gln group had a higher DE intake compared to Control and Arg + Gln groups (P = 0.038). Total number kits born per litter tended to increase in rabbit does supplemented with Arg and Gln, compared to Control and Arg + Gln groups (P = 0.095), but no effect of treatments on the number of weaned rabbits was observed (P = 0.15). Single supplementation of Arg and Gln increased the weight of the litters at 20 and 25 d respect to Control and Arg + Gln groups (P ≤ 0.021). Amino acid supplementation did not affect the milk production (P = 0.16), although it was positively correlated with the DE and DN intake (P < 0.001). There were no significant effects of treatments on body weight, chemical composition and energy content of rabbit does, but does supplemented with Arg or Gln tended to have a higher body energy content at the third insemination and at weaning than those from Control and Arg + Gln groups (P ≤ 0.099). Amino acid supplementation did not modify the replacement rate of rabbit does. In conclusion, the single supplementation of Arg and Gln had a positive effect on the weight of litters at weaning and litter size at birth, but no additive effect was observed for the combined supplementation of Arg and Gln.

IMPORTANCE:The incidence of depression in patients with head and neck cancer (HNC) is estimated to be as high as 40%. Previous studies have demonstrated an effect of depression on rehabilitation and survival in the posttreatment period. OBJECTIVE:To systematically review the relationship between depression and survival in patients with HNC undergoing curative treatment. EVIDENCE REVIEW:A search of electronic databases as well as gray literature was undertaken from January 1, 1974, to August 20, 2014, including MEDLINE (via Ovid), EMBASE (via Ovid), CINAHL, EBSCO, PsycINFO (via Ovid), Elsevier Scopus, and Institute for Scientific Information Web of Science Core Collection, using controlled vocabulary and medical subject headings representing HNC, depression, and survival. Articles in these databases were reviewed for inclusion by 2 independent reviewers according to predetermined eligibility criteria and were adjudicated by a third reviewer. The articles were then quantitatively scored using the GRACE (Good Research for Comparative Effectiveness) tool, a validated instrument for assessing the quality of observational studies. Qualitative assessment of each article was then undertaken. FINDINGS:A total of 654 references were retrieved across all databases. A review of the abstracts and full texts identified 3 articles, each describing a distinct, single study, including a total of 431 patients, that were eligible for analysis. Scores for the articles as assessed with the GRACE tool ranged from 9 to 11. In each of the 3 studies used in the analysis, the comparison groups were depressed and nondepressed patients as established by a standardized psychiatric assessment tool. Two of the 3 studies demonstrated a statistically significant difference in survival for patients with HNC and depression; however, a sensitivity analysis was not possible due to the incompatible statistical analyses performed in each study. CONCLUSIONS AND RELEVANCE:An association between depression and survival in patients with HNC is apparent; however, the strength and etiology of this association is not yet clear. Further directed and multi-institutional study is required to investigate this association and determine appropriate screening and management strategies.

Introduction The Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) has been recommended for depression screening in medically ill patients. Many existing HADS-D studies have used exploratory methods to select optimal cut-offs. Often, these studies report results from a small range of cut-off thresholds; cut-offs with more favourable accuracy results are more likely to be reported than others with worse accuracy estimates. When published data are combined in meta-analyses, selective reporting may generate biased summary estimates. Individual patient data (IPD) meta-analyses can address this problem by estimating accuracy with data from all studies for all relevant cut-off scores. In addition, a predictive algorithm can be generated to estimate the probability that a patient has depression based on a HADS-D score and clinical characteristics rather than dichotomous screening classification alone. The primary objectives of our IPD meta-analyses are to determine the diagnostic accuracy of the HADS-D to detect major depression among adults across all potentially relevant cut-off scores and to generate a predictive algorithm for individual patients. We are already aware of over 100 eligible studies, and more may be identified with our comprehensive search. Methods and analysis Data sources will include MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO and Web of Science. Eligible studies will have datasets where patients are assessed for major depression based on a validated structured or semistructured clinical interview and complete the HADS-D within 2 weeks (before or after). Risk of bias will be assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Bivariate random-effects meta-analysis will be conducted for the full range of plausible cut-off values, and a predictive algorithm for individual patients will be generated. Ethics and dissemination The findings of this study will be of interest to stakeholders involved in research, clinical practice and policy.

Introduction Studies of the diagnostic accuracy of depression screening tools often used data-driven methods to select optimal cut-offs. Typically, these studies report results from a small range of cut-off points around whatever cut-off score is identified as most accurate. When published data are combined in meta-analyses, estimates of accuracy for different cut-off points may be based on data from different studies, rather than data from all studies for each cut-off point. Thus, traditional meta-analyses may exaggerate accuracy estimates. Individual patient data (IPD) meta-analyses synthesise data from all studies for each cut-off score to obtain accuracy estimates. The 10-item Edinburgh Postnatal Depression Scale (EPDS) is commonly recommended for depression screening in the perinatal period. The primary objective of this IPD meta-analysis is to determine the diagnostic accuracy of the EPDS to detect major depression among women during pregnancy and in the postpartum period across all potentially relevant cut-off scores, accounting for patient factors that may influence accuracy (age, pregnancy vs postpartum). Methods and analysis Data sources will include Medline, Medline In-Process & Other Non-Indexed Citations, PsycINFO, and Web of Science. Studies that include a diagnosis of major depression based on a validated structured or semistructured clinical interview administered within 2 weeks of (before or after) the administration of the EPDS will be included. Risk of bias will be assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Bivariate random-effects meta-analysis will be conducted for the full range of plausible cut-off values. Analyses will evaluate data from pregnancy and the postpartum period separately, as well as combining data from all women in a single model. Ethics and dissemination This study does not require ethics approval. Dissemination will include journal articles and presentations to policymakers, healthcare providers and researchers. Systematic review registration PROSPERO 2015:CRD42015024785.

Background Head and neck cancer (HNC) is a debilitating disease due in part to its effects on function, including speech, swallowing, and cosmesis. Previous studies regarding depression in HNC have focused on demographic predictors, incidence, and quality of life studies. There is, however, a paucity of studies that objectively address depressive symptoms in HNC patients and the resultant effects on post-treatment functional performance status. The aim of this study was to assess the relationship between preoperative depressive symptoms (PDS) and postoperative functional performance status (PFPS), in addition to other predictors of rehabilitation and survival. Methods A prospective cohort study was undertaken at the University of Alberta, including all new adult HNC patients undergoing surgery as primary therapy for HNC from May 2013 to January 2014. Baseline depressive symptoms were measured on the Quick Inventory of Depressive Symptoms (QIDS) questionnaire 2 weeks preoperatively and PFPS was assessed 12 months postoperatively on the Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) scale. Secondary outcomes included completion of adjuvant therapy, narcotic dependence, return to detrimental habits, loss of follow-up, and length of hospital stay (LOHS). Differences between the Normal-Mild and Moderate-Severe QIDS groups were assessed using Mann–Whitney and Fischer Exact statistical analyses. Results Seventy-one patients were included in the study. Mild and Moderate-Severe PDS were 35.2 % and 18.3 %, respectively. Significantly lower FACT-HN scores were noted in the Moderate-Severe group at 12 months (p = 0.03). The risk ratio (RR) for FACT-HN score < 50 % at 12 months in the Moderate-Severe group was 5.66. In addition, significantly lower completion of adjuvant treatment (p = 0.03), significantly higher incidence of narcotic dependence (p = 0.004), and significantly higher LOHS (24 days vs. 18 days; p = 0.02) was observed in the Moderate-Severe group. There was no significant difference in loss of follow-up between the 2 groups (p = 0.64). Conclusions The incidence and severity of PDS in HNC patients treated with surgery is high (53.5 %). Patients with Moderate-Severe PDS have significantly decreased PFPS, increased narcotic use, decreased completion of adjuvant therapy, and a longer LOHS. HNC patients should be monitored closely for depressive symptoms.

Objectives:Depression in head and neck cancer (HNC) patients is undertreated and under‐recognized, yet has been shown to be present in up to 40% of patients. The objective in this study was to perform a systematic review of the literature regarding the optimal psychologic intervention for HNC patients with depressive symptomatology.Methods:A systematic review. PubMed, Medline, and ENCASE were searched in December 2013 for studies examining psychologic interventions in head and neck cancer patients. Results were screened by 2 independent reviewers. The level of evidence for each study and intervention were evaluated using criteria put forth by the Agency for Healthcare Research and Quality US Preventative Services Task Force. Subsequent analysis was then planned according to the criteria in the Cochrane Handbook for Systematic Reviews.Results:Eleven studies met inclusion criteria. Three studies were rated “good” for internal validity and 6 for external validity. Psychologic education and cognitive behavior therapy were evaluated by 8 studies, and antidepressant use was examined by 2 studies. Support group therapy was examined by 1 study. Meta‐analysis was precluded by significant heterogeneity. Strongest evidence for successful treatment of depression was demonstrated by psycho‐education.Conclusions:Evidence for the optimal psychologic intervention for depression in HNC patients is limited by the small number of studies examining treatment types, lack of high level of evidence in research methodology, and poor comparability of studies. Future studies should target a standardized assessment and diagnosis as well as evaluation of treatment type.

The medial prefrontal cortex (MPFC) is a key brain area in depressive symptomatology; specifically, glutamate (Glu) has been reported to play a significant role in major depression (MD) in this area. MPFC Glu levels are sensitive to ovarian hormone fluctuations and pregnancy and the postpartum period are associated with the most substantial physiological alterations of female hormones. It is therefore logical to measure MPFC Glu levels in women with postpartum depression (PPD). Using in vivo magnetic resonance spectroscopy (MRS) at a field strength of 3 T, we acquired single-voxel spectra from the MPFC of 12 women with PPD and 12 healthy controls (HCs) matched for postpartum scan timing. Water-referenced MPFC Glu levels were measured using a MRS technique that allowed us to be specific for Glu with very little glutamine contamination. The concentrations of other water-quantified brain metabolites such as glycerophosphorylcholine plus phosphorylcholine, N-acetylaspartate (NAA), and creatine plus phosphocreatine were measured in the same MR spectra. MPFC Glu levels were higher in women with PPD (7.21±1.20) compared to matched HCs (6.04±1.21). There were no differences between groups for other brain metabolites measured. These findings suggest an association between Glu dysregulation in the MPFC and PPD. Whether the pathophysiology of PPD differs from the pathophysiology of MD remains to be determined. Further investigations are needed to determine the chronological associations between the occurrence of symptoms of PPD and the onset of changes in MPFC Glu levels.

Neuroactive steroids (NASs) are rapid acting steroids that produce nongenomic effects through interactions with neurotransmitter receptors, Although research on NASs has focused on their actions as negative or positive allosteric modulators at GABA A receptors, there can also be interactions with other receptors, including glutamate receptors, 5-HT3 receptors, nicotinic receptors, sigma 1 receptors and voltage-or non-voltage-gated calcium channels. Recent studies in animal models and in humans have investigated the role of NASs, including pregnenolone, pregnenolone sulfate, dehydroepiandrosterone, dehydroepiandrosterone sulfate, progesterone, and a number of 3 alpha-reduced NASs (e.g. allopregnanolone, 5-alpha-dihydroprogesterone, 3 alpha,5 alpha-tetrahydroprogesterone, 3 alpha,5 alpha-tetrahydrodeoxycorticosterone) in depressive disorders. Although inconsistencies exist, alterations in levels of these NASs have been reported to be associated with major depressive disorder, postpartum depression, and premenstrual dysphoric disorder. In some cases, the actions of the NASs may involve interactions with brain-derived neurotrophic factor (BDNF) and/or the hypothalamic-pituitary-adrenal (HPA) axis. Antidepressant drugs have been shown to have effects on the levels and/or metabolism of NASs, and some NASs have been reported to have antidepressant effects in their own right after administration to animal models or humans. Although interactions appear to be complex, increasing evidence substantiates the importance of NASs in the pathophysiology and treatment of depressive disorders, and research in this area is reviewed in this paper.