Rebecca Anglin

Vitamin D deficiency and depression in adults: systematic review and meta-analysis

BACKGROUND There is conflicting evidence about the relationship between vitamin D deficiency and depression, and a systematic assessment of the literature has not been available. AIMS To determine the relationship, if any, between vitamin D deficiency and depression. METHOD A systematic review and meta-analysis of observational studies and randomised controlled trials was conducted. RESULTS One case-control study, ten cross-sectional studies and three cohort studies with a total of 31 424 participants were analysed. Lower vitamin D levels were found in people with depression compared with controls (SMD = 0.60, 95% CI 0.23-0.97) and there was an increased odds ratio of depression for the lowest v. highest vitamin D categories in the cross-sectional studies (OR = 1.31, 95% CI 1.0-1.71). The cohort studies showed a significantly increased hazard ratio of depression for the lowest v. highest vitamin D categories (HR = 2.21, 95% CI 1.40-3.49). CONCLUSIONS Our analyses are consistent with the hypothesis that low vitamin D concentration is associated with depression, and highlight the need for randomised controlled trials of vitamin D for the prevention and treatment of depression to determine whether this association is causal.

Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis.

OBJECTIVES:There is emerging concern that selective serotonin reuptake inhibitors (SSRIs) may be associated with an increased risk of upper gastrointestinal (GI) bleeding, and that this risk may be further increased by concurrent use of nonsteroidal anti-inflammatory (NSAID) medications. Previous reviews of a relatively small number of studies have reported a substantial risk of upper GI bleeding with SSRIs; however, more recent studies have produced variable results. The objective of this study was to obtain a more precise estimate of the risk of upper GI bleeding with SSRIs, with or without concurrent NSAID use.METHODS:MEDLINE, EMBASE, PsycINFO, the Cochrane central register of controlled trials (through April 2013), and US and European conference proceedings were searched. Controlled trials, cohort, case–control, and cross-sectional studies that reported the incidence of upper GI bleeding in adults on SSRIs with or without concurrent NSAID use, compared with placebo or no treatment were included. Data were extracted independently by two authors. Dichotomous data were pooled to obtain odds ratio (OR) of the risk of upper GI bleeding with SSRIs +/− NSAID, with a 95% confidence interval (CI). The main outcome and measure of the study was the risk of upper GI bleeding with SSRIs compared with placebo or no treatment.RESULTS:Fifteen case–control studies (including 393,268 participants) and four cohort studies were included in the analysis. There was an increased risk of upper GI bleeding with SSRI medications in the case–control studies (OR=1.66, 95% CI=1.44,1.92) and cohort studies (OR=1.68, 95% CI=1.13,2.50). The number needed to harm for upper GI bleeding with SSRI treatment in a low-risk population was 3,177, and in a high-risk population it was 881. The risk of upper GI bleeding was further increased with the use of both SSRI and NSAID medications (OR=4.25, 95% CI=2.82,6.42).CONCLUSIONS:SSRI medications are associated with a modest increase in the risk of upper GI bleeding, which is lower than has previously been estimated. This risk is significantly elevated when SSRI medications are used in combination with NSAIDs, and physicians prescribing these medications together should exercise caution and discuss this risk with patients.

The Psychiatric Manifestations of Mitochondrial Disorders: A Case and Review of the Literature

OBJECTIVE Mitochondrial disorders are caused by gene mutations in mitochondrial or nuclear DNA and affect energy-dependent organs such as the brain. Patients with psychiatric illness, particularly those with medical comorbidities, may have primary mitochondrial disorders. To date, this issue has received little attention in the literature, and mitochondrial disorders are likely underdiagnosed in psychiatric patients. DATA SOURCES This article describes a patient who presented with borderline personality disorder and treatment-resistant depression and was ultimately diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) 3271. We also searched the literature for all case reports of patients with mitochondrial disorders who initially present with prominent psychiatric symptoms by using MEDLINE (from 1948-February 2011), Embase (from 1980-February 2011), PsycINFO (from 1806-February 2011), and the search terms mitochondrial disorder, mitochondria, psychiatry, mental disorders, major depression, anxiety, schizophrenia, and psychosis. STUDY SELECTION Fifty cases of mitochondrial disorders with prominent psychiatric symptomatology were identified. DATA EXTRACTION Information about the psychiatric presentation of the cases was extracted. This information was combined with our case, the most common psychiatric manifestations of mitochondrial disorders were identified, and the important diagnostic and treatment implications for patients with psychiatric illness were reviewed. RESULTS The most common psychiatric presentations in the cases of mitochondrial disorders included mood disorder, cognitive deterioration, psychosis, and anxiety. The most common diagnosis (52% of cases) was a MELAS mutation. Other genetic mitochondrial diagnoses included polymerase gamma mutations, Kearns-Sayre syndrome, mitochondrial DNA deletions, point mutations, twinkle mutations, and novel mutations. CONCLUSIONS Patients with mitochondrial disorders can present with primary psychiatric symptomatology, including mood disorder, cognitive impairment, psychosis, and anxiety. Psychiatrists need to be aware of the clinical features that are indicative of a mitochondrial disorder, investigate patients with suggestive presentations, and be knowledgeable about the treatment implications of the diagnosis.

The mitochondrial genome and psychiatric illness

Psychiatric disorders are a leading cause of morbidity and mortality, yet their underlying pathophysiology remains unclear. Searches for a genetic cause of bipolar disorder, schizophrenia, and major depressive disorder have yielded inconclusive results. There is increasing interest in the possibility that defects in the mitochondrial genome may play an important role in psychiatric illness. We undertook a review of the literature investigating mitochondria and adult psychiatric disorders. MEDLINE, PsycINFO, and EMBASE were searched from their inception through September 2011, and the reference lists of identified articles were reviewed for additional studies. While multiple lines of evidence, including clinical, genetic, ultrastructural, and biochemical studies, support the involvement of mitochondria in the pathophysiology of psychiatric illness, many studies have methodological limitations and their findings have not been replicated. Clinical studies suggest that psychiatric features can be prominent, and the presenting features of mitochondrial disorders. There is limited but inconsistent evidence for the involvement of mitochondrial DNA haplogroups and mitochondria‐related nuclear gene polymorphisms, and for mitochondrial ultrastructural and biochemical abnormalities in psychiatric illness. The current literature suggests that mitochondrial dysfunction and mitochondrial genetic variations may play an important role in psychiatric disorders, but additional methodologically rigorous and adequately powered studies are needed before definitive conclusions can be drawn.

The Psychiatric Presentation of Mitochondrial Disorders in Adults

Although comorbid psychiatric illness is increasingly being recognized in patients with mitochondrial disorders, there has been relatively little attention to psychiatric symptomatology as the primary clinical presentation. The authors report detailed clinical, biochemical, neuroradiological, and genetic findings in a series of 12 patients with mitochondrial disorders in whom psychiatric symptoms were a prominent aspect of the clinical presentation. The psychiatric presentations included depression, anorexia nervosa, bipolar disorder, and obsessive-compulsive disorder. A review of the literature, in conjunction with the present series, indicates that psychiatric symptoms can be the presenting feature of mitochondrial disorders and highlights the importance of considering this diagnosis.

Testosterone suppression in opioid users: A systematic review and meta-analysis ☆

BACKGROUND Whether used for pain management or recreation, opioids have a number of adverse effects including hormonal imbalances. These imbalances have been reported to primarily involve testosterone and affect both males and females to the point of interfering with successful treatment and recovery. We conducted a systematic review and meta-analysis to determine the extent that opioids affect testosterone levels in both men and women, which may be relevant to improved treatment outcomes for opioid dependence and for pain management. METHODS We searched PubMed, EMBASE, PsycINFO, and CINAHL for relevant articles and included studies that examined testosterone levels in men and women while on opioids. Data collection was completed in duplicate. RESULTS Seventeen studies with 2769 participants (800 opioid users and 1969 controls) fulfilled the review inclusion criteria; 10 studies were cross-sectional and seven were cohort studies. Results showed a significant difference in mean testosterone level in men with opioid use compared to controls (MD=-164.78; 95% CI: -245.47, -84.08; p<0.0001). Methadone did not affect testosterone differently than other opioids. Testosterone levels in women were not affected by opioids. Generalizability of results was limited due to high heterogeneity among studies and overall low quality of evidence. CONCLUSIONS Our findings demonstrated that testosterone level is suppressed in men with regular opioid use regardless of opioid type. We found that opioids affect testosterone levels differently in men than women. This suggests that opioids, including methadone, may have different endocrine disruption mechanisms in men and women, which should be considered when treating opioid dependence.

Sex differences in outcomes of methadone maintenance treatment for opioid addiction: a systematic review protocol

BackgroundUse of methadone for the treatment of opioid addiction is an effective harm-reduction approach, although variability in treatment outcomes among individuals has been reported. Men and women with opioid addiction have been known to differ in factors such as opioid use patterns and characteristics at treatment entry; however, little has been reported about differences in methadone treatment outcomes between men and women. Therefore, we present a protocol for a systematic review which aims to provide a summary of existing literature on sex differences in outcomes of methadone treatment for opioid addiction.Methods/DesignElectronic search of PubMed/MEDLINE, EMBASE, PsycINFO, and CINAHL databases will be conducted using a priori defined search strategy. Two authors (MB and BBD) will independently screen potential articles for eligibility using pre-determined inclusion and exclusion criteria and extract key information using a data extraction form designed for this study. Discrepancies will be resolved using a third party (ZS). The primary outcome will be sex differences in response to treatment defined as abstinence from illicit opioid use. We will also assess sex differences in treatment outcomes including treatment retention, remission status post-treatment, polysubstance abuse, methadone dose, drug-related adverse events, health status, psychological status, mortality, criminal activity, high risk sexual behavior, social support/relations, and employment. A meta-analysis will be conducted if possible; risk of bias and overall quality of evidence will be assessed to determine confidence in the estimates.DiscussionWe anticipate that this review will highlight how men and women differ in methadone treatment outcomes and allow us to generate conclusions that can be applied to treatment in a clinical setting.Systematic review registrationPROSPERO CRD42013006549

Neuroleptic malignant syndrome: a neuroimmunologic hypothesis

Neuroleptic malignant syndrome is a fulminant and life-threatening toxidrome that occurs in an estimated 0.07% to 3.23% of patients treated with antipsychotic medication.[1][1],[2][2] Patients typically present with fever, rigidity, changes in mental status and autonomic instability, often after the

Methadone induces testosterone suppression in patients with opioid addiction

Sex hormones may have a role in the pathophysiology of substance use disorders, as demonstrated by the association between testosterone and addictive behaviour in opioid dependence. Although opioid use has been found to suppress testosterone levels in men and women, the extent of this effect and how it relates to methadone treatment for opioid dependence is unclear. The present multi-centre cross-sectional study consecutively recruited 231 patients with opioid dependence from methadone clinics across Ontario, Canada between June and December of 2011. We obtained demographic details, substance use, psychiatric history, and blood and urine samples from enrolled subjects. The control group included 783 non-opioid using adults recruited from a primary care setting in Ontario, Canada. Average testosterone level in men receiving methadone treatment was significantly lower than controls. No effect of opioids including methadone on testosterone level in women was found and testosterone did not fluctuate significantly between menstrual cycle phases. In methadone patients, testosterone level was significantly associated with methadone dose in men only. We recommend that testosterone levels be checked in men prior and during methadone and other opioid therapy, in order to detect and treat testosterone deficiency associated with opioids and lead to successful methadone treatment outcomes.

Psychiatric symptoms correlate with metabolic indices in the hippocampus and cingulate in patients with mitochondrial disorders

There is increasing recognition that mitochondrial dysfunction may have a critical role in the pathophysiology of major psychiatric illnesses. Patients with mitochondrial disorders offer a unique window through which we can begin to understand the association between psychiatric symptoms and mitochondrial dysfunction in vivo. Using proton magnetic resonance spectroscopy (1H-MRS), we investigated metabolic indices in mitochondrial patients in regions of the brain that have been implicated in psychiatric illness: the caudate, cingulate cortex and hippocampus. In all, 15 patients with mitochondrial disorders and 15 age- and sex-matched controls underwent a comprehensive psychiatric assessment, including the administration of standardized psychiatric rating scales, followed by single voxel 1H-MRS of the caudate, cingulate cortex and hippocampus to measure N-acetyl aspartate (NAA), creatine (Cr), glycerophosphocholine (GPC), myoinositol and glutamate+glutamine (Glx). Pearson’s correlation coefficients were used to determine correlations between metabolites and the psychiatric rating scales. Anxiety symptoms in these patients correlated with higher GPC, Glx, myoinositol and Cr in the hippocampus. Impaired level of function as a result of psychiatric symptoms correlated with higher Glx and GPC in the cingulate cortex. In summary, we found remarkably consistent, and statistically significant, correlations between anxiety and metabolic indices in the hippocampus in patients with mitochondrial disorders, while overall impairment of functioning due to psychiatric symptoms correlated with metabolic markers in the cingulate cortex. These findings lend support to the notion that mitochondrial dysfunction in specific brain regions can give rise to psychiatric symptoms. In particular, they suggest that metabolic processes in the hippocampus may have an important role in the neurobiology of anxiety.