Guest Commentary by Roger S. McIntyre
- Repeated Tetrahydrocannabinol Exposure in Adolescent Monkeys: Persistent Effects Selective for Spatial Working Memory
- Structural Brain Development and Depression Onset During Adolescence: A Prospective Longitudinal Study
- Randomized Trial of Electronic Personal Health Record for Patients with Serious Mental Illnesses
- Antidepressant Effects of Insulin in Streptozotocin Induced Diabetic Mice: Modulation of Brain Serotonin System
- Castelli Risk Indexes 1 and 2 are Higher in Major Depression but Other Characteristics of the Metabolic Syndrome are Not Specific to Mood Disorders
Am J Psychiatry. 2014;171:416-425.
The authors sought to determine whether 6 months of repeated intravenous THC administration compared with vehicle would result in 1) persistent adverse effects on performance improvement on spatial versus object working memory tasks and 2) ultra-sensitivity to the acute effects of THC on these tasks.
These intriguing findings provide powerful support for adolescent cannabis use as a risk factor for cognitive dysfunction. The deficits that were identified were selective for spatial memoranda and are persistent beyond the period of exposure.
The percentage of high school students reporting cannabis use in the past 12 months was higher than the percentage who reported alcohol use in several recent studies. Clinicians frequently encounter patients who complain of cognitive difficulties across the transnosological spectrum (e.g., schizophrenia, bipolar disorder, major depressive disorder). During the last five years, legitimate access to marijuana has been increasing in many countries and jurisdictions. Clinicians are often asked to address the risks associated with cannabis use in their patients. The data herein suggests that repeat exposure to cannabinoids exerts a detrimental effect that persists on selective measures of cognition.
Whittle S, Lichter R, Dennison M, et al.
Am J Psychiatry. 2014 Feb 28.
The aim of this study was to investigate whether the development of limbic and striatal volumes and prefrontal cortical thickness from early to mid-adolescence was associated with the onset of depressive disorders. The hypothesis was that adolescent onset depression was subserved by an abnormal developmental trajectory.
This is the first study to use a longitudinal design to assess whether structural development of the brain is associated with incident depression during adolescence. The authors determined that the normative pattern of change in the hippocampus, putamen and amygdala volumes for ages 12-16 was associated with incident depression. No association in development between prefrontal cortex thickness and depression was noted. This study underscores the complex relationship between neural development, sex and vulnerability to depression in adolescence. The changes observed herein were captured with longitudinal change measurement, which is a methodological improvement over extant studies.
Mood disorders are conceptualized along a developmental trajectory. Clinicians frequently encounter adolescents presenting with behavioural, affective and cognitive disturbances that interfere with functioning and result in significant interpersonal distress. The results of this study indicate for the first time that longitudinal changes can be identified in selective regions of interest before the declaration of the brain disorder. It is widely agreed that the health outcomes in psychiatric disorders are greater when accurate and timely detection occurs thwarting unnecessary illness progression. For myself as a clinician, these data provide an important piece of psychoeducation information for younger patients, underscoring that depressive disorders are brain disorders that are possibly progressive in some people. For many patients and families, but not all, the understanding of depression as a brain disorder mitigates against stigma, self-blame, and guilt. It is also hoped that destigmatization of the underlying causation of depression will enhance patient and family alliance with the multidisciplinary healthcare team, which is essential for optimal outcome.
Druss BG, Gi S, Glick G, et al.
Am J Psychiatry. 2014;171:360-368.
The authors sought to determine with a randomized trial design whether a mental health personal health record in a sample of patients with serious mental illness and comorbid medical disorders resulted in a better outcome than a control group. The overarching aim of this initiative is to facilitate improved health outcomes across both mental and physical domains that affect individuals with serious mental illness.
In this sample of adults with serious mental illness and comorbid medical disorders, a personal health record was associated with improved quality of preventative care and cardiometabolic care. The exchange of health information across providers along with patient portals increased the probability that care would be synchronized with clinical and laboratory data.
The results of this randomized and thoughtful study are highly relevant to the comprehensive management of adults with severe mental disorders and comorbid medical conditions. It has been amply documented that individuals with serious mental disorder are differentially affected by cardiometabolic and other non-communicable and communicable disorders. Convergent evidence also indicates that the occurrence of medical comorbidity complicates the psychiatric presentation and decreases overall health outcomes. Mortality studies indicate that the most common cause of excess and premature mortality in adults with serious illness is excess cardiometabolic disorders. Academic studies have provided compelling evidence that multidisciplinary, integrated, and accountable care improves value outcomes. Unfortunately, because of the balkanization of most health care systems, access to integrated units of care is not available to many individuals. The strategy herein, i.e. a personal health record with multi-provider access and patient portal, significantly improves disparate measures of health outcomes. These data underscore the importance of patient self-management in chronic disease and provide an important vehicle to complement multidisciplinary care toward the fundamental aim of improving outcome.
Gupta D, Kurhe Y, Radhakrishnan M.
Physiology & Behaviour. 2014;129:73-78.
The primary aim of this preclinical study was to determine if insulin modulated serotonin signaling in an animal model for depression. The impetus for this study is provided by the cross-sectional and longitudinal literature documenting a bidirectional relationship between mood disorders and diabetes mellitus.
These animal data provide a mechanistic understanding for the association between mood disorders and diabetes. Diabetic rats exhibit a significant decrease in central serotonin and increase MAO-A and MAO-B activity. This collection of observations could provide partial explanation for the increased susceptibility to depressive-like behavioural manifestations in animals rendered diabetic.
Clinicians often encounter patients with depression and diabetes. These preclinical data replicate previous results underscoring the cross-talk between peripheral metabolism and brain neurochemistry. To achieve optimal outcomes in depression in an adult with comorbid diabetes, it is absolutely essential that diabetes management receive contemporaneous management with the mental health aspects. It is widely reported that insufficient attention to concurrent medical disorders, e.g. diabetes, in an adult with depression results in higher rates of non-recovery, chronicity of depression, as well as adverse diabetic outcomes. The take-away message is holistic, multidimensional care is not only a principal but is now embroidered by scientific data documenting the cross-talk between brain and body.
Vargas HB, Nunes SO, Barbosa DS, et al.
Life Sci. 2014;102(1):65-71.
The authors sought to delineate whether Castelli risk indexes 1 and 2 are biomarkers of major depression or bipolar disorder, and whether biomarkers of the metabolic syndrome (i.e., lipid profile, increased insulin, glucose, HbA1c) are characteristics of major depression or bipolar disorder.
The major finding of this study is that major depression, but not bipolar disorder, is characterized by increased Castelli risk indices 1 and 2, which are more powerful coronary risk predictors than total cholesterol or HDL used separately. The implication of these findings is that major depressive disorder may increase atherogenic risk to a greater extent that bipolar disorder.
Psychiatry is increasingly pressing the point that personalized care is warranted. In the absence of biological markers, clinicians are unable to provide bespoke medical approaches and instead are providing for patients a more stratified approach. These data remind us that patients with mood disorders are at elevated risk for cardiometabolic disorders, but add to our knowledge by suggesting that the atherogenic risk, as proxied by the Castelli risk indices, may be higher in major depression than bipolar disorder. If these results are replicated, the clinical translation would be that amplified attention to traditional and emerging risk factor for cardiovascular disease is warranted for all individuals with mood disorders, perhaps to a greater extent those with major depression.