The Third Reviewer

Background: Cerebrovascular disease plays an important role in depressive disorder, especially in older adults. An understanding of vascular function in depression is important etiologically and to develop innovative treatments that may improve prognosis by ameliorating vascular damage.Methods: This study assessed endothelial function, arterial stiffness, and atherosclerosis in a variety of vessel beds in 25 elderly subjects with depressive disorder compared with 21 nondepressed control subjects. Subjects underwent pulse wave velocity, pulse wave analysis, carotid intima media thickness analysis, and magnetic resonance imaging. A subset (16 patients and 15 control subjects) had assessment of biopsied small artery dilatation to acetylcholine to further assess endothelial function.Results: The mean sample age was 72.4 years with an average age at onset for depression of 60 years. Mean carotid intima media thickness was significantly higher in depressed subjects (p < .01). Pulse wave velocity was 1.6 m/sec higher in depressed subjects (borderline significance). There was a significant reduction in the dilatation response to acetylcholine in preconstricted small arteries (p = .01). On magnetic resonance imaging, depressed subjects had significantly more dilated Virchow–Robin spaces in the basal ganglia (p = .01). Depressed subjects had greater volume of white matter lesions in all regions, but this did not reach statistical significance. There were no baseline differences in vascular risk.Conclusions: Depression in the elderly is associated with poorer endothelial function and more atherosclerosis. This is associated with a greater white matter hyperintensities lesion load and basal ganglia microangiopathy. The use of vasoprotective drugs to improve endothelial function or retard atherosclerosis as depression-modifying agents should be explored. . . . → Read More: Vascular Function in Older Adults with Depressive Disorder

For centuries, poets and folklore have asserted a relation between the heart (vascular system) and depression. The common metaphor of a “broken heart” is a symbol of the recognition of the link, and in fact “broken heart syndrome,” also called … . . . → Read More: Fish Oil, Blood Vessels, and Depression

We appreciate the comments of Dr. Fountoulakis on our study of electroretinogram (ERG) response in young nonaffected offspring at high risk to develop a psychiatric disorder (). The comments give us an opportunity to discuss the important methodologica… . . . → Read More: Important Differences in Methodology and Reliability of the Electro-oculogram and the Electroretinogram in Psychiatric Research

Recently, an article by Hebert et al. () reported a rod retinal response anomaly in high-risk offspring of patients with schizophrenia or bipolar disorder. These authors reported significant results mainly concerning the rod b-wave amplitude but only a… . . . → Read More: Retinal Response Anomalies in Patients with Mental Illness and High Risk Relatives

Background: The three-way interaction between the functional polymorphism in the serotonin transporter gene linked promoter region, the val66met polymorphism in the brain-derived neurotrophic factor gene, and childhood adversity in the prediction of de… . . . → Read More: Interaction Between Childhood Adversity, Brain-Derived Neurotrophic Factor val/met and Serotonin Transporter Promoter Polymorphism on Depression: The TRAILS Study

Background: Lipids appear to mediate depressive vulnerability in the elderly; however, sex differences and genetic vulnerability have not been taken into account in previous prospective studies.Methods: Depression was assessed in a population of 1040 w… . . . → Read More: Gender and Genotype Modulation of the Association Between Lipid Levels and Depressive Symptomatology in Community-Dwelling Elderly (The ESPRIT Study)

Bewernick et al. () demonstrated the antidepressant and antianxiety effects of deep brain stimulation (DBS) to the nucleus accumbens (NAc) in patients suffering from treatment-resistant depression. Deep brain stimulation has also been proposed in the m… . . . → Read More: Hypomania Following Bilateral Ventral Capsule Stimulation in a Patient with Refractory Obsessive-Compulsive Disorder

Background: Serotonin 1A receptors (5-HT1A) are implicated in major depressive disorder (MDD). We previously reported higher 5-HT1A binding potential (BPF) in antidepressant naive MDD subjects compared with control subjects, while other studies report … . . . → Read More: Higher Serotonin 1A Binding in a Second Major Depression Cohort: Modeling and Reference Region Considerations

Background: Major depressive disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available.Methods: We used a classifier approach on blood gene expressio… . . . → Read More: Stimulated Gene Expression Profiles as a Blood Marker of Major Depressive Disorder

Background: Depression has a strong genetic component but candidate gene studies conducted to date have not shown consistent associations.Methods: We conducted a genome-wide parametric and nonparametric linkage analysis in a large-scale family-based st… . . . → Read More: A Genome-Wide Screen for Depression in Two Independent Dutch Populations

Background: On the basis of evidence from studies showing the antidepressant effects of omega-3 polyunsaturated fatty acids and the inverse relation between fish consumption and the prevalence of depression, the phospholipid hypothesis seems promising … . . . → Read More: A Meta-Analytic Review of Polyunsaturated Fatty Acid Compositions in Patients with Depression

Background: Previous studies have provided somewhat inconsistent results about the effects of season of birth on the risk of suicidal behavior. Therefore, we decided to investigate this question in a large sample of suicide completers.Methods: We determined the season of birth-associated risk of completed suicide between the years 1970 and 2008 among all individuals who were born in the area of today’s Hungary between 1930 and 1939, 1941 and 1942, and 1944 and 1969.Results: The final sample of participants included around six and a half million people. About 80,000 completed suicides occurred among participants during the period investigated (the number of suicide completers in our study greatly exceeds the number of suicide completers in any previous studies). A significantly (p < .05) elevated risk of completed suicide was found among those individuals who were born in the high-risk period (spring and summer). Quantitatively, the biggest increase (7.6% [95% confidence interval: 5.4–9.9]) in suicide risk was detected among those who were born in July compared with the average risk of suicide in the population investigated. The associations between season of birth and the risk of completed suicide were stronger among male subjects than among female subjects and among those who committed suicide using violent methods than among those who chose nonviolent methods.Conclusions: Our results from a large sample of suicide completers from Hungary—a country with one of the highest suicide rates in the world over the last century—strongly support the concept that the season of birth is significantly associated with the risk of completed suicide. . . . → Read More: Season of Birth Is Significantly Associated with the Risk of Completed Suicide

Background: The limbic system-associated membrane protein (LAMP) promotes development of neurons of limbic origin. We have previously shown that genetic deletion of LAMP results in heightened reactivity to novelty and reduced anxiety-like behaviors in … . . . → Read More: Loss of Limbic System-Associated Membrane Protein Leads to Reduced Hippocampal Mineralocorticoid Receptor Expression, Impaired Synaptic Plasticity, and Spatial Memory Deficit

Background: Approximately 30% of patients with depression are resistant to antidepressant drugs. Repetitive transcranial magnetic stimulation (rTMS) has been found effective in combination with antidepressants in this patient group. The aim of this stu… . . . → Read More: Transcranial Low Voltage Pulsed Electromagnetic Fields in Patients with Treatment-Resistant Depression

Background: Everyday language relates depressed mood to visual phenomena. Previous studies point to a reduced sensitivity of subjective contrast perception in depressed patients. One way to assess visual contrast perception in an objective way at the l… . . . → Read More: Seeing Gray When Feeling Blue? Depression Can Be Measured in the Eye of the Diseased

Depression is a complex and heterogeneous disorder whose cause is poorly understood. Theories on the mechanisms of the disease have often focused on either its neurobiology or its cognitive and behavioral manifestations. Recently, studies exploring how… . . . → Read More: Reward and Punishment Processing in Depression

Background: Treatment adherence is a significant problem in patients with bipolar disorder. This study was designed to determine the efficacy of risperidone long-acting injectable (LAI) in the maintenance treatment of bipolar I disorder.Methods: Eligible patients with current or recent manic or mixed episodes (n = 559, aged 18–65 years) were treated with open-label oral risperidone for 3 weeks (period II) and open-label risperidone LAI for 26 weeks (n = 501; period III). Patients who maintained response (n = 303) were randomly allocated 1:1 to placebo injections (n = 149) or to continue risperidone LAI (n = 154) for up to 24 months (period IV).Results: Most (77%) patients on risperidone LAI received a dose of 25 mg every 2 weeks during period IV. Time to recurrence for any mood episode (primary outcome variable) was significantly longer in the risperidone LAI group versus placebo (p < .001); the difference was significant for time to recurrence of elevated-mood episode (p < .001) but not time to recurrence of depressive episode (p = .805). Weight gains ?7% (compared with the period’s baseline) occurred in 15% of patients in period III; in 12% of patients on risperidone LAI and 3% of patients on placebo in period IV.Conclusions: Risperidone LAI monotherapy significantly delayed the time to recurrence of mood episodes, versus placebo, in this controlled, randomized study in patients with bipolar I disorder. Risperidone LAI was tolerable and no new safety concerns emerged compared with previous studies of risperidone LAI. . . . → Read More: Risperidone Long-Acting Injectable Monotherapy in the Maintenance Treatment of Bipolar I Disorder