Placental Serotonin: Implications for the Developmental Effects of SSRIs and Maternal Depression.

Placental serotonin: implications for the developmental effects of SSRIs and maternal depression.

Front Cell Neurosci. 2013; 7: 47
Velasquez JC, Goeden N, Bonnin A

In addition to its role in the pathophysiology of numerous psychiatric disorders, increasing evidence points to serotonin (5-HT) as a crucial molecule for the modulation of neurodevelopmental processes. Recent evidence indicates that the placenta is involved in the synthesis of 5-HT from maternally derived tryptophan (TRP). This gives rise to the possibility that genetic and environmental perturbations directly affecting placental TRP metabolism may lead to abnormal brain circuit wiring in the developing embryo, and therefore contribute to the developmental origin of psychiatric disorders. In this review, we discuss how perturbations of the placental TRP metabolic pathway may lead to abnormal brain development and function throughout life. Of particular interest is prenatal exposure to maternal depression and antidepressants, both known to alter fetal development. We review existing evidence on how antidepressants can alter placental physiology in its key function of maintaining fetal homeostasis and have long-term effects on fetal forebrain development. HubMed – depression

 

D-serine as a gliotransmitter and its roles in brain development and disease.

Front Cell Neurosci. 2013; 7: 39
Horn MR, Sild M, Ruthazer ES

The development of new techniques to study glial cells has revealed that they are active participants in the development of functional neuronal circuits. Calcium imaging studies demonstrate that glial cells actively sense and respond to neuronal activity. Glial cells can produce and release neurotransmitter-like molecules, referred to as gliotransmitters, that can in turn influence the activity of neurons and other glia. One putative gliotransmitter, D-serine is believed to be an endogenous co-agonist for synaptic N-methyl-D-aspartate receptors (NMDARs), modulating synaptic transmission and plasticity mediated by this receptor. The observation that D-serine levels in the mammalian brain increase during early development, suggests a possible role for this gliotransmitter in normal brain development and circuit refinement. In this review we will examine the data that D-serine and its associated enzyme serine racemase are developmentally regulated. We will consider the evidence that D-serine is actively released by glial cells and examine the studies that have implicated D-serine as a critical player involved in regulating NMDAR-mediated synaptic transmission and neuronal migration during development. Furthermore, we will consider how dysregulation of D-serine may play an important role in the etiology of neurological and psychiatric diseases. HubMed – depression

 

Estimating Individualized Treatment Rules Using Outcome Weighted Learning.

J Am Stat Assoc. 2012 Sep 1; 107(449): 1106-1118
Zhao Y, Zeng D, Rush AJ, Kosorok MR

There is increasing interest in discovering individualized treatment rules for patients who have heterogeneous responses to treatment. In particular, one aims to find an optimal individualized treatment rule which is a deterministic function of patient specific characteristics maximizing expected clinical outcome. In this paper, we first show that estimating such an optimal treatment rule is equivalent to a classification problem where each subject is weighted proportional to his or her clinical outcome. We then propose an outcome weighted learning approach based on the support vector machine framework. We show that the resulting estimator of the treatment rule is consistent. We further obtain a finite sample bound for the difference between the expected outcome using the estimated individualized treatment rule and that of the optimal treatment rule. The performance of the proposed approach is demonstrated via simulation studies and an analysis of chronic depression data. HubMed – depression

 

The co-occurrence of common mental and physical disorders within Australian families: A national population-based study.

Aust N Z J Psychiatry. 2013 Apr 29;
Saha S, Stedman TJ, Scott JG, McGrath JJ

Objective:Because comorbidity between mental and physical disorders is commonly found in patients, it would be expected that this pattern would also be reflected at the family level. During a recent population-based survey of common mental disorders, respondents were asked about the presence of selected mental and physical disorders in their relatives. The aim of this research was to describe the within-family co-occurrence of selected common physical and mental disorders in a population-based sample.Methods:Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007. A modified version of the World Mental Health Survey Initiative of the Composite International Diagnostic Interview (WMH-CIDI 3.0, henceforth CIDI) was used to identify lifetime-ever common psychiatric disorders (anxiety disorders, depression, drug or alcohol disorders). The respondents were asked if any of their relatives had one of a list of psychiatric (anxiety, bipolar disorder, depression, drug or alcohol problem, schizophrenia) or general physical disorders (cancer, heart problems, intellectual disability, memory problems). We examined the relationship between the variables of interest using logistic regression, adjusting for potential confounding factors.Results:Compared to otherwise-well respondents, those who had a CIDI diagnosis of major depressive disorders, anxiety disorders, or drug or alcohol abuse/dependence were significantly more likely to have first-degree relatives with (a) the same diagnosis as the respondent, (b) other mental disorders not identified in the respondent, and (c) a broad range of general physical conditions.Conclusions:Individuals with common mental disorders report greater familial co-occurrence for a range of mental and physical disorders. When eliciting family histories, clinicians should remain mindful that both mental and physical disorders can co-occur within families. HubMed – depression

 


 

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