Urinary NGF level was

Urinary NGF level was measured in 38 normal controls and 70 patients with OAB.51 Patients were treated with tolterodine 4 mg once daily. The urinary NGF/Cr levels and urgency severity scale (USS) were compared at baseline, 1, 2, and 3 months after antimuscarinics and 1 month after http://www.selleckchem.com/products/a-769662.html discontinuing treatment.51 Urinary NGF/Cr level was significantly reduced at 3 months in 50 responders (1.10 ± 0.26 before vs 0.41 ± 0.09 after, P = .008), but not in 20 nonresponders (1.39 ± 0.54 before vs 1.30 ± 0.46 after, P = .879). After discontinuing antimuscarinic treatment for 1 month, Inhibitors,research,lifescience,medical however, urinary

NGF/Cr level was elevated in 23 responders (0.85 ± 0.33) and in 5 nonresponders (2.72 ± 1.41). The USS significantly changed with urinary NGF/Cr level in responders at different time points. The change of urinary NGF level Inhibitors,research,lifescience,medical is associated with the change of USS after antimuscarinic treatment and discontinued medication. The urinary NGF level could be a potential biomarker for evaluating therapeutic results of antimuscarinic therapy (Figure 7). Figure 7 Urinary nerve growth Inhibitors,research,lifescience,medical factor/creatinine

(NGF/Cr) levels were significantly reduced at 3 months in responders (A) but not in nonresponders (B). After discontinuation of antimuscarinic treatment for 1 month, urinary NGF/Cr level was elevated in both responders … Previous studies have shown that urinary NGF is a sensitive biomarker for the diagnosis of OAB.20,26,29 It is possible that NGF is taken up by sensory nerves and transported through the CNS in retrograde

fashion. Therefore, NGF production could be a biomarker for neuroplasticity via some common pathway involved in the pathogenesis of OAB.44 This Inhibitors,research,lifescience,medical study further demonstrated that urinary NGF level decreased in association with the reduction of urgency severity and increased when OAB symptoms recurred. Interestingly, a lag response time between changes in USS and NGF was noted in responders. The mechanism for this difference could be due to a subjective report of USS and time lag of NGF production decreases after antimuscarinic treatment. Inhibitors,research,lifescience,medical Patients with improved USS might still have incompletely solved underlying OAB pathophysiology. After 3 months of antimuscarinic treatment, USS had not decreased to zero and urinary NGF Phosphoprotein phosphatase levels also remained significantly higher than those of controls. The elevated urinary NGF level might imply the existence of residual inflammation in the CNS. Conclusions Measurement of urinary NGF level in patients with OAB and other urinary conditions provides insight into the underlying pathophysiology of this sensory disorder. Patients with OAB had significantly higher urinary NGF levels compared with controls and patients with increased bladder sensation. BOO with OAB or DO correlates with elevated urinary NGF that returns to normal after medical treatment of BOO. These results suggest that urinary NGF level is a promising biomarker for the diagnosis of OAB.

16-18 Proinflammatory cytokine levels are increased, along with

16-18 Proinflammatory cytokine levels are increased, along with performance in tests of psychomotor vigilance, and this has been reported to result from a modest sleep restriction to 6 hours per night.19 Reduced

sleep duration was reported to be associated with increased body mass and obesity in the NHANES study20 Sleep deprivation also causes cognitive impairment. The brain is the master regulator of the neuroendocrine, Inhibitors,research,lifescience,medical autonomic, and immune systems, along with behaviors that contribute to Selleckchem Azacitidine unhealthy or health lifestyles, which, in turn, influence the physiological processes of allostasis (Figure 3).2 Alterations in brain function by chronic stress can, therefore, have direct and indirect effects on the cumulative allostatic overload. Allostatic overload

resulting from chronic stress in animal models causes atrophy of neurons in the hippocampus Inhibitors,research,lifescience,medical and prefrontal cortex, brain regions involved in memory, selective attention, and executive function, and causes hypertrophy of neurons in the amygdala, a brain region involved in fear and anxiety, as well as aggression.21 Thus, the ability to learn and remember and make decisions may be compromised by chronic stress, and may be accompanied by increased levels of anxiety and Inhibitors,research,lifescience,medical aggression. Figure 3. Central role of the brain in allostasis and the behavioral and physiological response to stressors. Reproduced from reference 1: McEwen BS. Protective and damaging effects of stress mediators. N Engl J Med. 1998;338:171-179. Copyright Inhibitors,research,lifescience,medical © Massachusetts … Although sleep deprivation has not yet been studied In terms of all these aspects, there Is Increasing evidence, not only for

cognitive impairment resulting from sleep restriction, Inhibitors,research,lifescience,medical but also for altered levels of cytokines, oxidative stress markers, glycogen levels, and structural changes in the form of reduced dentate gyrus neurogenesis. With before respect to proinflammatory cytokines, IL-β messenger ribonucleic acid (mRNA) levels in brain are reported to increase following sleep deprivation by gen tie handling and to be higher in daytime (during the normal sleep period in rodents) than in darkness (during the normal activity time for rodents).22 Closely related to inflammatory processes through the actions of reduced nicotinamide adenine nucleotide phosphate (NADPH) oxidase23,24 is oxidative stress involving the generation of free radicals. Sleep deprivation in mice for 72 hours by the “flowerpot” or platform method has been reported to increase oxidative stress in hippocampus, as measured by increased lipid peroxidation and increased ratios of oxidized to reduced glutathione.

16 However, their differential binding preference for CRHR1 and C

16 However, their differential binding preference for CRHR1 and CRHR2 suggests that CRH and Ucn II have different functions in the click here stress response. The localization of Ucn III (Figure 1B) 14,17 in the brain is different from that of CRH,29 Ucn,20 and Ucn II.16 This latest discovered member of the CRH neuropeptide family is found in

the median preoptic area, the rostral perifornical area (a region lateral from the PVN in the hypothalamus), the posterior part of the BNST, and the medial nucleus of the amygdala (Figure 1B).14 Until now, unfortunately, no Inhibitors,research,lifescience,medical Fos studies have been published with Ucn III. It is relevant to note though that parts of the perifornical Inhibitors,research,lifescience,medical region project into the (CRHR2-rich) LS, an area in

which both Ucn-ir and piscine urotensin I-ir can be found.20 However, within the LS, Ucn-ir and urotensin I are differentially localized with Ucn-ir prevailing in the medial aspect of the iLS and urotensin I-ir concentrating in the ventrolateral aspect of this nucleus, ic, the site where CRH-R2 mRNA is also found (see also above). It may be speculated that, given the structural relationship between urocortins and urotensin, the immunoreactivity in the ventrolateral aspect of the iLS as revealed with the piscine urotensin I antiserum may actually be Ucn III. Recently, Ucn III-ir fibers were indeed found in this region of the LS (and Inhibitors,research,lifescience,medical in the VMH), which corresponds well with the sites of CRHR2 mRNA expression (P. E. Sawchenko, personal communication). Inhibitors,research,lifescience,medical CRHR1 and CRHR2 in anxiety, sleep/electroencephalographic regulation and HPA axis control: significance for clinical anxiety and depression In recent years, many studies have been performed

to delineate the specific role of CRHR1 and CRHR2 in stress-related physiological and behavioral processes to gain insight into anxiety and Inhibitors,research,lifescience,medical major depressive disorders. Various strategies have been employed including pharmacological approaches, mutant mice with functional deletions in one of the receptors, and antisense oligodeoxynucleotide (ODN) technology. These investigations have provided insight into the complexity of the contributions of CRHR1 and CRHR2 in the regulation of emotional behavior, HPA axis activity, and too autonomic function. For some processes, the roles of CRHR1 and CRHR2 seem clear, whereas for others they still need to be clarified. Anxiety CRH is highly implicated in the regulation of anxietyrelated behavior and is thought to play a pivotal role in anxiety and depressive disorders.24,30,31 Several lines of evidence point to the participation of CRHR1 in the effects of CRH. First, CRHR1 binds CRH with high affinity, in contrast to CRHR2. Second, CRHRl-deficient mice show decreased anxiety-related behavior.32,33 Third, transgenic mice overexpressing CRH show increased anxiety-related behavior34 (van Gaalen et al, unpublished data).

Yet, ironically, a significant, number of

Yet, ironically, a significant, number of clinical trials have been conducted to assess the impact of a variety of pharmacological agents on cognition in normal aging, AAMI, AACD, and MCI. Many of the therapeutic approaches to AD have been utilized in such populations, less often to assess the benefits for this population than as the first step in assessing their safety and efficacy for use in AD patients. Pharmacological approaches in AACD, MCI, and normal aging Neuro transmitter deficiencies Cholinergic deficits. Numerous studies suggest that central Inhibitors,research,lifescience,medical cholinergic activity declines with age. While

profound cell loss from the cortex itself has generally not, been observed, loss of subcortical cholinergic neurons may be associated with normal aging.13 Neurons located in the subcortical basal forebrain region provide cholinergic Inhibitors,research,lifescience,medical innervation to the hippocampus and neocortex. Degeneration of these neurons likely contributes to cognitive impairment. An age-related decrease in the presynaptic activity of CAT has been reported in humans.180 CAT is considered a marker of cholinergic neurons; thus its decline

with age indicates a loss of cholinergic neurons with increasing age. Since postsynaptic muscarinic receptor binding also Inhibitors,research,lifescience,medical decreases with age,181 it appears that both presynaptic and postsynaptic cholinergic degeneration are involved Inhibitors,research,lifescience,medical in the process of normal aging. Camptothecin manufacturer Baxter et al182 demonstrated in rodents that most of the age-related changes

in cholinergic markers were already present at ages at which behavioral impairment, was not yet maximal. A postmortem study in humans, however, somewhat, challenges this finding: cholinergic deficits, measured as activity of the cholinergic enzymes CAT and AChE, were apparent in elderly individuals with severe dementia, but not in individuals with moderate, mild, questionable, or no dementia.183 However, administration of the cholinergic antagonist scopolamine in humans has been Inhibitors,research,lifescience,medical found to impair the encoding of information into long-term memory and to impact other cognitive processes.22,184,185 Since a cholinergic antagonist, is associated with new impairments in memory and cognition, cholinergic enhancers, especially AChEIs, may ameliorate such impairments.186-188 Cholinergic enhancers (for example, arecoline, a muscarinic agonist, and choline, a precursor of ACh) have been tested on effects on performance of memory tasks in healthy volunteers after administration of the cholinergic antagonist methscopo lamine. Both drugs reversed scopolamine-induced impairment of serial learning.189 Poor baseline performers proved to be more vulnerable to both the enhancing effect, of the cholinergic agonist, and precursor and the impairment after cholinergic antagonist than good performers.

Cystic tumors

may be hypocellular, and result in false ne

Cystic tumors

may be hypocellular, and result in false negative results. Five to six separate FNAs may be necessary to achieve maximal accuracy compared to only two to three for other organ targets. It has been recommended that for optimal results, a pancreatic mass should be sampled with seven aspirations (1,17,18). If an onsite pathologist/cytologist is present to assess Inhibitors,research,lifescience,medical adequacy, the number of aspirations required may be reduced (19). Needle gauge does not appear to make a difference. Follow up Every effort should be made to review follow up as well as previous pathology on patients undergoing diagnostic or therapeutic procedures. Subsequent repeat cytologic biopsy specimens that are diagnostic, as well as Inhibitors,research,lifescience,medical correlation with the surgical specimens (if available) should be routinely performed. Also, information should be available to compare patient outcomes with the diagnoses previously rendered. Conclusions There are two major indications for pancreatic FNA, evaluation of a Inhibitors,research,lifescience,medical pancreatic mass, and documentation of malignancy prior to chemotherapy. Acknowledgements Disclosure: The authors declare no conflict of interest.
A 49-year old male with a history of human immunodeficiency virus (HIV) infection had initially presented 11 years ago with itching and burning in the perianal region.

He was diagnosed at that time with anal condylomata, and since then he has undergone several surgeries for excision of anal condylomata and repair of anal fistulae. Approximately eight years after the diagnosis of anal condylomata, pathology from a condyloma excision demonstrated the presence of high grade squamous dysplasia and CIS. Two years later (approximately Inhibitors,research,lifescience,medical 10 years after the original diagnosis of anal condylomata), the patient developed a right anterior

lateral fistula of the anus with recurrent condylomata, and excision was performed Inhibitors,research,lifescience,medical with pathology again demonstrating high grade squamous dysplasia. Within one month of his surgery, the patient developed severe rectal pain and bleeding. Physical exam was limited at this time due to patient discomfort. Magnetic resonance imaging of the pelvis demonstrated circumferential thickening of the anal canal measuring up to 1.7-cm, along with an 8.0-cm × 6.3-cm heterogeneously enhancing left perirectal first mass Selisistat concentration consistent with a lymph node conglomerate. Examination under anesthesia and proctoscopy were performed, demonstrating a 3.0-cm nodule at the anal verge associated with an 8.0-cm area of ulceration that extended to the distal rectum. Biopsies of the nodule and throughout the area of ulceration were performed. Pathology demonstrated the presence of a high grade neuroendocrine carcinoma, small cell type, with associated squamous CIS (Figures 1,​,2).2).

One of these would be to identify, prior to treatment, the medica

One of these would be to identify, prior to treatment, the medication that has the highest likelihood of benefitting the patient. Research has sought to indentify “endophenotypes” that could predict response or remission to specific antidepressants for individual patients. As defined by Gottesman and Gould,48 an endophenotype must meet five criteria: The endophenotype is associated with illness in the population. The endophenotype is heritable. The endophenotype is primarily state-independent (manifests in an individual whether or not illness is active). Within families, endophenotype and illness cosegregate. The endophenotype Inhibitors,research,lifescience,medical found in

affected family members is found in nonaffected Inhibitors,research,lifescience,medical family members at a higher rate than in the general population.

Endophenotypes thus are measureable characteristics or physiologic indices that fill “the gap between available descriptors and between the gene and the elusive disease process.”49 Exhaustive studies of clinical features, family history, as well as sleep patterns and neuroendocrine correlates, have identified general prognostic indicators for treatment outcome for depression.50,51 In some cases, the predictors may be useful for groups of patients with certain subtypes Inhibitors,research,lifescience,medical of depression (ie, psychotic depression).52 While some symptomatic and physiologic features in MDD patients demonstrate Inhibitors,research,lifescience,medical promise as

putative endophenotypes, many do not fulfill the actual criteria for an endophenotype or meet the goal of providing greater prognostic specificity than the definition of the illness itself.53 Some brain imaging findings also have demonstrated prognostic significance54-57 and may fulfill the criteria for an endophenotype.58 Part of the challenge in identifying true endophenotypes in MDD is that the physiologic and genetic underpinnings of MDD are complex and poorly understood. As a result, imaging findings Inhibitors,research,lifescience,medical may reflect confounds such as interindividual heterogeneity in brain structure or function unrelated to illness, or the effects of previous or concomitant medication treatment.58 No clinically meaningful endophenotypes predictive of response to specific medications in individual patients prior to the start of treatment yet have been identified.59,60 An alternative to the endophenotypic approach has been to examine genetic polymorphisms as possible outcome NATURE REVIEWS DRUG DISCOVERY predictors. Recent studies have suggested that common genetic variations may be associated with response to specific antidepressant medications.61-63 For example, some common polymorphisms in serotonin system genes have been shown to influence the outcome of SSRI treatment.62,64 Many of these results have not consistently replicated or do not allow the estimation of prediction accuracy in a clinical population.

In our study, no statistically significant difference in proporti

In our study, no statistically significant difference in proportion of patients with EUS findings suspicious for invasion regarding the presence of any visible lesion was noted. When

the type of lesion was analyzed, no statistically significant association between significant EUS findings and flat lesions (type 0-IIb) was found. Our results are consistent with the most recently published studies about this topic. Pech et al. (51) reported an unsatisfactory accuracy rate of 74% for T stage and 73% for N stage when comparing EUS staging before surgery with esophagectomy staging (n=179). T2 cancers are the most frequently overstaged by EUS, leading Inhibitors,research,lifescience,medical in a significant impact on making treatment decisions. Similarly to our data, Thomas et al. (52) Inhibitors,research,lifescience,medical reported that the role of EUS in the pretherapeutic algorithm for early Barrett’s neoplasia should be reconsidered with submucosal invasion detected only in 26% of patients

(n=50). The value of EUS is even more limited in patients with flat VL (0-IIb), where all of lesions are confined to the mucosa. In the same direction, a recent retrospective analysis of 131 patients with early esophageal cancer performed by the Amsterdam group (53) concluded that EUS exam has no clinical impact on the decision making for treatment. 24% of the Inhibitors,research,lifescience,medical 105 patients with unremarkable EUS findings underwent surgery after EMR due to submucosal involvement, positive resection margins, lymphovascular invasion or poor differentiation grade. In the other hand, 38% of the 26 patients with suspected submucosal invasion or LNM according to the EUS exams were successfully treated by endoscopic approach. A recent review established a global incidence of incidental findings (in radiological Inhibitors,research,lifescience,medical tests of 23.6%, Inhibitors,research,lifescience,medical which were detected in higher frequencies when CT scan was performed.

However, none of the included studies in this review had reported data from EUS exams (54). In this series, 10% (n=11) of patients had an additional diagnosis due to the EUS exam; in 6 of the 11 patients, these incidental findings were considered as significant according to the need for further learn more investigations, treatment or follow up (4 pancreatic lesions and 1 mediastinal mass). The only study published to date, which reports incidental finding rates on EUS (55), Annual Review of Biochemistry found an overall 38.5% incidence of additional ancillary diagnoses in 239 consecutive EUS exams performed for a variety of indications. Of these incidentally found conditions, 11.3% were considered clinically significant. These findings raise the question if a complete endosonographic exploration should be performed in every patient. There are several limitations to our study, including a retrospective design based on the information provided by clinical reports from a single center. This study presents a markedly low rate of patients with TNM staging reported on the final EUS diagnosis.

Low level of education and head

Low level of education and head trauma are examples of such delayed effects, but this is also true for hypertension, diabetes, hyperlipidemia, and more, where it is their midlife occurrence which is associated with the development of dementia in senescence. Not all the factors mentioned here are equally important (and data are missing on several), and some may be redundant to others. It is difficult to envisage that we shall ever be able to definitely confirm that manipulation of these risk factors can reduce the risk of dementia, and what is their quantitative effect singly or in different combinations. Nevertheless,

it Inhibitors,research,lifescience,medical is more than reasonable to promote physical health in order to prevent dementia. Since the prevalence of dementia doubles every 5 years after age 65, delaying the onset of dementia by 10 years Inhibitors,research,lifescience,medical could markedly reduce age-specific prevalence, particularly in people who are still in critical productive years by 75%. This is probably achievable.
While the United States population under the age of 65 has Inhibitors,research,lifescience,medical tripled since the beginning of the last century, the number of those over age 65 has increased 11-fold. At present, 1 in 8 Americans (33.2 million) are over age 65, up from 1 in 25 in 1900 (3.1 million). This trend is

expected to continue. Projections by the US Census Bureau indicate that the elderly population will more than double between now and the year Inhibitors,research,lifescience,medical 2050, to 80 million, when it is estimated that 1 in 5 Americans will be elderly.1 The prevalence of dementia rises steeply with age, doubling every 4 to 5 years from the age of 60, so that more than one third of individuals over 80 years of age are likely to have dementia.2 With increased life expectancy in the United States, the projected numbers of elderly Inhibitors,research,lifescience,medical people who will develop dementia will grow rapidly. There are no cures or preventive measures yet for dementia. Alzheimer’s disease (AD) remains the most common cause of dementia

in the elderly. The Nature Reviews Cancer risk factors for AD, other than age, include female gender, family history, and at least one apolipoprotein E4 (APOE4) allele.3 In addition, cardiocheck details vascular risk factors, established as risk factors for vascular dementia, have also been associated with AD.4 These risk factors are of special interest because of their potential modifiability so they may affect the course of disease. This paper reviews four well-established cardiovascular risk factors (type 2 diabetes, hypertension, cholesterol, and inflammation), for which there is longitudinal epidemiological evidence of increased risk of dementia, AD, mild cognitive impairment (MCI), and cognitive decline. No two longitudinal epidemiological studies of dementia have the same methodology, and they each study distinct populations.

1 PTSD symptoms This number of symptoms did not diminish by eve

1 PTSD symptoms. This number of symptoms did not diminish by even as much as one symptom over 2 years. Furthermore, PTSD diagnosis at lime 1 significantly predicted degree of functional impairment 1 and 2 years later. Strategies for addressing this challenge First, professionals must be aware that preschool children can develop PTSD. Only then can appropriate screening and referrals for assessment be triggered. Second, when conducting assessments, developmentally appropriate measures and criteria must be used so as not to miss the diagnosis. Third, AS-703026 price because Inhibitors,research,lifescience,medical of the traditional under-recognition of PTSD, which may be overshadowed by the more beliaviorally observable comorbid symptoms

of ODD and SAD, professionals must

be on alert when children present with sudden onset of new symptoms to evaluate for past traumatic events and do a thorough PTSD assessment. Inhibitors,research,lifescience,medical Challenge 4: assessment challenges The accurate assessment of PTSD is perhaps more timeconsuming, difficult, and emotional than for any other disorder. Details of a proper assessment are beyond the scope of this paper, but this section highlights three Inhibitors,research,lifescience,medical particular challenges. Interviewing burden and complexity for multiple traumatic events While the DSM-IV criteria do not restrict making the diagnosis to a single traumatic event, diagnostic interviews and self-report instruments that assess PTSD often ask respondents to select Inhibitors,research,lifescience,medical “the worst” traumatic event that he or she experienced and to rate all PTSD symptoms in relation to that specific event. Many children have experienced multiple traumatic events. One recent study indicates that 68% of all children in the US have experienced at least one potentially traumatic event (PTE), and half of these children have experienced multiple PTEs.32 It

is often difficult for children, particularly young children, to select only one traumatic event as “the worst” they have experienced. It is common for children who have Inhibitors,research,lifescience,medical experienced multiple PTEs to describe that they are experiencing some PTSD symptoms related to one trauma and other symptoms related to another trauma. No known study has specifically examined (i) children’s PTSD symptoms related to any Dimethyl sulfoxide traumatic event; versus (ii) children’s PTSD symptoms only related to the “worst” traumatic event they had experienced. A reasonable hypothesis is that significantly more symptoms would be reported in (i) than (ii). Suppose such a child reported domestic violence, traumatic death of a brother, and sexual abuse exposure. This child reports one re-experiencing, one avoidance, and one hyperarousal symptom related to domestic violence; two re-experiencing, two avoidance, and two hyperarousal symptoms related to the traumatic death; and one re-experiencing, two avoidance, and one hyper-arousal symptom related to sexual abuse.

48 A functional coding SNP rs6265 causes a Valine to Methionine c

48 A functional coding SNP rs6265 causes a Valine to Methionine change at codon 66, which leads to impaired intracellular trafficking and secretion of the mature BDNF protein. Carriers of the Met allele have significantly lower hippocampal volume than subjects homozygous for the Val allele.67 Although several studies have found an association between the Met allele and antidepressant response,63”68 the sample sizes were small, and the

results have been inconsistent.61 In addition to the Val66Met allele, a polymorphism in the 5′ untranslated selleck compound region of the BDNF gene (rs61 888800) was associated with antidepressant response in Mexican-American subjects.69 Inhibitors,research,lifescience,medical This observation requires replication.

Early life stress and deregulation of the hypothalamicpituitary-adrenal (IIPA) Inhibitors,research,lifescience,medical axis are also linked with depression treatment outcome;48,70 One of the important genes that has emerged from the UFA axis is FKBP5 (FK506 binding protein 51), a cochaperone of 90 kDa heat shock protein, which regulates glucocorticoid receptor sensitivity. Carriers of the TT genotype of rsl360780 polymorphism in intron 2 of Inhibitors,research,lifescience,medical FKBP5 were demonstrated to have a better treatment outcome than other genotypes.71 This observation was replicated in a separate sample in the same study, and in two other independent studies. Smaller investigations of Spanish and Korean populations failed to reproduce this association (see ref 72). Genetics of antidepressant-induced side effects Side effects of antidepressant treatment have emerged as important reasons for medication discontinuation and non compliance.

The first-generation TCAs and monoamine oxidase inhibitors (MAOIs) were primarily associated with Inhibitors,research,lifescience,medical sedation, weight gain, and anticholinergic side effects, including dry mouth, blurred vision, cardiac effects, and death by overdose. The newer antidepressants, Inhibitors,research,lifescience,medical including SSRIs and SNRIs, have better and safer side-effect profiles, but tend to cause nausea, diarrhea, nervousness, agitation, insomnia, and sexual side effects. Similar to studies of antidepressant response, the candidate genes extensively investigated in relation to antidepressant Resveratrol induced side effects are from the serotonergic system. The presence of the 5-HTTLPR L allele is generally associated with fewer treatment related side effects. Negative studies are also reported in the literature. A recent meta-analysis found the L allele conferred protection against antidepressant side effects for all antidepressants (OR 0.64) ,63 the significance of which became more robust when analyzed with SSRI-induced side effects only. The same meta-analysis found that the presence of the -1438 G/G polymorphism of HTR2A increased the risk of antidepressant side effects (OR 1.91). Several other pharmacodynamic genes were investigated with contradictory results.