BACKGROUND & AIMS: :Prenatal hypoxia induced by transient intrauterine ischemia is a serious clinical problem, and at present, effective treatments are lacking. Currently, it is unknown how prenatal hypoxia affects behaviors in adulthood. Therefore, we developed a mouse model that mimics prenatal hypoxia in humans using uterine artery occlusion in late gestation. We examined whether prenatal hypoxia induces behavioral changes in adult male and female offspring by conducting a series of behavioral tests. In adulthood, longer immobility was observed in the forced swim test in males, whereas females showed decreased inhibition in the prepulse inhibition test. We then investigated the effects of two different selective serotonin reuptake inhibitors (SSRIs), fluoxetine (FLX) and escitalopram (ESC), on these behavioral changes. These drugs affect the neurodevelopmental process and have long-term neurological consequences. FLX treatment from postnatal day 3 (P3) to P21 ameliorated the behavioral changes in both male and female mice. In comparison, ESC treatment ameliorated the behavioral changes only in female mice. Neurochemical analysis revealed that dopamine was increased in the female hippocampus, but not in males. Thus, neonatal SSRI treatment decreases dopamine levels in the hippocampus in females selectively. Our findings suggest that prenatal hypoxia is a risk factor for behavioral abnormalities in adulthood, and that neonatal SSRI treatment might have clinical potential for alleviating these long-term behavioral deficits.

背景与目标： 短暂性宫内缺血引起的产前缺氧是一个严重的临床问题，目前缺乏有效的治疗方法。目前，尚不清楚产前缺氧如何影响成年后的行为。因此，我们开发了一种小鼠模型，该模型在妊娠后期使用子宫动脉闭塞来模拟人类的产前缺氧。我们通过进行一系列行为测试，检查了产前缺氧是否会引起成年雄性和雌性后代的行为变化。成年后，男性在强迫游泳测试中观察到较长的不动，而女性在脉冲前抑制测试中表现出抑制作用降低。然后，我们研究了两种不同的选择性5-羟色胺再摄取抑制剂 (SSRIs) 氟西汀 (FLX) 和艾司西酞普兰 (ESC) 对这些行为变化的影响。这些药物会影响神经发育过程，并具有长期的神经后果。从出生后第3天 (P3) 到P21的FLX治疗改善了雄性和雌性小鼠的行为变化。相比之下，ESC治疗仅改善了雌性小鼠的行为变化。神经化学分析显示，多巴胺在雌性海马中增加，但在雄性中却没有。因此，新生儿SSRI治疗选择性地降低了女性海马中的多巴胺水平。我们的发现表明，产前缺氧是成年期行为异常的危险因素，新生儿SSRI治疗可能具有缓解这些长期行为缺陷的临床潜力。

BACKGROUND & AIMS: BACKGROUND:Approximately 50% of patients with major depressive disorder (MDD) do not respond after adequate first-line treatment with a selective serotonin reuptake inhibitor (SSRI). Special interest is paid to whether specialist level inpatient psychiatric care results differ from community studies. AIM:To compare switching alternatives after treatment failure with an SSRI; switching to venlafaxine (Dexcel Pharma Israel) versus switching to another SSRI in depressed inpatients. METHOD:A retrospective register study of inpatients was undertaken in a psychiatric tertiary care university center serving an urban catchment area in Israel with a population of more than 900,000. RESULTS:A total of 401 MDD inpatients were assigned to antidepressant treatment. Of these, 232 records (47 venlafaxine, 185 SSRI) were included in the analysis. Patients assigned to venlafaxine treatment were older (mean age 64.3 ± 15 years versus 53.6 ± 17; p<0.01) and had more comorbid physical disorders (80% versus 57%; p<0.001). In the primary analysis, there was no statistical difference between groups in reduction in CGI-S total scores. The secondary end point of achieving a CGI-S score of 2 or less (1 = normal, not at all ill or 2 = borderline mentally ill) was statistically significantly better for the venlafaxine treated inpatients (P=0.02). AEs were reported less than 10% of patients in both groups. CONCLUSION:Patients who remain severely depressed following treatment with an SSRI may gain benefit from the dual-action drug venlafaxine, rather than switching to another SSRI. These findings need to be further supported by prospective studies.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To evaluate the prevalence of new onset or worsening of anxiety symptoms, as well as their clinical implications, during the first 2 weeks of Selective Serotonin Reuptake Inhibitor (SSRI) pharmacotherapy for depression. METHOD:Adult outpatients with nonpsychotic major depressive disorder were enrolled in an 8-week acute phase SSRI treatment trial at 15 clinical sites across the United States. Worsening anxiety was defined as a greater than 2-point increase on the Beck Anxiety Inventory (BAI) between baseline and Week 2. New onset of anxiety symptoms was ascribed when the BAI baseline rating was 0 and the Week 2 value was greater or equal to 2 points on the BAI. RESULTS:Overall, after 2 weeks of treatment, 48.8% (98 of 201 participants) reported improvement in anxiety symptoms, 36.3% (73 of 201) reported minimal symptom change, and 14.9% (30 of 201) reported worsening of anxiety symptoms. No association was found between change in anxiety symptoms within the first 2 weeks and change in depressive symptoms or remission at the end of 8 weeks of treatment. For participants with clinically meaningful anxiety symptoms at baseline, however, worsening of anxiety during the first 2 weeks of treatment was associated with worsening depressive symptoms by 8 weeks (P = .054). CONCLUSIONS:The trajectory of anxiety symptom change early in SSRI treatment is an important indicator of eventual outcome for outpatients with major depression and baseline anxiety symptoms.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To compare healthcare utilization and costs for major depressive disorder (MDD) patients treated with escitalopram and who were switched to another SSRI for non-medical reasons versus those who did not switch. RESEARCH DESIGN AND METHODS:Patients were identified in the Ingenix Impact Database (2003-2006). The analysis group included patients who remained on escitalopram for ≥ 90 days and switched to another SSRI within 45 days of end of supply days for non-medical reasons; the control group included matched individuals who did not switch within 45 days. Switching for medical reasons was defined as switching within 7 days after having a hospitalization, an emergency room (ER) visit, or a psychotherapy visit. Outcomes (all-cause and MDD-related) were analyzed over 3 months and included use of hospital, ER, outpatient visits and professional services, and healthcare costs. Outcomes were compared between the two groups using descriptive statistics and regression analyses controlling for differences in baseline characteristics. Costs were inflation adjusted to 2006 US dollars. RESULTS:The study included 2,805 matched pairs. Compared to controls, switchers had higher rates of all-cause and MDD-related hospitalizations (relative risk [RR] = 1.4 and 2.0, respectively) and all-cause and MDD-related ER visits (RR = 1.2 and 1.6, respectively, all p ≤ 0.05). Results from multivariate analyses show that switchers had higher medical costs (+$138), drug costs (+$149) and total healthcare costs (+$322) compared to patients in the control group (all p < 0.0001). LIMITATIONS:This study's limitations include its short observational period and definition of switching for non-medical reasons. CONCLUSION:Patients who were switched to another SSRI for non-medical reasons after being stabilized on escitalopram used more resources and had higher healthcare costs within 3 months of switching than patients who did not switch.

背景与目标：

BACKGROUND & AIMS: PURPOSE:In clinical molecular imaging the interaction between antidepressant medication and SPECT ligands is a significant potential confound. This study measured nAChR availability, as determined by SPECT imaging, on and off selective serotonin reuptake inhibitors in first episode depressed patients. METHODS:Five patients in their first episode of major depressive disorder (MDD) on a single SSRI underwent [(123)I]5-I-A85380- SPECT neuroimaging prior to stopping their medication and again 6 weeks following medication cessation. Autoradiography of post mortem brain tissue with [(125)I]5-I-A85380 in the presence or absence of four commonly prescribed antidepressants was also assessed. RESULTS:SSRI antidepressants did not affect the relative binding availability of alpha4beta2 nicotinic acetylcholine receptors for the [(123)I]5-I-A85380 ligand in vivo. Radioligand binding in vitro was unaffected by a single, high pharmacological concentration of antidepressants. CONCLUSION:SPECT imaging studies using [(123)I]5-I-A85380 to measure alpha4beta2 nAChR availability in depressed patients are unlikely to be confounded to a major degree by concurrent antidepressant medication.

背景与目标：

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVE:The anti-oestrogen tamoxifen requires metabolic activation to endoxifen by cytochrome P450 (CYP) enzymes, predominantly CYP2D6. Potent CYP2D6-inhibiting antidepressants can seriously disrupt tamoxifen metabolism, probably influencing the efficacy of tamoxifen. For this reason, paroxetine and fluoxetine are recommended not to be used with tamoxifen in breast cancer patients. We investigated the effects of switching potent CYP2D6-inhibiting antidepressants to weak CYP2D6-inhibiting antidepressants on the plasma pharmacokinetics of tamoxifen. METHODS:Ten breast cancer patients who were treated with tamoxifen in combination with a potent CYP2D6-inhibiting antidepressant (paroxetine or fluoxetine) for at least 4 weeks were enrolled. Under close supervision by a psychiatrist, patients were switched to treatment with escitalopram or venlafaxine (weak CYP2D6-inhibiting antidepressants). Before and after the switch, pharmacokinetic blood sampling was performed over 24 h. Pharmacokinetic parameters were estimated using noncompartmental analysis. Adverse effects were recorded during the study. RESULTS:Endoxifen exposure was ~3-fold higher during escitalopram co-administration than during paroxetine or fluoxetine co-administration (median 387 nM·h [range 159-637 nM·h] versus 99.2 nM·h [range 70.0-210 nM·h]; P = 0.012; Wilcoxon signed-rank test). The ratio of endoxifen to N-desmethyltamoxifen and the ratio of 4-hydroxytamoxifen to tamoxifen increased by 3.3- and ~1.5-fold, reflecting increased CYP2D6 activity. Antidepressant switching did not result in psychiatric problems or antidepressant-related adverse effects. CONCLUSION:In this study, switching to the weak CYP2D6 inhibitor escitalopram was safe and feasible and resulted in clinically relevant rises in endoxifen concentrations. We therefore advise switching paroxetine and fluoxetine to escitalopram in patients using tamoxifen. However, switching should always be weighed in individual patients.

背景与目标：

BACKGROUND & AIMS: :We undertook an exclusive meta-analysis of cohort studies investigating the possible link between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and autism spectrum disorders (ASD) in children to further investigate our previous suggestion of confounding by indication. The point estimates regarding the following cohorts were extracted and pooled: (1) pregnant women who discontinued SSRI until 3 months before pregnancy; (2) pregnant women who were exposed to SSRI during pregnancy; and (3) pregnant women with maternal psychiatric disorder but no exposure to SSRI during pregnancy. Although the pooled point estimate of the first cohort showed a trend for increase, it did not reach significance. The pooled point estimates of the latter cohorts showed a significant association with ASD which strengthens our previous suggestion of confounding by indication. Future studies should be adequately designed to differentiate whether the previously suggested association is a result of maternal psychiatric disorder or SSRI exposure or both.

背景与目标： : 我们对队列研究进行了独家荟萃分析，调查了产前选择性5-羟色胺再摄取抑制剂 (SSRI) 暴露与儿童自闭症谱系障碍 (ASD) 之间的可能联系，以进一步研究我们先前的暗示因适应症而混淆的建议。提取并汇总了以下队列的点估计 :( 1) 怀孕前3个月停用SSRI的孕妇; (2) 怀孕期间暴露于SSRI的孕妇; (3) 患有母体精神疾病但怀孕期间未暴露于SSRI的孕妇。尽管第一个队列的汇总点估计显示出增加的趋势，但并未达到显着性。后者队列的汇总点估计显示与ASD有显着关联，这加强了我们先前的适应症混淆的建议。未来的研究应充分设计，以区分先前建议的关联是母亲精神病或SSRI暴露还是两者兼而有之。

BACKGROUND & AIMS: :We sought to determine differences in efficacy and tolerability between different doses of selective serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder (OCD) using meta-analysis. We identified 9 studies involving 2268 subjects that were randomized, double-blind placebo-controlled clinical trials that compared multiple, fixed-doses of selective serotonin reuptake inhibitors (SSRIs) to each other and to placebo in the treatment of adults with OCD. Change in Y-BOCS score, proportion of treatment responders, and dropouts (all-cause and due to side-effects) were determined for each included study. Weighted mean difference was used to examine mean change in Y-BOCS score. Pooled absolute risk difference was used to examine dichotomous outcomes. Meta-analysis was performed using a fixed effects model in RevMan 4.2.8. We found that compared with either low or medium doses, higher doses of SSRIs were associated with improved treatment efficacy, using either Y-BOCS score or proportion of treatment responders as an outcome. Dose of SSRIs was not associated with the number of all-cause dropouts. Higher doses of SSRIs were associated with significantly higher proportion of dropouts due to side-effects. These results suggests that higher doses of SSRIs are associated with greater efficacy in the treatment of OCD. This SSRI efficacy pattern stands in contrast to other psychiatric disorders like Major Depressive Disorder. This greater treatment efficacy is somewhat counterbalanced by the greater side-effect burden with higher doses of SSRIs. At present, there are insufficient data to generalize these findings to children or adolescents with OCD.

背景与目标： : 我们试图使用荟萃分析来确定不同剂量的选择性5-羟色胺再摄取抑制剂在强迫症 (OCD) 治疗中的疗效和耐受性差异。我们确定了9项涉及2268名受试者的研究，这些研究是随机，双盲安慰剂对照临床试验，比较了多个固定剂量的选择性5-羟色胺再摄取抑制剂 (SSRIs) 彼此以及安慰剂治疗成人强迫症。对于每个纳入的研究，确定了y-bocs评分的变化，治疗应答者的比例和辍学 (所有原因和副作用)。加权平均差用于检查y-bocs评分的平均变化。合并的绝对风险差异用于检查二分结局。使用RevMan 4.2.8中的固定效应模型进行荟萃分析。我们发现，与低剂量或中剂量相比，使用y-bocs评分或治疗应答者比例作为结果，较高剂量的SSRIs与改善的治疗效果相关。SSRIs的剂量与全因辍学的数量无关。较高剂量的ssri与由于副作用而导致的辍学率明显较高。这些结果表明，较高剂量的SSRIs与OCD治疗的疗效相关。这种SSRI功效模式与其他精神疾病 (例如重度抑郁症) 形成鲜明对比。这种更大的治疗效果在某种程度上被更高剂量的SSRIs带来的更大的副作用负担所抵消。目前，没有足够的数据将这些发现推广到患有强迫症的儿童或青少年。

BACKGROUND & AIMS: :Enduring sexual difficulties following treatment with selective serotonin reuptake inhibitor antidepressants have been reported to regulators since 1991, but it was only in 2006 that a formal post-SSRI sexual dysfunction syndrome was reported. The clinical, research and regulatory implications of this syndrome are considerable and researchers using epidemiological methods are well placed to map out the contours of the problem and perhaps pinpoint possible treatments.

背景与目标： : 1991年已向监管机构报告了使用选择性5-羟色胺再摄取抑制剂抗抑郁药治疗后的持续性困难，但仅2006年报告了正式的SSRI后性功能障碍综合征。该综合征的临床，研究和监管意义相当大，使用流行病学方法的研究人员可以很好地绘制问题的轮廓，并可能确定可能的治疗方法。

BACKGROUND & AIMS: :Sertraline and fluoxetine are selective serotonin re-uptake inhibitors (SSRIs) that are widely prescribed to treat depression. They exert their effects by inhibiting the presynaptic plasma membrane serotonin transporter (SERT). All SSRIs possess halogen atoms at specific positions, which are key determinants for the drugs' specificity for SERT. For the SERT protein, however, the structural basis of its specificity for SSRIs is poorly understood. Here we report the crystal structures of LeuT, a bacterial SERT homolog, in complex with sertraline, R-fluoxetine or S-fluoxetine. The SSRI halogens all bind to exactly the same pocket within LeuT. Mutation at this halogen-binding pocket (HBP) in SERT markedly reduces the transporter's affinity for SSRIs but not for tricyclic antidepressants. Conversely, when the only nonconserved HBP residue in both norepinephrine and dopamine transporters is mutated into that found in SERT, their affinities for all the three SSRIs increase uniformly. Thus, the specificity of SERT for SSRIs is dependent largely on interaction of the drug halogens with the protein's HBP.

背景与目标： : 舍曲林和氟西汀是选择性5-羟色胺再摄取抑制剂 (SSRIs)，广泛用于治疗抑郁症。它们通过抑制突触前质膜5-羟色胺转运蛋白 (SERT) 发挥作用。所有ssri都在特定位置具有卤素原子，这是决定药物对SERT特异性的关键决定因素。然而，对于SERT蛋白，其对SSRIs特异性的结构基础知之甚少。在这里，我们报告了与舍曲林，R-氟西汀或S-氟西汀复合的细菌SERT同源物LeuT的晶体结构。SSRI卤素都与LeuT中完全相同的口袋结合。SERT中该卤素结合口袋 (HBP) 的突变显着降低了转运蛋白对SSRIs的亲和力，但对三环抗抑郁药却没有。相反，当去甲肾上腺素和多巴胺转运蛋白中唯一非保守的HBP残基突变为SERT中发现的HBP残基时，它们对所有三个ssri的亲和力均增加。因此，SERT对SSRIs的特异性在很大程度上取决于药物卤素与蛋白质HBP的相互作用。

BACKGROUND & AIMS: :We sought to determine whether maca, a Peruvian plant, is effective for selective-serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. We conducted a double-blind, randomized, parallel group dose-finding pilot study comparing a low-dose (1.5 g/day) to a high-dose (3.0 g/day) maca regimen in 20 remitted depressed outpatients (mean age 36+/-13 years; 17 women) with SSRI-induced sexual dysfunction. The Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ) were used to measure sexual dysfunction. Ten subjects completed the study, and 16 subjects (9 on 3.0 g/day; 7 on 1.5 g/day) were eligible for intent-to-treat (ITT) analyses on the basis of having had at least one postbaseline visit. ITT subjects on 3.0 g/day maca had a significant improvement in ASEX (from 22.8+/-3.8 to 16.9+/-6.2; z=-2.20, P=0.028) and in MGH-SFQ scores (from 24.1+/-1.9 to 17.0+/-5.7; z=-2.39, P=0.017), but subjects on 1.5 g/day maca did not. Libido improved significantly (P<0.05) for the ITT and completer groups based on ASEX item #1, but not by dosing groups. Maca was well tolerated. Maca root may alleviate SSRI-induced sexual dysfunction, and there may be a dose-related effect. Maca may also have a beneficial effect on libido.

背景与目标： : 我们试图确定秘鲁植物玛卡是否对选择性5-羟色胺再摄取抑制剂 (SSRI) 诱导的性功能障碍有效。我们进行了一项双盲，随机，平行组剂量寻找试验研究，比较了低剂量 (1.5g/天) 与高剂量 (3.0g/天) maca方案在20名缓解的抑郁症门诊患者 (平均年龄36/-13岁); 17名女性) 患有SSRI诱导的性功能障碍。使用亚利桑那州性经验量表 (ASEX) 和马萨诸塞州综合医院性功能问卷 (MGH-SFQ) 来测量性功能障碍。10名受试者完成了研究，16名受试者 (9名3.0g/天; 7名1.5g/天) 基于至少一次基线后访视而符合意向治疗 (ITT) 分析。3.0g/天maca的ITT受试者在ASEX (从22.8 +/-3.8到16.9 +/-6.2; z =-2.20，P = 0.028) 和MGH-SFQ评分 (从24.1 +/-1.9到17.0 +/-5.7) 方面有显著改善; z =-2.39，P = 0.017)，但接受1.5g/天maca的受试者没有。基于ASEX项目 #1的ITT和completer组的性欲显著改善 (P<0.05)，但剂量组没有改善。玛卡的耐受性很好。玛咖根可能会减轻SSRI引起的性功能障碍，并且可能存在剂量相关的作用。玛卡也可能对性欲产生有益的影响。

BACKGROUND & AIMS: :Selective serotonin reuptake inhibitors (SSRIs) are an efficacious and effective treatment for pediatric obsessive-compulsive disorder (OCD) but have received scrutiny due to a potential side effect constellation called activation syndrome. While recent research introduced a subjective measure of activation syndrome, objective measures have not been tested. This pilot study, using data from a larger randomized-controlled trial, investigated the potential of actigraphy to provide an objective measure of activation symptoms in 44 youths with OCD beginning an SSRI medication regimen. Data were collected over the first four weeks of a multi-site, parallel, double-blind, randomized, placebo controlled psychopharmacological treatment study and statistical modeling was utilized to test how activation syndrome severity predicts daily and nightly activity levels. Results indicated that youths with higher activation symptoms had lower daytime activity levels when treatment averages were analyzed; in contrast youths who experienced onset of activation symptoms one week were more likely to have higher day-time and night-time activity ratings that week. Results support actigraphy as a potential objective measure of activation symptoms. Subsequent studies are needed to confirm these findings and test clinical applications for use by clinicians to monitor activation syndrome during SSRI treatment. National Institutes of Health (5UO1 MH078594-01); NCT00382291.

背景与目标： : 选择性5-羟色胺再摄取抑制剂 (SSRIs) 是治疗小儿强迫症 (OCD) 的有效方法，但由于潜在的称为激活综合征的副作用而受到审查。尽管最近的研究引入了激活综合征的主观度量，但尚未对客观度量进行测试。这项初步研究使用了一项较大的随机对照试验的数据，研究了在开始SSRI药物治疗方案的44名患有强迫症的年轻人中，激活成像技术提供了客观的激活症状的潜力。在多部位，平行，双盲，随机，安慰剂对照的心理药物治疗研究的前四周收集了数据，并利用统计模型来测试激活综合征的严重程度如何预测每日和每晚的活动水平。结果表明，当分析治疗平均值时，具有较高激活症状的年轻人的白天活动水平较低; 相比之下，一周出现激活症状的年轻人更有可能在该周具有较高的白天和夜间活动评分。结果支持作为激活症状的潜在客观度量。需要随后的研究来证实这些发现并测试临床应用，以供临床医生在SSRI治疗期间监测激活综合征。美国国立卫生研究院 (5UO1 MH078594-01); Nct00382291。

BACKGROUND & AIMS: :Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed to pregnant women. Therefore, research on in utero exposure to SSRIs can be helpful in informing patients and clinicians. The aim of this retrospective two-cohort study was to determine whether there is a statistically significant increase in Chiari I malformations (CIM) in children exposed to SSRIs during pregnancy. A total of 33 children whose mothers received a diagnosis of depression and took SSRIs during pregnancy (SSRI-exposed cohort) were matched to 66 children with no history of maternal depression and no SSRI exposure. In addition, 30 children whose mothers received a diagnosis of depression, but did not receive antidepressants during pregnancy (history of maternal depression cohort), were matched to 60 children with no history of maternal depression and no SSRI exposure. Main outcome was presence/absence of CIM on MRI scans at 1 and/or 2 years of age. Scans were reviewed by two independent neuroradiologists who were blind to exposure status. The SSRI-exposed children were significantly more likely to be classified as CIM than comparison children with no history of maternal depression and no SSRI exposure (18% vs 2%, p=0.003, OR estimate 10.32, 95% Wald confidence limits 2.04-102.46). Duration of SSRI exposure, SSRI exposure at conception, and family history of depression increased the risk. The history of maternal depression cohort did not differ from comparison children with no history of maternal depression and no SSRI exposure in occurrence of CIM (7% vs 5%, p=0.75, OR estimate 1.44, 95% Wald confidence limits 0.23-7.85). Replication is needed, as is additional research to clarify whether SSRIs directly impact risk for CIM or whether this relationship is mediated by severity of depressive symptoms during pregnancy. We would discourage clinicians from altering their prescribing practices until such research is available.

背景与目标： : 选择性5-羟色胺再摄取抑制剂 (SSRIs) 经常被处方给孕妇。因此，对子宫内ssri暴露的研究有助于告知患者和临床医生。这项回顾性两组研究的目的是确定怀孕期间暴露于SSRIs的儿童的Chiari I畸形 (CIM) 是否有统计学上的显着增加。共有33名母亲被诊断出患有抑郁症并在怀孕期间服用SSRI的儿童 (暴露于SSRI的队列) 与66名没有母亲抑郁症病史且没有SSRI暴露的儿童相匹配。此外，将30名母亲被诊断出患有抑郁症但在怀孕期间未接受抗抑郁药 (孕产妇抑郁症史队列) 的儿童与60名无孕产妇抑郁症史且无SSRI暴露的儿童进行匹配。主要结果是在1岁和/或2岁时MRI扫描中存在/不存在CIM。扫描由两名对暴露状态视而不见的独立神经放射科医生进行审查。暴露于SSRI的儿童比没有母亲抑郁症病史且没有SSRI暴露的比较儿童更有可能被归类为CIM (18% vs 2%，p = 0.003或估计10.32，95% Wald置信度限制2.04-102.46)。SSRI暴露的持续时间，受孕时的SSRI暴露以及抑郁症的家族史增加了风险。产妇抑郁史队列与没有产妇抑郁史且没有SSRI暴露的比较儿童在CIM发生方面没有差异 (7% vs 5%，p = 0.75，或估计1.44，95% Wald置信限0.23-7.85)。复制是必要的，另外的研究也需要阐明SSRIs是否直接影响CIM的风险，或者这种关系是否由怀孕期间抑郁症状的严重程度介导。在进行此类研究之前，我们不鼓励临床医生改变其处方实践。

BACKGROUND & AIMS: :Depression and anxiety during adolescence are complex disorders due to persistent effects on physiology and behavior. Selective-serotonin reuptake inhibitors (SSRI) are currently the most widely used pharmacological intervention for depression. Corticotropin-releasing factor one (CRF1) receptor antagonists represent a novel class of compounds that may have efficacy for depressive and anxiety disorders. This study used an animal model of chronic adolescent stress to determine the efficacy of the SSRI fluoxetine, and a novel CRF1 receptor antagonist, GSK876008, on prevention of the behavioral effects of chronic adolescent stress. Male rats were exposed to chronic social defeat stress, fluoxetine, and/or GSK876008 from postnatal day 28-50. Chronic stress-induced depressive-like behaviors were partially attenuated by either concurrent fluoxetine or GSK876008. Fluoxetine blunted body mass gain in the adolescents exposed to chronic stress. The collective data demonstrate similar efficacy between a SSRI and a CRF1 receptor antagonist in the attenuation of stress-induced anhedonia but fewer side effects were observed in those rats treated with the CRF1 receptor antagonist. These data suggest that CRF1 receptor antagonists may be a viable alternative for treatment of depressive behaviors in adolescents.

背景与目标： : 由于对生理和行为的持续影响，青春期的抑郁和焦虑是复杂的疾病。选择性5-羟色胺再摄取抑制剂 (SSRI) 是目前最广泛用于抑郁症的药物干预。促肾上腺皮质激素释放因子一 (CRF1) 受体拮抗剂代表一类新型化合物，可能对抑郁症和焦虑症具有功效。这项研究使用了慢性青少年压力的动物模型来确定SSRI氟西汀和新型CRF1受体拮抗剂GSK876008对预防慢性青少年压力的行为影响的功效。从出生后第28-50天开始，雄性大鼠暴露于慢性社交失败压力，氟西汀和/或GSK876008。同时使用氟西汀或gsk876008可以部分减轻慢性压力引起的抑郁样行为。氟西汀使暴露于慢性压力的青少年的体重增加减弱。集体数据表明，SSRI和CRF1受体拮抗剂在减轻应激诱导的缺乏感方面具有相似的功效，但在用CRF1受体拮抗剂治疗的大鼠中观察到较少的副作用。这些数据表明，CRF1受体拮抗剂可能是治疗青少年抑郁行为的可行替代方法。

BACKGROUND & AIMS: :Selective serotonin reuptake inhibitors (SSRIs) are apt to cause gastrointestinal adverse events such as nausea and dyspepsia. Gorei-san (TJ-17), which is composed of five herbs (Alismatis rhizoma, Atractylodis lanceae rhizoma, Polyporus, Hoelen, and Cinnamomi cortex), is a Japanese herbal medicine that has been used to treat nausea, dry mouth, edema, headache, and dizziness. The authors investigated the efficacy of TJ-17 for patients who experienced nausea or dyspepsia induced by SSRIs. Twenty outpatients who experienced nausea or dyspepsia induced by SSRIs were recruited for the study. Seventeen patients were female, three were male, and patient age ranged from 21 to 74 years (49.8 +/- 17.0 years). TJ-17 was added to the previous regimen. Nausea and dyspepsia disappeared completely in nine patients, decreased in four patients, decreased slightly in two patients, and did not change in five patients. No adverse events were associated with the addition of TJ-17 in any patient.

背景与目标： 选择性5-羟色胺再摄取抑制剂 (SSRIs) 容易引起胃肠道不良事件，如恶心和消化不良。Gorei-san (TJ-17) 是一种日本草药，已用于治疗恶心，口干，水肿，头痛和头晕。作者研究了TJ-17对患有SSRIs引起的恶心或消化不良的患者的疗效。本研究招募了20名患有SSRIs引起的恶心或消化不良的门诊患者。17例患者为女性，3例为男性，患者年龄为21至74岁 (49.8 +/- 17.0岁)。将TJ-17添加到先前的方案中。9例患者恶心和消化不良完全消失，4例减少，2例略有减少，5例无变化。在任何患者中，没有与增加TJ-17相关的不良事件。