Long term sertraline effects on neural structures in depressed and nondepressed adult female nonhuman primates.
Long term sertraline effects on neural structures in depressed and nondepressed adult female nonhuman primates.
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DOI：
10.1016/j.neuropharm.2015.06.011
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发表时间：
2015-12
影响因子：
4.7
通讯作者：
Shively CA
中科院分区：
文献类型：
--
作者：
Willard SL;Uberseder B;Clark A;Daunais JB;Johnston WD;Neely D;Massey A;Williamson JD;Kraft RA;Bourland JD;Jones SR;Shively CA
选择性血清素再摄取抑制剂（SSRIs）被广泛用于治疗情绪和其他疾病。然而，由于患者依从性和用药史的可变性，它们的神经效应很难研究，而且很少研究那些处方SSRIs治疗非情绪障碍的患者。在这里，我们评估了SSRI对抑郁和非抑郁猴子神经容量的影响。将42只合居食蟹猴随机分为预处理抑郁行为和体重平衡治疗组。对猴子进行训练，每天口服安慰剂或20mg/kg盐酸舍曲林，持续18个月，并记录抑郁和焦虑行为。在磁共振图像中测量抑郁症感兴趣的神经区域的体积，并通过2（抑郁，非抑郁）× 2（安慰剂，舍曲林）方差分析进行分析。舍曲林减少了焦虑（p=0.04），但没有减少抑郁行为（p=0.43）。抑郁组左Brodmann 's Area (BA)32小于非抑郁组（p<0.05）。舍曲林和抑郁状态相互作用影响左扣带前皮质（ACC）、左BA24、右海马（HC）和右前HC的体积（舍曲林与抑郁相互作用：均p < 0.05）。在安慰剂组中，抑郁猴子的右前HC和左前ACC比非抑郁猴子小。在非抑郁猴子中，舍曲林减少右HC体积，尤其是右前HC体积。在抑郁的猴子中，舍曲林增加左ACC体积。在非抑郁症猴子中，舍曲林减少了左BA24容量，导致非抑郁症猴子的BA24容量小于服用舍曲林的抑郁症猴子。这些观察结果表明，SSRIs对抑郁和非抑郁个体的神经结构的影响可能是不同的。
Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for mood and other disorders. However, their neural effects are difficult to study due to patient compliance and drug history variability, and rarely studied in those prescribed SSRIs for non-mood disorders. Here we evaluated SSRI effects on neural volumetrics in depressed and nondepressed monkeys. 42 socially-housed cynomolgus monkeys were randomized to treatment balanced on pretreatment depressive behavior and body weight. Monkeys were trained for oral administration of placebo or 20mg/kg sertraline HCl daily for 18 months and depressive and anxious behavior recorded. Volumes of neural regions of interest in depression were measured in magnetic resonance images and analyzed by 2 (depressed, nondepressed) × 2 (placebo, sertraline) ANOVA. Sertraline reduced anxiety (p=0.04) but not depressive behavior (p=0.43). Left Brodmann’s Area (BA)32 was smaller in depressed than nondepressed monkeys (main effect of depression: p<0.05). Sertraline and depression status interacted to affect volumes of left anterior cingulate cortex (ACC), left BA24, right hippocampus (HC), and right anterior HC (sertraline X depression interactions: all p’s < 0.05). In the Placebo group, depressed monkeys had smaller right anterior HC and left ACC than nondepressed monkeys. In nondepressed monkeys, sertraline reduced right HC volume, especially right anterior HC volume. In depressed monkeys sertraline increased left ACC volume. In nondepressed monkeys, sertraline reduced left BA24 volumes resulting in smaller BA24 volumes in nondepressed than sertraline-treated depressed monkeys. These observations suggest that SSRIs may differentially affect neural structures in depressed and nondepressed individuals.