Fear Conditioning, Extinction and Recall in Healthy Subjects and in Obsessive-compulsive Disorder Patients Pre and Post Treatment With Sertraline.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- Main functional neuroimaging measure
研究概览
简要总结
24 OCD patients and 24 healthy subjects will be submitted to a two-day fear conditioning paradigm during acquisition of functional magnetic resonance imaging (fMRI). OCD patients will be submitted to the paradigm at two timepoints: baseline and 4 weeks after treatment initiation with sertraline up to 200mg/day or maximum tolerated dosage. OCD patients are expected to demonstrate worsened extinction retention compared to healthy subjects at baseline. Sertraline treatment is expected to improve extinction retention compared to baseline and to normalize the brain regions being recruited with the conditioned stimuli presented during the recall phase.
详细描述
Fear conditioning paradigms are used to investigate the learning process of the fear response in patients with psychiatric disorders and healthy subjects. Patients with post traumatic stress disorder have been shown to fail to retrieve the memory of fear extinction during the recall phase of the fear conditioning paradigm when compared to healthy subjects. In one previous trial, obsessive-compulsive disorder (OCD) patients have demonstrated the same failure to recall extinction and the results from functional magnetic resonance imaging (fMRI) activation maps have shown different regions being recruited during recall when compared with healthy subjects. However, in that previous trial, some of the OCD patients included were already taking medication for OCD. In the current trial, we will evaluate 24 unmedicated OCD patients with a two-day fear conditioning paradigm before and after 4-weeks of treatment initiation with sertraline up to 200mg/day or maximum tolerated dosage. Sertraline is a first-line treatment option for OCD. At baseline, OCD patients will be compared to 24 healthy subjects. At post treatment, fear conditioning and fMRI results wil be compared to baseline. OCD patients are expected to demonstrate worsened extinction retention compared to healthy subjects at baseline. Sertraline treatment is expected to improve extinction retention compared to baseline and to normalize the brain regions being recruited with the conditioned stimuli presented during the recall phase. By "normalize" we mean that after treatment the regions being recruited will be the same as the ones recruited by healthy subjects during baseline, in other words, differences found at baseline regarding brain activation by the conditioned stimuli are expected to disappear after treatment.
Abbreviations: CS= conditioned stimuli, CS+= conditioned stimuli to shock, CS-=neutral conditioned stimuli, CS+E= extinguished conditioned stimuli to shock, CS+U=unextinguished conditioned stimuli to shock
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy controls
- •willingness to participate in research
- •OCD patients
- •willingness to participate in research
- •main diagnosis of OCD (psychiatric clinical evaluation)
- •minimum YBOCS (Yale Brown Obsessive-compulsive severity scale) score of 16 points
排除标准
- •Healthy controls
- •any current psychiatric diagnosis according to evaluation using semi structured interview for DSM IV diagnoses (SCID I)
- •any past psychiatric diagnoses except single major depression episode and simple phobia (evaluation by semi structure interview-SCID I)
- •current use of psychotropic medications (last use has to be at least 3 months prior to study initiation)
- •chronic use of any medications except vitamins and contraceptives
- •MRI exclusionary criteria (metal implants, recently made tatoos, claustrophobia, etc)
- •being pregnant
- •OCD patients
- •comorbidity with neurodevelopmental disorders (autism, mental retardation), current psychotic disorders, current substance dependence or abuse, bipolar mood disorder according to evaluation using semi structured interview for DSM IV diagnoses (SCID I)
- •current use of psychotropic medications (last use has to be at least 3 months prior to study initiation)
- •MRI exclusion criteria(metal implants, recently made tatoos, claustrophobia, etc)
- •being pregnant or at risk of becoming pregnant
研究组 & 干预措施
Sertraline open label
Sertraline hydrochloride up to 200mg/day or maximum tolerated dosage for 4-weeks.
干预措施: Sertraline Hydrochloride (Drug)
结局指标
主要结局
Main functional neuroimaging measure
时间窗: Baseline for both groups (OCD and helthy subjects), change from baseline to 4 weeks after treatment initiation only for intervention group
ventro medial prefrontal cortex (vmPFC) activation during recall phase
Main treatment outcome measure
时间窗: Change from baseline to 4 weeks after treatment initiation (only interventional group)
Yale Brown Obsessive Compulsive Scale reduction (final score minus initial score)
Main behavioral measure (extinction retention index)
时间窗: Baseline for both groups (OCD and helthy subjects), change from baseline to 4 weeks after treatment initiation only for intervention group
Equation: 100-((MEAN(2 first CS+E during recall)/MAXIMUM(2 last CS+E during extinction))\*100)
次要结局
- Secondary behavioral measure (learning- conditioning index, OCD patients pre and post treatment)(Change from baseline to 4 weeks after treatment initiation (only interventional group))
- Secondary behavioral measure (learning- conditioning index, OCD patients versus healthy subjects)(Baseline (all subjects))
- Secondary Behavioral Measure (context discrimination index based on skin conductance, OCD patients pre and post treatment)(Change from baseline to 4 weeks after treatment initiation (only interventional group))
- Secondary functional neuroimaging measure (functional activation maps for contrast CS+/CS- during conditioning phase, OCD patients pre and post treatment)(Change from baseline to 4 weeks after treatment initiation (only interventional group))
- Secondary functional neuroimaging measure (functional activation maps for contrast CS+E/CS- during recall phase comparing change between post and pre treatment)(Change between baseline and 4 weeks after treatment initiation (only interventional group))
- Main functional neuroimaging measure (activation maps for contrast CS+E versus CS-during recall phase,OCD patients versus healthy subjects)(Baseline (all subjects))
- Secondary functional neuroimaging measure (functional activation maps for contrast CS+/CS- during conditioning phase, OCD patients versus healthy subjects)(Baseline (all subjects))
- Main behavioral measure baseline comparison (extinction retention index OCD patients versus healthy subjects)(Baseline)
- Secondary Behavioral Measure (context discrimination index based on skin conductance, OCD patients versus healthy subjects)(Baseline (all subjects))
- Secondary functional neuroimaging measure (functional activation maps for contrast CS+E/CS- during recall phase of baseline measurement, OCD patients versus healthy subjects)(Baseline (all subjects))
研究者
Juliana Belo Diniz
Psychiatrist, principal investigator
University of Sao Paulo