Objective

Although the neural underpinnings of antisocial behavior have been studied extensively, research on pharmacologic interventions targeting specific neural mechanisms remains sparse. Hypoactivity of the amygdala and ventromedial prefrontal cortex (vmPFC) has been reported in antisocial adolescents, which could account for deficits in fear learning (amygdala) and impairments in decision making (vmPFC), respectively. Limited clinical research suggests positive effects of methylphenidate, a dopamine agonist, on antisocial behavior in adolescents. Dopamine is a key neurotransmitter involved in amygdala and vmPFC functioning. The objective of this study was to investigate whether methylphenidate targets dysfunctions in these brain areas in adolescents with antisocial behavior.

Method

A group of 42 clinical referred male adolescents (14–17 years old) with a disruptive behavior disorder performed a fear learning/reversal paradigm in a randomized double-blinded placebo-controlled pharmacologic functional magnetic resonance imaging study. Participants with disruptive behavior disorder were randomized to receive a single dose of methylphenidate 0.3 to 0.4 mg/kg (n = 22) or placebo (n = 20) and were compared with 21 matched healthy controls not receiving medication.

Results

In a region-of-interest analysis of functional magnetic resonance imaging data during fear learning, the placebo group showed hyporeactivity of the amygdala compared with healthy controls, whereas amygdala reactivity was normalized in the methylphenidate group. There were no group differences in vmPFC reactivity during fear reversal learning. Whole-brain analyses showed no group differences.

Conclusion

These findings suggest that methylphenidate is a promising pharmacologic intervention for youth antisocial behavior that could restore amygdala functioning.

Clinical trial registration information: Fear Conditioning During Specific Conditions in Antisocial Adolescents: A Neuroimaging Study. http://www.trialregister.nl/trialreg/index.asp; NTR4088.

中文翻译：

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哌醋甲酯在反社会青少年恐惧学习中的作用：随机对照fMRI试验。

客观的

尽管已经广泛研究了反社会行为的神经基础，但是针对特定神经机制的药物干预研究仍然很少。在反社会青少年中，杏仁核和腹侧前额叶皮层（vmPFC）的机能减退已有报道，这可能分别解释了恐惧学习的不足（杏仁体）和决策障碍（vmPFC）。有限的临床研究表明，多巴胺激动剂哌醋甲酯对青少年的反社会行为具有积极作用。多巴胺是参与杏仁核和vmPFC功能的关键神经递质。这项研究的目的是调查哌醋甲酯是否针对具有反社会行为的青少年在这些大脑区域的功能障碍。

方法

在一项随机双盲安慰剂对照药理功能磁共振成像研究中，一组42名临床上被提及的男性青少年（14-17岁）患有破坏性行为障碍，进行了恐惧学习/逆转范例。患有破坏性行为障碍的参与者被随机分配接受单剂量的哌醋甲酯0.3至0.4 mg / kg（n = 22）或安慰剂（n = 20），并与21名未接受药物治疗的健康对照者进行比较。

结果

在恐惧学习过程中功能性磁共振成像数据的关注区域分析中，与健康对照组相比，安慰剂组显示杏仁核反应性低，而哌醋甲酯组杏仁核反应性正常。在恐惧逆转学习过程中，vmPFC反应性没有组间差异。全脑分析显示无组间差异。

结论

这些发现表明，哌醋甲酯是一种有希望的药物干预措施，可用于年轻人的反社会行为，可以恢复杏仁核的功能。

临床试验注册信息：反社会青少年在特定条件下的恐惧条件：一项神经影像学研究。http://www.trialregister.nl/trialreg/index.asp; NTR4088。