Background

The putamen has been implicated in depressive disorders, but how its structure and function increase depression risk is not clearly understood. Here, we examined how putamen volume, neuronal density, and mood-modulated functional activity relate to family history and prospective course of depression.

Methods

The study includes 115 second- and third-generation offspring at high or low risk for depression based on the presence or absence of major depressive disorder in the first generation. Offspring were followed longitudinally using semistructured clinical interviews blinded to their familial risk; putamen structure, neuronal integrity, and functional activation were indexed by structural magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (N-acetylaspartate/creatine ratio), and functional MRI activity modulated by valence and arousal components of a mood induction task, respectively.

Results

After adjusting for covariates, the high-risk individuals had lower putamen volume (standardized betas, β-_left = −0.17, β-_right = −0.15, ps = .002), N-acetylaspartate/creatine ratio (β-_left= −0.40, β-_right= −0.37, ps < .0001), and activation modulated by valence (β-_left = −0.22, β-_right = −0.27, ps < .05) than low-risk individuals. Volume differences were greater at younger ages, and N-acetylaspartate/creatine ratio differences were greater at older ages. Lower putamen volume also predicted major depressive disorder episodes up to 8 years after the scan (β-_left = −0.72, p = .013; β-_right = −0.83, p = .037). Magnetic resonance spectroscopy and task functional MRI measures were modestly correlated (0.27 ≤ r ≤ 0.33).

Conclusions

Findings demonstrate abnormalities in putamen structure and function in individuals at high risk for major depressive disorder. Future studies should focus on this region as a potential biomarker for depressive illness, noting meanwhile that differences attributable to family history may peak at different ages based on which MRI modality is being used to assay them.

中文翻译：

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壳核结构和功能在家族性抑郁症风险中的作用：多模态成像研究

 背景

壳核与抑郁症有关，但其结构和功能如何增加抑郁风险尚不清楚。在这里，我们研究了壳核体积、神经元密度和情绪调节功能活动与家族史和抑郁症未来病程的关系。

 方法

该研究包括 115 名第二代和第三代后代，根据第一代是否患有重度抑郁症，分为高风险或低风险抑郁症。使用半结构化临床访谈对后代进行纵向随访，不了解其家族风险；壳核结构、神经元完整性和功能激活分别通过结构磁共振成像（MRI）、质子磁共振波谱（ N-乙酰天冬氨酸/肌酸比）以及由情绪诱导任务的效价和唤醒成分调节的功能性 MRI 活动来索引。

 结果

调整协变量后，高风险个体的壳核体积较低（标准化 β，β-_左= -0.17，β-_右= -0.15， p s = .002）、 N - 乙酰天冬氨酸/肌酸比率（β-_左= -0.40, β-_右= -0.37, p s < .0001)，并且通过化合价调节激活 (β-_左= -0.22, β-_右= -0.27, p s < .05) 高于低风险个体。年龄较小时体积差异较大，年龄较大时N-乙酰天冬氨酸/肌酸比率差异较大。较低的壳核体积还可以预测扫描后长达 8 年的重度抑郁症发作（β-_左= -0.72， p = .013；β-_右= -0.83， p = .037）。磁共振波谱和任务功能 MRI 测量有适度相关 (0.27 ≤ r ≤ 0.33)。

 结论

研究结果表明，重度抑郁症高危人群的壳核结构和功能存在异常。未来的研究应重点关注该区域，将其作为抑郁症的潜在生物标志物，同时指出，家族史引起的差异可能在不同年龄达到峰值，具体取决于使用 MRI 模式进行分析。