Fennema Diede, Barker Gareth J, O'Daly Owen, Duan Suqian, Carr Ewan, Goldsmith Kimberley, Young Allan H, Moll Jorge, Zahn Roland
Centre of Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, Centre for Affective Disorders, King's College London, London, United Kingdom.
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Biol Psychiatry Glob Open Sci. 2024 Mar 13;4(3):100308. doi: 10.1016/j.bpsgos.2024.100308. eCollection 2024 May.
A seminal study found higher subgenual frontal cortex resting-state connectivity with 2 left ventral frontal regions and the dorsal midbrain to predict better response to psychotherapy versus medication in individuals with treatment-naïve major depressive disorder (MDD). Here, we examined whether these subgenual networks also play a role in the pathophysiology of clinical outcomes in MDD with early treatment resistance in primary care.
Forty-five people with current MDD who had not responded to ≥2 serotonergic antidepressants ( = 43, meeting predefined functional magnetic resonance imaging minimum quality thresholds) were enrolled and followed over 4 months of standard care. Functional magnetic resonance imaging resting-state connectivity between the preregistered subgenual frontal cortex seed and 3 previously identified left ventromedial, ventrolateral prefrontal/insula, and dorsal midbrain regions was extracted. The clinical outcome was the percentage change on the self-reported 16-item Quick Inventory of Depressive Symptomatology.
We observed a reversal of our preregistered hypothesis in that higher resting-state connectivity between the subgenual cortex and the a priori ventrolateral prefrontal/insula region predicted favorable rather than unfavorable clinical outcomes ( = -0.43, = .006). This generalized to the sample including participants with suboptimal functional magnetic resonance imaging quality ( = -0.35, = .02). In contrast, no effects ( = 0.12, = -0.01) were found for connectivity with the other 2 preregistered regions or in a whole-brain analysis (voxel-based familywise error-corrected < .05).
Subgenual connectivity with the ventrolateral prefrontal cortex/insula is relevant for subsequent clinical outcomes in current MDD with early treatment resistance. Its positive association with favorable outcomes could be explained primarily by psychosocial rather than the expected pharmacological changes during the follow-up period.
一项开创性研究发现，在未经治疗的重度抑郁症（MDD）患者中，膝下前扣带回皮质与左侧两个腹侧额叶区域以及中脑背侧的静息态连接性更高，预示着其对心理治疗的反应优于药物治疗。在此，我们研究了这些膝下网络是否也在初级保健中对早期治疗抵抗的MDD临床结局的病理生理学中发挥作用。
招募了45名当前患有MDD且对≥2种血清素能抗抑郁药无反应的患者（n = 43，符合预定义的功能磁共振成像最低质量阈值），并在4个月的标准护理期间对其进行随访。提取了预先注册的膝下前扣带回皮质种子与3个先前确定的左侧腹内侧、腹外侧前额叶/脑岛以及中脑背侧区域之间的功能磁共振成像静息态连接性。临床结局是自我报告的16项抑郁症状快速清单上的百分比变化。
我们观察到预先注册的假设出现了反转，即膝下皮质与先验腹外侧前额叶/脑岛区域之间更高的静息态连接性预示着良好而非不良的临床结局（β = -0.43，P = 0.006）。这在包括功能磁共振成像质量欠佳的参与者的样本中也成立（β = -0.35，P = 0.02）。相比之下，与其他2个预先注册区域的连接性或全脑分析均未发现影响（β = 0.12，P = 0.01）（基于体素的家族性错误校正P < 0.05）。
膝下与腹外侧前额叶皮质/脑岛的连接性与当前对早期治疗抵抗的MDD的后续临床结局相关。其与良好结局的正相关主要可通过心理社会因素而非随访期间预期的药理学变化来解释。
