栏目: 论　著

摘要
• 摘要:   目的  研究重性精神疾病（精神分裂症、双相障碍和重性抑郁障碍）海马发育偏倚及其与认知功能的关系。  方法  采集174例首发未用药精神分裂症患者，169例双相障碍患者，184例未用药重性抑郁障碍患者和321例健康受试的结构磁共振成像数据，经Freesurfer预处理后得到海马体积。使用大脑发育常模计算海马发育偏倚分数。采集视觉记忆、注意力、空间工作记忆等认知功能数据。性别分层比较海马发育偏倚分数在对照组和疾病组之间的差异，探索年龄对海马发育偏倚分数的调节效应，计算海马发育偏倚分数与认知功能的相关性。  结果  重性精神疾病患者海马发育偏倚分数均低于健康对照（FDR-P<0.05）。调节效应分析显示低年龄组〔<（25.83～28.56）岁〕患者海马发育偏倚分数低于正常对照，高年龄组〔>（35.87～54.35）岁〕患者海马发育偏倚分数高于正常对照。男性精神分裂症患者的右侧海马发育偏倚分数与空间工作记忆错误数量成正相关（r=0.32，FDR-P=0.04）。  结论  本研究结果提示重性精神疾病患者中海马发育存在异常，且不同年龄海马发育异常存在差异。基于大脑发育常模的海马发育偏倚分数可以为进一步了解重性精神疾病提供新的视角。

  关键词:
  • 海马 / 
  • 大脑发育常模 / 
  • 偏倚分数 / 
  • 认知 / 
  • 重性精神疾病 
  Abstract:   Objective  To investigate hippocampal development deviation and its association with cognition in patients with major psychiatric disorders (MPDs), including schizophrenia, bipolar disorder and major depressive disorder.   Methods  The T1-weighted MRI data of 174 first-episode drug-naïve schizophrenia (FES) atients, 169 bipolar disorder (BD) patients, 184 major depressive disorder (MDD) patients, and 321 healthy controls were collected and their hippocampal volume was extracted after preprocessing with Freesurfer 5.3. A normative neurodevelopment model was applied to calculate the hippocampal deviation scores. Data on cognitive functions, including visual memory, attention, spatial working memory, were collected. Comparison by different sexes was made to identify difference between the hippocampal development deviation scores of the control group and those of the disease groups. We also investigated the moderating effect of age on the deviation score and explored the association between the deviation score and cognitive function.   Results  The hippocampal development deviation scores of patients with MPDs were significantly lower than those of the healthy controls (false discovery rate [FDR]-P<0.05). Analysis of the moderating effect of age revealed lower deviation scores in young patients (<[25.83-28.56] yr.) and higher deviation scores in old patients (>[35.87-54.35] yr.) in comparison with those of the healthy controls. The right hippocampal deviation scores in male FES patients were positively correlated with the number of errors for tasks concerning spatial working memory (r=0.32, FDR-P=0.04).   Conclusion  Our findings suggest abnormal hippocampal development in MPDs patients and its different distribution in MPDs patients of different age groups. The hippocampal development deviation score may provide a new perspective for further understanding of etiology in MPDs.

  Key words:
  • Hippocampus / 
  • Normative neurodevelopment model / 
  • Deviation score / 
  • Cognition / 
  • Major psychiatric disorders 
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  图  1  海马发育偏倚分数在不同组间的分布及比较

  Figure  1.  The distribution and comparison of hippocampal deviation scores between groups

  The X-axis represents the corrected hippocampal development deviation score. Colors represent Cohen's d effect size for deviation scores between groups. P values are false discovery rate (FDR)-corrected. The abbreviations are explained in the note to Table 1. ^* P<0.05, ^** P<0.01, ^*** P<0.001, vs. HCs.

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  图  2  年龄对海马发育偏倚分数的调节作用

  Figure  2.  Moderating effect of age on the hippocampal development deviation scores

  The green region represents the significance of moderating effect lower than 0.05. The red region indicates an insignificant moderating effect. The abbreviations are explained in the note to Table 1.

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  图  3  疾病组中海马发育偏倚分数与认知功能的关系

  Figure  3.  Association between hippocampal development deviation scores and cognitive scores in the disease groups

  The abbreviations are explained in the note to Table 1. ^* FDR-P<0.05.

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  表  1  一般人口学资料、认知功能及临床特征

  Table  1.   General demographic, cognitive, and clinical data

  Item	HCs (n=178)	FES (n=174)	BD (n=169)	MDD (n=184)	χ2/F	P
  Demographic information
  (Female/male)/case	105/73	96/78	93/76	115/69	2.78	0.43
  Age/yr.	24.20±9.26*	20.02± 6.98	25.55±9.19*	27.16±9.15*	21.80	<0.001
  Education years/year	13.93±4.42*	11.11±2.89	13.51±3.01*	13.60±3.58*	25.35	<0.001
  Onset age/yr.	−	18.91±6.85	−	−	−	−
  Duration of illness/d	−	−	55.73±65.79	32.97±46.96	−	−
  Cognitive evaluation
  DMS-PC	90.12±7.49*	77.71±14.03	86.28±9.18*, #	85.00±11.04*, #	37.55	<0.001
  IED-SC	8.43±1.31*	7.71±1.83	7.96±1.64#	8.33±2.66	4.72	<0.01
  RVP-TCR	250.24±24.01*	236.31±24.18	244.35±23.06*	246.43±23.08*	10.05	<0.001
  RVP-ML	406.35±94.41*	484.58±156.38	434.29±118.13*	427.97±115.40*	11.42	<0.001
  SWM-BE	20.84±20.48*	39.08±25.14	25.41±19.94*	25.35±18.55*	22.22	<0.001
  SWM-WE	2.65±6.16	3.45±5.42	2.26±3.51	1.93±3.01*	3.04	0.03
  Clinical evaluation
  HAMD TS	−	−	10.13±7.15	20.77±5.38	−	−
  YMRS TS	−	−	7.17±8.68	−	−	−
  PANSS TS	−	83.97±21.96	−	−	−	−
  PANSS PS	−	22.01±6.40	−	−	−	−
  PANSS NS	−	21.91±8.39	−	−	−	−
  PANSS GPS	−	40.06±11.51	−	−	−	−
  FES: first-episode drug-naïve schizophrenia; BD: bipolar disorder; MDD: major depressive disorder; HCs: healthy controls; DMS-PC: delay matching-to-sample percentage correction; IED-SC: intra/extradimensional set shift stage completed; RVP-TCR: rapid visual information processing total correct rejections; RVP-ML: rapid visual information processing mean latency; SWM-BE: spatial working memory between search errors; SWM-WE: spatial working memory within errors; HAMD: Hamilton rating scale for depression; YMRS: Young mania rating scale; PANSS: positive and negative syndrome scale; TS: total score; PS: positive scale; NS: negative scale; GPS: general psychopathology scale. －: unmeasured value. * P<0.05, vs. FES; # P<0.05, vs. HCs.

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  表  2  海马原始体积组间比较

  Table  2.   Comparison of hippocampal volume between groups

  Hippocampal volume	Female					Male
  	HCs (n=178)	FES (n=174)	BD (n=169)	MDD (n=184)		HCs (n=178)	FES (n=174)	BD (n=169)	MDD (n=184)
  Left	4049.02±324.37	3910.42±293.29*	3985.57±339.00	3983.99±320.98		4315.21±391.42	4275.51±347.52	4267.69±396.93	4376.88±332.80
  Right	4252.89±319.98	4113.06±353.55	4216.64±368.90	4190.97±341.60		4515.21±403.81	4548.47±362.95	4516.65±460.38	4619.37±362.84
  The abbreviations are explained in the note to Table 1. * P<0.05, vs. HCs.

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