Schulze Katja K, Hall Mei-Hua, McDonald Colm, Marshall Nicolette, Walshe Muriel, Murray Robin M, Bramon Elvira
Section of General Psychiatry, Social, Genetic Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, London, UK, and Psychology Research Laboratory, McLean Hospital, Belmont, MA, USA.
Biol Psychiatry. 2007 Jul 15;62(2):121-8. doi: 10.1016/j.biopsych.2006.08.006. Epub 2006 Nov 21.
Diminished suppression of the P50 response, a consistent finding in schizophrenia, has also been reported in patients with psychotic bipolar disorder. It is a promising endophenotype for schizophrenia, but its relationship to genetic liability in bipolar disorder is unknown. We therefore assessed whether diminished P50 suppression is associated with familial risk for psychotic bipolar disorder.
The P50 response was collected in a conditioning (C)--testing (T) paradigm from 42 outpatients with bipolar 1 disorder who had experienced psychotic symptoms and 44 of their unaffected first-degree relatives, all from families multiply affected with bipolar disorder or another non-organic psychotic disorder; 48 healthy control subjects were also studied. The T/C ratio was compared between the groups, with linear regression analyses and robust variance estimators for clustered data.
Both patients (estimated mean difference in T/C ratio to control subjects, 32, 95% confidence interval [CI] 15-48, p=.001) and unaffected relatives (20, 95% CI 7-32, p=.002) demonstrated higher T/C ratio, thus indicating diminished P50 suppression compared with control subjects.
To our knowledge, this is the first report of diminished P50 gating in unaffected relatives of psychotic bipolar disorder patients from multiply affected families. Our results suggest that impaired P50 gating is a putative endophenotype for psychotic bipolar disorder and thus might reflect the impact of susceptibility genes across psychosis.
P50反应抑制减弱是精神分裂症的一个常见表现,在伴有精神病性症状的双相情感障碍患者中也有报道。它是精神分裂症一种很有前景的内表型,但其与双相情感障碍遗传易感性的关系尚不清楚。因此,我们评估了P50反应抑制减弱是否与伴有精神病性症状的双相情感障碍的家族风险相关。
采用条件刺激(C)-测试(T)范式,收集了42例有精神病性症状的双相I型障碍门诊患者及其44名未患病的一级亲属的P50反应,所有患者均来自双相情感障碍或其他非器质性精神病性障碍的多患病家族;还研究了48名健康对照者。比较了各组之间的T/C比值,并对聚类数据进行了线性回归分析和稳健方差估计。
患者(T/C比值与对照者的估计平均差异为32,95%置信区间[CI]为15-48,p = 0.001)和未患病亲属(20,95%CI为7-32,p = 0.002)的T/C比值均较高,表明与对照者相比,P50反应抑制减弱。
据我们所知,这是首次报道来自多患病家族的伴有精神病性症状的双相情感障碍患者未患病亲属的P50门控减弱。我们的结果表明,P50门控受损是伴有精神病性症状的双相情感障碍的一种假定内表型,因此可能反映了易感性基因对精神病的影响。