Meller Tina, Lundberg Clara, Maj Carlo, Hoffmann Per, Forstner Andreas J, Nöthen Markus M, Nenadić Igor
Cognitive Neuropsychiatry Laboratory, Department of Psychiatry and Psychotherapy, Philipps Universität Marburg, Marburg 35039, Germany.
Center for Mind, Brain and Behavior (CMBB), Universities of Marburg, Gießen, and Darmstadt, Marburg, Germany.
Schizophr Bull. 2025 Mar 4;51(Suppl 2):S85-S94. doi: 10.1093/schbul/sbae161.
Schizotypy is a well-established phenotype for psychosis proneness and risk. Yet, its genetic underpinnings and relations to genetic bases of the schizophrenia spectrum are not well understood owing to conflicting findings. In a deep phenotyping approach, we hypothesized that genetic markers of risk for and to schizophrenia are differentially associated with (trait-level) dimensions of schizotypy and (state-level) prodromal symptoms.
In 367 (130 male, 237 female) psychiatrically healthy young adults, we assessed multiple schizotypy instruments (OLIFE, SPQ-B, Multidimensional Schizotypy Scales), aggregated into composite scores, and a measure of prodromal symptoms (PQ-16). Those were tested for direct and interactive associations with the polygenic risk score (PRS) for schizophrenia and a novel PRS for resilience to schizophrenia.
Both prodromal symptom number (rho = 0.16, pcorr = .018) and distress (rho = 0.14, pcorr = .027) were positively related to the schizophrenia PRS. Positive schizotypy showed a similar association but did not remain significant after correction (rho = 0.11, pcorr = .082). Schizophrenia PRS and disorganized schizotypy had a negative interactive effect on prodromal symptom distress (b = -0.10, pcorr = .048). The resilience score did not show any significant associations with any of the measures.
These results further support the idea of a (partially) shared genetic basis of schizophrenia and nonclinical, predominantly positive expressions of the psychosis spectrum but also indicate relevant distinctions between the 2, possibly related to other modulating factors or general (transdiagnostic) psychopathological risk. In line with previous findings, effects seem to be more robust for state- than trait-level markers, but these may also be influencing each other.
分裂型特质是一种公认的易患精神病和患病风险的表型。然而，由于研究结果相互矛盾，其遗传基础以及与精神分裂症谱系遗传基础的关系尚未得到充分理解。在一项深度表型分析中，我们假设精神分裂症患病风险和抵御精神分裂症的遗传标记与分裂型特质的（特质水平）维度和前驱症状的（状态水平）存在差异关联。
在367名（130名男性，237名女性）精神健康的年轻成年人中，我们评估了多种分裂型特质测量工具（OLIFE、SPQ - B、多维分裂型特质量表），将其汇总为综合得分，并测量了前驱症状（PQ - 16）。对这些指标进行测试，以探究它们与精神分裂症多基因风险评分（PRS）以及一种新的抵御精神分裂症的PRS之间的直接和交互关联。
前驱症状数量（rho = 0.16，pcorr = 0.018）和痛苦程度（rho = 0.14，pcorr = 0.027）均与精神分裂症PRS呈正相关。阳性分裂型特质显示出类似的关联，但校正后不再显著（rho = 0.11，pcorr = 0.082）。精神分裂症PRS与紊乱型分裂型特质对前驱症状痛苦程度有负向交互作用（b = -0.10，pcorr = 0.048）。抵御得分与任何测量指标均无显著关联。
这些结果进一步支持了精神分裂症与精神病谱系非临床、主要为阳性表现（部分）共享遗传基础的观点，但也表明两者之间存在相关差异，这可能与其他调节因素或一般（跨诊断）精神病理风险有关。与先前的研究结果一致，状态水平标记的效应似乎比特质水平标记更强，但两者也可能相互影响。
