Developmental Imaging and Psychopathology Laboratory, Department of Psychiatry, University of Geneva School of Medicine, Geneva, Switzerland.
Medical Image Processing Lab, Institute of Bioengineering, EPFL, Lausanne, Switzerland.
Transl Psychiatry. 2021 May 29;11(1):336. doi: 10.1038/s41398-021-01456-x.
Cognitive deficits in individuals at risk of psychosis represent a significant challenge for research, as current strategies for symptomatic treatment are often ineffective. Recent studies showed that atypical cognitive development predicts the occurrence of psychotic symptoms. Additionally, abnormal brain development is known to predate clinical manifestations of psychosis. Therefore, critical developmental stages may be the best period for early interventions expected to prevent cognitive decline and protect brain maturation. However, it is challenging to identify and treat individuals at risk of psychosis in the general population before the onset of the first psychotic symptoms. 22q11.2 deletion syndrome (22q11DS), the neurogenetic disorder with the highest genetic risk for schizophrenia, provides the opportunity to prospectively study the development of subjects at risk for psychosis. In this retrospective cohort study, we aimed to establish if early treatment with SSRIs in children and adolescents with 22q11DS was associated with long-term effects on cognition and brain development. We included 98 participants with a confirmed diagnosis of 22q11DS followed up 2-4 times (age range: 10-32). Thirty subjects without psychiatric disorders never received psychotropic medications, thirty had psychotic symptoms but were not treated with SSRIs, and 38 received SSRIs treatment. An increase in IQ scores characterized the developmental trajectories of participants receiving treatment with SSRIs, even those with psychotic symptoms. The thickness of frontal regions and hippocampal volume were also relatively increased. The magnitude of the outcomes was inversely correlated to the age at the onset of the treatment. We provide preliminary evidence that early long-term treatment with SSRIs may attenuate the cognitive decline associated with psychosis in 22q11DS and developmental brain abnormalities.
个体在出现精神病症状之前，认知缺陷是研究的重大挑战，因为当前针对症状的治疗策略通常效果不佳。最近的研究表明，非典型认知发展可预测精神病症状的发生。此外，已知异常的大脑发育早于精神病的临床表现。因此，关键的发育阶段可能是早期干预的最佳时期，以预防认知能力下降和保护大脑成熟。然而，在首次出现精神病症状之前，在普通人群中识别和治疗有精神病风险的个体具有挑战性。22q11.2 缺失综合征（22q11DS）是精神分裂症遗传风险最高的神经发育障碍，为前瞻性研究有精神病风险的个体的发展提供了机会。在这项回顾性队列研究中，我们旨在确定儿童和青少年患有 22q11DS 时，早期使用 SSRIs 治疗是否与认知和大脑发育的长期影响相关。我们纳入了 98 名经确诊患有 22q11DS 的参与者，这些参与者随访了 2-4 次（年龄范围：10-32 岁）。30 名无精神疾病的受试者从未接受过精神药物治疗，30 名患有精神病症状但未接受 SSRIs 治疗，38 名接受了 SSRIs 治疗。接受 SSRIs 治疗的参与者的 IQ 评分增加，具有特征性的发展轨迹，甚至那些有精神病症状的参与者也是如此。额叶区域的厚度和海马体体积也相对增加。结果的幅度与治疗开始时的年龄呈反比。我们提供了初步证据表明，早期长期使用 SSRIs 可能会减轻 22q11DS 中与精神病相关的认知能力下降和发育性大脑异常。
