Correia Banny Silva Barbosa, Nani João Victor, Waladares Ricardo Raniery, Stanisic Danijela, Costa Tássia Brena Barroso Carneiro, Hayashi Mirian A F, Tasic Ljubica
Instituto de Química, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-970, Brazil.
Departamento de Farmacologia, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo 04044-020, Brazil.
Biomedicines. 2021 Feb 26;9(3):235. doi: 10.3390/biomedicines9030235.
Schizophrenia (SCZ) treatment is essentially limited to the use of typical or atypical antipsychotic drugs, which suppress the main symptoms of this mental disorder. Metabolic syndrome is often reported in patients with SCZ under long-term drug treatment, but little is known about the alteration of lipid metabolism induced by antipsychotic use. In this study, we evaluated the blood serum lipids of a validated animal model for SCZ (Spontaneously Hypertensive Rat, SHR), and a normal control rat strain (Normotensive Wistar Rat, NWR), after long-term treatment (30 days) with typical haloperidol (HAL) or atypical clozapine (CLZ) antipsychotics. Moreover, psychostimulants, amphetamine (AMPH) or lisdexamfetamine (LSDX), were administered to NWR animals aiming to mimic the human first episode of psychosis, and the effects on serum lipids were also evaluated. Discrepancies in lipids between SHR and NWR animals, which included increased total lipids and decreased phospholipids in SHR compared with NWR, were similar to the differences previously reported for SCZ patients relative to healthy controls. Administration of psychostimulants in NWR decreased omega-3, which was also decreased in the first episode of psychosis of SCZ. Moreover, choline glycerophospholipids allowed us to distinguish the effects of CLZ in SHR. Thus, changes in the lipid metabolism in SHR seem to be reversed by the long-term treatment with the atypical antipsychotic CLZ, which was under the same condition described to reverse the SCZ-like endophenotypes of this validated animal model for SCZ. These data open new insights for understanding the potential influence of the treatment with typical or atypical antipsychotics on circulating lipids. This may represent an outcome effect from metabolic pathways that regulate lipids synthesis and breakdown, which may be reflecting a cell lipids dysfunction in SCZ.
精神分裂症（SCZ）的治疗基本上局限于使用典型或非典型抗精神病药物，这些药物可抑制这种精神障碍的主要症状。长期药物治疗的SCZ患者常出现代谢综合征，但对于抗精神病药物使用所诱导的脂质代谢改变却知之甚少。在本研究中，我们评估了经典型抗精神病药物氟哌啶醇（HAL）或非典型抗精神病药物氯氮平（CLZ）长期治疗（30天）后，一种经过验证的SCZ动物模型（自发性高血压大鼠，SHR）和正常对照大鼠品系（血压正常的Wistar大鼠，NWR）的血清脂质情况。此外，对NWR动物给予精神兴奋剂苯丙胺（AMPH）或赖氨酸安非他命（LSDX），旨在模拟人类首次精神病发作，并评估其对血清脂质的影响。SHR和NWR动物之间的脂质差异，包括SHR与NWR相比总脂质增加和磷脂减少，与先前报道的SCZ患者相对于健康对照的差异相似。对NWR动物给予精神兴奋剂会降低ω-3，这在SCZ首次精神病发作时也会降低。此外，胆碱甘油磷脂使我们能够区分CLZ对SHR的影响。因此，长期使用非典型抗精神病药物CLZ治疗似乎可以逆转SHR中的脂质代谢变化，在相同条件下，这种药物也可逆转这种经过验证的SCZ动物模型的类SCZ内表型。这些数据为理解典型或非典型抗精神病药物治疗对循环脂质的潜在影响提供了新的见解。这可能代表了调节脂质合成和分解的代谢途径的一种结果效应，这可能反映了SCZ中的细胞脂质功能障碍。
