精神分裂症是一种精神障碍[13] 其特征是精神病的持续或复发发作。[5] 主要症状包括幻觉 (通常听到声音), 妄想, 和杂乱无章的思维。[7] 其他症状包括社交退缩, 情绪表达减少, 和冷漠。[5][14] 症状通常是逐渐出现的, 从青年时期开始, 在许多情况下永远无法解决。[3][7] 没有客观的诊断测试; 该诊断用于描述可能源于多种不同原因的观察到的行为. 除了观察到的行为外, 医生还会记录病史，其中包括患者报告的经历, 以及其他熟悉此人的人的报告, 做出诊断时。[7] 诊断某人患有精神分裂症, 医生应该确认症状和功能障碍已经存在六个月 (帝斯曼-5) 或一个月 (ICD-11).[7][11] 许多精神分裂症患者还有其他精神障碍, 尤其是物质使用障碍, 抑郁症, 焦虑症, 和强迫症。[7][15][16][17]
关于 0.3% 到 0.7% 的人在一生中被诊断出患有精神分裂症。[18] 在 2017, 估计有 1.1 万新病例和 2019 总共 20 全球百万例。[2][19] 男性更容易受到影响，平均发病时间更早,[2] 尽管一些大型评论尚未发现该疾病患病率存在性别差异。[20][21] 精神分裂症的可能原因包括遗传和环境因素。[5] 遗传因素包括各种常见和罕见的遗传变异。[22] 可能的环境因素包括在城市长大, 青春期吸食大麻, 感染, 一个人的母亲或父亲的年龄, 以及怀孕期间营养不良。[5][23]
大约一半的精神分裂症患者从长远来看会有显着改善，不会进一步复发, 其中一小部分会完全康复。[7][24] 另一半将终生受到损害。[25] 在某些情况下，人们可能会反复入院。[24] 长期失业等社会问题, 贫困, 无家可归, 开发, 和受害通常与精神分裂症相关。[26][27] 与一般人群相比, 精神分裂症患者的自杀率较高 (关于 5% 全面的) 以及更多的身体健康问题,[28][29] 导致平均预期寿命下降 20 年。[10] 在 2015, 估计的 17,000 死亡与精神分裂症有关。[12]
主要治疗方法是抗精神病药物, 以及咨询的同时, 岗位培训, 和社会康复。[5] 多达三分之一的人对最初的抗精神病药物没有反应, 在这种情况下，可以使用抗精神病药氯氮平。[30] 在医生判断存在对自己或他人造成伤害的风险的情况下, 他们可能会强制短期非自愿住院。[31] 长期住院治疗用于少数严重精神分裂症患者。[32] 在一些支持服务有限或不可用的国家, 长期住院更为常见。[33]
体征和症状
德国艺术家奥古斯特·纳特勒（August Natterer）的《我的眼睛在显现的那一刻》, 谁患有精神分裂症
精神分裂症是一种以知觉显着改变为特征的精神障碍, 想法, 情绪, 和行为。[34] Symptoms are described in terms of positive, and negative, and cognitive symptoms.[3][35] The positive symptoms of schizophrenia are the same for any psychosis and are sometimes referred to as psychotic symptoms. These may be present in any of the different psychoses, and are often transient making early diagnosis of schizophrenia problematic. Psychosis noted for the first time in a person who is later diagnosed with schizophrenia is referred to as a first-episode psychosis (FEP).[36][37]
Positive symptoms
Positive symptoms are those symptoms that are not normally experienced, but are present in people during a psychotic episode in schizophrenia. They include delusions, hallucinations, and disorganized thoughts and speech, typically regarded as manifestations of psychosis.[36] Hallucinations most commonly involve the sense of hearing as hearing voices but can sometimes involve any of the other senses of taste, sight, smell, and touch.[38] They are also typically related to the content of the delusional theme.[39] Delusions are bizarre or persecutory in nature. Distortions of self-experience such as feeling as if one’s thoughts or feelings are not really one’s own, to believing that thoughts are being inserted into one’s mind, sometimes termed passivity phenomena, are also common.[40] Thought disorders can include thought blocking, and disorganized speech – speech that is not understandable is known as word salad.[3][41] Positive symptoms generally respond well to medication,[5] and become reduced over the course of the illness, perhaps related to the age-related decline in dopamine activity.[7]
Negative symptoms
Negative symptoms are deficits of normal emotional responses, or of other thought processes. The five recognised domains of negative symptoms are: blunted affect – showing flat expressions or little emotion; alogia – a poverty of speech; anhedonia – an inability to feel pleasure; asociality – the lack of desire to form relationships, and avolition – a lack of motivation and apathy.[42][43] Avolition and anhedonia are seen as motivational deficits resulting from impaired reward processing.[44][45] Reward is the main driver of motivation and this is mostly mediated by dopamine.[45] 有人认为，负面症状是多维的，可分为冷漠或缺乏动力两个子领域, 以及表情的减弱。[42][46] 冷漠包括无意志, 快感缺失, 和社交退缩; 表达减少包括钝感, 和alogia。[47] 有时，表达能力减弱被视为言语和非言语的。[48]
冷漠占大约 50 最常见的阴性症状的百分比，并影响功能结果和随后的生活质量. 冷漠与影响记忆和计划（包括目标导向行为）的认知处理中断有关。[49] 这两个子领域表明需要单独的治疗方法。[50] 缺乏痛苦——与抑郁和焦虑的经历减少有关，是另一个值得注意的负面症状。[51] A distinction is often made between those negative symptoms that are inherent to schizophrenia, termed primary; and those that result from positive symptoms, from the side effects of antipsychotics, substance use disorder, and social deprivation – termed secondary negative symptoms.[52] Negative symptoms are less responsive to medication and the most difficult to treat.[50] However if properly assessed, secondary negative symptoms are amenable to treatment.[46]
Scales for specifically assessing the presence of negative symptoms, and for measuring their severity, and their changes have been introduced since the earlier scales such as the PANNS that deals with all types of symptoms.[50] These scales are the Clinical Assessment Interview for Negative Symptoms (CAINS), and the Brief Negative Symptom Scale (BNSS) also known as second-generation scales.[50][51][53] 在 2020, ten years after its introduction, a cross-cultural study of the use of BNSS found valid and reliable psychometric evidence for the five-domain structure cross-culturally.[51] The BNSS is designed to assess both the presence and severity and change of negative symptoms of the five recognised domains, and the additional item of reduced normal distress.[51] BNSS can register changes in negative symptoms concerning psychosocial and pharmacological intervention trials. BNSS has also been used to study a proposed non-D2 treatment called SEP-363856. Findings supported the favouring of five domains over the two-dimensional proposition.[51]
Cognitive symptoms
See also: Visual processing abnormalities in schizophrenia
Cognitive deficits are the earliest and most constantly found symptoms in schizophrenia. They are often evident long before the onset of illness in the prodromal stage, and may be present in early adolescence, or childhood.[54][55] They are a core feature but not considered to be core symptoms, as are positive and negative symptoms.[56][57] 然而, their presence and degree of dysfunction is taken as a better indicator of functionality than the presentation of core symptoms.[54] Cognitive deficits become worse at first episode psychosis but then return to baseline, and remain fairly stable over the course of the illness.[58][59]
The deficits in cognition are seen to drive the negative psychosocial outcome in schizophrenia, and are claimed to equate to a possible reduction in IQ from the norm of 100 to 70–85.[60][61] Cognitive deficits may be of neurocognition (nonsocial) or of social cognition.[62] Neurocognition is the ability to receive and remember information, and includes verbal fluency, 记忆, reasoning, problem solving, speed of processing, and auditory and visual perception.[59] Verbal memory and attention are seen to be the most affected.[61][63] Verbal memory impairment is associated with a decreased level of semantic processing (relating meaning to words).[64] Another memory impairment is that of episodic memory.[65] An impairment in visual perception that is consistently found in schizophrenia is that of visual backward masking.[59] Visual processing impairments include an inability to perceive complex visual illusions.[66] Social cognition is concerned with the mental operations needed to interpret, and understand the self and others in the social world.[59][62] This is also an associated impairment, 面部情绪感知常常很困难。[67][68] 面部感知对于普通社交互动至关重要。[69] 认知障碍通常对抗精神病药物没有反应, 有许多干预措施可以用来尝试改善它们; 认知矫正疗法尤其有帮助。[57]
发病
更多信息: 精神分裂症的基本症状
See also: 儿童精神分裂症和青春期 § 大脑的变化
发病通常发生在十几岁到三十岁出头之间, 发病高峰发生在二十出头到二十岁左右的男性中, 以及二十多岁的女性。[3][7][11] 年龄之前发病 17 被称为早发型,[70] 并在 年龄之前 13, 有时会发生, 被称为儿童精神分裂症或极早发性精神分裂症。[7][71] 发病后期可能发生在 20 岁之间 40 和 60, 称为迟发性精神分裂症。[62] 年龄较晚发病 60, 这可能很难区分为精神分裂症, 被称为极迟发性精神分裂症样精神病。[62] 晚发表明女性受影响的比例较高; 他们的症状不太严重，需要较低剂量的抗精神病药物。[62] 后来发现男性早发的趋势被女性绝经后发育的增加所平衡. 绝经前产生的雌激素对多巴胺受体有抑制作用，但其保护作用可能会被基因超载所覆盖。[72] 患有精神分裂症的老年人数量急剧增加。[73] 估计 70% 精神分裂症患者有认知缺陷, 这些在早发型和晚发型疾病中最为明显。[62][74]
Onset may happen suddenly or may occur after the slow and gradual development of a number of signs and symptoms, a period known as the prodromal stage.[7] Up to 75% of those with schizophrenia go through a prodromal stage.[75] The negative and cognitive symptoms in the prodrome stage can precede FEP by many months and up to five years.[58][76] The period from FEP and treatment is known as the duration of untreated psychosis (DUP) which is seen to be a factor in functional outcome. The prodromal stage is the high-risk stage for the development of psychosis.[59] Since the progression to first episode psychosis is not inevitable, an alternative term is often preferred of at risk mental state.[59] Cognitive dysfunction at an early age impact a young person’s usual cognitive development.[77] 前驱阶段的识别和早期干预将最大限度地减少对教育和社会发展的相关干扰，并且一直是许多研究的重点。[58][76] 有人建议使用 D-丝氨酸等抗炎化合物可以预防向精神分裂症的转变。[58] 认知症状并非继发于阳性症状或抗精神病药物的副作用。[59]
首次精神病发作后，前驱阶段的认知障碍变得更严重 (之后他们回到基线，然后保持相当稳定), 尽早干预以防止这种转变至关重要。[58] 认知行为疗法的早期治疗是黄金标准。[76] 精神分裂症经常出现笨拙和精细运动丧失的神经软体征, which may resolve with effective treatment of FEP.[11][78]
Risk factors
Main article: Risk factors of schizophrenia
See also: Developmental psychobiology
Schizophrenia is described as a neurodevelopmental disorder with no precise boundary, or single cause, and is thought to develop from gene–environment interactions with involved vulnerability factors.[5][79][80] The interactions of these risk factors are complex, as numerous and diverse insults from conception to adulthood can be involved.[80] A genetic predisposition on its own, without interacting environmental factors, will not give rise to the development of schizophrenia.[80][81] The genetic component means that prenatally brain development is disturbed, and environmental influence affects the postnatal development of the brain.[82] Evidence suggests that genetically susceptible children are more likely to be vulnerable to the effects of environmental risk factors.[82]
Genetic
Estimates of the heritability of schizophrenia are between 70% 和 80%, which implies that 70% 到 80% of the individual differences in risk to schizophrenia is associated with genetics.[22][83] These estimates vary because of the difficulty in separating genetic and environmental influences, and their accuracy has been queried.[84][85] The greatest risk factor for developing schizophrenia is having a first-degree relative with the disease (risk is 6.5%); 多于 40% of identical twins of those with schizophrenia are also affected.[86] If one parent is affected the risk is about 13% and if both are affected the risk is nearly 50%.[83] 然而, DSM-5 points out that most people with schizophrenia have no family history of psychosis.[7] 精神分裂症候选基因研究的结果通常未能找到一致的关联,[87] 全基因组关联研究确定的遗传位点只能解释疾病变异的一小部分。[88]
已知许多基因与精神分裂症有关, 每一种的影响都很小，且传播和表达方式未知。[22][89][90] 将这些效应大小汇总为多基因风险评分至少可以解释 7% 精神分裂症责任的可变性。[91] 大约 5% 的精神分裂症病例被认为至少部分归因于罕见的拷贝数变异 (变异体); 这些结构变异与已知的基因组疾病有关，涉及 22q11.2 缺失 (迪乔治综合症) 和 17q12 (17q12微缺失综合征), 16p11.2 重复 (最常见的) 以及 15q11.2 处的缺失 (伯恩赛德-巴特勒综合征).[92] 其中一些 CNV 会使患精神分裂症的风险增加 20 倍之多, 并且经常与自闭症和智力障碍共存。[92]
CRHR1 和 CRHBP 基因与自杀行为的严重程度相关. 这些基因编码控制 HPA 轴所需的应激反应蛋白, 他们的相互作用会影响这个轴. 对压力的反应可能会导致 HPA 轴功能发生持久变化，可能会破坏负反馈机制, 体内平衡, 情绪调节导致行为改变。[81]
精神分裂症如何主要受到遗传影响的问题, 鉴于精神分裂症患者的生育率较低, 是一个悖论. 预计会选择增加精神分裂症风险的遗传变异，因为它们对生殖健康有负面影响. 已经提出了一些可能的解释, 包括与精神分裂症风险相关的等位基因赋予未受影响的个体健康优势。[93][94] 虽然一些证据并不支持这个想法,[85] 其他人则提出，大量各自贡献少量的等位基因可以持续存在。[95]
环境的
更多信息: 产前营养, 产前压力, 和污染的神经塑性效应
环境因素, 与晚年患精神分裂症的轻微风险相关的每项因素都包括缺氧, 感染, 产前母亲压力, 以及母亲在产前发育期间的营养不良。[96] 孕产妇肥胖也存在风险, 增加氧化应激, 多巴胺和血清素途径失调。[97] 母亲的压力和感染已被证明可以通过促炎细胞因子的增加来改变胎儿的神经发育。[98] 冬季或春季出生的风险较小，可能是由于缺乏维生素 D[99] 或产前病毒感染。[86] 怀孕期间或出生前后与风险增加相关的其他感染包括弓形虫和衣原体感染。[100] 增加的风险约为百分之五到百分之八。[101] 儿童时期大脑的病毒感染也与成年后患精神分裂症的风险有关。[102]
不良的童年经历 (ACE), 其严重形式被归类为童年创伤, 范围从被欺负或虐待, 直至父母去世。[103] 许多不良的童年经历会导致有毒压力并增加患精神病的风险。[103][104][105] 慢性创伤会促进整个神经系统的持久炎症失调。[106] 有人认为，早期压力可能通过免疫系统的这些改变导致精神分裂症的发展。[106] 精神分裂症是最后一个受益于 ACE 与成人心理健康结果之间联系的诊断。[107]
研究一致发现，儿童时期或成年后生活在城市环境中，患精神分裂症的风险会增加两倍,[28][108] 即使考虑到药物的使用, 民族, 以及社会群体的规模。[109] A possible link between the urban environment and pollution has been suggested to be the cause of the elevated risk of schizophrenia.[110]
Other risk factors of importance include social isolation, immigration related to social adversity and racial discrimination, family dysfunction, unemployment, and poor housing conditions.[86][111] Having a father older than 40 年, or parents younger than 20 years are also associated with schizophrenia.[5][112] It has been suggested that apart from gene-environment interactions, environment-environment interactions also be taken into account as each environmental risk factor on its own is not enough.[96]
Substance use
更多信息: Risk factors of schizophrenia § Substance use
About half of those with schizophrenia use recreational drugs, including cannabis, tobacco, and alcohol excessively.[113][114] 使用安非他明和可卡因等兴奋剂可能会导致暂时性兴奋性精神病, 其表现与精神分裂症非常相似. 很少, 饮酒也会导致类似的与酒精相关的精神病。[86][115] 精神分裂症患者也可以使用药物作为应对机制, 应对抑郁症, 焦虑, 无聊, 和孤独。[113][116] 大麻和烟草的使用与认知缺陷的发展无关, 有时会发现相反的关系，使用它们可以改善这些症状。[57] 然而, 物质使用障碍与自杀风险增加有关, 以及对治疗的不良反应。[117]
大麻的使用可能是精神分裂症发展的一个促成因素, 可能会增加那些已经处于危险之中的人患这种疾病的风险。[23] 增加的风险可能需要个体体内存在某些基因。[23] 它的使用与速率加倍相关。[118] 使用具有高水平活性成分四氢大麻酚的更有效的大麻品种 (四氢大麻酚), 进一步增加风险. 其中一种菌株被称为臭鼬。[119][120]
机制
Main article: 精神分裂症的发病机制
See also: 异常显着性
精神分裂症的诊断不是通过客观的诊断测试来做出的; 相反，诊断用于描述由许多不同原因引起的观察到的行为. 人们提出了许多模型来解释大脑功能改变与精神分裂症之间的联系。[28] 精神分裂症的普遍模型是神经发育障碍, 在症状变得明显之前发生的潜在变化被认为是由基因和环境之间的相互作用引起的。[121] 大量研究支持这一模型。[75] 孕产妇感染, 怀孕和分娩期间的营养不良和并发症是导致精神分裂症的已知危险因素, 通常出现在年龄之间 18-25 与神经发育的某些阶段重叠的时期。[122] 基因-环境相互作用导致神经回路缺陷，影响感觉和认知功能。[75]
提出的常见多巴胺和谷氨酸模型并不相互排斥; 每一种都被认为在精神分裂症的神经生物学中发挥着作用。[123] 最常见的模型是精神分裂症的多巴胺假说, 它将精神病归因于大脑对多巴胺能神经元失火的错误解释。[124] 这与妄想和幻觉的症状有直接关系。[125][126][127] 根据影响多巴胺受体的药物的有效性以及急性精神病期间多巴胺水平升高的观察，异常的多巴胺信号传导与精神分裂症有关。[128][129] 背外侧前额叶皮层 D1 受体的减少也可能是工作记忆缺陷的原因。[130][131]
精神分裂症的谷氨酸假说将谷氨酸能神经传递和影响丘脑和皮质之间连接的神经振荡之间的改变联系起来。[132] 研究表明，谷氨酸受体——NMDA 受体的表达减少, 苯环己哌啶和氯胺酮等谷氨酸阻断药物可以模仿与精神分裂症相关的症状和认知问题。[132][133][134] 尸检研究一致发现这些神经元的一部分无法表达 GAD67 (GAD1),[135] 除了大脑形态测量异常之外. 精神分裂症中异常的中间神经元子集负责工作记忆任务期间所需神经元的同步. 这些给出了以伽马波形式产生的神经振荡，其频率介于 30 和 80 赫兹. 精神分裂症患者的工作记忆任务和伽马波均受损, 这可能反映了异常的中间神经元功能。[135][136][137][138] 神经发育中可能被破坏的一个重要过程是星形细胞生成——星形胶质细胞的形成. 星形胶质细胞对于神经回路的形成和维持至关重要，据信这一作用的破坏可能导致包括精神分裂症在内的许多神经发育障碍。[139] 有证据表明，更深皮质层中星形胶质细胞数量的减少与星形胶质细胞中谷氨酸转运蛋白 EAAT2 表达的减少有关; 支持谷氨酸假说。[139]
执行职能缺陷, 比如规划, 抑制, 和工作记忆, 在精神分裂症中普遍存在. 虽然这些功能是可分离的, 他们在精神分裂症中的功能障碍可能反映了在工作记忆中表示目标相关信息的能力的潜在缺陷, 并利用它来指导认知和行为。[140][141] 这些损伤与许多神经影像学和神经病理学异常有关. 例如, 功能神经影像研究报告了神经处理效率降低的证据, 由此，背外侧前额叶皮层被更大程度地激活，以实现相对于工作记忆任务控制的一定水平的性能. 这些异常可能与尸检发现的神经纤维减少有关, 锥体细胞密度增加和树突棘密度减少证明. 这些细胞和功能异常也可能反映在结构神经影像学研究中，这些研究发现灰质体积减少与工作记忆任务缺陷相关。[142]
阳性症状与颞上回皮质变薄有关。[143] 阴性症状的严重程度与左内侧眶额皮质厚度减少有关。[144] 快感缺失, 传统上定义为体验快乐的能力降低, 常见于精神分裂症. 然而, 大量证据表明，精神分裂症患者的享乐反应是完整的,[145] 据报道，快感缺乏是与奖励相关的其他过程功能障碍的反映。[146] 全面的, 奖励预测的失败被认为会导致获得奖励所需的认知和行为的产生受损, 尽管有正常的享乐反应。[147]
据推测，在某些人中, 精神分裂症的发展与肠道功能障碍有关，例如非乳糜泻麸质敏感性或肠道微生物群异常。[148] 一部分精神分裂症患者对麸质的免疫反应与乳糜泻患者不同, 某些麸质敏感性血清生物标志物水平升高，例如抗麦胶蛋白 IgG 或抗麦胶蛋白 IgA 抗体。[149]
另一种理论将异常的大脑偏侧化与左撇子的发展联系起来，这在精神分裂症患者中更为常见。[150] 这种半球不对称的异常发展在精神分裂症中很明显。[151] 研究得出的结论是，这种联系是真实且可验证的效应，可能反映了偏侧化和精神分裂症之间的遗传联系。[150][152]
大脑功能的贝叶斯模型已被用来将细胞功能异常与症状联系起来。[153][154] 幻觉和妄想都被认为反映了对先前期望的不正确编码, 从而导致期望过度影响感官知觉和信念的形成. 在经批准的介导预测编码的电路模型中, NMDA 受体激活减少, 理论上可能会导致妄想和幻觉的阳性症状。[155][156][157]
诊断
Main article: 精神分裂症的诊断
没有客观的测试或生物标志物来确认诊断. 精神病可以在多种情况下发生，并且通常是短暂的，使得精神分裂症的早期诊断变得困难. 首次在后来被诊断为精神分裂症的人中发现精神病被称为首发精神病 (FEP).
标准
精神分裂症的诊断依据是《精神疾病诊断与统计手册》中的标准 (帝斯曼) 由美国精神病学协会或国际疾病和相关健康问题统计分类出版 (ICD) 世界卫生组织出版. 这些标准使用该人的自我报告经历和报告的行为异常, 随后进行精神评估. 精神状态检查是评估的重要组成部分。[158] 评估阳性和阴性症状严重程度的既定工具是阳性和阴性症状量表 (潘氏).[159] 这被认为存在与阴性症状相关的缺点, 和其他量表 – 阴性症状的临床评估访谈 (CAINS), 和简短负面症状量表 (BNSS) 已被介绍。[50] DSM-5, 发表于 2013, 给出了评估症状严重程度的量表，概述了症状的八个维度。[56]
DSM-5 规定被诊断为精神分裂症, 一个月内必须满足两项诊断标准, 对社会或职业功能产生重大影响至少六个月. 其中一个症状必须是妄想, hallucinations, 或言语杂乱无章. 第二个症状可能是阴性症状之一, 或严重混乱或紧张性行为。[7] 在诊断精神分裂症所需的六个月之前，可以对精神分裂症做出不同的诊断。[7]
在澳大利亚，诊断指南是症状严重到影响正常功能的六个月或更长时间。[160] 在英国，诊断是基于一个月内大部分时间都出现症状, 具有严重影响工作能力的症状, 学习, 或继续平凡的日常生活, 并排除其他类似条件。[161]
ICD 标准通常用于欧洲国家; DSM 标准主要在美国和加拿大使用, 并在研究中盛行. 在实践中, 两个系统之间的一致性很高。[162] 目前关于 ICD-11 精神分裂症标准的提案建议将自我紊乱作为一种症状。[40]
两个诊断系统之间一个未解决的主要差异是 DSM 中对功能受损结果的要求. 世卫组织 ICD 认为，并非所有精神分裂症患者都有功能缺陷，因此这些缺陷对于诊断并不具有特异性。[56]
所做的改变
两本手册都采用了精神分裂症谱系和其他精神障碍的章节标题; ICD 将其修改为精神分裂症谱系和其他原发性精神障碍。[56] 精神分裂症的定义与《精神分裂症》的定义基本相同。 2000 修订后的 DSM-IV 文本 (DSM-IV-TR). 然而, 随着 DSM-5 的发布, APA 删除了精神分裂症的所有子分类。[56] ICD-11 还删除了亚型. 从两者中删除的子类型, 紧张症已被重新列入 ICD-11 作为精神分裂症中可能存在的精神运动障碍。[56]
另一个重大变化是取消了之前对施耐德第一级症状的重视。[163] DSM-5 仍然使用精神分裂症的列表，但 ICD-11 不再包含它。[56] DSM-5 还建议更好地区分精神分裂症的现状与其历史进展, 以获得更清晰的整体特征。[163]
DSM-5 中已包含维度评估，涵盖待评级症状的八个维度 (使用量表评估症状维度的严重程度) – 其中包括五项诊断标准以及认知障碍, 狂热, 和抑郁症。[56] 这可以为个人添加有关治疗的相关信息, 预后, 和功能结果; 它还可以更准确地描述对治疗的反应。[56][164]
两个负面症状——无欲和情绪表达减少, 两本手册中都给予了更加突出的重视。[56]
合并症
许多精神分裂症患者可能患有一种或多种其他精神障碍, 比如恐慌症, 强迫症, 或物质使用障碍. 这些是需要治疗的单独疾病。[7] 当合并精神分裂症时, 物质使用障碍和反社会人格障碍都会增加暴力风险。[165] 共病物质使用障碍也会增加自杀风险。[117]
睡眠障碍通常与精神分裂症同时发生, 并且可能是复发的早期迹象。[166] Sleep disorders are linked with positive symptoms such as disorganized thinking and can adversely affect cortical plasticity and cognition.[166] The consolidation of memories is disrupted in sleep disorders.[167] They are associated with severity of illness, a poor prognosis, and poor quality of life.[168][169] Sleep onset and maintenance insomnia is a common symptom, regardless of whether treatment has been received or not.[168] Genetic variations have been found associated with these conditions involving the circadian rhythm, dopamine and histamine metabolism, and signal transduction.[170] Limited positive evidence has been found for the use of acupuncture as an add-on.[171]
Differential diagnosis
See also: Dual diagnosis and Comparison of bipolar disorder and schizophrenia
为了诊断精神分裂症，需要排除其他可能的精神病原因。[172] 持续少于一个月的精神病症状可能被诊断为短暂性精神病, 或作为精神分裂症. 精神病在其他特定的精神分裂症谱系和其他精神障碍中被列为 DSM-5 类别. 如果情绪障碍的症状与精神病症状同时存在，则诊断为分裂情感性障碍. 由一般医疗状况或物质引起的精神病称为继发性精神病。[7]
精神病症状可能出现在其他几种情况下, 包括双相情感障碍,[8] 边缘性人格障碍,[9] 物质中毒, 物质诱发的精神病, 以及一些戒毒综合症. 妄想症中也存在非奇异的妄想, 和社交恐惧症的社交退缩, 回避型人格障碍和分裂型人格障碍. 精神分裂型人格障碍的症状与精神分裂症相似，但不那么严重。[7] 精神分裂症与强迫症同时发生 (强迫症) 比偶然可以解释的频率要高得多, 尽管很难区分强迫症的强迫观念和精神分裂症的妄想。[173] 与创伤后应激障碍的症状可能有相当大的重叠。[174]
可能需要进行更全面的医学和神经学检查，以排除很少会产生精神病性精神分裂症样症状的医学疾病, 比如代谢紊乱, 全身感染, 梅毒, HIV相关神经认知障碍, 癫痫, 边缘叶脑炎, 和脑损伤. 中风, 多发性硬化症, hyperthyroidism, hypothyroidism, and dementias such as Alzheimer’s disease, 亨廷顿病, frontotemporal dementia, and the Lewy body dementias may also be associated with schizophrenia-like psychotic symptoms.[175] It may be necessary to rule out a delirium, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, and indicates an underlying medical illness. Investigations are not generally repeated for relapse unless there is a specific medical indication or possible adverse effects from antipsychotic medication. In children hallucinations must be separated from typical childhood fantasies.[7] It is difficult to distinguish childhood schizophrenia from autism.[71]
预防
Prevention of schizophrenia is difficult as there are no reliable markers for the later development of the disorder.[176] 有初步但非决定性的证据表明早期干预对于预防前驱症状阶段的精神分裂症是有效的。[177] 有一些证据表明，对首发精神病患者进行早期干预可能会改善短期结果, 但五年后这些措施收效甚微。[28] 认知行为疗法可能会降低一年后高危人群患精神病的风险[178] 并在该组中推荐, 由国家健康与护理卓越研究所 (好的).[34] 另一种预防措施是避免使用与疾病发展相关的药物, including cannabis, 可卡因, 和安非他明。[86]
首次发作精神病后服用抗精神病药物, 缓解后继续进行预防性维护以避免复发. 然而, it is recognised that some people do recover following a single episode and that long-term use of antipsychotics will not be needed but there is no way of identifying this group.[179]
管理
Main article: Management of schizophrenia
The primary treatment of schizophrenia is the use of antipsychotic medications, often in combination with psychosocial interventions and social supports.[28][180] Community support services including drop-in centers, visits by members of a community mental health team, supported employment,[181] and support groups are common. The time between the onset of psychotic symptoms to being given treatment – the duration of untreated psychosis (DUP) is associated with a poorer outcome in both the short term and the long term.[182]
认为患者病情严重的医生和法院可能会强制其自愿或非自愿入院. 在英国, 随着抗精神病药物的出现，被称为庇护所的大型精神病院在 20 世纪 50 年代开始关闭, 并意识到长期住院对康复的负面影响。[26] 这个过程被称为去机构化, 并开发了社区和支持服务来支持这一变化. 从 20 世纪 60 年代开始，许多其他国家纷纷效仿美国。[183] 仍有一小部分人医生和法院不同意出院。[26][32] 在一些缺乏必要的支持和社会服务的国家, 长期住院更为常见。[33]
药物
利培酮 (商品名利培酮) 是一种常见的非典型抗精神病药物.
精神分裂症的一线治疗是抗精神病药. 第一代抗精神病药, 现在称为典型抗精神病药, 是阻断 D2 受体的多巴胺拮抗剂, 并影响多巴胺的神经传递. 那些后来拿出来的, 第二代抗精神病药称为非典型抗精神病药, 也可以对另一种神经递质产生影响, 血清素. 抗精神病药物可以在使用后数小时内减轻焦虑症状，但对于其他症状，可能需要几天或几周才能充分发挥作用。[36][184] 它们对负面和认知症状影响不大, 额外的心理治疗和药物可能会有所帮助。[185] 没有一种抗精神病药物适合所有人的一线治疗, 因为人与人之间的反应和容忍度有所不同。[186] 在一次精神病发作后，如果十二个月内完全康复且没有任何症状，可以考虑停止用药. 反复复发会使长期前景恶化，并且第二次发作后复发的风险很高, 通常建议长期治疗。[187][188]
吸烟会增加某些抗精神病药物的代谢, 通过强烈激活 CYP1A2, 分解它们的酶, 吸烟者和非吸烟者之间的这些水平存在显着差异。[189][190][191] 建议吸烟者增加氯氮平的剂量 50%, 对于那些服用奥氮平的人 30%.[190] 戒烟的结果可能导致抗精神病药物的浓度增加，从而可能导致毒性, 因此需要监测效果以减少剂量; 许多症状可能明显恶化, 和极度疲劳, 癫痫发作也可能有复发的风险. 同样，那些重新开始吸烟的人可能需要相应调整剂量。[189][192] 改变效果是由于烟草烟雾中的化合物而不是尼古丁造成的; 因此，使用尼古丁替代疗法具有与戒烟同等的效果，但仍需要进行监测。[189]
关于 30 到 50 百分之百的精神分裂症患者无法接受自己患有疾病或不遵守建议的治疗方法。[193] 对于那些不愿意或无法定期服药的人, 可以使用长效抗精神病药物注射,[194] which reduce the risk of relapse to a greater degree than oral medications.[195] When used in combination with psychosocial interventions, they may improve long-term adherence to treatment.[196]
Research findings suggested that other neurotransmission systems, including serotonin, glutamate, GABA, and acetycholine, were implicated in the development of schizophrenia, and that a more inclusive medication was needed.[191] A new first-in-class antipsychotic that targets multiple neurotransmitter systems called lumateperone (ITI-007), was trialed and approved by the FDA in December 2019 for the treatment of schizophrenia in adults.[191][197][198] Lumateperone is a small molecule agent that shows improved safety, and tolerance. It interacts with dopamine, 血清素, and glutamate in a complex, uniquely selective manner, and is seen to improve negative and positive symptoms, and social functioning.[199] 鲁马特哌隆还被发现可以减少潜在的代谢功能障碍, 运动障碍发生率较低, 并且具有较低的心血管副作用，例如心率加快。[191]
副作用
典型的抗精神病药物与较高的运动障碍（包括静坐不能）发生率相关. 一些非典型症状与体重显着增加有关, 糖尿病和代谢综合征的风险。[200] 利培酮 (非典型的) 锥体外系症状发生率与氟哌啶醇相似 (典型的).[200] 一种罕见但可能致命的抗精神病药恶性综合征 (网络管理系统) 与使用抗精神病药物有关. 通过早期的认可, 及时干预率有所下降. 然而, 建议了解该综合征以便进行干预。[201] 另一种不太罕见的迟发性运动障碍可能是由于长期使用抗精神病药物引起的, 经过数月或数年的使用后形成. 更常报道的是使用典型的抗精神病药物。[202]
氯氮平与体重增加等副作用有关, 疲倦, 和过度流涎. 更严重的不良反应包括癫痫发作, 网络管理系统, 中性粒细胞减少症, 和粒细胞缺乏症 (白细胞计数降低) 其使用需要仔细监控。[203][204] 研究发现，NMS 和中性粒细胞减少症后的抗精神病药物治疗有时可能会成功地重新挑战 (重新启动) 与氯氮平。[205][206]
氯氮平也与血栓栓塞有关 (包括肺栓塞), 心肌炎, 和心肌病。[207][208] 对氯氮平相关肺栓塞的系统评价表明，这种不良反应往往是致命的, 并且它发病较早, 并且是剂量依赖性的. 研究结果建议在开始使用氯氮平治疗后考虑使用静脉血栓栓塞的预防疗法, 并持续六个月。[208] 使用氯氮平发生便秘的可能性增加三倍, 严重者可导致肠梗阻和肠缺血，导致许多人死亡。[203]
然而, 氯氮平产生严重不良反应的风险很低, 降低自杀风险会带来有益的效果, 和攻击性。[209][210] 典型的抗精神病药物和非典型的利培酮可能会产生性功能障碍的副作用。[86] 氯氮平, 奥氮平, 和喹硫平在各种心理治疗的帮助下对性功能产生有益影响。[211] 不需要的副作用导致人们停止治疗, 从而导致复发。[212]
Treatment resistant schizophrenia
About half of those with schizophrenia will respond favourably to antipsychotics, and have a good return of functioning.[213] 然而, positive symptoms persist in up to a third of people. Following two trials of different antipsychotics over six weeks, that also prove ineffective, they will be classed as having treatment resistant schizophrenia (TRS), and clozapine will be offered.[214][30] Clozapine is of benefit to around half of this group although it has the potentially serious side effect of agranulocytosis (白细胞计数降低) in less than 4% of people.[28][86][215] 之间 12 和 20 per cent will not respond to clozapine and this group is said to have ultra treatment resistant schizophrenia.[214][216] ECT may be offered to treat TRS as an add-on therapy, and is shown to sometimes be of benefit.[216] 一项审查得出的结论是，这种用途仅对中期 TRS 有影响，并且没有足够的证据支持其除该群体之外的用途。[217]
TRS 常常伴随着低生活质量, 以及更大的社会功能障碍。[218] TRS 可能是治疗不充分而非效率低下的结果; 由于未定期服用药物，它也可能是虚假标签, 或者根本没有。[210] 关于 16 最初对治疗有反应的人的百分比后来出现耐药性. 这可能与 AP 上的时间长度有关, 随着治疗变得不那么敏感。[219] 这一发现也支持多巴胺参与精神分裂症的发展。[210] 研究表明 TRS 可能是一种更具遗传性的形式。[220]
TRS 可能从首次发作的精神病中表现出来, 或复发. It can vary in its intensity and response to other therapies.[218] This variation is seen to possibly indicate an underlying neurobiology such as dopamine supersensitivity (DSS), glutamate or serotonin dysfunction, inflammation and oxidative stress.[214] Studies have found that dopamine supersensitivity is found in up to 70% of those with TRS.[221] The variation has led to the suggestion that treatment responsive and treatment resistant schizophrenia be considered as two different subtypes.[214][220] It is further suggested that if the subtypes could be distinguished at an early stage significant implications could follow for treatment considerations, and for research.[216] Neuroimaging studies have found a significant decrease in the volume of grey matter in those with TRS with no such change seen in those who are treatment responsive.[216] 在那些具有超治疗抵抗力的人中，灰质体积的减少幅度更大。[214][216]
肠道微生物群与 TRS 的发展之间存在联系. TRS 最常见的原因是负责药物有效性的基因突变. 其中包括控制药物对大脑靶标的可用性的肝酶基因, 以及负责这些目标的结构和功能的基因. 在结肠中，细菌编码的基因比人类基因组中存在的基因多一百倍. 只有一小部分摄入的药物到达结肠, 已经接触过小肠细菌, 并被门脉循环吸收. 然后，这一小部分会受到许多细菌群落的代谢作用. 药物的激活取决于细菌的成分和酶以及药物的特性, 因此，大量的个体差异会影响药物的有效性及其耐受性. 建议肠外施用抗精神病药物可以绕过肠道，更能成功地克服 TRS. 肠道微生物群的组成因人而异, 但他们被认为保持稳定. 然而, 门可以响应许多因素而变化，包括衰老, 饮食, 物质使用, 和药物——尤其是抗生素, 泻药, 和抗精神病药. 在聚全氟乙丙烯中, 精神分裂症与肠道微生物群的显着变化有关，肠道微生物群可以预测对治疗的反应。[222]
心理社会干预
更多信息: 精神分裂症的治疗§心理社会
包括几种类型的心理治疗在内的许多心理社会干预措施可能有助于治疗精神分裂症，例如: 家庭治疗,[223] 团体治疗, 认知矫正疗法,[224] 认知行为疗法, 和元认知训练。[225] 技能培训, 并帮助物质使用, 和体重管理——通常需要作为抗精神病药物的副作用, 还提供。[226] 在美国, 对首发精神病的干预措施已整合到称为协调专业护理的整体方法中 (CSC) 还包括对教育的支持。[36] 在英国，各个阶段的护理都是类似的方法，涵盖了许多推荐的治疗指南。[34] 目的是减少复发和住院次数。[223]
其他教育支持服务, 就业, and housing are usually offered. For people suffering from severe schizophrenia, and discharged from a stay in hospital, these services are often brought together in an integrated approach to offer support in the community away from the hospital setting. In addition to medicine management, housing, and finances, assistance is given for more routine matters such as help with shopping and using public transport. This approach is known as assertive community treatment (ACT) and has been shown to achieve positive results in symptoms, social functioning and quality of life.[227][228] Another more intense approach is known as intensive care management (ICM). ICM is a stage further than ACT and emphasises support of high intensity in smaller caseloads, (less than twenty). This approach is to provide long-term care in the community. 研究表明，ICM 可以改善许多相关结果，包括社会功能。[229]
一些研究几乎没有证据表明认知行为疗法的有效性 (认知行为治疗) 减轻症状或预防复发。[230][231] 然而, 其他研究发现 CBT 确实可以改善整体精神病症状 (与药物一起使用时) 并在加拿大得到推荐, 但这里发现它对社会功能没有影响, 复发, 或生活质量。[232] 在英国，建议将其作为治疗精神分裂症的附加疗法, 但不支持用于治疗难治性精神分裂症。[231][233] 艺术疗法被认为可以改善某些人的阴性症状, 并获得英国NICE推荐。[184][234] 然而这种做法, 被批评没有经过充分研究, 例如，澳大利亚指南中不推荐艺术疗法。[234][235][236] 同伴支持, 其中有精神分裂症个人经历的人, 互相提供帮助, 是有不明确的好处。[237]
其他
包括有氧运动在内的运动已被证明可以改善阳性和阴性症状, 认识, 工作记忆, 并提高生活质量。[238][239] 运动也被证明可以增加精神分裂症患者的海马体积. 海马体积的减少是与疾病发展相关的因素之一。[238] 然而, 仍然存在提高动力的问题, 并保持参与体育活动。[240] 建议进行监督会议。[239] 在英国，健康饮食建议与锻炼计划一起提供。[241]
精神分裂症经常发现饮食不足, 以及相关的维生素缺乏症，包括叶酸缺乏症, 维生素 D 和维生素 D 与精神分裂症和早逝（包括心脏病）的危险因素有关。[242][243] 精神分裂症患者的饮食可能是所有精神障碍中最糟糕的. 首次发作精神病患者的叶酸和维生素 D 水平明显较低。[242] 建议使用补充叶酸。[244] 还注意到锌缺乏。[245] 维生素 B12 也经常缺乏，这会导致更严重的症状. 补充 B 族维生素已被证明可以显着改善症状, 并扭转一些认知缺陷。[242] 研究还表明，肠道微生物群的明显功能障碍可能会受益于益生菌的使用。[245]
暴力
大多数精神分裂症患者并不具有攻击性, 并且更有可能成为暴力的受害者而不是施暴者。[7] 作为更广泛的社会排斥动态的一部分，精神分裂症患者通常受到暴力犯罪的剥削和伤害。[26][27] 被诊断患有精神分裂症的人也遭到强制注射毒品, 隔离和克制, 以高利率。[31][32]
精神分裂症患者实施暴力的风险很小. 有一些次要的亚组风险很高。[165] 这种风险通常与共病相关，例如物质使用障碍，尤其是酒精, 或患有反社会人格障碍。[165] 物质使用障碍密切相关, 其他风险因素与认知和社会认知缺陷有关，包括面部感知和洞察力，这些缺陷部分包含在心理障碍理论中。[246][247] 认知功能差, 决策, 面部感知可能会导致对情况做出错误判断，从而导致暴力等不当反应。[248] 这些相关的危险因素也存在于反社会人格障碍中，当反社会人格障碍作为共病障碍出现时，会大大增加暴力风险。[249][250]
评论于 2012 表明 6 在西方国家，被判犯有杀人罪的人中有百分之一被诊断为精神分裂症。[249] 另一项更广泛的审查将这个数字置于两者之间 5 和 20 百分比。[251] 研究发现，被判犯有杀人罪的人更有可能在精神病首次发作时犯下杀人罪, and this accounted for 38.5 percent (of the 5 到 20 percent of perpetrators who were diagnosed schizophrenic, so 2 到 7.7 percent of perpetrators total.)[251] The association between schizophrenia and violence is complex. Homicide is linked with young age, male sex, a history of violence, and a stressful event in the preceding year. Clinical risk factors are severe untreated psychotic symptoms – untreated due to either not taking medication or to the condition being treatment resistant.[249] A comorbid substance use disorder or an antisocial personality disorder increases the risk for homicidal behaviour by 8-fold, in contrast to the 2-fold risk in those without the comorbid disorders.[165] Rates of homicide linked to psychosis are similar to those linked to substance misuse, and parallel the overall rate in a region.[252] 精神分裂症在独立于药物滥用之外的暴力中扮演什么角色是有争议的, 但个人历史或精神状态的某些方面可能是因素。[253]
敌意是针对个人或群体的愤怒，具有冲动和攻击性的相关维度. 当这种冲动攻击在精神分裂症中很明显时，神经影像学表明调节与社交互动中的负面情绪相关的敌对思想和行为的神经回路出现故障. 该回路包括杏仁核, 纹状体, 前额皮质, 前扣带皮层, 岛岛, 和海马体. 据报道，急性精神病期间存在敌意, 以及出院后。[254] 已知低胆固醇水平之间存在关联, 和冲动, 和暴力. 一项审查发现，精神分裂症患者, 较低的胆固醇水平引发暴力行为的可能性是其他人的四倍. 这种关联也与精神分裂症自杀人数的增加有关. 有人建议，胆固醇水平可以作为暴力和自杀倾向的生物标志物。[255]
评论发现就在下面 10 与其他人相比，精神分裂症患者表现出暴力行为的百分比 1.6 占总人口的百分比. 过度的暴力风险与毒品或酒精有关，并使风险增加多达 4 倍. 暴力常常导致监禁. 氯氮平是一种有效的药物，可用于监狱等监狱环境. 然而, 许多非裔美国人患有良性种族中性粒细胞减少症，使他们无法使用最有效的药物氯氮平. 认知缺陷被认为在攻击行为的起源和维持中发挥着重要作用, 因此，认知矫正疗法可能有助于预防精神分裂症的暴力风险。[248]
预后
精神分裂症造成巨大的人力和经济成本。[5] 它会导致预期寿命缩短 20 年。[4][10] 这主要是因为它与肥胖有关, 饮食不良, 久坐的生活方式, 和吸烟, 自杀率上升所起的作用较小。[10][256] 抗精神病药物的副作用也可能增加风险。[10] 20 世纪 70 年代和 90 年代之间预期寿命的差异有所扩大。[257] 澳大利亚的一项研究表明，早期死亡率为 25 年, 并认为主要原因与心脏病有关。[207]
多项研究表明几乎 40% of those with schizophrenia die from complications of cardiovascular disease including heart attacks, and sudden cardiac death which is seen to be increasingly associated.[243] An underlying factor of sudden cardiac death may be Brugada syndrome (BrS) – BrS mutations that overlap with those linked with schizophrenia are the calcium channel mutations.[243] BrS may also be drug-induced from certain antipsychotics and antidepressants.[243] Primary polydipsia, or excessive fluid intake, is relatively common in people with chronic schizophrenia.[258][259] This may lead to hyponatremia which can be life-threatening. Antipsychotics can lead to a dry mouth, but there are several other factors that may contribute to the disorder. It is suggested to lead to a reduction in life expectancy by 13 per cent.[259] A study has suggested that real barriers to improving the mortality rate in schizophrenia are poverty, overlooking the symptoms of other illnesses, 压力, stigma, and medication side effects, and that these need to be changed.[260]
Schizophrenia is a major cause of disability. 在 2016 it was classed as the 12th most disabling condition.[261] 大约 75% of people with schizophrenia have ongoing disability with relapses[262] 和 16.7 million people globally are deemed to have moderate or severe disability from the condition.[263] Some people do recover completely and others function well in society.[264] Most people with schizophrenia live independently with community support.[28] 关于 85% are unemployed.[5] In people with a first episode of psychosis in schizophrenia a good long-term outcome occurs in 31%, an intermediate outcome in 42% and a poor outcome in 31%.[265] Males are affected more often than females, and have a worse outcome.[266] But according to some reports, there is no difference in prevalence.[20][21] Outcomes for schizophrenia appear better in the developing than the developed world.[267] These conclusions have been questioned.[268] Social problems, such as long-term unemployment, 贫困, 无家可归, 开发, stigmatization and victimization are common consequences, and lead to social exclusion.[26][27]
There is a higher than average suicide rate associated with schizophrenia estimated at around 5% 到 6%, most often occurring in the period following onset or first hospital admission.[11][29] Several times more (20 到 40%) attempt suicide at least once.[7][269] There are a variety of risk factors, including male gender, 沮丧, a high IQ,[269] heavy smoking,[270] and substance use.[117] Repeated relapse is linked to an increased risk of suicidal behavior.[179] The use of clozapine can reduce the risk of suicide and aggression.[210]
A strong association between schizophrenia and tobacco smoking has been shown in worldwide studies.[271][272] Smoking is especially high in those diagnosed with schizophrenia, with estimates ranging from 80 到 90% being regular smokers, as compared to 20% of the general population.[272] Those who smoke tend to smoke heavily, and additionally smoke cigarettes with high nicotine content.[39] Some propose that this is in an effort to improve symptoms.[273] Among people with schizophrenia use of cannabis is also common.[117]
流行病学
Main article: Epidemiology of schizophrenia
在 2017, the Global Burden of Disease Study estimated there were 1.1 million new cases, and in 2019 WHO reported a total of 20 全球百万例。[2][19] Schizophrenia affects around 0.3–0.7% of people at some point in their life.[18] It occurs 1.4 times more frequently in males than females and typically appears earlier in men[86] – the peak ages of onset are 25 years for males and 27 years for females.[274] Onset in childhood, 年龄之前 13 can sometimes occur.[7][71] Other reviews find no difference in the prevalence of schizophrenia between the sexes.[20][21] A later onset can occur between the ages of 40 和 60, known as late onset, and also after 60 known as very late onset.[62]
全世界, schizophrenia is the most common psychotic disorder.[74] The frequency of schizophrenia varies across the world,[7][275] within countries,[276] and at the local and neighborhood level.[277] This variation has been estimated to be fivefold.[5] It causes approximately one percent of worldwide disability adjusted life years[86] and resulted in 17,000 deaths in 2015.[12]
在 2000, the World Health Organization found the percentage of people affected and the number of new cases that develop each year is roughly similar around the world, with age-standardized prevalence per 100,000 ranging from 343 in Africa to 544 in Japan and Oceania for men, and from 378 in Africa to 527 in Southeastern Europe for women.[278] 关于 1.1% of adults have schizophrenia in the United States.[279] 然而, in areas of conflict this figure can rise to between 4.0 和 6.5%.[280]
History
期限 “schizophrenia” was coined by Eugen Bleuler.
Accounts of a schizophrenia-like syndrome are rare in records before the 19th century. The earliest cases detailed were reported in 1797, 和 1809.[281] Dementia praecox, meaning premature dementia was used by German psychiatrist Heinrich Schüle in 1886, and then in 1891 by Arnold Pick in a case report of hebephrenia. 在 1893 Emil Kraepelin used the term in making a distinction, known as the Kraepelinian dichotomy, between the two psychoses – dementia praecox, and manic depression (now called bipolar disorder).[10] Kraepelin believed that dementia praecox was probably caused by a systemic disease that affected many organs and nerves, affecting the brain after puberty in a final decisive cascade.[282] It was thought to be an early form of dementia, a degenerative disease.[10] When it became evident that the disorder was not degenerative it was renamed schizophrenia by Eugen Bleuler in 1908.[283]
The word schizophrenia translates as “splitting of the mind” and is Modern Latin from the Greek roots schizein (σχίζειν, “to split”) and phrēn, (φρεν, “mind”)[284] Its use was intended to describe the separation of function between personality, thinking, 记忆, and perception.[283]
The term schizophrenia used to be associated with split personality by the general population but that usage went into decline when split personality became known as a separate disorder, first as multiple identity disorder , and later as dissociative identity disorder.[285] 在 2002 in Japan the name was changed to integration disorder, and in 2012 in South Korea, the name was changed to attunement disorder.[28][286][287]
A molecule of chlorpromazine, the first antipsychotic developed in the 1950s.
In the early 20th century, the psychiatrist Kurt Schneider listed the psychotic symptoms of schizophrenia into two groups of hallucinations, and delusions. The hallucinations were listed as specific to auditory, and the delusional included thought disorders. These were seen as the symptoms of first-rank importance and were termed first-rank symptoms. Whilst these were also sometimes seen to be relevant to the psychosis in manic-depression, they were highly suggestive of schizophrenia and typically referred to as first-rank symptoms of schizophrenia. The most common first-rank symptom was found to belong to thought disorders.[288][289] 在 2013 the first-rank symptoms were excluded from the DSM-5 criteria.[163] First-rank symptoms are seen to be of limited use in detecting schizophrenia but may be of help in differential diagnosis.[290]
Before the 1960s, doctors in America primarily diagnosed nonviolent petty criminals and women with schizophrenia, categorizing the latter as ill for not performing their duties within patriarchy as wives and mothers. Official descriptions emphasized the “calm” nature of such persons. 然而, in the mid-to-late 1960s, psychiatrists began diagnosing black men as schizophrenic at much higher rates, often citing their civil rights and Black Power activism as delusions, and categorizing them as “hostile and aggressive.”[291][292]
From the 1960s until 1989, psychiatrists in the USSR and Eastern Bloc diagnosed thousands of people with sluggish schizophrenia,[293][294][295] based on “the assumption that symptoms would later appear,”[296] because the removal of legal rights from disabled people made it a convenient way to confine political dissidents.[297] The sluggish schizophrenia diagnosis has been discredited and internationally condemned.[298]
Psychiatrists committed psychosurgery on many of the first people they diagnosed as schizophrenic. These were notably frontal lobotomies carried out from the 1930s until the 1970s in the United States, and until the 1980s in France, involving either the removal of brain tissue from different regions or the severing of pathways,[299] now widely recognized as a grave human rights abuse.[299][300] In the 1930s a number of shock treatments were introduced which induced seizures (抽搐) or comas.[301] Insulin shock therapy involved the injecting of large doses of insulin in order to induce comas, which in turn produced hypoglycemia and convulsions.[301][300] The use of electricity to induce seizures was developed, and in use as electroconvulsive therapy (ECT) 经过 1938.[302] Stereotactic surgeries were developed in the 1940s.[302] In the mid-1950s scientists developed and introduced the first typical antipsychotic, chlorpromazine.[303] In the 1970s the first atypical antipsychotic clozapine, was introduced followed by the introduction of others.[304]
In the early 1970s in the US, the diagnostic model used for schizophrenia was broad and clinically based using DSM II. It had been noted that schizophrenia was diagnosed far more in the US than in Europe which had been using the ICD-9 criteria. The US model was criticised for failing to demarcate clearly those people with a mental illness, and those without. 在 1980 DSM III was published and showed a shift in focus from the clinically-based biopsychosocial model to a reason-based medical model.[305] DSM IV showed an increased focus to an evidence-based medical model.[306]
Subtypes of schizophrenia classified as paranoid, disorganized, catatonic, undifferentiated, and residual type were difficult to distinguish between and are no longer recognized as separate conditions by DSM-5 (2013)[307] or ICD-11.[308][309][310]
Society and culture
John Nash, an American mathematician and joint recipient of the 1994 Nobel Memorial Prize in Economic Sciences, 谁患有精神分裂症. His life was the subject of the 1998 book, A Beautiful Mind by Sylvia Nasar.
在 2002, the term for schizophrenia in Japan was changed from seishin-bunretsu-byō (精神分裂病, lit. “mind-split disease”) to tōgō-shitchō-shō (統合失調症, lit. “integration-dysregulation syndrome”) to reduce stigma.[311] The new name also interpreted as “integration disorder” was inspired by the biopsychosocial model; it increased the percentage of people who were informed of the diagnosis from 37 到 70% over three years.[286] A similar change was made in South Korea in 2012 to attunement disorder.[287] A professor of psychiatry, Jim van Os, has proposed changing the English term to psychosis spectrum syndrome.[312] 在 2013 with the reviewed DSM-5, the DSM-5 committee was in favor of giving a new name to schizophrenia but they referred this to WHO.[313]
In the United States, the cost of schizophrenia – including direct costs (outpatient, inpatient, 药物, and long-term care) and non-healthcare costs (law enforcement, reduced workplace productivity, and unemployment) – was estimated to be $62.7 billion in 2002.[314] In the UK the cost in 2016 was put at £11.8 billion per year with a third of that figure directly attributable to the cost of hospital and social care, and treatment.[5]
The book A Beautiful Mind chronicled the life of John Forbes Nash who had been diagnosed with schizophrenia and went on to win the Nobel Memorial Prize in Economic Sciences. This was later made into the film with the same name. An earlier documentary was made with the title A Brilliant Madness.
在 1964 a lengthy case study of three males diagnosed with schizophrenia who each had the delusional belief that they were Jesus Christ was published as a book. This has the title of The Three Christs of Ypsilanti, and a film with the title Three Christs was released in 2020. Such religious delusions are a fairly common feature in psychoses including schizophrenia.[315][316]
Media coverage relating to violent acts by people with schizophrenia reinforces public perception of an association between schizophrenia and violence.[317] Such sensationalist reporting stigmatizes schizophrenia more than any other mental illness.[318] In the UK guidelines are given for the reporting of different conditions. Its campaigns have shown a reduction in negative reporting.[318][319]
Research directions
一个 2015 Cochrane review found unclear evidence of benefit from brain stimulation techniques to treat the positive symptoms of schizophrenia, in particular auditory verbal hallucinations (AVHs).[321] Most studies focus on transcranial direct-current stimulation (tDCM), and repetitive transcranial magnetic stimulation (rTMS).[322] Techniques based on focused ultrasound for deep brain stimulation could provide insight for the treatment of AVHs.[322]
An active area of research as of 2020 is the study of potential biomarkers that would help in diagnosis and treatment of schizophrenia. Possible biomarkers include markers of inflammation,[323] neuroimaging,[324] brain-derived neurotrophic factor (脑源性神经营养因子),[325] and speech analysis. Some inflammatory markers such as C-reactive protein are useful in detecting levels of inflammation implicated in some psychiatric disorders but they are not disorder-specific. Other inflammatory cytokines are found to be elevated in first episode psychosis and acute relapse that are normalized after treatment with antipsychotics, and these may be considered as state markers.[326] Deficits in sleep spindles in schizophrenia may serve as a marker of an impaired thalamocortical circuit, and a mechanism for memory impairment.[167] MicroRNAs are highly influential in early neuronal development, and their disruption is implicated in several CNS disorders; circulating microRNAs (cimiRNAs) are found in body fluids such as blood and cerebrospinal fluid, and changes in their levels are seen to relate to changes in microRNA levels in specific regions of brain tissue. These studies suggest that cimiRNAs have the potential to be early and accurate biomarkers in a number of disorders including schizophrenia.[327][328]
