精神分裂症超高危人群的评估及干预研究

1 精神分裂症的前驱症状与超高危人群 精神分裂症由于早期识别和早期诊断困难,造成诊断治疗延迟和治疗困难,从而带来高自杀率、高衰退率、高残疾率.大约80%～90%的精神分裂症患者发展成精神病之前有一个较长的前驱期,前驱期症状大约持续1～5年[1-2].     

首发和慢性精神分裂症患者、正常对照者超氧化物歧化酶及脑源性神经营养因子水平的差异

背景有研究认为精神分裂症患者脑源性神经营养因子（brainderivedneurotrophiefactors，BDNF）含量降低，超氧化物歧化酶（superoxidedismutase，SOD）活性异常，但结果并不完全一致，可能与研究对象不同有关。目的探讨25例首发精神分裂症、慢性精神分裂症患者与正常人体内SOD活性、BDNF含量差异。评估病人组SOD、BDNF与临床特征的关系。方法收集符合美国精神障碍诊断与统计手册第4版诊断标准的首发精神分裂症住院患者78例，慢性精神分裂症住院患者67例，正常对照51名。以阳性和阴性综合征量表（PositiveandNegativeSyndromeScale，PANSS）评定精神症状，同时检测3组对象血SOD活性及BDNF含量。结果慢性精神分裂症患者组总超氧化物歧化酶（totalsuperoxidedismutase，T．SOD）与铜锌超氧化物歧化酶（CU—prozinc-superoxidedismutase，Cu-ZnSOD）活性最高，首发精神分裂症患者组次之，正常对照组最低。与之相反，慢性精神分裂症患者组血BDNF含量最低，首发精神分裂症患者组次之，正常对照组最高（所有差异均有统计学意义）。首发精神分裂症患者组的BDNF与Cu-ZnSOD呈负相关（r=一0．24，P=0．038），但在正常对照组与慢性精神分裂症患者组无此负相关；3组的BDNF与T-SOD均不相关。在未服药的首发精神分裂症患者中，精神症状的严重程度与血清Cu—ZnSOD水平存在显著负相关，（主要是阳性症状）与BDNF水平存在显著正相关，但在服药的慢性患者中无上述相关。结论与首发精神分裂症患者相比，慢性精神分裂症患者的血清SOD活性增加，血BDNF含量下降。首发精神分裂症患者的SOD活性与血BDNF含量与疾病严重程度相关，但此关联随着疾病进展而逐渐弱化。     

精神分裂症早期干预的研究进展

有关精神分裂症的早发现、早治疗，笔者拟从精神分裂症的危险因素、前驱症状、首发性精神病、鉴别诊断、早期药物干预、认知行为治疗等方面作一综述。     

精神分裂症阴性症状早期识别与治疗的重要意义北大核心CSCD

精神分裂症是一种由遗传、发育和环境等因素促发的复杂性精神疾病。该病往往在患者成年早期或青少年晚期出现明显的精神病发作（阳性症状）时才被诊断,也有部分患者为早发性精神分裂症（起病年龄13—18岁）和儿童精神分裂症（起病年龄〈13岁）。在确定诊断前患者多数都经历了早期症状的前驱期,亦称疾病未治疗期,与精神分裂症的低治愈率密切相关。     

精神分裂症超高危人群的神经影像学研究进展

精神分裂症被认为是一种神经发育障碍,其前驱期症状不具有特异性,对有前驱期症状的高危人群的评估标准主要综合了遗传因素与前驱期综合征表现及严重程度,神经影像学研究发现超高危人群存在脑结构和功能异常改变,根据这些异常对超高危人群进行临床诊断评估及病理机制探索,这对早期识别超高危人群,降低精神分裂症的发病率,改善预后,减轻疾病的治疗负担具有重要意义。     

精神分裂症前驱期的早期识别及诊断

对精神分裂症前驱期人群的及时而有效干预能预防精神分裂症的发生,从而改善疾病的预后。近二十年国内外研究者对前驱期的识别做了大量努力,目前主要以诊断工具作为主要识别手段,本文将从症状学、诊断工具、神经生物学方面对前驱期的早期发现进行论述。     

精神分裂症患者前驱症状的调查与分析

目的 调查与分析精神分裂症患者的前驱症状。方法 在有明显社会心理诱发因素的首发精神分裂症住院患者中，随机抽取100例作为精神分裂症组。在向危机干预中心求助的正常人群中，随机抽取100例作为危机干预组。并对两组的社会心理诱因和前驱症状进行比较分析。结果 正常人(危机干预组)在精神压力下产生的症状与有明显社会心理诱发的精神分裂症(精神分裂症组)的前驱症状元显著差异。结论 在危机干预过程中，警惕一些人群的症状表现可能就是精神分裂症的前驱症状。     

精神分裂症伴发强迫症状临床分析

对精神分裂症患者伴发强迫症状的有关情况作一了解。 1对象和方法 为2005年6月至12月我院住院患者，符合中国精神障碍分类与诊断标准第3版精神分裂症诊断标准；阳性与阴性症状量表（PANSS）评分≥60分；     

精神分裂症超高危人群的早期临床识别

对有精神分裂症前驱期表现的＂超高危人群＂进行早期识别和有效干预可以预防精神分裂症的发生。目前＂超高危人群＂临床识别标准主要综合了遗传高危（易感性）与前驱期综合征表现及严重程度（即：轻微的和/或短暂的精神病性症状与近期大体功能的显著衰退）。近期研究报道符合此标准的超高危人群在2年随访期内转化为精神分裂症的比例高达30%~35%。神经心理学和神经影像学研究显示＂超高危人群＂存在认知功能损害和脑结构与功能的异常。本文就近年来有关＂超高危人群＂的早期临床识别标准、诊断工具以及生物学预警因素的研究发现进行论述。     

女性精神分裂症患者月经状况观察

目的：了解女性精神分裂症患者月经变化的情况及相关因素的影响。方法：对142例符合中国精神障碍分类与诊断标准第3版精神分裂症诊断标准的女性患者与40例正常女性进行连续5个月的观察。结果：患者组中出现月经延长(时间≥1周)及停经的异常率为62．7％，对照组为30，0％。结论：住院女性精神分裂症患者月经异常情况严重，不同药物影响不同，与其他因素相比，药物的影响起主要作用．其他因素作用轻微。     

Antipsychotic drug treatment in the prodromal phase of schizophrenia

OBJECTIVE: The safety and tolerability of short-term treatment with a low dose of risperidone was evaluated in adolescents with prodromal symptoms and a family history of schizophrenia. METHOD: Four prodromal high-risk adolescents and six first-episode patients with schizophrenia were treated with average doses of 1.0 and 1.8 mg/day of risperidone, respectively, in an 8- to 12-week open-label trial. RESULTS: No significant treatment-related adverse events were noted. Severity of thought and behavior disturbance ratings declined by about 30%; performance on a test of verbal learning improved by about 100% during treatment in both prodromal and first-episode patients, changes that achieved statistical significance despite the small group sizes. CONCLUSIONS: These findings are preliminary and should not be used to guide health care decisions at this time. Randomized controlled trials are needed to determine whether antipsychotic drug treatment of prodromal patients can delay or prevent onset or attenuate the clinical course of schizophrenia.     

Neuropsychological impairment and psychopathology in first-episode schizophrenic patients related to the early course of illness

The objective of the present study was to explore whether the early course of illness including first onset of psychotic symptoms influences neuropsychological functioning and psychopathology in first-episode schizophrenics. Patients with a short prodromal period (n = 20) and patients with a long prodromal period (n = 20) and controls matched with regard to age, gender and education (n = 40) were administered a battery of standardized neuropsychological tests and psychopathological rating scales. The results indicate an overall difference in neuropsychological performance with the schizophrenic patients scoring lower than controls. Schizophrenic patients scored significantly lower in all subtests except in visual memory and abstraction/flexibility than controls. No significant difference between neuropsychological performance between patient samples was found. Psychopathology was more pronounced in the long prodromal period group rating higher on negative and affective symptoms compared with the short prodromal period group. The data suggests that neuropsychological deficits in first-episode schizophrenia are independent of the early course of schizophrenia, and although negative symptoms are associated with the length of the prodromal period, they do not imply greater neuropsychological impairment. Received: 30 May 1997 / Accepted: 10 October 1997     

Impaired mismatch negativity generation in prodromal subjects and patients with schizophrenia

BACKGROUND: Mismatch negativity (MMN) specifically the response to tone duration deviants has consistently been shown to be reduced in schizophrenia suggesting dysfunction in auditory sensory memory. As part of a multidimensional approach to the early recognition of psychosis, MMN was investigated as a possible risk factor for later development of psychosis in subjects with a prodromal syndrome. Forty-three prodromal subjects, 31 neuroleptic-free inpatients with schizophrenia and 33 healthy controls were studied. A prodromal state was defined by a cluster 'Cognitive Disturbances' as defined by the 'Bonn Scale for the Assessment of Basic Symptoms' (BSABS), which was found highly predictive of first-episode schizophrenia. To elicit MMN, a three-tone auditory oddball paradigm with 10% 'duration deviants' and 10% 'frequency deviants' was used. RESULTS: MMN amplitudes to tone duration deviants were significantly reduced in the patients with schizophrenia compared to controls. The putatively prodromal subjects also showed a slight, though non-significant reduction of the MMN amplitude that was intermediate between normal controls and patients with schizophrenia, and with a larger within-group variance. CONCLUSION: These results support the view that abnormalities in temporal processing are particularly pronounced in patients with schizophrenia. Prodromal subjects are a heterogeneous group with regard to outcome and time until transition to a first psychotic episode. Follow-up of these putatively prodromal subjects will show whether MMN amplitudes further reduce over time in those developing psychosis and if a reduction is state-dependent.     

Risk of suicide and suicidal ideation in psychosis: Results from an Italian multi-modal pilot program on early intervention in psychosis

Suicidality is high in schizophrenia, particularly in first-episode patients. Little is known about patients with prodromal symptoms of psychosis or otherwise high-risk persons.In a sample enrolled in an early intervention program implemented in Milan (Italy), a history of attempted suicide before enrollment was found in 6 first-episode schizophrenia (out of 87, 6.9%), and 7 high-risk of psychosis (out of 81, 8.6%) patients.In the first-episode group, a history of suicide attempts was related to a shorter duration of untreated psychosis. In the high-risk group, a family psychiatric history in first/second degree relatives of patients and a personal history of substance abuse were both associated with an enhanced risk of attempted suicide before enrollment.During the first year of treatment, 3 new attempted suicides were recorded among 57 (5.3%) high-risk patients, and none among first-episode patients (n = 58) (no dropout in the sample). The levels of suicide ideation on the BPRS did not differ by group at assessment, and significantly declined from assessment at entry to 1-year follow-up, except in seven HRP patients who become positive for core symptoms of schizophrenia, as measured on the BPRS.At enrollment, patients at high risk of psychosis had the same prevalence of past suicide attempts than first-episode schizophrenia patients: since suicide attempt is the most important predictor of a future suicidal attempt, the assessment of suicide risk should be given a privileged role in patients at high risk of psychosis as well.     

Reduction of auditory event-related P300 amplitude in subjects with at-risk mental state for schizophrenia

Neurophysiological methods allow the examination of cognitive-cortical functioning in patients with schizophrenia in its prodromal states. As revealed by previous studies, event-related potential components such as auditory evoked P300 associated with cognitive processes, such as attention and orientation, are known to be reduced in amplitude in acute and chronic as well as in medicated and unmedicated patients. It is, however, unclear whether a P300 amplitude reduction occurs before the schizophrenic psychosis is fully manifested. We studied patients in the prodromal phase of the schizophrenic disorder (i.e. subjects with an at-risk mental state showing attenuated psychotic symptoms or brief limited intermittent symptoms) as well as first-episode patients and chronic patients with schizophrenia and compared these groups to healthy subjects. The event-related P300 was recorded during an auditory oddball paradigm. Groups differed significantly from each other in the P300 amplitude at Pz (F(3/149)=2.532, p=0.02). Post-hoc tests revealed significantly lower P300 amplitudes of non-medicated prodromal (p=.03), first-episode (p=.01) and chronic patients (p=.001) compared to the healthy controls. The study revealed that there are neurophysiological changes as the reduction in P300 amplitudes begins early in schizophrenia at the prodromal phase, i.e. before a manifestation of full-blown psychosis, and that these changes seem to have a progressive course from prodromal to chronic state of schizophrenia as assumed in this cross-sectional study.     

哈伯因对精神分裂症记忆障碍的疗效

目的：探讨哈伯因对精神分裂症患者记忆功能障碍的疗效。方法：80例首发精神分裂症患者平分为哈伯因合并奎硫平治疗(合用组)和单用奎硫平治疗(单用组)，疗程8周。采用阳性与阴性症状量表(PANSS)、韦氏记忆量表修订版(WMS—RC)评定精神症状及记忆功能，分别于治疗前、治疗8周各评定1次。结果：治疗后两组患者记忆功能损害和精神症状均获得显著改善，两组间无显著差异，记忆功能的改善与精神症状的改善相关。结论：哈伯因对精神分裂症的记忆功能障碍疗效不明显。     

A psychological early intervention program for the prepsychotic prodromal state. A case report

We introduce a multimodular, psychological outpatient, intervention program for the treatment of the early prodromal stage which includes individual and group psychotherapy, cognitive training, and family support. The conceptual framework is comprised of the vulnerability and stress-coping concept for schizophrenia. We use cognitive-behavioural strategies which are derived from first-episode and relapse prevention in the treatment of schizophrenia and from the treatment of anxiety disorders and depression. We report the case of a 25-year-old college student in the early prodromal state who was treated by the program. His self-experienced neuropsychological deficits improved, depressive and anxiety symptoms decreased, and positive self-concept was stabilised. During the treatment period of 1 year, social deterioration and prepsychotic and psychotic symptoms were prevented.     

首发精神分裂症的早期症状调查

目的探讨精神分裂症早期症状的特异性。方法采用自编调查表,通过对42例首发精神分裂症与32例首发情感性精神障碍患者的回顾性调查,比较分析两者早期症状的发生率。结果精神分裂症患者早期多见有轻度阳性症状、某些阴性症状及个性的改变,比情感性精神障碍患者的发生率高且有显著性差异(P<0.05)。神经症性症状、情感性症状、社会功能障碍等发生率高但与情感性精神障碍没有显著性差异(P>0.05)。结论精神分裂症早期症状多种多样,某些轻微阳性和阴性症状发生率高,具有一定的特异性,应针对这些症状应进行早期干预。     

Determining the chronology and components of psychosis onset: The Nottingham Onset Schedule (NOS)

The Nottingham Onset Schedule (NOS) is a short, guided interview and rating schedule to measure onset in psychosis. Onset is defined as the time between the first reported/observed change in mental state/behaviour to the development of psychotic symptoms. Onset is conceptualised as comprising of (i) a prodrome of two parts: a period of 'unease' followed by 'non-diagnostic' symptoms; (ii) appearance of psychotic symptoms; and (iii) a build-up of diagnostic symptoms leading to a definite diagnosis. Twenty consecutive cases of first-episode psychosis were administered the NOS schedule to determine its psychometric properties including inter-rater and test-retest reliability. Its clinical and research potential as a reliable measure of duration of untreated psychosis (DUP) was assessed in a cohort of 99 cases of first-episode psychosis (56 schizophrenia, 43 affective psychoses). NOS identified all prodromal symptoms previously reported in other studies. There was high degree of inter-rater and test-retest reliability for all components of NOS. Duration of untreated psychosis was significantly longer (p<0.05) in schizophrenia (mean 179 days, S.D. 344; median 52 days) than in affective psychosis (mean 15 days, S.D. 116; median 12 days) but there were no gender differences between lengths of prodrome or treatment delays. The NOS provides a standardised and reliable way of recording early changes in psychosis and identifying relatively precise time points for measuring several durations in emerging psychosis. The scale is easy to use and is not time-consuming or labour intensive. Onset, as measured by NOS, is significantly longer in schizophrenic disorders than in affective psychosis. A small proportion of schizophrenia cases have very long DUP. Some cases with schizophrenia receive anti-psychotics in the prodromal phase, prior to the emergence of frank psychotic symptoms.