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。     

精神分裂症超高危人群心理社会及认知功能特点与干预方式研究进展

精神分裂症超高危人群(UHR)是指处于精神分裂症前驱期的人群.对UHR进行早期识别及干预可以提高临床疗效,延缓甚至阻止UHR向精神病的过渡,了解UHR的心理社会因素及认知功能特点,可为UHR的早期识别及干预提供思路.现对UHR的心理社会及认知功能特点与干预现状进行综述,以期为UHR的早期干预和有关学者开展相关研究提供参...     

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].     

精神分裂症超高危人群的评估和干预项目介绍

早期识别、评估并干预精神分裂症前驱期"超高危人群",可有效预防或延缓向精神病转化。近年来,新的评估干预项目在不同国家和地区全面开展。本研究对部分研究项目进行简要介绍。     

精神分裂症超高危人群前驱期症状的研究进展

精神分裂症是一种重性精神疾病,大多患者有前驱症状,了解发病的危险因素（遗传因素等）、早期症状的识别、诊断以及早期如何干预,对降低精神分裂症的发病及预后有重要的意义。本文从多方面进行归纳总结,阐述精神分裂症发病的可能因素,为寻找更加适合精神分裂症超高危人群的筛选方法以及恰当的早期干预提供依据。     

精神病临床高危灰质结构的研究进展

精神分裂症是一种大脑结构和功能异常的严重精神障碍。早期发现及干预处于精神分 裂症前驱期的个体可极大改善其预后。目前,对精神病临床高危（CHR）进行早期识别的客观指标较少。 随着神经影像学技术的发展,许多研究致力于通过大脑结构磁共振成像寻找 CHR 脑灰质生物标志物。 相关研究报道了 CHR 脑皮层及皮层下影像学的异常,但少有一致结论。现就 CHR 结构磁共振成像的研 究进展进行综述,旨在为临床实践及未来研究提供参考。     

精神分裂症超高危人群的评估及预防性干预研究进展

精神分裂症是一种复发率与致残率均很高的疾病,它的早期识别与干预对其预后至关重要.目前,研究者们开发出许多精神分裂症超高危人群的评估工具,同时社会心理治疗干预、药物干预、综合干预也应用于精神分裂症高危人群的早期干预.现就精神分裂症高危人群的评估及预防性干预研究进展进行综述.     

精神分裂症超高危人群预防性干预研究进展

精神分裂症是一种病因未明、病程迁延、治疗困难的重症精神疾病,按照目前的治疗水平,约有30%～50%左右的急性精神分裂症患者预后不良,社会功能严重受损。故对有精神分裂症前驱期表现的"超高危人群"尽早进行有效的干预,以延缓病程进展、改善其不良预后、减少疾病和残疾负担,成为当今精神医学     

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。     

首发精神分裂症前驱期症状学分析

目的：探讨首发精神分裂症患者前驱期的症状学特征。方法：对71例符合中国精神疾病分类方案与诊断标准第2版修订本精神分裂症诊断标准的首次发作患者，按照自编精神分裂症前驱症状调查表的32条症状进行检查，并与62名正常成年人进行对比分析。结果：首发精神分裂症患者所有的前驱症状正常人在某些情况下也可能出现，但发生率以患者明显较高。其中灵敏度≥0．25、阳性预测值≥0．70的症状是：个人卫生形象变差；行为怪异；情感不适切；赘述或话不切题；孤僻等。结论：这些前驱期表现有助于理解精神分裂症早期的发病过程，并为早期识别和干预提供参考。     

When things are not as they seem: detecting first‐episode psychosis upon referral to ultra high risk (‘prodromal’) clinics

The current paper examines a neglected function of ‘ultra high risk’ (UHR) clinics: to detect first‐episode psychosis (FEP) mistakenly identified as a prodrome. A clinical audit was conducted of referrals to a UHR service, the Personal Assessment and Crisis Evaluation Clinic, over a 12‐month period (April 2005–March 2006). In this audit, 11.4% of the total number of referrals (n= 149) and 11.9% of those who attended a first appointment were psychotic on referral. These figures indicate that a substantial proportion of individuals thought to be prodromal are in fact suffering FEP. UHR clinics minimize duration of untreated psychosis for FEP patients mistaken as prodromal.     

Testing the Ultra High Risk (prodromal) criteria for the prediction of psychosis in a clinical sample of young people

Criteria for identifying individuals at imminent risk for onset of a psychotic disorder, that is "prodromal" for psychosis, have recently been described. The current study set out to test the predictive validity of these criteria in a sample of help-seeking young people aged 15-24 years who were referred to, but not necessarily treated at, a psychiatric service. Ultra High Risk (UHR) status was determined at baseline and psychosis status was assessed at 6 month follow up. Baseline psychosocial functioning was also assessed as a possible predictor of psychosis. In the sample of 292 individuals, 119 (40.7%) met UHR criteria. Of these UHR+ people, 12 became psychotic within 6 months and 107 did not. Only one person not meeting UHR criteria developed psychosis in the follow up period. Sensitivity, specificity, positive predictive value and negative predictive value of UHR+ status for prediction of psychosis were, respectively, 0.923 (95% CI 0.621, 1), 0.616 (95% CI 0.556, 0.673), 0.101 (95% CI 0.056, 0.173) and 0.994 (95% CI 0.963, 1). UHR+ individuals were significantly more likely to become psychotic than UHR- individuals (Odds Ratio 19.3, 95% CI 2.5, 150.5). Low functioning at baseline was associated with psychosis onset in the whole sample and in the UHR group. The transition to psychosis rate was much lower than in previous samples. This may be a due to the sample being a more general one, not identified as possibly "prodromal". Other potential causes of this reduction in transition are also explored.     

White matter abnormalities in subjects at ultra high-risk for schizophrenia and first-episode schizophrenic patients

Schizophrenia is associated with neuroanatomical abnormalities. Gray matter decrease seems to predate first schizophrenic episode. Whether white matter abnormalities predate the onset of psychotic symptoms is unclear. We investigated this issue using voxel-based morphometry (VBM) of structural magnetic resonance images to examine individuals with prodromal symptoms who were at ultra high-risk (UHR) of developing schizophrenia and compared them to first-episode schizophrenic patients and healthy controls. White matter volume maps from high-resolution magnetic resonance T1 weighted whole brain images were analyzed in a cross-sectional study using SPM2 in 30 UHR patients, 23 first-episode schizophrenic patients and 29 healthy controls. UHR patients showed significant lower white matter volume in the right superior temporal lobe compared to healthy controls. First-episode patients with schizophrenia showed widespread smaller white matter volume bilaterally compared to UHR patients. This study provides first evidence for smaller white matter volume in the right temporal lobe of UHR patients, one of the key structures in the pathophysiology of schizophrenia. Furthermore, white matter abnormalities seem to progress after transition into schizophrenia.     

Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia

Background

Accumulating evidence from postmortem and magnetic resonance imaging (MRI) studies suggests that abnormalities of medial temporal lobe structures are critically involved in the pathogenesis of schizophrenia. It is still unclear, however, whether certain abnormalities are already present in individuals at ultra high-risk (UHR) for transition into psychosis. Recent studies involving patients at UHR showed contradictory results for hippocampal volume, and only 1 study reported that amygdalar volume was unchanged between healthy patients and those at UHR. Furthermore, no subregions of the hippocampus have been investigated in people at UHR.

Methods

We recruited 29 UHR patients, 23 first-episode patients and 29 age-and sex-matched healthy controls. We measured hippocampal and amygdalar volumes from MRI scans by use of BRAINS2 to manually trace the regions of interest. The hippocampi were divided in 2 regions: head and corpus/tail.

Results

Patients at UHR had significantly smaller volumes of the hippocampus corpus and tail bilaterally, but not of the head, compared with healthy controls. Group differences for the right hippocampus corpus and tail volume remained significant after we controlled for whole brain volume and other covariates. We found that UHR patients who later developed psychosis had smaller right hippocampus corpus and tail volumes than did those who did not develop psychosis. First-episode patients had significantly smaller left amygdalar volumes than did healthy individuals or those at UHR.

Limitations

Our study had a small sample size, and we were unable to control for the effects of medication.

Conclusion

Our findings suggest that parts of the hippocampal–amygdalar complex are involved in the pathogenesis of schizophrenia. Reduction of hippocampus corpus and tail volumes may be indicative of the prodromal phase of schizophrenia and represent risk factors for transition into psychosis. Further investigations are needed to determine whether structural changes of the left amygdala play a role during transition from the prodromal phase to the first manifest episode of schizophrenia.     

A case of rapid conversion to psychosis of delusional misidentification associated with derealisation,verbal memory impairment and FDG-PET imaging abnormalities

The delusional misidentification syndromes, occurring within the context of different nosological settings, such as schizophrenia, are psychopathological phenomena related to the experience of depersonalisation/derealisation. Extensive research indicates that individuals meeting specific “prodromal” criteria, such as attenuated psychotic symptoms, brief intermittent psychotic symptoms, or functional decline and family history of schizophrenia have increased risk for impending psychosis. Despite depersonalisation and/or derealisation often precede psychotic onset, they are not included among the prodromal criteria of the Australian–American approach. A 17-year-old boy with acute agitation, violent behaviour and aggression, and dissociative amnesia had a mild verbal memory impairment and temporo-limbic hypometabolism on the positron-emission tomography. The patient was assessed with both the ultra-high risk (UHR) and the basic symptom approaches and was not found to be prodromal with imminent risk of transition to psychosis. He was hospitalised briefly and 2 weeks after discharge he developed delusional misidentification. This case shows that even the integration of both UHR and basic symptoms criteria may give false negatives in the prediction of psychosis, especially in those cases in which a long prodromal phase is absent.     

Personality features in ultra-high risk for psychosis: A comparative study with schizophrenia and control subjects using the Temperament and Character Inventory-Revised (TCI-R)

Several variables have been identified as risk factors for conversion to overt psychosis in ultra-high risk for psychosis (UHR) individuals. Although almost two-thirds of them do not experience a transition to psychosis, they still exhibit functional disabilities. Other subjective developmental features may be useful for a more precise identification of individuals at UHR. Avoidant behaviors are consistently reported in schizophrenia and in UHR individuals and may be the reflection of a pattern of personality. Thus, personality features in UHR individuals deserves further research. The objective of the present study was to compare temperament and character dimensions between UHR individuals, patients with schizophrenia and healthy controls. One hundred participants (25 UHR individuals, 25 schizophrenia patients and 50 control subjects) where evaluated with the Temperament and Character Inventory-Revised (TCI-R). Univariate ANOVAs followed by Bonferroni tests were used. UHR individuals and schizophrenia patients exhibited higher levels of Harm Avoidance (HA) when compared to control subjects. For HA1 Anticipatory worry vs Uninhibited optimism and HA4 Fatigability & asthenia, UHR and schizophrenia groups showed similar scores and both groups were higher compared to control subjects. With respect to Cooperativeness (CO), UHR and schizophrenia reported lower scores than control subjects, in particular CO2 Empathy vs Social disinterest and CO3 Helpfulness vs unhelpfulness. This study replicates and extends the consideration of HA as a psychopathological related endophenotype and gives us further information of the possible role of personality features in the expression of some of the social dysfunctions observed both in prodromal subjects and schizophrenia patients.     

Prodromal psychosis screening in adolescent psychiatry clinics

Background: Research has identified a syndrome conferring ultra‐high risk (UHR) for psychosis, although UHR interviews require intensive staff training, time and patient burden. Previously, we developed the Prodromal Questionnaire (PQ) to screen more efficiently for UHR syndromes. Aims: This study examined the concurrent validity of the PQ against UHR status and preliminary predictive validity for later psychotic disorder. Method: We assessed a consecutive patient sample of 408 adolescents who presented to psychiatry clinics in Helsinki, Finland, seeking mental health treatment, including 80 participants who completed the Structured Interview for Prodromal Syndromes (SIPS). Results: A cut‐off score of 18 or more positive symptoms on the PQ predicted UHR diagnoses on the SIPS with 82% sensitivity and 49% specificity. Three of 14 (21%) participants with high PQ scores and SIPS UHR diagnoses developed full psychotic disorders within 1 year. Conclusions: Using the PQ and SIPS together can be an efficient two‐stage screening process for prodromal psychosis in mental health clinics.     

Deficit of theory of mind in individuals at ultra-high-risk for schizophrenia

BACKGROUND: Although a deficit in social cognition is regarded as an early indicator of schizophrenia, few studies have investigated social cognition in ultra-high-risk (UHR) individuals. METHODS: Our investigation involved subjects at UHR for psychosis (N=33) and an age- and IQ-matched healthy control (HC) group (N=36). Two types of theory of mind (ToM) tasks and a neuropsychological test battery were measured. RESULTS: Compared to the HC group, the UHR group performed significantly worse for ToM tasks, with the effect size at an intermediate level (0.64-0.68). Furthermore, the UHR group showed impaired performance in the executive and working memory tests, but not verbal memory tests. These deficits for ToM tests observed in the UHR group were significantly correlated with set-shifting tasks. CONCLUSIONS: Deficits in social cognition may be modest at the prodromal stage of schizophrenia and may be attributed to prefrontal dysfunction. To prevent or delay transition to psychosis, there is a need for specific preventive strategies targeting social functioning for the UHR group.     

Interpersonal sensitivity and functioning impairment in youth at ultra-high risk for psychosis

A personality trait that often elicits poor and uneasy interpersonal relationships is interpersonal sensitivity. The aim of the present study was to explore the relationship between interpersonal sensitivity and psychosocial functioning in individuals at ultra-high risk for psychosis as compared to help-seeking individuals who screened negative for an ultra-high risk of psychosis. A total sample of 147 adolescents and young adult who were help seeking for emerging mental health problems participated in the study. The sample was divided into two groups: 39 individuals who met criteria for an ultra-high-risk mental state (UHR), and 108 (NS). The whole sample completed the Interpersonal Sensitivity Measure (IPSM) and the Global Functioning: Social and Role Scale (GF:SS; GF:RS). Mediation analysis was used to explore whether attenuated negative symptoms mediated the relationship between interpersonal sensitivity and social functioning. Individuals with UHR state showed higher IPSM scores and lower GF:SS and GF:RS scores than NS participants. A statistically negative significant correlation between two IPSM subscales (Interpersonal Awareness and Timidity) and GF:SS was found in both groups. Our results also suggest that the relationship between the aforementioned aspects of interpersonal sensitivity and social functioning was not mediated by negative prodromal symptoms. This study suggests that some aspects of interpersonal sensitivity were associated with low level of social functioning. Assessing and treating interpersonal sensitivity may be a promising therapeutic target to improve social functioning in young help-seeking individuals.