Early detection is a crucial milestone in the prevention and treatment of schizophrenia spectrum psychosis, which might alter the course of schizophrenia. Currently, there are two complementary approaches to characterizing the clinical-high risk state of psychosis : the ultra-high risk (UHR) and basic symptoms criteria. Individuals at UHR have two phase-specific problems : heightened risk for the potential pathology of schizophrenia spectrum psychosis and the symptoms, distress and psychosocial functional impairment, which make them seek help. The clinical characteristics of UHR are similar to those of overt psychotic disorders in terms of psychopathological symptoms dimensions, psychosocial disability, neurocognitive and socio-cognitive impairments, history of trauma and abuse experience, lack of protective factors and dysfunctional metacognitive beliefs, and the comorbidity of psychiatric illness. Regarding the risk, the pretest risk probability of a psychotic disorder in each high-risk clinic is considered an important factor for predicting the power of an early detection strategy. For the distress and psychosocial disability, the strategies of the therapeutic intervention will be a focus of clinical attention. On the follow-up, one of third of the UHR individuals have sufficient positive symptom to fulfil the at-risk criteria. Most of the UHR individuals have suffered from comorbid psychiatric illness at the times of both baseline and follow-up, and there is no improvement of psychosocial functioning. Currently, it is essential to optimize the early detection and intervention strategy according to the referring and recruitment characteristics of each high-risk clinic in Korean practice situations.
Comorbidity ; Diagnosis* ; Follow-Up Studies ; Pathology ; Protective Factors ; Psychotic Disorders* ; Schizophrenia

Individuals at ultra-high-risk (UHR) for psychosis have become a major focus for research designed to explore markers for early detection of and clinical intervention in schizophrenia. In particular, structural magnetic resonance imaging studies in UHR individuals have provided important insight into the neurobiological basis of psychosis and have shown the brain changes associated with clinical risk factors. In this review, we describe the structural brain abnormalities in magnetic resonance images in UHR individuals. The current accumulated data demonstrate that abnormalities in the prefrontal and temporal cortex and anterior cingulate cortex occur before illness onset. These regions are compatible with the regions of structural deficits found in schizophrenia and first-episode patients. In addition, the burgeoning evidence suggests that such structural abnormalities are potential markers for the transition to psychosis. However, most findings to date are limited because they are from cross-sectional rather than longitudinal studies. Recently, researchers have emphasized neurodevelopmental considerations with respect to brain structural alterations in UHR individuals. Future studies should be conducted to characterize the differences in the brain developmental trajectory between UHR individuals and healthy controls using a longitudinal design. These new studies should contribute to early detection and management as well as provide more predictive markers of later psychosis.
Brain/abnormalities/*pathology ; Gyrus Cinguli/pathology ; Humans ; Longitudinal Studies ; *Magnetic Resonance Imaging ; Predictive Value of Tests ; Psychotic Disorders/diagnosis/*pathology ; Risk Factors ; Temporal Lobe/pathology

OBJECTIVES: Dopamine dysregulation has been regarded as one of the core pathologies in patients with schizophrenia. Since dopamine synthesis capacity has found to be inconsistent in patients with schizophrenia, current classification of patients based on clinical symptoms cannot reflect the neurochemical heterogeneity of the disease. Here we performed new subtyping of patients with first-episode psychosis (FEP) through biotype-based cluster analysis. We specifically suggested basal ganglia structural changes as a biotype, which deeply involves in the dopaminergic circuit. METHODS: Forty FEP and 40 demographically matched healthy participants underwent 3T T1 MRI. Whole brain parcellation was conducted, and volumes of total 6 regions of basal ganglia have been extracted as features for cluster analysis. We used K-means clustering, and external validation was conducted with Positive and Negative Syndrome Scale (PANSS). ResultsZZK-means clustering divided 40 FEP subjects into 2 clusters. Cluster 1 (n = 25) showed substantial volume decrease in 4 regions of basal ganglia compared to Cluster 2 (n = 15). Cluster 1 showed higher positive scales of PANSS compared with Cluster 2 (F = 2.333, p = 0.025). Compared to healthy controls, Cluster 1 showed smaller volumes in 4 regions, whereas Cluster 2 showed larger volumes in 3 regions. RESULTS: K-means clustering divided 40 FEP subjects into 2 clusters. Cluster 1 (n = 25) showed substantial volume decrease in 4 regions of basal ganglia compared to Cluster 2 (n = 15). Cluster 1 showed higher positive scales of PANSS compared with Cluster 2 (F = 2.333, p = 0.025). Compared to healthy controls, Cluster 1 showed smaller volumes in 4 regions, whereas Cluster 2 showed larger volumes in 3 regions. CONCLUSIONS: Two subgroups have been found by cluster analysis, which showed a distinct difference in volume patterns of basal ganglia structures and positive symptom severity. The result possibly reflects the neurobiological heterogeneity of schizophrenia. Thus, the current study supports the importance of paradigm shift toward biotype-based diagnosis, instead of phenotype, for future precision psychiatry.
Basal Ganglia* ; Brain ; Classification ; Cluster Analysis ; Diagnosis ; Dopamine ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Pathology ; Phenotype ; Polytetrafluoroethylene ; Population Characteristics ; Psychotic Disorders* ; Schizophrenia ; Weights and Measures