Gender Difference in the Prodromal Symptoms of First-episode Schizophrenia

To investigate the gender difference of early symptoms appearing before the onset of the psychotic symptoms in patients with first-episode schizophrenia, we reviewed the medical records of 63 patients (38 males, 25 females), who were hospitalized for first-episode schizophrenia. The frequency and duration of prodromal and psychotic symptoms, Clinical Global Impression scale scores, Global Assessment of Functioning (GAF) scale scores at admission, and other clinical characteristics were recorded for all patients. Overall, the most common prodromal symptoms were attenuated positive symptoms (89%), followed by mood symptoms (86%). Negative symptoms were the most common in male patients (97.4%), whereas attenuated positive symptoms were the most common in female patients (84%). Male patients demonstrated more frequent negative, cognitive, and obsessive-compulsive symptoms than female patients did and also showed a tendency of having negative symptoms for the longer period. Correlational analysis showed a significant negative correlation between the duration of negative symptoms and GAF scores at admission in male patients. Our findings suggest that different patterns of prodromal symptoms between male and female begin before the onset of the psychosis. Further prospective studies should be needed.This paper was supported by a grant (M103KV010012- 08K2201-01210) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea.Jeppesen P, 2008, PSYCHOL MED, V38, P1157, DOI 10.1017/S0033291708003449Cannon TD, 2008, ARCH GEN PSYCHIAT, V65, P28WILLHITE RK, 2008, SCHIZOPHR RES, V104, P237LAPPIN JM, 2007, BR J PSYCHIAT S, V51, pS123Goldstein JM, 2006, HORM BEHAV, V50, P612, DOI 10.1016/j.yhbeh.2006.06.029Rosen JL, 2006, SCHIZOPHR RES, V85, P124, DOI 10.1016/j.schres.2006.03.034Amminger GP, 2006, SCHIZOPHR RES, V84, P67, DOI 10.1016/j.schres.2006.02.018Barbui C, 2005, J CLIN PSYCHOPHARM, V25, P521, DOI 10.1097/01.jcp.0000185423.15891.02Perkins DO, 2005, AM J PSYCHIAT, V162, P1785Svirskis T, 2005, SCHIZOPHR RES, V75, P439, DOI 10.1016/j.schres.2004.11.002Norman RMG, 2005, J NERV MENT DIS, V193, P17, DOI 10.1097/01.nmd.0000149214.17924.d9Yung AR, 2004, SCHIZOPHR RES, V67, P131, DOI 10.1016/S0920-9964(03)00192-0Lieberman JA, 2003, AM J PSYCHIAT, V160, P1396McGlashan TH, 2003, SCHIZOPHR RES, V61, P7, DOI 10.1016/S0920-9964(02)00439-5Kinon BJ, 2003, PSYCHONEUROENDOCRINO, V28, P55, DOI 10.1016/S0306-4530(02)00127-0McGorry PD, 2002, ARCH GEN PSYCHIAT, V59, P921Gourzis P, 2002, SCHIZOPHRENIA BULL, V28, P415Norman RMG, 2001, PSYCHOL MED, V31, P381Bottlender R, 2000, SCHIZOPHR RES, V44, P145Cohen RZ, 2000, CAN J PSYCHIAT, V45, P544LEUNG A, 2000, ACTA PSYCHIAT SCAN S, V401, P3GOLDSTEIN JM, 2000, WOMEN SCHIZOPHRENIA, P111Hafner H, 1999, ACTA PSYCHIAT SCAND, V100, P105Pohjalainen T, 1998, MOL PSYCHIATR, V3, P256Behl C, 1997, MOL PHARMACOL, V51, P535Yung AR, 1996, AUST NZ J PSYCHIAT, V30, P587Larsen TK, 1996, SCHIZOPHRENIA BULL, V22, P241FOLNEGOVIC Z, 1994, SCHIZOPHR RES, V14, P83HAFNER H, 1993, BRIT J PSYCHIAT, V162, P80HAFNER H, 1992, SCHIZOPHR RES, V6, P209

Gender Difference in the Prodromal Symptoms of First-episode Schizophrenia

To investigate the gender difference of early symptoms appearing before the onset of the psychotic symptoms in patients with first-episode schizophrenia, we reviewed the medical records of 63 patients (38 males, 25 females), who were hospitalized for first-episode schizophrenia. The frequency and duration of prodromal and psychotic symptoms, Clinical Global Impression scale scores, Global Assessment of Functioning (GAF) scale scores at admission, and other clinical characteristics were recorded for all patients. Overall, the most common prodromal symptoms were attenuated positive symptoms (89%), followed by mood symptoms (86%). Negative symptoms were the most common in male patients (97.4%), whereas attenuated positive symptoms were the most common in female patients (84%). Male patients demonstrated more frequent negative, cognitive, and obsessive-compulsive symptoms than female patients did and also showed a tendency of having negative symptoms for the longer period. Correlational analysis showed a significant negative correlation between the duration of negative symptoms and GAF scores at admission in male patients. Our findings suggest that different patterns of prodromal symptoms between male and female begin before the onset of the psychosis. Further prospective studies should be needed

MRI study of the cavum septum pellucidum in obsessive-compulsive disorder

The cavum septum pellucidum (CSP), a putative marker of neurodevelopmental anomaly, has been associated with an increased risk of several psychiatric disorders. The purpose of this study was to evaluate the CSP in patients with obsessive-compulsive disorder (OCD) compared with healthy control subjects. Seventy-one patients with OCD and 71 healthy volunteers matched for age and sex were evaluated with magnetic resonance imaging. We evaluated the CSP using criteria employed in previous studies: presence of the CSP, length of the CSP, and overall size of the CSP, measured in five grades, ranging from grades 0 (no CSP) to 4 (severe CSP). We evaluated OCD symptom severity using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). The CSP presence was significantly greater in the OCD group (60.6%) than in control subjects (29.6%), and CSP size grade was significantly larger in the OCD group (chi(2) = 15.609, P = 0.004). CSP length showed no significant group difference. Among patients with OCD, those with a CSP had higher scores on the obsession subscale of the Y-BOCS than those without a CSP (Z = -2.358, P = 0.018), while they did not show significant difference from those without a CSP in the compulsion subscale of the Y-BOCS, age, duration of illness, or age at onset. These results indicate that neurodevelopmental alterations in midline structures might contribute to the pathogenesis of OCD.This paper was supported by a Grant (M103KV010012-08K2201-01210) from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology of the Republic of Korea.An SK, 2009, MOL PSYCHIATR, V14, P318, DOI 10.1038/sj.mp.4002129Takahashi T, 2008, SCHIZOPHR RES, V105, P236, DOI 10.1016/j.schres.2008.06.021Gilbert AR, 2008, J AFFECT DISORDERS, V109, P117, DOI 10.1016/j.jad.2007.12.223Choi JS, 2008, PROG NEURO-PSYCHOPH, V32, P1326, DOI 10.1016/j.pnpbp.2008.04.011Freeman JB, 2008, J AM ACAD CHILD PSY, V47, P593, DOI 10.1097/CHI.0b013e31816765f9Kang DH, 2008, NEUROREPORT, V19, P609Grisham JR, 2008, EUR ARCH PSY CLIN N, V258, P107, DOI 10.1007/s00406-007-0789-0Yoo SY, 2008, J KOREAN MED SCI, V23, P24, DOI 10.3346/jkms.2008.23.1.24Saito Y, 2008, RADIOLOGY, V246, P536, DOI 10.1148/radiol.2462061469Scoffings DJ, 2008, CLIN RADIOL, V63, P210, DOI 10.1016/j.crad.2007.07.008Gu BM, 2008, BRAIN, V131, P155, DOI 10.1093/brain/awm277CHA KR, 2008, DEPRESS ANXIETYTHOMANN PA, 2008, PSYCHOL MED, P1Yoo SY, 2007, ACTA PSYCHIAT SCAND, V116, P211, DOI 10.1111/j.1600-0447.2007.01046.xHong SB, 2007, EUR ARCH PSY CLIN N, V257, P185, DOI 10.1007/s00406-006-0655-5Kim MJ, 2007, BIPOLAR DISORD, V9, P274Flashman LA, 2007, PSYCHIAT RES-NEUROIM, V154, P147, DOI 10.1016/j.pscychresns.2006.09.001Kitis A, 2007, PROG NEURO-PSYCHOPH, V31, P254, DOI 10.1016/j.pnpbp.2006.06.022Dickey CC, 2007, SCHIZOPHR RES, V89, P49, DOI 10.1016/j.schres.2006.08.004Fontenelle LF, 2006, PROG NEURO-PSYCHOPH, V30, P327, DOI 10.1016/j.pnpbp.2005.11.001Sherman PM, 2006, ACTA NEUROCHIR, V148, P359, DOI 10.1007/s00701-005-0652-xAigner M, 2005, PSYCHIAT RES-NEUROIM, V140, P173, DOI 10.1016/j.pscychresns.2005.03.002Sachdev PS, 2005, AUST NZ J PSYCHIAT, V39, P757Mergl R, 2005, FORTSCHR NEUROL PSYC, V73, P504, DOI 10.1055/s-2004-830173Ha TH, 2005, NEUROSCI LETT, V384, P172, DOI 10.1016/j.neulet.2005.04.078Riffkin J, 2005, PSYCHIAT RES-NEUROIM, V138, P99, DOI 10.1016/j.pscychresns.2004.11.007Pian KLH, 2005, PSYCHIAT RES-NEUROIM, V138, P89, DOI 10.1016/j.pscychresns.2004.12.003Kasai K, 2004, SCHIZOPHR RES, V71, P65, DOI 10.1016/j.schres.2003.12.010Born CM, 2004, EUR ARCH PSY CLIN N, V254, P295, DOI 10.1007/s00406-004-0496-zLee JM, 2004, NEUROIMAGE, V22, P831, DOI 10.1016/j.neroimage.2004.02.004Aouizerate B, 2004, PROG NEUROBIOL, V72, P195, DOI 10.1016/j.pneurobio.2004.02.004Dazzan P, 2004, BRAIN, V127, P143, DOI 10.1093/brain/awh015Gross-Isseroff R, 2003, WORLD J BIOL PSYCHIA, V4, P129Kwon JS, 2003, J NEUROL NEUROSUR PS, V74, P962Kim KJ, 2003, BIOL PSYCHIAT, V54, P76, DOI 10.1016/S0006-3223(03)01830-9McCrory P, 2002, BRIT J SPORT MED, V36, P157Bystritsky A, 2001, DEPRESS ANXIETY, V14, P214Bradshaw JL, 2000, BRAIN LANG, V73, P297Nopoulos P, 2000, J NEUROPSYCH CLIN N, V12, P344Gilbert AR, 2000, ARCH GEN PSYCHIAT, V57, P449Nopoulos PC, 1998, AM J PSYCHIAT, V155, P1074Rosenberg DR, 1998, BIOL PSYCHIAT, V43, P623Kwon JS, 1998, AM J PSYCHIAT, V155, P509Shioiri T, 1996, PSYCHOL MED, V26, P431FIRST MB, 1996, STRUCTURED CLIN INTEDEGREEF G, 1992, PSYCHIAT RES-NEUROIM, V45, P1GOODMAN WK, 1989, ARCH GEN PSYCHIAT, V46, P1006SARWAR M, 1989, AM J NEURORADIOL, V10, P989PAULS DL, 1986, ARCH GEN PSYCHIAT, V43, P1180

Diagnostic value of structural and diffusion imaging measures in schizophrenia

Objectives: Many studies have attempted to discriminate patients with schizophrenia from healthy controls by machine learning using structural or functional MRI. We included both structural and diffusion MRI (dMRI) and performed random forest (RF) and support vector machine (SVM) in this study. Methods: We evaluated the performance of classifying schizophrenia using RF method and SVM with 504 features (volume and/or fractional anisotropy and trace) from 184 brain regions. We enrolled 47 patients and 23 age- and sex-matched healthy controls and resampled our data into a balanced dataset using a Synthetic Minority Oversampling Technique method. We randomly permuted the classification of all participants as a patient or healthy control 100 times and ran the RF and SVM with leave one out cross validation for each permutation. We then compared the sensitivity and specificity of the original dataset and the permuted dataset. Results: Classification using RF with 504 features showed a significantly higher rate of performance compared to classification by chance: sensitivity (87.6% vs. 47.0%) and specificity (95.9 vs. 48.4%) performed by RF, sensitivity (89.5% vs. 48.0%) and specificity (94.5% vs. 47.1%) performed by SVM. Conclusions: Machine learning using RF and SVM with both volume and diffusion measures can discriminate patients with schizophrenia with a high degree of performance. Further replications are required

Regional Differences in Serotonin Transporter Occupancy by Escitalopram:An [(11)C]DASB PK-PD Study

Background and objective Escitalopram is one of the most commonly prescribed selective serotonin reuptake inhibitors (SSRIs). It is thought to act by blocking the serotonin transporter (SERT). However, its dose-SERT occupancy relationship is not well known, so it is not clear what level of SERT blockade is achieved by currently approved doses. Methods To determine the dose-occupancy relationship, we measured serial SERT occupancy using [C-11] DASB [3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile] positron emission tomography (PET) and plasma drug concentrations after the administration of escitalopram in 12 healthy volunteers. We then built a pharmacokinetic-pharmacodynamic model to characterize the dose-occupancy relationship in the putamen and the dorsal raphe nucleus. Results Escitalopram at approved doses occupied less SERT than expected and the SERT occupancy showed regional effects [occupancy was higher in the dorsal raphe nucleus than in the putamen (p < 0.001)]. The drug concentration when 50 % of receptors are occupied (EC50) value and Hill coefficient were significantly different between the putamen (EC50 4.30, Hill coefficient 0.459) and the dorsal raphe nucleus (EC50 2.89, Hill coefficient 0.817). Conclusions Higher doses of escitalopram than 20 mg are needed to achieve 80 % or greater SERT occupancy. Higher occupancy by escitalopram in the dorsal raphe nucleus relative to the striatum may explain the delayed onset of action of SSRIs by modulating autoreceptor function. The prevention of the 5-HT1A autoreceptor-mediated negative feedback could be a strategy for accelerating the clinical antidepressant effects.N

Cavum septum pellucidum in subjects at ultra-high risk for psychosis: compared with first-degree relatives of patients with schizophrenia and healthy volunteers

OBJECTIVE: The cavum septum pellucidum (CSP) is a space between the two leaflets of the septum pellucidum, and is a putative marker of disturbance in early brain development. We examined whether CSP was present more frequently in subjects at ultra-high risk (UHR) for psychosis compared to first-degree relatives of patients with schizophrenia (genetic high risk, GHR) and healthy controls (HC). METHODS: We evaluated CSP in 87 subjects (30 UHR, 23 GHR, and 34 HC) according to a published grading system using high-resolution magnetic resonance imaging (MRI) with 0.45-mm slice thickness. We also assessed two other criteria: presence of CSP on at least one MRI slice, and abnormally large CSP (i.e., > or =6 mm in length). Correlational analysis between CSP measures and clinical symptoms was also examined. RESULTS: Based on the grading scale, the UHR group exhibited a significantly higher incidence of abnormal CSP (grades 2, 3, and 4) compared to the HC group, but there were no significant differences in the incidence of abnormal CSP between the UHR and GHR or the GHR and HC groups. There were no significant differences among the groups in the presence of CSP on at least one MRI slice or abnormally large CSP based on the length of CSP. In addition, no significant correlations between CSP measures and clinical symptoms were found. CONCLUSION: These findings suggest that abnormal CSP might be associated with susceptibility to psychosis, although the CSP itself might be a normal anatomical variant. Further studies using a larger sample are needed to clarify issues on neurodevelopmental perspective in subjects at high risk for psychosis

Impaired migration of autologous induced neural stem cells from patients with schizophrenia and implications for genetic risk for psychosis

Stem cell technologies have presented explicit evidence of the neurodevelopmental hypothesis of schizophrenia. However, few studies investigated relevance of the schizophrenia genetic liability and the use of genetic reprogramming on pluripotent stem cells to the impaired neurodevelopment shown by stem cells. Therefore, this study sought to investigate the cellular phenotypes of induced neural stem cells (iNSCs) derived without genetic modification from patients with schizophrenia and from genetic high risk (GHR) individuals. Three patients with a diagnosis of schizophrenia, 3 GHR individuals who had two or more relatives with schizophrenia, and 3 healthy volunteers participated. iNSCs were derived using a small molecule-based lineage switch method, and their gene expression levels and migration capabilities were examined. Demographic characteristics were not different among the groups (age, chi(2) = 5.637, P = .060; education, chi(2) = 2.111, P = .348). All participants stayed well during the follow-up except one GHR individual who developed psychosis 1.5 years later. Migration capacity was impaired in iNSCs from patients with schizophrenia (SZ-iNSCs) compared to iNSCs from GHR individuals or controls (P < .001). iNSCs from a GHR individual who later developed schizophrenia showed migratory impairment that was similar to SZ-iNSCs. Gene expression levels of Sox2 in SZ-iNSCs were significantly lower than those in controls (P = .028). Defective migration in genetically unmodified SZ-iNSCs is the first direct demonstration of neurodevelopmental abnormalities in schizophrenia. Additionally, alterations in gene expression in SZ-iNSCs suggest mechanisms by which genetic liability leads to aberrant neurodevelopment.N