First-episode Treatment-naive Patients Research Articles

Decreased dorsal attention network homogeneity as a potential neuroimaging biomarker for major depressive disorder

BackgroundGaining insight into abnormal functional brain network homogeneity (NH) has the potential to aid efforts to target or otherwise study major depressive disorder (MDD). The NH of the dorsal attention network (DAN) in first-episode treatment-naive MDD patients, however, has yet to be studied. As such, the present study was developed to explore the NH of the DAN in order to determine the ability of this parameter to differentiate between MDD patients and healthy control (HC) individuals. MethodsThis study included 73 patients with first-episode treatment-naive MDD and 73 age-, gender-, and educational level-matched healthy controls. All participants completed the attentional network test (ANT), Hamilton Rating Scale for Depression (HRSD), and resting-state functional magnetic resonance imaging (rs-fMRI) analyses. A group independent component analysis (ICA) was used to identify the DAN and to compute the NH of the DAN in patients with MDD. Spearman's rank correlation analyses were used to explore relationships between significant NH abnormalities in MDD patients, clinical parameters, and executive control reaction time. ResultsRelative to HCs, patients exhibited reduced NH in the left supramarginal gyrus (SMG). Support vector machine (SVM) analyses and receiver operating characteristic curves indicated that the NH of the left SMG could be used to differentiate between HCs and MDD patients with respective accuracy, specificity, sensitivity, and AUC values of 92.47 %, 91.78 %, 93.15 %, and 65.39 %. A significant positive correlation was observed between the left SMG NH values and HRSD scores among MDD patients. ConclusionsThese results suggest that NH changes in the DAN may offer value as a neuroimaging biomarker capable of differentiating between MDD patients and healthy individuals.

Depth-dependent abnormal cortical myelination in first-episode treatment-naïve schizophrenia.

Myelination is key to effective message passing in the central nervous system and is likely linked to the pathogenesis of schizophrenia (SZ). Emerging evidence indicates that a large portion of intracortical myelin insulates inhibitory interneurons that are highly relevant to pathogenesis of schizophrenia. Here for the first time, we characterized intracortical myelination across the entire cortical surface in first‐episode treatment‐naïve patients with schizophrenia (FES) using T1w/T2w ratio of structural MRI, FES patients exhibited significantly higher myelin content in the left inferior parietal lobe, supramarginal gyrus, and superior temporal gyrus in the superficial layer, as well as left IPL in the middle layer, but significantly lower myelin content in the left middle insula and posterior cingulate gyrus. Years of education, a proxy for onset of functional decline, significantly altered the relationship between abnormal parietal and posterior cingulate myelination and clinical symptoms, indicating that the pathoplastic role of myelination hinges on the age of onset of functional decline. In addition, higher myelination generally related to better cognitive function in younger subjects but worse cognitive function in older subjects. We conclude that FES is characterized by increased myelination of the superficial layers of the parietal–temporal association cortex, but reduced myelination of the cingulo‐insular midcortical layer cortex. Intracortical myelin content affects both cognitive functioning and symptom burden in FES, with the effect conditional upon age and timing of onset of functional decline. These results suggest myelination might be a critical biological target for procognitive interventions in SZ.

Hsa_circRNA_101237: A Novel Diagnostic and Prognostic Biomarker and Potential Therapeutic Target for Multiple Myeloma.

BackgroundIt has been demonstrated that circular RNA (circRNA) plays a crucial role in the occurrence and development of tumors, but the diagnostic and predictive value of most circRNAs in tumor patients remains unclear, especially for multiple myeloma (MM).MethodsHigh-throughput circRNA microarray-based sequencing was used to identify the differentially expressed circRNAs in MM. qRT-PCR was then employed to detect hsa_circRNA_101237 expression levels in the bone marrow tissues from 143 MM patients (65 first-episode treatment-naive patients and 78 patients with recurrent/refractory disease), MM cells and bortezomib-resistant MM cell lines. Whether hsa_circRNA_101237 can be used as a potential biomarker and therapeutic target for MM was investigated.ResultsThe average expressions of hsa_circRNA_101237 in the bone marrow tissues from MM patients (especially those with recurrent/refractory disease), MM cells and bortezomib-resistant MM cell lines were increased significantly (P<0.01). hsa_circRNA_101237 was overexpressed in patients positive for 13q14 deletion, 1q21 amplification, P53 deletion, and t(4,14) and t(14,16). hsa_circRNA_101237 was closely related to prognosis of the patients, and its high expression was associated with shorter OS and PFS. In addition, those overexpressing hsa_circRNA_101237 were less responsive to bortezomib treatment. Bioinformatic analysis indicated that hsa_circRNA_101237 interacted with 11 miRNAs and 10 candidate mRNAs. This finding may shed new light on the subsequent studies on the working mechanism and functions.ConclusionIt was first reported that hsa_circRNA_101237 was significantly upregulated in MM. It was indicated that hsa_circRNA_101237 may be a novel biomarker for MM, and it plays a significant role in the occurrence and development of MM.

Disconnectivity between the raphe nucleus and subcortical dopamine-related regions contributes altered salience network in schizophrenia

Numerous studies strongly have suggested the significant role of serotonin in the pathomechanism of schizophrenia. However, few studies have directly explored the altered serotonin function in schizophrenia. In the current study, we explored the altered serotonin function in first-episode treatment-naive patients with schizophrenia with resting-state functional magnetic resonance imaging. A total 42 first-episode treatment-naive patients with schizophrenia and carefully matched healthy controls are included in the study. Considering that the raphe nucleus providing a substantial proportion of the serotonin innervation to the forebrain, the raphe nucleus was chosen as the seed to construct voxel-based functional connectivity (FC) maps. In the results, subcortical dopamine-related regions presented decreased FC with the raphe nucleus, such as the bilateral striatum, pallidum, and thalamus, in patients with schizophrenia. Decreased FC in these regions was significantly correlated with the total negative scores in PANSS. Furthermore, these regions presented with decreased FC connection to salience network. Our results presented that the raphe nucleus played an important role in the dysfunction of subcortical DA-related regions, and contributed to the altered salience network in schizophrenia. Our study emphasized the importance of the raphe nucleus in the pathophysiology of schizophrenia.

Connectivity between the anterior insula and dorsolateral prefrontal cortex links early symptom improvement to treatment response

BackgroundEarly improvement (EI) following treatment with antidepressants is a widely reported predictor to the treatment response. This study aimed to identify the resting-state functional connectivity (rs-FC) and its related clinical features that link the treatment response at the time of EI. MethodsThis study included 23 first-episode treatment-naive patients with MDD. After 2 weeks of antidepressant treatment, these patients received 3.0 Tesla resting-state functional magnetic resonance imaging scanning and were subgrouped into an EI group (N = 13) and a non-EI group (N = 10). Using the anterior insula (rAI) as a seed region, this study identified the rs-FC that were associated with both EI and the treatment response at week 12, and further tested the associations of the identified rs-FC with either the clinical features or the early symptom improvement. ResultsRs-FC between rAI and the left dorsolateral prefrontal cortex (dlPFC) was associated with EI (t21 = −6.091, p = 0.022 after FDR correction for multiple comparisons). This rs-FC was also associated with an interaction between EI and the treatment response at the week 12 (t21 = −5.361, p = 6.37e-5). Moreover, among the clinical features, this rs-FC was associated with the early symptom improvement in the insomnia, somatic symptoms, and anxiety symptoms, and these early symptom improvements were associated with the treatment response. ConclusionRs-FC between the rAI and the left dlPFC played a crucial role in the early antidepressant effect, which linked the treatment response. The early treatment effect relating to rAI may represent an early symptom improvement in self-perceptual anxiety, somatic symptoms and insomnia.

Progressive brain structural changes after the first year of treatment in first-episode treatment-naive patients with deficit or nondeficit schizophrenia

Progressive brain volume atrophy has been reported in patients with schizophrenia. However, whether this progress differs between patients with primary negative symptoms (deficit schizophrenia; DS) and those without such symptoms (nondeficit schizophrenia; NDS) is unknown. Here, we examined grey matter volume (GMV) and white matter volume (WMV) changes over 12 months in 34 first-episode treatment-naive patients with schizophrenia (14 DS and 20 NDS) and 32 healthy controls (HCs) using structural magnetic resonance imaging and voxel-based morphometry. At baseline, compared to HCs, patients with DS but not NDS had less WMV in bilateral posterior limb of the internal capsule (PLIC) and cerebellar tonsil (P < 0.05, FDR corrected) and smaller GMV in the cerebellar culmen (P < 0.05, FWE corrected). At follow-up, NDS group showed WMV reduction in bilateral PLIC (P < 0.05, FDR corrected), while DS group showed no progressive WMV changes. While both patient groups exhibited GMV reduction in the hippocampus and insular cortex, patients with NDS showed additional GMV loss in the frontal and cingulate cortex and a selective increase in GMV in the left thalamus (P < 0.05 FWE corrected). Our study revealed double dissociations in developmental brain volume changes in the first year after clinical contact for psychosis in DS versus NDS patients.

Rare damaging variants in DNA repair and cell cycle pathways are associated with hippocampal and cognitive dysfunction: a combined genetic imaging study in first-episode treatment-naive patients with schizophrenia

Schizophrenia is a complex neurodevelopmental disorder where changes in both hippocampus and memory-related cognitive functions are central. However, the exact relationship between neurodevelopmental-genetic factors and hippocampal-cognitive dysfunction remains unclear. The general aim of our study is to link the occurrence of rare damaging mutations involved in susceptibility gene pathways to the structure and function of hippocampus in order to define genetically and phenotypically based subgroups in schizophrenia. In the present study, by analyzing the exome sequencing and magnetic resonance imaging data in 94 first-episode treatment-naive schizophrenia patients and 134 normal controls, we identified that a cluster of rare damaging variants (RDVs) enriched in DNA repair and cell cycle pathways was present only in a subgroup including 39 schizophrenic patients. Furthermore, we found that schizophrenic patients with this RDVs show increased resting-state functional connectivity (rsFC) between left hippocampus (especially for left dentate gyrus) and left inferior parietal cortex, as well as decreased rsFC between left hippocampus and cerebellum. Moreover, abnormal rsFC was related to the deficits of spatial working memory (SWM; that is known to recruit the hippocampus) in patients with the RDVs. Taken together, our data demonstrate for the first time, to our knowledge, that damaging rare variants of genes in DNA repair and cell cycle pathways are associated with aberrant hippocampal rsFC, which was further relative to cognitive deficits in first-episode treatment-naive schizophrenia. Therefore, our data provide some evidence for the occurrence of phenotypic alterations in hippocampal and SWM function in a genetically defined subgroup of schizophrenia.

Regional homogeneity associated with overgeneral autobiographical memory of first-episode treatment-naive patients with major depressive disorder in the orbitofrontal cortex: A resting-state fMRI study

BackgroundOvergeneral autobiographical memory (OGM) is involved in the onset and maintenance of depression. Recent studies have shown correlations between OGM and alterations of some brain regions by using task-state functional magnetic resonance imaging (fMRI). However, the correlation between OGM and spontaneous brain activity in depression remains unclear. The purpose of this study was to determine whether patients with major depressive disorder (MDD) show abnormal regional homogeneity (ReHo) and, if so, whether the brain areas with abnormal ReHo are associated with OGM. MethodsTwenty five patients with MDD and 25 age-matched, sex-matched, and education-matched healthy controls underwent resting-state fMRI. All participants were also assessed by 17-item Hamilton Depression Rating Scale and autobiographical memory test. The ReHo method was used to analyze regional synchronization of spontaneous neuronal activity. ResultsPatients with MDD, compared to healthy controls, exhibited extensive ReHo abnormalities in some brain regions, including the frontal, temporal, and occipital cortex. Moreover, ReHo value of the orbitofrontal cortex was negatively correlated with OGM scores in patients with MDD. LimitationsThe sample size of this study was relatively small, and the influence of physiological noise was not completely excluded. ConclusionsThese results suggest that abnormal ReHo of spontaneous brain activity in the orbitofrontal cortex may be involved in the pathophysiology of OGM in patients with MDD.

Clozapine Clinic: The Need of the Hour

Back to table of contents Previous article Next article CommentaryNo AccessClozapine Clinic: The Need of the HourAndrew Hughes, M.D., Balwinder Singh, M.D., M.S.Andrew HughesSearch for more papers by this author, M.D., Balwinder SinghSearch for more papers by this author, M.D., M.S.Published Online:19 Apr 2017https://doi.org/10.1176/appi.ajp-rj.2016.110702AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Despite advances, psychiatrists continue to struggle with the safe and effective treatment of schizophrenia. Clozapine is a second-generation antipsychotic with a unique D2 dissociation constant, high affinity for D1- and D4-dopaminergic receptors, and potent antagonism of serotonergic and alpha-adrenergic receptors. Unfortunately, many physicians are reluctant to prescribe clozapine due to potentially fatal side effects such as agranulocytosis, myocarditis, cardiomyopathy, paralytic ileus, and aspiration pneumonia (1). We would like to call for an increase in clozapine clinics as a possible solution to this problem.While various guidelines suggest second-generation antipsychotics as the initial pharmaceutical treatment for a first psychotic break, there is no consensus on which antipsychotic is best. Despite consistent evidence of superior efficacy, improved outcomes, and improved morbidity, clozapine is “strikingly underutilized” (2). Studies of physicians’ prescribing practices reveal that only small portions of patients with treatment-resistant schizophrenia are treated with clozapine (3). Since the introduction of newer second-generation antipsychotics, clozapine use has decreased in the United States, from 11% of the total second-generation antipsychotics prescribed in 1999 to less than 5% in 2002 (3).Clozapine’s low prescription rate is likely related to its side-effect profile, as previous investigations have reported prescriber fear as a major factor for noninitiation (4). As a result, many clinicians decide to avoid clozapine altogether. Those who prescribe it may be unacquainted with its usage, resulting in treatment errors such as underdosing, unneeded discontinuation, and poor or inadequate side-effect intervention (1).To further complicate the prescription of clozapine, patients with schizophrenia often have an inherent tendency toward poor adherence. Interestingly, a randomized controlled trial (RCT) conducted in first-episode treatment-naive patients with schizophrenia have suggested that clozapine may have superior efficacy in the initial year of treatment, mostly due to greater adherence (5). In another RCT, patients receiving clozapine were also found to remit significantly faster and remain in remission longer than those taking a first-generation antipsychotic (chlorpromazine) (6).We believe the above barriers to prescription and adherence could be addressed with clozapine clinics. In such clinics, trained staff members have the resources, knowledge, and experience required to provide safer, more closely monitored treatment. Furthermore, clozapine clinics allow for time specifically dedicated to contacting patients and encouraging consistent follow-up. Finally, clozapine clinics can deliver focused supplementary training for psychiatric residents and other medical professionals. These professionals can gain confidence and experience with clozapine prescription in a controlled environment before continuing on to individual practices. Massachusetts General Hospital recently tested this idea and found that a 6-week direct patient contact clinic (along with accompanying curriculum-based instruction) effectively increased knowledge in participating residents (7).Clozapine clinics can improve multiple facets of schizophrenia treatment. They can expand clozapine’s accessibility, enhance clinician familiarity and competency, and provide better residency training for more effective use among desired communities. These benefits can be used to improve individual patient’s quality of life while playing an important role in the successful treatment of schizophrenia.Dr. Hughes is a first-year resident in the Department of Psychiatry, Oregon Health and Science University, Portland, Ore., and Dr. Singh is a fourth-year resident in the Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, Fargo, N.D.For further details on the use of clozapine, see the articles by Gören et al. in Psychiatric Services.

The CHRM3 gene is implicated in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia.

The genetic influences in human brain structure and function and impaired functional connectivities are the hallmarks of the schizophrenic brain. To explore how common genetic variants affect the connectivities in schizophrenia, we applied genome-wide association studies assaying the abnormal neural connectivities in schizophrenia as quantitative traits. We recruited 161 first-onset and treatment-naive patients with schizophrenia and 150 healthy controls. All the participants underwent scanning with a 3 T-magnetic resonance imaging scanner to acquire structural and functional imaging data and genotyping using the HumanOmniZhongHua-8 BeadChip. The brain-wide association study approach was employed to account for the inherent modular nature of brain connectivities. We found differences in four abnormal functional connectivities [left rectus to left thalamus (REC.L-THA.L), left rectus to right thalamus (REC.L-THA.R), left superior orbital cortex to left thalamus (ORBsup.L-THA.L) and left superior orbital cortex to right thalamus (ORBsup.L-THA.R)] between the two groups. Univariate single nucleotide polymorphism (SNP)-based association revealed that the SNP rs6800381, located nearest to the CHRM3 (cholinergic receptor, muscarinic 3) gene, reached genomic significance (p = 1.768 × 10-8) using REC.L-THA.R as the phenotype. Multivariate gene-based association revealed that the FAM12A (family with sequence similarity 12, member A) gene nearly reached genomic significance (nominal p = 2.22 × 10-6, corrected p = 0.05). Overall, we identified the first evidence that the CHRM3 gene plays a role in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia. Identification of these genetic variants using neuroimaging genetics provides insights into the causes of variability in human brain development, and may help us determine the mechanisms of dysfunction in schizophrenia.

Sex-Specific Patterns of Aberrant Brain Function in First-Episode Treatment-Naive Patients with Schizophrenia.

Male and female patients with schizophrenia show significant differences in a number of important clinical features, yet the neural substrates of these differences are still poorly understood. Here we explored the sex differences in the brain functional aberrations in 124 treatment-naïve patients with first-episode schizophrenia (61 males), compared with 102 age-matched healthy controls (50 males). Maps of degree centrality (DC) and amplitude of low-frequency fluctuations (ALFF) were constructed using resting-state functional magnetic resonance imaging data and compared between groups. We found that: (1) Selective DC reduction was observed in the right putamen (Put_R) in male patients and the left middle frontal gyrus (MFG) in female patients; (2) Functional connectivity analysis (using Put_R and MFG as seeds) found that male and female patients have disturbed functional integration in two separate networks, i.e., the sensorimotor network and the default mode network; (3) Significant ALFF alterations were also observed in these two networks in both genders; (4) Sex specific brain functional alterations were associated with various symptoms in patients. These results suggested that sex-specific patterns of functional aberration existed in schizophrenia, and these patterns were associated with the clinical features both in male and female patients.

Lack of association of COMT Val158Met polymorphism with attention and executive function in patients with schizophrenia

To explore the association of a functional polymorphism Val158Met of COMT gene and attention and executive function in first-episode treatment-naive patients with schizophrenia and healthy controls. Trail making test (TMT) and clinical performances were evaluated in 103 first-episode treatment-naive patients with schizophrenia and 99 healthy controls. Polymorphism of COMT Val158Met was analyzed using polymerase chain reaction-restriction fragment length polymorphism method. A general linear model was used to investigate the effect of genotype subgroups on the attention and executive function. There was a significant difference between control subjects and patients with schizophrenia on the TMT-A and B. However, no significant difference among Val/Val, Val/Met and Met/Met on the TMT-A and B in control subjects and patients with schizophrenia was detected. The association among COMT Met variant and trail making testing (attention and executive function) has been replicated. However, no association of COMT Met variant with disruption of dopaminergic influence on neurocognitive function was detected. This may be due to the heterogeneity of population.

Poster #S82 FAILURES IN THE FACIAL EMOTION RECOGNITION IN PATIENTS WITH SCHIZOPHRENIA, SIBLINGS, AND CONTROL SUBJECTS

(mean change -8.2, sd 10.3, z=−1.66, p=0.09), and marginal increase (mean change -0.4, sd 9.52, z=0.27, p=0.78) in this subscale in the risperidone group. We found an inverse, significant association between Subjective secondary effects, as measured with the UKU scale, and negative (Spearman’s rho=−0.65, p=0.02) symptoms improvement in at 12 months. Discussion: Our data, although preliminary, suggest that clozapine may have a slightly superior efficacy in the initial year of treatment of firstepisode treatment-naive patients with schizophrenia. The worsening of negative symptoms in the risperidone group seems attributable to secondary effects of the drug. Taken together with the larger attrition in this group, a better tolerability is suggested for clozapine. The larger improvements in Total and Negative symptom scores with clozapine may point to a superior efficacy in the earlier stages of illness, to be confirmed upon inclusion of a larger number of cases and follow-up completion.

Extensive brain structural network abnormality in first-episode treatment-naive patients with schizophrenia: morphometrical and covariation study

Alterations in gray matter (GM) are commonly observed in schizophrenia. Accumulating studies suggest that the brain changes associated with schizophrenia are distributed rather than focal, involving interconnected networks of areas as opposed to single regions. In the current study we aimed to explore GM volume (GMV) changes in a relatively large sample of treatment-naive first-episode schizophrenia (FES) patients using optimized voxel-based morphometry (VBM) and covariation analysis. High-resolution T1-weighted images were obtained using 3.0-T magnetic resonance imaging (MRI) from 86 first-episode drug-naive patients with schizophrenia and 86 age- and gender-matched healthy volunteers. Symptom severity was evaluated using the Positive and Negative Syndrome Scale (PANSS). GMV was assessed using optimized VBM and in 16 regions of interest (ROIs), selected on the basis of a previous meta-analysis. The relationships between GMVs in the ROIs were examined using an analysis of covariance (ANCOVA). The VBM analysis revealed that first-episode patients showed reduced GMV in the hippocampus bilaterally. The ROI analysis identified reductions in GMV in the left inferior frontal gyrus, bilateral hippocampus and right thalamus. The ANCOVA revealed different patterns of regional GMV correlations in patients and controls, including of inter- and intra-insula, inter-amygdala and insula-postcentral gyrus connections. Schizophrenia involves regional reductions in GMV and changes in GMV covariance in the insula, amygdala and postcentral gyrus. These findings were evident at the onset of the disorder, before treatment, and therefore cannot be attributable to the effects of chronic illness progression or medication.

EPA-0090 – Cognitive and mri brain morphometric correlates with comt gene val158met polymorphism in first-episode treatment-naïve patients with schizophrenia

Objective Catechol-O-methyltransferase (COMT) play an important role in modulating cortical dopaminergic catabolism and has been associated with schizophrenia. However, it remains unclear that if the variations in dopamine signaling affect the gray matter (GM) structural maturation in typically developing individuals, and whether such effect are disrupted in schizophrenia patients. This study aims (1) to explore the relationship between the functional polymorphisms Val158Met of COMT gene and GM volume in first-episode treatment-naive patients with schizophrenia and healthy controls, (2) to investigate the influence of COMT Val158Met on TMT performance, (3) to investigate the relationship among GM volume, cognitive deficit and psychiatric symptoms. Method Whole GM volume which was computed by an automated SPM and clinical performances were evaluated in 150 first-episode treatmentnaive patients with schizophrenia and 100 healthy controls. In addition, 2-sample t-tests was used to explore the main effect of diagnostic group, a full factorial model was used to obtain genotype-by-diagnostic interaction in the volume of GM according to genotypes of above the polymorphism, and multiple regression was used to explore the correlation whole GM volume with TMT measurements and clinical syndromes, with age and sex as covariance. Results A significant GM volume reduced in the right precentral gyrus [MNI: 37 -16 70], right cerebellum anterior lobe [MNI: 6 -56 26] and left Postcentral gyrus [MNI: -8 -36 80] (P Conclusion These findings suggest that COMT Metvariant was associated with disruption of dopaminergic in?eunces on GM maturation and may be the pathogenesis of schizophrenia, and maybe that the abnormal GM structure were association with cognitive function and clinical syndromes.

2675 – Pattern recognition memory in first-episode treat-naive deficit and nondeficit schizophrenia patients

Objective To investigate the difference of visual pattern memory among first-episode treatment-naive patients with deficit and nondeficit schizophrenia. Methods 199 first-episode treatment-naive patients with schizophrenia, and 148 controls were recruited. Schedule for the Deficit Syndrome (SDS) was used to categorize the patients into deficit or nondeficit subtype. Pattern Recognition Memory (PRM) was used to test the immediate and delayed mode of visual pattern memory. Positive and Negative Symptom Scale PANSS was used to assess the degree of patients symptoms. Results The PRM immediate mode and delayed mode percent correct was significant lower and time latency was significant longer in two subtypes of patients. There were no significant difference in the performance of immediate mode of PRM between deficit and nondeficit patients[(86.49 ± 15.34) vs . (87.28 ± 16.00), P =0.960]. But the impairment was more severe in patients with deficit schizophrenia [percent correct (63.10 ± 19.17) vs . (70.69 ± 15.34), P vs . 3527.40 ± 3649.08 P =0.024] in the delayed mode. And PRM has no significant correlation with the negative symptoms of deficit schizophrenia. Conclusion There were significant difference in the performance of immediate and delayed mode of PRM between patients and controls. The difference between first-episode treatment-naive deficit schizophrenia and nondeficit schizophrenia was only in delayed mode of PRM, and has no correlation with the primary negative symptoms. The deficit schizophrenia is a subtype of schizophrenia with unique impairment of cognitive functions.

Aberrant intrinsic brain activity and cognitive deficit in first-episode treatment-naive patients with schizophrenia

Given the important role of the default mode network (DMN) in cognitive function and the well-known neurocognitive deficit in schizophrenia, it is intriguing to examine systematically the relationship between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia. Method First-episode, treatment-naive patients with schizophrenia (FES) (n = 115) and healthy controls (n = 113) underwent resting-state functional magnetic resonance imaging (fMRI) scans and neurocognitive tests. Intrinsic neural activities evaluated by using the fragment amplitude of low-frequency fluctuations (fALFF) and the resting-state functional connectivity assessed by seed-based correlational analysis were compared between patients and controls. Aberrant intrinsic activities and DMN connectivity in patients were then correlated to neurocognitive performance and clinical symptoms. Compared to controls, patients with FES showed decreased fALFF in the bilateral medial prefrontal cortex (MPFC) and the orbitofrontal cortex (OFC), and increased fALFF in the bilateral putamen. Increased functional connectivity with the DMN was observed in the left insula and bilateral dorsolateral PFC (DLPFC) in patients with FES. In patients, aberrant fALFF in the bilateral OFC were correlated with cognitive processing speed; fALFF in the left OFC and right putamen were correlated with the clinical factors excited/activation and disorganization; and increased DMN functional connectivity in the left insula was correlated with the clinical factors positive, excited/activation, disorganization and neurocognitive deficit in the domain of sustained attention. These associations between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia may provide important insights into the neural mechanism of the disease.

Blunted serotonergic responsivity in neuroleptic-naïve patients at first-episode of schizophrenia

Objective To determine whether serotonergic responsivity, as assessed in platelets, is blunted in treatment-naïve patients with first episode psychosis, similar to observations in chronic schizophrenia. Methods Serotonin (5-HT)-amplified platelet aggregation was determined in 26 first-episode treatment-naive patients with psychosis (14 with schizophrenia, 12 with mood disorders with psychosis) and 16 matched healthy comparison subjects. Platelet aggregation was measured in fresh whole blood after stimulation with 5.0 μM adenosine diphosphate (ADP) alone and with the addition of 0.2 μg and 1.0 μg 5-HT. Results Healthy subjects showed expected robust increases in platelet aggregation (+ 106% and + 146% at 0.2 μg and 1.0 μg 5-HT, respectively). By contrast, patients with schizophrenia showed almost no changes in aggregation (+ 6% and + 3%), while patients with mood disorders showed intermediate increases (+ 59% and + 66%). Conclusions Blunted platelet serotonergic responsivity appears to be independent of treatment effects. To determine whether this is trait-related factor will require prospective studies.

Eye tracking abnormalities in schizophrenia: evidence for dysfunction in the frontal eye fields

Background: Eye tracking deficits are robust abnormalities in schizophrenia, but the neurobiological disturbance underlying these deficits is not known. Methods: To clarify the pathophysiology of eye tracking disturbances in schizophrenia, we tested 12 first-episode treatment-naive schizophrenic patients and 10 matched healthy individuals on foveofugal and foveopetal step-ramp pursuit tasks. Results: On foveopetal tasks, the initiation of pursuit eye movements was delayed in schizophrenic patients, and their steady-state pursuit gain was reduced particularly at slower target speeds (8 and 16 deg/sec). In foveofugal step-ramp tasks, their primary catch-up saccades were normal in latency and accuracy, but their postsaccadic pursuit in the first 100 msec after the primary catch-up saccade was significantly reduced even relative to their slow steady-state pursuit, especially during and immediately after an acute episode of illness. Conclusions: These observations indicate that motion-sensitive areas in posterior temporal cortex provide sufficiently intact information about moving targets to guide accurate catch-up saccades, but that the sensory processing of motion information is not being used effectively for pursuit eye movements. Low-gain pursuit after the early stage of pursuit initiation suggests that the use of extraretinal signals about target motion (e.g., anticipatory prediction) only partially compensates for this deficit. The pattern of low-gain pursuit, impaired pursuit initiation, and intact processing of motion information for catch-up saccades but not pursuit eye movements, was consistent in the schizophrenic patients tested at five time points over a 2-year follow-up period, and implicates the frontal eye fields or their efferent or afferent pathways in the pathophysiology of eye tracking abnormalities in schizophrenia.