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BackgroundThe thickness of the cortical mantle is a sensitive measure for identifying alterations in cortical structure. We aimed to explore whether first episode schizophrenia patients already show a significant cortical thinning and whether cortical thickness anomalies may significantly influence clinical and cognitive features.MethodWe investigated regional changes in cortical thickness in a large and heterogeneous sample of schizophrenia spectrum patients (n=142) at their first break of the illness and healthy controls (n=83). Magnetic resonance imaging brain scans (1.5 T) were obtained and images were analyzed by using brains2. The contribution of sociodemographic, cognitive and clinical characterictics was investigated.ResultsPatients showed a significant total cortical thinning (F=17.55, d=−0.62, p<0.001) and there was a diffuse pattern of reduced thickness (encompassing frontal, temporal and parietal cortices) (all p's<0.001, d's>0.53). No significant group×gender interactions were observed (all p's>0.15). There were no significant associations between the clinical and pre-morbid variables and cortical thickness measurements (all r's<0.12). A weak significant negative correlation between attention and total (r=−0.24, p=0.021) and parietal cortical thickness (r=−0.27, p=0.009) was found in patients (thicker cortex was associated with lower attention). Our data revealed a similar pattern of cortical thickness changes related to age in patients and controls.ConclusionsCortical thinning is independent of gender, age, age of onset and duration of the illness and does not seem to significantly influence clinical and functional symptomatology. These findings support a primary neurodevelopment disorder affecting the normal cerebral cortex development in schizophrenia. [ABSTRACT FROM PUBLISHER]

Evidence so far indicates the consistent association between brain structural abnormalities and schizophrenia already present at the early phases of the illness. This study investigates the specificity of brain structural abnormalities in schizophrenia by using region-of-interest method of volumetric analysis in a heterogeneous sample of schizophrenia spectrum patients at their first break of the illness. 225 subjects, comprising 82 schizophrenia patients, 36 schizophreniform disorder patients and 24 patients with non-schizophrenic non-affective psychoses, and 83 healthy individuals underwent a magnetic resonance imaging brain scan. Quantitative brain morphometric variables were assessed: cortical CSF, lateral ventricle, total brain tissue, white matter and cortical and subcortical gray matter volumes. The contribution of sociodemographic, cognitive and clinical characteristics was controlled. Compared with controls, schizophrenia (P=0.017) and schizophreniform disorder (P=0.023) patients showed an increase in cortical CSF volume. Schizophrenia patients had also markedly enlarged lateral ventricle volume compared to controls (P=0.026). The patients with non-schizophrenic non-affective psychoses did not significantly differ in lateral ventricle and cortical CSF volumes from controls. Compared with controls, schizophrenia and schizophreniform disorder patients demonstrated a significant decrease in total brain tissue (-1.30% and -1.12% respectively). Thalamic volume was reduced (-3.84%) in schizophrenia patients compared to controls (P=0.040). Clinical and cognitive variables were not significantly related with morphological changes. The brain changes found in patients with a first episode of schizophrenia spectrum disorders are robustly associated with the diagnoses of schizophrenia and schizophreniform disorder and are independent of relevant intervening variables. [ABSTRACT FROM AUTHOR]

The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=−0.46), amygdala (d=−0.31), thalamus (d=−0.31), accumbens (d=−0.25) and intracranial volumes (d=−0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.

The post-central gyrus (PoCG) has received little attention in brain imaging literature. However, some magnetic resonance imaging (MRI) studies have detected the presence of PoCG abnormalities in patients with schizophrenia. Fifty-six first-episode schizophrenia patients, selected through the program of first-episode psychosis (PAFIP) and carefully assessed for dimensional psychopathology and cognitive functioning, and 56 matched healthy controls were scanned twice over 1-year follow-up. PoCG gray matter volumes were measured at both time-points and compared between the groups. Differences in volume change over time and the relationship between PoCG volume and clinical and cognitive variables were also investigated. The right PoCG volume was significantly smaller in patients than in controls at the 1-year follow-up; furthermore, it was significantly smaller in male patients compared with male controls, with no differences in female. Although there was no significant time by group interaction in the overall sample, a trend-level interaction was found for the right PoCG in males. This is the first study, as per our knowledge, to focus on PoCG in first-episode schizophrenia patients. The presence of PoCG abnormalities in the first year of schizophrenia suggests a possible contribution to the pathophysiology of the illness, probably as part of a more extensive network of abnormalities., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: DISC1 gene is one of the main candidate genes for schizophrenia since it has been associated to the illness in several populations. Moreover, variations in several DISC1 polymorphisms, and in particular Ser704Cys SNP, have been associated in schizophrenic patients to structural and functional modifications in two brain areas (pre-frontal cortex and hippocampus) that play a central role in the genesis of psychotic symptoms. This study tested the association between Ser704Cys DISC1 polymorphism and the clinical onset of psychosis., Methods: Two hundred and thirteen Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped for rs821616 (Ser704Cys) SNP of the DISC1 gene. The clinical severity of the illness was assessed using SAPS and SANS scales. Other clinical and socio-demographic variables were recorded to rule out possible confounding effects., Results: Patients homozygous for the Ser allele of the Ser704Cys DISC1 SNP had significantly (p<0.05) higher rates at the positive symptoms dimension (SAPS-SANS scales) and hallucinations item, compared to Cys carriers., Conclusion: DISC1 gene variations may modulate the clinical severity of the psychosis at the onset of the disorder.

Objective: The purpose of this study was to verify whether male patients with psychosis have greater neurocognitive impairment than female patients at illness onset., Method: Participants with a first episode of psychosis (74 women/86 men) and healthy controls (62 women/97 men) were assessed with an extensive neuropsychological test battery., Results: Women in the clinical group were older at illness onset and had achieved higher formal education than men. This trend was the same for the control group. The patient group presented with lower premorbid IQ compared to healthy controls, and performed below for most neuropsychological tests. Women scored higher than men on a test of verbal memory, whereas men scored higher than women on a test of reaction time, visual memory, and a planning task. There were no group-by-sex interactions for any of the neuropsychological tests., Conclusion: The present study shows that at the onset of psychosis there are no differences between males and females in neuropsychological performance. The differential pattern of cognitive performance observed is similar to that in healthy males and females. Furthermore, females with a late onset of psychosis may represent a subgroup with specific visuospatial and problem solving impairments., (© 2013.)

Background: The course of cognitive function in first-episode psychosis (FEP) patients suggests that some individuals are normal or near normal whereas some cases present a marked decline. The goal of the present longitudinal study was to identify neuroanatomical differences between deficit and non-deficit patients., Methods: Fifty nine FEP patients with neuroimage and neurocognitive information were studied at baseline and 3 year after illness onset. A global cognitive function score was used to classify deficit and non-deficit patients at baseline. Analysis of covariances and repeated-measures analysis were performed to evaluate differences in brain volumes. Age, premorbid IQ, and intracranial volume were used as covariates. We examined only volumes of whole brain, whole brain gray and white matter, cortical CSF and lateral ventricles, lobular volumes of gray and white matter, and subcortical (caudate nucleus and thalamus) regions., Results: At illness onset 50.8% of patients presented global cognitive deficit. There were no significant differences between neuropsychological subgroups in any of the brain regions studied at baseline [all F(1, 54) ≤ 3.42; all p ≥ 0.07] and follow-up [all F(1, 54) ≤ 3.43; all p ≥ 0.07] time points. There was a significant time by group interaction for the parietal tissue volume [F(1, 54) = 4.97, p = 0.030] and the total gray matter volume [F(1, 54) = 4.31, p = 0.042], with the deficit group showing a greater volume decrease., Conclusion: Our results did not confirm the presence of significant morphometric differences in the brain regions evaluated between cognitively impaired and cognitively preserved schizophrenia patients at the early stages of the illness. However, there were significant time by group interactions for the parietal tissue volume and the total gray matter volume during the 3-year follow-up period, which might indicate that cognitive deficit in schizophrenia would be associated with progressive brain volume loss.

Introduction: Functional gene polymorphisms modulating neuroplasticity might mediate brain longitudinal structural changes in schizophrenia. The present study aimed to explore possible effects of BDNF Val66Met polymorphism variations on progressive structural brain changes after 3 years from the first episode of psychosis., Method: Patients were part of a large epidemiological and longitudinal intervention program of first-episode psychosis, carried out at the University Hospital Marqués de Valdecilla, Cantabria, Spain. Eighty first-episode patients and 54 healthy controls were included in the final analyses. Brain magnetic resonance imaging (baseline and 3-year follow-up) and BDNF genotype, and clinical and functional outcome were investigated., Results: We did not detect significant association between brain changes and BDNF Val66Met polymorphism variations in patients and controls (all p>0.060). At baseline, there were no significant associations between brain anomalies and BDNF genotype. Functional deficits were similar in Met-carrier and Val homozygote patients after 3-year follow-up (X(2) = 0.66; p = 0.564); there was no relationship between significant volume change across time and functional outcome. Otherwise, Met-carrier controls had significant high rates of alcohol-consumption (p = 0.019) compared to Val homozygote controls., Conclusion: Our findings do not support the notion that BDNF genotype variations may mediate brain macroscopic morphological changes across time., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate., Methods: A prospective, randomized, open-label study was carried out to compare the long-term neurocognitive effectiveness of haloperidol, olanzapine, and risperidone in the first episode of schizophrenia spectrum disorders. A final sample of 79 patients randomized to haloperidol (N = 28), olanzapine (N = 23), or risperidone (N = 28) who completed clinical and cognitive evaluations at baseline and 3-year follow-up was included in the final analysis. Forty-one healthy individuals were also included in the final analysis. The main outcome measure was cognitive changes at 3-year follow-up. Due to the fact that some of the patients had switched their initially prescribed antipsychotic medication during the course of the study (6 out of 28 in haloperidol group, 18 out of 23 in olanzapine group, and 24 out of 28 in risperidone group continued with the initial study drug at 3-year assessment), we have also conducted a per protocol analysis., Results: Overall, cognitive changes were similar in the three treatment groups and controls, although a greater improvement in Rey Auditory Verbal Learning Test, Digit Symbol, and Iowa Gambling Test was found in the treatment groups. The better performance observed on Rey Auditory Verbal Learning Test and Digit Symbol in olanzapine treatment group was likely explained by the lower prevalence of use of antimuscarinic drugs. These results were essentially similar to those found in the intention-to-treat analysis., Conclusions: The major conclusion of this study is that haloperidol, olanzapine, and risperidone have not demonstrated substantial neurocognitive effectiveness, improving cognitive deficits present in the early phases of the illness. The study also underscores the importance of exploring new drugs for the treatment of cognitive impairments and associated functional disabilities in schizophrenia.

Background: Imaging evidence indicates that brain alterations are primary to the full-blown onset of schizophrenia and seem to progress across time. The potential effects of antipsychotic medication on brain structure represent a key factor in understanding brain changes in psychosis. We aimed to investigate the effects of low doses of haloperidol, risperidone and olanzapine on cortical thickness., Method: We investigated the effects of risperidone (N=16), olanzapine (N=18) and low doses of haloperidol (N=18) in cortical thickness changes during 1-year follow-up period in a large and heterogeneous sample of schizophrenia spectrum patients. The relationship between cortical thickness changes and clinical and cognitive outcome was also assessed. A group of 45 healthy volunteers was also longitudinally evaluated. Magnetic resonance imaging brain scans (1.5T) were obtained and images were analyzed by using BRAINS2., Results: There were no significant effects of time (F(1,47)<1.66; P>0.204), treatment group (F(2,47)<1.47; P>0.242) or group-by-time interaction (F(2,47)<1.82; P>0.174) for any of the cortical thickness variables. When the group of healthy controls was included in the analyses, it is of note that group-by-time interaction showed a significant result for the frontal lobe at trend level (F(3,81)=2.686; P=0.052). After the Bonferroni adjustment for multiple comparisons, there were no significant associations between changes in cortical thickness and clinical and cognitive outcome., Conclusions: Low doses of haloperidol, risperidone, and olanzapine seem to equally affect gray matter cortical thickness, overall and lobes, at the medium-term (1 year). The clinical effectiveness of treatments was not significantly related to changes in cortical thickness., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The aim of this study was to use a region-of-interest approach with magnetic resonance imaging to examine the volume of the straight gyrus volume change in first-episode schizophrenia-spectrum patients compared with healthy subjects over a 1-year follow-up period. We did not find a differential pattern of volumetric change between the two groups., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Previous investigations have revealed sex-specific differences in brain morphometry. The effect of sex on cortical thickness may be influencing cognitive differences between sexes. With this exploratory study, we aimed to investigate the effect of sex in MRI-based cerebral cortex morphometry in healthy young volunteers and how the variability in cortical measures might affect cognitive functioning in men and women. 76 young healthy volunteers (45 men and 31 women) underwent a 1.5 T MR scan and 53 of them completed a comprehensive cognitive battery. Overall no gross significant differences between sexes were found in cortical thickness, surface area and curvature indexes. However, there was a significant group by hemisphere interaction in the total cortical thickness (F(1,72)=5.02; p=0.03). A greater leftward asymmetry was observed in cortical thickness in males. Only females show significant associations between cortical thickness and cognitive functioning (IQ and executive functioning). In conclusion, our findings do not support the notion of sexual dimorphism in cortical mantle morphology. The results also suggest that variability in cortical thickness may affect cognitive functioning in females but not in males., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Previous studies on the straight gyrus have shown inconsistent results in first-episode schizophrenia. In the present study, straight gyrus morphometry in first-episode schizophrenia-spectrum patients was investigated by using a region-of-interest methodology. 141 schizophrenia-spectrum patients and 81 healthy subjects were studied. Magnetic resonance imaging brain scans (1.5 T) were obtained and images were analyzed by using BRAINS2. The main resulting measurements were straight gyrus gray matter volume and cortical surface area. Patients with schizophrenia-spectrum disorders did not significantly differ from controls in the straight gyrus morphometric variables evaluated (p>0.115). There was neither significant group-by-side (p>0.199) or group-by-gender interaction (p>0.096). Clinical variables were not significantly related with straight gyrus morphology. Our results, based on a large and representative sample, do not confirm the presence of significant straight gyrus morphometric anomalies in schizophrenia-spectrum disorders, after controlling for potential confounding variables., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Studies of the temporal pole (TP) in schizophrenia patients are not consistent. The aim of this study was to investigate morphometric anomalies of the TP in first-episode schizophrenia patients. Patients did not significantly differ from controls in the TP morphometric variables evaluated. Clinical variables were not significantly related to the TP., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Overall and regional cortical thinning has been observed at the first break of schizophrenia. Due to the fact that structural abnormalities in the insular cortex have been described in schizophrenia, we investigated insular thickness anomalies in first episode schizophrenia. Participants comprised 118 schizophrenia patients and 83 healthy subjects. Magnetic resonance imaging brain scans (1.5T) were obtained, and images were analyzed by using BRAINS2. The contribution of sociodemographic, cognitive and clinical characterictics was controlled. Schizophrenia patients demonstrated a significant right insular thinning, and a significant group by gender interaction was found for left insular thickness. Post-hoc comparisons revealed that male schizophrenia patients had a significant left insular thinning compared with healthy male subjects. There were no significant associations between insular thickness, the severity of symptoms at baseline and cognitive measurements and premorbid variables. The fact that insular thinning is already present at early phases of the illness and is independent of intervening variables offers evidence for the potential of these changes to be a biological marker of the illness.

Evidence so far indicates that the consistent association between insular cortex abnormalities and schizophrenia is already present at early phases of the illness. In the present investigation we aimed to study the specificity of insular structural abnormalities in schizophrenia by using region-of-interest morphometry to assess insular cortex morphological characteristics in the same heterogeneous sample of schizophrenia-spectrum patients. The 225 subjects, comprising 82 schizophrenia patients, 36 schizophreniform disorder patients and 24 patients with nonschizophrenic non-affective psychoses, and 83 healthy individuals were investigated. Magnetic resonance imaging brain scans (1.5T) were obtained and images analysed to evaluate insular cortex morphometric variables. The main resulting measurements were for insular gray matter volume and cortical surface area. The contribution of sociodemographic and clinical characteristics was controlled. Patients with schizophrenia-spectrum disorders did not significantly differ from controls in the insular cortex morphometric variables evaluated (all P's>0.11). Clinical variables were not significantly related with insular morphological changes. Noteworthy is the fact that none of the group morphological measurements varied significantly by gender or hemisphere. Neither did we find significant differences when patients with schizophrenia and with other non-affective psychoses were compared. Contrary to our initial hypotheses, we were unable to demonstrate significant morphometric anomalies in a large and heterogeneous sample of patients with a first-episode of schizophrenia-spectrum disorders.

Background: The effect of antipsychotic drugs on brain morphology is under debate. Here we investigate the effects of risperidone, olanzapine and low doses of haloperidol on cortical and subcortical morphometry in first episode drug naïve patients with non-affective psychosis., Methods: Morphological variables were measured in three treatment groups (haloperidol=18; risperidone=16; olanzapine=18) and in healthy subjects (N=38) at baseline and after one year. The relationship between brain morphometric changes and changes in clinical scores was also assessed., Results: At one year, the three antipsychotics had had an equal effect on the gray matter cortical structure, overall and lobes (all p's>0.121.). A significant time-by-group interaction was found in lateral ventricle volume (F2,47=5.65; p=0.006). Post-hoc comparisons revealed a significant increase in lateral ventricles in patients treated with risperidone (p=0.009). Patients exposed to atypicals (olanzapine and risperidone) exhibited a decrease in caudate nucleus volume (p=0.001). In general, brain changes did not account in any significant manner for clinical changes over time in any treatment group., Conclusions: We conclude that low doses of haloperidol, risperidone and olanzapine seem to have an equal effect on the gray matter cortical structure after 1 year of treatment. In contrast to typical antipsychotics, atypicals have differential effects on lateral ventricle and caudate nucleus volumes.

Aim: The aim of the study was to analyse the treated incidence of schizophrenia in Cantabria (Northern Spain) and the sociodemographic risk factors associated with the illness onset., Methods: Data were obtained from patients included in the Cantabria's Clinical Programme on First-Episode Psychosis (schizophrenia spectrum DSM-IV diagnosis) from 2001 to 2005, from the Cantabria first-episode schizophrenia study (carried out between 1988 and 1989) and from the 2001 Spanish census., Results: Annual incidence was 1.38 per 10,000 inhabitants in the risk-ageperiod. Identified risk factors were male gender (relative risk (RR): 1.61), age 15-25 years (RR: 3.48), unemployment (RR: 2.82), single status (RR: 5.88), low educational level (RR: 4.38), urban environment (RR: 1.62) and cannabis consumption (odds ratio: 12.83). The incidence in females was significantly lower than the one obtained 15 years ago., Conclusions: The reported factors suggest that underlying biological and social factors modulate the risk of psychosis. This balance operates differently in males and females., (© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Asia Pty Ltd.)

Studies of schizophrenia that combine imaging and genetic approaches attempt to map structural brain anomalies associated with genetic risk variants. The aim of the present study was to investigate whether variations in the interleukin-1 receptor antagonist (IL-1RN) were associated with structural brain characteristics of 73 minimally medicated first-episode non-affective psychotic patients. We did not find evidence for association between genetic variation in the IL-1RN gene and brain morphometry at early phases of the illness.

Background: Structural brain anomalies are present at early phases of psychosis. The objective was to examine the impact of Catechol-O-Methyltransferase (COMT) gene variations on brain morphology in first-episode non-affective psychosis. We hypothesized that the low activity-COMT (COMT(L)) allele would be associated with the presence of structural brain changes as assessed by quantitative magnetic resonance imaging (MRI)., Methods: Fifty-two males and 23 females underwent COMT genotyping and MRI. Patients were categorized into three genetic subgroups: COMT(H/H), COMT(L/H) and COMT(L/L). MRI data were analyzed using BRAINS2. Global and lobar volumes of grey matter (GM) and cerebrospinal fluid (CSF) were compared among the three groups after controlling for total intracranial volume and age of illness onset., Results: COMT(L) carriers showed a significant enlargement of the lateral ventricles (F = 7.13, p = 0.009), right lateral ventricle (F = 5.99, p = 0.017) and left lateral ventricle (F = 6.22, p = 0.015). No other significant differences in any of the brain structures were found among subgroups., Conclusions: Our findings suggest that genetic variations of COMT can contribute to the enlargement of the lateral ventricles described in early phases of non-affective psychosis.

Structural studies have inconsistently shown the presence of thalamic volume differences in patients with schizophrenia. However, only a few studies have examined the relation between thalamic structure and clinical and cognitive variables in early phases of the illness. Thalamic volumes in right-handed minimally treated first episode patients with non-affective psychosis (N=61) relative to those of right-handed healthy comparison subjects (N=40) were measured. Thalamic volumes in the right and left hemispheres and total thalamic volume were automatically segmented and analyzed using BRAINS2. Analysis of covariance was used to control for intracranial volume. Clinical symptoms were assessed by total scores of BPRS, SAPS and SANS. The relationship between three cognitive dimensions (verbal learning and memory, speed processing/executive functioning and sustained attention/vigilance), and thalamic volume was evaluated. The impact of the duration of untreated illness, untreated psychosis and prodrome period in thalamic morphometry was also explored. Right, left, and total thalamic volumes of the patients with non-affective psychosis were significantly smaller than those of the healthy subjects. Larger thalamic volumes were associated with an earlier age of onset, a poorer cognitive functioning and a more severe negative symptomatology. Thalamic volumetric differences between patients with non-affective psychosis and healthy controls are already present at early phases of the illness. However, further investigations are warranted to fully clarify the relationship between those structural anomalies and clinical and cognitive outcomes.

Objective: Striatal dysfunction has been traditionally implicated in the pathophysiology of schizophrenia. The purpose of this study is to examine the relationship between caudate nucleus volumes and clinical and cognitive features of schizophrenic patients in an early phase of their illness., Methods: Caudate nucleus volumes in previously untreated first episode patients with non-affective psychosis (N=76) and healthy comparison subjects (N=45) were measured. Caudate nucleus volume in the right and left hemispheres were automatically segmented and analyzed using BRAINS2. Analysis of covariance was used to control for intracranial volume. Severity of clinical symptoms was assessed using SAPS and SANS total scores. The relationship between cognitive dimensions, and caudate nucleus volume was evaluated. Finally, we examined the correlation between caudate volumes and the duration of untreated illness (DUI), duration of untreated psychosis (DUP) and duration of prodrome period (DPP)., Results: Right, left, and total caudate nucleus volumes did not differ significantly between patients and controls. Those patients with a longer DUP have smaller caudate nucleus. In addition, caudate nucleus volume was positively correlated with the severity of psychotic symptomatology. No significant associations were found between caudate nucleus volume and cognitive functioning., Conclusion: This group of first episode schizophrenia patients did not exhibit significant volumetric anomalies of the caudate nucleus. Despite this lack of volumetric abnormalities, a delay in receiving antipsychotic treatment and the severity of initial positive symptomatology were significantly associated with reduced caudate volume.