Antagonistic gene activities determine the formation of pattern elements along the mediolateral axis of the Arabidopsis fruit.

The Arabidopsis fruit mainly consists of a mature ovary that shows three well defined territories that are pattern elements along the mediolateral axis: the replum, located at the medial plane of the flower, and the valve and the valve margin, both of lateral nature. JAG/FIL activity, which includes the combined functions of JAGGED (JAG), FILAMENTOUS FLOWER (FIL), and YABBY3 (YAB3), contributes to the formation of the two lateral pattern elements, whereas the cooperating genes BREVIPEDICELLUS (BP) and REPLUMLESS (RPL) promote replum development. A recent model to explain pattern formation along the mediolateral axis hypothesizes that JAG/FIL activity and BP/RPL function as antagonistic lateral and medial factors, respectively, which tend to repress each other. In this work, we demonstrate the existence of mutual exclusion mechanisms between both kinds of factors, and how this determines the formation and size of the three territories. Medial factors autonomously constrain lateral factors so that they only express outside the replum, and lateral factors negatively regulate the medially expressed BP gene in a non-autonomous fashion to ensure correct replum development. We also have found that ASYMMETRIC LEAVES1 (AS1), previously shown to repress BP both in leaves and ovaries, collaborates with JAG/FIL activity, preventing its repression by BP and showing synergistic interactions with JAG/FIL activity genes. Therefore AS gene function (the function of the interacting genes AS1 and AS2) has been incorporated in the model as a new lateral factor. Our model of antagonistic factors provides explanation for mutant fruit phenotypes in Arabidopsis and also may help to understand natural variation of fruit shape in Brassicaceae and other species, since subtle changes in gene expression may cause conspicuous changes in the size of the different tissue types.

Decreased glutathione levels predict loss of brain volume in children and adolescents with first-episode psychosis in a two-year longitudinal study.

Progressive loss of cortical gray matter (GM), as measured by magnetic resonance imaging, has been described early in the course of first-episode psychosis. This study aims to assess the relationship between oxidative balance and progression of cortical GM changes in a multicenter sample of first-episode early-onset psychosis (EOP) patients from baseline to two-year follow-up. A total of 48 patients (13 females, mean age 15.9±1.5 years) and 56 age- and gender-matched healthy controls (19 females, 15.3±1.5 years) were assessed. Magnetic resonance imaging (MRI) scans performed both at the time of the first psychotic episode and 2 years later were used for volumetric measurements of left and right gray matter regions (frontal, parietal, and temporal lobes) and total sulcal cerebrospinal fluid (CSF). Total glutathione (GSH) blood levels were determined at baseline. In patients, after controlling for possible confounding variables, lower baseline GSH levels were significantly associated with greater volume decrease in left frontal (B=0.034, 95% confidence interval (CI): 0.011 to 0.056, r=0.620, p=0.006), parietal (B=0.039, 95% CI: 0.020 to 0.059, r=0.739, p=0.001), temporal (B=0.026, 95% CI: 0.016 to 0.036, r=0.779, p<0.001), and total (B=0.022, 95% CI: 0.014 to 0.031, r=0.803, p<0.001) gray matter, and with greater increase in total CSF (B=-0.560, 95% CI: -0.270 to -0.850, r=-0.722, p=0.001). Controls did not show significant associations between brain volume changes and GSH levels. GSH deficit during the first psychotic episode was related to greater loss of cortical GM two years later in patients with first-episode EOP, suggesting that oxidative damage may contribute to the progressive loss of cortical GM found in patients with first-episode psychosis.

Progressive brain changes in children and adolescents with first-episode psychosis.

CONTEXT: Progressive loss of brain gray matter (GM) has been reported in childhood-onset schizophrenia; however, it is uncertain whether these changes are shared by pediatric patients with different psychoses. OBJECTIVE: To examine the progression of brain changes in first-episode early-onset psychosis and their relationship to diagnosis and prognosis at 2-year follow-up. DESIGN: Prospective, multicenter, naturalistic, 2-year follow-up study. SETTING: Six child and adolescent psychiatric units in Spain. PARTICIPANTS: A total of 110 patients and 98 healthy controls were recruited between March 1, 2003, and November 31, 2005. Magnetic resonance imaging of the brain was performed for 61 patients with schizophrenia (n = 25), bipolar disorder (n = 16), or other psychoses (n = 20) and 70 controls (both at baseline and after 2 years of follow-up). Mean age at baseline was 15.5 years (patients) and 15.3 years (controls). MAIN OUTCOME MEASURES: The GM and cerebrospinal fluid (CSF) volumes in the total brain and frontal, parietal, and temporal lobes. RESULTS: Compared with controls, patients with schizophrenia showed greater GM volume loss in the frontal lobe during the 2-year follow-up (left: -3.3 vs -0.6 cm(3), P = .004; right: -3.7 vs -0.8 cm(3), P = .005) and left frontal CSF volume increase (left: 6.7 vs 2.4 cm(3), P = .006). In addition to frontal volume, changes for total GM (-37.1 vs -14.5 cm(3), P = .001) and left parietal GM (-4.3 vs -2.2 cm(3), P = .04) were significantly different in schizophrenic patients compared with controls. No significant differences emerged for patients with bipolar disease. Greater left frontal GM volume loss was related to more weeks of hospitalization, whereas severity of negative symptoms correlated with CSF increase in patients with schizophrenia. CONCLUSIONS: Patients with schizophrenia or other psychoses showed greater loss of GM volume and increase of CSF in the frontal lobe relative to controls. Progressive changes were more evident in patients with schizophrenia than those with bipolar disorder. These changes in specific brain volumes after onset of psychotic symptoms may be related to markers of poorer prognosis.

Regional specificity of thalamic volume deficits in male adolescents with early-onset psychosis.

BACKGROUND: Thalamic volume deficits are associated with psychosis but it is unclear whether the volume reduction is uniformly distributed or whether it is more severe in particular thalamic regions. AIMS: To quantify whole and regional thalamic volume in males with early-onset psychosis and healthy male controls. METHOD: Brain scans were obtained for 80 adolescents: 46 individuals with early-onset psychosis with a duration of positive symptoms less than 6 months and 34 healthy controls. All participants were younger than 19 years. Total thalamic volumes were assessed using FreeSurfer and FSL-FIRST, group comparisons of regional thalamic volumes were studied with a surface-based approach. RESULTS: Total thalamic volume was smaller in participants with early-onset psychosis relative to controls. Regional thalamic volume reduction was most significant in the right anterior mediodorsal area and pulvinar. CONCLUSIONS: In males with minimally treated early-onset psychosis, thalamic volume deficits may be most pronounced in the anterior mediodorsal and posterior pulvinar regions, adding strength to findings from post-mortem studies in adults with psychosis.

Mathematically gifted adolescents use more extensive and more bilateral areas of the fronto-parietal network than controls during executive functioning and fluid reasoning tasks.

The main goal of this study was to investigate the neural substrates of fluid reasoning and visuospatial working memory in adolescents with precocious mathematical ability. The study population comprised two groups of adolescents: 13 math-gifted adolescents and 14 controls with average mathematical skills. Patterns of activation specific to reasoning tasks in math-gifted subjects were examined using functional magnetic resonance images acquired while the subjects were performing Raven's Advanced Progressive Matrices (RAPM) and the Tower of London (TOL) tasks. During the tasks, both groups showed significant activations in the frontoparietal network. In the math-gifted group, clusters of activation were always bilateral and more regions were recruited, especially in the right hemisphere. In the TOL task, math-gifted adolescents showed significant hyper-activations relative to controls in the precuneus, superior occipital lobe (BA 19), and medial temporal lobe (BA 39). The maximum differences between the groups were detected during RAPM tasks at the highest level of difficulty, where math-gifted subjects showed significant activations relative to controls in the right inferior parietal lobule (BA 40), anterior cingulated gyrus (BA 32), and frontal (BA 9, and BA 6) areas. Our results support the hypothesis that greater ability for complex mathematical reasoning may be related to more bilateral patterns of activation and that increased activation in the parietal and frontal regions of math-gifted adolescents is associated with enhanced skills in visuospatial processing and logical reasoning.

Constitutive activation of B-Raf in the mouse germ line provides a model for human cardio-facio-cutaneous syndrome.

RASopathies are a class of developmental syndromes that result from congenital mutations in key elements of the RAS/RAF/MEK signaling pathway. A well-recognized RASopathy is the cardio-facio-cutaneous (CFC) syndrome characterized by a distinctive facial appearance, heart defects, and mental retardation. Clinically diagnosed CFC patients carry germ-line mutations in four different genes, B-RAF, MEK1, MEK2, and K-RAS. B-RAF is by far the most commonly mutated locus, displaying mutations that most often result in constitutive activation of the B-RAF kinase. Here, we describe a mouse model for CFC generated by germ-line expression of a B-RafLSLV600E allele. This targeted allele allows low levels of expression of B-RafV600E, a constitutively active B-Raf kinase first identified in human melanoma. B-Raf+/LSLV600E mice are viable and display several of the characteristic features observed in CFC patients, including reduced life span, small size, facial dysmorphism, cardiomegaly, and epileptic seizures. These mice also show up-regulation of specific catecholamines and cataracts, two features detected in a low percentage of CFC patients. In addition, B-Raf+/LSLV600E mice develop neuroendocrine tumors, a pathology not observed in CFC patients. These mice may provide a means of better understanding the pathophysiology of at least some of the clinical features present in CFC patients. Moreover, they may serve as a tool to evaluate the potential therapeutic efficacy of B-RAF inhibitors and establish the precise window at which they could be effective against this congenital syndrome.

Variations in the shape of the frontobasal brain region in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) emerges during childhood through young adulthood coinciding with the late phases of postnatal brain development when fine remodeling of brain anatomy takes place. Previous research has suggested the existence of subtle anatomical alterations in OCD involving focal volume variations in different brain regions including the frontal lobes and basal ganglia. We investigated whether anatomical changes might also involve variations in the shape of the frontobasal region. A total of 101 OCD patients and 101 control subjects were examined using magnetic resonance imaging. A cross-sectional image highly representative of frontal-basal ganglia anatomy was selected in each individual and 25 reliable anatomical landmarks were identified to assess shape changes. A pixel-wise morphing approach was also used to dynamically illustrate the findings. We found significant group differences for overall landmark position and for most individual landmarks delimiting the defined frontobasal region. OCD patients showed a deformation pattern involving shortening of the anterior-posterior dimension of the frontal lobes and basal ganglia, and enlargement of cerebrospinal fluid spaces around the frontal opercula. In addition, we observed significant correlation of brain tissue shape variation with frontal sinus size. Identification of a global change in the shape of the frontobasal region may further contribute to characterizing the nature of brain alterations in OCD. The coincidence of brain shape variations with morphological changes in the frontal sinus indicates a potential association of OCD to late development disturbances, as the frontal sinus macroscopically emerges during the transition between childhood and adulthood.

Trait and state attributes of insight in first episodes of early-onset schizophrenia and other psychoses: a 2-year longitudinal study.

BACKGROUND: Increasing evidence supports the important role of illness state and individual characteristics in insight. METHODS: Insight, as measured with the Scale to Assess Unawareness of Mental Disorder, over the first 2 years of early-onset first-episode psychosis and its correlations with clinical, socio-demographic, cognitive, and structural brain variables are studied. RESULTS: (1) insight at 2 years is poorer in schizophrenia spectrum disorders (SSDs) than in subjects with other psychoses; (2) the more severe the psychosis, the worse the insight. In SSD, depressive symptoms, poorer baseline executive functioning, lower IQ, longer duration of untreated psychosis (DUP), and poorer premorbid infancy adjustment are associated with poorer insight; frontal and parietal gray matter (GM) reductions at baseline correlate with worse insight into having psychotic symptoms at 2 years; (3) insight into having a mental disorder (Scale to Assess Unawareness of Mental Disorder [SUMD]1) at 1 year, DUP, and baseline IQ are the most consistent variables explaining different aspects of insight at 2 years in SSD patients. IQ and SUMD1 at 1 year, together with left frontal and parietal GM volumes, explain 80% of the variance of insight into having specific psychotic symptoms in SSD patients (adjusted R(2) = 0.795, F = 15.576, P < .001). CONCLUSION: Insight is a complex phenomenon that depends both on severity of psychopathology and also on disease and subject characteristics, such as past adjustment, IQ, DUP, cognitive functioning, frontal and parietal GM volumes, and age, gender, and ethnicity.

Multicenter study of brain volume abnormalities in children and adolescent-onset psychosis.

The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of "schizophrenia" or "other psychosis" showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents.

Brain morphology and neurological soft signs in adolescents with first-episode psychosis.

BACKGROUND: Adolescents with first-episode psychosis have increased severity of neurological soft signs when compared with controls, but it is unclear whether increased severity of neurological soft signs is an expression of specific structural brain deficits. AIMS: To examine whether increased severity of neurological soft signs was associated with decreased brain volumes in adolescents with first-episode psychosis. METHOD: Brain scans were obtained for 70 adolescents (less than 18 years of age) with first-episode psychosis (duration of positive symptoms less than 6 months). Volumes were assessed using voxel-based morphometry and through segmentation of anatomical structures. RESULTS: Increased severity of sensory integration neurological soft signs correlated with smaller right and left thalamus volume, whereas increased severity of sequencing of complex motor acts neurological soft signs correlated with smaller right caudate volume. CONCLUSIONS: Neurological soft signs may be an easy-to-assess marker of region-specific structural brain deficits in adolescents with first-episode psychosis.

Gyral and sulcal cortical thinning in adolescents with first episode early-onset psychosis.

BACKGROUND: Psychosis is associated with volumetric decreases of cortical structures. Whether these volumetric decreases imply abnormalities in cortical thickness, surface, or cortical folding is not clear. Due to differences in cytoarchitecture, cortical gyri and sulci might be differentially affected by psychosis. Therefore, we examined differences in gyral and sulcal cortical thickness, surface, folding, and volume between a minimally treated male adolescent population with early-onset first-episode psychosis (EOP) and a healthy control group, with surface-based morphometry. METHODS: Magnetic resonance imaging brain scans were obtained from 49 adolescent EOP patients and 34 healthy control subjects. Subjects were younger than 18 years (age range 12 years-18 years), and EOP patients had a duration of positive symptoms of <6 months. RESULTS: Early-onset first-episode psychosis was associated with local bilateral cortical thinning and volume deficits in both the gyri and sulci of the superior temporal cortex and the inferior, middle, medial, and superior prefrontal cortex. In the pars triangularis and opercularis cortex of patients, gyral cortical thickness was thinner, whereas sulcal thickness was not. Patients exhibited cortical thinning together with a decreased degree of cortical folding in the right superior frontal cortex. CONCLUSIONS: Cortical thinning of both gyri and sulci seem to underlie most cortical volume deficits in adolescent patients with EOP. Except for the right superior frontal region, the degree of cortical folding was normal in regions showing decreased cortical thickness, suggesting that the process of cortical thinning in adolescent patients with EOP primarily takes place after the formation of cortical folds.

Antagonistic interactions between Arabidopsis K-homology domain genes uncover PEPPER as a positive regulator of the central floral repressor FLOWERING LOCUS C.

Plant floral transition is a major developmental switch regulated by an integrated network of pathways. Arabidopsis FLOWERING LOCUS K (FLK), a protein with three KH RNA-binding domains, operates in the autonomous flowering-promotive pathway by decreasing the transcript levels of the key flowering repressor FLOWERING LOCUS C (FLC). Here we report that PEPPER (PEP), an FLK paralog previously shown to affect vegetative and pistil development, antagonizes FLK by positively regulating FLC. Lack of PEP function rescues the flk late-flowering phenotype with a concomitant decrease in FLC RNA levels. Loss of HUA2, another FLC activator encoding an RNA-binding protein, further rescues flk, being flk hua2 pep triple mutants virtually wild-type regarding flowering time. Consistently, PEP overexpression determines high levels of FLC transcripts and flowering delay. Genetic and molecular analyses indicate that FLK and PEP act independently of FCA, another important FLC repressor in the autonomous pathway. In addition, we present data suggesting that PEP may affect FLC expression at both transcriptional and post-transcriptional levels. Overall, our results uncover PEP as a new factor for FLC upregulation, underscoring the importance of RNA-binding activities during developmental timing of flowering.

Assessment of the increase in variability when combining volumetric data from different scanners.

In multicenter MRI studies, pooling of volumetric data requires a prior evaluation of compatibility between the different machines used. We tested the compatibility of five different scanners (2 General Electric Signa, 2 Siemens Symphony, and a Philips Gyroscan) at five different sites by repeating the scans of five volunteers at each of the sites. Using a semiautomatic method based on the Talairach atlas, and SPM algorithms for tissue segmentation (multimodal T1 and T2, or T1-only), we obtained volume measurements of the main brain lobes (frontal, parietal, occipital, temporal) and for each tissue type. Our results suggest that pooling of multisite data adds small error for whole brain measurements, intersite coefficient of variation (CV) ranging from 1.8 to 5.2%, respectively, for GM and CSF. However, in the occipital lobe, intersite CV can be as high as 11.7% for WM and 17.3% for CSF. Compared with the intersite, intrasite CV values were always much lower. Whenever possible, T1 and T2 tissue segmentation methods should be used because they yield more consistent volume measurements between sites than T1-only, especially when some of the scans were obtained with different sequence parameters and pixel size from those of the other sites. Our study shows that highest compatibility among scanners would be obtained using equipments of the same manufacturer and also image acquisition parameters as similar as possible. After validation, data from a specific ROI or scanner showing values markedly different from the other sites might be excluded from the analysis.

Progression of brain volume changes in adolescent-onset psychosis.

Little is known about the changes that take place in the adolescent brain over the first few years following the onset of psychosis. The present longitudinal study builds on an earlier cross-sectional report demonstrating brain abnormalities in adolescent-onset psychosis patients with a recent-onset first episode of psychosis. Magnetic resonance imaging studies were obtained at baseline and 2 years later from 21 adolescents with psychosis and 34 healthy controls matched for age, gender, and years of education. Whole-brain volumes and gray matter (GM) and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured at baseline and at 2-year follow-up. In the frontal lobe, the rate of GM volume loss was significantly higher in male patients (2.9% and 2.0%, respectively, for left and right) than in controls (1.2% and 0.7%, respectively, for left and right). In the left frontal lobe, male patients showed a significantly higher rate of CSF volume increase than controls (8.6% vs 6.4%). These differences in rates of volume change were observed in male and female patients, although only males showed significant time x diagnosis interactions. This negative finding in females should be interpreted with caution as the study was underpowered to detect change in women due to limited sample size. An exploratory analysis revealed that schizophrenia and nonschizophrenia psychotic disorders showed similar volume change patterns relative to controls. Change in clinical status was not correlated with longitudinal brain changes. Our results support progression of frontal lobe changes in males with adolescent-onset psychosis.

Regional gray matter volume deficits in adolescents with first-episode psychosis.

OBJECTIVE: The current study combined baseline voxel-based morphometry and 1-year clinical follow-up assessments to examine whether and where regional gray matter (GM) volumes differed between a control group and diagnostic subgroups of early-onset first-episode psychosis (FEP). METHOD: Magnetic resonance imaging brain scans were obtained from 70 patients with early-onset FEP, and 51 non-FEP controls. Early-onset FEP was defined as age younger than 18 years and a duration of positive symptoms of less than 6 months. The age range of the sample was 7 to 18 years. After a 1-year follow-up, patients were stratified into three subgroups: schizophrenia (n = 25), bipolar I disorder (n = 20), and other psychoses (n = 25). Regional GM volumes of each patient subgroup were compared with those of the control group. RESULTS: A follow-up diagnosis of schizophrenia was associated with GM volume deficits in the left medial and left middle frontal gyrus; bipolar I disorder was related to a GM volume deficit in the left medial frontal gyrus; and not having a follow-up diagnosis of schizophrenia or bipolar disorder was associated with smaller bilateral GM volumes in the insula and right middle occipital gyrus. CONCLUSIONS: Left medial frontal GM volume deficits were common in the groups with schizophrenia and bipolar I disorder, which may point to shared underlying pathological findings.

Alteration of the shoot radial pattern in Arabidopsis thaliana by a gain-of-function allele of the class III HD-Zip gene INCURVATA4.

Class III HD-Zip (HD-Zip III) family genes play key roles in a number of fundamental developmental programs in Arabidopsis thaliana, such as embryo patterning, meristem initiation and homeostasis, lateral organ polarity and vascular development. Semidominant gain-of-function alleles of the HD-Zip III genes PHABULOSA (PHB), PHAVOLUTA (PHV) and REVOLUTA (REV) disrupt the negative regulation of these genes by a mechanism of microRNA interference. We provide evidence that the gain-of-function icu4-1 allele of INCURVATA4, a gene encoding the HD-Zip III transcription factor ATHB15/CORONA (CNA), stimulates the production of vascular tissues, supporting a role for ICU4 in promoting vascular development. Occasionally, homozygous mutants for this allele show a reduced number of thick shoot vascular bundles, although normal collateral polarity remains unchanged. Genetic analysis of icu4-1 and phb-1D, a gain-of-function allele of the related PHB gene, revealed antagonism in lateral organ polarity between both mutations and a synergistic interaction in shoots, with transformation of the polarized collateral bundles into a radialized amphivasal pattern. These results indicate that the precise regulation of HD-Zip III genes confers positional information which is required to establish the number and pattern of vascular bundles in the stem. In addition, we present results that suggest an interaction between ICU4 function and auxin signaling.

Findings of proton magnetic resonance spectometry in the dorsolateral prefrontal cortex in adolescents with first episodes of psychosis.

Knowledge of the neurobiology of early onset psychosis is limited. We used proton magnetic resonance spectroscopy to investigate the possible existence of dorsolateral prefrontal brain biochemical abnormalities in adolescents with psychosis and to determine possible differential effects related to specific psychotic diagnoses. We measured the ratios of N-acetyl-aspartate (NAA), choline (Cho), and creatine (Cr) to water in two groups of adolescents with a first episode of psychosis (schizophrenia n=8; non-schizophrenia n=15) and in 32 healthy controls matched for age, gender, and years of education. Proton magnetic resonance spectroscopy at 1.5 T was used to study two 6.75-cc voxels placed in the left and right dorsolateral prefrontal region. The schizophrenia patients presented statistically significant reductions in NAA/water levels in the left dorsolateral prefrontal voxel as compared with non-schizophrenia patients and healthy controls. No significant differences were detected between groups for NAA/water in the right dorsolateral prefrontal voxel or for Cho/water and Cr/water levels in any hemisphere. A reduction of the NAA/water level in the left dorsolateral prefrontal region may be selectively present at the onset of psychosis during adolescence in patients who later progress to schizophrenia, but not in those who later progress to other psychotic disorders.

1H MR spectroscopy in the assessment of gliomatosis cerebri.

OBJECTIVE: Gliomatosis cerebri is a rare brain tumor with a short survival time; for this reason, it is difficult to establish the degree of aggressivity in vivo. The MR spectroscopic findings on this tumor often do not agree with choline level. The purpose of this study was to evaluate whether MR spectroscopy can be used to measure tumor choline levels and whether the findings give useful information about tumor growth rate and patient survival time. SUBJECTS AND METHODS: We performed MRI and 1H MR spectroscopic studies on seven treatment-naive patients with gliomatosis cerebri and on 16 healthy volunteers. We then analyzed the association between survival time and levels of choline (Cho) and N-acetyl aspartate (NAA) normalized to creatine (Cr). RESULTS: The results showed a statistically significant (p = 0.05) inverse relation between Cho/Cr ratio and survival time. In addition, NAA/Cr ratio was significantly lower in the patient group than in the control group (p = 0.001). CONCLUSION: Cho/Cr ratio measured with MR spectroscopy seems to be related to survival time, possibly explaining the inconsistent findings previously reported for this parameter.

Structural neuroimaging in adolescents with a first psychotic episode.

OBJECTIVE: The objective of the present study is to replicate findings in first-episode psychosis reporting a smaller volume in brain structures in a population with adolescent onset. METHOD: Magnetic resonance imaging studies were performed on 23 psychotic adolescents (12-18 years old, 17 males, 6 females) consecutively admitted to an adolescent inpatient unit and on 37 normal controls (13-18 years, 23 males, 14 females) matched for age, sex, and years of education. Diagnosis was made at baseline on the basis of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version and confirmed after 12 months of follow-up. Total brain volume and gray matter, white matter, and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured bilaterally using a segmentation method based on the Talairach grid system. RESULTS: Male patients showed significantly larger volumes than did male controls in overall CSF and left frontal and right parietal sulci CSF. Male patients also showed significantly lower volumes of gray matter in the right and left frontal lobes. No significant volumetric differences were found in females. There were no differences between individuals with a diagnosis of schizophrenia at follow-up and the rest of the patients. CONCLUSIONS: This study suggests that larger CSF and lower gray matter volumes in the frontal lobes may be a nonspecific vulnerability marker for psychosis in male adolescents.

Increase in gray matter and decrease in white matter volumes in the cortex during treatment with atypical neuroleptics in schizophrenia.

The effects of atypical antipsychotic treatment on the brain volume deficits associated with schizophrenia are poorly understood. We assessed the brain volumes of eleven healthy controls and 29 patients with schizophrenia, using magnetic resonance imaging at baseline and at follow-up after two years of treatment with atypical neuroleptics. Two groups of patients were analyzed: treatment-naïve patients (n = 17) and chronic treatment-resistant patients (n = 12). Treatment-naïve patients received risperidone during the follow-up period, whereas chronic patients received clozapine. Gray matter (GM) and white matter (WM) volumes in the frontal, parietal, occipital, and temporal lobes were measured. Contrary to the controls, both groups of patients presented GM increases and WM decreases in the parietal and occipital lobes (p < .005). Frontal GM also increased in the chronic group with clozapine. There was a significant (p < .001) inverse relationship between the baseline volumes (GM deficit/WM excess) and the longitudinal change. These GM and WM changes were not related to changes in weight. Thus, treatment with risperidone and clozapine in schizophrenia may have an effect on gray and white matter volume and needs further exploration.