Association of increased abdominal adiposity at birth with altered ventral caudate microstructure.

BACKGROUND: Neonatal adiposity is associated with a higher risk of obesity and cardiometabolic risk factors in later life. It is however unknown if central food intake regulating networks in the ventral striatum are altered with in-utero abdominal growth, indexed by neonatal adiposity in our current study. We aim to examine the relationship between striatal microstructure and abdominal adipose tissue compartments (AATCs) in Asian neonates from the Growing Up in Singapore Toward healthy Outcomes mother-offspring cohort. STUDY DESIGN: About 109 neonates were included in this study. Magnetic resonance imaging (MRI) was performed for the brain and abdominal regions between 5 to 17 days of life. Diffusion-weighted imaging of the brain was performed for the derivation of caudate and putamen fractional anisotropy (FA). Abdominal imaging was performed to quantify AATCs namely superficial subcutaneous adipose tissue (sSAT), deep subcutaneous adipose tissue (dSAT), and internal adipose tissue (IAT). Absolute and percentage adipose tissue of total abdominal volume (TAV) were calculated. RESULTS: We showed that AATCs at birth were significantly associated with increased FA in bilateral ventral caudate heads which are part of the ventral striatum (sSAT: ßleft = 0.56, p < 0.001; ßright = 0.65, p < 0.001, dSAT: ßleft = 0.43, p < 0.001; ßright = 0.52, p < 0.001, IAT: ßleft = 0.30, p = 0.005; ßright = 0.32, p = 0.002) in neonates with low birth weights adjusted for gestational age. CONCLUSIONS: Our study provides preliminary evidence of a potential relationship between neonatal adiposity and in-utero programming of the ventral striatum, a brain structure that governs feeding behavior.

Polygenic risk for neuropsychiatric disease and vulnerability to abnormal deep grey matter development.

Neuropsychiatric disease has polygenic determinants but is often precipitated by environmental pressures, including adverse perinatal events. However, the way in which genetic vulnerability and early-life adversity interact remains obscure. We hypothesised that the extreme environmental stress of prematurity would promote neuroanatomic abnormality in individuals genetically vulnerable to psychiatric disorders. In 194 unrelated infants (104 males, 90 females), born before 33 weeks of gestation (mean gestational age 29.7 weeks), we combined Magnetic Resonance Imaging with a polygenic risk score (PRS) for five psychiatric pathologies to test the prediction that: deep grey matter abnormalities frequently seen in preterm infants are associated with increased polygenic risk for psychiatric illness. The variance explained by the PRS in the relative volumes of four deep grey matter structures (caudate nucleus, thalamus, subthalamic nucleus and lentiform nucleus) was estimated using linear regression both for the full, mixed ancestral, cohort and a subsample of European infants. Psychiatric PRS was negatively associated with lentiform volume in the full cohort (ß = -0.24, p = 8 × 10-4) and a European subsample (ß = -0.24, p = 8 × 10-3). Genetic variants associated with neuropsychiatric disease increase vulnerability to abnormal lentiform development after perinatal stress and are associated with neuroanatomic changes in the perinatal period.

Differential abnormalities of the head and body of the caudate nucleus in attention deficit-hyperactivity disorder.

The aim of the study is to present a new method for the segmentation of the caudate nucleus and use it to compare the caudate heads and bodies of an attention deficit-hyperactivity disorder (ADHD) group with those of a control group. We used a 1.5-T system to acquire magnetic resonance brain scans from 39 children with ADHD, as defined by DSM-IV TR, and 39 age, handedness and IQ matched controls. The new method for caudate head and body segmentation was applied to obtain semi-automatic volumes and asymmetric patterns. Bilateral volumetric measures of the head, body, and head-body of the caudate nuclei were compared within groups and between ADHD and control groups. Although the group factor was not significant, there were first and second order interactions. The analysis of simple effects showed that the right body and right head+body of the ADHD group was significantly smaller than in the control group, although the ADHD right caudate head was bigger. No ADHD within-group caudate differences were found. Controls showed a significantly larger left caudate head and a significantly bigger caudate right body and right head+body. Our new method for segmenting the caudate nucleus detected differential abnormalities of the right caudate head and body in the ADHD group, explaining previous heterogeneous findings in the literature.

Shape deformity of the corpus striatum in obsessive-compulsive disorder.

Volumetric changes of striatal structures based on magnetic resonance imaging (MRI) have been inconsistent in patients with obsessive-compulsive disorder (OCD) due to methodological limitations. The purpose of this study was to investigate shape deformities of the corpus striatum in patients with OCD. We performed 3-D shape deformation analysis of the caudate nucleus, the putamen, and the globus pallidus in 36 patients with OCD and 36 healthy normal subjects. Shape analysis showed deformity of the striatal structures, especially the caudate nucleus. Outward deformities in the superior, anterior portion of the bilateral caudate were observed in patients with OCD. In addition, an outward deformity in the inferior, lateral portion of the left putamen was also detected. These results suggest that patients with OCD have shape deformities of the corpus striatum, especially the caudate nucleus, compared with healthy normal subjects, and that shape analysis may provide an important complement to volumetric MRI studies in investigating the pathophysiology of OCD.

Validity of large-deformation high dimensional brain mapping of the basal ganglia in adults with Tourette syndrome.

The basal ganglia and thalamus may play a critical role for behavioral inhibition mediated by prefrontal, parietal, temporal, and cingulate cortices. The cortico-basal ganglia-thalamo-cortical loop with projections from frontal cortex to striatum, then to globus pallidus or to substantia nigra pars reticulata, to thalamus and back to cortex, provides the anatomical substrate for this function. In-vivo neuroimaging studies have reported reduced volumes in the thalamus and basal ganglia in individuals with Tourette Syndrome (TS) when compared with healthy controls. However, patterns of neuroanatomical shape that may be associated with these volume differences have not yet been consistently characterized. Tools are being developed at a rapid pace within the emerging field of computational anatomy that allow for the precise analysis of neuroanatomical shape derived from magnetic resonance (MR) images, and give us the ability to characterize subtle abnormalities of brain structures that were previously undetectable. In this study, T1-weighted MR scans were collected in 15 neuroleptic-naïve adults with TS or chronic motor tics and 15 healthy, tic-free adult subjects matched for age, gender and handedness. We demonstrated the validity and reliability of large-deformation high dimensional brain mapping (HDBM-LD) as a tool to characterize the basal ganglia (caudate, globus pallidus and putamen) and thalamus. We found no significant volume or shape differences in any of the structures in this small sample of subjects.

Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug.

The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound. Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and 19 matched controls participated. Patients were randomly assigned to treatment with either low doses of the typical antipsychotic drug, zuclopenthixol, or the atypical compound, risperidone. High-resolution magnetic resonance imaging (MRI) scans were obtained in patients before and after 12 weeks of exposure to medication and in controls at baseline. Caudate nucleus, nucleus accumbens, and putamen volumes were measured. Compared with controls, absolute volumes of interest (VOIs) were smaller in patients at baseline and increased after treatment. However, with controls for age, gender and whole brain or intracranial volume, the only significant difference between patients and controls was a Hemisphere x Group interaction for the caudate nucleus at baseline, with controls having larger left than right caudate nuclei and patients having marginally larger right than left caudate volumes. Within patients, the two medication groups did not differ significantly with respect to volume changes after 3 months of low dose treatment in any of the VOIs. Nevertheless, when medication groups were examined separately, a significant volume increase in the putamen was evidenced in the risperidone group. The altered asymmetry in caudate volume in patients suggests intrinsic basal ganglia pathology in schizophrenia, most likely of neurodevelopmental origin.

The neuroradiological findings of children with developmental language disorder.

PURPOSE: To investigate the general characteristics of glucose metabolism distribution and the functional deficit in the brain of children with developmental language delay (DLD), we compared functional neuroradiological studies such as positron emission tomography (PET) of a patient group of DLD children and a control group of attention- deficit hyperactivity disorder (ADHD) children. PATIENTS AND METHODS: Seventeen DLD children and 10 ADHD children under 10 years of age were recruited and divided into separate groups consisting of children less than 5 years of age or between 5 and 10 years of age. The PET findings of 4 DLD children and 6 control children whose ages ranged from 5 to 10 years were compared by Statistical Parametric Mapping (SPM) analysis. RESULTS: All of the DLD children revealed grossly normal findings in brain MRIs, however, 87.5% of them showed grossly abnormal findings in their PET studies. Abnormal findings were most frequent in the thalamus. The patient group showed significantly decreased glucose metabolism in both frontal, temporal and right parietal areas (p < 0.005) and significantly increased metabolism in both occipital areas (p < 0.05) as compared to the control group. CONCLUSION: This study reveals that DLD children may show abnormal findings on functional neuroradiological studies, even though structural neuroradiological studies such as a brain MRI do not show any abnormal findings. Frequent abnormal findings on functional neuroradiological studies of DLD children, especially in the subcortical area, suggests that further research with quantitative assessments of functional neuroradiological studies recruiting more DLD children and age-matched normal controls could be helpful for understanding the pathophysiology of DLD and other disorders confined to the developmental disorder spectrum.

Asymmetry of basal ganglia in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatry disorder with several key symptoms, such as inattentiveness, impulsivity and hyperactivity. Neuropsychiatry studies have implicated the frontostriatal circuit in the pathological physiology of the disorder. Using magnetic resonance imaging (MRI), we examined the basal ganglia in 13 ADHD patients and eight unaffected comparison children. The volume of caudate, putamen and globus pallidus was measured. In the ADHD patients, we detected an increased left > right asymmetry of the basal ganglia. This reversal of asymmetry in the globus pallidus and caudate nucleus were statistically significant. These finding provide further evidence of morphological brain abnormalities in ADHD.

Volume increases in striatum associated with positive symptom reduction in schizophrenia: a preliminary observation.

Eleven drug-free patients with a DSM-IV diagnosis of schizophrenia who were in a period of psychotic exacerbation were treated with antipsychotics for 4 weeks. To evaluate treatment-associated changes in the basal ganglia and in psychotic symptomatology, the patients were studied with magnetic resonance imaging and with the Scale for the Assessment of Positive Symptoms. Serial assessments of striatal volumes and psychotic symptoms were performed at baseline and at 4 weeks of treatment; dual assessments of striatal volumes were also performed in 11 untreated normal controls. Patients and controls did not differ in striatal volumes at baseline, but the patients demonstrated a significant posttreatment increase in striatal tissues (caudate-putamen). An increase in left striatum was not associated with drug treatment itself, but with a reduction of positive symptoms.

A manual and automated MRI study of anterior cingulate and orbito-frontal cortices, and caudate nucleus in obsessive-compulsive disorder: comparison with healthy controls and patients with schizophrenia.

Functional imaging and neuropsychological data suggest that interconnected brain structures including the orbito-frontal cortex (OFC), anterior cingulate cortex (ACC) and caudate nucleus (CN) are involved in the pathophysiology of obsessive-compulsive disorder (OCD), but structural imaging studies investigating these regions have yielded inconclusive results. This may be due to inconsistencies in the identification of anatomical boundaries and methodologies utilised (i.e. automated vs. manual tracing). This magnetic resonance imaging study used manual tracing to measure volumes of selected brain regions (OFC, ACC and CN) in OCD patients and compared them with samples of healthy (HC) and psychiatric (schizophrenia; SCZ) controls (n=18 in each group). Concurrently, automated voxel-based analysis was also used to detect subtle differences in cerebral grey and white matter. For the OCD vs. HC comparison, there were no significant volumetric differences detected using the manual or the automated method (although the latter revealed a deficit in the subcortical white matter of the right temporal region). A direct comparison of the two patient groups showed no significant differences using the manual method. However, a moderate effect size was detected for OFC grey matter (reduced in SCZ), which was supported by findings of reduced OFC volume in the automated analysis. Automated analyses also showed reduced volumes in the dorsal (white matter) and ventral ACC (grey and white matter), as well as the left posterior cingulate (grey and white matter) in SCZ. The findings suggest that in contrast to findings in SCZ, there are very few (if any) gross structural anomalies in OCD.

Caudate size in first-episode neuroleptic-naive schizophrenic patients measured using an artificial neural network.

BACKGROUND: Structural brain imaging studies have demonstrated an increase in caudate volume in schizophrenic patients medicated with typical neuroleptics and a volume decrease following treatment with atypical neuroleptics. The measurement of striatal volume in patients who have never been treated with neuroleptics may indicate whether these changes are superimposed on intrinsic basal ganglia pathology in schizophrenia or are solely neuroleptic-induced. METHODS: We studied 36 first-episode, neuroleptic-naive schizophrenic patients and 43 control subjects using an artificial neural network (ANN) to identify and measure the caudate nucleus. The resulting volumes were analyzed using an ANCOVA controlling for intracranial volume, age, gender, and socioeconomic status. RESULTS: The mean volume difference between the caudate nuclei of patients and control subjects was .297 mL, the caudate nuclei of the patients being smaller than those of controls. When we covaried for intracranial volume, this was a statistically significant difference in caudate volume (n = 79; df = 1,75; F = 4.18; p > .04). CONCLUSIONS: Caudate nuclei of neuroleptic naive schizophrenic patients are significantly smaller than those of controls. This suggests that patients suffering from schizophrenia may have intrinsic pathology of the caudate nucleus, in addition to the pathology observed as a consequence of chronic neuroleptic treatment.

Longitudinal study of brain morphology in first episode schizophrenia.

BACKGROUND: Beginning with Kraepelin, schizophrenia has been viewed as a progressive disorder. Although numerous studies of the longitudinal course of schizophrenia have demonstrated the clinical deterioration that occurs predominantly in the early stages of the illness, the pathophysiology of this clinical phenomenon has not been established. This aspect of the illness may be of critical importance to understanding the pathogenesis of schizophrenia and determining preventive therapeutic strategies. Abnormalities in brain morphology have been consistently described in schizophrenia, but it is not known when in the natural history of the illness they arise and whether they are progressive. Previous studies of brain morphology have been inconclusive, in part because of the variability of methods for image acquisition and analysis, assessment of patients already at chronic stages of their illness with extensive prior treatment exposure, and inadequate periods of follow-up. METHODS: To address these questions we examined 107 patients in their first episode of schizophrenia or schizoaffective disorder and 20 healthy volunteers using high resolution magnetic resonance imaging (MRI) and clinical assessments of psychopathology and treatment outcome for periods of up to 6 years. Fifty-one patients and 13 control subjects had MRIs after at least 12 months of follow-up. RESULTS: Results confirm the findings of ventricular enlargement and anterior hippocampal volume reductions in first episode schizophrenia patients that have been previously reported. In addition, we found changes in selected structures over time in relation to treatment outcome, including increases in ventricular volume that were associated with poor outcome patients. Contrary to our hypothesis, there were no significant reductions in cortical and hippocampal volumes over time. CONCLUSIONS: The finding of progressive ventricular enlargement in patients with poor outcome schizophrenia is consistent with the hypothesis that persistent positive and negative symptoms result in progressive brain changes in the form of ventricular enlargement, possibly due to neurodegeneration rather than the confounding effects of treatment. Future studies of first episodes of schizophrenia should utilize higher resolution imaging techniques that compare clinically well characterized patients with and without poor outcome and recurrent symptoms to control subjects who are well matched to patients for age and gender. There is also a need to control for treatment effects of typical antipsychotic medication on brain structure.

Caudate volume changes in first episode psychosis parallel the effects of normal aging: a 5-year follow-up study.

We investigated whether the caudate nuclei volume (CNV) of 15 first episode psychosis patients increased after 5 years of treatment with either atypical antipsychotics or low doses of typical antipsychotics. Caudate volumes were measured from magnetic resonance imaging (MRI) scans in 15 patients and 10 healthy controls. Both groups demonstrated a significant 9% decline in caudate volume. We were unable to replicate previous reports of caudate enlargement in patients receiving antipsychotic treatment.

Computed tomography and neurological soft signs in obsessive-compulsive disorder.

Computed tomography was used to compare the following three groups: obsessive-compulsive disorder (OCD) patients with high scores on a soft neurological sign examination, OCD patients with low soft neurological sign scores, and control subjects. Neuranatomical structures were measured using quantitative volumetric analysis. OCD patients with high soft sign scores had significantly increased ventricular volumes compared with OCD patients with low soft sign scores and control subjects. Caudate and lenticular nucleus volumes did not differ between groups.

A volumetric magnetic resonance imaging study of monozygotic twins discordant for bipolar disorder.

Six monozygotic (MZ) twin pairs discordant for bipolar disorder were compared with normal MZ twins with magnetic resonance imaging (MRI) on volumes of basal ganglia (BG), amygdala-hippocampus (AH), and cerebral hemisphere. Caudate nuclei were larger in both affected and unaffected bipolar twins than in normal MZ twins. The right hippocampus was smaller in the sick vs. well bipolar twins. The hippocampus was also less asymmetric in the affected bipolar twins than in the well cotwins and the normal MZ twins. These anatomical structures continue to be of interest in bipolar disorder research.

Attention deficit-hyperactivity disorder and asymmetry of the caudate nucleus.

The neurologic basis of attention deficit-hyperactivity disorder (ADHD) is poorly understood. Based on previous studies that have implicated metabolic deficiencies in the caudate-striatal region in ADHD, we employed magnetic resonance imaging to investigate patterns of morphology of the head of the caudate nucleus in normal and ADHD children. In normal children, 72.7% evidenced a left-larger-than-right (L > R) pattern of asymmetry, whereas 63.6% of the ADHD children had the reverse (L < R) pattern of asymmetry of the head of the caudate nucleus. This reversal of normal asymmetry in ADHD children was due to a significantly smaller left caudate nucleus. The reversal in asymmetry of the head of the caudate was most notable in ADHD males. These results suggest that normal (L > R) morphologic asymmetry in the region of the caudate nucleus may be related to asymmetries observed in neurotransmitter systems implicated in ADHD. The behavioral symptoms of ADHD may reflect disinhibition from normal levels of dominant hemispheric control, possibly correlated with deviations in asymmetric caudate-striatal morphology and deficiencies in associated neurotransmitter systems.

Neuroimaging communality between schizophrenia and obsessive compulsive disorder: a putative basis for schizo-obsessive disorder?

Four major brain regions have been repeatedly implicated in the pathophysiology of obsessive compulsive disorder (OCD) in in vivo neuroimaging studies: the caudate nucleus, the orbitofrontal cortex, the anterior cingulate gyrus and the mediodorsal thalamic nucleus. The present review describes the neuroimaging studies on schizophrenia, pertaining to these brain regions. Our working hypothesis is that such common brain regions, if dysfunctional in schizophrenic patients, would be candidates for a neural network subserving the newly emerging syndrome of schizo-obsessive disorder. Findings, though, are controversial. We conclude that further studies, aimed at specific monitoring of these brain regions, in patients suffering from the schizo-obsessive syndrome are warranted.

[Attention deficit hyperactivity disorder. Cerebral asymmetry observed on magnetic resonance]. / Trastorno por déficit de atención con hiperactividad. Asimetrías cerebrales observadas en resonancia magnética.

INTRODUCTION: Anatomical and functional neuroimaging data from subjects with Attention Deficit Hyperactivity Disorder (ADHD) have consistently implicated a reversal of cerebral asymmetry and suggested a fronto-striatal dysfunction in this disorder. OBJECTIVE: The aim of this study is to investigate the brain asymmetries in a homogeneous and non-medicated sample of adolescents with ADHD who had been previously studied in our laboratory. PATIENTS AND METHODS: T1-weighted magnetic resonance images were obtained for 11 adolescents with ADHD and 19 control subjects. Frontal and posterior brain regions, caudate nucleus, and ventricular system were quantitatively measured. RESULTS: A reversed pattern of asymmetry for the caudate nucleus (right > left) was found in ADHD when compared to the control group. We also found a reversed pattern of asymmetry for the frontal lobe (right < left) and a smaller right frontal volume (prefrontal specifically) in the ADHD subjects most severely impaired. Right caudate and frontal measures were inversely correlated. CONCLUSIONS: ADHD is associated with fronto-striatal abnormalities, which may be explicable via extant neurodevelopmental theories. Enlargement of the right caudate nucleus may suggest the failure of a process of synaptic 'pruning' by which attentional functions could be improperly transferred from the basal ganglia to frontal regions during development.