Biomedical subjects

Matcheri S Keshavan

Publications and source records attributed to Matcheri S Keshavan.

At least 91 records · Page 5Linked to original sources

PubMed2003

Membrane phospholipid abnormalities of basal ganglia in never-treated schizophrenia: a 31P magnetic resonance spectroscopy study.

BACKGROUND: Studies in schizophrenia using in vivo (31)P magnetic resonance spectroscopy (MRS) have mostly focused on the association cortices, including the frontal and temporal lobes. Striatum has also been implicated in schizophrenia, although neuroleptic exposure in the patients is a potential confound limiting interpretation of earlier studies. We examined membrane phospholipid abnormality in the basal ganglia using (31)P MRS in neuroleptic-naive schizophrenia patients. METHODS: Never-treated, DSM-IV schizophrenia patients (n=20) and age- and gender-matched healthy control subjects (n=30) underwent in vivo 1-D 31P MRS of both basal ganglia using an image-selected technique on a 1.5-T magnetic resonance imaging scanner. A neuroradiologist blind to clinical data measured the phosphomonoester (PME) and phosphodiester (PDE) from the spectra. RESULTS: The schizophrenia patients showed significantly and bilaterally elevated levels of PME/PDE ratios in basal ganglia as compared with control subjects. There were no significant differences in the ratios between the two sides in either patient or control groups. Phosphomonoester/phosphodiester ratio did not correlate with illness duration. Lower Positive and Negative Syndrome Scale scores were associated with lower PME/PDE ratio. CONCLUSIONS: The basal ganglia of never-treated schizophrenia patients show features suggestive of reduced breakdown and/or increased synthesis of membrane phospholipids. Lack of correlation between illness duration and the membrane phosphorus moiety ratio may be consistent with a nonprogressive, possibly neurodevelopmental etiopathogenesis.

Adult↗

PubMed2003

Psychosis proneness and ADHD in young relatives of schizophrenia patients.

Symptoms resembling the attentional deficit hyperactivity disorder (ADHD) are frequently observed in young relatives at risk for schizophrenia (HR). We examined the frequency of the ADHD syndrome and its relationship to psychosis related psychopathology and neurobehavioral abnormalities in young HR subjects (n=29) and healthy comparison subjects (HC; n=30). Thirty-one percent of HR subjects (n=9) had ADHD as a lifetime Axis-I diagnosis (HR-A). Compared to healthy comparison subjects, the HR-A group had impaired neurological function. The HR-A group but not the HR subjects without ADHD had higher scores on the Chapman's magical ideation and perceptual aberration scales. Thus, ADHD-like features are more prevalent in the HR population than the one described in the general population and are associated with more frequent psychosis-like clinical features. Longitudinal studies can clarify whether an "ADHD subgroup" within HR subjects predict an increased risk for future emergence of schizophrenia.

Adolescent↗

PubMed2003

Phosphorus magnetic resonance spectroscopy: its utility in examining the membrane hypothesis of schizophrenia.

A novel approach to understanding the pathophysiology of schizophrenia has been the investigation of membrane composition and functional perturbations, referred to as the "Membrane Hypothesis of Schizophrenia." The evidence in support of this hypothesis has been accumulating in findings in patients with schizophrenia of reductions in phospholipids and essential fatty acids various peripheral tissues. Postmortem studies indicate similar reductions in essential fatty acids in the brain. However, the use of magnetic resonance spectroscopy (MRS) has provided an opportunity to examine aspects of membrane biochemistry in vivo in the living brain. MRS is a powerful, albeit complex, noninvasive quantitative imaging tool that offers several advantages over other methods of in vivo biochemical investigations. It has been used extensively in investigating brain biochemistry in schizophrenia. Phosphorus MRS (31P MRS) can provide important information about neuronal membranes, such as levels of phosphomonoesters that reflect the building blocks of neuronal membranes and phosphodiesters that reflect breakdown products. 31P MRS can also provide information about bioenergetics. Studies in patients with chronic schizophrenia as well as at first episode prior to treatment show a variety of alterations in neuronal membrane biochemistry, supportive of the membrane hypothesis of schizophrenia. Below, we will briefly review the principles underlying 31P MRS and findings to date. Magnetic resonance spectroscopy (MRS) is a powerful, albeit complex, imaging tool that permits investigation of brain biochemistry in vivo. It utilizes the magnetic resonance imaging hardware. It offers several advantages over other methods of in vivo biochemical investigations. MRS is noninvasive, there is no radiation exposure, does not require the use of tracer ligands or contrast media. Because of it is relatively benign, repeated measures are possible. It has been used extensively in investigating brain biochemistry in schizophrenia.

Brain↗

PubMed2003

White matter hyperintensities in bipolar and unipolar patients with relatively mild-to-moderate illness severity.

BACKGROUND: Increased rates of white matter hyperintense lesions have been reported in mood disorder patients. However, the potential effects of age and illness severity on reported findings are not fully established. We examined the rates of hyperintense lesions in adult, non-elderly bipolar and unipolar patients, with a relatively mild-to-moderate illness severity, and in matched healthy controls. METHOD: We examined brain MRI images in 24 bipolar (19-56 years, mean+/-S.D.=34.2+/-9.9 years) and 17 unipolar patients (24-59 years, 42.8+/-9.2 years), and 38 healthy controls (21-59 years, 36.8+/-9.7 years). T2-weighted and proton-density axial MRI images were obtained at 1.5 Tesla. The lesions were rated by two independent raters, using a semi-quantitative rating scale. RESULTS: There were no significant differences in the frequency of hyperintensities between bipolar or unipolar patients and healthy controls. Age was related to the presence of subcortical gray matter hyperintensities for the whole sample. Among the unipolar patients, length of illness and presence of mood disorder in a first-degree relative were related to deep and periventricular white matter lesions, respectively. LIMITATIONS: The methodology utilized for measurement of the white matter hyperintensities was semi-quantitative. CONCLUSIONS: Increased rates of white matter hyperintensities do not appear to be present in a group of relatively young mood disorder patients, with relatively mild to moderate illness severity. These brain lesions may be more directly related to late-life and more severe cases of these illnesses.

Adult↗

PubMed2003

Neuropsychological performance and regional cerebral blood flow in obsessive-compulsive disorder.

Convergent findings from neuropsychological and neuroimaging studies have suggested that neural dysfunction in frontal-subcortical circuits may play a central role in the pathophysiology of obsessive-compulsive disorder (OCD). To further examine the relationship between these two sets of findings we investigated both neuropsychological functions and regional cerebral blood flow (rCBF) in a combined study. Fourteen unmedicated patients fulfilling DSM-IV criteria for OCD and 14 healthy controls matched for age, gender, handedness, and education were assessed on neuropsychological tests that included Trail Making Test (TMT), Rey Complex Figure Test (RCF) (copy and 5-min recall), Verbal Fluency Test (VFT), and Wisconsin Card Sorting Test (WCST). rCBF was studied with 99 mTc-hexamethyl-propyleneamine-oxime (HMPAO) single photon emission computed tomography (SPECT). Patients performed more poorly than controls (P<.05) on RCF (copy), VFT, and WCST (perseverative errors). Spearman's correlations indicated that severity of OCD correlated inversely with performance on the RCF (copy and recall scores) and positively with rCBF in the right thalamus. Positive correlations were observed between nonperseverative errors (WCST) and rCBF in frontal areas and anterior cingulate. Perseverative errors (WCST) correlated negatively with rCBF in the right thalamus. These findings are consistent with most previously published studies and suggest neural dysfunctions in the frontal-subcortical circuits probably more pronounced in the right hemisphere. They also extend the existing research, showing associations between deficits in cortical-subcortical circuitry and performance on neuropsychological tests of controlled attention and visuospatial functions.

Adolescent↗

PubMed2003

Measurement of the orbitofrontal cortex: a validation study of a new method.

The orbital frontal cortex (OFC) plays a critical role in the pathophysiology of several neuropsychiatric disorders. Few morphometric neuroimaging studies have examined the OFC using different methodologies and have reported discrepant values. Substantial variability in gyri and sulci across individuals as well as unclear landmarks underline the difficulties in obtaining accurate and reliable measurements. We propose a new geometrical method for measuring the OFC taking into account individual brain variability. The OFC was defined by using the intercommissural line and the inferior edge of the frontal lobe as the main landmarks. The medial and lateral subdivisions of OFC were also separately measured using the olfactory sulcus as the boundary to distinguish between them. After resampling and refitting, 10 scans were independently traced by two trained researchers using BRAINS software. Talairach coordinates were identified on each scan from the OFC and surrounding adjacent brain regions to assess the validity of this method. Brain regions were assigned using Talairach Daemon system. OFC volumes were comparable with those previously reported. Sensitivity and specificity for OFC gray matter were 87.6 and 84.8%, respectively. Intraclass coefficients (ICCs) for gray, white, and total OFC were 0.995, 0.994, and 0.997, respectively. ICCs for OFC medial and lateral subdivisions ranged between 0.996 and 0.998. This method appears to be a valid method for measuring the OFC with excellent reliability. This uncomplicated approach is easy to apply and has the potential to be a valuable alternative to the previously published methods.

Adult↗

PubMed2003

Early and late neurodevelopmental influences in the prodrome to schizophrenia: contributions of genes, environment, and their interactions.

Both early (i.e., pre- and perinatal periods) and late (i.e., adolescent period) neurodevelopmental processes are thought to participate in the etiology and pathophysiology of schizophrenia. However, whether markers of these processes would be expected to predict an imminent onset of psychosis, as is hoped in the current generation of prodromal research programs, depends on whether their disruptions result from genetic factors shared by patients and some of their unaffected relatives, nongenetic factors specific to those who manifest the illness phenotype, or combinations of these sets of influences. Here we present recent work deriving primarily from high-risk and family-study (i.e., "genetic high-risk") designs, which provide a framework for investigating the neural changes that may occur proximally to the initial onset of psychosis. This work indicates that some of the alterations in brain function and structure in schizophrenia are primarily genetically mediated and also appear in some of patients' unaffected first degree relatives, while other alterations are present in individuals who manifest the illness phenotype but not in relatives at genetic risk (Cannon et al. 2002a, 2002c; Van Erp et al. 2002). Whereas the primarily genetically mediated deficits shared by at-risk but nonsymptomatic relatives are not likely to show differential change in the premorbid period and may be necessary but clearly not sufficient for the development of psychotic symptoms, the deficits specific to patients who manifest the illness phenotype are good candidates for marking the neurobiological processes associated with the emergence of psychotic symptoms at the time of schizophrenia onset. Preliminary results from longitudinal studies of individuals ascertained initially in a prodromal (i.e., "clinical high-risk") state appear to be interpretable within this framework. A number of questions arising from this line of inquiry need to be addressed in the current generation of prodromal research programs: To what extent do the neural systems affected by early and late neurodevelopmental influences overlap? Is there likely to be a schizophrenia-related disturbance in the processes associated with adolescent brain maturation, or are these maturational processes themselves intact, participating in psychosis onset only indirectly, by promoting a neurobiological context in which the early neurodevelopmental disturbances can be expressed in psychotic symptoms? What pattern of changes observable from in vivo imaging studies is consistent with a reduction in neuropil volume? We develop a framework for addressing these questions and evaluating their implications for understanding the roles of early and late neurodevelopmental influences in the etiology and pathophysiology of schizophrenia.

Adult↗

PubMed2003

Prolonged untreated illness duration from prodromal onset predicts outcome in first episode psychoses.

Several, although not all, studies suggest that prolonged duration of untreated illness (DUI) predicts poor outcome in psychotic disorders such as schizophrenia. It is unclear whether this association can be explained by factors such as baseline deficits or poor premorbid adjustment. First episode psychotic patients were evaluated at 1 and 2 years following baseline evaluations. Predictive measures showing significant correlations with outcome were entered in multiple regression analyses with Strauss-Carpenter scale (SC) and Global Assessment of Functioning scale (GAF) outcome scores as dependent variables. Illness duration computed from the onset of the prodrome (DUI-pro), used both as a dichotomous and as a continuous measure, highly significantly predicted both GAF and SC scores at 2 years. On the other hand, baseline functioning significantly predicted the 1-year but not the 2-year outcome. When Premorbid Adjustment Scale (PAS) scores were additionally entered into the analyses in a smaller subset, the relation between DUI-pro and the 2-year outcome scores remained significant. Significant associations were also seen between outcome and baseline neuropsychological deficits involving attention and memory. Further research is needed to examine whether prolonged untreated illness is simply associated with poor outcome or plays a causal role in relation to outcome. The latter, if true, would strongly support therapeutic intervention efforts in the prodromal and early psychotic phases of schizophrenia.

Adolescent↗

PubMed2003

A review and new report of medial temporal lobe dysfunction as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric family study of the parahippocampal gyrus.

A central question in schizophrenia research is which brain abnormalities are independent of psychosis and which evolve before and after psychosis begins. This question can be addressed by longitudinal neuroimaging studies beginning in the prodrome, but at present there is only one published study. We reviewed the literature on structural brain imaging in persons with chronic and first episode schizophrenia, nonpsychotic persons at genetic high risk, and persons thought to be at risk for imminent psychosis ("prodromal" persons). Medial temporal lobe (MTL), especially hippocampal, volume alterations are among the most robust brain vulnerabilities for schizophrenia. Because verbal declarative memory (VDM) deficits are prominent and the parahippocampal gyrus (PHG) is considered to be centrally involved with the hippocampus in VDM processing, we analyzed PHG data from a family study of schizophrenia. Patients with schizophrenia and nonpsychotic relatives from "multiplex" families (families with multiple persons with schizophrenia) had significantly smaller right parahippocampal anterior (PHa) volumes than controls. Marginally significant findings were observed for the left PHa. Unexpectedly, relatives from "simplex" families (families with only one person with schizophrenia) had significantly larger PH posterior volumes than controls and did not differ from controls on PHa. Results provide some support for the hypothesis that the vulnerability to schizophrenia includes abnormal volumes of the PHG. These data provide additional support for the hypothesis that some MTL abnormalities in schizophrenia are independent of psychosis, at least in families with presumably high genetic loading. Implications of genetic risk studies for prodromal research are discussed.

Adult↗

PubMed2003

Diagnostic specificity and neuroanatomical validity of neurological abnormalities in first-episode psychoses.

OBJECTIVE: Neurological abnormalities are frequently seen in patients with first-episode psychotic disorders but are generally considered to be diagnostically nonspecific, neurologically nonlocalizing, and, hence, "soft." This study examined the neuroanatomical correlates and diagnostic specificity of abnormal findings on the neurological examination in first-episode schizophrenia and other psychotic disorders. METHOD: Neuroleptic-naive patients with schizophrenia (N=90) and with nonschizophrenia psychoses (N=39) and carefully matched healthy subjects (N=93) were compared on total and factor scores for a reliable subset of Neurological Evaluation Scale items. The relationship between neurological examination abnormalities and alterations in the relevant brain structures as assessed by magnetic resonance imaging was examined in a subset of subjects. RESULTS: Factor scores for repetitive motor task abnormalities were higher in both patient groups, relative to the healthy group, and did not distinguish between the patient groups. Factor scores for abnormalities in cognitively demanding and perceptual tasks were markedly higher in the schizophrenia group, relative to both comparison groups, and were not different between the nonschizophrenia psychoses group and the healthy comparison group. Higher scores for the cognitive/perceptual abnormalities factor were correlated with smaller volumes of the left heteromodal association cortex. CONCLUSIONS: Neurological signs may serve as expedient bedside measures that are potentially useful in the assessment of idiopathic psychoses, and cognitive/perceptual neurological signs may have a measure of diagnostic specificity. These findings provide neurobiological validation of abnormal findings on the neurological examination. These abnormalities may reflect discrete neuroanatomical alterations in schizophrenia and may have a localizing value.

Adult↗

PubMed2003

Motor performance and anatomic magnetic resonance imaging (MRI) of the basal ganglia in autism.

This study was conducted to examine the volume of the basal ganglia in individuals with autism and to evaluate whether performance on specific motor tasks correlated with the volume of these structures. Volumetric measurements of the caudate nucleus and putamen were obtained from magnetic resonance images (MRI) of 40 non-mentally retarded individuals with autism and 41 healthy controls. Motor performance was assessed in these subjects by using the Finger Tapping Test, the Grooved Pegboard Test, and the measurement of Grip Strength. No volumetric differences of the basal ganglia were found between the two groups after adjusting for brain volume. The autistic subjects' performance was slower on the Grooved Pegboard Test and weaker on Grip Strength. Our findings suggest that the motor deficits observed in autism may not be related to structural abnormalities of the basal ganglia, and other brain regions, such as the cerebellum and the frontal lobe, may be involved in the pathophysiology of motor disturbances in autism.

Adolescent↗

PubMed2003

Obstetric complications correlate with neurobehavioral and brain structural alterations in young relatives at risk for schizophrenia.

As complications of pregnancy and birth may be important risk factors for the development of schizophrenia, studying the "roots" of schizophrenia in high-risk offspring may better elucidate the interface between biology, environment, and susceptibility to illness. Using magnetic resonance imaging (MRI), neurobehavioral assessments and obstetric histories, we found several significant correlations between these multiple factors, suggesting that birth complications may be a nonspecific etiopathogenic risk factor for psychopathology in young relatives at risk for schizophrenia.

Adolescent↗

PubMed2002

Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study.

BACKGROUND: Previous investigations suggest that maltreated children evidence alterations of chemical mediators of stress and adverse brain development. Previous anatomical magnetic resonance imaging (MRI) brain studies have not controlled for socioeconomic status. METHODS: In this study, 28 psychotropic naïve children and adolescents with maltreatment-related posttraumatic stress disorder (PTSD) and 66 sociodemographically similar healthy control subjects underwent comprehensive clinical assessments and anatomical MRI brain scans. RESULTS: Compared with control subjects, subjects with PTSD had smaller intracranial, cerebral, and prefrontal cortex, prefrontal cortical white matter, and right temporal lobe volumes and areas of the corpus callosum and its subregions (2, 4, 5, 6, and 7), and larger frontal lobe cerebrospinal fluid (CSF) volumes than control subjects. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller in subjects with PTSD, whereas right, left, and total lateral ventricles and frontal lobe CSF were proportionally larger than in control subjects, after adjustment for cerebral volume. Brain volumes positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Significant gender x group effect demonstrated greater lateral ventricular volume increases in maltreated male subjects with PTSD than maltreated female subjects with PTSD. No hippocampal differences were seen. CONCLUSIONS: These data provide further evidence to suggest that maltreatment-related PTSD is associated with adverse brain development. These data also suggest that male children may be more vulnerable to these effects.

Adolescent↗

PubMed2002

Decreased left amygdala and hippocampal volumes in young offspring at risk for schizophrenia.

Abnormalities in the structural integrity and connectivity of the medial temporal and the prefrontal cortex are well documented in schizophrenia, but it is unclear if they represent premorbid indicators of neuropathology. Studies of young relatives at high-risk for schizophrenia (HR) provide an opportunity to clarify this question. We herein provide data from a magnetic resonance imaging (MRI) study of these structures in young offspring of schizophrenia patients. A series of 17 young HR offspring of schizophrenic patients were compared with 22 healthy comparison subjects (HC). Morphometric comparisons of the right and left dorsolateral prefrontal cortex (DLPFC), and the anterior and posterior amygdala-hippocampal (A-H) complex were conducted using high-resolution whole brain T(1) weighted brain images. Compared with the HC group, HR subjects had significant decreases in intracranial volume. The volumes of the left anterior and posterior A-H complex were reduced in the HR subjects after adjusting for intracranial volume. HR subjects also showed a significant leftward (Right>Left) asymmetry of the anterior A-H complex compared to the HC subjects. No significant changes were seen in the DLPFC. Thus, lateralized alterations in the volume of the left A-H complex are evident in unaffected young offspring of schizophrenia patients and may be of neurodevelopmental origin. Follow-up studies are needed to examine the predictive value of these measures for future emergence of schizophrenia in at-risk individuals.

Adolescent↗

PubMed2002

Correlations between peripheral polyunsaturated fatty acid content and in vivo membrane phospholipid metabolites.

BACKGROUND: There is evidence for membrane abnormalities in schizophrenia. It is unclear whether the observed membrane deficits in peripheral cells parallel central membrane phospholipid metabolism. To address this question we examined the relations between red blood cell polyunsaturated fatty acids and brain phospholipid metabolites from different regions of interest in schizophrenia and healthy subjects. METHODS: Red blood cell membrane fatty acids were measured by capillary gas chromatography and in vivo brain phospholipid metabolite levels were measured using a multi-voxel (31)P Magnetic Resonance Spectroscopy technique on 11 first-episode, neuroleptic-naïve schizophrenic subjects and 11 normal control subjects. RESULTS: Both the total polyunsaturated fatty acids and the individual 20:4(n-6) contents were significantly correlated with the freely-mobile phosphomonoester [PME(s-tau(c))] levels (r =.5643, p =.0062 and r =.6729, p =.0006, respectively). The 18:2(n-6) polyunsaturated fatty acids content correlated positively with freely-mobile phosphodiester [PDE(s-tau(c))] levels (r =.5573, p =.0071). The above correlations were present in the combined right and left prefrontal region of the brain, while other regions including the basal ganglia, occipital, inferior parietal, superior temporal and centrum semiovale yielded no significant correlations. CONCLUSIONS: Our preliminary data support the association between the decreased red blood cell membrane phospholipid polyunsaturated fatty acids content and the decreased building blocks [PME(s-tau(c))] and breakdown products [PDE(s-tau(c))] of membrane phospholipids in the prefrontal region of first-episode, neuroleptic-naïve schizophrenic subjects.

Adolescent↗

PubMed2002

Increased gray matter volume in lithium-treated bipolar disorder patients.

Lithium's neurotrophic effects have been reported in several in vitro and ex vivo studies. Preliminary human studies with magnetic resonance imaging (MRI) and spectroscopy have recently provided evidence of lithium-induced increases in gray matter volumes and N-acetyl-aspartate levels. In order to further examine the hypothesis that lithium treatment would relate to detectable increases in gray matter brain content, we blindly measured gray and white matter volumes in MRI images of 12 untreated and 17 lithium-treated bipolar patients and 46 healthy controls. Using multivariate analysis of covariance with age and gender as covariates, we found that total gray matter volumes were significantly increased in lithium-treated (747.9 +/- 69.8 cm(3)) compared with untreated patients (639.2 +/- 91.2 cm(3); F = 10.6; d.f. = 1, 25; P = 0.003) and healthy individuals (675.8 +/- 61.8 cm(3); F = 17.4; d.f. = 1, 59; P < 0.001), suggesting in vivo effects of lithium on gray matter, which could possibly reflect lithium's neurotrophic effects.

Analysis of Variance↗

PubMed2002

Superior temporal gyrus volumes in maltreated children and adolescents with PTSD.

BACKGROUND: The structure and function of the superior temporal gyrus (STG), a structure involved in receptive and nonverbal auditory and language processing, is understudied in posttraumatic stress disorder (PTSD). Event-related potential abnormalities were previously reported in PTSD, implicating the existence of dysfunction in the primary auditory cortex and adjacent anterior auditory cortex of the STG in adult PTSD. METHODS: Anatomic magnetic resonance imaging (MRI) volumetric analysis of the superior temporal gyrus were performed in 43 maltreated children and adolescents with PTSD and 61 nonmaltreated healthy control subjects. RESULTS: Unadjusted STG gray matter volumes were larger in maltreated subjects with PTSD than in control subjects, whereas STG white matter volumes were smaller in maltreated subjects with PTSD than in control subjects. After adjusting for differences in cerebral volume, right, left, and total superior temporal gyrus volumes were relatively larger in PTSD subjects compared with control subjects. After covarying for differences in cerebral gray matter volumes, regression analysis showed that PTSD subjects had significantly greater STG gray matter volumes in most, and in particularly right-sided STG measurements. Furthermore, findings of significant side-by-diagnosis interactions for STG and STG gray but not white matter STG volumes suggest that there is a more pronounced right > left asymmetry in total and posterior STG volumes but a loss of the left > right asymmetry seen in total, anterior, and posterior STG gray matter volumes in PTSD subjects compared with control subjects. CONCLUSIONS: These STG findings may suggest developmental alterations in maltreatment-related pediatric PTSD.

Adolescent↗

PubMed2002

Superior temporal gyrus volumes in pediatric generalized anxiety disorder.

BACKGROUND: The essential symptoms of generalized anxiety disorder (GAD) are intrusive worry about everyday life circumstances and social competence, and associated autonomic hyperarousal. The amygdala, a brain region involved in fear and fear-related behaviors in animals, and its projections to the superior temporal gyrus (STG), thalamus, and to the prefrontal cortex are thought to comprise the neural basis of our abilities to interpret social behaviors. Larger amygdala volumes were previously reported in pediatric GAD; however, the brain regions involved in social intelligence were not examined in this pilot study. METHODS: Magnetic resonance imaging (MRI) was used to measure the STG, thalamus, and prefrontal volumes in 13 medically healthy child and adolescent subjects with generalized anxiety disorder (GAD) and 98 comparison subjects, who were at low familial risk for mood and psychotic disorders. Groups were similar in age, gender, height, weight, handedness, socioeconomic status, and full-scale IQ. RESULTS: The total, white matter, and gray matter STG volumes were significantly larger in GAD subjects compared with control subjects. Thalamus and prefrontal lobe volumes did not differ between groups. Findings of significant side-by-diagnosis interactions for STG and STG white matter volumes suggest that there is a more pronounced right > left asymmetry in total and STG white matter volumes in pediatric GAD subjects compared with control subjects. A significant correlation between the STG white matter percent asymmetry index with the child report of the Screen for Child Anxiety Related Emotional Disorders Scale was seen. CONCLUSIONS: These data agree with previous work implicating posterior right-hemispheric regions in anxiety disorders and may suggest developmental alterations in pediatric GAD.

Adolescent↗