Estimates of milk constituents from lactating bonnet macaque (Macaca radiata) mothers between two and seven months post-partum.

BACKGROUND: The literature regarding milk composition in non-human primates collected across offspring development is limited. We assayed milk samples from bonnet macaque (Macaca radiata) mothers as part of studies characterizing development of this species. METHODS: Milk was obtained when possible longitudinally from seven lactating bonnet macaque mothers. Samples were frozen until analysis. Individual samples were analyzed to determine the concentrations of electrolytes including sodium, potassium, calcium, chloride, and magnesium, as well as urea, protein, lipids, glucose, and lactose. RESULTS: A trend for increased lipids as well as protein percentage was noted with increasing infant age. Chloride and calcium showed an increase with age, whereas other electrolytes remained relatively stable across development. CONCLUSIONS: The composition of the milk of this particular macaque species was similar to other Old World primates as well as humans. These data add to the limited information available on milk constituents among mammals.

An extended motor network generates beta and gamma oscillatory perturbations during development.

This study examines the time course and neural generators of oscillatory beta and gamma motor responses in typically-developing children. Participants completed a unilateral flexion-extension task using each index finger as whole-head magnetoencephalography (MEG) data were acquired. These MEG data were imaged in the frequency-domain using spatial filtering and the resulting event-related synchronizations and desynchronizations (ERS/ERD) were subjected to voxel-wise statistical analyses to illuminate time-frequency specific activation patterns. Consistent with adult data, these children exhibited a pre-movement ERD that was strongest over the contralateral post-central gyrus, and a post-movement ERS response with the most prominent peak being in the contralateral precentral gyrus near premotor cortices. We also observed a high-frequency (approximately 80 Hz) ERS response that coincided with movement onset and was centered on the contralateral precentral gyrus, slightly superior and posterior to the beta ERS. In addition to pre- and post-central gyri activations, these children exhibited beta and gamma activity in supplementary motor areas (SMA) before and during movement, and beta activation in cerebellar cortices before and after movement. We believe the gamma synchronization may be an excellent candidate signal of basic cortical motor control, as the spatiotemporal dynamics indicate the primary motor cortex generates this response (and not the beta oscillations) which is closely yoked to the initial muscle activation. Lastly, these data suggest several additional neural regions including the SMA and cerebellum are involved in basic movements during development.

Schizoaffective disorder - a possible MEG auditory evoked field biomarker.

We recorded magnetoencephalographic auditory steady state responses (SSR) from eight schizoaffective (SAD) subjects and compared the resulting data with previously published findings in persons with schizophrenia (SZ) and controls. SAD subjects exhibited SSR responses similar to controls in the left hemisphere and greater than controls in the right hemisphere, whereas SZ subjects exhibited deficits in both amplitude and phase control in both hemispheres. Our findings suggest preservation of GABAergic inhibitory interneuronal control of layer 3 pyramidal cell activity in primary auditory cortex in SAD.

Brain size and brain/intracranial volume ratio in major mental illness.

BACKGROUND: This paper summarizes the findings of a long term study addressing the question of how several brain volume measure are related to three major mental illnesses in a Colorado subject group. It reports results obtained from a large N, collected and analyzed by the same laboratory over a multiyear period, with visually guided MRI segmentation being the primary initial analytic tool. METHODS: Intracerebral volume (ICV), total brain volume (TBV), ventricular volume (VV), ventricular/brain ratio (VBR), and TBV/ICV ratios were calculated from a total of 224 subject MRIs collected over a period of 13 years. Subject groups included controls (C, N = 89), and patients with schizophrenia (SZ, N = 58), bipolar disorder (BD, N = 51), and schizoaffective disorder (SAD, N = 26). RESULTS: ICV, TBV, and VV measures compared favorably with values obtained by other research groups, but in this study did not differ significantly between groups. TBV/ICV ratios were significantly decreased, and VBR increased, in the SZ and BD groups compared to the C group. The SAD group did not differ from C on any measure. CONCLUSIONS: In this study TBV/ICV and VBR ratios separated SZ and BD patients from controls. Of interest however, SAD patients did not differ from controls on these measures. The findings suggest that the gross measure of TBV may not reliably differ in the major mental illnesses to a degree useful in diagnosis, likely due to the intrinsic variability of the measures in question; the differences in VBR appear more robust across studies. Differences in some of these findings compared to earlier reports from several laboratories finding significant differences between groups in VV and TBV may relate to phenomenological drift, differences in analytic techniques, and possibly the "file drawer problem".

MEG auditory evoked fields suggest altered structural/functional asymmetry in primary but not secondary auditory cortex in bipolar disorder.

OBJECTIVES: Objective physiological indices independently characterizing affective and schizophreniform psychoses would contribute to our understanding of the nature of their relationships. Magnetoencephalography (MEG)-based metrics of altered structural/functional asymmetry in the superior temporal gyrus have previously been found to characterize schizophrenia at the level of both the primary auditory (AI) and the secondary auditory (AII) cortex. This study examines these markers in patients with bipolar disorder, with the goal of improved understanding of the patterns of brain asymmetry that may independently characterize affective and schizophreniform psychosis. METHODS: We studied 17 euthymic bipolar subjects and 17 matched controls. Auditory evoked fields were generated by both 40 Hz auditory stimuli eliciting steady state gamma band (SSR), activating the AI cortex, and discrete 1 kHz tone pips, activating the AII cortex. MEG was recorded from the hemisphere contralateral to the ear stimulated using a 37-channel MEG system. Source location estimates were calculated in both left and right hemispheres. Neuroanatomical location estimates for medial Heschl's gyri were determined from magnetic resonance images for correlation with MEG source locations. RESULTS: Bipolar subjects failed to demonstrate normal laterality of SSR AI responses, indicating altered patterns of asymmetry at the level of AI cortex, but demonstrated normal asymmetry of AII responses (right anterior to left). Medial Heschl's gyri centroids were similarly lateralized in both groups, however (right anterior to left), dissociating function from structure in the AI cortex in the bipolar group. CONCLUSIONS: The findings are compatible with altered functional/structural relationships, including diminished left-right hemisphere asymmetry of the AI, but not the AII cortex in bipolar disorder. In schizophrenia, both the AI and AII cortices exhibit such derangements; thus, the findings support both shared and nonshared features of auditory cortical disruption between the two disorders. This functional disorganization may help explain previously reported decreases in amplitude and phase synchrony of SSR gamma band responses in bipolar subjects, suggesting impaired neocortical synchrony in AI, possibly at a cortico-thalamic level, but perhaps not extending to heteromodal association cortex, and may relate to the cognitive impairments found in bipolar disorder.

Aberrant high-frequency desynchronization of cerebellar cortices in early-onset psychosis.

Sensorimotor integration deficits are routinely observed in both schizophreniform and mood-disordered psychoses. Neurobiological theories of schizophrenia and related psychoses have proposed that aberrations in large-scale cortico-thalamic-cerebellar-thalamic-cortical loops may underlie integration abnormalities, and that such dysfunctional connectivity may be central to the pathophysiology. In this study, we utilized a basic mechanoreception task to probe cortical-cerebellar circuitry in early-onset psychosis. Ten adolescents with psychosis and 10 controls completed unilateral tactile stimulation of the right and left index finger, as whole-head magnetoencephalography (MEG) data were acquired. MEG data were imaged in the frequency domain, using spatial filtering, and the resulting event-related synchronizations and desynchronizations (ERS/ERD) were subjected to voxel-wise analyses of group and task effects using statistical parametric mapping. Our results indicated bilateral ERD activation of cerebellar regions and postcentral gyri in both groups during stimulation of either hand. Interestingly, during left finger stimulations, adolescents with psychosis exhibited greater alpha and gamma ERD activity in right cerebellar cortices relative to controls. Subjects with psychosis also showed greater ERD in bilateral cerebellum and the right postcentral gyrus during right finger stimulation, and these differences were statistically stronger for higher frequency bins. Lastly, controls exhibited greater alpha ERS of the right postcentral gyrus during right finger stimulation. These findings provide new data on the neurodevelopmental trajectory of basic mechanoreception in adolescents, and also indicate aberrant cerebellar functioning in early-onset psychoses, especially in the right cerebellum, which may be the crucial dysfunctional node in cortico-thalamic-cerebellar-thalamic-cortical circuits.

Cortical gamma generators suggest abnormal auditory circuitry in early-onset psychosis.

Neurobiological theories of schizophrenia and related psychoses have increasingly emphasized impaired neuronal coordination (i.e., dysfunctional connectivity) as central to the pathophysiology. Although neuroimaging evidence has mostly corroborated these accounts, the basic mechanism(s) of reduced functional connectivity remains elusive. In this study, we examine the developmental trajectory and underlying mechanism(s) of dysfunctional connectivity by using gamma oscillatory power as an index of local and long-range circuit integrity. An early-onset psychosis group and a matched cohort of typically developing adolescents listened to monaurally presented click-trains, as whole-head magnetoencephalography data were acquired. Consistent with previous work, gamma-band power was significantly higher in right auditory cortices across groups and conditions. However, patients exhibited significantly reduced overall gamma power relative to controls, and showed a reduced ear-of-stimulation effect indicating that ipsi- versus contralateral presentation had less impact on hemispheric power. Gamma-frequency oscillations are thought to be dependent on gamma-aminobutyric acidergic interneuronal networks, thus these patients' impairment in generating and/or maintaining such activity may indicate that local circuit integrity is at least partially compromised early in the disease process. In addition, patients also showed abnormality in long-range networks (i.e., ear-of-stimulation effects) potentially suggesting that multiple stages along auditory pathways contribute to connectivity aberrations found in patients with psychosis.

An institutional postdoctoral research training program: predictors of publication rate and federal funding success of its graduates.

OBJECTIVE: The National Institute of Mental Health funds institutional National Research Service Awards (NRSA) to provide postdoctoral research training. While peer-reviewed publications are the most common outcome measure utilized, there has been little discussion of how publications should be counted or what factors impact the long-term publication rates of trainees in these programs. METHODS: The authors reviewed current curricula vitae from 92 graduates of an institutional NRSA and from the faculty mentors of that program to assess publications through 2005. Publications were weighted based on peer versus non-peer-reviewed and authorship position. Trainee and mentor factors were assessed for their impact on publication rates and on becoming principal investigators of larger scale federal grants such as a National Institutes of Health (NIH) R01. RESULTS: Weighted publication scores correlate with total publication rates at such a high rate that the two scores can be used interchangeably. Forty-three percent of graduates average at least one publication per year after completing the postdoctoral program; 20% were listed as an independent investigator on a larger federal grant. The number of publications published during postdoctoral training and additional funded training beyond that provided by the institutional NRSA are correlated with increased posttraining program publication rates; other factors including gender, terminal degree, number of publications prior to postdoctoral training, and mentor variables had no significant impact. Additional funded training, male gender, and increased time since completion of the training are associated with increased likelihood of larger grant federal funding. CONCLUSION: Weighting publications by whether they were peer-reviewed and by authorship position appears to have little benefit over a simple counting of the number of publications. Publication during research training and the pursuit of funding for additional individual research training may be appropriate short-term goals within an institutional research training program.

Cortical source estimates of gamma band amplitude and phase are different in schizophrenia.

Reductions in gamma band phase synchrony and evoked power have been reported in schizophrenic subjects in response to auditory stimuli. These results have been observed in the EEG at one or two electrode sites. We wished to extend these results using magnetic field data to estimate the responses at the neural generators themselves in each hemisphere. Whole head magnetoencephalographic (MEG) recordings were used to estimate the phase and amplitude behavior of sources in primary auditory cortex in both hemispheres of schizophrenic and comparison subjects. Both ipsi- and contralateral cases were evaluated using a driving (40 Hz modulated 1 kHz carrier) and a non-driving (1 kHz tone) stimulus. We used source space projection (SSP) to collapse the magnetic field data into estimates of the time course of source strengths in individual trials. Complex wavelet based time-frequency decomposition was used to compute inter-trial phase locking factor (PLF), and mean evoked and induced amplitude for each cortical generator. Schizophrenic subjects showed reduced SSP PLF and evoked source strength for contralateral generators responding to the driving stimulus in both hemispheres. For the pure tone stimulus, only the left hemisphere PLF's in the transient window were reduced. In contrast, subjects with schizophrenia exhibited higher induced 40 Hz power to both stimulus types, consistent with the reduced PLF findings. The method of SSP combined with wavelet based complex demodulation produces a significant improvement in signal-to-noise ratio, and directly estimates the activity of the cortical generators responsible for gamma band auditory MEG evoked fields. Schizophrenic subjects exhibit significant impairment of generation and phase locking of this activity in auditory cortex, suggesting an impairment of GABA-ergic inhibitory interneuronal modulation of pyramidal cell activity.

Children and adolescents with autism exhibit reduced MEG steady-state gamma responses.

BACKGROUND: Recent neuroimaging studies of autism have indicated reduced functional connectivity during both cognitive tasks and rest. These data suggest long-range connectivity may be compromised in this disorder, and current neurological theories of autism contend disrupted inter-regional interactions may be an underlying mechanism explaining behavioral symptomatology. However, it is unclear whether deficient neuronal communication is attributable to fewer long-range tracts or more of a local deficit in neural circuitry. This study examines the integrity of local circuitry by focusing on gamma band activity in auditory cortices of children and adolescents with autism. METHODS: Ten children and adolescents with autism and 10 matched controls participated. Both groups listened to 500 ms duration monaural click trains with a 25 ms inter-click interval, as magnetoencephalography was acquired from the contralateral hemisphere. To estimate 40 Hz spectral power density, we performed time-frequency decomposition of the single-trial magnetic steady-state response data using complex demodulation. RESULTS: Children and adolescents with autism exhibited significantly reduced left hemispheric 40 Hz power from 200-500 ms post-stimulus onset. In contrast, no significant between group differences were observed for right hemispheric cortices. CONCLUSIONS: The production and/or maintenance of left hemispheric gamma oscillations appeared abnormal in participants with autism. We interpret these data as indicating that in autism, particular brain regions may be unable to generate the high-frequency activity likely necessary for binding and other forms of inter-regional interactions. These findings augment connectivity theories of autism with novel evidence that aberrations in local circuitry could underlie putative deficiencies in long-range neural communication.

Neuromagnetic evidence of broader auditory cortical tuning in schizophrenia.

Deficits in basic auditory perception have been described in schizophrenia. Previous electrophysiological imaging research has documented a structure-function disassociation in the auditory system and altered tonotopic mapping in schizophrenia. The present study examined auditory cortical tuning in patients with schizophrenia. Eighteen patients with schizophrenia and 15 comparison subjects were recorded in a magnetoencephalographic (MEG) experiment of auditory tuning. Auditory cortical tuning at 1 kHz was examined by delivering 1 kHz pure tones in conjunction with pure tones at 5 frequencies surrounding and including 1 kHz. Source reconstruction data were examined for evidence of frequency specificity for the M100 component. There was a significant broadening of tuning in the schizophrenia group evident for the source amplitude of the M100. The frequently reported reduction in anterior-posterior source asymmetry for individuals with schizophrenia was replicated in this experiment. No relationships between symptom severity ratings and MEG measures were observed. This finding suggests that the frequency specificity of the M100 auditory evoked field is disturbed in schizophrenia, and may help explain the relatively poor behavioral performance of schizophrenia patients on simple frequency discrimination tasks.

Aberrant functional organization and maturation in early-onset psychosis: evidence from magnetoencephalography.

Studies of the location of somatosensory and auditory cortical responses have shown anomalous hemispheric asymmetries in a variety of neurodevelopmental disorders. To date, abnormal asymmetries in the somatosensory region have shown greater specificity, being reported only in psychotic adults. This study examines the functional organization of the somatosensory cortices using magnetoencephalography in adolescents with childhood-onset psychotic disorders. Eighteen young outpatients with history of psychotic illness and 15 healthy adolescents participated. Both groups underwent stimulation of the index finger as magnetoencephalography was acquired from the contralateral hemisphere. Neural generators of the M50 somatosensory response were modeled using an equivalent current dipole for each hemisphere, and later investigated for systematic variation with diagnosis. Consistent with adult psychosis data, adolescent patients showed hemispheric symmetry in the anterior-posterior dimension. In controls, a reversed pattern of hemispheric asymmetry was observed relative to previous findings in normal adults [Reite, M., Teale, P., Rojas, D.C., Benkers, T.L., Carlson, J., 2003. Anomalous somatosensory cortical localization in schizophrenia. American Journal of Psychiatry 160, 2148-2153], but trend-level correlations suggested source location became more adult-like during the transition from adolescence to adulthood. Source parameters also exhibited robust inter-hemispheric correlations only in adolescent controls. In sum, source locations, patterns of cerebral lateralization, and inter-hemispheric correlations all distinguish patients from their normally developing cohort. These findings suggest aberrant maturation underlies the reduction in cerebral laterality associated with psychosis.

A voxel-based morphometry study of gray matter in parents of children with autism.

Previous structural imaging studies of autistic individuals have identified gray matter abnormalities. It remains unclear, however, which abnormalities contribute to the etiology of autism and, among these abnormalities, which reflect genetic factors. Using voxel-based morphometry, we compared regional gray matter volume in 23 parents of autistic children to an age and sex-matched control sample. We identified relative local gray matter volume increases and decreases in the parent group that are consistent with previous research with autistic individuals. Further, differences were identified in regions that are functionally associated with social-cognitive and motor processes that are impaired in autism. This investigation constitutes the first whole-brain study of regional brain volume in the parents of autistic children, and suggests that a number of structural changes observed in autism may be familial.

Development of the 40Hz steady state auditory evoked magnetic field from ages 5 to 52.

OBJECTIVE: Adults exhibit strong auditory 40 Hz magnetic steady state responses (SSR). Although EEG measured SSR has been studied in children, the developmental course of the magnetic SSR is unknown. METHODS: Sixty-nine healthy subjects ranging in age from 5 to 52 years participated in a magnetoencephalographic (MEG) study. Stimuli were monaural 500 ms duration click trains with a 25 ms inter-click interval. Contralateral magnetic responses for both hemispheres were recorded with a 37-channel MEG system. Responses were averaged and examined using wavelet-based time-frequency analysis. Source analyses were also conducted on a subset of the data. RESULTS: Gamma power from 200 to 500 ms post-stimulus onset was computed and was significantly related to subject age in both hemispheres. Hemispheric asymmetry was observed for the anterior-posterior SSR source locations, suggestive of asymmetry similar to that previously described for the SSR and other auditory evoked magnetic field components. CONCLUSIONS: The 40 Hz power findings are generally consistent with previous EEG studies of steady state responses in children showing age-related changes in the 40 Hz SSR. SIGNIFICANCE: Age-related changes in the strength of the magnetic 40 Hz SSR may continue to develop well beyond early childhood, which should be taken into consideration in planning future studies using adolescents and young adults.

Regional gray matter volumetric changes in autism associated with social and repetitive behavior symptoms.

BACKGROUND: Although differences in brain anatomy in autism have been difficult to replicate using manual tracing methods, automated whole brain analyses have begun to find consistent differences in regions of the brain associated with the social cognitive processes that are often impaired in autism. We attempted to replicate these whole brain studies and to correlate regional volume changes with several autism symptom measures. METHODS: We performed MRI scans on 24 individuals diagnosed with DSM-IV autistic disorder and compared those to scans from 23 healthy comparison subjects matched on age. All participants were male. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using voxel-based morphometry (VBM). RESULTS: Controlling for age and total gray matter volume, the volumes of the medial frontal gyri, left pre-central gyrus, right post-central gyrus, right fusiform gyrus, caudate nuclei and the left hippocampus were larger in the autism group relative to controls. Regions exhibiting smaller volumes in the autism group were observed exclusively in the cerebellum. Significant partial correlations were found between the volumes of the caudate nuclei, multiple frontal and temporal regions, the cerebellum and a measure of repetitive behaviors, controlling for total gray matter volume. Social and communication deficits in autism were also associated with caudate, cerebellar, and precuneus volumes, as well as with frontal and temporal lobe regional volumes. CONCLUSION: Gray matter enlargement was observed in areas that have been functionally identified as important in social-cognitive processes, such as the medial frontal gyri, sensorimotor cortex and middle temporal gyrus. Additionally, we have shown that VBM is sensitive to associations between social and repetitive behaviors and regional brain volumes in autism.

Planum temporale volume in children and adolescents with autism.

Previous research has revealed a lack of planum temporale (PT) asymmetry in adults with autism. This finding is now extended to children and adolescents with the disorder. MRI scans were obtained from 12 children with autism and 12 gender, handedness and age-matched comparison participants. The volume of gray matter in the PT and Heschl's gyrus (HG) in both hemispheres was measured. PT volume was larger in the left hemisphere than in the right in the comparison, but not the autism group. This specifically reflected reduced volume of the left PT in the autism group. There were noted differences in the overall morphological appearance of the right Sylvian fissure in the autism group, but no volumetric difference in the right PT. No differences in HG volumes were observed between the two groups. Lack of PT asymmetry may suggest an early neurodevelopmental disturbance in autism.

Reduced laterality of the source locations for generators of the auditory steady-state field in schizophrenia.

BACKGROUND: Reduced hemispheric asymmetry of evoked field generators in schizophrenia in secondary auditory cortex has been replicated with mixed success. This disparity is possibly due to the complex nature of the 100-msec generators typically investigated. In this study, we evaluated a source located in primary auditory cortex, responsible for the steady-state response, to determine whether similar asymmetries were present. METHODS: Contralateral evoked fields were recorded with a 37-channel neuromagnetometer in response to 40-Hz pulse trains. Dipole models were used to localize the sources in both hemispheres of schizophrenic subjects (n = 17) and normal control subjects (n = 18). RESULTS: Control subjects were asymmetrically lateralized, with sources in the right hemisphere approximately 6 mm further anterior than those on the left. In contrast, schizophrenic subjects showed no significant difference between hemispheres. CONCLUSIONS: The findings support theories linking schizophrenia to disturbed asymmetry of temporal lobe function. The steady-state response, having a more discrete Heschl's gyrus generator location, may be better suited for evaluating auditory asymmetry.

Alterations in tonotopy and auditory cerebral asymmetry in schizophrenia.

BACKGROUND: Deficits in basic auditory perception have been described in schizophrenia. Previous electrophysiologic imaging research has documented a structure-function disassociation in the auditory system in schizophrenia. This study examines whether the most fundamental level of auditory cortical organization, tonotopy, is altered in schizophrenia. METHODS: The tonotopic organization for five tone frequencies in 19 patients with schizophrenia and 22 comparison subjects was evaluated using magnetoencephalography. Auditory evoked magnetic field dipole locations were examined for the N100m component for each frequency. RESULTS: The expected linear relationship between depth and frequency was found in the comparison subjects but not in the schizophrenia group (p <.004). In addition, normal anterior-posterior asymmetry of the N100m was found to be reduced at all five stimulation frequencies employed in the study (p <.04). No relationships between clinical symptom ratings and either tonotopy or asymmetry were observed. CONCLUSIONS: This finding suggests that the tonotopic organization of the auditory cortex in schizophrenia is disturbed and may help explain the relatively poor behavioral performance of schizophrenia patients on simple frequency discrimination tasks. Alterations in fundamental sensory organization may underlie or interact with higher order cognitive mechanisms to produce changes in cognitive task performance.

Anomalous somatosensory cortical localization in schizophrenia.

OBJECTIVE: Schizophrenia has been reported to be associated with altered localization of regions responding to sound in the auditory cortex, suggesting possible cortical reorganization accompanying the disorder, but it is not clear whether such disturbances are present in any primary sensory cortex other than the auditory. This study examines magnetoencephalographic localization of field sources evoked by tactile stimulation generated in area 3b of the primary somatosensory cortex in patients with schizophrenia compared with normal subjects. METHOD: A total of 29 subjects participated; 14 were patients with schizophrenia, and 15 were normal comparison subjects. Equivalent current dipole generators in both hemispheres were used to model the sources of the 50-msec latency somatosensory evoked field (M50) components produced by contralateral tactile mechanoreceptor stimulation of the tip of the index finger. RESULTS: Compared with normal subjects, patients with schizophrenia demonstrated reversed asymmetry (left anterior to right) and relatively anterior and inferior displacement of the M50 equivalent current dipole location in the left hemisphere. CONCLUSIONS: Cerebral lateralization and localization of the M50 distinguished patients with schizophrenia from normal subjects. These findings suggest the possibility of anatomical displacement and/or disturbed organization of the primary sensory cortex in schizophrenia.

Hippocampus and amygdala volumes in parents of children with autistic disorder.

OBJECTIVE: Structural and functional abnormalities in the medial temporal lobe, particularly the hippocampus and amygdala, have been described in people with autism. The authors hypothesized that parents of children with a diagnosis of autistic disorder would show similar changes in these structures. METHOD: Magnetic resonance imaging scans were performed in 17 biological parents of children with a diagnosis of DSM-IV autistic disorder. The scans were compared with scans from 15 adults with autistic disorder and 17 age-matched comparison subjects with no personal or familial history of autism. The volumes of the hippocampus, amygdala, and total brain were measured in all participants. RESULTS: The volume of the left hippocampus was larger in both the parents of children with autistic disorder and the adults with autistic disorder, relative to the comparison subjects. The hippocampus was significantly larger in the adults with autistic disorder than in the parents of children with autistic disorder. The left amygdala was smaller in the adults with autistic disorder, relative to the other two groups. No differences in total brain volume were observed between the three groups. CONCLUSIONS: The finding of larger hippocampal volume in autism is suggestive of abnormal early neurodevelopmental processes but is partly consistent with only one prior study and contradicts the findings of several others. The finding of larger hippocampal volume for the parental group suggests a potential genetic basis for hippocampal abnormalities in autism.