Adolescent Binge Drinking Is Associated With Accelerated Decline of Gray Matter Volume.

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan-Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results of this study highlight the negative effects of binge drinking on the developing brain. Our results present novel findings that cortical GMV decreases were greater in closer proximity to binge drinking episodes in a dose-response manner. This relation suggests a causal effect and raises the possibility that normal growth trajectories may be reinstated with alcohol abstinence.

Trajectories of brain development reveal times of risk and factors promoting resilience to alcohol use during adolescence.

Alcohol use disorder (AUD) is recognized as harmful for the developing brain. Numerous studies have sought environmental and genetic risk factors that predict the development of AUD, but recently identified resilience factors have emerged as protective. This chapter reviews normal processes of brain development in adolescence and emerging adulthood, delineates disturbed growth neurotrajectories related to heavy drinking, and identifies potential endogenous, experiential, and time-linked brain markers of resilience. For example, concurrent high dorsolateral prefrontal activation serving inhibitory control and low nucleus accumbens activation serving reward functions engender positive adaptation and low alcohol use. Also discussed is the role that moderating factors have in promoting risk for or resilience to AUD. Longitudinal research on the effects of all levels of alcohol drinking on the developing brain remains crucial and should be pursued in the context of resilience, which is a promising direction for identifying protective biomarkers against developing AUDs.

The neural correlates of priming emotion and reward systems for conflict processing in alcoholics.

Emotional dysregulation in alcoholism (ALC) may result from disturbed inhibitory mechanisms. We therefore tested emotion and alcohol cue reactivity and inhibitory processes using negative priming. To test the neural correlates of cue reactivity and negative priming, 26 ALC and 26 age-matched controls underwent functional MRI performing a Stroop color match-to-sample task. In cue reactivity trials, task-irrelevant emotion and alcohol-related pictures were interspersed between color samples and color words. In negative priming trials, pictures primed the semantic content of an alcohol or emotion Stroop word. Behaviorally, both groups showed response facilitation to picture cue trials and response inhibition to primed trials. For cue reactivity to emotion and alcohol pictures, ALC showed midbrain-limbic activation. By contrast, controls activated frontoparietal executive control regions. Greater midbrain-hippocampal activation in ALC correlated with higher amounts of lifetime alcohol consumption and higher anxiety. With negative priming, ALC exhibited frontal cortical but not midbrain-hippocampal activation, similar to the pattern observed in controls. Higher frontal activation to alcohol-priming correlated with less craving and to emotion-priming with fewer depressive symptoms. The findings suggest that neurofunctional systems in ALC can be primed to deal with upcoming emotion- and alcohol-related conflict and can overcome the prepotent midbrain-limbic cue reactivity response.

Callosal involvement in a lateralized stroop task in alcoholic and healthy subjects.

To investigate the role of interhemispheric attentional processes, 25 alcoholic and 28 control subjects were tested with a Stroop match-to-sample task and callosal areas were measured with magnetic resonance imaging. Stroop color-word stimuli were presented to the left or right visual field (VF) and were preceded by a color cue that did or did not match the word's color. For matching colors, both groups showed a right VF advantage; for nonmatching colors, controls showed a left VF advantage, whereas alcoholic subjects showed no VF advantage. For nonmatch trials, VF advantage correlated with callosal splenium area in controls but not alcoholic subjects, supporting the position that information presented to the nonpreferred hemisphere is transmitted via the splenium to the hemisphere specialized for efficient processing. The authors speculate that alcoholism-associated callosal thinning disrupts this processing route.

Brain responses to emotional salience and reward in alcohol use disorder.

Heightened neural responsiveness of alcoholics to alcohol cues and social emotion may impede sobriety. To test mesocorticolimbic network responsivity, 10 (8 men) alcohol use disorder (AUD) patients sober for 3 weeks to 10 months and 11 (8 men) controls underwent fMRI whilst viewing pictures of alcohol and non-alcohol beverages and of emotional faces (happy, sad, angry). AUD and controls showed similarities in mesocorticolimbic activity: both groups activated fusiform for emotional faces and hippocampal and pallidum regions during alcohol picture processing. In AUD, less fusiform activity to emotional faces and more pallidum activity to alcohol pictures were associated with longer sobriety. Using graph theory-based network efficiency measures to specify the role of the mesocorticolimbic network nodes for emotion and reward in sober AUD revealed that the left hippocampus was less efficiently connected with the other task-activated network regions in AUD than controls when viewing emotional faces, while the pallidum was more efficiently connected when viewing alcohol beverages. Together our findings identified lower occipito-temporal sensitivity to emotional faces and enhanced striatal sensitivity to alcohol stimuli in AUD than controls. Considering the role of the striatum in encoding reward, its activation enhancement with longer sobriety may reflect adaptive neural changes in the first year of drinking cessation and mesocorticolimbic system vulnerability for encoding emotional salience and reward potentially affecting executive control ability and relapse propensity during abstinence.

Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study.

BACKGROUND: We sought to determine whether the brain dysmorphology previously observed cross-sectionally in people with schizophrenia progresses over time and whether such progression is related to the severity of the illness course. SUBJECTS AND METHODS: Men with chronic schizophrenia (n = 24) and control men (n = 25) received 2 brain magnetic resonance imaging scans, on average 4 years apart. Changes in brain volume were adjusted for head-repositioning error and expressed as slopes (cubic centimeters per year). Clinical course severity for the schizophrenic patients was assessed using the mean of time 1 and time 2 Brief Psychiatric Rating Scale (BPRS) scores and the percentage of time the patient was hospitalized during the interscan interval. RESULTS: Schizophrenic patients exhibited faster volume decline than control subjects in right frontal gray matter and bilateral posterior superior temporal gray matter, as well as faster cerebrospinal fluid volume expansion in right frontal sulci, left lateral ventricle, and bilateral prefrontal and posterior superior temporal sulci. Faster rates of frontal sulcal expansion were related to greater BPRS total and positive symptom scores and longer time hospitalized. Prefrontal gray matter decline and sulcal expansion were associated with greater BPRS negative symptom scores and longer time hospitalized. Temporal lobe gray matter decline was associated with greater BPRS total and negative symptom scores. CONCLUSIONS: This controlled study revealed that patients with chronic schizophrenia exhibited accelerated frontotemporal cortical gray matter decline and cortical sulcal and lateral ventricular expansion. Further, greater clinical severity was associated with faster rates of frontotemporal brain volume changes. These observations are consistent with a progressive pathophysiological process but need to be replicated in a larger sample.

Widespread cerebral gray matter volume deficits in schizophrenia.

Magnetic resonance imaging was used to investigate whether the structural brain differences commonly observed in patients with schizophrenia as compared with normal control subjects are specific to gray or white matter, and furthermore whether such abnormalities are localizable to circumscribed cortical regions. Accordingly, 22 patients meeting DSM-III-R criteria for schizophrenia and 20 healthy community volunteers, all 23 to 45 years old, received magnetic resonance imaging scans. Seven axial magnetic resonance imaging sections of 5-mm thickness were segmented into cerebrospinal fluid, gray matter, and white matter compartments and used for volumetric quantification. For the healthy control subjects, age correlated significantly with the percentage of all magnetic resonance imaging sections taken up by gray matter but not white matter. After correcting for the normal effect of age, the schizophrenic group was found to have significantly less gray matter than the control group but no difference in white matter; ventricular volume was 34% greater in the schizophrenic group. The schizophrenic group had less gray matter in all six cortical subregions analyzed; these differences attained statistical significance for all but the parietal measure. These findings have implications for studies of localized gray matter abnormalities and suggest that regional brain volume measurements need to be expressed in the context of possible widespread gray matter volume deficits in schizophrenia.

Proton magnetic resonance spectroscopic imaging of cortical gray and white matter in schizophrenia.

OBJECTIVE: To apply in vivo proton magnetic resonance spectroscopy imaging estimates of N-acetylaspartate (NAA), a neuronal marker, to clarify the relative contribution of neuronal and glial changes to the widespread volume deficit of cortical gray matter seen in patients with schizophrenia with magnetic resonance images. METHODS: Ten male veterans meeting criteria of the DSM-IV, for schizophrenia and 9 healthy age-matched men for comparison were scanned using spectroscopic, anatomical, and field-map sequences. Instrument and collection variables were standardized to allow an estimation of comparable values for NAA, choline, and creatine for all subjects. Metabolite values from each voxel on 3 upper cortical slices were regressed against the gray tissue proportion of that voxel to derive estimates of gray and white matter NAA, creatine, and choline concentrations. RESULTS: The volume of cortical gray matter was reduced in patients with schizophrenia, but NAA signal intensity from a comparable region was normal. In contrast, the volume of cortical white matter was normal in patients with schizophrenia, but NAA signal intensity from a comparable region was reduced. CONCLUSIONS: The lack of reduction in gray matter NAA signal intensity suggests that the cortical gray matter deficit in these patients involved both neuronal and glial compartments rather than a neurodegenerative process in which there is a decrease in the neuronal relative to the glial compartment. Reduced white matter NAA signal intensity without a white matter volume deficit may reflect abnormal axonal connections.

A controlled study of cortical gray matter and ventricular changes in alcoholic men over a 5-year interval.

BACKGROUND: We report on structural brain changes during a 5-year period in healthy control and alcoholic men. METHODS: Alcoholic patients (n = 16), from an initial group of 58 who underwent brain magnetic resonance imaging scanning while in treatment, were rescanned with the same acquisition sequence approximately 5 years later. Control subjects (n = 28) spanning the same age range also were scanned twice at a comparable interval. Changes in brain volume were corrected for error due to differences in head placement between scans and expressed as slopes (cubic centimeters per year), percentage of change over baseline for the control subjects, and standardized change for the alcoholic patients. The alcoholic patients varied considerably in the percentage of time that symptoms of alcohol dependence were present and in the amount of alcohol consumed during follow-up. RESULTS: The cortical gray matter diminished in volume over time in the control subjects, most prominently in the prefrontal cortex, while the lateral and third ventricles enlarged. The alcoholic patients showed similar age-related changes with a greater rate of gray matter volume loss than the control subjects in the anterior superior temporal lobe. The amount of alcohol consumed during follow-up predicted the rate of cortical gray matter volume loss, as well as sulcal expansion. The rate of ventricular enlargement in alcoholic patients who maintained virtual sobriety was comparable to that in the control subjects. CONCLUSIONS: During a 5-year period, brain volume shrinkage is exaggerated in the prefrontal cortex in normal aging with additional loss in the anterior superior temporal cortex in alcoholism. The association of cortical gray matter volume reduction with alcohol consumption over time suggests that continued alcohol abuse results in progressive brain tissue volume shrinkage.

Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging.

BACKGROUND: Current investigations suggest that brain white matter may be qualitatively altered in schizophrenia even in the face of normal white matter volume. Diffusion tensor imaging provides a new approach for quantifying the directional coherence and possibly connectivity of white matter fibers in vivo. METHODS: Ten men who were veterans of the US Armed Forces and met the DSM-IV criteria for schizophrenia and 10 healthy, age-matched control men were scanned using magnetic resonance diffusion tensor imaging and magnetic resonance structural imaging. RESULTS: Relative to controls, the patients with schizophrenia exhibited lower anisotropy in white matter, despite absence of a white matter volume deficit. In contrast to the white matter pattern, gray matter anisotropy did not distinguish the groups, even though the patients with schizophrenia had a significant gray matter volume deficit. The abnormal white matter anisotropy in patients with schizophrenia was present in both hemispheres and was widespread, extending from the frontal to occipital brain regions. CONCLUSIONS: Despite the small sample size, diffusion tensor imaging was powerful enough to yield significant group differences, indicating widespread alteration in brain white matter integrity but not necessarily white matter volume in schizophrenia.

In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) and normal aging result in cortical gray matter volume deficits. The extent to which the remaining cortex is functionally compromised can be estimated in vivo with magnetic resonance spectroscopic imaging. OBJECTIVE: To assess the effects of age and dementia on gray matter and white matter concentrations of 3 metabolites visible in the proton spectrum: N-acetyl compounds, present only in living neurons; creatine plus phosphocreatine, reflecting high-energy phosphate metabolism; and choline, increasing with membrane synthesis and degradation. METHOD: Fifteen healthy young individuals, 19 healthy elderly individuals, and 16 patients with AD underwent 3-dimensional magnetic resonance spectroscopic imaging and memory and language testing. RESULTS: Gray matter N-acetyl compound concentrations (signal intensity corrected for the amount of brain tissue contributing to the magnetic resonance spectroscopic imaging signal) was significantly reduced only in patients with AD, even though both the AD and elderly control groups had substantial gray matter volume deficits relative to the young control group. Both the healthy elderly and AD groups had abnormally high gray matter creatine plus phosphocreatine concentrations. Gray matter choline concentrations were higher in the elderly than the younger controls, and even higher in the AD group than in the elderly control group. Functional significance of these findings was supported by correlations between poorer performance on recognition memory tests and lower gray matter N-acetyl compounds in elderly controls and higher gray matter creatine plus phosphocreatine and choline concentrations in patients with AD. CONCLUSION: Cortical gray matter volume deficits in patients with AD are accompanied by disease-related increases in gray matter choline concentrations suggestive of cellular degeneration and reduced N-acetyl compound concentrations, with possible effects on behavioral function.

Contribution of alcohol abuse to cerebellar volume deficits in men with schizophrenia.

BACKGROUND: It is controversial whether cerebellar tissue volume deficits occur in schizophrenia and, if so, what regions and tissue types are affected. Complicating such investigations is the high incidence of alcoholism comorbidity in patients with schizophrenia that itself can contribute to cerebellar abnormalities. METHOD: We studied 61 healthy men (control subjects), 25 men with alcoholism, 27 men with schizophrenia, and 19 men comorbid for schizophrenia and alcoholism with the use of magnetic resonance imaging. Cerebellar structures were outlined manually, tissue classification was determined statistically, and regional volumes were corrected for normal variation in head size and age. RESULTS: Patients with schizophrenia alone had enlarged fourth ventricles (1.5 SD relative to controls) but showed no cerebellar tissue volume deficits. The alcoholic group had gray and white matter vermian deficits (-0.5 SD), most prominent in anterior superior lobules, and gray matter hemisphere deficits (-0.8 SD), but not fourth ventricle enlargement. The comorbid group had cerebellar hemisphere (-1.3 SD) and vermian gray matter volume deficits (-0.7 SD) and fourth ventricular enlargement (1.6 SD); these abnormalities were greater than in either single-diagnosis group, despite significantly lower levels of alcohol consumption compared with the alcoholic group. Gray matter volume in the anterior superior vermis correlated with lifetime alcohol consumption in the schizophrenic and comorbid groups when combined. CONCLUSIONS: Cerebellar tissue volume deficits were detected in schizophrenia only when accompanied by alcoholism. By contrast, fourth ventricular enlargement occurred in schizophrenia even without alcoholism, although it was exacerbated by alcoholism. These findings support a model of cerebellar supersensitivity to alcohol-related tissue volume deficits in schizophrenia.

Structural magnetic resonance imaging abnormalities in men with severe chronic schizophrenia and an early age at clinical onset.

BACKGROUND: Early age at onset of schizophrenia often signifies a more severe form of the illness. However, the relationship between age at onset and brain abnormalities has not been established. We assessed temporal-limbic morphometry in severely ill men with chronic schizophrenia who had a relatively early onset of illness and examined the relationships among regional brain volumes, clinical symptoms, and age at illness onset. METHOD: Temporal lobe, superior temporal gyrus, hippocampus, temporal horn, lateral ventricles, third ventricle, and frontoparietal volumes were measured on magnetic resonance imaging data from 56 schizophrenic men (mean [SD] age at illness onset, 16.6 [4.2] years) recruited from a state hospital and 52 age- and range-matched healthy control men. RESULTS: Patients had significantly smaller gray matter volumes in the temporal lobe, superior temporal gyrus, and frontoparietal regions; smaller temporal lobe white matter volumes; and larger cerebrospinal fluid volumes for temporal lobe sulci and the 3 ventricular measures. There were no group differences in hippocampal volumes. Psychotic symptom subscores from the Brief Psychiatric Rating Scale were selectively correlated with smaller left posterior superior temporal gyrus gray matter volumes. None of the brain measurements were significantly correlated with age at illness onset. CONCLUSIONS: Data from this unique sample of severely ill schizophrenic men emphasize a pattern of structural abnormalities involving the cortex, but not the hippocampus, in schizophrenia. Furthermore, these data support theories suggesting that superior temporal gyrus abnormalities contribute selectively to psychotic symptoms and that the extent of structural abnormalities is unrelated to age of clinical symptom onset.

A deficit profile of executive, memory, and motor functions in schizophrenia.

This study examined the neuropsychological deficits associated with schizophrenia and the interrelationships among multiple dissociable cognitive and motor functions. The tests were selected for their previously demonstrated sensitivity to circumscribed brain pathology and included four functional domains: executive functions, short-term memory and production, motor ability, and declarative memory. Each test composite was divided according to verbal versus nonverbal material or left- versus right-hand performance; this distinction permitted functions principally subserved by the left or right cerebral hemispheres to be tested separately. Data reduction was theoretically driven by the test selection and was achieved first by standardizing the scores of each test for age-related differences observed in the normal control group, and then by calculating test composite scores as an average of the age-corrected Z-scores of the tests comprising a functional composite. The schizophrenic group was impaired equivalently on all composites for both cerebral hemispheres; on average, the Z-scores of the patients were 1 standard deviation below those of the control group. The cognitive test composite scores were highly intercorrelated but showed only weak associations with motor ability. Multiple regression analyses suggested that symptom severity was a significant predictor of the Declarative Memory and Short-Term Memory/Production composite scores after accounting for disease duration, whereas disease duration uniquely contributed to the Executive Functions composite scores after controlling for symptom severity. Even though the schizophrenics as a group showed an equivalent level of deficit across all test composites, 1) the deficits were associated with different aspects of psychiatric symptomatology, 2) the motor deficit was independent of the cognitive deficits, and 3) each neuropsychological domain contributed independently to the deficit pattern. Thus, what appears to be a generalized functional deficit in schizophrenia may actually be, at least in part, combinations of multiple specific deficits.

The contribution of constructional accuracy and organizational strategy to nonverbal recall in schizophrenia and chronic alcoholism.

The Rey-Osterrieth complex figure was used to assess the separate influences of the constructional accuracy and the organizational strategy employed while copying the figure on the later, incidental recall of the figure. We tested a model, which hypothesized that subjects who copied the main framework of the figure holistically would be more likely to achieve good copy accuracy scores and to reproduce the figure more accurately at recall than subjects who used a piecemeal approach during copy. Subjects included 68 detoxified, chronic alcoholics (ALC), 28 patients with schizophrenia (SZ), and 69 normal control subjects (NCS). The results showed that the ALC and the SZ groups, on average, had lower accuracy and strategy scores at copy than did the NCS group, and furthermore, that the combined contributions of copy accuracy and copy strategy accounted for group differences at recall. A path analysis revealed that, for all three groups, copy strategy had a significant direct effect on copy accuracy. Moreover, copy accuracy and copy strategy made independent contributions to recall accuracy within the ALC and NCS groups; by contrast, within the SZ group, copy strategy made an independent contribution to recall performance but copy accuracy did not. These results suggest that (1) organizational strategy can influence constructional accuracy at both copy and recall; (2) copy accuracy and strategy have the potential to influence recall independently; and (3) the recall deficit in ALC could be attributed to abnormalities in both accuracy and strategy at copy, whereas in SZ it could be attributed only to strategy abnormalities. The deficits observed on the complex figure test in the ALC and SZ were primarily nonmnemonic and were related to ability in figure construction and organizational strategy.

Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia.

This study examined whether the neuropsychological deficits observed in patients with schizophrenia were related to cortical gray matter volume deficits in these patients. All subjects were men and included 34 patients with DSM-III-R Schizophrenia and 47 age-matched healthy controls. Subjects received a battery of 21 tests, assessing four different functional domains: executive functions, short-term memory and production, declarative memory, and motor ability. MRI volumes were corrected for normal variation in head size and age, and neuropsychological test scores were corrected for normal variation in age. The schizophrenic group had significantly smaller cortical gray matter volumes (p < .05) and lower test scores in all functional domain than the control group (p = .0001). Within the schizophrenic group, lower scores in each domain were significantly correlated with smaller total cortical gray matter volumes; however, no predictable relationships were observed between neuropsychological test performance and the volumes of specific cortical regions.

Patterns of regional cortical dysmorphology distinguishing schizophrenia and chronic alcoholism.

BACKGROUND: This study used magnetic resonance imaging (MRI) to compare the extent and pattern of tissue volume deficit and cerebrospinal fluid volume enlargement in chronic alcoholics and schizophrenics. METHODS: The subjects included 62 detoxified chronic alcoholics (26-63 years), 71 schizophrenics (23-63 years), and 73 controls spanning the adult age range (21-70 years). MRI volumes were adjusted for normal variation in head size and age established from the control group. RESULTS: Both patient groups showed widespread cortical gray matter volume deficits compared with controls, but only the alcoholics had white matter volume deficits. The schizophrenics had significantly greater volume deficits in the prefrontal and anterior superior temporal gray matter than in the more posterior cortical regions. By contrast, the deficits in the alcoholics were relatively homogeneous across the cortex. For white matter, the deficits in the alcoholics were greatest in the prefrontal and temporal-parietal regions. Although both patient groups had abnormally larger cortical sulci and lateral and third ventricles than the controls, the alcoholics had significantly larger sulcal volumes in the frontal, anterior, and posterior parietal-occipital regions than the schizophrenics. CONCLUSIONS: This quantitative MRI study revealed different patterns of regional cortical volume abnormalities in schizophrenics and alcoholics. The schizophrenic group exhibited cortical gray matter volume deficits of modestly greater magnitude than that observed in the alcoholic group, and the alcoholics but not the schizophrenics exhibited cortical white matter volume deficits.

Volumetric MRI assessment of temporal lobe structures in schizophrenia.

This magnetic resonance imaging (MRI) study was designed to investigate whether patients with schizophrenia have focal or lateralized deficits in the volumes of temporal lobe structures. Estimated volumes of the temporal lobes, hippocampi, superior temporal gyri, lateral ventricles, third ventricle, temporal horns of the lateral ventricles, and a frontal-parietal reference area (FPRA) were quantified for each hemisphere. The schizophrenic group had less gray matter (GM) in the temporal lobes and the FPRA relative to controls. Ventricular volumes were significantly larger in the schizophrenic group, as was cerebrospinal fluid (CSF) volume for temporal lobe sulci. No significant differences in hippocampal volumes emerged between groups. The magnitude of GM deficit was not greater in the temporal lobes relative to the FPRA. These results confirm the presence of bilateral GM volume deficits of the temporal lobes in schizophrenia but do not support the hypothesis that structural changes preferentially affect the temporal lobes or the left cerebral hemisphere.

Gray matter deficits in young onset schizophrenia are independent of age of onset.

This study examined whether the degree of brain dysmorphology observable in adulthood was related to onset age of schizophrenic symptoms. Brain magnetic resonance imaging (MRI) scans were acquired in 57 men with schizophrenia, whose age at MRI was 19-53 years, and whose symptom onset ranged from age 7 to 29 years; all were inpatients in a state hospital. Volumes of intracranial space, cortical gray matter (GM) and white matter (WM), and cerebrospinal fluid (CSF) in lateral and third ventricles and cortical sulci were derived from MRI scans and corrected by regression analysis for variations attributable to age and head size, quantified in a control sample of healthy community volunteers. The schizophrenic patients had larger volumes of cortical and ventricular CSF and smaller volumes of cortical GM but not WM than age-matched controls, whether or not volumes were adjusted for head size and age norms. Age of onset did not correlate with any of the five age-adjusted brain measures. Neither current age, length of illness, nor symptom severity correlated with age-normalized volumes of cortical GM, sulcal CSF, or ventricular CSF. These observations are consistent with the theory that brain structure deficits 1) first develop prior to symptom onset (perhaps during the prenatal and/or early childhood process of GM development); 2) probably establish a vulnerability to subsequent dysfunctionality; but 3) are nonprogressive.

Brain dysmorphology in adults with congenital rubella plus schizophrenialike symptoms.

Brain morphology was quantified with magnetic resonance imaging (MRI) in adult patients with congenital rubella who also had schizophrenialike symptoms. MRIs were compared with those of adult early-onset schizophrenic patients without congenital rubella and age-matched healthy control subjects. The rubella patients had significantly smaller intracranial volumes and shorter stature than the schizophrenic patients or the controls; however, both patient groups had smaller cortical gray matter, but not white matter, volumes than the control group, even when the MRI volumes were corrected for head size and age. In addition, both patient groups showed significant enlargement of the lateral ventricles but not cortical sulci when compared with expected values of normal adults of the same age and head size. Overall, the pattern of dysmorphology was identical in the rubella and the schizophrenic groups. The observations in the rubella group are consistent with a developmental lesion that limits full brain growth, with the small intracranial volume due at least in part to a severe cortical gray matter volume deficit. Thus, the brain dysmorphology of congenital rubella may provide an instance of prenatal viral infection that models the schizophrenic pattern and provides indirect support for a developmental hypothesis of the neuropathogenesis of schizophrenia.