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Borderline personality disorder (BPD) is characterized by greater intensity of reactions to unpleasant emotional cues and a slower-than-normal return of these responses to baseline. Habituation is defined as decreased response to repeated stimulation. Affect-modulated startle (AMS), a translational psychophysiological approach, is mediated by the amygdala and used to study emotion processing in both humans and animals. This is the first study to examine the specificity of habituation anomalies in BPD during passive emotional and neutral picture processing.A total of 90 participants were studied: patients with BPD (n = 35), patients with schizotypal personality disorder (n = 26; included as a psychopathological comparison group), and healthy control subjects (n = 29). Participants received rigorous clinical assessments, and patients were unmedicated. AMS was examined during a series of intermixed unpleasant, neutral, and pleasant pictures.Compared with the other groups, patients with BPD showed greater overall AMS during unpleasant pictures and prolonged habituation of startle amplitude during unpleasant pictures from early to later trials. The groups did not differ in AMS during neutral or pleasant pictures or self-reported picture valence. Among the patients with BPD, prolonged habituation to unpleasant pictures was associated with greater symptom severity and suicidal/self-harming behavior.These findings 1) indicate that abnormal processing of and habituation to unpleasant pictures is observed in BPD but not schizotypal personality disorder, suggesting that these deficits are not simply characteristics of personality disorders in general; 2) are consistent with studies showing deficient amygdala habituation to unpleasant pictures in BPD; and 3) have significant implications for clinical assessment and treatment of BPD, e.g., alternative therapies for BPD such as gradual exposure to unpleasant emotional stimuli or amygdala neurofeedback may aid habituation deficits.

Suicide research/clinical work remain in dire need of effective tools that can better predict suicidal behavior. A growing body of literature has started to focus on the role that neuroimaging may play in helping explain the path towards suicide. Specifically, structural alterations of rostral anterior cingulate cortex (rost-ACC) may represent a biological marker and/or indicator of suicide risk in Major Depressive Disorder (MDD). Furthermore, the construct of "grit," defined as perseverance for goal-attainment and shown to be associated with suicidality, is modulated by rost-ACC. The aim was to examine relationships among rost-ACC gray matter volume, grit, and suicidality in U.S. Military Veterans. Participants were age-and-sex-matched Veterans with MDD: with suicide attempt (MDD+SA:n = 23) and without (MDD-SA:n = 37). Groups did not differ in depression symptomatology. Participants underwent diagnostic interview, clinical symptom assessment, and 3T-MRI-scan. A Group (SA-vs.-No-SA) x Cingulate-region (rostral-caudal-posterior) x Hemisphere (left-right) mixed-model-multivariate-ANOVA was conducted. Left-rost-ACC was significantly smaller in MDD+SA, Group x Cingulate-region x Hemisphere-interaction. Lower grit and less left-rost-ACC gray matter each predicted suicide attempt history, but grit level was a more robust predictor of SA. Both structural alterations of rost-ACC and grit level represent potentially valuable tools for suicide risk assessment.

Schizotypal personality disorder (SPD) resembles schizophrenia, but with attenuated brain abnormalities and the absence of psychosis. The thalamus is integral for processing and transmitting information across cortical regions and widely implicated in the neurobiology of schizophrenia. Comparing thalamic connectivity in SPD and schizophrenia could reveal an intermediate schizophrenia-spectrum phenotype to elucidate neurobiological risk and protective factors in psychosis. We used rsfMRI to investigate functional connectivity between the mediodorsal nucleus (MDN) and pulvinar, and their connectivity with frontal and temporal cortical regions, respectively in 43 healthy controls (HCs), and individuals in the schizophrenia-spectrum including 45 psychotropic drug-free individuals with SPD, and 20 individuals with schizophrenia-related disorders [(schizophrenia (n = 10), schizoaffective disorder (n = 8), schizophreniform disorder (n = 1) and psychosis NOS (n = 1)]. Individuals with SPD had greater functional connectivity between the MDN and pulvinar compared to individuals with schizophrenia. Thalamo-frontal (i.e., between the MDN and rostral middle frontal cortex) connectivity was comparable in SPD and HCs; in SPD greater connectivity was associated with less symptom severity. Individuals with schizophrenia had less thalamo-frontal connectivity and thalamo-temporal (i.e., pulvinar to the transverse temporal cortex) connectivity compared with HCs. Thalamo-frontal functional connectivity may be comparable in SPD and HCs, but abnormal in schizophrenia, and that this may be protective against psychosis in SPD.

This is a selective review of the work of Buchsbaum and colleagues. It revisits and pays tribute to four decades of publications employing positron emission tomography (PET) with F-18fluorodeoxyglucose (FDG) to examine the neurobiology of schizophrenia-spectrum disorders (including schizotypal personality disorder (SPD) and schizophrenia). Beginning with a landmark FDG-PET study in 1982 reporting hypofrontality in unmedicated schizophrenia patients, Buchsbaum and colleagues published high-impact work on regional glucose metabolic rate (GMR) abnormalities in the spectrum. Several key discoveries were made, including the delineation of schizophrenia-spectrum abnormalities in frontal and temporal lobe, cingulate, thalamus, and striatal regions using three-dimensional mapping with coregistered MRI and PET. These findings indicated that SPD patients have less marked frontal lobe and striatal dysfunction compared with schizophrenia patients, possibly mitigating frank psychosis. Additionally, these investigations were among the first to conduct early seed-based functional connectivity analyses with FDG-PET, showing aberrant cortical-subcortical circuitry and, in particular, revealing a thalamocortical circuitry abnormality in schizophrenia. Finally, pioneering work employing the first double-blind randomized antipsychotic (haloperidol) vs. placebo FDG-PET study design in schizophrenia indicated that GMR in the striatum, more than in any other region, was related to clinical response.

Both autism spectrum disorder (ASD) and schizophrenia are often characterized as disorders of white matter integrity. Multimodal investigations have reported elevated metabolic rates, cerebral perfusion and basal activity in various white matter regions in schizophrenia, but none of these functions has previously been studied in ASD. We used 18fluorodeoxyglucose positron emission tomography to compare white matter metabolic rates in subjects with ASD (n = 25) to those with schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of stereotaxically placed regions-of-interest. Both subjects with ASD and schizophrenia showed increased metabolic rates across the white matter regions assessed, including internal capsule, corpus callosum, and white matter in the frontal and temporal lobes. These increases were more pronounced, more widespread and more asymmetrical in subjects with ASD than in those with schizophrenia. The highest metabolic increases in both disorders were seen in the prefrontal white matter and anterior limb of the internal capsule. Compared to normal controls, differences in gray matter metabolism were less prominent and differences in adjacent white matter metabolism were more prominent in subjects with ASD than in those with schizophrenia. Autism spectrum disorder and schizophrenia are associated with heightened metabolic activity throughout the white matter. Unlike in the gray matter, the vector of white matter metabolic abnormalities appears to be similar in ASD and schizophrenia, may reflect inefficient functional connectivity with compensatory hypermetabolism, and may be a common feature of neurodevelopmental disorders.

Despite considerable phenomentological differences between borderline personality disorder (BPD) and schizotypal personality disorder (SPD), research increasingly provides evidence that some BPD symptoms overlap with SPD symptoms (e.g., disturbed cognitions). We examined the cingulate, a brain region implicated in the pathophysiology of both disorders, to determine similarities/differences between the groups, and similarities/differences from healthy controls (HC's). 3T structural and diffusion tensor magnetic resonance imaging scans were acquired in BPD (n = 27), SPD (n = 32), HC's (n = 34). Results revealed that BPD patients exhibited significantly lower FA in posterior cingulate white matter compared to HC's (p = 0.04), but SPD patients did not.

Autism spectrum disorders and schizophrenia have been variously characterized as separate nosological entities with overlapping deficits in social cognition or diametrical extremes of a phenotypic continuum. This study aimed to determine how these models apply to comparative morphometric data. MRI scans of the brain were obtained in 49 subjects with schizophrenia, 20 subjects with autism and 39 healthy controls. Images were parcellated into 40 Brodmann areas and entered into repeated-measures ANOVA for between-group comparison of global and localized gray and white matter volumes. A pattern of lower gray mater volumes and greater white matter volumes was found in subjects with schizophrenia in comparison to subjects with autism. For both gray and white matter, this pattern was most pronounced in regions associated with motor-premotor and anterior frontal cortex, anterior cingulate, fusiform, superior and middle temporal gyri. Patient groups tended to diverge from healthy controls in opposite directions, with greater-than-normal gray matter volumes and lower-than-normal white matter volumes in subjects with autism and reversed patterns in subjects with schizophrenia. White matter reductions in subjects with autism were seen in posterior frontal lobe and along the cingulate arch. Normal hemispheric asymmetry in the temporal lobe was effaced in subjects with autism and schizophrenia, especially in the latter. Nearly identical distribution of changes and diametrically divergent volumetry suggest that autism and schizophrenia may occupy opposite extremes of the same cognitive continuum.

This is a selective review of the work of Buchsbaum and colleagues. It revisits and pays tribute to four decades of publications employing positron emission tomography (PET) with

The corpus callosum has been implicated as a region of dysfunctional connectivity in schizophrenia, but the association between age and callosal pathology is unclear. Magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI) were performed on adults (n=34) and adolescents (n=17) with schizophrenia and adult (n=33) and adolescent (n=15) age- and sex-matched healthy controls. The corpus callosum was manually traced on each participant’s MRI, and the DTI scan was co-registered to the MRI. The corpus callosum was divided into five anteroposterior segments. Area and anisotropy were calculated for each segment. Both patient groups demonstrated reduced callosal anisotropy; however, the adolescents exhibited reductions mostly in anterior regions while the reductions were more prominent in posterior regions of the adults. The adolescent patients showed greater decreases in absolute area as compared with the adult patients, particularly in the anterior segments. However, the adults showed greater reductions when area was considered relative to whole brain white matter volume. Our results suggest that the initial stages of the illness are characterized by deficiencies in frontal connections, and the chronic phase is characterized by deficits in the posterior corpus callosum; or, alternatively, adolescent-onset schizophrenia may represent a different or more severe form of the illness.

Several models have been proposed to account for observed overlaps in clinical features and genetic predisposition between schizophrenia and autism spectrum disorder. This study assessed similarities and differences in topological patterns and vectors of glucose metabolism in both disorders in reference to these models. Co-registered 18fluorodeoxyglucose PET and MRI scans were obtained in 41 schizophrenia, 25 ASD, and 55 healthy control subjects. AFNI was used to map cortical and subcortical regions of interest. Metabolic rates were compared between three diagnostic groups using univariate and multivariate repeated-measures ANOVA. Compared to controls, metabolic rates in schizophrenia subjects were decreased in the frontal lobe, anterior cingulate, superior temporal gyrus, amygdala and medial thalamic nuclei; rates were increased in the occipital cortex, hippocampus, basal ganglia and lateral thalamic nuclei. In ASD subjects metabolic rates were decreased in the parietal lobe, frontal premotor and eye-fields areas, and amygdala; rates were increased in the posterior cingulate, occipital cortex, hippocampus and basal ganglia. In relation to controls, subjects with ASD and schizophrenia showed opposite changes in metabolic rates in the primary motor and somatosensory cortex, anterior cingulate and hypothalamus; similar changes were found in prefrontal and occipital cortices, inferior parietal lobule, amygdala, hippocampus, and basal ganglia. Schizophrenia and ASD appear to be associated with a similar pattern of metabolic abnormalities in the social brain. Divergent maladaptive trade-offs, as postulated by the diametrical hypothesis of their evolutionary relationship, may involve a more circumscribed set of anterior cingulate, motor and somatosensory regions and the specific cognitive functions they subserve.

The cingulate cortex frequently shows gray matter loss with age as well as gender differences in structure and function, but little is known about whether individual cingulate Brodmann areas show gender-specific patterns of age-related volume decline. This study examined age-related changes, gender differences, and the interaction of age and gender in the relative volume of cingulate gray matter in areas 25, 24, 31, 23, and 29, over seven decades of adulthood. Participants included healthy, age-matched men and women, aged 20-87 (n=70). Main findings were as follows: (1) The whole cingulate showed significant age-related volume declines (averaging 5.54% decline between decades, 20s-80s). Each of the five cingulate areas also showed a significant decline with age, and individual areas showed different patterns of decline across the decades: Smaller volume with age was most evident in area 31, followed by 25 and 24. (2) Women had relatively larger cingulate gray matter volume than men overall and in area 24. (3) Men and women showed different patterns of age-related volume decline in area 31, at midlife and late in life. By delineating normal gender differences and age-related morphometric changes in the cingulate cortex over seven decades of adulthood, this study improves the baseline for comparison with structural irregularities in the cingulate cortex associated with psychopathology. The Brodmann area-based approach also facilitates comparisons across studies that aim to draw inferences between age- and gender-related structural differences in the cingulate gyrus and corresponding differences in cingulate function.

Consistent with the clinical picture of milder symptomatology in schizotypal personality disorder (SPD) than schizophrenia, morphological studies indicate SPD abnormalities in temporal lobe regions but to a much lesser extent in prefrontal regions implicated in schizophrenia. Lower fractional anisotropy (FA), a measure of white-matter integrity within prefrontal, temporal, and cingulate regions has been reported in schizophrenia but has been little studied in SPD.The study aim was to examine temporal and prefrontal white matter FA in 30 neuroleptic-naïve SPD patients and 35 matched healthy controls (HCs). We hypothesized that compared with HCs, SPD patients would exhibit lower FA in temporal lobe and anterior cingulum regions but relative sparing in prefrontal regions.We acquired diffusion tensor imaging (DTI) in all participants and examined FA in the white matter underlying Brodmann areas (BAs) in dorsolateral prefrontal (BAs 44, 45, and 46), temporal lobe (BAs 22, 21, and 20), and cingulum (BAs 25, 24, 31, 23, and 29) regions with a series of analyses using multivariate analysis of variance.Compared with HCs, the SPD group had significantly lower FA in the left temporal lobe but not prefrontal regions. In the cingulum, FA was lower in the SPD group in the posterior regions (BAs 31 and 23), higher in the anterior (BA 25) regions and lower overall in the right but not the left cingulum. Among the SPD group, lower FA in the cingulum was associated with more severe negative symptoms (e.g., odd speech).Similar to schizophrenia, our results indicate cingulum-temporal lobe FA abnormalities in SPD and suggest that cingulum abnormalities are associated with negative symptoms.

This study examined the main and interactive effects of age and sex on relative glucose metabolic rate (rGMR) within gray matter of 39 cortical Brodmann areas (BAs) and the cingulate gyrus using (18)FDG-PET during a verbal memory task in 70 healthy normal adults, aged 20-87 years. Women showed significantly greater age-related rGMR decline in left cingulate gyrus than men (BAs 25, 24, 23, 31, 29). Both groups showed a decline in the anterior cingulate--a neuroanatomical structure that mediates effective cognitive-emotional interactions (BAs 32, 24, 25), while the other frontal regions did not show substantial decline. No sex differences in rGMR were identified within temporal, parietal and occipital lobes. Sex differences were observed for rGMR within subcomponents of the cingulate gyrus with men higher in BA25 and BA29, but lower in BA24 and BA 23 compared to women. For men, better memory performance was associated with greater rGMR in BA24, whereas in women better performance was associated with orbitofrontal-BA12. These results suggest that both age-related metabolic decline and sex differences within frontal regions are more marked in medial frontal and cingulate areas, consistent with some age-related patterns of affective and cognitive change.

Background: Pathological gambling (PG) is a disorder classified as an impulse control disorder (DSM-IV) bridging impulsive, compulsive and addictive behaviors. The striatum and thalamus are supposed to be involved in the pathophysiological substrate of these behaviors. An increased relative glucose metabolic rate (rGMR) in patients with a diagnosis of PG had previously been reported in the medial and orbitofrontal cortex. We extended our studies to include functional alterations of the striatum and thalamus in a cohort of patients with PG before and after treatment with lithium. Methods: Twenty-one patients with PG who met lifetime comorbid bipolar spectrum diagnoses and a comparison group of 21 age- and sex-matched controls underwent a baseline positron emission tomography (PET) scan. Sixteen of these patients entered a randomized double-blind placebo-controlled parallel-group-design trial of lithium and underwent a follow-up PET scan at week 10. Anatomical MRI were obtained and the structures outlined on consecutive axial slices. These individual hand-drawn templates were used to identify structures on the PET scan of each patient, and the rGMR was measured. Results: The PG patients had a decrement of the rGMR in the ventral parts of the striatum and thalamus, and an increment of the rGMR in the dorsal parts as compared with the controls. Lithium treatment increased the ventral caudate rGMR to a trend level in the patients, but had no effect on the metabolism of either the putamen or the thalamus. Conclusion: Because of their extensive connectivity to the frontal cortex, striatal and thalamic functional alteration may contribute to faulty decision making processes in PG patients. By increasing the ventral rGMR of the caudate nucleus, lithium treatment may reduce cognitive dysfunction and symptoms in PG patients.

Sertindole, a 2nd generation antipsychotic with low movement disorder side effects, was compared with haloperidol in a 6-week crossover study. Fifteen patients with schizophrenia (mean age=42.6, range=22-59, 11 men and 4 women) received sertindole (12-24 mg) or haloperidol (4-16 mg) for 6 weeks and then received a FDG-PET scan and an anatomical MRI. Patients were then crossed to the other treatment and received a second set of scans at week 12. Dose was adjusted by a physician blind to the medication type. Brodmann areas were identified stereotaxically using individual MRI templates applied to the coregistered FDG-PET image. Sertindole administration was associated with higher dorsolateral prefrontal cortex metabolic rates than haloperidol and lower orbitofrontal metabolic rates than haloperidol. This effect was greatest for gray matter of the dorsolateral Brodmann areas 8, 9, 10, 44, 45, and 46. Patients were further contrasted with an approximately age and sex-matched group of 33 unmedicated patients with schizophrenia and with a group of 55 normal volunteers. Sertindole administration was associated with greater change toward normal values and away from the values found in the unmedicated comparison group for dorsolateral prefrontal cortex gray matter and white matter underlying medial prefrontal and cingulate cortex. These results are consistent with the low motor side-effect profile of sertindole, greater improvement on prefrontal cognitive tasks with sertindole than haloperidol, and with the tendency of 2nd generation antipsychotic drugs to have greater frontal activation than haloperidol.

Previous studies have reported continued focal gray matter loss after the clinical onset of schizophrenia. Longitudinal assessments in chronic illness, of white matter in particular, have been less conclusive. We used diffusion-tensor and structural magnetic resonance imaging in 16 healthy subjects and 49 chronic schizophrenia patients, subdivided into good-outcome (n=23) and poor-outcome (n=26) groups, scanned twice 4 years apart. Fractional anisotropy, gray matter and white matter volumes were parcellated into the Brodmann’s areas and entered into multiway ANCOVAs. At baseline, schizophrenia patients had 1) lower anisotropy in frontoparietal white matter, 2) larger posterior frontal white matter volumes, and 3) smaller frontal, temporal, and parietal gray matter volumes. On follow-up, healthy subjects showed a more pronounced 1) decline in anisotropy, 2) expansion of regional white matter volumes, and 3) reduction in regional gray matter volumes than schizophrenia patients. Good-outcome patients showed a more pronounced decline in white matter anisotropy and a less pronounced increase in white matter volumes than poor-outcome patients. Poor-outcome patients displayed a greater gray matter loss throughout the brain than good-outcome patients. In the chronic phase of the illness, longitudinal changes in both gray and white matter are in the direction of an effacement of between-group differences among schizophrenia patients and healthy subjects. Similarly, preexisting white matter differences between good-outcome and poor-outcome patients diminish over time. In contrast, gray matter volumes in poor-outcome patients continue to decline more rapidly than in patients with good outcome. These patterns are consistent with earlier onset of aging-associated changes in schizophrenia.

Magnetic resonance imaging (MRI) studies have revealed fronto-temporal cortical gray matter volume reductions in schizophrenia. However, to date studies have not examined whether age- and sex-matched unmedicated schizotypal personality disorder (SPD) patients share some or all of the structural brain-imaging characteristics of schizophrenia patients. We examined cortical gray/white matter volumes in a large sample of unmedicated schizophrenia-spectrum patients (n = 79 SPD, n = 57 schizophrenia) and 148 healthy controls. MRI images were reoriented to standard position parallel to the anterior–posterior commissure line, segmented into gray and white matter tissue types, and assigned to Brodmann areas (BAs) using a postmortem-histological atlas. Group differences in regional volume of gray and white matter in the BAs were examined with MANOVA. Schizophrenia patients had significantly reduced gray matter volume widely across the cortex but more marked in frontal and temporal lobes. SPD patients had reductions in the same regions but only about half that observed in schizophrenia and sparing in key regions including BA10. In schizophrenia, greater fronto-temporal volume loss was associated with greater negative symptom severity and in SPD, greater interpersonal and cognitive impairment. Overall, our findings suggest that increased prefrontal volume in BA10 and sparing of volume loss in temporal cortex (BAs 22 and 20) may be a protective factor in SPD which reduces vulnerability to psychosis.

Background: Pathological gambling affects 1–3% of the adult population, and has high comorbidity. Although mood stabilizers and serotonin reuptake inhibitors have shown some efficacy in the treatment of this condition, there is little known about how these pharmacological interventions work. Methods: Twenty-one patients with pathological gambling, who met lifetime comorbid bipolar spectrum diagnoses, received baseline PET scans. Sixteen of these patients were entered into a randomized double-blind placebo-controlled parallel group design trial of lithium, and received follow-up PET scans at 10 weeks. A comparison group of 32 age- and sex-matched controls was also available. Anatomical MRIs were obtained as a structural template. Results: In patients with pathological gambling, relative glucose metabolic rates (rGMR) in the orbitofrontal cortex and medial frontal cortex were significantly increased at baseline compared to normal controls. Lithium increased rGMR further in the orbitofrontal cortex, heightening normal/patient differences, but it also increased the rGMR of the posterior cingulate and the dorsolateral frontal cortex normalizing the metabolic rate in these regions. Conclusion: Cortical areas implicated in impulse control disorders show increased rGMR in pathological gambling at baseline. Lithium treatment, while alleviating the symptoms, further increases rGMR in these areas.

Preliminary data suggest an association of posterior cortical gray matter reduction with poor outcome in schizophrenia. We made a systematic MRI assessment of regional gray and white matter volumes, parcellated into 40 Brodmann’s areas, in 104 patients with schizophrenia (51 with good outcomes, 53 with poor outcomes) and 41 normal comparison subjects, and investigated correlations of regional morphometry with outcome and severity of the illness. Schizophrenia patients displayed differential reductions in frontal and to a lesser degree temporal gray matter volumes in both hemispheres, most pronounced in the frontal pole and lateral temporal cortex. White matter volumes in schizophrenia patients were bilaterally increased, primarily in the frontal, parietal, and isolated temporal regions, with volume reductions confined to anterior cingulate gyrus. In patients with schizophrenia as a group, higher illness severity was associated with reduced temporal gray matter volumes and expanded frontal white matter volumes in both hemispheres. In comparison to good-outcome group, patients with poor outcomes had lower temporal, occipital, and to a lesser degree parietal gray matter volumes in both hemispheres and temporal, parietal, occipital, and posterior cingulate white matter volumes in the right hemisphere. While gray matter deficits in the granular cortex were observed in all schizophrenia patients, agranular cortical deficits in the left hemisphere were peculiar to patients with poor outcomes. These results provide support for frontotemporal gray matter reduction and frontoparietal white matter expansion in schizophrenia. Poor outcome is associated with more posterior distribution (posteriorization) of both gray and white matter changes, and with preferential impairment in the unimodal visual and paralimbic cortical regions.

There is increasing evidence demonstrating that circuits involving the frontal lobe, striatum, temporal lobe, and cerebellum are abnormal in individuals with schizophrenia, which suggests that metabolic activity in the white matter connecting these areas should be investigated.The authors obtained [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and matching T1-weighted magnetic resonance imaging (MRI) on 170 subjects. Participants were 103 normal volunteers and 67 unmedicated patients with schizophrenia (N=61) or schizoaffective disorder (N=6). The images were coregistered and warped to standard space for significance probability mapping.Compared with normal volunteers, patients showed higher relative metabolic rates in the frontal white matter, corpus callosum, superior longitudinal fasciculus, and white matter core of the temporal lobe. Elevated activity in white matter was most pronounced in the center of large white matter tracts, especially the frontal parts of the brain and the internal capsule. The white matter elevation did not appear to be entirely related to changes in gray matter/white matter brain proportions, whole brain metabolic rate bias, or excess head motion in patients, but this cannot be ruled out without absolute glucose determinations. Patients also showed significantly lower relative glucose metabolism in the frontal and temporal lobes, caudate nucleus, cingulate gyrus, and mediodorsal nucleus of the thalamus relative to normal volunteers, which is consistent with earlier studies.In comparisons of unmedicated schizophrenia patients with normal volunteers, relative metabolic increases are apparent in white matter in patients with schizophrenia as well as decreases in gray matter. Inefficiency in brain circuitry, defects in white matter leading to enhanced energy need, white matter damage, and alterations in axon packing density are among the possible explanations for these schizophrenia-related findings of relatively increased metabolism in white matter.

Background Prior voxelwise studies of white matter anisotropy found widespread reductions involving all major fiber tracts of the schizophrenic brain. We set out to confirm these exploratory findings and evaluate their relation to illness severity using a hypothesis-driven region-of-interest approach. Methods 104 schizophrenia patients (51 with good outcomes, 53 with poor outcomes) and 41 matched comparison subjects participated in the study. Regions of interest were selected on the basis of published voxelwise findings and placed within major fiber tracts using Talairach's stereotaxic coordinates. Results Fractional anisotropy reductions in schizophrenia patients were confirmed in the left cingulum, anterior thalamic radiation, fronto-occipital and inferior longitudinal fasciculi, as well as bilaterally in the corpus callosum, anterior and posterior limbs of internal capsule, superior longitudinal fasciculus, optic radiation, and frontotemporal extrafascicular white matter. Anisotropy reductions were more extensive in patients with poor outcomes (“Kraepelinian”), particularly in the posterior corpus callosum, fronto-occipital fasciculus, left optic radiation and frontotemporal white matter. Lower anisotropy in the right hemisphere tracts was associated with more prominent positive symptomatology, whereas negative symptoms were inversely associated with anisotropy values in both hemispheres. Conclusions These results support a global neural disconnectivity in schizophrenia patients, which is more severe in those with poor clinical outcomes.

Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a core symptom of borderline personality disorder (BPD). We examined relative glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine) with (18)fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26 impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala were visually traced on MRI scans co-registered to PET scans; rGMR was obtained for ventral and dorsal regions of the amygdala and Brodmann areas within the prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo: Controls showed significant positive correlations between right orbitofrontal (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak correlations between amygdala and the anterior PFC, with no distinction between dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls showed positive correlations between OFC and amygdala regions, whereas patients showed positive correlations between dorsolateral PFC and amygdala. Group differences between interregional correlational matrices were highly significant. Amygdala volume/metabolism: No group differences were found for amygdala volume, or metabolism in the placebo condition or in response to meta-chloropiperazine (m-CPP). We demonstrated a tight coupling of metabolic activity between right OFC and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in IED-BPD. We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls.

We acquired diffusion tensor images on 33 normal adults aged 22–64 and 15 adolescents aged 14–21. We assessed relative anisotropy in stereotaxically located regions of interest in the internal capsule, corpus callosum, anterior thalamic radiations, frontal anterior fasciculus, fronto-occipital fasciculus, temporal lobe white matter, cingulum bundle, frontal inferior longitudinal fasciculus, frontal superior longitudinal fasciculus, and optic radiations. All of these structures except the optic radiations, corpus callosum, and frontal inferior longitudinal fasciculus exhibited differences in anisotropy between adolescents and adults. Areas with anisotropy increasing with age included the anterior limb of the internal capsule, superior levels of the frontal superior longitudinal fasciculus and the inferior portion of the temporal white matter. Areas with anisotropy decreasing with age included the posterior limb of the internal capsule, anterior thalamic radiations, fronto-occipital fasciculus, anterior portion of the frontal anterior fasciculus, inferior portion of the frontal superior longitudinal fasciculus, cingulum bundle and superior portion of the temporal axis. Sex differences were found in the majority of areas but were most marked in the cingulum bundle and internal capsule. These results suggest continuing white matter development between adolescence and adulthood.

Objective Disparate white matter fractional anisotropy (FA) findings have been reported in patients with schizophrenia in recent years. This may in part reflect heterogeneity of subjects in the studies, including differences in outcome and severity of the illness. We examined whether there is a relationship between white matter FA and outcome in patients with schizophrenia. Method Diffusion-tensor images were obtained in 41 normal subjects and 104 patients with schizophrenia, divided into good-outcome ( n = 51) and poor-outcome (Kraepelinian; n = 53) subtypes based on their ability for self-care. White matter FA and its relationship to regional tissue volumes were evaluated across 40 individual Brodmann's areas using a semi-automated parcellation technique. Results Overall white matter FA was lower in schizophrenia patients than normal subjects, with regional reductions in widespread temporoparietal and selected prefrontal white matter regions. In schizophrenia patients, lower regional white matter FA was associated with lower regional gray matter volumes. In comparison to normal subjects, overall white matter FA was reduced in patients with poor outcomes in both hemispheres, but to a lesser extent and only in the right hemisphere in good-outcome patients. Lower regional FA was associated with larger regional white matter volumes in good-outcome group. Conclusions Global FA reductions implicate white matter as tissue type in the pathophysiology of schizophrenia. In contrast to poor outcome, good outcome in schizophrenia patients may be associated with less extensive FA reductions, higher FA in regional frontal and cingulate white matter, and correlated increases in regional white matter volumes, particularly in the left hemisphere.

Methods based on the analysis of metabolic and volumetric interregional correlations have been used in neuroimaging research, yet metabolic and volumetric interregional correlations for identical regions of interest have never been compared in the same group of subjects. Magnetic resonance and [18F]-fluorodeoxyglucose positron emission tomography brain images were acquired in 59 healthy subject. Correlation matrices for relative glucose metabolic rates during a verbal learning task and for relative gray matter volumes were compiled between the manually traced mediodorsal, centromedian, and pulvinar nuclei of the thalamus and 39 cortical Brodmann's areas. Metabolic correlations between the cortex and these thalamic nuclei followed the known patterns of anatomical connectivity in non-human primates. Intercorrelations of the mediodorsal nucleus were widespread with the prefrontal cortex (9 out of 10 Brodmann's areas in the left hemisphere) and temporal lobe (10 out of 11 Brodmann's areas in the left hemisphere) while the pulvinar correlated only with the parietal and occipital cortical areas. Different correlation patterns were observed for the regional gray matter volumes whereby only the pulvinar yielded extensive cortical intercorrelations, primarily with the occipital, parietal, anterior cingulate, and orbitofrontal areas in the right hemisphere. Metabolic thalamocortical correlations were much more extensive for the mediodorsal and centromedian nuclei whereas structural correlations were more extensive for the pulvinar. Therefore, metabolic and volumetric correlational methods are sensitive to different aspects of interregional relations in the brain and their comparison in the same group of subjects may render complementary and only partially overlapping connectivity information.

In patients with autism, behavioral deficits as well as neuroimaging studies of the anterior cingulate cortex suggest ventral rather than dorsal striatal and thalamic abnormalities in structure and function. The authors used imaging studies to map volumetric and metabolic differences within the entire dorsoventral extent of the striatum and thalamus.Magnetic resonance imaging (MRI) and positron emission tomography (PET) were used to measure volumes and metabolic activity in the thalamus, caudate, and putamen in 17 patients with autism or Asperger's disorder and 17 age- and sex-matched comparison subjects. Subjects performed a serial verbal learning test during the [(18)F]-fluorodeoxyglucose uptake period. The regions of interest were outlined on contiguous axial MRI slices. After PET/MRI coregistration, region-of-interest coordinates were applied to the PET scan for each individual. Between-group differences in metabolism were assessed by three-dimensional statistical probability mapping.The patients with autism spectrum disorders had greater volumes of the right caudate nucleus than comparison subjects as well as a reversal of the expected left-greater-than-right hemispheric asymmetry. Patients also had lower relative glucose metabolic rates bilaterally in the ventral caudate, putamen, and thalamus. Patients with autism had lower metabolic activity in the ventral thalamus than those with Asperger's disorder, but they did not differ from comparison subjects in metabolic activity in the caudate nucleus.These results are consistent with a deficit in the anterior cingulate-ventral striatum-anterior thalamic pathway in patients with autism spectrum disorders. The results also suggest an important role for the caudate in helping support working-memory demands.

Background Neurons in the basal ganglia are connected to areas of prefrontal cerebral cortex involved in higher cognitive functions, and these connections occur primarily via the thalamus. In patients with bipolar disorder, regardless of age, neuroimaging studies have consistently reported an increased number of white matter hyperintensities, indicating possible alterations in striatum-thalamus and thalamus-prefrontal cortex connections. Methods In the current study, we acquired high-resolution magnetic resonance imaging (MRI) and diffusion tensor (DT) scans of 40 patients with bipolar spectrum (BPS) illnesses (bipolar type I = 17, bipolar type II = 7, cyclothymia = 16) and 36 sex- and age-matched control subjects. Two researchers, without knowledge of diagnosis, outlined the caudate, putamen, and thalamus on contiguous axial MRI slices. We measured the volumes of the basal ganglia, thalamus, and gray/white matter of the frontal cortex. Results Bipolar spectrum patients as a single group did not differ from control subjects in thalamus and the basal ganglia volumes, but the cyclothymia patients had reductions in the volumes of putamen and the thalamus compared with control subjects. The BPS patients had significantly reduced volume of the white and the gray matter of the frontal cortex. Furthermore, compared with control subjects, BPS patients as a group showed alterations in anisotropy of the internal capsule adjacent to the striatum and thalamus and the frontal white matter. Conclusions Our findings indicate that BPS patients may have distinct anatomical alterations in brain structures involved in the regulation of mood and cognition, as well as alterations in these structures’ connection to related brain areas.

Background : The cingulate gyrus, which is involved in affect, attention, memory and higher executive functions, has been implicated as a dysfunctional region in schizophrenia. Postmortem studies report cytoarchitectural changes in the anterior cingulate gyrus (ACG) and functioning imaging studies show correlations between the degree of hypometabolism of the anterior cingulate and clinical symptoms in schizophrenia. Methods : Unmedicated patients with schizophrenia ( n =27) and schizotypal personality disorder (SPD) ( n =13), as well as sex- and age-matched control subjects ( n =32), were studied with 18 F-fluorodeoxyglucose positron emission tomography (PET) scans and magnetic resonance imaging (MRI). As a control over mental activity, all subjects performed a verbal working memory task during the PET protocol. The cingulate gyrus was first outlined on the MRI scans and, after coregistration, the coordinates were applied to the PET scans to yield a three-dimensional metabolic map of the cingulate gyrus for each subject. A statistical resampling method was used to analyze the metabolic differences between groups. Results : Compared with controls, patients with schizophrenia had lower relative glucose metabolic rates in the left anterior cingulate and the right posterior cingulate gyrus (PCG) assessed by 3-D significance probability mapping. SPD patients had higher glucose metabolic rates (GMRs) in the left posterior cingulate than did controls. Furthermore, volumetric measurement with MRI showed the left anterior cingulate and Brodmann area 24′ to be smaller in schizophrenic patients than controls. Conclusions : Compared with controls, patients with schizophrenia have metabolic and volumetric reductions in a cingulate gyrus area that is related to higher executive functions. Schizotypal patients rely more on sensory association areas to perform a cognitive task than do controls and seem to be a group that is partially distinct in its physiological and functional characteristics.

A new Brodmann area (BA) delineation approach was applied to FDG-PET scans of autistic patients and healthy volunteers (n = 17 in each group) to examine relative glucose metabolism (rGMR) during performance of a verbal memory task. In the frontal lobe, patients had lower rGMR in medial/cingulate regions (BA 32, 24, 25) but not in lateral regions (BA 8–10) compared with healthy controls. Patients had higher rGMR in occipital (BA 19) and parietal regions (BA 39) compared with controls, but there were no group differences in temporal lobe regions. Among controls, better recall and use of the semantic-clustering strategy was associated with greater lateral and medial frontal rGMR, while decreased rGMR in medial-frontal regions was associated with greater perseverative/intrusion errors. Patients failed to show these patterns. Autism patients have dysfunction in some but not all of the key brain regions subserving verbal memory performance, and other regions may be recruited for task performance.

Prior diffusion tensor imaging (DTI) studies examining schizotypal personality disorder (SPD) and schizophrenia, separately have shown that compared with healthy controls (HCs), patients show frontotemporal white matter (WM) abnormalities. This is the first DTI study to directly compare WM tract coherence with tractography and fractional anisotropy (FA) across the schizophrenia spectrum in a large sample of demographically matched HCs (n = 55), medication-naive SPD patients (n = 49), and unmedicated/never-medicated schizophrenia patients (n = 22) to determine whether (a) frontal-striatal-temporal WM tract abnormalities in schizophrenia are similar to, or distinct from those observed in SPD; and (b) WM tract abnormalities are associated with clinical symptom severity indicating a common underlying pathology across the spectrum. Compared with both the HC and SPD groups, schizophrenia patients showed WM abnormalities, as indexed by lower FA in the temporal lobe (inferior longitudinal fasciculus) and cingulum regions. SPD patients showed lower FA in the corpus callosum genu compared with the HC group, but this regional abnormality was more widespread in schizophrenia patients. Across the schizophrenia spectrum, greater WM disruptions were associated with greater symptom severity. Overall, frontal-striatal-temporal WM dysconnectivity is attenuated in SPD compared with schizophrenia patients and may mitigate the emergence of psychosis.

Background: Prepulse inhibition (PPI) of the startle reflex reflects early stages of information processing and is modulated by selective attention. Animal models indicate medial frontal-thalamic circuitry is important in PPI modulation. We report data from the first functional magnetic resonance imaging (fMRI) study examining whether attending to or ignoring a prepulse differentially activates brain areas within this circuitry. Methods: Ten healthy subjects received structural and functional MRI. During fMRI acquisition, subjects heard intermixed attended and ignored tones serving as prepulses to the startle stimulus. Regions of interest were traced on structural MRI and coregistered to fMRI images. Results: Greater amplitude fMRI blood-oxygen-level-dependent response to attended than ignored PPI conditions occurred in the right thalamus, and bilaterally in the anterior and mediodorsal thalamic nuclei, whereas the startle-alone condition showed deactivation. In transitional medial cortex (Brodmann Area 32), which is involved in affective processing of noxious stimuli, the startle-alone condition elicited the greatest response, the attended-PPI condition showed the smallest response, and the ignored-PPI condition was intermediate. Conclusions: These findings extend animal models to humans by indicating thalamic involvement in the modulation of PPI. Further fMRI investigations may elucidate other key structures in the circuitry underlying normal and disordered modulation of PPI.

Cytoarchitectonic changes in the anterior cingulate cortex, hippocampus, subiculum, entorhinal cortex, amygdala, mammillary bodies, and septum were reported in a postmortem study of autism. Previously, the authors found smaller cingulate volume and decreased metabolism of the cingulate in seven autistic patients. In this study, they measured the volume and glucose metabolism of the amygdala, hippocampus, and cingulate gyrus in an expanded group of 17 patients with autism spectrum disorders (autism [N=10] or Asperger's disorder [N=7]) and 17 age- and sex-matched healthy volunteers.Subjects performed a serial verbal learning test during (18)F-deoxyglucose uptake. The amygdala, hippocampus, and cingulate gyrus were outlined on magnetic resonance imaging scans, volumes of the structures were applied to matching coregistered positron emission tomography scans, and three-dimensional significance probability mapping was performed.Significant metabolic reductions in both the anterior and posterior cingulate gyri were visualized in the patients with autism spectrum disorders. Both Asperger's and autism patients had relative glucose hypometabolism in the anterior and posterior cingulate as confirmed by analysis of variance; regional differences were also found with three-dimensional significance probability mapping. No group differences were found in either the metabolism or the volume of the amygdala or the hippocampus. However, patients with autism spectrum disorders showed reduced volume of the right anterior cingulate gyrus, specifically in Brodmann's area 24'.Compared with age- and sex-matched healthy volunteers, patients with autism spectrum disorders showed significantly decreased metabolism in both the anterior and posterior cingulate gyri.

Disturbances in fronto-striatal circuitry have been postulated to be important in schizophrenia. Positron emission tomography typically shows decreased metabolic rates in these areas relative to other brain areas in schizophrenia. After treatment with typical neuroleptics, striatal metabolic rates are increased, but other brain areas tend not to show significant changes. Atypical neuroleptics less markedly affect striatal metabolic rates, but show wider cortical effects. In order to examine fronto-striatal circuitry, a technique for visualizing the correlations between metabolic rates in all brain areas was applied in 33 controls and 27 unmedicated schizophrenic patients. Correlation images revealed strong fronto-striatal connections in controls, but weak fronto-striatal links in schizophrenic patients. Changes in striatal circuits, also reflected in recent anatomical studies, may be important for understanding antipsychotic effects.

Coregistered positron emission tomography (PET)/magnetic resonance imaging (MRI) was used to characterize brain function in 70 volunteers, aged 20–87 years, during a verbal memory task. Frontal activity showed an age-related decline that remained significant after statistical control for sulcal atrophy. Analyses of young and old subgroups matched for memory scores revealed that young good performers activated frontal regions, whereas old good performers relied on occipital regions. Although activating different cortical regions, good performers of all ages used the same cognitive strategy—semantic clustering. Age-related functional change may reflect dynamic re-allocation in a network of brain areas, not merely anatomically fixed neuronal loss or diminished capacity to perform.

Attentional modulation of the startle reflex was studied in 16 unmedicated schizophrenia patients and 15 control individuals during the 18F-2-deoxyglucose uptake period for positron emission tomography. In a task involving attended, ignored, and novel tones that served as prepulses, control individuals showed greater prepulse inhibition (PPI) at 120 ms and greater prepulse facilitation at 4,500 ms during attended than during ignored prepulses; the amount of PPI and facilitation during novel prepulses was intermediate. In contrast, patients failed to show differential PPI at 120 ms and tended to show greater facilitation at 4,500 ms during novel prepulses. For control individuals, greater PPI was associated with higher relative metabolic activity rates in prefrontal (Brodmann Areas 8, 9, and 10 bilaterally) and lower in visual cortex. Patients showed this relationship only for Area 10 on the left. Patients also had low metabolism in superior, middle, and inferior prefrontal cortex. Consistent with animal models, our results demonstrate the importance of the functional integrity of prefrontal cortex to PPI modulation.

Obiective : This study reports the first paired measurements of glucose metabolism and volume of the anterior cingulate gyrus in autism. Method: Magnetic resonance imaging (MRI) and positron emission tomography (PET) scans of seven high-functioning autistic patients and seven sex- and age-matched normal volunteers were coregistered. After the anterior cingulate gyri were outlined on the MRI images, the volumes of the structures were measured and corrected for brain volume. The volumes were then applied to the PET images and metabolic maps were obtained. Results: Right anterior cingulate area 24' was significantly smaller in relative volume, and both area 24 and area 24' were metabolically less active, in the autistic patients than in the normal subjects. Conclusions: Autism may be characterized by structural and functional alterations in the anterior cingulate gyrus.

Mounting evidence suggests that white matter abnormalities and altered subcortical-cortical connectivity may be central to the pathology of schizophrenia (SZ). The anterior limb of the internal capsule (ALIC) is an important thalamo-frontal white-matter tract shown to have volume reductions in SZ and to a lesser degree in schizotypal personality disorder (SPD). While fractional anisotropy (FA) and connectivity abnormalities in the ALIC have been reported in SZ, they have not been examined in SPD. In the current study, magnetic resonance (MRI) and diffusion tensor imaging (DTI) were obtained in age- and sex-matched individuals with SPD (n=33) and healthy controls (HCs; n=38). The ALIC was traced bilaterally on five equally spaced dorsal-to-ventral axial slices from each participant's MRI scan and co-registered to DTI for the calculation of FA. Tractography was used to examine tracts between the ALIC and two key Brodmann areas (BAs; BA10, BA45) within the dorsolateral prefrontal cortex (DLPFC). Compared with HCs, the SPD participants exhibited (a) smaller relative volume at the mid-ventral ALIC slice level but not the other levels; (b) normal FA within the ALIC; (c) fewer relative number of tracts between the most-dorsal ALIC levels and BA10 but not BA45 and (d) fewer dorsal ALIC-DLPFC tracts were associated with greater symptom severity in SPD. In contrast to prior SZ studies that report lower FA, individuals with SPD show sparing. Our findings are consistent with a pattern of milder thalamo-frontal dysconnectivity in SPD than schizophrenia.

Background Borderline personality disorder (BPD) is characterized by an inability to regulate emotional responses. The amygdala is important in learning about the valence (goodness and badness) of stimuli and functions abnormally in BPD. Methods Event-related functional magnetic resonance imaging (MRI) was employed in three groups: unmedicated BPD ( n = 33) and schizotypal personality disorder ( n = 28) participants and healthy control subjects ( n = 32) during a task involving an intermixed series of unpleasant, neutral, and pleasant pictures each presented twice within their respective trial block/run. The amygdala was hand-traced on each participant's structural MRI scan and co-registered to their MRI scan. Amygdala responses were examined with a mixed-model multivariate analysis of variance. Results Compared with both control groups, BPD patients showed greater amygdala activation, particularly to the repeated emotional but not neutral pictures, and a prolonged return to baseline for the overall blood oxygen level-dependent response averaged across all pictures. Despite amygdala overactivation, BPD patients showed blunted self-report ratings of emotional but not neutral pictures. Fewer dissociative symptoms in both patient groups were associated with greater amygdala activation to repeated unpleasant pictures. Conclusions The increased amygdala response to the repeated emotional pictures observed in BPD was not observed in schizotypal patients, suggesting diagnostic specificity. This BPD-related abnormality is consistent with the well-documented clinical feature of high sensitivity to emotional stimuli with unusually strong and long-lasting reactions. The finding of a mismatch between physiological and self-report measures of emotion reactivity in BPD patients suggests they may benefit from treatments targeting emotion recognition.

Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule. Electronic supplementary material The online version of this article (doi:10.1007/s00406-011-0202-x) contains supplementary material, which is available to authorized users.

It has been proposed that schizophrenia results partly from altered brain connectivity. The anterior cingulate cortex in particular has been demonstrated to be affected in schizophrenia, with studies reporting reduced volume, altered neuronal arrangement, decreased anisotropy in diffusion tensor images, and hypometabolism. We used a 3T Siemens scanner to acquire structural and diffusion tensor imaging in age-and sex-matched groups of 41 adults with chronic schizophrenia, 6 adults with recent-onset schizophrenia, and 38 healthy control subjects. We manually traced the anterior and posterior cingulate gyri on all subjects and then compared the volume and anisotropy across groups for the left and right anterior and posterior cingulate gyri. The anterior cingulate gyrus was divided axially into six equal segments, and the posterior cingulate gyrus into two segments. Volume was calculated for the anterior and posterior gyri, and average anisotropy was then calculated for each individual segment, looking separately at gray and white matter. We found decreased overall relative left and right gray matter volume in the anterior cingulate gyrus in persons with schizophrenia compared with healthy controls. Additionally, in both gray and white matter of the cingulate, we found that recent-onset patients had the highest anisotropy, chronic patients had the lowest, and controls were intermediate. These results provide additional evidence for the presence of both white and gray matter abnormalities in the cingulate gyrus, which has been implicated in schizophrenia.

Superior temporal gyrus (STG/BA22) volume is reduced in schizophrenia and to a milder degree in schizotypal personality disorder (SPD), representing a less severe disorder in the schizophrenia spectrum. SPD and Borderline personality disorder (BPD) are severe personality disorders characterized by social and cognitive dysfunction. However, while SPD is characterized by social withdrawal/anhedonia, BPD is marked by hyper-reactivity to interpersonal stimuli and hyper-emotionality. This is the first morphometric study to directly compare SPD and BPD patients in temporal lobe volume.We compared three age-, sex-, and education-matched groups: 27 unmedicated SPD individuals with no BPD traits, 52 unmedicated BPD individuals with no SPD traits, and 45 healthy controls. We examined gray matter volume of frontal and temporal lobe Brodmann areas (BAs), and dorsal/ventral amygdala from 3-T magnetic resonance imaging.In the STG, an auditory association area reported to be dysfunctional in SPD and BPD, the SPD patients had significantly smaller volume than healthy controls and BPD patients. No group differences were found between BPD patients and controls. Smaller BA22 volume was associated with greater symptom severity in SPD patients. Reduced STG volume may be an important endophenotype for schizophrenia-spectrum disorders. SPD is distinct from BPD in terms of STG volume abnormalities which may reflect different underlying pathophysiological mechanisms and could help discriminate between them.

Findings of white matter pathology as indicated by diffusion tensor anisotropy values in schizophrenia are well established, but the differences in this measure between the onset of the disease and the chronic state are not well known. To investigate the differences between these states in the progression of the disease of schizophrenia we acquired 1.5 T diffusion tensor anisotropy images on 35 adult patients with schizophrenia and schizoaffective disorder, 23 adolescents having their first psychotic episode, and age and sex matched controls (33 adults and 15 adolescents). Regions of interest in major cortical white matter tracts chosen as salient to the prefrontal executive deficit in schizophrenia were assessed using stereotaxic coordinates from the Talairach and Tournoux atlas. Regions of each tract along anterior-posterior and/or inferior-superior directions in both hemispheres were evaluated in multiway ANOVA. Tracts between the frontal lobe and other brain regions, but not temporal, occipital and interhemispheric tracts, showed a differential aging pattern in normals and patients indicating that the white matter pathology in these regions is not stable between the onset and the chronic state in schizophrenia. This suggests that tracts involved in the connectivity of the temporal lobe white matter deficits were already well in place in adolescent patients, while frontal lobe pathology continues to develop from adolescence to adulthood.