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Background Schizophrenia may involve dysfunction to primary auditory, speech, and language processes governed by the superior temporal gyrus (STG). These processes are implicated in hallucinations, delusions, and thought disorder. The current study explored the relationship between unreality symptoms (hallucinations and delusions) and specific STG substructures, including Heschl’s gyrus (HG) and planum temporale (PT). Methods Twenty-five right-handed men within their first episode of psychosis were assessed using the Positive and Negative Syndrome Scale (PANSS) for the presence of hallucinations and delusional behavior (a composite score of delusions, grandiosity, suspiciousness, and unusual thought content). T1-weighted magnetic resonance imaging (MRI) scans were acquired using a 1.5 Tesla scanner. Stereological measurements of HG and PT volume were obtained. Linear regression methods explored the relationship between regional volumes and symptoms. Results Reductions in left HG were associated with hallucinations and delusions. Increases in left PT were associated with delusional behavior. Conclusions Current results implicate HG dysfunction in unreality symptoms in men with recent-onset schizophrenia.

Background: Dysfunctions in brain regions known to be involved in affect and mood states are thought to be implicated in depression and may have a role in determining the type and symptoms of this illness. Methods: Functional magnetic resonance imaging was used to elucidate neural correlates of cognitive generation of affect, using a previously published paradigm of evoking affect with picture-caption pairs, in patients with unipolar, treatment-resistant depression. Results: Compared with control participants, patients showed relatively decreased response in the anterior cingulate (rostral; right) with both negative and positive picture-caption pairs and in the medial frontal gyrus and hippocampus (all left) with positive picture-caption pairs. They demonstrated increased response in the inferior (right) and middle temporal gyri (left) with negative picture-caption pairs, and in the parahippocampal gyrus (right), inferior frontal gyrus (left), subgenual cingulate (right), striatum (right), and brain stem (left) with positive picture-caption pairs. Conclusions: Reduced medial/middle prefrontal and hippocampal activity may account for positive affect disturbances and temporal lobe hyperactivity for negative affect disturbances in treatment-resistant depression. The results also corroborate previous observations from resting positron emission tomography studies and further elucidate the association between hypoactive rostral cingulate and nonresponsiveness to treatment in depression.

Background: Hippocampal volume reduction has been repeatedly demonstrated in schizophrenia. The relative contribution of genetic and environmental factors to this is unclear. Methods: To address this question, we compared volumetric measurements of the left and right hippocampus, obtained using stereological methods from brain MRI scans, from two groups of patients with schizophrenia as well as healthy controls ( n = 26). Patients ( n = 27) in the first group, had no family history of schizophrenia and had experienced severe pregnancy and birth complications (PBCs). The second group comprised of patients ( n = 21) without a history of severe PBCs from families multiply affected with schizophrenia. Results: Reduction of the left hippocampal volume was associated with the diagnosis of schizophrenia but was present only in patients with a history of severe PBCs; in this group the smaller the hippocampal volume, the earlier the onset of psychosis. Conclusions: Our findings suggest that environmental factors, in this case severe PBCs, make a significant contribution to hippocampal abnormalities in schizophrenia.

Background Neurocognitive deficits are severe in first-episode psychosis. Methods Patients (N = 263) with first-episode psychosis (schizophrenia, schizoaffective, or schizophreniform disorders) were randomly assigned to double-blind treatment with olanzapine (mean 11.30 mg/day) or haloperidol (mean 4.87 mg/day) for 104 weeks. A neurocognitive battery was administered at baseline (n = 246) and 12 (n = 167), 24 (n = 126), 52 (n = 89), and 104 (n = 46) weeks during treatment. Weighted principal component and unweighted composite scores were derived from individual tests. Results Both treatment groups demonstrated significant improvement on both composite scores. On the basis of the weighted composite score, olanzapine had greater improvement than haloperidol only at 12 (p = .014) and 24 (p = .029) weeks. For the unweighted composite, olanzapine had significantly better improvement compared with haloperidol only at week 12 (p = .044). At week 12 only, olanzapine improved performance on the Digit Symbol and Continuous Performance Test significantly more than haloperidol. Conclusions Both antipsychotic agents appeared to improve neurocognitive functioning among first-episode psychosis patients with schizophrenia. A significantly greater benefit in terms of neurocognitive improvement was found with olanzapine than with haloperidol at weeks 12 and 24.

Background Region of interest studies have identified a number of structure-cognition associations in schizophrenia and revealed alterations in structure-cognition relationship in this population. Methods We examined the relationship of structural brain alterations, identified using voxel-based morphometry, to cognitive deficits in 45 schizophrenia patients relative to 43 healthy control subjects and tested the hypothesis that structure-cognition relationship is altered in schizophrenia. Results Patients had smaller total brain, gray matter, and white matter volumes. Regional alterations were left-hemisphere specific, including: gray matter reduction of inferior frontal, lingual, and anterior superior temporal gyri; white matter reduction of posterior and occipital lobes; and gray matter increase of the putamen and the precuneus. Smaller whole brain and gray matter volumes were associated with lower premorbid intelligence quotient (IQ) and poorer performance on IQ-dependent cognitive measures in patients and to a similar extent in control subjects. Larger precuneus was associated with better immediate verbal memory in patients, whereas verbal and nonverbal memory were positively associated with inferior frontal gyrus volume in control subjects. Smaller occipital white matter volume was associated with slower information processing speed in patients but not in control subjects. Conclusions Regional volume alterations are associated with specific cognitive deficits in schizophrenia. Some structure-cognition relationships differentiate this population from healthy control subjects.

Background Studies using proton magnetic resonance spectroscopy in schizophrenia have demonstrated abnormality of N-acetylaspartate but are confounded by the effects of phase of illness and medication. There is mounting evidence that antipsychotic medication influences N-acetylaspartate. Methods A group of first-episode patients who had received no, or minimal, antipsychotic medication was examined at baseline and after 3 months treatment. Normal comparison subjects were examined at the same interval. Ratios of N-acetylaspartate, creatine plus phosphocreatine, and choline-containing compounds in the left prefrontal cortex, hippocampus, and basal ganglia were measured. Results The mean duration of symptoms for all patients was 31.6 (SD 26.1) weeks. A significant reduction of hippocampal N-acetylaspartate/creatine plus phosphocreatine was found in the antipsychotic-naive group relative to those previously treated and to controls at baseline ( F = 7.3, p Conclusions Hippocampal N-acetylaspartate/creatine plus phosphocreatine appears to be selectively affected early in the course of illness. The finding of neurochemical differences between treatment naive and previously treated patients confirms the relevance of medication status in proton magnetic resonance spectroscopy studies. Further investigation of the influence of medication at this stage of illness is warranted.

Background We examined monozygotic twins concordant and discordant for schizophrenia to clarify the role of genetic and environmental factors in determining brain abnormalities. Methods Magnetic resonance imaging brain scans were obtained from 14 monozygotic twin pairs concordant and 10 monozygotic pairs discordant for schizophrenia, as well as 17 pairs of monozygotic control twins. Twenty-two discordant sibling-pairs and 56 pairs of unrelated control subjects were included to assess the extent of genetic control over these structures. Results Within-pair similarities for whole brain volume increased as pair members were more closely related genetically (monozygotic twins > siblings > unrelated control subjects). Schizophrenic twins, whether from concordant or discordant pairs, had smaller whole brain volumes than control twins. The probands of discordant pairs showed more abnormalities in hippocampal, third and lateral ventricular volumes than concordant twins. Conclusions Whole brain volume is under high genetic control and smaller whole brain volume is a reflection of the genetic liability to develop schizophrenia. The variation in hippocampal and ventricular volumes within discordant monozygotic pairs indicates a role for environmental factors in determining these volume abnormalities in schizophrenia. Such factors may also underlie the more extensive morphometric deviations in patients from monozygotic discordant twins than in their counterparts from concordant twins.

Background There is evidence for hippocampal volume loss in schizophrenia, but the etiology of this remains unclear. The aim of our study was to assess the contribution of familial liability and obstetric complications to hippocampal volume reduction in schizophrenia. Methods Hippocampal volumes were obtained using stereological methods from magnetic resonance scans performed on 35 schizophrenic probands from multiply affected families and 63 of their unaffected relatives, as well as 31 schizophrenic probands from families with no other affected members, 33 of their unaffected relatives, and 68 control subjects. Results Probands with schizophrenia, regardless of family history, had significant volume reduction of the left hippocampus. Hippocampal volume was not significantly reduced in either group of relatives. Obstetric complications were associated with left hippocampal volume reduction. Conclusions We failed to find evidence that hippocampal volume loss is associated with familial liability to schizophrenia but have confirmed the association between hippocampal volume reduction and exposure to obstetric complications.

Background: Local alterations in morphological parameters are poorly characterized in several brain regions widely implicated in schizophrenia neuropathology. Methods: Surface-based anatomical modeling was applied to magnetic resonance data to obtain three-dimensional (3D) average anatomical maps and measures of location, shape, asymmetry, and volume for the lateral ventricles, hippocampus, amygdala, and superior temporal gyrus in schizophrenic ( n = 25; 15 male) and normal subjects ( n = 28; 15 male) matched for demographic variables. For all regions, intra-group variability was visualized and group differences assessed statistically to discriminate local alterations in anatomy across sex and diagnosis. Results: Posterior hippocampal volumes, lengths, and widths were reduced in patients. The right amygdala showed volume increases in schizophrenia patients versus controls. Ventricular enlargements, pronounced in the left hemisphere, occurred in the superior and lateral dimensions in patients, and these effects interacted with gender. Superior horn anterior extremes, inferior horn volumes, and hippocampal asymmetries exhibited gender effects. Significant group differences were absent in superior temporal gyrus parameters. Finally, regional variability profiles differed across groups. Conclusions: Clear morphometric differences of the lateral ventricles, hippocampus, and amygdala indicate regional displacements and shape distortions in several functional systems in schizophrenia. Alterations in these structures as mapped in 3D may provide the foundation for establishing brain abnormalities not previously defined at such a local level.

To determine whether abnormal patterns of cerebral activation previously detected in chronic schizophrenia are also present in the first episode, functional magnetic resonance imaging (fMRI) was used to compare brain function in first episode and chronic schizophrenia during a verbal working memory task. Six male, right-handed first episode schizophrenic patients were matched to chronic patients on PANSS scores. One first episode patient was antipsychotic naive; all others were receiving conventional antipsychotics. There was no significant difference in mean daily dose of chlorpromazine equivalents. Two age-matched control groups were used. There was no significant difference between any of the four groups on estimated premorbid IQ. All subjects underwent fMRI while performing a verbal working memory task (the two-back task) incorporating a periodic design. An analysis of variance (p , .01) on a voxel-wise basis was used to compare the first episode group (controls-patients) and the chronic group (controlspatients). The only significant difference in task performance between the four groups was in reaction time during the two back task: Both patient groups had reaction times slower than their respective controls (p , .05). There was no significant difference in activation pattern between the first episode group (controls-patients) and the chronic group (controls-patients). Abnormal patterns of cerebral activation in first episode schizophrenia are similar to those in chronic schizophrenia. Previously detected abnormalities in chronic schizophrenia cannot therefore be solely ascribed to psychosis symptomatology, long-term exposure to antipsychotics, or to post-onset disease progression.

Baselinebodyweigh~i.e. at the timeof startingthe newmedication, and BodyMass J.ndex(BMJ= weight(kg) + height(meters)squared)was comparedto thebodyweightandBMIfollowing4 to6 monthsoftreatment withthesameantipsychotic agent.Therewasnosi@ficantchangeinbody weightorBMIin thegrouptreatedwithrisperidone(baseline= 80.9kg z 15.9,follow-up= 80.5kg * 15.1;matchedpairt = 0.52,p=ns) andBMI (baseline= 28.7* 5.8,follow-up= 28.5 f 5.4;matchedpair t = 0.59, p=ns).However, inthegrouptreatedwitholarrr.apinethemwasa si@ficant increaseinbothbodyweight(baseline= 83.7kg * 26.7,follow-up= 86.0 kg~ 27.2;~~h~@t = 5.3,p