Low maternal hemoglobin during pregnancy and diminished neuromotor and neurocognitive performance in offspring with schizophrenia.

Objective: Previous research has linked maternal anemia during pregnancy with increased risk for schizophrenia in offspring. However, no study has sought to determine whether this early insult leads to a more severe form of the disorder, characterized by worsened motor and neurocognitive functioning.

Method: Subjects were 24 cases diagnosed with schizophrenia and 22 controls from the Developmental Insult and Brain Anomaly in Schizophrenia (DIBS) study.

Maternal-fetal blood incompatibility and neuromorphologic anomalies in schizophrenia: Preliminary findings.

Prior research has shown that maternal-fetal Rhesus (Rh) and ABO blood incompatibility increase the risk for schizophrenia. In the present study, the relationship between blood incompatibility and volumes of brain structures previously implicated in schizophrenia was assessed in schizophrenia cases and controls from a large birth cohort. Rh/ABO incompatible cases had significantly reduced cortical gray matter volume compared to compatible cases, a finding which appears to be driven by significant volume reductions in the dorsolateral prefrontal cortex and inferior frontal cortex.

Structural brain alterations in schizophrenia following fetal exposure to the inflammatory cytokine interleukin-8.

Background: Maternal infection during pregnancy has been repeatedly associated with increased risk for schizophrenia. Nevertheless, most viruses do not cross the placenta; therefore, the damaging effects to the fetus appear to be related to maternal antiviral responses to infection (e.g.

Cognitive decline in schizophrenia from childhood to midlife: a 33-year longitudinal birth cohort study.

Background: We examined cognitive deficits before and after onset of schizophrenia in a longitudinal study that: 1) covers a long time interval; 2) minimizes test unreliability by including the identical measure at both childhood and post-onset cognitive assessments; and 3) minimizes bias by utilizing a population-based sample in which participants were selected neither for signs of illness in childhood nor for being at risk for schizophrenia.

Methods: Participants in the present study, Developmental Insult and Brain Anomaly in Schizophrenia (DIBS), were ascertained from an earlier epidemiologic study conducted in Oakland, CA. The original version of the Peabody Picture Vocabulary Test (PPVT), a test of receptive vocabulary, was administered at age 5 or 9 and repeated as part of the DIBS study at an average age of 40.

Prenatal exposure to maternal infection and executive dysfunction in adult schizophrenia.

Objective: Executive dysfunction is one of the most prominent and functionally important cognitive deficits in schizophrenia. Although strong associations have been identified between executive impairments and structural and functional prefrontal cortical deficits, the etiological factors that contribute to disruption of this important cognitive domain remain unclear. Increasing evidence suggests that schizophrenia has a neurodevelopmental etiology, and several prenatal infections have been associated with risk of this disorder.

Prenatal infection and cavum septum pellucidum in adult schizophrenia.

Increased length of the cavum septum pellucidum (CSP) and in utero infection are each associated with increased risk of schizophrenia. Hence, we examined whether prenatal infections are related to CSP length in schizophrenia patients. In a well-characterized birth cohort, in utero infection was assessed using serologic biomarkers or physician diagnoses.

Automatic relevance determination for identifying thalamic regions implicated in schizophrenia.

There have been many theories about and computational models of the schizophrenic disease state. Brain imaging techniques have suggested that abnormalities of the thalamus may contribute to the pathophysiology of schizophrenia. Several studies have found the thalamus to be altered in schizophrenia, and the thalamus has connections with other brain structures implicated in the disorder.

The Wisconsin Card Sort Test and P300 responses to novel auditory stimuli in schizophrenic patients.

The authors studied the relationship between performance on the Wisconsin Card Sort Test (WCST) and P300 activity in schizophrenics and normal controls. Fourteen male predominantly medicated schizophrenics and matched non-ill controls were administered the WCST and tests of temporal lobe (delayed verbal and spatial memory) and general intellectual functioning (Shipley). Patients were rated with negative and positive symptom scales extracted from the Brief Psychiatric Rating Scale.

N-acetylaspartate reductions in the mediodorsal and anterior thalamus in men with schizophrenia verified by tissue volume corrected proton MRSI.

Objective: Deficits in the mediodorsal and anterior nuclei of the thalamus may contribute to the psychopathological symptoms of schizophrenia. These thalamic nuclei have been found to be abnormal in schizophrenia and have close connections with other brain structures implicated in the disorder. We therefore examined schizophrenia-related alterations in brain metabolite levels specifically in the mediodorsal and anterior thalamic subregions.

Decreased cortical gray and cerebral white matter in male patients with familial bipolar I disorder.

Background: Previous MRI studies of bipolar disorder have failed to consistently demonstrate cortical gray or cerebral white matter tissue loss, as well as sulcal or ventricular enlargement. The inconsistencies are most likely due to the clinical and gender heterogeneity of the study populations as well as the different MRI acquisition and processing techniques. The objective of this study was to determine if there was a cortical gray matter and cerebral white matter deficit as well as sulcal and ventricular enlargement in a homogeneous sample of euthymic male patients with familial bipolar I disorder.

Lower concentration of hippocampal N-acetylaspartate in familial bipolar I disorder.

Objective: Previous studies attempting to identify neuropathological alterations in the hippocampus in bipolar disorder have been inconclusive. The objective of this study was to determine if the concentration of N-acetylaspartate, a neuronal and axonal marker, was lower in subjects with familial bipolar I disorder than in healthy comparison subjects, suggesting possible neuronal loss, neuronal dysfunction, or neuropil reduction in bipolar I disorder.

Method: N-acetylaspartate, choline, and creatine in the right and left hippocampus were measured in 15 euthymic male patients with familial bipolar I disorder and 20 healthy male comparison subjects by using proton magnetic resonance spectroscopy ((1)H-MRS).

Anterior hippocampal volume reduction in male patients with schizophrenia.

Quantitative high resolution magnetic resonance imaging (MRI) was utilized to measure anterior, posterior, and total hippocampal volumes in 27 male patients with chronic schizophrenia and 24 male controls. To optimize measurement techniques, hippocampal volumes were: (1) acquired with 1.4-mm slices; (2) excluded with the amygdala; (3) normalized for position; and (4) corrected for total intracranial volume (ICV).

Magnetic resonance imaging of the thalamus in male patients with schizophrenia.

Thalamic abnormalities have been hypothesized to explain much of the psychopathology in schizophrenia, however, quantitative magnetic resonance imaging (MRI) studies have yielded discrepant results as to whether there are thalamic volume alterations. The current study utilized high resolution MRI and an axial voluming protocol to determine if there was a significant reduction in the volume of the thalamus in patients with schizophrenia. Quantitative analysis was performed on magnetic resonance images of the brain in 41 male medicated schizophrenic patients and 39 male normal control subjects similar in age, education and handedness.

Evidence for altered cerebellar vermis neuronal integrity in schizophrenia.

To determine if there was evidence for altered neuronal integrity in the cerebellar vermis of patients with schizophrenia, the authors measured N-acetyl-aspartate (NAA, a putative neuronal/axonal marker) using in vivo proton magnetic resonance spectroscopic imaging (1H-MRSI) in 20 chronically medicated male patients with schizophrenia and 15 male comparison subjects. Relative contributions of cerebrospinal fluid, gray matter, and white matter to each MRSI voxel were determined using an MRI tissue segmentation technique. The percentage of tissue was used as a co-variate to determine the extent to which tissue composition contributed to NAA differences.

Increased thalamic N-acetylaspartate in male patients with familial bipolar I disorder.

N-Acetylaspartate (NAA) in the anterior and mediodorsal thalamic regions was measured using proton magnetic resonance spectroscopic imaging (1H-MRSI) in 15 euthymic male patients with familial bipolar I disorder and compared to values in 15 male control subjects to determine if there was evidence for altered neuronal/axonal integrity. MRI tissue segmentation methods were also utilized to obtain tissue-contribution estimates for each MRSI voxel. Relative to the comparison group, the patients with bipolar I disorder demonstrated significantly higher NAA and creatine in both the right and left thalamus.

Reduced concentrations of thalamic N-acetylaspartate in male patients with schizophrenia.

Objective: The authors measured N-acetylaspartate (a putative neuronal marker) in the right and left thalamus of 17 male patients with schizophrenia using in vivo proton magnetic resonance spectroscopic imaging ((1)H MRSI).

Method: (1)H MRSI was performed on 17 medicated male patients with schizophrenia and 10 male comparison subjects. Concentrations of N-acetylaspartate, creatine, and choline were determined in the thalamic regions bilaterally.

Proton magnetic resonance spectroscopy of the human brain in schizophrenia.

In vivo proton magnetic resonance spectroscopy (1H MRS) has been utilized by neuroimaging laboratories in recent years to reliably measure compounds such as N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and to a lesser extent glutamate and glutamine in the human brain. To date, the most consistently replicated findings in schizophrenia are reduced NAA measures in the hippocampal regions. Since NAA is thought to be a neuronal/axonal marker and a measure of neuronal/axonal integrity, hippocampal NAA reductions have been interpreted as strong evidence for neuronal/axonal loss or dysfunction in this brain region.

Reduced hippocampal N-acetylaspartate without volume loss in schizophrenia.

Quantitative magnetic resonance imaging (MRI) can measure total gray matter volume but cannot discriminate between neurons and glia. Proton magnetic resonance spectroscopic imaging (1H MRSI) measures N-acetylaspartate (NAA) which is a selective marker of neuronal loss or neuronal dysfunction. The objective of this study was to obtain quantitative measures of hippocampal volume and hippocampal NAA to determine if there was evidence for hippocampal neuronal dysfunction or neuronal loss in schizophrenia.

Hippocampal neuronal dysfunction in schizophrenia as measured by proton magnetic resonance spectroscopy.

Background: Previous neuropathological and neuroimaging studies have documented neuronal loss in the hippocampal region in schizophrenia. N-acetylaspartate (NAA) is a neuronal/axonal marker that may be utilized to assess neuronal loss or dysfunction by proton magnetic resonance spectroscopy (1H MRS). This study measured NAA, choline, and creatine in the hippocampal region of patients with schizophrenia using in vivo proton magnetic resonance spectroscopic imaging (1H MRSI).

Proton magnetic resonance spectroscopy of the anterior cingulate region in schizophrenia.

The authors measured N-acetylaspartate (NAA, a putative neuronal marker), choline and creatine in the anterior cingulate region of 26 schizophrenic patients and 16 control subjects using in vivo proton magnetic resonance spectroscopic imaging (1H MRSI). Relative to the control group, the patients with schizophrenia demonstrated significantly lower NAA in both the right and left anterior cingulate regions. There was no association between NAA and duration of illness or medication dosage.

Decreased left frontal lobe N-acetylaspartate in schizophrenia.

Objective: The authors measured N-acetylaspartate (a putative neuronal marker), using in vivo proton magnetic resonance spectroscopic imaging (1H-MRSI), in the frontal lobes of schizophrenic patients and normal subjects.

Method: Frontal lobe 1H-MRSI was performed bilaterally on 24 medicated schizophrenic patients and 15 healthy comparison subjects. Levels of N-acetylaspartate, creatine, and choline were determined.

Asymmetry of temporal lobe phosphorous metabolism in schizophrenia: a 31phosphorous magnetic resonance spectroscopic imaging study.

In vivo 31Phosphorous magnetic resonance spectroscopic imaging (31P MRSI) was performed on 18 chronic schizophrenic patients and 14 normal controls to determine if there was asymmetry of high-energy phosphorous metabolism in the temporal lobes of schizophrenic patients. Temporal lobe phosphorous metabolites were also correlated with severity of psychiatric symptomatology as assessed by the Brief Psychiatric Rating Scale (BPRS). Schizophrenics demonstrated significantly higher right relative to left temporal phosphocreatine/adenosine triphosphate (PCr/ATP), phosphocreatine/inorganic phosphate (PCr/Pi), and PCr as well as significantly lower right relative to left temporal ATP.

Abnormal frontal lobe phosphorous metabolism in bipolar disorder.

Objective: Abnormalities in frontal lobe phosphorous metabolism in patients with bipolar disorder have been reported, but many of the patients studied were receiving lithium. In this study, medication-free bipolar patients were examined to determine abnormalities in frontal lobe high-energy phosphorous metabolism.

Method: In vivo phosphorous-31 magnetic resonance spectroscopic imaging was performed on 12 unmedicated, euthymic bipolar patients and 16 healthy comparison subjects.

Effects of chronic alcohol abuse and HIV infection on brain phosphorus metabolites.

We examined the effects of human immunodeficiency virus (HIV) infection and chronic alcohol consumption on cerebral phosphorus metabolites to determine if chronic alcohol abuse is a risk factor for the progression of neurological effects of HIV infection. We studied 15 HIV- alcoholics, 8 HIV- light/nondrinkers, 32 HIV+ alcoholics, and 41 HIV+ light/nondrinking men, with both HIV+ groups having similar CD4 lymphocyte counts. We used localized 31-phosphorus magnetic resonance spectroscopy after magnetic resonance imaging to examine two brain volumes in superior white matter and subcortical gray matter.

Decreased temporal lobe phosphomonoesters in bipolar disorder.

In vivo [31P]magnetic resonance spectroscopic imaging ([31P]MRSI) was performed on 12 unmedicated, euthymic bipolar patients and 14 control subjects to determine if there were alterations in high-energy P metabolism in the temporal lobes of bipolar patients. Compared with the control group, the patients with bipolar disorder demonstrated significantly lower phosphomonoesters (PME) in both the left and right temporal lobes. No other group differences in P metabolites or lateralized asymmetries were noted.