Cortical gray matter volume deficits in schizophrenia: a replication

We sought to replicate an earlier finding of widespread deficit in cortical gray matter in schizophrenia by testing new samples of 22 schizophrenic patients and 27 controls between the ages of 21-46 years. Brain values for both patients and controls were standardized against age and head size norms derived from a larger control group (n = 73) spanning a wider age range (21-70). Compared to the new age-matched controls, the new schizophrenic sample showed a deficit in gray matter volume affecting the cortex as a whole and enlargement of the lateral and third ventricles. Thus, widespread cortical gray matter deficit is a replicable feature of the brain dysmorphology of schizophrenia in young to middle-aged men.     

Aging does not affect gray matter asymmetry.

Previous research has shown that asymmetry of brain activity is decreased in older adults. This study investigates whether cortical gray matter asymmetry also shows age-related differences, and whether gray matter asymmetry differs between cognitively stable persons and persons who have shown profound age-related declines in cognitive functioning. In addition, we have examined whether prodromal dementia affects the study outcome. The gray matter volumes of seven prefrontal and temporal regions of interest were delineated on T1-weighted MRI scans in 70 adults aged between 52 and 84 years. Statistical analyses were conducted with and without participants who developed dementia within 6 years after the MRI scan session. It was found that asymmetry did not differ over the age range of 52–84 years of age. This result did not change when data from participants who were diagnosed with dementia within 6 years after MRI assessment were excluded from the analysis. In addition, no gray matter asymmetry differences were found between cognitively stable participants and participants who showed cognitive decline. We conclude that alterations in gray matter asymmetry may not be part of the healthy aging process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Information processing in schizophrenia and bipolar disorder: a discriminant analysis

Schizophrenia and bipolar disorder are two distinct categories of mental disorders in the DSM-IV. However, it is often difficult to make a differential diagnosis because of the overlapping symptoms. A potential adjunct in the classification of schizophrenia and bipolar disorder is the application of information processing models, as patients with schizophrenia and possibly those with bipolar disorder have information processing deficits. A study was conducted in which a computerized battery of information processing tasks (called COGLAB) was administered to three participant groups: patients with schizophrenia, patients with bipolar disorder, and normal controls. The tasks included the Mueller-Lyer illusion, reaction time, size estimation, a variant of the Wisconsin Card Sorting Test, backward masking, and Asarnow continuous performance. Discriminant analyses were used to investigate the differences among the three groups. Results indicated that COGLAB correctly classified 75.5% of the cases of schizophrenia and bipolar disorder. The Mueller-Lyer illusion and the number of perseverative errors on the card sort most powerfully discriminated the two groups.     

Modal attention asymmetry in patients with schizophrenia and bipolar disorder.

This cross-sectional study examined modal attention asymmetries in patients with schizophrenia (n?=?47) and bipolar disorder (n?=?42), as contrasted to a matched-sample comparison group of normal participants (n?=?89). A test of continuous auditory and visual attention was the primary measure. The data were analyzed from 2 experimental conditions: simple modal responses (auditory and visual) and modal switching responses (ipsimodal and cross-modal switching). In the simple modal condition, patients with schizophrenia demonstrated a visual over auditory asymmetry; patients with bipolar disorder showed no differences. In modal switching conditions, however, patients with bipolar disorder displayed a significant auditory over visual asymmetry. No main effect was detected between medications and attention functioning. Results are discussed in light of differentiating these 2 populations on the basis of modal specificity of attention functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal discounting of rewards in patients with bipolar disorder and schizophrenia.

Patients with bipolar disorder (BD) and schizophrenia (SZ) often show decision-making deficits in everyday circumstances. A failure to appropriately weigh immediate versus future consequences of choices may contribute to these deficits. We used the delay discounting task in individuals with BD or SZ to investigate their temporal decision making. Twenty-two individuals with BD, 21 individuals with SZ, and 30 healthy individuals completed the delay discounting task along with neuropsychological measures of working memory and cognitive function. Both BD and SZ groups discounted delayed rewards more steeply than did the healthy group even after controlling for current substance use, age, gender, and employment. Hierarchical multiple regression analyses showed that discounting rate was associated with both diagnostic group and working memory or intelligence scores. In each group, working memory or intelligence scores negatively correlated with discounting rate. The results suggest that (a) both BD and SZ groups value smaller, immediate rewards more than larger, delayed rewards compared with the healthy group and (b) working memory or intelligence is related to temporal decision making in individuals with BD or SZ as well as in healthy individuals. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Sex differences in neuropsychological performance and social functioning in schizophrenia and bipolar disorder.

Objective: To investigate sex differences in neurocognition and social functioning in schizophrenia and bipolar disorder and the possible role of sex as a moderator of this relationship. Method: Participants with schizophrenia (60 women/94 men), bipolar I disorder (55 women/51 men), and healthy controls (158 women/182 men) were assessed with an extensive neuropsychological test battery and a social functioning questionnaire. Results: We found significant main effects of sex for neuropsychological tests (p     

Masculinized finger-length ratios of boys, but not girls, are associated with attention-deficit/hyperactivity disorder.

Gonadal hormones may exert permanent organizational effects on sexually dimorphic finger-length ratios and sexually dimorphic behavior expressed in childhood attention deficit- hyperactivity disorder (ADHD). This study extended recent work examining associations between finger-length ratios (specifically, 2D:4D) and ADHD in a well-characterized, clinically diagnosed, community-recruited sample of boys and girls. A multistage, diagnostic procedure was utilized to identify 113 children with ADHD and 137 non-ADHD comparison children. Right-hand digit ratios showed significant mean differences by gender, as well as associations with ADHD diagnosis. Boys with ADHD had more masculinized digit ratios than control-group boys. More masculine right 2D:4D and 3D:4D ratios were correlated with parent- and teacher-rated inattentive and hyperactive-impulsive symptoms in boys but not in girls. Masculinized finger-length ratios were associated with hyperactive-impulsive and oppositional- defiant symptoms, but associations were largest with symptoms of inattention. It is concluded that prenatal, organizational effects of gonadal hormones may play a role in the development of ADHD and contribute to explaining sex differences in the prevalence rates of this childhood disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A voxel-based method for the statistical analysis of gray and white matter density applied to schizophrenia

We describe a novel technique for characterizing regional cerebral gray and white matter differences in structural magnetic resonance images by the application of methods derived from functional imaging. The technique involves automatic scalp-editing of images followed by segmentation, smoothing, and spatial normalization to a symmetrical template brain in stereotactic Talairach space. The basic idea is (i) to convert structural magnetic resonance image data into spatially normalized images of gray (or white) matter density, effected by segmenting the images and smoothing, and then (ii) to use Statistical Parametric Mapping to make inferences about the relationship between gray (or white) matter density and symptoms (or other pathophysiological measures) in a regionally specific fashion. Because the whole brain sum of gray (or white) matter indices is treated as a confound, the analysis reduces to a characterization of relative gray (or white) matter density on a voxel by voxel basis. We suggest that this is a powerful approach to voxel-based statistical anatomy. Using the technique, we constructed maps of the regional cerebral gray and white matter density correlates of syndrome scores (distinct psychotic symptoms) in a group of 15 schizophrenic patients. There was a negative correlation between the score for the reality distortion syndrome and regional gray matter density in the left superior temporal lobe (P = 0.01) and regional white matter density in the corpus callosum (P < 0.001). These abnormalities may be associated with functional changes predisposing to auditory hallucinations and delusions. This method permits the detection of structural differences within the entire brain (as opposed to selected regions of interest) and may be of value in the investigation of structural gray and white matter abnormalities in a variety of brain diseases.     

Familial leukoencephalopathy in bipolar disorder

OBJECTIVE: Imaging studies of patients with bipolar disorder demonstrate changes in deep white matter and subcortical gray nuclei that are seen as focal hyperintensities on T2-weighted magnetic resonance imaging (MRI). The objective of this study was to examine MRIs in a family with a strong history of bipolar disorder to look for possible MRI abnormalities in members with and without affective illness. METHOD: The authors obtained MRIs of 21 members of a family with a strong history of bipolar disorder. Eight of the family members studied had bipolar illness, one had symptoms of bipolar disorder but did not meet full DSM-III-R criteria, two had unipolar disorder, and 10 did not have bipolar disorder. RESULTS: Fifteen of the 21 family members had MRI findings, including six of 10 family members who had no affective disorder and all of those with bipolar disorder. Lesions of both white matter and subcortical gray nuclei were found. CONCLUSIONS: Although the clinical significance of these MRI findings is unknown, the high prevalence of MRI findings in both affected and unaffected family members suggests that MRI findings may potentially serve as a biological marker for bipolar disorder. Recent genetic studies have established a link between familial leukoencephalopathy and chromosome 19. If leukoencephalopathy appears to be related to bipolar disorder, it may allow clearer characterization of the genetics of the disorder.     

Lamotrigine in rapid-cycling bipolar disorder

BACKGROUND: We evaluated the antidepressant and mood-stabilizing effects of lamotrigine, a novel anticonvulsant, in a group of rapid-cycling bipolar patients. Most were already nonresponders or poor partial responders to other conventional mood-stabilizing agents. METHODS: This open, naturalistic, and prospective study was conducted with five rapid-cycling bipolar patients (DSM-IV). Each received lamotrigine titrated to a minimum dose of 150 mg/day as monotherapy or in combination with other psychotropic agents. Patients were assessed with the Global Assessment Scale (GAS), Beck Depression Inventory (BDI), and Young Mania Rating Scale (YMRS) for evidence of cycling mood. RESULTS: Lamotrigine was used at a mean +/- SD dose of 185.0 +/- 33.5 mg/day for 225.8 +/- 28.0 days. Random regression modeling of data showed significant dose- and time-dependent improvements in depressive symptoms and social function of patients taking lamotrigine (Dose: z = 2.17, p < .03 for BDI, z = 4.44, p < .001 for GAS; Time: z = -3.79, p < .001 for BDI, z = 2.16, p < .03 for GAS). Further random regression modeling analysis of change over time in symptoms prior to lamotrigine compared with symptoms during lamotrigine treatment showed a significant treatment by time effect for GAS (z = 2.40, p < .016) and a trend for BDI scores (z = -1.79, p < .073). No significant time or dosage effect or time by treatment effect was observed for YMRS. Finally, t statistics showed a significant reduction in mean BDI scores following treatment with lamotrigine (t = -5.26, p < .006). Lamotrigine was well tolerated by all patients; only one patient experienced several side effects, which were probably due to interaction between several psychotropic medications. CONCLUSION: Lamotrigine augmentation therapy and monotherapy appeared to have mood-stabilizing and antidepressant efficacy in the treatment of five rapid-cycling bipolar patients. The effect persisted for an average of 7.5 months.     

Comparing prefrontal gray and white matter contributions to intelligence and decision making in schizophrenia and healthy controls.

The authors examined the relationship between neuropsychological performance and MRI of the orbital frontal cortex (OFC) and diffusion tensor imaging (DTI) of the cingulum bundle (CB) within groups of patients with schizophrenia and healthy subjects. The authors analyzed data from subjects, who had participated in prior MRI, DTI, and neuropsychological studies (Nakamura et al., 2008; Nestor et al., 2008). In comparison to healthy subjects, patients showed the expected reductions across CB fractional anisotropy (white matter) and OFC gray matter volume as well as lower neuropsychological scores. In addition, in comparison to healthy subjects, patients showed a very different pattern of functional-anatomical correlates. For patients, CB white matter but not OFC gray matter correlated with various aspects of intelligence, including general abilities and working memory. For controls, OFC gray matter but not CB white matter correlated with scores on tests of intelligence and decision making. These results point to the potentially important role of CB white matter in the neuropsychological disturbance in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese

The mitochondrial uncoupling protein (UCP) in the mitochondrial inner membrane of mammalian brown adipose tissue generates heat by uncoupling oxidative phosphorylation. This process protects against cold and regulates energy balance. Manipulation of thermogenesis could be an effective strategy against obesity. Here we determine the role of UCP in the regulation of body mass by targeted inactivation of the gene encoding it. We find that UCP-deficient mice consume less oxygen after treatment with a beta3-adrenergic-receptor agonist and that they are sensitive to cold, indicating that their thermoregulation is defective. However, this deficiency caused neither hyperphagia nor obesity in mice fed on either a standard or a high-fat diet. We propose that the loss of UCP may be compensated by UCP2, a newly discovered homologue of UCP; this gene is ubiquitously expressed and is induced in the brown fat of UCP-deficient mice.     

Thought disorder in adolescent-onset schizophrenia

The nature of the thinking disturbances found in adolescent-onset psychotic conditions is not as well-characterized as the thought disorders found in adult psychotic patients. We used the Thought Disorder Index to examine whether schizophrenic patients in whom psychotic symptoms appear in adolescence show the same characteristic features of thought disorder as do adult schizophrenics. Quantitative and qualitative features of thought disorder were assessed in psychiatric inpatients with adolescent-onset schizophrenia, psychotic depression, and nonpsychotic conditions compared with normal control adolescents. Elevated thought disorder occurred in all groups of adolescents hospitalized for an acute episode of psychiatric illness. The magnitude of the elevation and the frequency of occurrence of disordered thinking were greatest in the psychotic adolescents. The qualitative features of the thought disturbances found in the schizophrenic adolescents were distinct from those observed in adolescents with psychotic depression. The thinking of the schizophrenic adolescents resembled that of adult schizophrenics. In both conditions thought disorder is characterized by idiosyncratic word usage, illogical reasoning, perceptual confusion, loss of realistic attunement to the task, and loosely related ideas.     

M2, M3 and M4, but not M1, muscarinic receptor subtypes are present in rat spinal cord

Muscarinic receptors in the spinal cord have been shown to mediate antinociception and alter blood pressure. Currently, there is much interest in identifying which muscarinic receptor subtypes regulate these functions. Toward that end, this study aimed to identify and localize the muscarinic receptor subtypes present in spinal cord using in vitro receptor autoradiography with [3H]-pirenzepine and [3H]-N-methylscopolamine. The results showed that M2 binding sites were distributed throughout the dorsal and ventral horns, whereas M3 binding sites were localized to laminae I to III of the dorsal horn. Only background levels of M1 binding sites were detected. Saturation binding assays using [3H]-pirenzepine in spinal cord homogenates confirmed the absence of M1 receptors. Competition membrane receptor assays using [3H]-N-methylscopolamine and the unlabeled antagonists pirenzepine, 11-2[(-[(diethylamino)methyl]-1-piperidinyl)-acetyl]-5, 11-dihydro 6H-pyrido(2, 3-b)(1, 4) benzodiazepine-one, methoctramine, and methoctramine in combination with atropine corroborated the autoradiographic findings and also revealed the presence of M4 binding sites. The finding that M2 and M3 binding sites were localized to the superficial laminae of the dorsal horn where nociceptive A delta and C fibers terminate suggests the possibility that either or both of these muscarinic receptor subtypes modulate antinociception. The present demonstration of M4 binding sites in spinal cord is consistent with the possibility that M2 and/or M4 receptors are involved in the regulation of blood pressure at the spinal level.     

Quinolinate immunoreactivity in experimental rat brain tumors is present in macrophages but not in astrocytes

Experimental tumors of the central nervous system were investigated with antibodies to quinolinate to assess the cellular distribution of this endogenous neurotoxin. In advanced F98 and RG-2 glioblastomas and E367 neuroblastomas in the striatum of rats, variable numbers of quinolinate immunoreactive cells were observed in and around the tumors, with the majority being present within tumors, rather than brain parenchyma. The stained cells were morphologically variable, including round, complex, rod-shaped, and sparsely dendritic cells. Neuroblastoma and glioma cells were unstained, as were neurons, astrocytes, oligodendrocytes, ependymal cells, endothelial cells, and cells of the choroid plexus and leptomeninges. Glial fibrillary acidic protein immunoreactivity was strongly elevated in astrocytes surrounding the tumors. Dual labeling immunohistochemistry with antibodies to quinolinate and glial fibrillary acidic protein demonstrated that astrocytes and the cells containing quinolinate immunoreactivity were morphologically disparate and preferentially distributed external and internal to the tumors, respectively, and no dual labeled cells were observed. Lectin histochemistry with Griffonia simplicifolia B4 isolectin and Lycopersicon esculentum lectin demonstrated numerous phagocytic macrophages and reactive microglia in and around the tumors whose distribution was similar to that of quinolinate immunoreactive cells, albeit much more numerous. Dual labeling studies with antibodies to quinolinate and the lectins demonstrated partial codistribution of these markers, with most double-labeled cells having the morphology of phagocytes. The present findings suggest the possibility that quinolinate may serve a functional role in a select population of inflammatory cell infiltrates during the immune response to brain neoplasms.     

Failure of positive but not negative emotional valence to enhance memory in schizophrenia.

Abnormalities in the integration of emotion and cognition have long been considered hallmark characteristics of schizophrenia. Study authors used a well-established emotional memory model from the neuroscience literature to assess the facilitative impact of emotional valence of information on long-term memory consolidation in schizophrenia. Participants with schizophrenia (n=33) indicated somewhat higher levels of emotional intensity in response to emotional images than did healthy (n=28) participants. However, when recognition memory was tested 24 hr later, schizophrenia participants did not show enhancement of memory for positive images as was found in healthy participants. Their memory enhancement for negative images did not differ from that of healthy participants. Correlations between self-reported physical and social anhedonia were significantly inversely correlated with intensity ratings of positive stimuli during the encoding phase for healthy participants but were negligible for schizophrenia participants. These results suggest a failure to adequately integrate positive emotional experience in memory consolidation processes in schizophrenia participants, despite appropriate initial response to positive stimuli, which may contribute to symptoms such as anhedonia by reducing the long-term impact of positive experiences in motivating hedonic behavior in day-to-day life. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immunoreactivity of glycoprotein IIb is present in metastasized but not in non-metastasized primary malignant melanoma

Glycoprotein IIb-IIIa (integrin alpha IIb beta3) is an adhesive receptor involved in platelet aggregation and adhesion to the extracellular matrix. Previous studies showed the presence of IIb-IIIa-like glycoproteins on cells of melanoma cell lines and on cells of lymph node metastases. This study evaluates the presence of glycoprotein IIb-IIIa subunits on cells of primary cutaneous malignant melanomas with (n = 4) and without (n = 9) metastases over a period of 6 years and on naevus cells (n = 4). Monoclonal antibodies directed against the subunits of the glycoprotein IIb-IIIa receptor were used on paraffin-embedded sections and evaluated by means of immunohistochemistry. The glycoprotein IIb subunit was exclusively present on cells of metastatic melanomas. It was not found on non-metastatic melanomas or benign melanocytes. These data favour the role of the integrin receptor glycoprotein IIb-IIIa in the metastatic behaviour of malignant melanomas.     

White matter lesions account for all age-related declines in speed but not in intelligence.

MRI scans measured white matter lesion prevalence (WMLP) in 65 people ages 65-84 years who also took 17 cognitive tests: 3 tests of general fluid intelligence, 3 of vocabulary, 2 of episodic and 3 of working memory, 2 of processing speed, and 4 of frontal and executive function. Entry of age with WMLP into regression equations as predictors of test scores showed that inferences about the functional relationships between markers of brain aging and cognitive impairments are seriously misleading if they are based on simple correlations alone. A new finding that WMLP accounts for all of the age-related variance between individuals in tests of speed and executive ability but for none of the age-related variance in intelligence revises current hypotheses that gross brain changes affect general fluid intelligence and other mental abilities solely through their effects on information-processing speed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)