Normal Comparison Subjects Research Articles

Development of shared information in communication despite hippocampal amnesia

This study investigated the ability of individuals with amnesia to acquire referential labels across a series of collaborative, dynamic interactions with a communication partner. Despite their inability to learn arbitrary relations in paired-associate learning, the amnesic patients showed remarkably robust collaborative learning across trials, at a rate equal to that of normal comparison subjects. The amnesic participants' learning resulted in their arriving at labels for a set of abstract shapes (tangrams), thus facilitating rapid and efficient communication. The labels generated and used by the amnesics during interactions with their partners became simpler across trials, with most labels stabilizing long before the end of training and then being used consistently throughout; moreover, they endured long after the task had ended. These findings have important implications for understanding the memory systems involved in semantic learning and in acquiring shared knowledge ('common ground') among communication partners, and the nature of hippocampal-dependent versus hippocampal-independent learning.

Regional specificity of chandelier neuron axon terminal alterations in schizophrenia

Background: The axon terminals of GABAergic chandelier cells form linear arrays, termed cartridges, that synapse on the axon initial segment of neocortical pyramidal cells. These cartridges are immunoreactive for the GABA membrane transporter-1, and the density of GABA membrane transporter-1-immunoreactive cartridges in the prefrontal cortex has been reported to be reduced in schizophrenia. The goal of this study was to determine if reductions in the density of GABA membrane transporter-1-immunoreactive cartridges in schizophrenia are restricted to the prefrontal cortex. Methods: Relative GABA membrane transporter-1-immunoreactive cartridge density was determined in auditory association area 42, a region previously implicated in the pathophysiology of schizophrenia, in 14 matched pairs of subjects with schizophrenia and normal comparison subjects. The results were compared with similar data from prefrontal area 46 in the same subjects. Results: Mean GABA membrane transporter-1-immunoreactive cartridge density in area 42 was decreased by 9.8% in layers II–IIIa, and by 11.9% in layer VI in subjects with schizophrenia, although these differences did not achieve statistical significance. However, the magnitude of the reductions in the density of GABA membrane transporter-1-immunoreactive cartridges in area 42 of the subjects with schizophrenia was not significantly smaller than those in area 46. Conclusions: In subjects with schizophrenia, alterations in chandelier neuron axon cartridges appear to be more marked in the prefrontal cortex than in another cortical region implicated in the illness, although such changes might not be restricted to the prefrontal cortex.

Sustained Remission of Schizophrenia

Back to table of contents Previous article Next article Letter to the EditorFull AccessSustained Remission of SchizophreniaROBERT PAUL LIBERMAN, M.D., and ALEX KOPELOWICZ, M.D., ROBERT PAUL LIBERMANSearch for more papers by this author, M.D., and ALEX KOPELOWICZSearch for more papers by this author, M.D., Los Angeles, Calif.Published Online:1 Sep 2005https://doi.org/10.1176/appi.ajp.162.9.1763AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: In their article on sustained remission of schizophrenia in older outpatients, Dilip V. Jeste, M.D., and Lisa A. Auslander, Ph.D. (1), matched 12 patients with sustained remission with 12 still-symptomatic schizophrenia patients and 12 normal comparison subjects. Their finding of no statistical differences on a composite measure of neurocognitive functioning between the schizophrenia patients who were or were not in sustained remission was viewed as an example of the persistence of neurocognitive deficits even in patients whose symptoms were low or nil. In their article, they did not specify the criteria used for defining sustained remission in terms of quantitative levels of symptoms, nor did they report the age-appropriate, psychosocial functional status of the patients, such as peer relations, independent recreational activities, employment or volunteer work, or the ability to live without supervision of finances and medication management. Because neurocognitive capacities are known to be much more related to psychosocial functioning than to symptoms, it is important to include personal functioning in studies relating neurocognition to good outcomes.In a study using the same design, we matched 28 middle-aged schizophrenia patients who were in sustained remission and living independently for 2 years or more with 28 still-symptomatic schizophrenia patents and 28 normal comparison subjects. To meet our criteria for sustained remission, or recovery, we required the patients to score 4 or less on the Brief Psychiatric Rating Scale, to work or attend school at least half-time, to live independently (without supervision of their finances and medication management), and to have at least one social activity per week with a peer without professional involvement.We found that neurocognitive performance on tests tapping executive functioning, verbal fluency, and verbal working memory was the same for the recovered schizophrenic patients and their matched normal comparison subjects and significantly better than that of the still-symptomatic patients (2). The only cognitive functioning that remained significantly different between the recovered patients and the normal subjects was early visual processing, as measured by the Forced-Choice Span on Apprehension Test (3), which is viewed as an enduring vulnerability or “trait marker” for schizophrenia.Because the criteria for sustained remission and psychosocial functioning were not specified in the article by Drs. Auslander and Jeste, it was not possible to compare the results with our study strictly; however, it is worth pointing out that the article by Drs. Auslander and Jeste 1) collapsed their neurocognitive tests into a global index and 2) used statistical tests with a tiny sample to determine mean differences between the groups on neurocognitive, quality of life, and social functioning rather than evaluating differences between subsamples that achieved or did not achieve categorical definitions of symptomatic and functional recovery.If Drs. Auslander and Jeste could assign specific criteria to their definitions of “sustained remission” or “psychosocial functioning,” it might be possible to determine how many of their small group actually achieved an operationalized construct of recovery that might reflect differences in neurocognition between recovered and nonrecovered patients. Identifying neurocognitive and other malleable predictors and correlates of optimal clinical improvement and recovery can contribute to a growing database that would be relevant for targeting treatment interventions with resultant improvements in services for persons with schizophrenia (4).We are delighted that other investigators have begun to develop criteria for recovery from schizophrenia and are conducting research on this elusive but much-desired outcome. We agree with Drs. Auslander and Jeste that patients with schizophrenia would have considerably greater opportunities for recovery if systems of care provided services that offered combined comprehensive, continuous, coordinated, compassionate, consumer-oriented, and evidence-based psychosocial rehabilitation.

Forward and Backward Visual Masking in Unaffected Siblings of Schizophrenic Patients

Visual masking tasks assess the earliest stages of visual processing. This study examined visual masking performance for forward and backward masking tasks in siblings of schizophrenic patients and healthy comparison subjects. A staircase method was used to ensure that unmasked target identification was equivalent across subjects to eliminate differences due to discrimination of simple perceptual inputs. Four computerized visual masking tasks were administered to 43 siblings of patients and 42 normal comparison subjects. The tasks included: 1) locating a target; 2) identifying a target with a high-energy mask; 3) identifying a target with a low-energy mask; and 4) a paracontrast/metacontrast procedure with nonoverlapping target and mask. Across masking conditions, there was a significant group by forward/backward interaction, meaning that siblings showed a larger difference from control subjects in backward versus forward masking. This group difference was more pronounced in the location condition. These results support the theory that visual masking procedures may be indicators of vulnerability to schizophrenia. The pattern of findings in this report (larger group differences on backward versus forward masking and on the location condition) suggests that the activity of transient visual channels may be particularly linked to vulnerability.

Lateralized cognitive dysfunction and psychotic symptoms in schizophrenia

Our understanding of hemispheric asymmetries in schizophrenia can be attributed to extensive neuropsychological and neuroimaging research on this topic; however, it has yet to be determined whether lateralized cognitive dysfunction represents a single core trait in schizophrenia or whether the lateralized impairments are domain specific. To test whether lateralized deficits are core features in schizophrenia we examined performance across a wide range of lateralized cognitive domains including attention, fluency, recognition memory, perception, and arousal. We also examined the relationship between lateralized impairments and psychotic and affective symptoms to determine whether abnormal hemispheric asymmetries were possibly state-related. The sample consisted of 43 subjects with schizophrenia and 66 normal healthy comparison subjects without psychiatric illness. Schizophrenia subjects exhibited abnormal right hemisphere performance on a test of recognition memory and abnormal left hemisphere performance on a measure of arousal. These findings suggest that lateralized cognitive disturbances in schizophrenia do not represent a single core lateralized deficit. Regarding the symptom analyses, severity of positive symptoms was related to right hemisphere cognitive impairment (including fluency and recognition memory), whereas severity of negative symptoms was related to left hemisphere cognitive impairment (including fluency). Overall, our findings suggest that lateralized dysfunction can occur in both hemispheres in schizophrenia, and that the positive psychotic symptoms may relate more to right hemisphere impairment, whereas negative psychotic symptoms may related more to left hemisphere impairment.

Reduced Left Angular Gyrus Volume in First-Episode Schizophrenia

Research suggests that the normal left-greater-than-right angular gyrus volume asymmetry is reversed in chronic schizophrenia. The authors examined whether angular gyrus volume and asymmetry were abnormal in patients with first-episode schizophrenia. Magnetic resonance imaging scans were obtained from 14 inpatients at their first hospitalization for psychosis and 14 normal comparison subjects. Manual editing was undertaken to delineate postcentral, supramarginal, and angular gyri gray matter volumes. Group comparisons revealed that the left angular gyrus gray matter volume in patients was 14.8% less than that of the normal subjects. None of the other regions measured showed significant group volume or asymmetry differences. Patients with new-onset schizophrenia showed smaller left angular gyrus volumes than normal subjects, consistent with other studies showing parietal lobe volume abnormalities in schizophrenia. Angular gyrus pathology in first-episode patients suggests that the angular gyrus may be a neuroanatomical substrate for the expression of schizophrenia.

Validity and Reliability of a Taiwan Chinese Version of the Community Screening Instrument for Dementia

The Community Screening Instrument for Dementia (CSI-D) has been reported to be sensitive. The authors examined the reliability and validity of a Chinese (Taiwanese) version of the CSI-D for elderly patients. Four groups were tested with the CSI-D: 31 with mild or moderate dementia; 32 non-dementia, depressed subjects; and 34 low-education, and 30 high-education normal-comparison subjects. Patients with dementia or depression were selected from outpatients of two hospitals. Testing was carried out in either the community or outpatient setting. The internal consistency, interrater reliability, and test-retest reliability of the CSI-D were good. The CSI-D was highly correlated with scores on the Mini-Mental State Examination and 10-word-list-learning task. Correlation with the Montgomery-Asberg Depression Rating Scale was not significant. Receiver Operating Characteristic analysis suggested that the CSI-D was a good instrument in differentiating dementia from depression and normal subjects with low education. It had good sensitivity and specificity. Education was related to the cognitive scores but not related to informant scores. The combination of an informant interview with a cognitive test enhanced the performance of the CSI-D. The Taiwan Chinese version of the CSI-D is psychometrically sound, brief, easy to complete, and therefore suitable as a screening instrument for dementia in Taiwan. The study reinforces earlier suggestions that the informant interview yields improved validity for detecting dementia.

Validity and Reliability of a Taiwan Chinese Version of the Community Screening Instrument for Dementia

<h3>Objective</h3> The Community Screening Instrument for Dementia (CSI-D) has been reported to be sensitive. The authors examined the reliability and validity of a Chinese (Taiwanese) version of the CSI-D for elderly patients. <h3>Methods</h3> Four groups were tested with the CSI-D: 31 with mild or moderate dementia; 32 non-dementia, depressed subjects; and 34 low-education, and 30 high-education normal-comparison subjects. Patients with dementia or depression were selected from outpatients of two hospitals. Testing was carried out in either the community or outpatient setting. <h3>Results</h3> The internal consistency, interrater reliability, and test–retest reliability of the CSI-D were good. The CSI-D was highly correlated with scores on the Mini-Mental State Examination and 10-word-list-learning task. Correlation with the Montgomery-Asberg Depression Rating Scale was not significant. Receiver Operating Characteristic analysis suggested that the CSI-D was a good instrument in differentiating dementia from depression and normal subjects with low education. It had good sensitivity and specificity. Education was related to the cognitive scores but not related to informant scores. The combination of an informant interview with a cognitive test enhanced the performance of the CSI-D. <h3>Conclusions</h3> The Taiwan Chinese version of the CSI-D is psychometrically sound, brief, easy to complete, and therefore suitable as a screening instrument for dementia in Taiwan. The study reinforces earlier suggestions that the informant interview yields improved validity for detecting dementia.

Lamina-Specific Reductions in Dendritic Spine Density in the Prefrontal Cortex of Subjects With Schizophrenia

In a previous study the authors found that dendritic spine density was reduced on prefrontal pyramidal neurons in layer 3 of subjects with schizophrenia. From a neural circuitry perspective, understanding the pathophysiological significance of this finding requires knowledge of whether pyramidal neurons in other cortical layers are similarly affected. The authors' goal was to determine whether their finding in layer 3 was also present in other cortical layers in the same group of subjects with schizophrenia. Spine density and other dendritic measures were made for pyramidal neurons in layers 5 and 6 of prefrontal area 46 in the brains of deceased subjects with schizophrenia, subjects with other psychiatric disorders, and normal comparison subjects. None of the dendritic measures for layer 5 or 6 pyramidal neurons differed across the subject groups, but the within-subject differences in spine density between deep layer 3 and layer 5 or 6 pyramidal neurons were significantly greater in the patients with schizophrenia than in the comparison subjects. These findings are consistent with the idea that prefrontal pyramidal neurons involved in corticocortical and/or thalamocortical connections are preferentially affected in schizophrenia.

Hippocampus, VI: Depression and the Hippocampus

Back to table of contents Previous article Next article Images in NeuroscienceFull AccessHippocampus, VI: Depression and the HippocampusAlexander Neumeister, M.D., , Dennis S. Charney, M.D., , and Wayne C. Drevets, M.D., Alexander NeumeisterSearch for more papers by this author, M.D., West Haven, Ct., Dennis S. CharneySearch for more papers by this author, M.D., New York, N.Y., and Wayne C. DrevetsSearch for more papers by this author, M.D., Bethesda, Md.Published Online:1 Jun 2005https://doi.org/10.1176/appi.ajp.162.6.1057AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Recent evidence suggests that the hippocampus may be disordered in patients with major depressive disorder, with the speculation that disease-associated elevated cortisol levels might mediate alterations in hippocampal physiology and, consequently, alter cognitive performance in persons with the illness. In support of this are reports from several laboratories that have shown a reduction in hippocampal volume in the illness that is most severe in those with early age at onset, many previous episodes, longer durations of untreated illness, and a childhood abuse history. It appears that the posterior segment of the hippocampus is most consistently involved in the volume reduction in patients with major depressive disorder. Cognitive studies show that learning and memory are altered in major depressive disorder, consistent with an abnormality in the posterior hippocampus. Cellular changes in the posterior hippocampus in patients with major depressive disorder have still to be elucidated, but there is evidence of an involvement of an alteration in the serotonin and neurotropin systems. Of interest is that a reduction of mRNA for the serotonin 5-HT1a receptor has been demonstrated in patients with major depressive disorder. It is not clear whether this represents a primary abnormality specific to depression or, alternatively, whether reduced 5-HT1a receptor expression results from abnormal interaction between neurotropins (such as brain-derived neurotrophic factor) and serotonin receptors. Illustrated here is an approach to analyzing volume in the human hippocampus. Using anatomically specific criteria, hippocampal regions of interest were defined on anterior to posterior structural MRI scans (Figure, left). We averaged the volumes for these hippocampal regions of interest across all medication-free depressed patients and contrasted these with matched normal comparison subjects. Consistent with previous data from medicated patients, hippocampal volumes were reduced in persons with major depressive disorder, and these reductions were restricted to the posterior regions (Figure, right). We speculate that this volume reduction represents cellular alterations in 5-HT1a and neurotropin mechanisms, possibly related to elevated cortisol levels.One might consider that these kinds of changes underlie the alterations in learning and memory associated with major depressive disorder.Address reprint requests to Dr. Tamminga, UT Southwestern Medical Center, Department of Psychiatry, 5323 Harry Hines Blvd., #NC5.914, Dallas, TX 75390-9070; [email protected] (e-mail). Figure. The four magnetic resonance images of the medial temporal cortex show the most anterior (a) to posterior (d) regions of interest, respectively, of the hippocampus. The graph shows the average total, posterior, and anterior hippocampal volumes for depressed versus normal subjects and shows the posterior volume reduction in those with major depressive disorder. FiguresReferencesCited byDetailsCited byReduced Sulcal Depth in Central Sulcus of Major Depressive DisorderExperimental Neurobiology, Vol. 31, No. 5Sex-specific hippocampus volume changes in obstructive sleep apneaNeuroImage: Clinical, Vol. 20BMC Psychiatry, Vol. 18, No. 1Investigative Magnetic Resonance Imaging, Vol. 19, No. 1, Vol. 209PLoS ONE, Vol. 7, No. 5Neurosurgery Clinics of North America, Vol. 22, No. 2Research in Developmental Disabilities, Vol. 32, No. 5Indo-Pacific Journal of Phenomenology, Vol. 10, No. 2Emotion Modelling Towards Affective Pathogenesis1 December 2009 | Australasian Psychiatry, Vol. 17, No. 6Beyond Neurobiological Reductionism14 August 2009 | Theory & Psychology, Vol. 19, No. 4Peripheral biomarker composite associated with smaller hippocampal volumeNeuroReport, Vol. 19, No. 13Functional Magnetic Resonance in PsychiatryTopics in Magnetic Resonance Imaging, Vol. 19, No. 2The role of hippocampus in the pathophysiology of bipolar disorderBehavioural Pharmacology, Vol. 18, No. 5-6Neuroimaging Clinics of North America, Vol. 17, No. 4Current Opinion in Psychiatry, Vol. 20, No. 1 Volume 162Issue 6 June 2005Pages 1057-1057 Metrics PDF download History Published online 1 June 2005 Published in print 1 June 2005

Bolus transit patterns in healthy subjects: a study using simultaneous impedance monitoring, videoesophagram, and esophageal manometry

Impedance monitoring (Imp) measures bolus transit. Combining Imp with manometry (EM) allows the effect of contractile patterns on transit to be assessed. The objective of this study is to identify bolus transit patterns in normal subjects, correlate Imp findings with the gold standard barium esophagram (Ba), and compare bolus transit with concomitant EM findings. Simultaneous Ba-Imp-EM was performed for 2 min in 15 normal volunteers (women, 11; age, 43 yr). Combined impedance-pressure sites were 5, 10, 15, 20 cm above the lower esophageal sphincter (LES). Boluses (10 ml) of 45% barium mixed with 0.9% NaCl were swallowed at > or = 20-s intervals (5-6 swallows/subject). Imp and Ba showed three bolus transit patterns, and the two methods were in agreement on the pattern type in 97% (83/86) of swallows. Normal bolus transit was found in 73% (61/83), and each had normal peristalsis and contraction amplitude. Stasis in the proximal esophagus occurred in 7 of 83 swallows despite normal manometric parameters in 4 of 7 swallows. Retrograde escape of a residue of incompletely cleared bolus from just above the LES to the site 5 cm above occurred in 14 of 83 swallows. Retrograde escape was triggered by the next swallow, occurred despite normal manometric parameters, and did not occur if the swallow interval was >30 s. In 55% (47/86) of swallows, air accumulated in the distal esophagus and persisted there for a mean of 3.6 s until cleared into the stomach. We conclude that impedance monitoring is a valid transit test and describe bolus transit patterns in normal subjects for comparison with patients with esophageal motility disorders.

Higher Levels of Basal Serial CSF Cortisol in Combat Veterans With Posttraumatic Stress Disorder

Results of basal peripheral cortisol measures in posttraumatic stress disorder (PTSD) have been variable. The authors' goal was to measure CSF cortisol concentrations, which more accurately reflect brain glucocorticoid exposure, in subjects with or without PTSD. CSF was withdrawn from a subarachnoid catheter and plasma from a venous catheter, both indwelling, over a 6-hour interval to determine hourly plasma ACTH and cortisol concentrations and hourly CSF cortisol levels in eight well-characterized combat veterans with PTSD and eight matched healthy volunteers. Mean CSF cortisol concentrations were significantly higher in the subjects with PTSD (3.18 ng/ml, SD=0.33) than in the normal volunteers (2.33 ng/ml, SD=0.50), largely due to higher CSF cortisol concentration nadirs. No group differences were observed in either plasma ACTH or peripheral (plasma or urinary free) cortisol. CSF corticotropin-releasing hormone and CSF cortisol concentrations were positively and significantly correlated. Despite normal peripheral cortisol indexes in the veterans with PTSD, their CNS exposure to cortisol was greater than that of normal comparison subjects.

P50 Suppression in Individuals at Risk for Schizophrenia: The Convergence of Clinical, Familial, and Vulnerability Marker Risk Assessment

Identification of individuals at risk for the development of schizophrenia is important because it can lead to a greater understanding of the early stages of the illness. The aim of the present study was to determine whether individuals "at risk" for schizophrenia have deficits in P50 suppression, a preattentive measure of sensory gating. Thirty-one at-risk and 21 normal comparison subjects were referred to the CARE (Cognitive Assessment and Risk Evaluation) Program at University of California San Diego. The primary aim of the CARE Program is to identify individuals who are at the greatest risk for conversion to psychosis, with a combination of clinical, familial, and vulnerability markers, including P50 suppression. As a group, the at-risk subjects had modestly lower levels (effect size=.43) of P50 suppression (55.1%, SD=39.8) relative to comparison subjects (71.5%, SD=34.7). At-risk subjects with a first-degree relative with schizophrenia had profoundly deficient P50 suppression (16.4%, SD=33.8) compared with other at-risk (p<.05) and comparison subjects (p<.005). Ongoing longitudinal follow-up studies will determine whether it is possible to improve the predictive validity of the clinical and familial variables by using P50 suppression alone or in combination with other measures in determining which individuals are at greatest risk for schizophrenia.

Beyond hypofrontality: A quantitative meta‐analysis of functional neuroimaging studies of working memory in schizophrenia

Although there is considerable evidence that patients with schizophrenia fail to activate the dorsolateral prefrontal cortex (DLPFC) to the degree seen in normal comparison subjects when performing working memory or executive tasks, hypofrontality may be coupled with relatively increased activity in other brain regions. However, most imaging studies of working memory in schizophrenia have focused on DLPFC activity. The goal of this work is to review functional neuroimaging studies that contrasted patients with schizophrenia and healthy comparison subjects during a prototypical working memory task, the n-back paradigm, to highlight areas of hyper- and hypoactivation in schizophrenia. We utilize a quantitative meta-analysis method to review 12 imaging studies where patients with schizophrenia were contrasted with healthy comparison subjects while performing the n-back paradigm. Although we find clear support for hypofrontality, we also document consistently increased activation in anterior cingulate and left frontal pole regions in patients with schizophrenia compared to that in controls. These data suggest that whereas reduced DLPFC activation is reported consistently in patients with schizophrenia relative to healthy subjects, abnormal activation patterns are not restricted to this region, raising questions as to whether the pathophysiological dysfunction in schizophrenia is specific to the DLPFC and about the relationship between impaired performance and aberrant activation patterns. The complex pattern of hyper- and hypoactivation consistently found across studies implies that rather than focusing on DLPFC dysregulation, researchers should consider the entire network of regions involved in a given task when making inferences about the biological mechanisms of schizophrenia.

Cortical intercorrelations of temporal area volumes in schizophrenia

Background Abnormal temporal connections with other cortical areas may underlie some of the most prominent cognitive deficits described in schizophrenia. In order to evaluate the relationship between temporal and other cortical regions in schizophrenia, we examined the intercorrelations of volumetric measures of gray and white matter for each Brodmann's area of the temporal lobe with volumes in the rest of the cortex in patients with schizophrenia and normal comparison subjects. Methods MR images were acquired in normal subjects ( n=46) and patients with schizophrenia ( n=106), divided into good-outcome ( n=52) and poor-outcome (Kraepelinian; n=54) subtypes; and correlational patterns between the volumes of individual Brodmann's areas were compared and examined in relation to outcome. Results Positive frontotemporal intercorrelations were significantly stronger while negative frontotemporal intercorrelations were weaker in schizophrenia patients as compared to normal subjects. Correlations between the right temporal pole and other temporal regions were significantly weaker in schizophrenia patients than in controls. When compared to normal controls and good-outcome patients, schizophrenia patients with poor outcomes showed a selective pattern of stronger gray matter correlations between the medial temporal vs. primary visual and between primary auditory vs. dorsolateral prefrontal cortices, all in the left hemisphere. Conclusions Strengthening of positive associations among the temporal and extratemporal (mainly frontal and occipital) regions as well as weakening of regional intercorrelations within the temporal lobe in patients appear to constitute the major differences of correlational patterns in schizophrenia patients and normal subjects. Present findings may be implicated in object recognition deficits seen in patients with schizophrenia, as well as in purportedly deficient spatial and semantic processing of both auditory and visual information that may be associated with poor outcome.

Attentional and neurocognitive characteristics of high-risk offspring of parents with schizophrenia compared with DSM-IV attention deficit hyperactivity disorder children

Offspring of individuals with schizophrenia are at increased baseline risk for a range of early mental disorders. Studies investigating the premorbid characteristics of individuals with schizophrenia indicate that they suffer from social, behavioral, attentional and neurocognitive impairments, often resembling attention deficit hyperactivity disorder (ADHD). In this study, we compared the executive functioning and general intelligence among three groups: (i) children and adolescents with DSM-IV ADHD ( n=41), (ii) “high-risk” (HR) offspring of parents with DSM-IV schizophrenia, and (iii) normal comparison subjects ( n=35). Our results indicated that both HR and ADHD groups had lower Verbal IQ scores. ADHD cases had significantly lower percent correct and total errors in Wisconsin Cart Sorting Test when compared with normal comparison subjects. The HR cases also had lower Performance IQ scores as well as worse abstraction–flexibility and comprehension performance. The HR group was further stratified with (HR-A) and without (HR-NA) comorbid ADHD, and HR-A subjects were significantly noted to be more impaired on most tests. The overall worse performance of HR offspring was attributable to significantly lower performance among the HR-A youth. Further, our results suggested that the most profoundly impaired HR subjects were in fact children and adolescents who also met criteria for ADHD. Future studies with broader neuropsychological test batteries are necessary to investigate the differences and similarities between ADHD and the HR-A subgroup.

Deficits in Social Knowledge Following Damage to Ventromedial Prefrontal Cortex

Patients with damage to the frontal lobes frequently exhibit impaired social behavior, but it is not clear which specific processes are disrupted. The authors investigated the ability to interpret nonverbal emotional expression in patients with lesions involving ventromedial (N=20) or dorsolateral prefrontal cortex (N=9) and in healthy volunteers (N=23). As hypothesized, only patients with ventromedial prefrontal lesions showed impaired task performance relative to normal comparison subjects. These results suggest that deficits in social knowledge, namely difficulty interpreting nonverbal emotional expression, contribute to the aberrant social behavior observed following ventromedial prefrontal cortex lesions.

Familial cognitive deficits in schizophrenia

Susceptibility to schizophrenia is considered familial, but the mechanism for transmission has not been found. Since widespread cognitive deficits have been found in patients with schizophrenia, several of these have been proposed as candidate familial endophenotypes that may or may not be predictive of who develops the illness. The current study examines these candidates in individuals from 32 families with at least 2 members having the diagnosis of chronic schizophrenia and normal comparison subjects using an extensive neuropsychological battery. Consistent with previous literature, family members with schizophrenia were significantly impaired on all measures compared with controls. Well relatives demonstrated significantly worse performance on a measure of verbal learning, delayed visual recall, perceptual-motor, and pure motor speed. Expressive and receptive language, but not other functions, were highly correlated within both concordant for schizophrenia and discordant sibling pairs, suggesting that they are familial vulnerability endophenotypes, but not predictive of whom becomes ill. On the other hand, some measures of perceptual-motor, pure motor speed, and frontal/executive functioning were significantly correlated in concordant, but not discordant pairs. These latter correlations suggest that some cognitive measures may be genetically related to the illness.

Correlations between MRI-assessed volumes of the thalamus and cortical Brodmann's areas in schizophrenia

Background We compared the thalamic–cortical volumetric correlational patterns in patients with schizophrenia and normal comparison subjects, and evaluated their relations to outcome. Methods High-resolution MR images were acquired in patients with schizophrenia ( n=106) and normal comparison subjects ( n=42). Patients were divided into good-outcome ( n=52) and poor-outcome (Kraepelinian, n=54) subtypes based on their ability for self-care. Correlations between the relative gray and white matter volumes of the individual cortical Brodmann's areas and five dorsoventral levels of the thalamus were assessed. Results Compared to normal subjects, schizophrenia patients lacked significant thalamic gray matter volume correlations with the prefrontal and medial temporal cortical regions in the right hemisphere, and with frontal, cingulate, posterior parietal and occipital regions in the left hemisphere, while normal white matter volume cortical–thalamic correlations along the cingulate gyrus and in the temporal lobe were not found in schizophrenia patients in both hemispheres. In contrast to both normal comparison subjects and good-outcome group, schizophrenia patients with poor outcomes showed significant bilateral gray matter volume correlations between the dorsal thalamus and ventral prefrontal cortex, while the group differences in the white matter volume correlations were mostly restricted to the cingulate arch. Conclusions Whereas patients with schizophrenia exhibit deficiencies in cortical–thalamic correlational patterns, poor outcome is associated with abnormal interregional correlations not observed in either normal subjects or patients with good outcomes. This latter finding may be explained by a core neurodevelopmental disturbance that results in aberrant cortical–thalamic connectivity in poor-outcome schizophrenia.

Hippocampal Volume Measurement in Older Adults With Bipolar Disorder

Decreased hippocampal volumes have been noted in unipolar depressed subjects, especially in elderly patients and those with cognitive impairment. Initial studies of mixed-aged bipolar subjects and controls have had conflicting findings, with most noting no difference; however this region has not been examined in older bipolar subjects. The authors examined the hippocampal volumes of 36 older bipolar subjects (mean age: 58 years) and 29 older normal-comparison (NC) subjects (mean age: 61), using logistic-regression analyses to control for age and gender. Differences between late- and early-onset (before age 45) bipolar subjects were also examined. The left hippocampus was noted to be enlarged in older bipolar subjects, compared with the older NC group (sex and age controlled). No differences were noted in hippocampal volumes by age at onset nor number of previous episodes. The increase in hippocampal volume may be associated with the use of lithium, but not valproic acid. Left-hippocampal volume is increased in older bipolar subjects compared with NC subjects. The differences were not explained by age at onset, current mood state, or cognitive status, but may be associated with exposure to lithium. This finding would support previous observations about the neural-plasticity effect of lithium.