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Meta-analysis of magnetic resonance imaging studies of the corpus callosum in schizophrenia.
OBJECTIVES: The corpus callosum plays a pivotal role in inter-hemispheric transfer and integration of information. Magnetic resonance studies have reported callosal abnormalities in schizophrenia but findings have been inconsistent. Uncertainty has persisted despite a meta-analytic evaluation of this structure several years ago. We set out to perform a further meta-analysis with the addition of the numerous reports published on the subject to test the hypothesis that the corpus callosum is abnormal in schizophrenia. METHOD: A systematic search was carried out to identify suitable magnetic resonance studies which reported callosal areas in schizophrenia compared to controls. Results from the retrieved studies were compared in a meta-analysis whilst the influence of biological and clinical variables on effect size was ascertained with meta-regression analysis. RESULTS: Twenty-eight studies were identified. Corpus callosum area was reduced in schizophrenia in comparison to healthy volunteers. This effect was larger in first episode patients. Similarly, heterogeneity detected among the studies was associated with course of illness indicating that chronic subjects with schizophrenia showed larger callosal areas. There was no evidence of publication bias. CONCLUSIONS: This study confirms the presence of reduced callosal areas in schizophrenia. The effect is of a larger magnitude at first presentation and less so in subjects with a chronic course generally medicated with antipsychotics.
The effects of escitalopram on working memory and brain activity in healthy adults during performance of the n-back task.
RATIONALE: Psychotropic medication affects cognition and brain function, making it a potential confounder in functional neuroimaging studies of psychiatric patients. OBJECTIVE: To determine whether the sub-acute administration of an antidepressant (escitalopram) would induce differences in cognitive performance and associated brain function, which could be observed within the normal power of a functional imaging study. MATERIALS AND METHODS: Healthy adults (N=10) received a short course of escitalopram (10 mg/day for 7 days). Participants performed a parametric working memory (WM) task during BOLD fMRI, both while medication-free and after medication. To control for order effects, the medication-free examination was completed by half the subjects before starting medication and by the other half at least one week after medication. RESULTS: Escitalopram had no significant effect on WM accuracy or reaction time. Preliminary analysis of the imaging data revealed no significant (p(corrected)<0.05) differences in memory-load-dependent activation between conditions. However, small volume correction analysis of regions that were significant prior to correction for multiple comparisons highlighted between condition differences in regions likely to be susceptible to antidepressant effects (i.e. thalamus, anterior cingulate and inferior frontal gyrus). CONCLUSIONS: These results suggest that the sub-acute administration of antidepressants in healthy controls does not affect cognitive or hemodynamic function in healthy adults to a magnitude greater than one standard deviation unit. Therefore, the confounding effect of antidepressants on signal intensity in imaging studies of medicated, depressed individuals may be limited.
Personality correlates of happiness and sadness: EPQ-R and TPQ compared
This study assesses the relative strengths of the Eysenck Personality Questionnaire-Revised (EPQ-R) and the Tridimensional Personality Questionnaire (TPQ) as predictors of mood states. This study adds to the relatively few published reports assessing the relationships between Cloninger's (TPQ) and normal mood. 870 students completed the TPQ, EPQ-R, the State and Trait Anxiety Inventory (STAI), the Befindlichskeitskala (BFS), the General Health Questionnaire 28 (GHQ-28) and the Oxford Happiness Inventory (OHI). Harm Avoidance (TPQ), Neuroticism (EPQ-R) and Extraversion (EPQ-R) correlated highly with both positive and negative mood (r from .4 to above .6). Harm Avoidance (r between .46 and .60) and Neuroticism (r from .42 to .63) were equally the best predictors of negative mood but Harm Avoidance was the best predictor of Happiness (r = -.67 women, -.69 men). Harm Avoidance has a high correlation with both Extraversion (r = -.60) and Neuroticism (r = .68). Psychoticism played a small but significant role in explaining the variance in mood. The traits of Harm Avoidance and Neuroticism have a high influence on mood state. Those low on Harm Avoidance tend to be emotionally stable (low Neuroticism) Extraverts. The role of Psychoticism on mood needs to be explored further. © 2004 Elsevier Ltd. All rights reserved.
The structure of Cloninger's Tridimensional Personality Questionnaire in a British sample
This study adds to the very few published reports of the structure of the Tridimensional Personality Questionnaire (TPQ) at both the item and subscale levels. The TPQ was completed by 897 students from Universities within Edinburgh. Exploratory factor analysis was run on the items and the 12 subscales as described by Cloninger, Przybeck, and Svrakic (1991). Harm Avoidance showed high internal consistency both for the whole scale and the subscales; however, this was not the case for Reward Dependence and Novelty Seeking. A three factor solution was extracted from analysis at the scale level which gives support to Cloninger's model. However, when analysis was carried out at the item level, three and four factor solutions were extracted with only one factor, that of Harm Avoidance, resembling Cloninger's model. The four factors extracted were provisionally named Harm Avoidance, Conscientiousness, Sociability and Impulsiveness. These more closely resemble factors from the Five Factor Model (Costa & McCrae, 1992) and Eysenck's three factor model (Eysenck, Eysenck, & Barrett, 1985) than Cloninger's theory. It may be necessary to adapt Cloninger's model for a British sample, and more generally to question the psychometric structure of the TPQ. © 2003 Elsevier Ltd. All rights reserved.
A voxel-based analysis of cerebral perfusion in dementia and depression of old age.
Thirty-nine elderly depressed patients as well as 15 demented patients with Alzheimer's disease and 11 healthy volunteers were imaged at rest with a high resolution single-slice 12-detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-Exametazime (HM-PAO). Statistical parametric maps were computed to compare early- and late-onset depressed, Alzheimer patients and healthy volunteers and to examine associations between regional perfusion and clinical and MRI variables. Patients with late-onset depression showed reductions in temporal lobe perfusion compared with early-onset depression and controls. Alzheimer patients had the expected reduced perfusion in temporoparietal and prefontal cortex, as well as basal ganglia, compared with healthy controls. Compared with depressed patients, they showed a relative reduction in temporoparietal cortex, only. This difference was more pronounced between Alzheimer patients and early onset, compared to late-onset patients with depression. Periventricular white matter changes on MRI were associated with temporal lobe reductions of tracer uptake in depression. In the Alzheimer group, deep white matter MRI changes were associated with frontal perfusion deficits. Our results support a vulnerability hypothesis, which predicts that patients with late-onset depression will show more brain changes than patients with an early onset of their illness. Statistical parametric mapping in patients with organic psychiatric brain syndromes is feasible and promising as a clinical and research method.
Hypofrontality revisited: a high resolution single photon emission computed tomography study in schizophrenia.
Hypofrontality or reduced activity in the prefrontal cortex, measured as reduced frontal perfusion or glucose uptake, has gained the status of an established finding in the medical literature on schizophrenia. Many relevant studies, however, have potential sources of bias, such as small subject numbers, or unreliable performance of activation tasks by the patients during the scanning procedure. Seventy patients with non-affective and non-organic psychoses were recruited--most qualifying for DSM III-R schizophrenia or schizophreniform psychosis (n = 60)--together with 20 healthy volunteers. They underwent single photon emission computed tomography with 99mTc-exametazime, carried out at rest. Tracer uptake was normalised to the occipital cortex. Group differences in tracer uptake were predicted in anterior regions of interest (prefrontal cortex and mesial frontal/cingulate cortex). Actively psychotic (including schizophrenic) patients not taking any drugs showed increased uptake in the prefrontal cortex. Reduced tracer uptake occurred in the mesial frontal cortex of schizophrenic patients, particularly if they were taking drugs. Relatively increased prefrontal tracer uptake associated with relatively decreased mesial frontal uptake characterised the patients in comparison with the controls. Generalised hypofrontality is, therefore, not a feature of schizophrenic patients at rest whether taking drugs or not.
Serum iron and transferrin in acute neuroleptic induced akathisia.
Thirty acute psychiatric patients were examined prospectively at the beginning of neuroleptic treatment for acute psychotic symptoms and on average 16 days later. Two alternative hypotheses were examined: 1) neuroleptic treatment affects the levels of serum iron and transferrin; 2) acute akathisia developing during the initial few weeks of treatment is associated with low levels of serum iron and transferrin, either initially or at follow up or both. Serum iron levels did not change on repeat measurement, while there was a small, but significant decrease of serum transferrin. There was a significantly greater decrease in iron and transferrin levels in patients with akathisia on follow up compared with non-akathisics. In addition, akathisia ratings were highly correlated with serum transferrin levels on follow up.
Parkinson's disease in Aberdeen: survival after 3.5 years.
The increasing age of the general population and of patients suffering from Parkinson's disease suggests that a reappraisal of mortality rates and factors related to increased mortality should be carried out. A 3.5 year follow-up of a whole population sample of 267 patients and 233 controls matched by age, sex and general practitioner, yielded a relative mortality rate of 2.35 (99%-confidence interval: 1.60-3.43). Factors predicting death within the follow-up period were: cognitive impairment, old age, late age of onset, long history of smoking, lower blood pressure, and a variety of signs, symptoms and sequelae of Parkinson's disease associated with decreased mobility. However, age less than 70 years, age of onset before 66 years, absence of kyphosis or normal Webster posture score, mild impairment on the Hoehn & Yahr scale (1-2), or no impairment in a 10-question mental status questionnaire (9-10), were not associated with an increased risk of death.
The effects of APOE on brain activity do not simply reflect the risk of Alzheimer's disease.
Possession of the APOE-ε4 allele is the best established genetic risk factor for sporadic Alzheimer's disease (AD), while the ε2 allele may confer protection against the disease. Previous functional magnetic resonance imaging (fMRI) studies have shown an effect of APOE genotype on brain function, typically by comparing only ε4 carriers with noncarriers. Here we included a wide range of genotype groups to determine how closely the effects of APOE on brain function are related to differences in relative risk for AD. We used functional magnetic resonance imaging (fMRI) to compare the pattern of activation during an episodic encoding task and during a counting Stroop task in 76 adults, aged 32 to 55, with different APOE genotypes (23 ε2/ε3, 20 ε3/ε3, 26 ε3/ε4, and 7 ε4/ε4). Strikingly, participants with an increased risk (ε4 carriers) and with a decreased risk (ε2 carriers) for AD both showed increased activation, relative to ε3 homozygotes, during both tasks. The increased activation was due to decreased deactivation or paradoxical activation of nontask-related regions of the brain, which suggests an intrinsic effect of APOE on the differentiation of functional cortical networks. These results question the often assumed link between APOE, the blood oxygenation level dependent (BOLD) response, and AD risk.
Lexical and semantic fluency discrepancy scores in aMCI and early Alzheimer's disease.
Episodic memory is compromised in amnestic mild cognitive impairment (aMCI), but lesser deficits in other cognitive domains are also commonly observed and may be helpful in identifying this group. The relative difference in performance on lexical and semantic fluency tasks may be a sensitive and specific measure in aMCI and early Alzheimer's disease (AD). We compared four groups of participants, 35 early AD, 47 aMCI, 24 healthy controls, and 18 depressive out-patient controls, on semantic and lexical fluency as well as other neuropsychological tests. Early AD and aMCI patients showed a distinct pattern of semantic impairment in the two fluency measures compared with the healthy and depressive controls. The findings implicate early failure of the semantic memory system in aMCI and AD and suggest that consideration of the discrepancy in performance on semantic and lexical fluency measures may help in the early identification of AD.
Suicidal thoughts in young people: Their frequency and relationships with personality factors
Suicide is one of the leading causes of death in adolescents and young people. This study aims to identify factors associated with suicidal thinking in young people. Levels of suicidal thinking in a large student population (n = 1039) were assessed using the GHQ-28; regression analysis identified personality (trait) and mood (state) correlates of suicidal thoughts. All volunteers were recruited from Universities in Edinburgh. Over 10% of students stated that they had suicidal thoughts within the last few weeks. Men scored slightly higher than women on suicidal thoughts. Variables relating to emotionality were the largest predictors of suicidal thoughts. Gender differences have also been reported in the relationship between self-rated mental health and suicide rates: males who had scored highly on the GHQ-28 had a higher suicide risk than females. Longitudinal studies in both men and women that assess personality predictors of self-harm and suicides are needed to control for confounders in non-randomised studies of suicide risk. © 2007 Elsevier Ltd. All rights reserved.
The effect of electroconvulsive therapy on autobiographical memory: a systematic review.
OBJECTIVES: In the last 20 years, an increasing number of articles have been published about effects of electroconvulsive therapy (ECT) on memory. Here, we review autobiographical memory studies in particular because there have been conflicting reports about the extent and persistence of ECT effects and the period before treatment from which memories are most likely to be affected. METHODS: Five psychological and medical databases (MEDLINE, PubMed, PsychINFO, ScienceDirect, and Web of Knowledge) were searched from 1980 to 2007, yielding 15 studies of ECT and autobiographical memory. RESULTS: Evidence suggests that autobiographical memory impairment does occur as a result of ECT. Objective measures found memory loss to be relatively short term (<6 months posttreatment), whereas subjective accounts reported amnesia to be more persistent (>6 months post-ECT). Electroconvulsive therapy predominantly affects memory of prior personal events that are near the treatment (within 6 months). Autobiographical memory loss is reduced by using brief pulse ECT rather than sine wave-unilateral positioning of electrodes rather than bilateral-and by titrating electrical current relative to the patient's own seizure threshold. CONCLUSIONS: Further research is required to determine memory loss associated with ECT, controlling for the direct effects of the depressive state.
fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia.
Schizophrenia is a highly heritable disorder that typically develops in early adult life. Structural imaging studies have indicated that patients with the illness, and to some extent their unaffected relatives, have subtle deficits in several brain regions, including prefrontal and temporal lobes. It is, however, not known how this inherited vulnerability leads to psychosis. This study used a covert verbal initiation fMRI task previously shown to elicit frontal and temporal activity (the Hayling sentence completion task) to examine this issue. A large (n = 69) number of young participants at high risk of developing schizophrenia for genetic reasons took part, together with a matched group of healthy controls (n = 21). At the time of investigation, none had any psychotic disorder, but on detailed interview some of the high-risk participants (n = 27) reported isolated psychotic symptoms. The study aimed to determine: (i) whether there were activation differences that occurred in all subjects with a genetic risk of schizophrenia (i.e. 'trait' effects); and (ii) whether there were activation differences that only occurred in those at high risk who had isolated psychotic symptoms ('state' effects). No activation differences were found in regions commonly reported to be abnormal in the established illness, namely the dorsolateral prefrontal cortex or in the temporal lobes, but group differences of apparent genetic cause were evident in medial prefrontal, thalamic and cerebellar regions. In addition, differences in activation in those with symptoms were found in the intraparietal sulcus. No significant differences in performance were found between the groups, and all subjects were antipsychotic naïve. These findings therefore suggest that vulnerability to schizophrenia may be inherited as a disruption in a fronto-thalamic-cerebellar network, and the earliest changes specific to the psychotic state may be related to hyperactivation in the parietal lobe.
Oral amino acid load mimicking hemoglobin results in reduced regional cerebral perfusion and deterioration in memory tests in patients with cirrhosis of the liver.
This study tests the hypothesis that administration of an oral amino acid load mimicking hemoglobin in patients with cirrhosis of the liver causes deterioration in neuropsychological function and a reduction in regional cerebral perfusion. Eight overnight fasted, metabolically stable cirrhotic patients with no evidence of overt hepatic encephalopathy were studied prior to and 4 h after simulating an upper gastrointestinal bleed by oral administration of 75 g of a solution mimicking the amino acid composition of hemoglobin. Neuropsychological function was measured using a test battery. Peripheral venous blood was collected for the measurement of ammonia and amino acid concentrations. Regional cerebral perfusion was measured using a head SPECT scanner following intravenous administration of technetium-99m hexamethyl propylamineoxime. The amino acid solution resulted in significant deterioration in the immediate and delayed story recall tests. Ammonia concentration increased from a median of 87 (range 67-94) micromol/L to 105 (98-112) micromol/L at 4 h after the simulated bleed (p < 0.01). The concentration of almost all amino acids increased; only isoleucine levels decreased following the upper gastrointestinal bleed. SPECT analysis showed a significant reduction in cerebral perfusion after the simulated bleed in both temporal lobes, left superior frontal gyrus, and right parietal and cingulate gyrus. An oral amino acid load mimicking hemoglobin in cirrhotic patients produces hyperammonemia and hypoisoleucinemia and causes a significant deterioration in memory tests, probably due to a reduction in regional cerebral perfusion. The model of simulating the metabolic effects of an upper gastrointestinal bleed in patients with cirrhosis of the liver seems to be useful in studying the metabolism of hepatic encephalopathy.
Regional cerebral blood flow in IDDM patients: effects of diabetes and of recurrent severe hypoglycaemia.
Chronic hyperglycaemia and recurrent severe hypoglycaemia have both been implicated as causing cerebral damage in patients with diabetes. Although cognitive dysfunction and intellectual impairment have been demonstrated in patients with recurrent severe hypoglycaemia, structural correlates have not been described, and it is not known whether specific functional changes occur in the brains of affected patients. Regional cerebral blood flow was estimated by SPECT with 99mTechnetium Exametazime in 20 patients with IDDM. Ten patients had never experienced severe hypoglycaemia and 10 had a history of recurrent severe hypoglycaemia. Patient results were compared with 20 age- and sex-matched healthy volunteers. We observed differences between the two patient groups and the control group. Tracer uptake was greater in diabetic patients in the superior pre-frontal cortex. This effect was particularly pronounced in the group who had a history of previous severe hypoglycaemia. Patients with a history of recurrent hypoglycaemia also had a relative reduction in tracer uptake to the calcarine cortex. This suggests an alteration in the pattern of baseline regional cerebral blood flow in diabetic patients with frontal excess and relative posterior reduction in cerebral blood flow.
The effects of progressive abstinence from alcohol on red blood cell proton NMR relaxation times and water content.
Red blood cell proton relaxation times T1 and T2 were measured in samples from chronic alcoholic patients abstinent for varying periods from 1 week to over 6 months. T1 and T2 were elevated in the early stages of abstinence and declined to the values of controls after 8 weeks. Changes in the water content of the red blood cells and the mean corpuscular volume paralleled these changes but were more closely associated with T2. It is suggested that T1 and T2 may reflect different aspects in water content and free-to-bound ratio of water. The significance of these findings is discussed in the context of changes previously observed in the brains of alcoholic patients, and in rats fed a diet supplemented with alcohol for 6 months.