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Identifying patients at risk of perinatal mood disorders.
Perinatal mental illness influences obstetric outcomes, mother-baby interactions and longer term emotional and cognitive development of the child. Psychiatric disorders have consistently been found to be one of the leading causes of maternal deaths, often through suicide. Postnatal depression and puerperal psychosis are two disorders most commonly associated with the perinatal period. The most efficient strategy to identify patients at risk relies on focussing on clinically vulnerable subgroups: enquiries about depressive symptoms should be made at the usual screening visits. Attention should be paid to any sign of poor self-care, avoidance of eye contact, overactivity or underactivity, or abnormalities in the rate of speech. Particular care should be taken to ask about suicidal ideation and thoughts of harming others, including the baby. One of the most important risk factors is a previous history of depression. The degree of risk is directly correlated with severity of past episodes. Both antenatal and postnatal depression are being increasingly recognised in men. Puerperal psychosis is rare (1 to 2 per 1,000). Sixty per cent of women with puerperal psychosis already have a diagnosis of bipolar disorder or schizoaffective disorder. Women with a personal history of postpartum psychosis or bipolar affective disorder should be considered as high risk for postpartum psychosis. All pregnant women who are identified as being at high risk should have a shared care plan for their late pregnancy and early postnatal psychiatric management. Women with current mood disorder of mild or moderate severity who have a first-degree relative with a history of bipolar disorder or postpartum psychosis should be referred for psychiatric assessment.
The influence of ApoE4 on clinical progression of dementia: a meta-analysis.
OBJECTIVE: ApoE4 is a risk factor for the development of Alzheimer's disease, and has a functional role suggesting its importance in the neuropathology of dementia. We present a meta-analysis to investigate whether ApoE4 also affects the clinical progression of dementia in terms of cognitive decline or mortality. METHODS: We searched Medline, Embase and PsychINFO from 1990 until April 2009, for case control or cohort studies which investigated the effect of ApoE4 on progression of dementia. We identified 427 studies; 17 were suitable for inclusion. In total, there were 1733 participants with dementia at baseline, of whom 975 were heterozygous or homozygous for ApoE4. RESULTS: There was no significant difference in cognitive decline (random-model effect size = 0.02; 95% C.-I.: -0.09 to 0.14; p = 0.67) or mortality (random-model pooled odds ratio = 0.74; 95% C.-I.: 0.36 to 1.53; p = 0.41) based on the presence of ApoE4. There was no significant heterogeneity between studies using cognitive decline as an outcome. In meta-regressions of cognitive decline, duration of symptoms, age, gender and frequency of participants with ApoE4 in the samples did not contribute to outcome. CONCLUSION: Different ApoE alleles do not modify the speed of clinical progression of dementia in a way that would be detectable in a sample of 1700 patients.
A hierarchy of happiness? Mokken scaling analysis of the Oxford Happiness Inventory
The items of the Oxford Happiness Inventory (OHI), a self-report assessment of happiness, are subjected to an analysis for hierarchy among its items. By using Mokken scaling analyses we can assess whether items can reliably be ordered between persons as severity indicators on a latent trait; in this case, a latent trait of Happiness. OHI item-level data from 1024 participants were entered into the Mokken Scaling Procedure (MSP) seeking reliable scales with H > 0.30. 12 OHI items formed a reliable and statistically significant hierarchy. However, the MSP values indicate a 'weak' scale. The 'most difficult' (happiest) item on the scale is 'feeling energetic' and the 'least difficult' (least happy) is 'I have fun'. Items in the scale are consistent with what is already known about both happiness and low mood. The reduction in the OHI's items from 29 to 12 in the Mokken scale may have utility making it more accessible to participants as well as identifying items with reliably different levels of 'difficulty'. © 2010 Elsevier Ltd. All rights reserved.
Managing bipolar disorder in primary care.
Bipolar disorder is relatively common, at least twice as common as schizophrenia, and eminently treatable. It is also perfectly suited to the well established outpatient model practised in general practice and psychiatry. All GP practices should include people with a diagnosis of bipolar disorder on their case register of people with severe mental illness. It is not possible to exclude a bipolar diagnosis categorically if there are only symptoms of depression. Most patients will have had a (hypo)manic episode by their 30s. The lifetime prevalence of bipolar affective disorder proper is 1%, with a further 1.2% presenting with milder hypomanic symptoms (so-called bipolar II disorder). Relaxing diagnostic symptom criteria increases the frequency of depressed patients who develop symptoms of mania for any length of time to 50%. The lifetime course of the illness tends to be dominated by depressive episodes: half the time is estimated to be spent in the euthymic (well) state, 12% in a manic state and 38% in a depressed state. Any depressed patient should be asked about periods in the past when (s)he has been elated in mood, found it unnecessary to sleep, talked a lot, spent excessive amounts of money etc. Treatment for bipolar disorder has to be divided into: treatment of mania, treatment of bipolar depression and prophylaxis of mood swings in either direction. Antidepressant treatments are unlikely to help manic symptoms, at worst they can precipitate or aggravate them. Antimanic treatments are unlikely to help symptoms of depression but an exception to this rule would be a genuine mood stabiliser, such as lithium. Patients with bipolar disorder should have an annual physical health review. This will include monitoring for weight gain, lipid levels, plasma glucose levels, smoking status and alcohol use, as well as blood pressure.
Chronic, treatment-resistant depression and right fronto-striatal atrophy.
BACKGROUND: Treatment-resistant depression (TRD) is relatively common but its neurobiological basis is poorly understood. Fronto-striatal structural brain changes have been reported in patients with depression but their association with treatment resistance and chronicity has not been established. METHOD: Magnetic resonance images of 20 patients with TRD were compared with images of 20 recovered patients and 20 healthy controls. Images were compared using a voxel-based analysis (VBA) method; the results were validated by conventional volumetric analysis. The clinical associations of magnetic resonance imaging (MRI) changes with illness duration and severity were examined by VBA. RESULTS: Only the TRD group exhibited right fronto-striatal atrophy, and subtle MRI changes in the left hippocampus on VBA. Atrophy was confirmed on volumetric analysis, the degree correlating with the cumulative number of electroconvulsive therapy (ECT) treatments received, suggesting an acquired deficit. CONCLUSIONS: This is the first study to demonstrate fronto-striatal atrophy in patients with depression with poor outcome; the atrophy is more marked in those with more severe illness.
Increased cortical inhibition in depression: a prolonged silent period with transcranial magnetic stimulation (TMS).
BACKGROUND: Motor slowing in depression may be associated with a relative dopaminergic (DA) deficit. Bradykinesia in Parkinson's syndrome is associated with an abnormally short silent period (SP) using transcranial magnetic stimulation (TMS). We hypothesized that depression would also be associated with a short SP. METHODS: Sixteen patients with DSM-IV depression and 19 matched controls participated. SPs were elicited by exercising the contralateral abductor policis brevis (APB) during TMS. RESULTS: The SP was significantly increased in the patient group. No correlation was found between SP and depression score. CONCLUSION: A long SP suggests increased motor cortical inhibition in depression. This finding is inconsistent with the hypothesis of behavioural motor slowing in depression being associated with Parkinsonian-like mechanisms including the dopaminergic deficit. There is a need for studies incorporating larger patient groups to investigate potential correlations between SP and depression indices.
Brain activation during an auditory 'oddball task' in schizophrenia measured by single photon emission tomography.
BACKGROUND: The study examines the effect of an auditory discrimination task on regional brain perfusion in schizophrenic patients. METHODS: Twenty patients were examined with single photon emission tomography (SPET), both resting and performing an auditory two-tone 'oddball' discrimination task. Statistical parametric mapping (SPM'95) was used to identify local activation effects and correlations between event related potential measures and regional perfusion. RESULTS: Compared with rest, patients activated left superior temporal gyrus during the task, together with right caudate. There was a (negative) correlation between P300-amplitude and perfusion during the activation procedure in both caudate nuclei and in the left lingual gyrus. No correlations were observed with P300-latency. Compared with healthy volunteers examined in earlier studies, our patients showed no frontal activation. This might be due to slightly different task demands in this study, but more likely to activation-hypofrontality in schizophrenic patients compared with controls. CONCLUSION: Auditory discrimination tasks can be used in schizophrenic patients to control their 'mental set' during brain perfusion studies with SPET. This approach can yield information about specific brain mechanisms associated with such tasks, and may make comparison with healthy volunteers easier.
Correlation of auditory 'oddball' P300 with verbal memory deficits in schizophrenia.
BACKGROUND: The study attempts to recruit well known 'cognitive' event related potential measures as an objective estimate of cognitive and specific memory impairment in schizophrenia. METHODS: We examined 19 schizophrenic patients and 28 healthy controls using an auditory discrimination task to elicit event related potentials, and a number of neuropsychological tests, including tests of general intellectual ability, putative frontal lobe function and verbal memory. RESULTS: The late positive deflection presumed to be associated with stimulus evaluation (P300) was of lower amplitude and had a longer latency in the patients compared with controls of similar age and sex. We found correlations between P300 amplitude and latency, and neuropsychological performance scores in patients. There were correlations between decreased P300 amplitude and lower IQ and poorer memory performance, in particular, abnormal semantic clustering, discriminability and intrusion errors. Increased P300 latency was correlated with lower pre-morbid IQ, poorer total memory scores and serial clustering, but paradoxically less relative retrieval deficit and fewer intrusion errors. CONCLUSIONS: These findings suggest that abnormal P300 is generally more likely to occur in patients with memory impairment.
Korsakoff's syndrome, cognition and clonidine.
Eighteen patients suffering from Alcoholic Korsakoff's Syndrome participated in a placebo-controlled double-blind cross-over trial of clonidine 0.3 mg b.d. for two weeks versus matched placebo for two weeks. A detailed neuropsychological assessment was carried out at the end of each treatment phase and staff ratings of behaviour were also obtained. Clonidine treatment resulted in no significant improvement over placebo on any of the cognitive measures employed. The results contradict previous smaller studies which had suggested that chronic treatment with clonidine had a memory-enhancing effect in Korsakoff's syndrome.
Cognitive function in major depression.
Forty patients with a major depressive episode were divided into equal endogenous and neurotic sub-groups using the Newcastle scale. They were all rated on the 17-item Hamilton scale and with a variety of neuropsychological tests. They were compared with 20 age- and education-matched control subjects. Both endogenous and neurotic groups had impaired memory function on the auditory verbal learning test; recall and recognition were equally impaired suggesting that effort was not a major determinant of performance. The endogenous group was more impaired on digit symbol substitution and the Trail making test (A and B). Impairment was correlated with symptom scores on the Hamilton and Newcastle scales, even after allowing for the effect of age. It is concluded that the conventional distinction between organic and functional impairment breaks down in severe depressive illness. The implications of this for clinical neuropsychological testing and the anatomy of the brain dysfunction in depressive illness are discussed.
Event related potentials, reaction time, and cognitive performance in idiopathic Parkinson's disease.
Sixteen non-demented patients with idiopathic Parkinson's disease (PD) with varying degrees of cognitive impairment and sixteen age-, sex- and education-matched normal controls were examined with (1) an auditory oddball paradigm requiring counting or a motor response in separate determinations, (2) a reaction time task with movement time component and (3) a detailed clinical and neuropsychological test battery. Patients were impaired on a number of neuropsychological tests. They also showed an increased P2 and N2 latency, but no significant increase in P3 latency. Their response initiation times and reaction times during the oddball experiment were not different from controls, whereas movement time was significantly increased. Increased peak latencies, particularly for N2, were moderately associated with Parkinsonian motor impairment in patients and with the Benton Multiple Choice Visual Retention Test in patients and controls. Movement time was associated with P3 latency only in controls and in both groups with the Benton Multiple Choice Visual Retention Test. The observed pattern of results suggests that in non-demented PD patients ERP peak latencies, visuo-spatial task performance and Parkinsonian motor impairment share a significant degree of variance. While impairments in neuropsychological tests and delay in the earlier peaks P2 and N2 do not appear to be sensitive to medication with L-DOPA, normal P3 latencies might indicate good pharmacological symptom control in the absence of dementia.
The effect of different high-pass filter settings on peak latencies in the event-related potentials of schizophrenics, patients with Parkinson's disease and controls.
Eighteen schizophrenic patients, 16 patients with idiopathic Parkinson's disease, and the same numbers of age, sex and education matched controls were examined with oddball experiments for the generation of P3. Individual averages were high-pass filtered at different cut-off frequencies with single-pole digital filters with equivalent analogue Butterworth filter profiles. The purpose of this procedure was to simulate analogue high-pass filters used in clinical studies from different centres and to examine their potential effect on group differences. Increasing high-pass filters resulted in a phase lead for all peaks examined (N1, P2, N2, P3). The only group differences were found for P3, which showed a greater phase lead in controls than in the patient groups, usually resulting in a more pronounced group difference. Similar wave forms and filter properties could be modelled by synthetic wave forms consisting of sine waves of different frequencies.
Differential diagnosis in dementia using the cerebral blood flow agent 99mTc HM-PAO: a SPECT study.
One of the potential clinical uses of the new cerebral blood flow agent 99mTc-hexamethylpropyleneamineoxime (HM-PAO) is the investigation of dementia, in particular to differentiate between dementia of the Alzheimer type (DAT) and multiinfarct dementia (MID). In this study 27 patients, 17 with DAT and 10 with MID, and three normal volunteers were imaged both with single photon emission CT and magnetic resonance. The HM-PAO perfusion deficits were much more common in the DAT group than in the MID group, especially in the temporoparietooccipital (TPO) regions. The two groups of patients were found to be significantly different (p less than 0.02), as regards the frequency of occurrence of bilateral TPO perfusion deficits. Four of the 17 DAT patients did not have bilateral TPO deficits but these included the three least impaired patients as assessed by psychometric testing.
Nuclear magnetic resonance imaging and single photon emission tomography with radio-iodine labelled compounds in the diagnosis of dementia.
White matter lesions and T1 changes were identified using NMR and then compared between groups of patients suffering from dementia of the Alzheimer type (DAT), Multiple infarct dementia (MID) and normal controls. All DAT and MID patients were also imaged with a gamma camera using 123Iodo-n-isopropyl-amphetamine, a radiopharmaceutical whose uptake in the brain follows the regional blood flow. While NMR was not able to differentiate between DAT and MID, 19 out of 21 DAT patients compared to four out of 18 MID patients showed bilateral parietal lesions on IMP scans.
alpha4beta2-nicotinic receptor binding with 5-IA in Alzheimer's disease: methods of scan analysis.
Five patients with Alzheimer's disease and five healthy volunteers were examined by SPECT with the nicotinic receptor ligand 123I-5-IA-85380. Patients were scanned before and after 6 weeks of treatment with donepezil. Quantification by regions of interest was reliable and the optimal normalisation procedure used cerebellar ratios. We found relative reductions in 5-IA binding capacity in patients in thalamus, frontal and central regions of interest of approximately one standard deviation unit (Cohen's d = 1). Reductions in binding after treatment with the acetylcholinesterase inhibitor donepezil of the same magnitude occurred in the brain stem. The study was clearly too small to confirm group differences, but it suggests that 5-IA can be used to examine both group differences and treatment effects in patients with Alzheimer's disease.
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.