Conscientiousness and medication adherence: a meta-analysis.

BACKGROUND: Approximately a quarter to a half of all people fail to take their medication regimen as prescribed (i.e. non-adherence). Conscientiousness, from the five-factor model of personality, has been positively linked to adherence to medications in several recent studies. PURPOSE: This study aimed to systematically estimate the strength and variability of this association across multiple published articles and to identify moderators of this relationship. METHOD: A literature search identified 16 studies (N = 3,476) that met the study eligibility criteria. Estimates of effect sizes (r) obtained in these studies were meta-analysed. RESULTS: Overall, a higher level of conscientiousness was associated with better medication adherence (r = 0.15; 95 % CI, 0.09, 0.21). Associations were significantly stronger in younger samples (r = 0.26, 95 % CI, 0.17, 0.34; k = 7). CONCLUSION: The small association between conscientiousness and medication adherence may have clinical significance in contexts where small differences in adherence result in clinically important effects.

Late effects of a brief psychological intervention in patients with intermittent claudication in a randomized clinical trial.

BACKGROUND: The authors previously reported the early results of a trial of a brief psychological intervention to increase physical activity in patients with intermittent claudication. After 4 months, participants in the intervention group walked a mean of 1576 more steps per day than control group participants. The present study followed the original participants to determine whether this behaviour change was maintained over 2 years. METHODS: This was a randomized single-centre parallel-group trial. Fifty-eight patients newly diagnosed with intermittent claudication were assigned randomly to one of two groups. The control group (30 patients) received usual care: lifestyle advice and consultation with a vascular surgeon to agree a treatment plan. The treatment group (28) received usual care plus a brief psychological intervention designed to modify illness and walking beliefs, and develop a personalized walking action plan. The primary outcome was daily steps measured by pedometer. Secondary outcomes included revascularization rate, quality of life and perceived pain-free walking distance. Follow-up was conducted at 1 and 2 years. Between-group differences were analysed by analysis of co-variance. RESULTS: Participants in the brief psychological intervention group walked significantly more than those in the control group. The mean difference at 1 year was 1374 (95 per cent confidence interval 528 to 2220) steps per day and the difference at 2 years was 1630 (495 to 2765) steps per day. CONCLUSION: Modifying illness and walking beliefs, and assisting patients to develop a personalized walking action plan led to increases in walking behaviour in patients with claudication that were maintained for 2 years. REGISTRATION NUMBER: ISRCTN28051878 (http://www.controlled-trials.com).

Randomized clinical trial of a brief psychological intervention to increase walking in patients with intermittent claudication.

BACKGROUND: Increased walking is often recommended for patients with intermittent claudication (IC). Current methods to increase walking in these patients increase capability but not daily behaviour. This trial assessed whether a brief psychological intervention could increase daily walking at 4 months. METHODS: This randomized, single-centre, parallel-group trial was conducted between April 2008 and July 2010. Patients newly diagnosed with IC were randomly assigned into two groups. All clinical staff involved in patient management were blinded to allocation. The control group received usual care plus researcher contact, and the treatment group received usual care and a brief psychological intervention to modify illness and walking beliefs and to develop a personalized walking action plan. The psychological intervention was delivered in two 1-h sessions in participants' homes. The primary outcome was daily steps measured by pedometer 4 months later. Analyses were by intention to treat. RESULTS: Of 109 patients screened, 72 were eligible for inclusion; 58 patients consented to participate and were randomly allocated to usual care (30) or brief psychological intervention (28). All 58 participants were included in the analysis of the primary outcome. Compared with controls at 4-month follow-up, participants who received the psychological intervention walked a mean of 1575·63 (95 per cent confidence interval 731·97 to 2419·29) more steps per day. There were no adverse events. CONCLUSION: A brief psychological intervention significantly increased daily walking in patients with IC at 4 months. This study provided support for a potentially new direction in the treatment of IC. REGISTRATION NUMBER: ISRCTN28051878 (http://www.controlled-trials.com).

Examining the effect of spinal cord injury on emotional awareness, expressivity and memory for emotional material.

The prevailing view on the effects of spinal cord injury (SCI) on emotion is that it dampens emotional experience due to a loss of peripheral bodily feedback, with the higher the lesion on the spinal cord the greater the reduction in the intensity of emotional experience. This view persists despite many studies showing an absence of such an emotional impairment in people with SCI. This study specifically aimed to investigate whether total cervical-6 spinal cord transection (i) reduces emotional expressivity and emotional awareness (ii) impairs memory for emotional material. The study contained three groups: 24 patients with SCI, 20 orthopaedic injury control (OIC) patients and 20 young adult controls. A mixed factor design was employed to examine between group and within subject differences. Participants completed the Levels of Emotional Awareness Scale (LEAS), the Berkeley Expressivity Questionnaire (BEQ), and viewed an emotionally arousing slide presentation. Thirty minutes post viewing, participants completed memory tests for the presentation. SCI patients reported greater present levels of emotional expressivity compared with perceived levels prior to their injuries. SCI and OIC groups did not differ on any of the emotional awareness variables. There was also no evidence that SCI leads to impairment in memory for emotional events. This study's findings contradict the mainstream view in the cognitive neuroscience of emotion that SCI dampens emotional experience.

Neuropsychological functioning, illness perception, mood and quality of life in chronic fatigue syndrome, autoimmune thyroid disease and healthy participants.

BACKGROUND: This study attempted to longitudinally investigate neuropsychological function, illness representations, self-esteem, mood and quality of life (QoL) in individuals with chronic fatigue syndrome (CFS) and compared them with both healthy participants and a clinical comparison group of individuals with autoimmune thyroid disease (AITD). METHOD: Neuropsychological evaluation was administered at two time points, five weeks apart. Twenty-one individuals with CFS, 20 individuals with AITD and 21 healthy participants were matched for age, pre-morbid intelligence, education level and socio-economic status (SES). All groups also completed measures of illness perceptions, mood, self-esteem and QoL at both time points. RESULTS: The CFS group showed significantly greater impairment on measures of immediate and delayed memory, attention and visuo-constructional ability, and reported significantly higher levels of anxiety and depression. After controlling for the effects of mood, the CFS group still demonstrated significant impairment in attention. The CFS group also reported significantly lower self-reported QoL than the AITD and healthy participants. In terms of illness perceptions, the AITD group believed that their condition would last longer, that they had more treatment control over their condition, and reported less concern than the CFS group. CONCLUSIONS: These results suggest that the primary cognitive impairment in CFS is attention and that this is not secondary to affective status. The lower treatment control perceptions and greater illness concerns that CFS patients report may be causally related to their affective status.

Exploring the psychology of suicidal ideation: A theory driven network analysis.

Two leading theories within the field of suicide prevention are the interpersonal psychological theory of suicidal behaviour (IPT) and the integrated motivational-volitional (IMV) model. The IPT posits that suicidal thoughts emerge from high levels of perceived burdensomeness and thwarted belongingness. The IMV model is a multivariate framework that conceptualizes defeat and entrapment as key drivers of suicide ideation. We applied network analysis to cross-sectional data collected as part of the Scottish Wellbeing Study, in which a nationally representative sample of 3508 young adults (18-34 years) completed a battery of psychological measures. Network analysis can help us to understand how the different theoretical components interact and how they relate to suicide ideation. Within a network that included only the core factors from both models, internal entrapment and perceived burdensomeness were most strongly related to suicide ideation. The core constructs defeat, external entrapment and thwarted belonginess were mainly related to other factors than suicide ideation. Within the network of all available psychological factors, 12 of the 20 factors were uniquely related to suicide ideation, with perceived burdensomeness, internal entrapment, depressive symptoms and history of suicide ideation explaining the most variance. None of the factors was isolated, and we identified four larger clusters: mental wellbeing, interpersonal needs, personality, and suicide-related factors. Overall, the results suggest that relationships between suicide ideation and psychological risk factors are complex, with some factors contributing direct risk, and others having indirect impact.

Single-photon emission computed tomography with 99mTc-exametazime in unmedicated schizophrenic patients.

We examined 20 actively psychotic unmedicated schizophrenic patients and 20 matched control subjects by using single-photon emission, computed tomography (SPECT) with 99mtechnetium-exametazime. Patients showed a hyperfrontal pattern of tracer uptake with significant relative increases in superior prefrontal cortex. This abnormality was less pronounced in patients with higher symptom scores for psychomotor poverty. In addition, patients showed associations between certain schizophrenic syndrome scores, such as psychomotor poverty, disorganization, and reality distortion, and tracer uptake to a number of cortical and subcortical brain regions. This syndrome-related pattern of tracer uptake was, at least in part, consistent with similar associations previously reported in chronically medicated schizophrenic patients. SPECT therefore provides a readily available method to examine the relationship between symptom pattern and regional brain metabolism in psychotic patients. Any observed patterns of association will depend on the current mental and medication status of the patients examined.

Decision making in patients with spinal cord damage: afferent feedback and the somatic marker hypothesis.

Damasio has proposed an influential model of human decision making - the somatic marker hypothesis (Damasio AR. Descates' Error. London: Papermac/Macmillan, 1994), where he argues that somatic feedback to the brain influences decision making in man. It is proposed that when choosing between options that differ in relative risk, a somatic marker (e.g. a 'gut feeling') feeds back to the brain and influences cognitive appraisal. In the present study patients who had suffered a complete tetraplegia at the level of the sixth cervical vertebra were compared with matched healthy control subjects. As the spinal injury group have reduced somatic/peripheral feedback via the spinal cord, it was predicted, based on the somatic marker hypothesis, that they may demonstrate riskier behaviour than controls. All subjects completed the Iowa Gambling Task, a computerised card playing game where the player is instructed to try and win as much money as possible over 100 selections from one of four decks. The rules are not disclosed in advance, and the player gradually 'learns' that two of the decks are 'high risk' and lead to significant financial losses. Healthy individuals have previously been shown to learn to avoid the risky decks, whereas patients with medial frontal lobe damage (Bechara A, Damasio AR, Damasio H, Anderson SW. Insensitivity to future consequences following damage to human prefrontal cortex. Cognition 1994;50:7-15) and those with peripheral neuropathy (Bechara A, Tranel D, Wilson J, Heberlein AS, Ross M, Damasio AR, 1998. Impaired decision-making in peripheral neuropathy. Society for Neuroscience Abstracts 24:1176) select an excessive number from the risky decks, and consequently lose money. In the present study there were no significant differences between the spinal sectioned and healthy control groups in either card selection strategy or net financial outcome. This result suggests that in terms of the somatic marker hypothesis, feedback to the brain from the periphery via the cranial vagus and other nerves and the hormonal route may be equally or more influential than afferent feedback transmitted via the spinal cord.

Unilateral voluntary hand movement and regional cerebral uptake of technetium-99m-exametazime in human control subjects.

The study examines the sensitivity of a region of interest approach to detect functional changes in brain metabolism with SPECT and split-dose 99mTc-exametazime by replicating a simple hand movement experiment previously carried out with PET. Regional uptake of 99mTc-exametazime was determined in 12 healthy controls before and during a thumb-digit opposition task. Analysis of regional uptake was carried out blind to the hand used in the opposition task and showed a significant unilateral activation effect in a pericentral region of interest with opposite results in left- and right-handed activation. The maximum contralateral increase in tracer uptake was 16% before and 26% after correction for back diffusion. This is in good agreement with previous results employing absolute cerebral blood flow determination with PET and confirms the usefulness of 99mTc-exametazime SPECT for the examination of functional metabolic changes.

Benzodiazepine receptor antagonism improves reaction time in latent hepatic encephalopathy.

Endogenous benzodiazepine-like substances are thought to play a role in the development of hepatic encephalopathy (HE). Ten patients with sub-clinical or latent hepatic encephalopathy (LHE) and ten normal controls were cognitively assessed pre- and post-infusion of 0.2 mg of the benzodiazepine (BZ) antagonist flumazenil in a placebo-controlled, cross-over, double-blind design. Flumazenil infusion resulted in a significant improvement in simple reaction time in patients, but not in controls. Saline infusion had no effect on any of the cognitive measures in either group. Flumazenil appeared to have a particular enhancing effect on the cognitive, as opposed to the motor, component of the reaction time task. This finding supports the view that the benzodiazepine/GABA system is implicated in the bradyphrenia that is characteristic of chronic liver disease, even before hepatic encephalopathy is apparent. We conclude that benzodiazepine receptor antagonism may improve cognitive function, particularly speed of information processing, in patients with latent hepatic encephalopathy.

Effects of fluvoxamine treatment on cognitive functioning in the alcoholic Korsakoff syndrome.

Eight patients suffering from the alcoholic Korsakoff syndrome (AKS) were entered in a double-blind cross-over trial of fluvoxamine 200 mg per day for 4 weeks versus matched placebo for 4 weeks. At the end of each phase, patients were assessed using a detailed neuropsychological test battery. Verbal fluency performance was significantly impaired following fluvoxamine treatment. No significant differences emerged on any of the other cognitive test measures when fluvoxamine was compared with placebo. However, two of the patients developed a major depressive episode while receiving fluvoxamine.

Executive function and uptake of 99mTc-exametazime shown by single photon emission tomography after oral idazoxan in probable Alzheimer-type dementia.

Preliminary reports suggest improved executive function in patients with lobar dementia after treatment with single doses of the alpha 2 adrenoceptor antagonist, idazoxan. The potential for use in probable Alzheimer-type dementia prompted the present study. Fifteen patients with probable Alzheimer-type dementia were examined twice with neuropsychological measures and 14 also with single photon emission tomography (SPET) after a single double blind oral administration of 40 mg idazoxan or placebo in a balanced cross-over design. Brain perfusion maps were spatially transformed into standard stereotactic space and compared pixel-by-pixel. A parametric analysis was used to examine the relationship between the drug effect, verbal fluency and brain perfusion. Two to 3 h after idazoxan, measures of reaction time, Stroop test, category fluency and anxiety were unchanged. Verbal fluency (letter) and spatial working memory were impaired and performance on the Tower of London test in a sub-set of patients showed a trend to impairment in the idazoxan condition. Idazoxan produced a modest relative activation in left thalamus and inferior occipital cortex: decreases occurred in inferior anterior cingulate and left insular cortex. There were significant correlations on both days between measures of fluency and brain perfusion in left lateral prefrontal cortex. The reduced performance with idazoxan was directly correlated with reduced perfusion in left lateral prefrontal cortex, supporting an important interaction between drug and task performance. The imaging component of the study therefore suggested that activation of frontal networks is necessary for performing fluency tasks in Alzheimer-type dementia. Brain networks involving prefrontal cortex are the locus for the primary cognitive effects of noradrenergic drugs. The direction of the effect of any dose of agonist or antagonist may depend critically upon the age and pathology of the experimental subjects and the relationship between performance, noradrenergic drive and task difficulty.

Associative learning in acutely ill and recovered schizophrenic patients.

Eight acutely ill deluded schizophrenic patients were compared with eight matched recovered patients on an associative learning task. Ten word pair associations were presented over five trials. Subsequently the subjects were presented with ten novel pairings over three trials, one word from the first pair associated with a new partner. Recovered patients performed better than acutely ill patients on both stages of the task. This result does not support the neuropsychological model of Gray et al. (1991) which predicts that acute schizophrenia is characterised by a weakening of the effect of previous experience on new learning.

Benzodiazepine-like substances and hepatic encephalopathy : implications for treatment.

Hepatic encephalopathy is a neuropsychiatric syndrome that can complicate acute and chronic liver disease. Recent research has focused on the role benzodiazepine-like substances play in the pathogenesis of this disorder. It has been proposed that potentiation of the action of the neuroinhibitory transmitter γr-aminobutyric acid (GABA) through the binding of endogenous benzodiazepine agonists to the benzodiazepine receptor binding site accounts for the clinical and biochemical features of this condition.Increased levels of endogenous benzodiazepine-like substances have been noted in animal models of hepatic encephalopathy. In human studies, levels of these substances of up to 10 times those found in the body fluids of nonencephalopathic controls have been reported. The existence of such markedly elevated levels cannot be satisfactorily explained with reference to possible pharmaceutical or dietary origins.Further support for the role of benzodiazepines in the mediation of hepatic encephalopathy comes from the therapeutic effect reported after administration of the benzodiazepine receptor antagonist flumazenil. Improvements in the severity of hepatic encephalopathy have been documented in rats with fulminant hepatic failure given flumazenil, although results have been inconsistent according to the dose of flumazenil used and the procedure employed to induce the encephalopathy. Transient, but distinct, improvements in the grade of hepatic encephalopathy have also been documented in several human studies. In a placebo-controlled study involving patients with mild hepatic encephalopathy, a low dose of flumazenil (0.2 mg/kg) resulted in a significant improvement in reaction time.Research now needs to identify whether the beneficial effect of flumazenil is due to its antagonistic or inverse agonistic properties, and also to clarify the mechanisms by which the differential response to the drug in animal models of fulminant hepatic failure is mediated.

An analysis of memory dysfunction in major depression.

15 patients suffering from DSM-III-R major depression were compared with 15 age-, sex- and intelligence-matched controls on a battery of memory tests, aimed at fractionating memory dysfunction in depression. Patients were unimpaired relative to controls on measures of short-term memory, recognition, semantic memory and implicit memory. There was no evidence of a hedonic bias in recall of positive vs. negatively valenced stimuli, nor was there any correlation between depression severity and level of memory impairment. Psychotic patients did not demonstrate greater memory impairment relative to nonpsychotic depressed patients. As a group, however, depressed patients demonstrated deficits in psychomotor speed and in free recall of material (both immediate and delayed). The selective recall deficit suggests that material has been encoded but that patients are particularly impaired with regard to search and retrieval processes.

State changes in brain activity shown by the uptake of 99mTc-exametazime with single photon emission tomography in major depression before and after treatment.

Twenty-eight patients with a major depressive episode previously investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, were followed up at an interval of 9-28 months with the same investigation after full recovery. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. The uptake of 99mTc-Exametazime was expressed relative to calcarine/occipital cortex. Sixteen patients were scanned when optimally matched for drug treatment (4) or on both occasions drug free (12). The other 12 patients were fully recovered but could not be matched for drug status; these patients showed significantly more retardation, diurnal mood variation and guilt at presentation. Significant bilateral increases in tracer uptake were confined to basal ganglia and inferior anterior cingulate cortex in the matched group, where there were additional increases in thalamus and posterior cingulate cortex on the right side. There were no statistically discernible changes in the neocortex in the matched sample. The unmatched sample yielded inconclusive evidence of increased tracer uptake in left temporal cortex. The findings give a potential focus to the neuropharmacological analysis of depressive illness because the topography of the state change in brain function implicates dopamine function.

The effect of anxiety induction on the regional uptake of 99mTc-exametazime in simple phobia as shown by single photon emission tomography (SPET).

Ten patients suffering from DSM-III-R simple phobia were studied under two conditions: (a) while listening to a 4 min relaxation tape, and (b) while listening to a 4 min audio tape describing exposure to the phobic stimulus. During each condition, subjects were injected with 99mTc-Exametazime, a marker of regional cerebral blood flow. Subjective and psychophysiological measures indicated a marked effect of the anxiety induction procedure. Ratio analysis of the SPET data revealed reductions in tracer uptake largely confined to posterior cerebral regions bilaterally. Analysis of brain regions of interest normalised to the whole brain slice showed reductions confined to right temporal/occipital regions. In general there was no clear association between subjective and physiological variables and changes in regional uptake of tracer as a consequence of the anxiety induction procedure. The changes in tracer uptake were dissimilar to those previously reported for other cognitive activation paradigms, providing some reassurance that those functional brain changes were not artefacts of non-specific changes in state anxiety. These posterior brain changes may reflect alterations in activation of the GABA/benzodiazepine complex.

Single photon emission tomography with 99mTc-exametazime in major depression and the pattern of brain activity underlying the psychotic/neurotic continuum.

Forty patients with a major depressive episode were investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, an intravenous ligand taken into brain in proportion to regional cerebral blood flow, thereby providing an estimate of regional metabolism. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. They also completed a range of neuropsychological tests. They were compared with 20 control subjects matched for age, gender, premorbid intelligence and education. The uptake of 99mTc-exametazime was expressed for a range of anatomically defined regions of interest relative to calcarine/occipital cortex. The depressed group showed reduced uptake in the majority of cortical and sub-cortical regions examined, most significantly in temporal, inferior frontal and parietal areas. Unexpectedly, there was a strong positive association between uptake and scores on the Newcastle scale, especially in cingulate areas and frontal cortex. After removing the variance attributable to the Newcastle ratings, however, there emerged the expected negative association between Hamilton scores and anterior tracer uptake. The associations between neuropsychological impairment and regional brain uptake of tracer in part reflected the pattern seen with the Newcastle scale: for example, impairment of memory function correlated with higher uptake into posterior cingulate areas. We propose that depressive illness may be characterised by two processes. One leads to an overall reduction in anterior neocortical function, perhaps related to symptom severity. The other mechanism is manifest as relatively increased function, most notably within cingulate and frontal areas of the cerebral cortex in association with psychotic symptoms. The findings offer new understanding of the brain states underlying depressive illness and a potential focus to subsequent neuropharmacological analysis.

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.

Diurnal variation of mood and neuropsychological function in major depression with melancholia.

20 DSM-III-R melancholics with clinically evident diurnal symptoms and 20 controls were assessed with a battery of neuropsychological tests, a test of maximum voluntary hand-grip, and neuroendocrine measures of hypothalamic-pituitary-adrenal axis function morning and evening in a 24-h period, using a balanced design. The morning pattern of neuropsychological impairment in the melancholics was comprehensive, affecting attention and concentration/working memory, episodic memory, reaction time and, strikingly, the speed of simultaneous match to sample, which was performed more slowly than the version of the task delayed to 0 or 4 s. The melancholics were significantly weaker than controls, on a measure of maximal voluntary contraction. Significantly improved neuropsychological function was seen in the melancholic patients in the evening, in line with diurnal improvement in mood; there was also a large increase in strength. Slowing on the digit symbol substitution test, the simultaneous match to sample task, total errors on the match to sample and hand-grip remained impaired in the evening compared to controls; other neuropsychological measures were no longer statistically different from control values which were often worsened. Neuroendocrine measures showed significantly raised levels of cortisol and ACTH morning and evening in the melancholics. Morning cortisol in the melancholics correlated with the diurnal improvement in neuropsychological functioning. The results have implications for the timing of neuropsychological assessment in major depression. Indices of neuropsychological and motor function may be as reliable quantitative estimates of illness severity as subjective estimates of mood.