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The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.

Previous research has demonstrated cognitive-enhancing effects of modafinil in humans and generated evidence for its therapeutic potential in psychiatric disorders. The neurochemical basis of these effects remains unresolved although a role for α1-adrenoceptors has been hypothesised. In this within-subject, double-blind, placebo-controlled study, 12 healthy male adults received modafinil (300 mg), the α1-adrenoceptor antagonist prazosin (3 mg), both together and placebo on separate occasions at least 5 days apart. Cognitive effects were assessed using a well-validated testing battery focusing on executive and working memory functions. Blood pressure, heart rate and salivary α-amylase (sAA) were measured at hourly intervals. Cognitive effects of modafinil and prazosin were identified at the difficult levels of the One-Touch Stockings of Cambridge (OTSOC) planning task. Prazosin antagonized the error-reducing effect of modafinil when the agents were given together. In contrast, the combined agents acted synergistically to increase time taken to complete OTSOC problems compared with placebo. The tachycardic and sAA-elevating effects of prazosin were also potentiated by concurrent modafinil administration. The current data suggest that the cognitive effects of modafinil on performance accuracy and latency are dissociable in terms of their neurochemical mechanisms. Our findings support the hypothesised involvement of α1-adrenoceptors in some of the cognitive-enhancing effects of modafinil and warrant further investigation. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Although poor neuropsychological test performance is well documented in schizophrenia, how closely it resembles that seen in patients with brain damage in terms of cognitive failures in daily life and stability over time has been little studied.MethodThirty patients with chronic schizophrenia, 24 patients with frontal or temporal brain damage and 30 healthy controls were given a battery of memory and executive tests. Carers of the two patient groups also completed questionnaires rating memory and executive failures in daily life. Testing was repeated 6 weeks later. RESULTS: The schizophrenia and the brain-damaged patients were significantly impaired on most, but not all tests. The degree of carer-rated memory or executive failure was similar in the two groups, but the schizophrenia patients were rated as having significantly more executive failures than memory failures, whereas the brain-damaged patients showed the reverse pattern. Both groups of patients showed similar consistency of performance across sessions. CONCLUSIONS: Neuropsychological impairment in schizophrenia resembles that seen in patients with brain damage, not only in terms of overall severity, but also in terms of stability and the degree to which poor test performance translates into cognitive failures in daily life. [ABSTRACT FROM AUTHOR]

ABSTRACTDepressive disorders are amongst the leading causes of disability and mortality worldwide and, as such, it is predicted that by 2010 only cardio-ischaemic disorders will provide a greater burden. In addition to the sizable emotional, individual and social burden, depressive disorders cost an estimated US$83.1 billion per year in the United States alone. In spite of effective treatments, a large proportion of sufferers go on to experience recurrences. With successive recurrences, the likelihood of subsequent episodes increases. Despite this, research to date has tended to focus on first episodes or else has not distinguished between episodes. This editorial review highlights a number of differences between first and recurrent episodes which, in turn, recommend more longitudinal, recurrence-oriented, treatments. We also examine the findings from acute tryptophan depletion studies which, it is speculated, help to understand the differences between successive episodes. The overall aim, however, is to highlight the importance of recurrence in depression and to stimulate debate. [ABSTRACT FROM AUTHOR]

Background. The idea that superior cognitive function acts as a protective factor against dementia and the consequences of head injury is well established. Here we suggest the hypothesis that cognitive reserve is also important in neuropsychiatric disorders including schizophrenia, bipolar disorder and depression.Method. We review the history of passive and active models of reserve, and apply the concept to neuropsychiatric disorders. Schizophrenia is used as an exemplar because the effects of premorbid IQ and cognitive function in this disorder have been extensively studied.Results. Cognitive reserve may impact on neuropsychiatric disorders in three ways: by affecting the risk for developing the disorder, in the expression of symptoms within disorders, and in patients' functional outcome. Cognitive failure below a certain threshold may alone, or in combination with common psychiatric symptoms, produce neuropsychiatric syndromes.Conclusions. Consideration of cognitive reserve may considerably improve our understanding of individual differences in the causes and consequences of neuropsychiatric disorders. For these reasons, the concept of cognitive reserve should be incorporated in future studies of neuropsychiatric disorder. It may be possible to enhance cognitive reserve through pharmacological or non-pharmacological means, such as education, neurocognitive activation or other treatment programmes. [ABSTRACT FROM AUTHOR]

Background. Depression is usually the predominant affective state in bipolar disorder. There are few studies, with discrepant views, examining the extent of cognitive impairment in patients with bipolar depression. To our knowledge, there are no previous studies examining decision-making ability or whether there is an affective attentional bias in bipolar depression.Method. We ascertained 24 depressed bipolar I patients from acute psychiatric hospital wards and out-patient clinics and 26 age- and IQ-matched healthy controls. Using computerized tests we evaluated their performance on 'neutral' (non-emotional) cognitive tasks (i.e. memory, attention and executive function) and on novel tasks of emotional cognition (i.e. the decision-making task and the affective go/no-go task).Results. Accuracy measures were significantly impaired on tests of visual and spatial recognition and attentional set-shifting in bipolar depression compared with age- and IQ-matched controls. The quality of decision-making was also significantly impaired in the patients. A mood-congruent attentional bias for 'sad' targets was not evident on the affective go/no-go task.Conclusions. We found widespread evidence of significant cognitive impairment and impaired quality of decision-making in symptomatically severe depressed bipolar patients. This cognitive impairment may contribute to difficulties with daily living, decision-making and the ability to engage and comply with psychological and drug treatments. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although many studies have reported impairments of neurocognitive performance in patients with anorexia nervosa (AN), these have involved a wide range of assessment methods and some findings are inconsistent. METHOD: Twenty-five female in-patients with a DSM-IV diagnosis of AN, identified from three units specializing in the treatment of eating disorders, volunteered for the study. Twenty-five non-clinical control subjects were recruited, matched for age, gender and estimated IQ. Subjects were assessed with a range of computer-administered neurocognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), which has been validated in many studies of neuropsychiatric disorders. RESULTS: The patient group showed significant but moderate impairments (i.e. less than one standard deviation below the mean performance of the control group) on tests of spatial recognition memory, a planning task and rapid visual information processing, while a subgroup of patients (n = 14) showed greater degrees of impairments on at least one of these tests. The degrees of impairments did not correlate with body mass index (BMI). No impairments were observed on tests of spatial span, pattern recognition memory, spatial working memory, matching-to-sample, paired associates learning and set-shifting. CONCLUSIONS: The findings, in relation to a mean BMI of 15.3, are compatible with, in general, subtle impairments in neurocognition in AN. However, in those patients with relatively severe degrees of impairments, these may have adverse effects on complex tasks of social and occupational functioning. Further research is needed on the nature of relevant causal mechanisms, including the effects of potentially confounding variables. [ABSTRACT FROM AUTHOR]

Background. The use of strategies to aid performance when undertaking neuropsychological tasks is dependent on intact fronto-striatal circuitry, and growing evidence suggests impaired spontaneous use of strategies in patients with obsessive-compulsive disorder (OCD). However, studies to date have not examined the effects of strategy training on task performance in OCD or in trichotillomania (compulsive hair-pulling, a condition that has been argued to share overlap with OCD in terms of phenomenology and co-morbidity).Method. The ability to generate novel visuospatial sequences using a computer interface was examined before and after undertaking optimal strategy training in 20 OCD patients, 17 trichotillomania patients, and 20 controls (matched for age, education, and IQ).Results. OCD patients failed to improve ability to generate novel sequences above baseline despite successfully completing strategy training to the same extent as other groups. In contrast, performance of trichotillomania patients improved significantly after training to the same extent as controls. Groups did not differ on memory span, trial-by-trial action monitoring, or ability to generate novel visuospatial sequences prior to strategy training.Conclusions. Strategy implementation deficits, suggestive of cognitive inflexibility and fronto-striatal dysfunction, appear integral to the neurocognitive profile of OCD but not trichotillomania. Future research should investigate cognitive flexibility in obsessive-compulsive spectrum disorders using a variety of paradigms, and clarify the contribution of specific neural structures and transmitter systems to deficits reported. [ABSTRACT FROM AUTHOR]

Background. Demonstrating specific cognitive impairments in psychotic disorders is difficult. However, specific deficits in memory and executive functions have often been claimed. The Cambridge Neuropsychological Test Automated Battery (CANTAB) tasks of IDED attention-shifting (an executive task) and visuospatial paired associates learning (PAL, a memory task) require intact frontal and temporo-hippocampal functioning, respectively; both have been suggested as markers of disease progress in psychosis.Method. Seventy-one subjects with a first-episode psychosis or at-risk mental state were assessed on these two tasks during referral to a specialist service, the Cambridge-based CAMEO early intervention team.Results. Performance on the two tasks was dissociated. Poor performance on the PAL test was associated with increased symptom levels and poorer global function, while failure on the IDED executive test was not found to have significant clinical associations. Duration of illness was not associated with performance on either task.Conclusions. Visuospatial PAL failure may be a marker of clinical severity at the onset of psychosis while IDED performance may reflect a more stable, trait-like impairment. Dissociated performance on the executive and associative learning tasks may reflect independent, neurally dissociated impairments that do not arise in a fixed order. This may explain some of the heterogeneity of cognitive function seen in early psychosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cognitive performance was compared in the genetically and neurobiologically related disorders of Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD), in three domains of executive function: planning, decision-making and inhibitory response control. METHOD: Twenty TS patients, twenty OCD patients and a group of age- and IQ-matched normal controls completed psychometric and computerized cognitive tests and psychiatric rating scales. The cognitive tests were well-characterized in terms of their sensitivity to other fronto-striatal disorders, and included pattern and spatial recognition memory, attentional set-shifting, and a Go/No-go set-shifting task, planning, and decision-making. RESULTS: Compared to controls, OCD patients showed selective deficits in pattern recognition memory and slower responding in both pattern and spatial recognition, impaired extra-dimensional shifting on the set-shifting test and impaired reversal of response set on the Go/No-go test. In contrast, TS patients were impaired in spatial recognition memory, extra-dimensional set-shifting, and decision-making. Neither group was impaired in planning. Direct comparisons between the TS and OCD groups revealed significantly different greater deficits for recognition memory latency and Go/No-go reversal for the OCD group, and quality of decision-making for the TS group. CONCLUSIONS: TS and OCD show both differences (recognition memory, decision-making) and similarities (set-shifting) in selective profiles of cognitive function. Specific set-shifting deficits in the OCD group contrasted with their intact performance on other tests of executive function, such as planning and decision-making, and suggested only limited involvement of frontal lobe dysfunction, possibly consistent with OCD symptomatology. [ABSTRACT FROM AUTHOR]

BACKGROUND: It is now accepted that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. However, relative to the considerable literature concerning the profile of neurocognitive deficits associated with this disorder in childhood, equivalent investigations in adult populations have been less common. The current study examined cognitive function in adults diagnosed with ADHD employing well-validated neuropsychological tasks. METHOD: Nineteen adult patients who satisfied DSM-IV criteria for ADHD and 19 matched (gender, age and verbal IQ), non-clinical control subjects were recruited. Patients were either unmedicated or had abstained from a psychostimulant medication regime for at least 24 h prior to neurocognitive assessment. A functionally wide-ranging test battery was administered. RESULTS: Relative to controls, ADHD adults performed significantly worse on spatial working memory, planning, and attentional-set shifting tests and were significantly slower to respond to target stimuli on the go/no-go task. In contrast, the two subject groups performed equivalently on decision-making and pattern/spatial recognition memory assessments. CONCLUSIONS: The demonstration of neuropsychological dysfunction in the adult ADHD cohort provides some support for the validity of this diagnosis in adulthood. In particular, there is broad consistency between the cognitive profile revealed in the current investigation and that previously demonstrated in a study of medication-naïve ADHD children. There is evidence that frontostriatal function is especially disrupted. [ABSTRACT FROM AUTHOR]

Unilateral neglect, an attentional deficit in detecting and acting on information coming from one side of space, is a relatively common consequence of right hemisphere stroke. Although neglect has been observed following damage to a variety of brain structures, to date no reports exist of neglect phenomena arising from Huntington's Disease (HD). However, reports in the animal and human literature suggest that neglect is possible following damage to a primary site for Huntington's pathology, the basal ganglia. Here we present a patient (BG) with genetically proven HD who, in the context of the mild intellectual, executive and attentional impairments associated with the disorder, showed a remarkably severe and stable neglect for left space. MRI and electrophysiological results make it unlikely that the spatial bias could be accounted for by basic sensory loss. In addition, behavioural investigation indicated that, although BG's neglect operated in a very striking manner along body-centred co-ordinates (missing almost all information presented to her left), more general limitations in visual attention were apparent to the left-side of information presented entirely to the right of the body midline. Further evidence is presented showing that the neglect was manifest on tactile and auditory tasks as well as those presented in the visual domain. The presence of neglect in HD in this case is novel and somewhat puzzling, particularly as flourodeoyglucose positron emission tomography revealed bilateral caudate hypoperfusion. Reducing the statistical threshold on this analysis revealed a potential frontal hypometabolism that was more marked in the right than left hemisphere. However, as this was only apparent at a threshold below that normally considered acceptable (due to the resulting number of false positives), this possible account of the neglect must be viewed very cautiously. [ABSTRACT FROM AUTHOR]

Objectives: Eleven patients with idiopathic normal pressure hydrocephalus (NPH) were selected from an initial cohort of 43 patients. The patients with NPH fell into two distinctive subgroups: preshunt, group 1 (n=5) scored less than 24 on the mini mental state examination (MMSE) and were classified as demented and group 2 (n=6) scored 24 or above on the MMSE and were classified as non-demented.Methods: All patients were neuropsychologically assessed on two occasions: preshunt and then again 6 months postshunt. Group 1 completed the mini mental state examination (MMSE) and the Kendrick object learning test (KOLT). In addition to the MMSE and KOLT, group 2 completed further tasks including verbal fluency and memory and attentional tasks from the CANTAB battery. Nine of the 11 patients also underwent postshunt MRI.Results: Group 1, who, preshunt, performed in the dementing range on both the MMSE and KOLT, showed a significant postoperative recovery, with all patients now scoring within the normal non-demented range. Group 2, although showing no signs of dementia according to the MMSE and KOLT either preshunt or postshunt, did show a specific pattern of impairment on tests sensitive to frontostriatal dysfunction compared with healthy volunteers, and this pattern remained postoperatively. Importantly, this pattern is distinct from that exhibited by patients with mild Alzheimer's disease. Eight of the nine patterns of structural damage corresponded well to cognitive performance.Conclusions: These findings are useful for three main reasons: (1) they detail the structural and functional profile of impairment seen in NPH, (2) they demonstrate the heterogeneity found in this population and show how severity of initial cognitive impairment can affect outcome postshunt, and (3) they may inform and provide a means of monitoring the cognitive outcome of new procedures in shunt surgery. [ABSTRACT FROM AUTHOR]