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Suppression of negative thoughts has been observed under experimental conditions among patients with major depressive disorder (MDD) but has never been examined among patients with bipolar disorder (BD). Patients with BD (n = 36), patients with MDD (n = 20), and healthy controls (n = 20) completed a task that required unscrambling 6-word strings into 5-word sentences, leaving out 1 word. The extra word allowed the sentences to be completed in a negative, neutral, or "hyperpositive" (manic/goal-oriented) way. Participants completed the sentences under conditions of cognitive load (rehearsing a 6-digit number), reward (a bell tone), load and reward, or neither load nor reward. We hypothesized that patients with BD would engage in more active suppression of negative and hyperpositive thoughts than would controls, as revealed by their unscrambling more word strings into negative or hyperpositive sentences. Under conditions of load or reward and in the absence of either load or reward, patients with BD unscrambled more negative sentences than did controls. Under conditions of reward, patients with BD unscrambled more negative sentences than did patients with MDD. Patients with BD also reported more use of negative thought suppression than did controls. These group differences in negative biases were no longer significant when current mood states were controlled. Finally, the groups did not differ in the proportion of hyperpositive sentence completions in any condition. Thought suppression may provide a critical locus for psychological interventions in BD.

Background: Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4-6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual.Methods/design: The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient's antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms - Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed.Discussion: This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients.Trial Registration: ClinicalTrials.gov, ID: NCT02790970 . Registered on 30 March 2016. [ABSTRACT FROM AUTHOR]

In 1997, neuropsychological and neuroimaging evidence supported the involvement of the frontal lobes and indeed the brain in depression. This was a challenge to conventional phenomenology and linked with the imperative to use neuroscience to understand major mental illness. Since that time, we are seeing ever more convincing evidence for the genetic basis of mental illness (including depression), relevant abnormality in grey and white matter and neuropsychological analysis of brain function. It has proved more difficult to pin down structural abnormality in major depression at the cellular level, but a focus on glial cells is increasingly justified by the evidence. Neuroscience continues to be a buttress against anti-scientific impulses in psychiatry and can help attract young people to enter it as a profession. [ABSTRACT FROM AUTHOR]

Background: Despite lithium's being the most effective drug for bipolar disorder and in clinical use for decades, we still know very little about its early effects relevant to its mode of action.Methods/design: The Oxford Lithium Trial is a double-blind, randomised, placebo-controlled study of 6-week lithium treatment in participants with bipolar disorder and mood instability. Its aim is to identify early clinical, neurocognitive and biological effects. Participants (n = 40) will undergo an intensive battery of multi-modal investigations, including remote monitoring of mood, activity and physiology, as well as cognitive testing, fMRI and magnetoencephalography, together with biochemical and gene expression measurements to assess renal, inflammatory and circadian effects.Discussion: The findings derived from this trial may be of value in predicting subsequent therapeutic response or side effects, not only relevant to the use of lithium but also providing a potential signature to help in more rapid evaluation of novel mood stabilisers. In this respect, OxLith is a step towards the development of a valid experimental medicine model for bipolar disorder.Trial Registration: ISRCTN91624955 . Registered on 22 January 2015. [ABSTRACT FROM AUTHOR]

Hales SA, Deeprose C, Goodwin GM, Holmes EA. Cognitions in bipolar affective disorder and unipolar depression: imagining suicide. Bipolar Disord 2011: 13: 651-661. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S. Objective: Bipolar disorder has the highest rate of suicide of all the psychiatric disorders. In unipolar depression, individuals report vivid, affect-laden images of suicide or the aftermath of death (flashforwards to suicide) during suicidal ideation but this phenomenon has not been explored in bipolar disorder. Therefore the authors investigated and compared imagery and verbal thoughts related to past suicidality in individuals with bipolar disorder (n = 20) and unipolar depression (n = 20). Methods: The study used a quasi-experimental comparative design. The Structured Clinical Interview for DSM-IV was used to confirm diagnoses. Quantitative and qualitative data were gathered through questionnaire measures (e.g., mood and trait imagery use). Individual interviews assessed suicidal cognitions in the form of (i) mental images and (ii) verbal thoughts. Results: All participants reported imagining flashforwards to suicide. Both groups reported greater preoccupation with these suicide-related images than with verbal thoughts about suicide. However, compared to the unipolar group, the bipolar group were significantly more preoccupied with flashforward imagery, rated this imagery as more compelling, and were more than twice as likely to report that the images made them want to take action to complete suicide. In addition, the bipolar group reported a greater trait propensity to use mental imagery in general. Conclusions: Suicidal ideation needs to be better characterized, and mental imagery of suicide has been a neglected but potentially critical feature of suicidal ideation, particularly in bipolar disorder. Our findings suggest that flashforward imagery warrants further investigation for formal universal clinical assessment procedures. [ABSTRACT FROM AUTHOR]

Objective. To ascertain whether a small sample of patients with chronic pelvic pain experienced any pain-related cognitions in the form of mental images. Patients. Ten women with chronic pelvic pain consecutively referred from a tertiary referral center by the physicians in charge of their treatment. Outcome measures. An interview was used to determine the presence, emotional valence, content, and impact of cognitions about pain in the form of mental images and verbal thoughts. The Brief Pain Inventory (BPI), Pain Catastrophizing Scale (PCS), Spontaneous Use of Imagery Scale (SUIS), and Hospital Anxiety and Depression Scale (HADS) were completed. Results. In a population of patients with a prolonged duration of pain and high distress, all patients reported experiencing cognitions about pain in the form of mental images. For each patient, the most significant image was both negative in valence and intrusive. The associated emotionalbehavioral pattern could be described within a cognitive behavioral therapy framework. Eight patients also reported coping imagery. Conclusion. Negative pain-related cognitions in the form of intrusive mental imagery were reported by women with chronic pelvic pain. Targeting such imagery has led to interesting treatment innovation in the emotional disorders. Thus, imagery, hitherto neglected in pain phenomenology, could provide a novel target for cognitive behavioral therapy in chronic pain. These exciting yet preliminary results require replication and extension in a broader population of patients with chronic pain. [ABSTRACT FROM AUTHOR]

Abstract: This is a report arising from an ECNP expert meeting. Recent studies have focussed on cognitive problems in manic-depressive illness and a few have addressed premorbid neuropsychological functioning. The results are not fully consistent but seem to point to a neurodegenerative model, rather than a neurodevelopmental one, for some cognitive domains. There is agreement that cognitive dysfunction is highly correlated with psychosocial functioning. The neurobiological and clinical implications of recent findings will be discussed. Treatments to reduce subsyndromal symptoms and relapses may indirectly improve neurocognitive deficits and this should be better documented. Moreover, neurocognitive impairment in bipolar disorder should be considered a potential therapeutic target, so that research should focus on new drugs and psychological interventions, including neurocognitive rehabilitation, addressed to improve not only the cognition but also the functional outcome of this population. [Copyright &y& Elsevier]

Transcranial magnetic stimulation (TMS) using a double-cone coil over the medial frontal cortex has the potential to clarify the function of the anterior cingulate cortex (ACC) in cognition, emotion and mood disorders. Following demonstration of disruption of performance on psychological tasks closely linked to cingulate function using this TMS technique, the current study aimed to directly measure the regional distribution of physiological effects of stimulation in the brain with H215O PET. Experiment 1 assessed the effect of increasing numbers of pulse trains of TMS on regional cerebral blood flow (rCBF). Experiment 2 assessed the capacity of medial frontal TMS to modulate brain activity associated with the Stroop task using medial parietal TMS as a control site of stimulation. SPM99 analyses, using the ACC as a region of interest, revealed clusters of increased rCBF during medial frontal TMS in Brodmann area 24 and reduced rCBF in more ventral ACC, the latter occurring in both experiments. In a whole-brain analysis, striking changes in rCBF were observed distal to the ACC following medial frontal TMS. Although TMS reliably affected Stroop task performance in early trials, there was no interaction between TMS and Stroop condition in rCBF. Our results suggest that medial frontal TMS using the double-cone coil can affect ACC activity. However, a number of more distal cortical areas were also affected in these experiments. These additional changes may reflect either ‘downstream’ effects of altered cingulate cortex activity or direct effects of the coil. [ABSTRACT FROM AUTHOR]

Objectives: Patients with chronic fatigue syndrome complain of physical and mental fatigue that is worsened by exertion. It was predicted that the cognitive and motor responses to vigorous exercise in patients with chronic fatigue syndrome would differ from those in depressed and healthy controls.Methods: Ten patients with chronic fatigue syndrome, 10 with depressive illness, and 10 healthy controls completed cognitive and muscle strength testing before and after a treadmill exercise test. Measures of cardiovascular functioning and perceived effort, fatigue, and mood were taken during each stage of testing.Results: Depressed patients performed worst on cognitive tests at baseline. During the treadmill test, patients with chronic fatigue syndrome had higher ratings of perceived effort and fatigue than both control groups, whereas patients with depression reported lower mood. After exertion, patients with chronic fatigue syndrome showed a greater decrease than healthy controls on everyday tests of focused (p=0.02) and sustained (p=0.001) attention, as well as greater deterioration than depressed patients on the focused attention task (p=0.03). No between group differences were found in cardiovascular or symptom measures taken during the cognitive testing.Conclusions: Patients with chronic fatigue syndrome show a specific sensitivity to the effects of exertion on effortful cognitive functioning. This occurs despite subjective and objective evidence of effort allocation in chronic fatigue syndrome, suggesting that patients have reduced working memory capacity, or a greater demand to monitor cognitive processes, or both. Further insight into the pathophysiology of the core complaints in chronic fatigue syndrome is likely to be realised by studying the effects of exercise on other aspects of everyday functioning. [ABSTRACT FROM AUTHOR]

Objective: The authors' goal was to characterize cognitive flexibility and verbal learning in relatives of patients with bipolar disorder and in euthymic patients with recurrent major depression. Method: The intradimensional/extradimensional shift task and California Verbal Learning Test were administered to 27 first-degree relatives of probands with bipolar I disorder, 15 euthymic outpatients with recurrent unipolar depression, and 47 healthy comparison subjects. Results: The relatives of patients with bipolar I disorder and the euthymic patients with unipolar depression were more likely to fail the intradimensional/extradimensional shift task than the healthy comparison subjects, The impairments at the extradimensional shift stage were pronounced. Verbal learning, delayed recall, and recognition were unimpaired in all groups. Conclusions: Attentional set shifting may represent an endophenotype in mood disorder, related to underlying vulnerability rather than the actual disease phenotype. [ABSTRACT FROM AUTHOR]

Background: Cognitive dysfunction occurs in depression and can persist into remission. It impacts on patient functioning but remains largely unrecognised, unmonitored and untreated. We explored understanding of cognitive dysfunction in depression among UK clinicians.Methods: A multi-step consultation process. Step 1: a multi-stakeholder steering committee identified key themes of burden, detection and management of cognitive dysfunction in depression, and developed statements on each to explore understanding and degree of agreement among clinicians. Step 2: 100 general practitioners (GPs) and 100 psychiatrists indicated their level of agreement with these statements. Step 3: the steering committee reviewed responses and highlighted priority areas for future education and research.Results: There was agreement that clinicians are not fully aware of cognitive dysfunction in depression. Views of the relationship between cognitive dysfunction and other depressive symptom severities was not consistent with the literature. In particular, there was a lack of recognition that some cognitive dysfunction can persist into remission. There was understandable uncertainty around treatment options, given the current limited evidence base. However, it was recognised that cognitive dysfunction is an area of unmet need and that there is a lack of objective tests of cognition appropriate for depressed patients that can be easily implemented in the clinic.Limitations: Respondents are likely to be 'led' by the direction of the statements they reviewed. The study did not involve patients and carers.Conclusions: UK clinicians should undergo training regarding cognitive dysfunction in depression, and further research is needed into its assessment, treatment and monitoring. [ABSTRACT FROM AUTHOR]

Background: In bipolar disorder (BD), little is known about how deficits in neurocognitive functions such as decision-making are related to phase of illness. We predicted that manic, depressed, and euthymic bipolar patients (BPs) would display impaired decision-making, and we tested whether clinical characteristics could predict patients'' decision-making performance. Methods: Subjects (N = 317; age range: 18–65 years) including 167 BPs (45 manic and 32 depressed inpatients, and 90 euthymic outpatients) and 150 age-, IQ-, and gender-matched healthy control (HC) participants, were included within three university psychiatric hospitals using a cross-sectional design. The relationship between predictor variables and decision-making was assessed by one-step multivariate analysis. The main outcome measures were overall decision-making ability on the Iowa Gambling Task (IGT) and an index of sensitivity to punishment frequency. Results: Manic, depressed, and euthymic BPs selected significantly more cards from the risky decks than HCs (p < .001, p < .01, and p < .05, respectively), with no significant differences between the three BD groups. However, like HCs, BPs preferred decks that yielded infrequent penalties over those yielding frequent penalties. In multivariate analysis, decision-making impairment was significantly (p < .001) predicted by low level of education, high depressive scores, family history of BD, use of benzodiazepines, and nonuse of serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants. Conclusions: BPs have a trait-related impairment in decision-making that does not vary across illness phase. However, some subtle differences between the BD groups in the individual deck analyses may point to subtle state influences on reinforcement mechanisms, in addition to a more fundamental trait impairment in risk-sensitive decision making. [Copyright &y& Elsevier]

Background: Depressed mood alters the pain experience. Yet, despite its clear clinical relevance, little is known about the cognitive and neural mechanisms underlying this phenomenon. We tested an experimental manipulation to unravel the interaction between depressed mood and pain. We hypothesized that dysregulation of the neural circuitry underlying emotion regulation is the mechanism whereby pain processing is affected during depressed mood. Methods: Using functional magnetic resonance imaging, we compared the effects of sad and neutral cognitive mood inductions on affective pain ratings, pain-specific cognitions, and central pain processing of a tonic noxious heat stimulus in 20 healthy volunteers. Results: The increase in negative pain-specific cognitions during depressed mood predicted the perceived increase in pain unpleasantness. Following depressed mood induction, brain responses to noxious thermal stimuli were characterized by increased activity in a broad network including prefrontal areas, subgenual anterior cingulate cortex, and hippocampus, as well as significantly less deactivation when compared with pain responses in a neutral mood. The participants who reported the largest increase in pain unpleasantness after the sad mood induction showed greater inferior frontal gyrus and amygdala activation, linking changes in emotion regulation mechanisms with enhancement of pain affect. Conclusions: Our results inform how depressed mood and chronic pain co-occur clinically and may serve to develop and translate effective interventions using pharmacological or psychological treatment. [Copyright &y& Elsevier]

Background: A tendency to orient attention toward threatening stimuli may be involved in the etiology of anxiety disorders. In keeping with this, both psychological and pharmacological treatments of anxiety reduce this negative attentional bias. It has been hypothesized, but not proved, that psychological interventions may alter the function of prefrontal regions supervising the allocation of attentional resources. Methods: The current study examined the effects of a cognitive training regime on attention. Participants were randomly assigned to one of two training conditions: “attend-threat” training, which increases negative attentional bias, or “avoid-threat” training, which reduces it. The behavioral effects of training were assessed using a sample of 24 healthy participants. Functional magnetic resonance imaging data were collected in a further 29 healthy volunteers using a protocol that allowed the influence of both stimuli valence and attention to be discriminated. Results: Cognitive training induced the expected attentional biases in healthy volunteers. Further, the training altered lateral frontal activation to emotional stimuli, with these areas responding specifically to violations of the behavioral rules learned during training. Connectivity analysis confirmed that the identified lateral frontal regions were influencing attention as indexed by activity in visual association cortex. Conclusions: Our results indicate that frontal control over the processing of emotional stimuli may be tuned by psychological interventions in a manner predicted to regulate levels of anxiety. This directly supports the proposal that psychological interventions may influence attention via an effect on the prefrontal cortex. [Copyright &y& Elsevier]

Background: Cognitive dysfunction persists in the euthymic phase of bipolar disorder and may provide a marker of underlying neuropathology and disease vulnerability. This study aimed to replicate a deficit in sustained attention in euthymic bipolar patients and investigate sustained attention in first-degree relatives of bipolar probands and in remitted patients with major depressive disorder. Methods: The rapid visual information processing (RVIP) task was used to measure sustained attention in 15 euthymic patients with bipolar disorder and 15 control subjects in experiment 1 and in 27 first-degree relatives of bipolar probands, 15 remitted patients with major depressive disorder, and 46 control subjects in experiment 2. Results: Sustained attention deficit was confirmed in the euthymic bipolar patients in experiment 1, but the deficit was not statistically significant in remitted major depressed patients or in the relatives of bipolar probands. Conclusions: A deficit of sustained attention is not present in patients with recurrent major depression tested during remission nor is it discriminable in the first-degree relatives of bipolar probands. Thus, the confirmed abnormality in euthymic bipolar patients may be acquired as a consequence of bipolar illness. However, future studies of relatives will require larger sample sizes to exclude or utilize small genetic effects. [Copyright &y& Elsevier]