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There is considerable international interest in online education of patients with bipolar disorder, yet little understanding of how patients use the Internet and other sources to seek information. 1171 patients with a diagnosis of bipolar disorder in 17 countries completed a paper-based, anonymous survey. 81% of the patients used the Internet, a percentage similar to the general public. Older age, less education, and challenges in country telecommunications infrastructure and demographics decreased the odds of using the Internet. About 78% of the Internet users looked online for information on bipolar disorder or 63% of the total sample. More years of education in relation to the country mean, and feeling very confident about managing life decreased the odds of seeking information on bipolar disorder online, while having attended support groups increased the odds. Patients who looked online for information on bipolar disorder consulted medical professionals plus a mean of 2.3 other information sources such as books, physician handouts, and others with bipolar disorder. Patients not using the Internet consulted medical professionals plus a mean of 1.6 other information sources. The percentage of patients with bipolar disorder who use the Internet is about the same as the general public. Other information sources remain important.

Objective Despite recent research demonstrating associations between violence and depression in adults, links in adolescents are uncertain. This study aims to assess the longitudinal associations between young people’s depression and later violent outcomes. Method We used data from three cohorts with different measurements of depression exposures and subsequent violent outcomes. In a Dutch community cohort Research on Adolescent Development And Relationships (RADAR; N = 623) and a population-based British birth cohort Avon Longitudinal Study of Parents and Children (ALSPAC; N = 4,030), we examined the longitudinal links between adolescent depressive symptoms and violent behaviors from age 13 to 17 years. In a total Finnish birth cohort (FBC 1987; N = 57,526), we estimated risk of violent convictions in individuals clinically diagnosed with depression from age 15 to 27 years. Results During a mean follow-up period of 4 years, the adjusted odds ratio (aOR) of violent behaviors per unit of increase in depressive symptoms was 1.7 (95% CI = 1.2–2.5) in the Dutch RADAR community sample and 1.8 (95% CI = 1.4–2.3) in the British ALSPAC birth cohort. In the FBC 1987 cohort, the aOR of violent convictions was 2.1 (95% CI = 1.7–2.7) among individuals with a depression diagnosis compared with general population controls without depression. All risk estimates were adjusted for family socioeconomic status and previous violence. Conclusion Consistent findings across three longitudinal studies suggest that clinical guidelines should consider recommending risk assessment for violence in young people with depression. The benefits of targeting risk management in subgroups by gender need further investigation.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10(-7)) and thalamus (d=-0.148; P=4.27 × 10(-3)) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10(-5)) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.Molecular Psychiatry advance online publication, 9 February 2016; doi:10.1038/mp.2015.227. ispartof: Molecular Psychiatry vol:21 issue:12 pages:1710-1716 ispartof: location:England status: published

Background Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information. Methods A 39 question, paper-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating equations to account for correlated data. Results 976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general search engine. The primary reasons for searching were drug side effects (51 %), to learn anonymously (43 %), and for help coping (39 %). About 1/3 rated their search skills as expert, and 2/3 as basic or intermediate. 59 % preferred a website on mental illness and 33 % preferred Wikipedia. Only 20 % read or participated in online support groups. Most patients (62 %) searched a couple times a year. Online information seeking helped about 2/3 to cope (41 % of the entire sample). About 2/3 did not discuss Internet findings with their doctor. Conclusion Online information seeking helps many patients to cope although alternative information sources remain important. Most patients do not discuss Internet findings with their doctor, and concern remains about the quality of online information especially related to prescription drugs. Patients may not rate search skills accurately, and may not understand limitations of online privacy. More patient education about online information searching is needed and physicians should recommend a few high quality websites. Electronic supplementary material The online version of this article (doi:10.1186/s40345-016-0058-0) contains supplementary material, which is available to authorized users.

Lithium is a widely used and effective treatment for mood disorders. In the short term, patients may experience transitory gastrointestinal (GI) side effects or mild tremor, whilst a proportion of patients develop a reversible nephrogenic diabetes insipidus. Endocrine disorders—goitre, hypothyroidism, hyperthyroidism, hyperparathyroidism and weight gain—may occur in the long term. Exacerbation or development of skin and hair conditions due to lithium therapy has been reported in the literature, but good quality evidence is still needed to verify this association. Regular monitoring whilst taking lithium is essential to identify patients at risk of developing adverse effects and to provide safe and effective treatment.

The discovery of lithium has important lessons for psychiatry at several levels: in relation to strategies for drug discovery, in understanding the bipolar phenotype, in how insight into lithium’s mechanism of action and unique pharmacology relates to its positive actions on the one hand and its adverse effects on the other. Lithium’s pharmacology remains of interest, and a lithium mimetic is overdue. All these elements continue to place lithium at the heart of future research in bipolar disorder, just as it has occupied this place in its past. Moreover, findings on neuroprotection may herald new future indications and applications.

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.

BackgroundAberrant emotional biases have been reported in bipolar disorder (BD), but results are inconsistent. Despite the clinical relevance of chronic mood variability in BD, there is no previous research investigating how the extent of symptom fluctuations in bipolar disorder might relate to emotional biases. This exploratory study investigated, in a large cohort of bipolar patients, whether instability in weekly mood episode symptoms and other clinical and demographic factors were related to emotional bias as measured in a simple laboratory task.MethodParticipants (N = 271, BDI = 206, BDII = 121) completed an ‘emotional categorization and memory’ task. Weekly self-reported symptoms of depression and mania were collected prospectively. In linear regression analyses, associations between cognitive bias and mood variability were explored together with the influence of demographic and clinical factors, including current medication.ResultsGreater accuracy in the classification of negative words relative to positive words was associated with greater instability in depressive symptoms. Furthermore, greater negative bias in free recall was associated with higher instability in manic symptoms. Participants diagnosed with BDII, compared with BDI, showed overall better word recognition and recall. Current antipsychotic use was associated with reduced instability in manic symptoms but this did not impact on emotional processing performance.ConclusionsEmotional processing biases in bipolar disorder are related to instability in mood. These findings prompt further investigation into the underpinnings as well as clinical significance of mood instability.

Media reports suggest high rates of gambling amongst professional footballers but little is known about how footballers develop and then seek help for gambling problems. Here, we report the findings of in-depth, qualitative interviews with 11 British professional footballers who had, or who were, being treated for gambling problems at a residential clinic. These individuals experienced gambling as a highly salient feature of life as a professional football player in UK professional leagues. Often gambling began as part of social networks of young players, but then progressed to gambling problematically in isolation. Factors that facilitated this transition included structural aspects of professional football as an occupation (e.g. high salaries, spare time, gambling as a shared leisure pursuit) as well as the competitive and emotional challenges of the game (e.g. loss of form, injury or contract release and their effects upon mood). Seeking help was delayed by a reluctance to disclose problems to peers and club managers, but facilitated by recommendations from other players with similar experiences.

Background: Psychoeducation is an effective adjunct to medications in bipolar disorder (BD). Brief psychoeducational approaches have been shown to improve early identification of relapse. However, the optimal method of delivery of psychoeducation remains uncertain. Here, our objective was to compare a short therapist-facilitated vs. self-directed psychoeducational intervention for BD. Methods: BD outpatients who were receiving medication-based treatment were randomly assigned to 5 psychoeducation sessions administered by a therapist (Facilitated Integrated Mood Management; FIMM; n=60), or self-administered psychoeducation (Manualized Integrated Mood Management; MIMM; n=61). Follow-up was based on patients' weekly responses to an electronic mood monitoring programme over 12 months. Results: Over follow-up, there were no group differences in weekly self-rated depression symptoms or relapse/readmission rates. However, knowledge of BD (assessed with the Oxford Bipolar Knowledge questionnaire (OBQ)) was greater in the FIMM than the MIMM group at 3 months. Greater illness knowledge at 3 months was related to a higher proportion of weeks well over 12 months. Limitations: Features of the trial may have reduced the sensitivity to our psychoeducation approach, including that BD participants had been previously engaged in self-monitoring. Conclusions: Improved OBQ score, while accelerated by a short course of therapist-administered psychoeducation (FIMM), was seen after both treatments. It was associated with better outcome assessed as weeks well. When developing and testing a new psychosocial intervention, studies should consider proximal outcomes (e.g., acquired knowledge) and their short-term impact on illness course in bipolar disorder.

Gambling problems have been linked to suicidal ideation and enhanced risk of suicide attempts. However, we know very little about the factors associated with either thoughts or acts of self-harm amongst people who gamble. A web-based study of 4125 online gamblers (79% males; mean age 35.5 years), analysed using hierarchical multiple regression, revealed that self-reported non-gambling-related self-harm was negatively related to age and marital status, and positively related to problematic alcohol use. Self-reported acts of self-harm both related and unrelated to gambling were associated with drug misuse. Thoughts and acts of gambling-related self-harm were associated with problem gambling, gambling involvement and parental problem gambling. All types of self-harm were associated with mood disorder symptoms, unemployment and certain gambling motivations. When tailoring assessment and interventions for individuals at risk for gambling-related deliberate self-harm, it is important to recognize that contributory factors may include some that differ from those for deliberate self-harm in general, and that there is potential value in evaluating gambling involvement and motivations, and history of parental gambling.

Increased activity within known reward-processing neurocircuitry (eg, ventral striatum, VS) has been reported among medicated individuals with bipolar disorder (BD) I and II. However, such findings are confounded by the potential ameliorative effects of mood-stabilizing and antipsychotic medications on neural activations. This study tests the hypothesis that a pathophysiological locus of alterations in reward processing is present within the striatum in antipsychotic and lithium-naive individuals with BD. Twenty antipsychotic and lithium-naive individuals with BD II or BD not-otherwise specified (NOS) and 20 matched healthy comparison individuals participated in functional magnetic resonance imaging during the performance of a monetary incentive delay task. Between-group comparisons were conducted using small-volume correction focusing on orthogonal a priori regions of interest centered in the VS and dorsal striatum (DS), respectively. During reward anticipation, unmedicated individuals with BD II/NOS had decreased activity within the DS (but not VS). During loss anticipation, on the other hand, decreased activation within both the VS and DS was observed. Across all participants, DS activity (during reward anticipation) was positively associated with putamen volume. This is the first report of decreased dorsal and ventral striatal activity among unmedicated individuals with BD II/NOS. These data contradict a simple 'reward hypersensitivity' model of BD, and add to a growing body of literature suggesting that blunted reward processing may be a vulnerability factor for both mood- and addiction-related disorders.

We describe four patients with a clinical diagnosis of senile dementia of Alzheimer's type (AD) in which increased eating was a prominent feature. In three of these cases the increase in eating was associated with a gain in weight and in two cases with a change in food preference. None of the patients had other features of the Kluver-Bucy syndrome, nor was these patients' change in behavior attributable to the taking of medication. We argue that these changes in eating are probably due to underlying brain pathology and not mediated through memory impairment. Indeed, from the neuropathological changes found in AD, it might be predicted that changes in eating would occur in this disorder.

BACKGROUND: Aripiprazole is an atypical antipsychotic with a pharmacological and clinical profile distinct from other atypical antipsychotics. SCOPE: A European multidisciplinary advisory panel of university-based experts in bipolar disorders convened in April 2010 to review new clinical guidelines for the management of mania and the role of aripiprazole in its treatment. This report describes the consensus reached on how best to use aripiprazole in the treatment of mania. FINDINGS: Current guidelines recommending aripiprazole for first-line treatment of mania have not generally translated to clinical practice. The panel agreed that clinicians may not feel sufficiently knowledgeable on how to use aripiprazole effectively in mania, and that the perception that aripiprazole is less sedating than other antipschotics may hamper its use. There was consensus about the importance of ensuring that clinicians understood the distinction between antimanic efficacy and sedation. Most acutely manic patients may require night-time sedation, but continuous daytime sedation is not necessarily indicated and may interfere with long-term compliance. If sedation is necessary, guidelines recommend the use of adjunctive benzodiazepines only for a short-time. CONCLUSIONS: Clinical practice guidelines widely recommend aripiprazole as a first-line treatment for mania. Although clinical trials may not represent all patient subpopulations, they show that aripiprazole is well tolerated and has a long-term stabilizing potential. The successful use of aripiprazole rests on using the appropriate initial dose, titrating and adjusting the dose as needed and using appropriate concomitant medication to minimize any short-term adverse events. Low incidence of sedation makes aripiprazole a reasonable long-term treatment choice. If short-term sedation is required an adjunctive sedative agent can be added and removed when no longer needed. Clinical considerations should influence treatment choice, and a better distinction between sedation and antimanic effects should be an educational target aimed to overcome potential barriers for using non-sedative antimanic agents such as aripiprazole.

OBJECTIVES: Via an international panel of experts, this paper attempts to document, review, interpret, and propose operational definitions used to describe the course of bipolar disorders for worldwide use, and to disseminate consensus opinion, supported by the existing literature, in order to better predict course and treatment outcomes. METHODS: Under the auspices of the International Society for Bipolar Disorders, a task force was convened to examine, report, discuss, and integrate findings from the scientific literature related to observational and clinical trial studies in order to reach consensus and propose terminology describing course and outcome in bipolar disorders. RESULTS: Consensus opinion was reached regarding the definition of nine terms (response, remission, recovery, relapse, recurrence, subsyndromal states, predominant polarity, switch, and functional outcome) commonly used to describe course and outcomes in bipolar disorders. Further studies are needed to validate the proposed definitions. CONCLUSION: Determination and dissemination of a consensus nomenclature serve as the first step toward producing a validated and standardized system to define course and outcome in bipolar disorders in order to identify predictors of outcome and effects of treatment. The task force acknowledges that there is limited validity to the proposed terms, as for the most part they represent a consensus opinion. These definitions need to be validated in existing databases and in future studies, and the primary goals of the task force are to stimulate research on the validity of proposed concepts and further standardize the technical nomenclature.

BACKGROUND: Single photon emission tomography (SPET) with the dopamine D2/3 ligand 123I-IBZM gives a semi-quantitative estimate of dopamine binding. In depressed patients, we predicted evidence of reduced function, i.e. increased binding, particularly in more retarded patients. METHODS: Fifteen depressed patients with major depressive illness and 15 healthy, age- and sex- matched volunteerS were examined with a clinical and neuropsychological test battery and high resolution IBZM-SPET. Estimates for specific binding were computed by averaging striatum to whole slice or frontal uptake ratios over 8-10 scans acquired from 70 min after tracer injection. RESULTS: Using whole slice as reference, left striatal uptake ratios did not significantly differ for patients from controls. Right ratios were significantly higher in patients than controls (P = 0.03). There were significant correlations between IBZM binding in left and right striatum and measures of reaction time and verbal fluency. CONCLUSIONS: Increased IBZM binding in striatum probably reflects reduced dopamine function, whether due to reduced release of dopamine, or secondary up-regulation of receptors. The observed abnormalities may be trait or state related, an issue that needs to be addressed with longitudinal study designs. The possible role of medication as a confounding variable requires further exploration.

Several theoretical studies have suggested that large samples of randomly ascertained siblings can be used to ascertain phenotypically extreme individuals and thereby increase power to detect genetic linkage in complex traits. Here, we report a genetic linkage scan using extremely discordant and concordant sibling pairs, selected from 34,580 sibling pairs in the southwest of England who completed a personality questionnaire. We performed a genomewide scan for quantitative-trait loci (QTLs) that influence variation in the personality trait of neuroticism, or emotional stability, and we established genomewide empirical significance thresholds by simulation. The maximum pointwise P values, expressed as the negative logarithm (base 10), were found on 1q (3.95), 4q (3.84), 7p (3.90), 12q (4.74), and 13q (3.81). These five loci met or exceeded the 5% genomewide significance threshold of 3.8 (negative logarithm of the P value). QTLs on chromosomes 1, 12, and 13 are likely to be female specific. One locus, on chromosome 1, is syntenic with that reported from QTL mapping of rodent emotionality, an animal model of neuroticism, suggesting that some animal and human QTLs influencing emotional stability may be homologous.

This study assessed daily rest-activity patterns in euthymic, medication-naive bipolar phenotype individuals. The Mood Disorder Questionnaire was used to identify 19 bipolar phenotype individuals and 21 controls. Participants wore an Actiwatch-L for 2 weeks to assess their sleep behaviour and circadian rest-activity rhythmicity. Bipolar phenotype individuals had increased movement during sleep, as assessed by the fragmentation index, greater activity levels during their least active 5 h (2 am–7 am), and lower circadian relative amplitude compared to controls. Higher activity levels during sleep affecting circadian amplitude in young adults with the bipolar phenotype may be associated with vulnerability for developing mood disorder.

OBJECTIVE: Acute administration of an antidepressant increases positive affective processing in healthy volunteers, an effect that may be relevant to the therapeutic actions of these medications. The authors investigated whether this effect is apparent in depressed patients early in treatment, prior to changes in mood and symptoms. METHOD: In a double-blind, placebo-controlled, between-groups randomized design, the authors examined the effect of a single 4-mg dose of the norepinephrine reuptake inhibitor reboxetine on emotional processing. Thirty-three depressed patients were recruited through primary care clinics and the community and matched to 31 healthy comparison subjects. Three hours after dosing, participants were given a battery of emotional processing tasks comprising facial expression recognition, emotional categorization, and memory. Ratings of mood, anxiety, and side effects were also obtained before and after treatment. RESULTS: Depressed patients who received placebo showed reduced recognition of positive facial expressions, decreased speed in responding to positive self-relevant personality adjectives, and reduced memory for this positive information compared to healthy volunteers receiving placebo. However, this effect was reversed in patients who received a single dose of reboxetine, despite the absence of changes in subjective ratings of mood or anxiety. CONCLUSIONS: Antidepressant drug administration modulates emotional processing in depressed patients very early in treatment, before changes occur in mood and symptoms. This effect may ameliorate the negative biases in information processing that characterize mood and anxiety disorders. It also suggests a mechanism of action compatible with cognitive theories of depression.

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 neural 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.

INTRODUCTION: Erythropoietin (Epo) has neurotrophic effects and may be a novel therapeutic agent in the treatment of depression. We have found antidepressant-like effects of Epo on emotional processing and mood in healthy volunteers. OBJECTIVE: The current study aimed to explore the effects of Epo on the neural processing of emotional information in depressed patients. MATERIALS AND METHODS: Seventeen patients with acute major depressive disorder were randomised to receive Epo (40,000 IU) or saline iv in a double-blind, parallel-group design. On day 3, we assessed neural responses to positive, negative and neutral pictures during fMRI followed by picture recall after the scan. Mood and blood parameters were assessed at baseline and on day 3. RESULTS: Epo reduced neural response to negative vs. positive pictures 3 days post-administration in a network of areas including the hippocampus, ventromedial prefrontal and parietal cortex. After the scan, Epo-treated patients showed improved memory compared with those that were given placebo. The effects occurred in the absence of changes in mood or haematological parameters, suggesting that they originated from direct neurobiological actions of Epo. CONCLUSIONS: These findings are similar to the effects of conventional antidepressants and opposite to the negative biases in depression. The central effects of Epo therefore deserve further investigation as a potential antidepressant mechanism.

Bipolar disorder is a major cause of disability, and the prevention of relapse is a key management goal. Pharmacological interventions, effectively delivered through enhanced clinical care, are central to long-term management. This article summarises the available evidence for a range of pharmacological options, and provides guidance on common issues in clinical management in line with current practice guidelines. The use of medications for long-term prophylaxis should be considered in all patients meeting criteria for bipolar I disorder. Increasing high-quality evidence from randomised trials informs management decisions relating to both novel agents, such as lamotrigine and olanzapine, and longer-established therapies, such as lithium and valproate, in monotherapy. Medications taken long-term in bipolar disorder differ in the extent to which they protect against manic and depressive relapse. Consequently, the emerging challenge is to understand how combination treatments can enhance efficacy and effectiveness based on data from controlled trials rather than random polypharmacy. Clinical care can be enhanced with effective education about the illness, and the use of strategies to improve treatment adherence and the recognition and management of stressors or prodromal symptoms. Where available, a range of specific psychological interventions can be effective as an adjunct to medication. When discontinuation of prophylaxis is necessary, gradual tapering of dose over weeks or months is recommended.

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: The amygdala is believed to play a key role in processing emotionally salient, threat-relevant, events that require further online processing by cortical regions. Emotional disorders such as depression and anxiety have been associated with hyperactivity of the amygdala, but it is unknown whether antidepressant treatment directly affects amygdala responses to emotionally significant information. Methods: The current study assessed the effects of 7 days administration of the selective serotonin reuptake inhibitor (SSRI), citalopram, on amygdala responses to masked presentations of fearful and happy facial expressions in never-depressed volunteers using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging. A double-blind, between-groups design was used with volunteers randomized to 20 mg/day citalopram versus placebo. Results: Volunteers receiving citalopram showed decreased amygdala responses to masked presentations of threat compared with those receiving placebo. Citalopram also reduced responses within the hippocampus and medial prefrontal cortex (mPFC) specifically during the fear-relevant stimuli. These neural differences were accompanied by decreased recognition of fearful facial expressions assessed after the scan. By contrast, there was no effect of citalopram on the neural or behavioral response to the happy facial expressions. Conclusions: These results suggest a direct effect of serotonin potentiation on amygdala response to threat-relevant stimuli in humans. Such effects may be important in the therapeutic actions of antidepressants in depression and anxiety.

Bipolar Disorder is a neglected disease. In the last twenty years fewer than 2,000 articles have been published with mania or bipolar disorder in the title, compared to 11,000 for schizophrenia and 19,000 for depression (data from EMBASE). This relative neglect of bipolar disorder is true both for neurobiological investigations and for investigations of treatment. Interest is reviving, I believe, in no small part because of the consistent support by the Stanley Foundation. Genuine advances in understanding neurobiology and treatment may be now be possible. The presentations made at this meeting are testimony to that.

Objectives: The initial design of the BALANCE (Bipolar Affective disorder: Lithium / ANtiConvulsant Comparative Evaluation) Trial of maintenance treatment for bipolar disorder was based on the experience of previous trials in bipolar disorder and psychiatry and on the methods developed for large randomized trials in other areas of medicine. This report describes the adaptations to the initial design and trial procedures following the initial phases of the study. The rationale for the trial and full protocol have been published elsewhere. Methods: A pilot study and start-up phase were used to check the tolerability of the interventions, refine the trial design and develop trial procedures that are acceptable to both clinicians and patients. Results: Changes to the procedures included: the dropping of masking of allocated treatment from clinicians and participants; introduction of the use of postal delivery to supply medication; and dispensing with the proposed schedule of regular follow up appointments. In addition, support was made available to participating psychiatrists who often had limited experience of participating in randomized trials. Conclusions: Pilot studies and start-up phases are essential to refine clinical trial design and allow development of procedures that are both methodologically rigorous and flexible and robust enough to promote recruitment and follow up. BALANCE is now actively recruiting in the UK and USA.

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 emotional-behavioral 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.

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.

Background Bipolar disorder (BD) is associated with high-risk behaviors, such as gambling and impulsivity. However, little is known about the psychological factors that influence these behaviors or their significance for the development of the disorder. In this study, we investigated the effects of highlighting rewards versus highlighting punishments in the risky decision-making of euthymic individuals with bipolar disorder. Methods Twenty euthymic, medication-free men and women with previously undiagnosed bipolar II or bipolar disorder not otherwise specified and 20 age- and IQ-matched healthy men and women completed a computerized risky decision-making task in which mathematically equivalent dilemmas were presented in terms of opportunities to gain rewards ("positively-framed") or to avoid suffering losses ("negatively-framed"). The dependent measures were the proportion of risk-seeking choices (and deliberation times) when making decisions in positively versus negatively framed dilemmas. Results As expected, healthy control participants made more risky-seeking choices in response to the negatively framed dilemmas compared with the positively framed dilemmas. However, this effect was significantly attenuated in BD participants who also took significantly longer to make risk-averse responses to the positively framed dilemmas. The BD participants overestimated the number of bad outcomes arising out of positively framed dilemmas. Conclusions These data demonstrate that risky choice in BD is associated with reduced sensitivity to emotional contexts that highlight rewards or punishments, possibly reflecting altered valuations of prospective gains and losses associated with behavioral options.

Day-time plasma beta-endorphin/beta-lipotrophic hormone (beta-ENDO/beta-LPH), ACTH and cortisol have been determined in 26 patients with major depression and 25 controls. beta-ENDO/beta-LPH and cortisol were significantly elevated in patients, while ACTH was not. Cortisol levels were significantly negatively correlated with age in controls as were beta-ENDO/beta-LPH and ACTH. In patients, by contrast, cortisol levels were positively, albeit not significantly, related to age. Peptide levels were not related to age in the patient group. Instead, beta-ENDO/beta-LPH was negatively correlated with clinical ratings of symptom severity in patients and positively associated with an acute psychosocial precipitant. The findings cast further light on beta-ENDO/beta-LPH as a measure of hypothalamic-pituitary over activity in depressive illness. A negative association with symptom severity suggests that beta-ENDO/beta-LPH responses are, like those of ACTH, down-regulated in the course of depressive illness.

We analyse time series from 100 patients with bipolar disorder for correlates of depression symptoms. As the sampling interval is non-uniform, we quantify the extent of missing and irregular data using new measures of compliance and continuity . We find that uniformity of response is negatively correlated with the standard deviation of sleep ratings ( ρ = –0.26, p = 0.01). To investigate the correlation structure of the time series themselves, we apply the Edelson–Krolik method for correlation estimation. We examine the correlation between depression symptoms for a subset of patients and find that self-reported measures of sleep and appetite/weight show a lower average correlation than other symptoms. Using surrogate time series as a reference dataset, we find no evidence that depression is correlated between patients, though we note a possible loss of information from sparse sampling.

BackgroundDespite frequent use, little is known about the metabolic and endocrine side-effects of antipsychotics in individuals with intellectual disability.AimsTo compare indices of obesity, glucose, lipids and prolactin between antipsychotic-treated and antipsychotic-naive individuals with intellectual disability and also between participants with intellectual disability and controls from the general population.MethodObservational study comparing 138 antipsychotic-treated and 64 antipsychotic-naive participants with intellectual disability in one National Health Service trust with general population controls.ResultsAntipsychotic treatment comprised: risperidone 48%, olanzapine 18%, thioxanthenes 10%, other 24%; monotherapy 95% of participants; mean treatment duration 8 years; median daily chlorpromazine equivalent dose 108mg (range 16–667). Metabolic indices were the same or more favourable in the intellectual disability group than the general population control group but overweight/obesity and type 2 diabetes were more prevalent in the women in the intellectual disability group than the control group. Metabolic indices were similar, statistically or clinically, between the antipsychotic-treated and the antipsychotic-naive groups but there was a non-significant trend towards a higher rate of type 2 diabetes in the antipsychotic group. A total of 100% and 70% of participants on amisulpride/sulpiride and risperidone respectively had hyperprolactinaemia, with secondary hypogonadism in 77% and 4% of affected women and men.ConclusionsAntipsychotics, on average, did not increase metabolic risk, although the existence of a susceptible subgroup at risk of diabetes cannot be excluded. Some antipsychotics induced hyperprolactinaemic hypogonadism, requiring active management. However, our findings suggest that antipsychotics at the low doses routinely prescribed for people with intellectual disability are generally safe in relation to metabolic adverse effects, even if efficacy remains poorly defined.

BackgroundThe aetiology of treatment-resistant major depression is little understood; its apparent intractability may reflect brain abnormality.MethodMagnetic resonance images of the brains of 20 subjects with major depression lasting for two years or more were compared with 20 healthy control subjects and 20 other subjects who had completely recovered from depression. Subjects were individually matched for age, gender, years of education and premorbid IQ. Grey matter was segmented from the images, and compared between groups on a voxel-by-voxel basis.ResultsSubjects with chronic depression showed reduced grey matter density in the left temporal cortex including the hippocampus. There was also a trend for reduction in the right hippocampus. Left hippocampal grey matter density was correlated with measures of verbal memory, supporting the functional significance of the observed magnetic resonance imaging changes.ConclusionsOur results potentially challenge the accepted view of depression as a functional and fully reversible illness, implying instead that more permanent brain changes may be associated with chronicity. Confirmatory longitudinal and prospective studies are required to determine whether these differences pre-date the onset of depression or are the result of the chronic illness process or its treatment.

BackgroundDiagnosing mental illness is a central role for psychiatrists. Correct diagnosis informs both treatment and prognosis, and facilitates accurate communication. We sought to explore how psychiatrists distinguished two common psychiatric diagnoses: bipolar disorder (BD) and borderline personality disorder (BPD).MethodsWe conducted a qualitative study of psychiatrists to explore their practical experience. We then sought to validate these results by conducting a questionnaire study testing the theoretical knowledge and practical experience of a large number of UK psychiatrists. Finally we studied the assessment process in NHS psychiatric teams by analysing GP letters, assessments by psychiatrists, and assessment letters.ResultsThere was broad agreement in both the qualitative and questionnaire studies that the two diagnoses can be difficult to distinguish. The majority of psychiatrists demonstrated in survey responses a comprehensive understanding DSM-IV-TR criteria although many felt that these criteria did not necessarily assist diagnostic differentiation. This scepticism about diagnostic criteria appeared to strongly influence clinical practice in the sample of clinicians we observed. In only a minority of assessments were symptoms of mania or BPD sufficiently assessed to establish the presence or absence of each diagnosis.ConclusionClinical diagnostic practice was not adequate to differentiate reliably BD and BPD. The absence of reliable diagnostic practice has widespread implications for patient care, service provision and the reliability of clinical case registries.

Remitted bipolar patients were compared to remitted unipolar patients and healthy controls on a self concept task assessing degree of self- compartmentalization (clustering of self-aspects based on valence) and self-complexity (the degree of relatedness versus differentiation across self-aspects). Similar to the findings of Taylor et al. (Cognitive Therapy and Research, 31(1), 83-96, 2007) the bipolar and unipolar groups showed higher levels of self compartmentalization than healthy controls. No differences were found on the self complexity measure. © 2010 Springer Science+Business Media, LLC.

Rationale: Glutathione (GSH) is a key scavenger for cellular free radicals, and patients with bipolar disorder may have lowered GSH levels in plasma and in post-mortem brain tissue. Objectives: The objective of the current study was to use magnetic resonance spectroscopy (MRS) to measure cortical GSH levels in young people with bipolar disorder to determine if lowered GSH might be a useful biomarker of vulnerability to the illness. Methods: We studied 13 patients with DSM-IV bipolar disorder and 11 healthy age-matched controls using proton MRS in conjunction with the SPECIAL acquisition technique. Voxels were placed in prefrontal and occipital cortex. All patients were clinically euthymic at the time of study and unmedicated. GSH and other relevant neurometabolites were measured relative to creatinine. Results: There was no difference in GSH levels between bipolar participants and controls in either prefrontal or occipital cortex. Similarly, participants showed no difference from controls in other measured cortical metabolites including γ-aminobutyric acid, glutamate and N-acetylaspartate. Conclusions: This pilot study suggests that levels of cortical GSH are unlikely to be a useful trait biomarker of bipolar disorder in young people with a history of relatively mild mood instability at an early stage of illness. Lowered GSH levels may be relevant to bipolar pathophysiology in more severely ill patients, particular those with significant current mood disturbance. © 2013 Springer-Verlag Berlin Heidelberg.

Objective: We aimed to assess whether outcome followed a worse course after acute lithium withdrawal. Method: Data were acquired by review of the clinical records on 14 cases and 28 controls matched for age, gender and time on lithium for about 7 years following discontinuation. Results: Significant differences were found between cases and controls. Cases experienced more episodes of depression and total affective relapse. The log-rank test revealed a significantly lower survival probability in cases than controls (P

BackgroundMood instability is a common reason for psychiatric referral. Very little is known about how patients with unstable mood experience assessment and diagnosis.AimsTo investigate the experiences of assessment and diagnosis among patients with mood instability and to suggest improvements to this process.MethodQualitative study, gathering data through individual interviews with 28 people experiencing mood instability and receiving a psychiatric assessment in secondary care.ResultsParticipants described the importance of receiving an explanation for their symptoms; the value of a good interpersonal relationship with their clinician(s); being listened to and acknowledged; and being involved in and informed about clinical decisions. These needs were not, however, consistently met. Receiving a psychiatric diagnosis, including a diagnosis of bipolar disorder or borderline personality disorder, evoked both positive and negative responses among participants, relating to stigma, personal understanding and responsibility, prognosis and treatment.ConclusionsPatients with mood instability seek explanation for their symptoms and difficulties, empathetic care and consistent support as much as cure. Clinicians may incorrectly assume what patients' attitudes towards diagnosis are, a mismatch which may hamper the development of a strong therapeutic relationship. Clear, patient-centred communication, which acknowledges the patient's experience, may result in greater patient engagement and satisfaction.

Current gold standard in the treatment of depression includes pharmacotherapeutic and psychotherapeutic strategies together with social support. Due to the actually discussed controversies concerning the differential efficacy of antidepressants, a contribution to a comprehensive clarification seems to be necessary to avert further deterioration and uncertainty from patients, relatives, and their treating psychiatrists and general practitioners. Both efficacy and clinical effectiveness of antidepressants in the treatment of depressive disorders can be confirmed. Clinically meaningful antidepressant treatment effects were confirmed in different types of studies. Methodological issues of randomized controlled studies, meta-analyses, and effectiveness studies will be discussed. Furthermore, actual data about the differential efficacy and effectiveness of antidepressants with distinct pharmacodynamic properties and about outcome differences in studies using antidepressants and/or psychotherapy are discussed. This is followed by a clinically oriented depiction-the differential clinical effectiveness of different pharmacodynamic modes of action of antidepressants in different subtypes of depressive disorders. It can be summarized that the spectrum of different antidepressant treatments has broadened during the last decades. The efficacy and clinical effectiveness of antidepressants is statistically significant and clinically relevant and proven repeatedly. For further optimizing antidepressant treatment plans, clearly structured treatment algorithms and the implementation of psychotherapy seem to be useful. A modern individualized antidepressant treatment in most cases is a well-tolerated and efficacious tool to minimize the negative impact of the otherwise devastating and life-threatening outcome of depressive disorders.

Objective Irritable bowel syndrome (IBS) is frequently associated with mood disorder. However, it is typically difficult to distinguish between disturbed mood as a causal agent and disturbed mood as a consequence of the experience of IBS. This report considers the association between mood and symptom severity in a patient with diarrhea-predominant IBS and stable, rapid cycling bipolar disorder with a predominantly depressive course. Such a case provides an important opportunity to determine the direction of the relationship between mood and IBS symptom severity because the fluctuations of mood in bipolar disorder are assumed to be driven largely by biological, rather than psychosocial, processes. Methods The study was carried out prospectively, with ratings of mood and IBS symptom severity made daily by the patient for a period of almost 12 months. Results The patient experienced regular and substantial changes in mood as well as fluctuations in the level of IBS symptoms during the study period. Contrary to expectation, the correlation between mood and IBS symptom severity on the same day suggested that the patient experienced less severe IBS symptoms during periods of more severe depression. However, time series analysis revealed no significant association between these two processes when serial dependence within each series was controlled for. Conclusions The unusual co-occurrence of IBS with bipolar disorder provides direct evidence to indicate that depression does not necessarily lead to an increase in the reported severity of IBS, at least in the context of bipolar disorder, and may under certain circumstances actually be associated with a reduction in the severity of IBS symptoms. Factors that might moderate the relationship between depression and symptom severity are discussed.

Bipolar disorder is rapidly becoming the primary diagnosis in adult psychiatry. It represents a wide spectrum of disorder all sharing common features of elated and depressed mood. The early descriptions of symptom-free euthymia have long been dismissed and the chronic and enduring deficits associated with the disorder are beginning to be better understood. The course of the disorder remains uncertain especially in light of the recently observed increases in children receiving the diagnosis. There is growing interest in the elated states seen as a common adolescent phenotype.There is a simplified view of the illness as an episodic course interspersed with euthymia, short-term treatments being used in acute episodes and long-term treatments being indefinite and intended to prevent new episodes. However, subsyndromes, co-morbidities and a variety of chronic symptoms are common in bipolar disorder. In practice, they often drive treatment decisions. Chronic symptoms are usually related to anxiety, depression or cognition and are a disabling aspect of the long-term outcome. Unfortunately, there is little to guide the selection of treatment to reduce the impact of these symptoms since they have almost never been the subject of clinical trials.The use of medication in combinations is the usual practice in bipolar disorder. The argument to favour this in guidelines is highly pragmatic, but there is a growing evidence base to support it. Lithium remains a key benchmark treatment for comparing alternatives in long term efficacy. Its effects against suicide are particularly important.

Structural magnetic resonance imaging (MRI) studies using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) have been inconsistent in demonstrating impairments in gray matter (GM) and white matter (WM) structures in bipolar disorder (BD). This may be a consequence of significant confounding effects of medication, illness history and selection of controls in existing studies. Study of bipolar II or not-otherwise-specified (BD II/NOS) disorder provides a solution to these confounds and a bridge to unipolar cases across the affective spectrum. Thirty-eight euthymic, antipsychotic- and mood stabilizer-naïve young adults (mean age = 20.9 years) with BD II/NOS and 37 age-, cognitive ability- and gender-matched healthy controls (HCs) underwent MRI. Voxel-wise and regional gray matter volume comparisons were conducted using voxel-based morphometry (VBM). Tract-based spatial statistics (TBSS) were used to assess whole-brain WM, as indexed using fractional anisotropy (FA), mean diffusivity (MD), parallel and perpendicular diffusion values. No between-group differences were observed for whole-brain VBM comparisons. By contrast, in comparison to HCs, participants with BD II/NOS had significant widespread reductions in FA and increased MD and perpendicular diffusion values in virtually all the major cortical white matter tracts. These data suggest pathophysiological involvement of WM microstructures – but not GM macrostructures – in high functioning BD II/NOS patients at an early age and before significant clinical adversity has been recorded. We propose that white matter development is a valid candidate target for understanding genetic and environmental antecedents to bipolar disorder and mood disorder more generally., Highlights • Antipsychotic- and mood stabilizer-naïve bipolar II/NOS participants underwent MRI. • Data analysis included tract-based spatial statistics and voxel-based morphometry. • Bipolar II/NOS participants had widespread reductions in fractional anisotropy. • We report alterations in white – but not gray – matter structures in bipolar II/NOS.

The intake of food is critical for the survival of any organism. There are complex homeostatic mechanisms that ensure that when food is restricted the drive to eat increases. However, there is now growing evidence that behaviors such as dieting, during which eating behavior is purposefully modified for cosmetic or health reasons, may affect other behaviors, including mood and the ability to cope under stressful circumstances. Conversely, stress can alter food intake, and the degree to which this occurs seems to depend to some extent on preexisting eating patterns. © 2007 Copyright © 2007 Elsevier Inc. All rights reserved.

Reply by the current authors to the comments made by Carlin and Hardisty on the original article. Carlin and Hardisty question whether, in our postmortem study of 14,691 suicides in Sweden during 1992-2004, the methodology was sensitive enough to allow any conclusions. In addition, they question our disclosure of funding and consultancy arrangement. There was no funding for the study. Author disclosure information was submitted with the paper. It was the Journal's decision not to publish it because it was deemed not relevant to the study or paper.

An association between salivary cortisol levels and neuroticism has recently been reported, but it is unclear whether this association is unique to neuroticism or extends to other personality measures. The present study investigated early morning salivary cortisol levels in individuals selected for high and low extraversion. Thirty-three healthy volunteers were selected on the basis of their score on the extraversion sub-scale of the Eysenck Personality Questionnaire, and provided fasting saliva samples upon waking and at 15-min intervals for the next hour. Repeated measures ANOVA indicated a main effect of time (p < 0.001). The main effect of group (p = 0.196) and the group × time interaction (p = 0.588) were on-significant. Our data support the dissociation of the neurobiological correlates of behavioral traits. Unlike in the case of neuroticism, extraversion appears not to be associated with variability in early morning salivary cortisol level. © 2005 Elsevier Ltd. All rights reserved.