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Bipolar disorder is a relatively common mental illness, characterised by recurrent episodes of mania (or hypomania) and major depression, and associated with a significant burden of morbidity and premature mortality. Physicians across all specialities are likely to encounter individuals with the condition within their clinical practice. This short review provides an up-to-date overview of the clinical features, epidemiology, pathophysiology, evidence-based management, prognosis and future directions for treatment and research in bipolar disorder. Aspects of cross-specialty relevance are highlighted, including the physical health burden associated with the condition, and the side effects and safety considerations of medication regimes used in bipolar disorder. [ABSTRACT FROM AUTHOR]

Key Points: Questions: Are hypothesized associations between familial risk of depression and lower cognitive performance evident across the life span for both family history and genetic risk measures? Findings: In this cohort study including 57 308 participants from 4 cohorts, among the 3 younger cohorts (age range, 6 to 42 years), family history of depression was primarily associated with lower performance in the memory domain, whereas in the older cohort (age range, 44 to 83 years), the associations were shown for processing speed, attention, and executive function. Associations were similar in the polygenic risk score analyses and were evident even in participants who had never been depressed themselves but had a family history of depression. Meaning: In this study, whether assessed by family history or genetic data, depression in prior generations was associated with lower cognitive performance in offspring, which has important implications for understanding and addressing potentially modifiable risk factors. This cohort study evaluates associations between familial risk of depression and cognitive performance in 4 independent cohorts with varied depth of assessment, using both family history and genetic risk measures. Importance: Cognitive impairment in depression is poorly understood. Family history of depression is a potentially useful risk marker for cognitive impairment, facilitating early identification and targeted intervention in those at highest risk, even if they do not themselves have depression. Several research cohorts have emerged recently that enable findings to be compared according to varying depths of family history phenotyping, in some cases also with genetic data, across the life span. Objective: To investigate associations between familial risk of depression and cognitive performance in 4 independent cohorts with varied depth of assessment, using both family history and genetic risk measures. Design, Setting, and Participants: This study used data from the Three Generations at High and Low Risk of Depression Followed Longitudinally (TGS) family study (data collected from 1982 to 2015) and 3 large population cohorts, including the Adolescent Brain Cognitive Development (ABCD) study (data collected from 2016 to 2021), National Longitudinal Study of Adolescent to Adult Health (Add Health; data collected from 1994 to 2018), and UK Biobank (data collected from 2006 to 2022). Children and adults with or without familial risk of depression were included. Cross-sectional analyses were conducted from March to June 2022. Exposures: Family history (across 1 or 2 prior generations) and polygenic risk of depression. Main Outcomes and Measures: Neurocognitive tests at follow-up. Regression models were adjusted for confounders and corrected for multiple comparisons. Results: A total of 57 308 participants were studied, including 87 from TGS (42 [48%] female; mean [SD] age, 19.7 [6.6] years), 10 258 from ABCD (4899 [48%] female; mean [SD] age, 12.0 [0.7] years), 1064 from Add Health (584 [49%] female; mean [SD] age, 37.8 [1.9] years), and 45 899 from UK Biobank (23 605 [51%] female; mean [SD] age, 64.0 [7.7] years). In the younger cohorts (TGS, ABCD, and Add Health), family history of depression was primarily associated with lower performance in the memory domain, and there were indications that this may be partly associated with educational and socioeconomic factors. In the older UK Biobank cohort, there were associations with processing speed, attention, and executive function, with little evidence of education or socioeconomic influences. These associations were evident even in participants who had never been depressed themselves. Effect sizes between familial risk of depression and neurocognitive test performance were largest in TGS; the largest standardized mean differences in primary analyses were −0.55 (95% CI, −1.49 to 0.38) in TGS, −0.09 (95% CI, −0.15 to −0.03) in ABCD, −0.16 (95% CI, −0.31 to −0.01) in Add Health, and −0.10 (95% CI, −0.13 to −0.06) in UK Biobank. Results were generally similar in the polygenic risk score analyses. In UK Biobank, several tasks showed statistically significant associations in the polygenic risk score analysis that were not evident in the family history models. Conclusions and Relevance: In this study, whether assessed by family history or genetic data, depression in prior generations was associated with lower cognitive performance in offspring. There are opportunities to generate hypotheses about how this arises through genetic and environmental determinants, moderators of brain development and brain aging, and potentially modifiable social and lifestyle factors across the life span. [ABSTRACT FROM AUTHOR]

"Breaking through Depression: New Treatments and Discoveries for Healing" by Philip Gold is a highly recommended book that provides a refreshing change from the many popular science books in the mental health and neuroscience fields that lack evidence and rely on self-promotion. Gold, an expert clinician scientist with 50 years of experience, effectively communicates complex science in simple language. He explores the causes and treatment of depression, emphasizing the importance of combining biological treatments with long-term psychotherapeutic approaches. The book also covers topics such as antidepressants, genetics, circadian rhythms, hormones, psychedelics, and ketamine. While the book is US-centric and focuses on the achievements of researchers from certain institutions, it offers valuable insights and compassion for those interested in the science and treatment of depression. [Extracted from the article]

Non-alcoholic fatty liver disease (NAFLD) and depression are common disorders and have bidirectional contributing relationships to metabolic syndrome. We aimed to determine whether a fasting serum signature of recent, self-reported depressive symptoms could be identified in a heterogeneous NAFLD cohort using nuclear magnetic resonance (NMR)-based metabolomics integrated with clinical chemistry. Serum nuclear magnetic resonance (NMR) metabolite profiles and corresponding clinical chemistry were compared between patients with depressive symptoms in the last 12-months (n = 81) and patients without recent depressive symptoms (n = 137 controls) using multivariate statistics. Orthogonal partial least squares discriminant analysis (OPLS-DA) of the biochemical and metabolomic data identified NAFLD patients with recent depression with a cross-validated accuracy of 61.5%, independent of age, sex, medication, and other comorbidities. This led to the development of a diagnostic algorithm with AUC 0.83 for future testing in larger clinical cohorts. Serum triglycerides, VLDL cholesterol, and the inflammatory biomarker GlycA were key metabolites increased in patients with recent depressive symptoms, while serum glutamine level was reduced. Here, serum NMR metabolite analysis provides a link between disturbed lipid metabolism, inflammation, and active mental health issues in NAFLD, irrespective of disease severity. [ABSTRACT FROM AUTHOR]

Background: Generalized anxiety and depression are extremely prevalent and debilitating. There is evidence for age and sex variability in symptoms of depression, but despite comorbidity it is unclear whether this extends to anxiety symptomatology. Studies using questionnaire sum scores typically fail to address this phenotypic complexity. Method: We conducted exploratory and confirmatory factor analyses on Generalized Anxiety Disorder (GAD‐7) and Patient Health Questionnaire (PHQ‐9) items to identify latent factors of anxiety and depression in participants from the Genetic Links to Anxiety and Depression Study (N = 35,637; 16–93 years). We assessed age‐ and sex‐related variability in latent factors and individual symptoms using multiple logistic regression. Results: Four factors of mood, worry, motor, and somatic symptoms were identified (comparative fit index [CFI] = 0.99, Tucker–Lewis Index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.07, standardized root mean square residuals [SRMR] = 0.04). Symptoms of irritability (odds ratio [OR] = 0.81) were most strongly associated with younger age, and sleep change (OR = 1.14) with older age. Males were more likely to report mood and motor symptoms (p <.001) and females to report somatic symptoms (p <.001). Conclusion: Significant age and sex variability suggest that classic diagnostic criteria reflect the presentation most commonly seen in younger males. This study provides avenues for diagnostic adaptation and factor‐specific interventions. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic and mitigation measures are likely to have a marked effect on mental health. It is important to use longitudinal data to improve inferences.Aims: To quantify the prevalence of depression, anxiety and mental well-being before and during the COVID-19 pandemic. Also, to identify groups at risk of depression and/or anxiety during the pandemic.Method: Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) index generation (n = 2850, mean age 28 years) and parent generation (n = 3720, mean age 59 years), and Generation Scotland (n = 4233, mean age 59 years). Depression was measured with the Short Mood and Feelings Questionnaire in ALSPAC and the Patient Health Questionnaire-9 in Generation Scotland. Anxiety and mental well-being were measured with the Generalised Anxiety Disorder Assessment-7 and the Short Warwick Edinburgh Mental Wellbeing Scale.Results: Depression during the pandemic was similar to pre-pandemic levels in the ALSPAC index generation, but those experiencing anxiety had almost doubled, at 24% (95% CI 23-26%) compared with a pre-pandemic level of 13% (95% CI 12-14%). In both studies, anxiety and depression during the pandemic was greater in younger members, women, those with pre-existing mental/physical health conditions and individuals in socioeconomic adversity, even when controlling for pre-pandemic anxiety and depression.Conclusions: These results provide evidence for increased anxiety in young people that is coincident with the pandemic. Specific groups are at elevated risk of depression and anxiety during the COVID-19 pandemic. This is important for planning current mental health provisions and for long-term impact beyond this pandemic. [ABSTRACT FROM AUTHOR]

Background: Recent work suggests that antihypertensive medications may be useful as repurposed treatments for mood disorders. Using large-scale linked healthcare data we investigated whether certain classes of antihypertensive, such as angiotensin antagonists (AAs) and calcium channel blockers, were associated with reduced risk of new-onset major depressive disorder (MDD) or bipolar disorder (BD). Method: Two cohorts of patients treated with antihypertensives were identified from Scottish prescribing (2009–2016) and hospital admission (1981–2016) records. Eligibility for cohort membership was determined by a receipt of a minimum of four prescriptions for antihypertensives within a 12-month window. One treatment cohort (n = 538 730) included patients with no previous history of mood disorder, whereas the other (n = 262 278) included those who did. Both cohorts were matched by age, sex and area deprivation to untreated comparators. Associations between antihypertensive treatment and new-onset MDD or bipolar episodes were investigated using Cox regression. Results: For patients without a history of mood disorder, antihypertensives were associated with increased risk of new-onset MDD. For AA monotherapy, the hazard ratio (HR) for new-onset MDD was 1.17 (95% CI 1.04–1.31). Beta blockers' association was stronger (HR 2.68; 95% CI 2.45–2.92), possibly indicating pre-existing anxiety. Some classes of antihypertensive were associated with protection against BD, particularly AAs (HR 0.46; 95% CI 0.30–0.70). For patients with a past history of mood disorders, all classes of antihypertensives were associated with increased risk of future episodes of MDD. Conclusions: There was no evidence that antihypertensive medications prevented new episodes of MDD but AAs may represent a novel treatment avenue for BD. [ABSTRACT FROM AUTHOR]

Background: Severe mental illness (SMI), comprising schizophrenia, bipolar disorder and major depression, is associated with higher myocardial infarction (MI) mortality but lower coronary revascularisation rates. Previous studies have largely focused on schizophrenia, with limited information on bipolar disorder and major depression, long-term mortality or the effects of either sociodemographic factors or year of MI. We investigated the associations between SMI and MI prognosis and how these differed by age at MI, sex and year of MI.Methods: We conducted a national retrospective cohort study, including adults with a hospitalised MI in Scotland between 1991 and 2014. We ascertained previous history of schizophrenia, bipolar disorder and major depression from psychiatric and general hospital admission records. We used logistic regression to obtain odds ratios adjusted for sociodemographic factors for 30-day, 1-year and 5-year mortality, comparing people with each SMI to a comparison group without a prior hospital record for any mental health condition. We used Cox regression to analyse coronary revascularisation within 30 days, risk of further MI and further vascular events (MI or stroke). We investigated associations for interaction with age at MI, sex and year of MI.Results: Among 235,310 people with MI, 923 (0.4%) had schizophrenia, 642 (0.3%) had bipolar disorder and 6239 (2.7%) had major depression. SMI was associated with higher 30-day, 1-year and 5-year mortality and risk of further MI and stroke. Thirty-day mortality was higher for schizophrenia (OR 1.95, 95% CI 1.64-2.30), bipolar disorder (OR 1.53, 95% CI 1.26-1.86) and major depression (OR 1.31, 95% CI 1.23-1.40). Odds ratios for 1-year and 5-year mortality were larger for all three conditions. Revascularisation rates were lower in schizophrenia (HR 0.57, 95% CI 0.48-0.67), bipolar disorder (HR 0.69, 95% CI 0.56-0.85) and major depression (HR 0.78, 95% CI 0.73-0.83). Mortality and revascularisation disparities persisted from 1991 to 2014, with absolute mortality disparities more apparent for MIs that occurred around 70 years of age, the overall mean age of MI. Women with major depression had a greater reduction in revascularisation than men with major depression.Conclusions: There are sustained SMI disparities in MI intervention and prognosis. There is an urgent need to understand and tackle the reasons for these disparities. [ABSTRACT FROM AUTHOR]

Children and adolescents commonly suffer from sleep and circadian rhythm disturbances, which may contribute to poorer mental health and wellbeing during this critical developmental phase. Many studies however rely on self-reported sleep measures. This study assessed whether accelerometry data collection was feasible within the school setting as a method for investigating the extent of sleep and circadian disruption, and associations with subjective wellbeing, in Scotland. Fourteen days of wrist-worn accelerometry data were collected from 69 pupils, aged 10–14 years. Objective measures of sleep timing, sleep duration and circadian rest-activity patterns were derived. Questionnaires assessed subjective sleep timing, depressive symptoms, and experiences of wearing the accelerometer. Pupils slept on average less than 8 hours per night, failing to meet standard age-specific recommendations. Sleep timing was later and duration longer on weekends compared to weekdays (B = 0.87, 95% confidence interval (CI) 0.70, 1.04; B = 0.49, 95% CI 0.29, 0.69), indicating social jetlag. Lower daytime activity was correlated with higher depressive symptoms (r = -0.84, p = 0.008). Compared to primary school pupils, secondary pupils had shorter sleep window duration and lower circadian relative amplitude. Over half of participants reported some discomfort/inconvenience wearing the accelerometer. These data highlight that inadequate sleep is prevalent in this sample of schoolchildren. Future, larger scale investigations will examine in more detail the associations between sleep, circadian function and physical activity with mental health and wellbeing. [ABSTRACT FROM AUTHOR]

Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is strongly linked with persistent disability in people with mood disorders, but the factors that explain cognitive impairment in this population are unclear.Aims: To estimate the total effect of (a) bipolar disorder and (b) major depression on cognitive function, and the magnitude of the effect that is explained by potentially modifiable intermediate factors.Method: Cross-sectional study using baseline data from the UK Biobank cohort. Participants were categorised as having bipolar disorder (n = 2709), major depression (n = 50 975) or no mood disorder (n = 102 931 and n = 105 284). The outcomes were computerised tests of reasoning, reaction time and memory. The potential mediators were cardiometabolic disease and psychotropic medication. Analyses were informed by graphical methods and controlled for confounding using regression, propensity score-based methods and G-computation.Results: Group differences of small magnitude were found on a visuospatial memory test. Z-score differences for the bipolar disorder group were in the range -0.23 to -0.17 (95% CI -0.39 to -0.03) across different estimation methods, and for the major depression group they were approximately -0.07 (95% CI -0.10 to -0.03). One-quarter of the effect was mediated via psychotropic medication in the bipolar disorder group (-0.05; 95% CI -0.09 to -0.01). No evidence was found for mediation via cardiometabolic disease.Conclusions: In a large community-based sample in middle to early old age, bipolar disorder and depression were associated with lower visuospatial memory performance, in part potentially due to psychotropic medication use. Mood disorders and their treatments will have increasing importance for population cognitive health as the proportion of older adults continues to grow.Declaration Of Interest: I.J.D. is a UK Biobank participant. J.P.P. is a member of the UK Biobank Steering Committee. [ABSTRACT FROM AUTHOR]

Background: Most people with bipolar disorder spend a significant percentage of their lifetime experiencing either subsyndromal depressive symptoms or major depressive episodes, which contribute greatly to the high levels of disability and mortality associated with the disorder. Despite the importance of bipolar depression, there are only a small number of recognised treatment options available. Consecutive treatment failures can quickly exhaust these options leading to treatment-resistant bipolar depression (TRBD). Remarkably few studies have evaluated TRBD and those available lack a comprehensive definition of multi-therapy-resistant bipolar depression (MTRBD).AimsTo reach consensus regarding threshold definitions criteria for TRBD and MTRBD.Method: Based on the evidence of standard treatments available in the latest bipolar disorder treatment guidelines, TRBD and MTRBD criteria were agreed by a representative panel of bipolar disorder experts using a modified Delphi method.Results: TRBD criteria in bipolar depression was defined as failure to reach sustained symptomatic remission for 8 consecutive weeks after two different treatment trials, at adequate therapeutic doses, with at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. MTRBD included the same initial definition as TRBD, with the addition of failure of at least one trial with an antidepressant, a psychological treatment and a course of electroconvulsive therapy.Conclusions: The proposed TRBD and MTRBD criteria may provide an important signpost to help clinicians, researchers and stakeholders in judging how and when to consider new non-standard treatments. However, some challenging diagnostic and therapeutic issues were identified in the consensus process that need further evaluation and research.Declaration of interestIn the past 3 years, M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eli Lilly, Grunbiotics, Glaxo SmithKline, Janssen Cilag, LivaNova, Lundbeck, Merck, Mylan, Otsuka, Pfizer and Servier. A.C. has received fees for lecturing from pharmaceutical companies namely Lundbeck and Sunovion. A.J.C. has in the past 3 years received honoraria for speaking from Astra Zeneca and Lundbeck, honoraria for consulting from Allergan, Janssen, Lundbeck and LivaNova and research grant support from Lundbeck. G.M.G. holds shares in P1Vital and has served as consultant, advisor or CME speaker for Allergan, Angelini, Compass pathways, MSD, Lundbeck, Otsuka, Takeda, Medscape, Minervra, P1Vital, Pfizer, Servier, Shire and Sun Pharma. J.G. has received research funding from National Institute for Health Research, Medical Research Council, Stanley Medical Research Institute and Wellcome. H.G. received grants/research support, consulting fees or honoraria from Gedeon Richter, Genericon, Janssen Cilag, Lundbeck, Otsuka, Pfizer and Servier. R.H.M.-W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, Liva Nova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. R.M. has received research support from Big White Wall, Electromedical Products, Johnson and Johnson, Magstim and P1Vital. S.N. received honoraria from Lundbeck, Jensen and Otsuka. J.C.S. has received funds for research from Alkermes, Pfizer, Allergan, J&J, BMS and been a speaker or consultant for Astellas, Abbott, Sunovion, Sanofi. S.W has, within the past 3 years, attended advisory boards for Sunovion and LivaNova and has undertaken paid lectures for Lundbeck. D.J.S. has received honoraria from Lundbeck. T.S. has reported grants from Pathway Genomics, Stanley Medical Research Institute and Palo Alto Health Sciences; consulting fees from Sunovion Pharamaceuticals Inc.; honoraria from Medscape Education, Global Medical Education and CMEology; and royalties from Jones and Bartlett, UpToDate and Hogrefe Publishing. S.P. has served as a consultant or speaker for Janssen, and Sunovion. P.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. E.V. received grants/ research support, consulting fees or honoraria from Abbott, AB-Biotics, Allergan, Angelini, Dainippon Sumitomo, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka and Sunovion. L.N.Y. has received grants/research support, consulting fees or honoraria from Allergan, Alkermes, Dainippon Sumitomo, Janssen, Lundbeck, Otsuka, Sanofi, Servier, Sunovion, Teva and Valeant. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has also previously received funding for investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth. P.R.A.S. has received research funding support from Corcept Therapeutics Inc. Corcept Therapeutics Inc fully funded attendance at their internal conference in California USA and all related expenses. He has received grant funding from the Medical Research Council UK for a collaborative study with Janssen Research and Development LLC. Janssen Research and Development LLC are providing non-financial contributions to support this study. P.R.A.S. has received a presentation fee from Indivior and an advisory board fee from LivaNova. [ABSTRACT FROM AUTHOR]

BMS-911278 was identified as a potent triple reuptake inhibitor potentially useful for the treatment of depression. The original racemic synthesis suffered from tedious and low recovery resolution and HPLC separation, as well as low-yielding hazardous N -demethylation at the API step. To support further preclinical studies, a scalable enantioselective synthesis was developed. Herein, we report an efficient asymmetric synthesis of BMS-911278 featuring two key steps: an enantioselective Miyaura reaction and an intramolecular regioselective cyclization. [ABSTRACT FROM AUTHOR]

Background: Chronic pain is highly prevalent and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with major depressive disorder (MDD) is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS). We then sought to replicate any significant findings in the United Kingdom Biobank study.Methods and Findings: Using family-based mixed-model analyses, we examined the contribution of genetics and shared family environment to chronic pain by spouse, sibling, and household relationships. These analyses were conducted in GS:SFHS (n = 23,960), a family- and population-based study of individuals recruited from the Scottish population through their general practitioners. We then examined and partitioned the correlation between chronic pain and MDD and estimated the contribution of genetic factors and shared environment in GS:SFHS. Finally, we used data from two independent genome-wide association studies to test whether chronic pain has a polygenic architecture and examine whether genomic risk of psychiatric disorder predicted chronic pain and whether genomic risk of chronic pain predicted MDD. These analyses were conducted in GS:SFHS and repeated in UK Biobank, a study of 500,000 from the UK population, of whom 112,151 had genotyping and phenotypic data. Chronic pain is a moderately heritable trait (heritability = 38.4%, 95% CI 33.6% to 43.9%) that is significantly concordant in spouses (variance explained 18.7%, 95% CI 9.5% to 25.1%). Chronic pain is positively correlated with depression (ρ = 0.13, 95% CI 0.11 to 0.15, p = 2.72x10-68) and shows a tendency to cluster within families for genetic reasons (genetic correlation = 0.51, 95%CI 0.40 to 0.62, p = 8.24x10-19). Polygenic risk profiles for pain, generated using independent GWAS data, were associated with chronic pain in both GS:SFHS (maximum β = 6.18x10-2, 95% CI 2.84 x10-2 to 9.35 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 5.68 x 10-2, 95% CI 4.70x10-2 to 6.65x10-2, p < 3x10-4). Genomic risk of MDD is also significantly associated with chronic pain in both GS:SFHS (maximum β = 6.62x10-2, 95% CI 2.82 x10-2 to 9.76 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 2.56x10-2, 95% CI 1.62x10-2 to 3.63x10-2, p < 3x10-4). Limitations of the current study include the possibility that spouse effects may be due to assortative mating and the relatively small polygenic risk score effect sizes.Conclusions: Genetic factors, as well as chronic pain in a partner or spouse, contribute substantially to the risk of chronic pain for an individual. Chronic pain is genetically correlated with MDD, has a polygenic architecture, and is associated with polygenic risk of MDD. [ABSTRACT FROM AUTHOR]

Background: The relative contribution of demographic, lifestyle and medication factors to the association between affective disorders and cardiometabolic diseases is poorly understood.Aims: To assess the relationship between cardiometabolic disease and features of depresion and bipolar disorder within a large population sample.Method: Cross-sectional study of 145 991 UK Biobank participants: multivariate analyses of associations between features of depression or bipolar disorder and five cardiometabolic outcomes, adjusting for confounding factors.Results: There were significant associations between mood disorder features and 'any cardiovascular disease' (depression odds ratio (OR) = 1.15, 95% CI 1.12-1.19; bipolar OR = 1.28, 95% CI 1.14-1.43) and with hypertension (depression OR = 1.15, 95% CI 1.13-1.18; bipolar OR = 1.26, 95% CI 1.12-1.42). Individuals with features of mood disorder taking psychotropic medication were significantly more likely than controls not on psychotropics to report myocardial infarction (depression OR = 1.47, 95% CI 1.24-1.73; bipolar OR = 2.23, 95% CI 1.53-3.57) and stroke (depression OR = 2.46, 95% CI 2.10-2.80; bipolar OR = 2.31, 95% CI 1.39-3.85).Conclusions: Associations between features of depression or bipolar disorder and cardiovascular disease outcomes were statistically independent of demographic, lifestyle and medication confounders. Psychotropic medication may also be a risk factor for cardiometabolic disease in individuals without a clear history of mood disorder. [ABSTRACT FROM AUTHOR]

Background: Comorbid chronic pain and depression is a challenging dyad of conditions to manage in primary care and reporting has shown to vary by ethnic group. Whether the relationship between depression and chronic pain varies by ethnicity is unclear. This study aims to explore chronic pain and depression reporting across ethnic groups and examine whether this association differs, independently of potential confounding factors. Methods: Cross-sectional study of UK Biobank participants with complete data on chronic pain and probable lifetime history of depression, who reported their ethnic group as White, Asian/Asian British or Black/Black British. Chronic pain classification: present if participants had ≥ 1 site of body pain (up to seven sites or "pain all over the body" could be selected) that lasted ≥ 3 months; extent of chronic pain categories: 0, 1, 2-3, 4-7 sites or pain all over the body. Probable depression classification: an algorithm of low mood, anhedonia and help-seeking behaviour. Relationship between depression and presence/extent of chronic pain assessed using logistic/ multinomial regression models (odds ratio (OR); relative risk ratio (RRR), 95 % confidence intervals), adjusted for sociodemographic, lifestyle, and morbidity factors; and a final adjustment for current depressive symptoms. Results: The number of participants eligible for inclusion was 144,139: 35,703 (94 %) White, 4539 (3 %) Asian, and 3897 (3 %) Black. Chronic pain was less (40.5 %, 45.8 %, 45.0 %, respectively) and depression more (22.1 %, 12.9 %, 13.8 %, respectively) commonly reported in White participants than Asian and Black participants. Statistically significant associations between depression and presence/extent of chronic pain persisted following adjustment for potential confounding variables; this relationship was strongest for Black participants (presence of chronic pain: OR 1.86 (1.52, 2.27); RRR 1 site 1.49 (1.16, 1.91), 2-3 sites 1.98 (1.53, 2.56), 4-7 sites 3.23 (2.09, 4.99), pain all over the body 3.31 (2.05, 5.33). When current depressive symptoms were considered these relationships were attenuated. Conclusions: Chronic pain and depression reporting varies across ethnic groups. Differences in health seeking behaviour between ethnic groups may impact on the results reported. Clinicians, particularly in primary care, need to be aware of the cultural barriers within certain ethic groups to expressing concern over mood and to consider their approach accordingly. [ABSTRACT FROM AUTHOR]

Background Chronic pain has a strong association with major depressive disorder (MDD), but there is a relative paucity of studies on the association between chronic multisite pain and bipolar disorder (BD). Such studies are required to help elucidate the complex biological and psychological overlap between pain and mood disorders. The aim of this study is to investigate the relationship between chronic multisite pain and mood disorder across the unipolar-bipolar spectrum. Methods We conducted a cross-sectional study of 149,611 UK Biobank participants. Self-reported depressive and bipolar features were used to categorise participants into MDD and BD groups and a non-mood disordered comparison group. Multinomial logistic regression was used to establish whether there was an association between extent of chronic pain (independent variable) and mood disorder category (dependent variable), using no pain as the referent category, and adjusting for a wide range of potential sociodemographic, lifestyle and comorbidity confounders. Results Multisite pain was significantly more prevalent in participants with BD and MDD, for example, 4-7 pain sites: BD 5.8%, MDD 4.5%, and comparison group 1.8% (p < 0.001). A relationship was observed between extent of chronic pain and risk of BD and persisted after adjusting for confounders (relative to individuals with no chronic pain): 2-3 sites RRR of BD 1.84 (95% CI 1.61, 2.11); 4-7 sites RRR of BD 2.39 (95%CI 1.88, 3.03) and widespread pain RRR of BD 2.37 (95%CI 1.73, 3.23). A similar relationship was observed between chronic pain and MDD: 2-3 sites RRR of MDD 1.59 (95%CI 1.54, 1.65); 4-7 sites RRR of MDD 2.13 (95%CI 1.98, 2.30); widespread pain RRR of MDD 1.86 (95%CI 1.66, 2.08). Conclusions Individuals who report chronic pain and multiple sites of pain are more likely to have MDD and are at higher risk of BD. These findings highlight an important aspect of comorbidity in MDD and BD and may have implications for understanding the shared neurobiology of chronic pain and mood disorders. [ABSTRACT FROM AUTHOR]

Background Previous studies on the association between adiposity and mood disorder have produced contradictory results, and few have used measurements other than body mass index (BMI). We examined the association between probable major depression and several measurements of adiposity: BMI, waist circumference (WC), waist-hip-ratio (WHR), and body fat percentage (BF%). Methods We conducted a cross-sectional study using baseline data on the sub-group of UK Biobank participants who were assessed for mood disorder. Multivariate logistic regression models were used, adjusting for potential confounders including: demographic and life-style factors, comorbidity and psychotropic medication. Results Of the 140,564 eligible participants, evidence of probable major depression was reported by 30,145 (21.5%). The fully adjusted odds ratios (OR) for obese participants were 1.16 (95% confidence interval (CI) 1.12, 1.20) using BMI, 1.15 (95% CI 1.11, 1.19) using WC, 1.09 (95% CI 1.05, 1.13) using WHR and 1.18 (95% CI 1.12, 1.25) using BF% (all p < 0.001). There was a significant interaction between adiposity and gender (p = 0.001). Overweight women were at increased risk of depression with a dose response relationship across the overweight (25.0-29.9 kg/m²), obese I (30.0-34.9 kg/m²), II (35.0-39.9 kg/m²) and III (≥40.0 kg/m²) categories; fully adjusted ORs 1.14, 1.20, 1.29 and 1.48, respectively (all p < 0.001). In contrast, only obese III men had significantly increased risk of depression (OR 1.29, 95% CI 1.08, 1.54, p = 0.006). Conclusion Adiposity was associated with probable major depression, irrespective of the measurement used. The association was stronger in women than men. Physicians managing overweight and obese women should be alert to this increased risk. [ABSTRACT FROM AUTHOR]

Objectives: UK Biobank is a landmark cohort of over 500,000 participants which will be used to investigate genetic and non-genetic risk factors for a wide range of adverse health outcomes. This is the first study to systematically assess the prevalence and validity of proposed criteria for probable mood disorders within the cohort (major depression and bipolar disorder). Methods: This was a descriptive epidemiological study of 172,751 individuals assessed for a lifetime history of mood disorder in relation to a range of demographic, social, lifestyle, personality and health-related factors. The main outcomes were prevalence of a probable lifetime (single) episode of major depression, probable recurrent major depressive disorder (moderate), probable recurrent major depressive disorder (severe), probable bipolar disorder and no history of mood disorder (comparison group). Outcomes were compared on age, gender, ethnicity, socioeconomic status, educational attainment, functioning, self-reported health status, current depressive symptoms, neuroticism score, smoking status and alcohol use. Results: Prevalence rates for probable single lifetime episode of major depression (6.4%), probable recurrent major depression (moderate) (12.2%), probable recurrent major depression (severe) (7.2%) and probable bipolar disorder (1.3%) were comparable to those found in other population studies. The proposed diagnostic criteria have promising validity, with a gradient in evidence from no mood disorder through major depression and probable bipolar disorder in terms of gender distribution, socioeconomic status, self-reported health rating, current depressive symptoms and smoking. Significance: The validity of our proposed criteria for probable major depression and probable bipolar disorder within this cohort are supported by these cross-sectional analyses. Our findings are likely to prove useful as a framework for a wide range of future genetic and non-genetic studies. [ABSTRACT FROM AUTHOR]

Background: Offspring of mothers with depression are at heightened risk of psychiatric disorder. Many mothers with depression have comorbid psychopathology. How these co-occurring problems affect child outcomes has rarely been considered.Aims: To consider whether the overall burden of co-occurring psychopathology in mothers with recurrent depression predicts new-onset psychopathology in offspring.Method: Mothers with recurrent depression and their adolescent offspring (9-17 years at baseline) were assessed in 2007 and on two further occasions up to 2011. Mothers completed questionnaires assessing depression severity, anxiety, alcohol problems and antisocial behaviour. Psychiatric disorder in offspring was assessed using the Child and Adolescent Psychiatric Assessment.Results: The number of co-occurring problems in mothers (0, 1 or 2+) predicted new-onset offspring disorder (odds ratio (OR) = 1.80, 95% CI 1.17-2.77, P = 0.007). Rates varied from 15.7 to 34.8% depending on the number of co-occurring clinical problems. This remained significant after controlling for maternal depression severity (OR = 1.73, 95% CI 1.03-2.89, P = 0.040).Conclusions: The burden of co-occurring psychopathology among mothers with recurrent depression indexes increased risk of future onset of psychiatric disorder for offspring. This knowledge can be used in targeting preventive measures in children at high risk of psychiatric disorder. [ABSTRACT FROM AUTHOR]

The classification and diagnosis of mood disorders have been the subject of much debate over the last 150 years and remain extremely important for contemporary psychiatric practice. Although the DSM (Diagnostic and Statistical Manual) and ICD (International Classification of Diseases) classifications of major depression and bipolar disorder have been very helpful for research and practice, recent work suggests that it may be appropriate to consider a return to a broader view of the bipolar spectrum. Here we review the evolving concept of bipolar spectrum disorders with particular reference to dimensional aspects of symptoms and the interfaces between unipolar depression and bipolar disorder and between bipolar disorder and psychosis. [ABSTRACT FROM AUTHOR]

This study examines the role of abuse-specific maternal support in the association between parent depressive symptoms and child externalizing problems in a sample of children with a history of sexual abuse. In total, 106 mother-child dyads were studied. The association between maternal depressive symptoms and child delinquency behaviors was found to partially operate through abuse-specific maternal support, which was assessed via parent report. Implications of the findings for parenting programs are discussed, and future research directions are considered. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder is complex and can be difficult to diagnose. It is often misdiagnosed as recurrent major depressive disorder.Aims: We had three main aims. To estimate the proportion of primary care patients with a working diagnosis of unipolar depression who satisfy DSM-IV criteria for bipolar disorder. To test two screening instruments for bipolar disorder (the Hypomania Checklist (HCL-32) and Bipolar Spectrum Diagnostic Scale (BSDS)) within a primary care sample. To assess whether individuals with major depressive disorder with subthreshold manic symptoms differ from those individuals with major depressive disorder but with no or little history of manic symptoms in terms of clinical course, psychosocial functioning and quality of life.Method: Two-phase screening study in primary care.Results: Three estimates of the prevalence of undiagnosed bipolar disorder were obtained: 21.6%, 9.6% and 3.3%. The HCL-32 and BSDS questionnaires had quite low positive predictive values (50.0 and 30.1% respectively). Participants with major depressive disorder and with a history of subthreshold manic symptoms differed from those participants with no or little history of manic symptoms on several clinical features and on measures of both psychosocial functioning and quality of life.Conclusions: Between 3.3 and 21.6% of primary care patients with unipolar depression may have an undiagnosed bipolar disorder. The HCL-32 and BSDS screening questionnaires may be more useful for detecting broader definitions of bipolar disorder than DSM-IV-defined bipolar disorder. Subdiagnostic features of bipolar disorder are relatively common in primary care patients with unipolar depression and are associated with a more morbid course of illness. Future classifications of recurrent depression should include dimensional measures of bipolar symptoms. [ABSTRACT FROM AUTHOR]

Background: Building on previous research with adolescents that examined demographic variables and other forms of substance abuse in relation to non-medical use of prescription drugs (NMUPD), the current study examined potentially traumatic events, depression, posttraumatic stress disorder (PTSD), other substance use, and delinquent behavior as potential correlates of past-year non-medical use of prescription drugs. Method: A nationally representative sample of 3,614 non-institutionalized, civilian, English-speaking adolescents (aged 12–17 years) residing in households with a telephone was selected. Demographic characteristics, traumatic event history, mental health, and substance abuse variables were assessed. NMUPD was assessed by asking if, in the past year, participants had used a prescription drug in a non-medical manner. Multivariable logistic regressions were conducted for each theoretically derived predictor set. Significant predictors from each set were then entered into a final multivariable logistic regression to determine significant predictors of past-year NMUPD. Results: NMUPD was endorsed by 6.7% of the sample ( n = 242). The final multivariable model showed that lifetime history of delinquent behavior, other forms of substance use/abuse, history of witnessed violence, and lifetime history of PTSD were significantly associated with increased likelihood of NMUPD. Conclusions: Risk reduction efforts targeting NMUPD among adolescents who have witnessed significant violence, endorsed abuse of other substances and delinquent behavior, and/or endorsed PTSD are warranted. Interventions for adolescents with history of violence exposure or PTSD, or those adjudicated for delinquent behavior, should include treatment or prevention modules that specifically address NMUPD. [ABSTRACT FROM AUTHOR]

Debate has arisen over whether posttraumatic stress disorder (PTSD) is most accurately conceptualized as representing a discrete clinical syndrome or an extreme reaction to traumatic life events. Recent taxometric research using predominately adult samples appears to support a dimensional model of PTSD, raising questions about the utility of current psychiatric nosology which depicts PTSD as a distinct entity. The present study sought to use taxometric procedures to examine the latent structure of posttraumatic stress reactions among a national epidemiologic sample of 2,885 adolescents. Results were consistent with previous taxometric studies in supporting a dimensional model of posttraumatic stress reactions. The implications of these findings for public policy, as well as the etiology and assessment of posttraumatic stress reactions, are discussed. [ABSTRACT FROM AUTHOR]

Objectives: Studies have suggested that episode polarity at illness onset in bipolar disorder may be predictive of some aspects of lifetime clinical characteristics. We here examine this possibility in a large, well-characterized sample of patients with bipolar I disorder. Methods: We assessed polarity at onset in patients with bipolar I disorder (N = 553) recruited as part of our ongoing studies of affective disorders. Lifetime clinical characteristics of illness were compared in patients who had a depressive episode at first illness onset (n = 343) and patients who had a manic episode at first illness onset (n = 210). Results: Several lifetime clinical features differed between patients according to the polarity of their onset episode of illness. A logistic regression analysis showed that the lifetime clinical features significantly associated with a depressive episode at illness onset in our sample were: an earlier age at illness onset; a predominantly depressive polarity during the lifetime; more frequent and more severe depressive episodes; and less prominent lifetime psychotic features. Conclusions: Knowledge of pole of onset may help the clinician in providing prognostic information and management advice to an individual with bipolar disorder. [ABSTRACT FROM AUTHOR]

Abstract: Background: It is widely held that there are no differences in the symptom profile of male and female depression. Studies to date that have found differences have used different methodologies and had inconsistent findings. Here we compare the clinical profile of major depression for men and women from a sample of almost 600 well-characterized individuals with recurrent major depressive disorder (MDD). Methods: Subjects were recruited as part of a large genetic-epidemiological study of MDD. Clinical assessments included semi-structured interviews and case-note review. Clinical profiles during ‘worst ever’ (WE) depressive episode were scored using the OPCRIT checklist. Profiles for 199 males were compared to 399 females. Results: Females with depression tended to have an earlier age-at-onset (p <0.0001), exhibited more frequent depressive episodes (p <0.005), had a greater number of depressive symptoms (p <0.001), and reported much higher rates of atypical depressive features (p <0.007) during their WE episode of depression. Logistic regression analysis identified that earlier age-at-onset of depression, excessive self-reproach and diminished libido were the best predictors of female depression. Limitations: Retrospective recall by subjects of depressive symptoms, which may be prone to recall bias. Conclusions: There are differences in the clinical course and symptom profile of male and female depression. Further study is required to identify the biological correlates of these differences and to characterize their clinical importance. [Copyright &y& Elsevier]

Objective: Patients with remitted major depressive disorder (MDD) and bipolar disorder have persistent impairments in executive function and verbal memory that may represent endophenotypic abnormalities. In this study, we examine neurocognitive function in a sample of euthymic young adults with bipolar spectrum disorder (BSD) (Can J Psychiatry 2002; 47: 125–134) and compare this to well-matched samples of young adults with recurrent MDD and controls. Method: Twenty-one euthymic young adult patients with BSD were compared with 42 young adult patients with MDD and 33 controls on a neuropsychological battery assessing attention, executive function and verbal memory. Results: Patients with BSD were significantly more impaired than MDD patients and controls on tests of executive function and verbal memory. MDD patients did not differ significantly from controls on verbal memory function but performed less well on a test of executive function. Conclusion: Euthymic young adults with BSD had greater impairment on neurocognitive measures associated with prefrontal and hippocampal function than MDD patients and controls. This is a reflection of a strong bipolar diathesis in the BSD group rather than being a consequence of a more severe unipolar illness. [ABSTRACT FROM AUTHOR]

Abstract: Background: The personality dimensions of harm avoidance (HA) and self-directedness (SD), as measured by the Temperament and Character Inventory (TCI), have been widely associated with depression and there is preliminary evidence that they may represent trait markers for depression. However, many studies in this area are limited by the use of heterogeneous samples of depressed patients and by the confounding effect of depressed mood during personality testing. The current study compares TCI personality dimension scores in a group of euthymic young adults with recurrent early-onset major depressive disorder (RE-MDD) to well-matched euthymic controls. Methods: Fifty-two young adults with a past history of RE-MDD were recruited from consecutive referrals to a psychiatric clinic at a university health service. Eighty nine controls were also recruited. Euthymia was established in patients by a score of less than 9 on the Hamilton Rating Scale for Depression (HRSD) and in controls by a Becks Depression Inventory (BDI) score of less than 10. All participants completed the TCI-125. Results: Patients and controls were well matched in terms of sociodemographic profile. Euthymic RE-MDD patients scored significantly higher than controls on the temperament dimension of harm avoidance (HA; mean score 14.5 versus 7.8, p &#60;0.0001) and significantly lower than controls on the character dimension of self-directedness (SD; mean score 14.1 versus 19.9, p &#60;0.0001). Covariance analysis suggested that both HA and SD contributed independently to the familial risk of depression. Limitations: Subjects and controls all came from relatively affluent social backgrounds—these findings may not generalise to more socioeconomically diverse populations. The possibility of a ‘scarring effect’ of depressive episodes on self-reported personality dimension scores cannot be excluded. Conclusions: High HA and low SD represent trait markers for liability to recurrent major depressive disorder in young adults. Further research is needed to replicate these findings and to assess the contribution that the experience of depressive episodes makes to self-reported personality dimension scores. [Copyright &y& Elsevier]

Abstract: Background: In young adults it can be difficult to differentiate between an early bipolar illness and borderline personality disorder. There are considerable areas of clinical overlap between cyclothymic temperament, bipolar-spectrum disorders and borderline characteristics. The aim of this study was to measure borderline characteristics in young adults during an index depressive episode and to compare three diagnostic groups: DSM-IV bipolar affective disorder (BPAD); bipolar spectrum disorder (BSD); and DSM-IV recurrent major depressive disorder (MDD). Methods: Eighty-seven young adults with a current episode of major depression and at least one previous episode of depression were recruited from consecutive referrals to a psychiatric clinic. Diagnoses were based on the Structured Clinical Interview for DSM-IV (SCID-1) and recently proposed structured diagnostic criteria for BSD [Ghaemi, S.N., Ko, J.Y., Goodwin, F.K., 2002. Cade''s Disease and beyond: misdiagnosis, antidepressant use and a proposed definition for bipolar spectrum disorder. Can. J. Psychiatry 47, 125–134.]. All patients also completed the borderline questions from the screening questionnaire of the International Personality Disorders Examination (IPDE). Results: Diagnostically, the cohort of 87 patients divided into three groups: 14 with BPAD; 27 with BSD; and 46 with MDD. None of the subjects fulfilled DSM-IV or ICD-10 diagnostic criteria for personality disorder and all three groups were well matched in terms of age, gender distribution, ethnicity, socioeconomic and educational status, age at onset of illness, and severity of index depressive episode. Both of the bipolar-depressed groups reported significantly higher median levels of borderline characteristics than the MDD group (p &#60;0.0001). Three of the borderline characteristics emerged as potentially useful in differentiating bipolar depression from unipolar depression: ‘I''ve never threatened suicide or injured myself on purpose’ (sensitivity=0.93; positive predictive value [PPV]=56.7); ‘I have tantrums or angry outbursts’ (sensitivity 0.66; PPV=65.6%); and ‘Giving in to some of my urges gets me into trouble’ (sensitivity=0.76; PPV=59.6%). Limitations: All of the subjects were recruited from a university health service clinic and as such are unlikely to be representative of patients from more diverse socio-economic backgrounds. No structured diagnostic assessment of personality disorder was administered. The diagnostic criteria for BSD are not yet fully validated. Conclusions: Young adults with bipolar depression exhibit significantly higher levels of borderline personality pathology than those with unipolar depression. Those borderline screening questions that reflect cyclothymic characteristics or depressive mixed states may be of practical use to clinicians in helping to differentiate between bipolar depression and unipolar depression in young adults. [Copyright &y& Elsevier]

Using a national probability household sample of 4,008 women, we estimated the prevalence and correlates of formal and informal help seeking. One-year prevalences of formal help seeking (e.g., seeking help from professional) and informal help seeking (e.g., seeking help from a relative or friend) were 10.6 and 6.6%, respectively. In the final multivariable model, increased likelihood of informal help seeking was associated with younger age, history of sexual assault, and past-year diagnoses of posttraumatic stress disorder (PTSD) and major depressive episode (MDE). Similarly, increased likelihood of formal help seeking was associated with younger age. Caucasian racial/ethnic status, history of sexual assault, history of physical assault, and past-year diagnoses of PTSD and MDE. Implications for helping professionals and public education programs are discussed. [ABSTRACT FROM AUTHOR]

Background: Young adults with early-onset major depressive disorder (MDD) may be at high risk of progression to bipolar disorder. Although hypomanic symptoms are common in young people with depression, many do not reach the strict DSM-IV and ICD-10 criteria for hypomania. We used an emerging innovative framework for bipolar spectrum to evaluate this question. Methods: Consecutive referrals to a psychiatric outpatient clinic at a university health service were assessed for recurrent episodes of depression. DSM-IV diagnoses were based on a SCID-1 interview. We used two approaches to delineate bipolar spectrum. The first focused on bipolar spectrum disorder (BSD, as defined by Ghaemi et al. [Can. J. Psychiatry 47 (2002) 125]), and the second on a symptoms perspective based on MDD with a history of hypomanic symptoms, using a 15-point hypomanic symptoms checklist with a cut-off ≥8 or more symptoms (modified from J. Affect. Disord. 73 (2003) 39 and J. Affect. Disord. 73 (2003) 73). Data were also obtained on family history of affective disorder, course and number of episodes of depression, symptom severity, psychosocial functioning, suicidality and deliberate self-harm, and drug and alcohol use. Results: High rates of bipolar and bipolar spectrum disorder were identified. Under DSM-IV, 14 subjects (16.1%) had bipolar affective disorder and 73 subjects (83.9%) had recurrent MDD. Depending on the method used to diagnose bipolar spectrum, between 47.1% and 77.0% of the total cohort could be so diagnosed. Hypomanic symptom counts, irrespective of duration, yielded the highest estimates for bipolar spectrum. High rates of pharmacological hypomania were also identified: 12 subjects (16.4%) with recurrent MDD group reported this, and all could be diagnosed with bipolar spectrum. Limitations: The reliability of using the 15-point hypomanic scale for the diagnostic assignments was not tested. All subjects were recruited from a university health service and, given the affluence of their parents, findings may not generalise to other populations. Most importantly, because bipolar family history and pharmacological hypomania were part of the diagnostic criteria of the BSD group, they could not be used as external validators for Ghaemi''s BSD construct. Conclusions: Bipolar disorders emerge as extremely common in this cohort of young adults with recurrent depression. Antidepressant-induced hypomania and high scores on a hypomanic symptoms checklist help to identify patients who are likely to have a bipolar spectrum illness, but who do not meet DSM-IV criteria for bipolar disorder. This is a preliminary study, and further evidence from external validating strategies are needed to verify the bipolar status of these patients in a larger and unselected cohort representing a broader socio-economic demographic profile. [Copyright &y& Elsevier]

We examined the prevalence of pre- and post-combat traumatic events in the histories of 129 combat veterans referred to be evaluated for PTSD and examined the impact of these non-combat traumatic events on self-reported psychiatric symptoms. Participants were consecutive referrals to a Veterans Affairs outpatient post-traumatic stress disorder (PTSD) clinic who completed structured interviews, self-report measures (e.g., Minnesota Multiphasic Personality Inventory-2; MMPI-2), and a trauma history questionnaire as part of their routine clinical evaluations. Findings show that non-combat trauma was prevalent in this sample, with 65% (21% pre-combat) reporting physical assaults and 12% (11% pre-combat) reporting sexual assaults. Overall, history of sexual or physical assaults did not appear to be systematically related to reported symptom level. However, chi square analyses revealed a consistent over-representation of veterans who reported sexual trauma in the category suggestive of response exaggeration (i.e., MMPI-2 F-K validity index > or = 13). Finally, a hierarchical regression equation predicting F-K scores was computed, but accounted for only 15.9% of the variance in F-K. Presence of sexual assault history was the only predictor associated with a more pronounced response set suggestive of exaggeration or deception. These findings tentatively indicate that if history of sexual or physical assault has an impact on symptom reporting in combat veterans evaluated for PTSD, it is of modest magnitude. [ABSTRACT FROM AUTHOR]

Highlights from the article: Su24new common genetic variants associated with chronic pain: conditional false discovery rate analysis with major depressive disorder B Background: b Chronic pain is defined as pain lasting longer than 12 weeks. Six CPG-associated and nine MDD-associated SNPs were found at cFDR <= 0.01, in comparison with three and zero MDD and CPG-associated SNPs respectively found via the original GWAS analyses.

Post-inflammatory behaviours in rodents are widely used to model human depression and to test the efficacy of novel anti-depressants. Mice injected with lipopolysaccharide (LPS) display a depressive-like phenotype twenty-four hours after endotoxin administration. Despite the widespread use of this model, the mechanisms that underlie the persistent behavioural changes after the transient peripheral inflammatory response remain elusive. The study of the metabolome, the collection of all the small molecule metabolites in a sample, combined with multivariate statistical techniques provides a way of studying biochemical pathways influenced by an LPS challenge. Adult male CD-1 mice received an intraperitoneal injection of either LPS (0.83 mg/kg) or saline, and were assessed for depressive-like behaviour 24 h later. In a separate mouse cohort, pro-inflammatory cytokine gene expression and 1H nuclear magnetic resonance (NMR) metabolomics measurements were made in brain tissue and blood. Statistical analyses included Independent Sample t-tests for gene expression data, and supervised multi-variate analysis using orthogonal partial least squares discriminant analysis for metabolomics. Both plasma and brain metabolites in male mice were altered following a single peripheral LPS challenge that led to depressive-like behaviour in the forced swim test. The plasma metabolites altered by LPS are involved in energy metabolism, including lipoproteins, glucose, creatine, and isoleucine. In the brain, glutamate, serine, and N-acetylaspartate (NAA) were reduced after LPS, whereas glutamine was increased. Serine-modulated glutamatergic signalling and changes in bioenergetics may mediate the behavioural phenotype induced by LPS. In light of other data supporting a central imbalance of glutamate-glutamine cycling in depression, our results suggest that aberrant central glutaminergic signalling may underpin the depressive-like behaviours that result from both inflammation and non-immune pathophysiology. Normalising glutaminergic signalling, rather than seeking to increase serotonergic signalling, might prove to be a more coherent approach to the development of new treatments for mood disorder. [ABSTRACT FROM AUTHOR]

The diagnostic boundary between recurrent unipolar depression and bipolar disorder may not be clear-cut and, further, the symptoms of unipolar depression compared with bipolar depression (although similar) are subtly different. Here we review the potential implications for clinical practice and research of new thinking about the relationship between recurrent unipolar depression and bipolar disorder. [ABSTRACT FROM AUTHOR]

The authors call for improvements in the diagnosis and treatment of bipolar spectrum disorders in British primary care setting. They say based on studies, people who are at risk to develop these disorders are those who have unipolar depression, have family history and are resistant to antidepressants. They add that there are limited diagnostic criteria for hypomania, resulting to placing bipolar symptoms into a broad diagnostic category of unipolar depression. They recommend the use of the Bipolar Spectrum Diagnostic Scale to determine hypomania.

It is commonly -- but wrongly -- assumed that there are no important differences between the clinical presentations of major depressive disorder and bipolar depression. Here we compare clinical course variables and depressive symptom profiles in a large sample of individuals with major depressive disorder (n=593) and bipolar disorder (n=443). Clinical characteristics associated with a bipolar course included the presence of psychosis, diurnal mood variation and hypersomnia during depressive episodes, and a greater number of shorter depressive episodes. Such features should alert a clinician to a possible bipolar course. This is important because optimal management is not the same for bipolar and unipolar depression. [ABSTRACT FROM AUTHOR]

Background: Identifying the phenotypic manifestations of increased genetic liability for depression (MDD) and bipolar disorder (BD) can enhance understanding of their aetiology. The polygenic risk score (PRS) derived using data from genome-wide-association-studies can be used to explore how genetic risk is manifest in different samples.Aims: In this systematic review, we review studies that examine associations between the MDD and BD polygenic risk scores and phenotypic outcomes.Methods: Following PRISMA guidelines, we searched EMBASE, Medline and PsycINFO (from August 2009 - 14th March 2016) and references of included studies. Study inclusion was based on predetermined criteria and data were extracted independently and in duplicate.Results: Twenty-five studies were included. Overall, both polygenic risk scores were associated with other psychiatric disorders (not the discovery sample disorder) such as depression, schizophrenia and bipolar disorder, greater symptom severity of depression, membership of a creative profession and greater educational attainment. Both depression and bipolar polygenic risk scores explained small amounts of variance in most phenotypes (< 2%).Limitations: Many studies did not report standardised effect sizes. This prevented us from conducting a meta-analysis.Conclusions: Polygenic risk scores for BD and MDD are associated with a range of phenotypes and outcomes. However, they only explain a small amount of the variation in these phenotypes. Larger discovery and adequately powered target samples are required to increase power of the PRS approach. This could elucidate how genetic risk for bipolar disorder and depression is manifest and contribute meaningfully to stratified medicine. [ABSTRACT FROM AUTHOR]

Background Our current knowledge about predictors of admission and re-admission to hospital as a result of major depressive disorder (MDD) is limited. Here we present a descriptive analysis of factors which are associated with MDD hospitalisations within a large population cohort. Methods We linked participants of the Scottish Health Survey (SHS) to historical and prospective hospital admission data. We combined information from the SHS baseline interview and historical hospitalisations to define a range of exposure variables. The main outcomes of interest were: (1) first time admission for MDD occurring after the SHS interview; and (2) readmission for MDD. We used Cox regression to determine the association between each predictor and each outcome, after adjusting for age, gender and deprivation quintile. Results 52,990 adult SHS participants were included. During a median follow-up of 4.5 years per participant, we observed 530 first-time admissions for MDD. A relatively wide range of factors – encompassing social, individual health status, and lifestyle-related exposures – were associated with this outcome ( p <0.05). Among the 530 participants exhibiting a de novo admission for MDD during follow-up, 118 were later re-admitted. Only older age (over 70) and a prior non-depression related psychiatric admission were associated with readmission for MDD. Limtations MDD was defined using records of International Classification of Disease hospital discharge codes rather than formal diagnostic assessments. Conclusion These findings have implications for mental health service organisation and delivery and should stimulate future research on predictive factors for admission and readmission in MDD [ABSTRACT FROM AUTHOR]

Background: Depression is highly heterogeneous in its clinical presentation. Those with attention deficit/hyperactivity disorder (ADHD) may be at risk of a more chronic and impairing depression compared to those with depression alone according to studies of young people. However, no studies to date have examined ADHD in recurrently depressed adults in mid-life.Method: In a sample of women in mid-life (n=148) taken from a UK based prospective cohort of adults with a history of recurrent depression, we investigated the prevalence of ADHD and the association of ADHD with clinical features of depression.Results: 12.8% of the recurrently depressed women had elevated ADHD symptoms and 3.4% met DSM-5 diagnostic criteria for ADHD. None of the women reported having a diagnosis of ADHD from a medical professional. ADHD symptoms were associated with earlier age of depression onset, higher depression associated impairment, a greater recurrence of depressive episodes and increased persistence of subthreshold depression symptoms over the study period, higher levels of irritability and increased risk of self-harm or suicide attempt. ADHD symptoms were associated with increased risk of hospitalisation and receiving non-first-line antidepressant medication.Limitations: ADHD was measured using a questionnaire measure. We focussed on mothers in a longitudinal study of recurrent depression, so the findings may not apply to males or other groups.Conclusions: Higher ADHD symptoms appear to index a worse clinical presentation for depression. Clinical implications include that in women with early onset, impairing and recurrent depression, the possibility of underlying ADHD masked by depression needs to be considered. [ABSTRACT FROM AUTHOR]

Background: We examined whether seasonal variations in depressive symptoms occurred independently of demographic and lifestyle factors, and were related to change in day length and/or outdoor temperature.Methods: In a cross-sectional analysis of >150,000 participants of the UK Biobank cohort, we used the cosinor method to assess evidence of seasonality of a total depressive symptoms score and of low mood, anhedonia, tenseness and tiredness scores in women and men. Associations of depressive symptoms with day length and mean outdoor temperature were then examined.Results: Seasonality of total depressive symptom scores, anhedonia and tiredness scores was observed in women but not men, with peaks in winter. In women, increased day length was associated with reduced reporting of low mood and anhedonia, but with increased reporting of tiredness, independent of demographic and lifestyle factors. Associations with day length were not independent of the average outdoor temperature preceding assessment.Limitations: This was a cross-sectional investigation - longitudinal studies of within-subject seasonal variation in mood are necessary. Outcome measures relied on self-report and measured only a subset of depressive symptoms.Conclusion: This large, population-based study provides evidence of seasonal variation in depressive symptoms in women. Shorter days were associated with increased feelings of low mood and anhedonia in women. Clinicians should be aware of these population-level sex differences in seasonal mood variations in order to aid recognition and treatment of depression and subclinical depressive symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Background: The under-recognition of hypomanic symptoms by both clinicians and patients is a major clinical problem which contributes to misdiagnosis and diagnostic delay in patients with bipolar disorder. The recent development of validated screening instruments for hypomania, such as the Hypomania Checklist (HCL-32), may help to improve the detection of bipolar disorder. In this study, we assess whether it is possible to reduce the number of items on the HCL-32 without any loss in the screening tool''s ability to reliably differentiate between bipolar disorder (BD) and major depressive disorder (MDD). Methods: Using our large samples of patients with DSM-IV defined bipolar I disorder (BD-I) (n =230) and recurrent MDD (n =322), we performed item correlations in order to identify potentially redundant items in the HCL-32. We then tested the performance of a shortened 16-item HCL questionnaire within a separate sample of patients with BD (including BD-I, BD-II and BD-NOS) (n =59) and MDD (n =76). Results: The structure of the 16-item HCL demonstrated two main factors similar to those identified for the HCL-32 (an ‘active-elated’ factor and a ‘risk-taking/irritable’ factor). A score of 8 or more on a shortened 16-item version of the HCL had excellent ability to distinguish between BD and MDD. The sensitivity (83%) and specificity (71%) of the 16-item version were very similar to those for the full 32-item HCL. Limitations: The HCL-16 was derived after subjects had completed the full HCL-32. It will be important to test the validity of a ‘stand-alone’ 16-item HCL questionnaire. Conclusions: A shortened 16-item HCL (the HCL-16) is potentially a useful screening tool for hypomania within busy clinical settings. [Copyright &y& Elsevier]

Abstract: Objective: There is currently a great deal of interest in the use of affective temperaments as possible intermediate phenotypes for bipolar disorder. However, much of the literature in this area is conflicting. Our aims were to test the hypothesis of a gradient in affective temperament scores, as measured by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A), from bipolar disorder type I (BP-I), through bipolar disorder type II (BP-II), recurrent major depressive disorder (MDD-R), and a control group (CG) in the largest sample to date of 927 subjects. Methods: Non parametric tests were used to compare TEMPS-A scores between diagnostic groups and multinomial logistic regression was used to test the association between TEMPS-A scores and diagnosis while controlling for current mood state, age and gender. Results: Although the BP-II group scored higher than the BP-I and MDD-R groups on several TEMPS-A subscales, these differences were not significant when confounding variables were controlled for. The dysthymic subscale differentiated between affected and controls and the anxious subscale differentiated the MDD-R group from controls. Limitations: The cross-sectional design did not allow us to evaluate potential longitudinal changes of temperament scores, which were assessed only with a self-report questionnaire. Conclusion: We failed to find evidence of a gradient in affective temperament scores. Both unipolar and bipolar patients reported high dysthymic scores relative to controls, perhaps supporting a unitary view of depression across the bipolar–unipolar spectrum. Taking account of potential confounders will be important in future studies which seek to use affective temperaments as intermediate phenotypes in genetic research. [Copyright &y& Elsevier]

B Background: b Epidemiology has convincingly demonstrated that people suffering from serious mental illness (such as schizophrenia, bipolar disorder and major depressive disorder) have an excess risk of obesity, diabetes and cardiovascular disease. The CNTN5 locus has been associated with a number of cardiometabolic traits, serious mental illness and suicidal behaviour, and might represent a mechanism common to mental and physical illness. B Discussion: b Multiple signals which influence related endophenotypes of relevance to psychiatric disorders were identified within the CNTN5 locus and were consistent across diverse ancestry groups. [Extracted from the article]