Nick Craddock

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.

Background: Individuals with a mental health disorder appear to be at increased risk of medical illness.Aims: To examine rates of medical illnesses in patients with bipolar disorder (n = 1720) and to examine the clinical course of the bipolar illness according to lifetime medical illness burden.Method: Participants recruited within the UK were asked about the lifetime occurrence of 20 medical illnesses, interviewed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and diagnosed according to DSM-IV criteria.Results: We found significantly increased rates of several medical illnesses in our bipolar sample. A high medical illness burden was associated with a history of anxiety disorder, rapid cycling mood episodes, suicide attempts and mood episodes with a typically acute onset.Conclusions: Bipolar disorder is associated with high rates of medical illness. This comorbidity needs to be taken into account by services in order to improve outcomes for patients with bipolar disorder and also in research investigating the aetiology of affective disorder where shared biological pathways may play a role.Declarations of interest: None.

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%). 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. 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). 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.

Bipolar disorders affect between 3–5% of the population and are associated with considerable lifelong impairment. Since much of the morbidity associated with bipolar disorder is caused by recurrent depressive symptoms, which are often only poorly responsive to antidepressants, there is a need to develop alternative, non-pharmacological interventions. Psychoeducational interventions have emerged as promising long-term therapeutic options for bipolar disorder. The study is an exploratory, individually randomised controlled trial. The intervention known as 'Beating Bipolar' is a psychoeducational programme which is delivered via a novel web-based system. We will recruit 100 patients with a diagnosis of DSM-IV bipolar disorder (including type I and type II) currently in clinical remission. The primary outcome is quality of life. This will be compared for those patients who have participated in the psychoeducational programme with those who received treatment as usual. Quality of life will be assessed immediately following the intervention as well as 10 months after randomisation. Secondary outcomes include current depressive and manic symptoms, number of episodes of depression and mania/hypomania experienced during the follow-up period, global functioning, functional impairment and insight. An assessment of costs and a process evaluation will also be conducted which will explore the feasibility and acceptability of the intervention as well as potential barriers to effectiveness. Bipolar disorder is common, under-recognised and often poorly managed. It is a chronic, life-long, relapsing condition which has an enormous impact on the individual and the economy. This trial will be the first to explore the effectiveness of a novel web-based psychoeducational intervention for patients with bipolar disorder which has potential to be easily rolled out to patients. Current Controlled Trials ISRCTN81375447

Objectives:  The frequent comorbidity of panic and affective disorders has been described in previous studies. However, it is not clear how panic disorder comorbidity in unipolar disorder and bipolar disorder is related to illness course.Methods:  We compared lifetime clinical characteristics of illness and items of symptomatology in samples of individuals with bipolar I disorder (n = 290) and unipolar disorder (n = 335) according to the lifetime presence of recurrent panic attacks.Results:  We found significant differences in clinical course of illness characteristics that were shared across the unipolar and bipolar samples according to the lifetime presence of panic attacks. We also found a number of differences according to the presence of panic attacks that may be specific to the diagnostic group.Conclusions:  Distinguishing patients who have mood disorder diagnoses, especially bipolar I disorder, according to the lifetime presence of panic attacks may not only be of use in clinical practice, but may also be informative for aetiological research, such as molecular genetic studies.

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.

Summary: 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.

Objective:To examine whether variation at two common polymorphisms, T102C and −1438AG, of the serotonin 2A gene (5HT2A) are involved in the puerperal triggering mechanism of bipolar affective puerperal psychosis.Method:A total of 242 parous women diagnosed with bipolar disorder were genotyped for the two polymorphisms. Of these, 165 women had experienced a manic or psychotic episode, according to DSM‐IV criteria, within 6 weeks of childbirth (the puerperal psychosis group).The comparison group comprised of 77 parous women who had not experienced psychiatric disturbance following childbirth.Results:No significant differences between genotype or allelic frequencies were found between the two groups for either polymorphism.Conclusion:The results indicate that variation at two common polymorphisms of the5HT2Agene does not appear to play a major role in the development of bipolar affective puerperal psychosis.