Mixed Depression Research Articles

QT Prolongation-induced Seizures Masquerading as Depression with Mixed Features

IntroductionSevere mental disorders experience premature mortality mostly from physical causes. When a patient with a history of bipolar disorder is admitted to the emergency room (ER) for psychiatric symptoms, these are routinely interpreted as a psychiatric disturbance. However, a careful history should be performed to correctly interpret key clinical information to rule out somatic etiology and establish adequate diagnosis.ObjectivesTo describe a patient whose presenting symptoms were misdiagnosed as psychiatric relapse, rather than serious somatic comorbidity debut.MethodsA 70-year-old man, with a history of type I bipolar disorder and multiple cardiovascular conditions, was admitted to the ER for self-referred nervousness, depressed mood, insomnia, and suicidal thoughts. Symptoms had greatly worsened the previous week to his consultation with paroxysmal episodes of severe anxiety, feelings of strangeness, and sensations of unpleasant odors.ResultsDuring observation, the patient was found lying down with loss of consciousness, urinary incontinence, and amnesia of the event. Generalized tonic-clonic seizures were observed by neurologists while mental status examination was being performed. After symptoms were oriented as having a neurological etiology, the patient suffered cardiac arrest and defibrillation was required. After admittance to the intensive care unit and inpatient cardiology care, the patient was discharged from the hospital with the diagnosis of ventricular fibrillation due to drug-induced QT prolongation. There was no evidence of mixed depression or seizures once the cardiac dysfunction was identified and treated.ConclusionsThe psychiatric symptoms were the clinical manifestation of a generalized seizure-like activities that were attributed to transient cerebral hypoperfusion secondary to ventricular fibrillation.DisclosureNo significant relationships.

Mediators of symptom improvement in transdiagnostic internet cognitive behavioural therapy for mixed anxiety and depression

ABSTRACT Objectives Transdiagnostic internet cognitive behavioural therapy (iCBT) improves depression and anxiety symptoms, but the factors mediating these improvements are unknown. Design In a secondary analysis of a randomised controlled trial, we compared the impact of a transdiagnostic iCBT program (n = 39) on emotion regulation, repetitive negative thinking, and experiential avoidance relative to treatment-as-usual (TAU) control (n = 35). The extent to which changes in these processes mediated treatment gains in iCBT relative to TAU was also explored. Intention-to-treat mixed models were used to assess outcomes, and unmoderated simple mediation models were used to explore mediators of change of each outcome (depression/anxiety). Results Results showed iCBT outperformed TAU in reducing all three processes, with largebetween-group effect sizes for repetitive negative thinking (g = 1.04), and medium effect sizes for emotion regulation (g = 0.78), and experiential avoidance (g = 0.54). Changes in symptoms of depression and anxiety were partly mediated through pre-to-post changes in all three variables, but not pre-to-mid-treatment changes. Conclusion These findings provide evidence that transdiagnostic iCBT for depression and anxiety improves emotion regulation, reduces repetitive thinking and experiential avoidance, and provides preliminary evidence that symptom improvements are associated with improvements in these variables. KEY POINTS What is already known about this topic: (1) Transdiagnostic interventions aim to target the common symptoms and the functional emotional, cognitive, and behavioural processes shared across emotional disorders. (2) Transdiagnostic internet-delivered cognitive behavioural therapy (iCBT) improves depression and anxiety symptoms. (3) However, the factors mediating these symptom improvements are largely unknown. What this topic adds: (1) Transdiagnostic iCBT for depression and anxiety improves emotion regulation and reduces repetitive thinking and experiential avoidance in participants with an anxiety and/or depressive disorder. (2) Symptom improvements are associated with improvements in these transdiagnostic variables; emotion regulation, repetitive negative thinking, and experiential avoidance appear to be significant mediators of post-treatment improvements in symptoms of depression and anxiety. (3) Targeting these shared underlying processes is likely important to improve symptoms of depression and anxiety.

The influence of personality disorder in predicting suicidal behaviour in common mental disorders: A 30-year study.

Two hundred ten patients with anxiety and depressive disorders were followed up over 30 years. Personality status was assessed at baseline using the Personality Assessment Schedule (PAS), an instrument that classifies personality disorder in a similar way to the new ICD‐11 classification. Assessments of suicidal behaviour were made at 5, 12 and 30 years and suicidal thoughts at 12 and 30 years and analysed by personality status, clinical diagnosis and scores on the General Neurotic Syndrome Scale, a combined diagnosis of mixed anxiety depression and personality dysfunction. Suicide attempts were most frequent in the first 5 years of the study and reduced over time. Baseline personality status was the best predictor of suicide attempts at 5 years (no personality disorder 29.3%, personality disorder 51.6%, p = 0.006), and at 12 years (no personality disorder 11.9%, personality disorder 25.7%, p = 0.042), but no important differences were found at 30 years, when comorbid mental state disorder was the strongest predictor (p < 0.001). Similar but less marked findings were found for the general neurotic syndrome. It is concluded that the presence of personality disorder is a robust predictor of suicidal behaviour in the shorter term but in the long‐term comorbid pathology is a better predictor.

The Relationship Between CBT-Mindedness and iCBT Outcomes Amongst a Large Adult Sample

BackgroundPredicting response to cognitive behavior therapy (CBT) assists efforts to enhance treatment outcome when predictive factors are modifiable prior to, or during, treatment. The extent to which clients hold beliefs and attitudes consistent with CBT (termed CBT-mindedness) is a relatively new concept with research suggesting it predicts response to CBT amongst small samples of adults with anxiety. This study aimed to investigate CBT-mindedness amongst a larger clinical population receiving internet-delivered CBT (iCBT).Method1132 adults with anxiety, depression or mixed anxiety and depression who accessed iCBT with or without therapist support via the THIS WAY UP clinic completed a brief self-report measure of CBT-mindedness along with measures of distress, anxiety, and depression. Measures were completed pre- and post-treatment.ResultsThe 3-factor structure of the CBT Suitability Scale (CBT-SUITS) was confirmed and scores were unrelated or very weakly related to symptoms/distress. CBT-mindedness increased amongst treatment completers. CBT-mindedness predicted post-treatment distress (but not symptoms), and change in CBT-mindedness predicted lower post-treatment symptoms and distress.ConclusionsThe CBT-SUITS represents a psychometrically sound measure of CBT-mindedness. Results amongst this large sample of adults accessing iCBT in a community service indicate that CBT-mindedness (or CBT-mindedness change) is an important predictor of therapy response.

GLP-1 agonist liraglutide improves ouabain-induced mania and depressive state via GSK-3β pathway

Bipolar disorder (BD) is a severe mental illness characterized by aberrant mood changes between hypomania and mania or mixed states and depression. Metabolic changes also accompany disease progression and cause significant morbidity. Symptomatic treatment options are available, but asymptomatic patients and poor drug responders are significant problems. Based on the most common pharmacological agent that is used in the treatment, lithium and its main mechanisms of action, oxidative stress, and glycogen synthase kinase-3β (GSK-3β) signaling are extensively investigated. However, knowledge about the effects of compounds that positively affect oxidative stress and GSK-3β signaling, such as glucagon-like peptide-1 (GLP-1) mimetics, liraglutide, is still missing. Therefore, in this study, we aimed to investigate the effects of liraglutide on the ouabain-induced bipolar disease model in rats. After intracerebroventricular single dose ouabain administration, animals were treated with 100, 200, and 400 µg/kg liraglutide (s.c.) and valproic acid (200 mg/kg, i.p.) for 10 d. The locomotion and depressive states of animals were assessed by an open field, forced swimming test, and sucrose preference tests. Serum total antioxidant (TAS) and oxidant states (TOS) and glutathione, malonyl dialdehyde (MDA) levels in the brain tissue were determined. GSK-3β phosphorylation was evaluated by western blotting. Our results demonstrated that liraglutide attenuated ouabain-induced hyperlocomotion and depressive state. Additionally, liraglutide prevented oxidative stress after ouabain administration. Decreased GSK-3β phosphorylation due to the ouabain insult was alleviated by liraglutide treatment. These findings indicate that the manic and depressive-like behaviors are ameliorated by liraglutide, which exerted antioxidant action, possibly improving GSK-3β phosphorylation.

Mixed Depression: A Mini-Review to Guide Clinical Practice and Future Research Developments.

The debate on mixed states (MS) has been intense for decades. However, several points remain controversial from a nosographic, diagnostic, and therapeutic point of view. The different perspectives that have emerged over the years have turned into a large, but heterogeneous, literature body. The present review aims to summarize the evidence on MS, with a particular focus on mixed depression (MxD), in order to provide a guide for clinicians and encourage the development of future research on the topic. First, we review the history of MS, focusing on their different interpretations and categorizations over the centuries. In this section, we also report alternative models to traditional nosography. Second, we describe the main clinical features of MxD and list the most reliable assessment tools. Finally, we summarize the recommendations provided by the main international guidelines for the treatment of MxD. Our review highlights that the different conceptualizations of MS and MxD, the variability of clinical pictures, and the heterogeneous response to pharmacological treatment make MxD a real challenge for clinicians. Further studies are needed to better characterize the phenotypes of patients with MxD to help clinicians in the management of this delicate condition.

Distractibility, anxiety, irritability, and agitation symptoms are associated with the severity of depressive and manic symptoms in mixed depression.

To explore whether there is an association between distractibility, anxiety, irritability, and agitation (DAIA) symptoms and the severity of depressive and manic symptoms. Patients with unipolar and bipolar disorder (I and II) and mixed depression were evaluated. DAIA symptoms were assessed using previously described definitions. The full analysis set comprised 100 patients. The severity of depressive symptoms in mixed depression, assessed by Montgomery-Åsberg Depression Rating Scale (MADRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample, influenced mainly by anxiety. The severity of manic symptoms in mixed depression, assessed by Young Mania Rating Scale (YMRS), was significantly associated with the presence of two or more DAIA symptoms in the bipolar sample and three or four DAIA symptoms in the unipolar sample. DAIA symptoms were associated with greater severity of manic symptoms in mixed depression. DAIA symptoms must be evaluated in all patients with mixed features and are associated with the severity of depressive and manic symptoms in mixed depression.

Psychological disorders in patients with orthopaedic oncological diseases and their coping strategies.

This study aimed to determine the prevalence and risk factors of anxiety and depression among orthopaedic oncology patients, their quality of life and coping strategies. This cross-sectional study recruited patients from the outpatient orthopaedic oncology clinic at a tertiary institution. Data were collected from self-report questionnaires: Hospital Anxiety and Depression Scale Hospital Anxiety Depression Scale, World Health Organization Quality of Life (WHOQOL-BREF) and Brief Coping with Problems Experienced (Brief COPE). Risk factors were analyzed with multiple logistic regression. 191 patients were recruited. The median age was 39.4 years old (IQR 35.0). 29.8% had anxiety, 16.2% had depression, and 15.2% had mixed anxiety and depression. Quality of life median scores differed significantly between patients with anxiety and no anxiety and patients with depression and no depression (p < 0.001). Patients with mixed anxiety and depression had a more inferior quality of life (p < 0.001). Age, psychological health and radiotherapy were inversely associated with anxiety. Physical and psychological health were significantly associated with less depression. Ongoing chemotherapy was significantly associated with anxiety and depression. The commonest coping strategies were denial, behavioural disengagement, venting and self-blame. Anxiety and depression are prevalent among orthopaedic oncology patients. Patients with mixed anxiety and depression had a more inferior quality of life. Patients with ongoing chemotherapy had higher risks of anxiety and depression. The commonest coping strategies were denial, behavioural disengagement, venting and self-blame. Psychosocial evaluation followed by appropriate psychiatric referrals and consultations could be established to facilitate orthopaedic oncology patients during their course of treatment.

Treatment-resistant mixed anxiety and depression A genuine mental illness or an expression of overlooked disorders?

Treatment-resistant mixed anxiety and depression A genuine mental illness or an expression of overlooked disorders?

Management of psychiatric disorders in patients with cancer.

Management of psychiatric disorders in patients with cancer.

Mixed Depression: A Survey on Psychopathological, Diagnostic, and Therapeutic Approaches among a Sample of Italian Psychiatrists

Background: The Diagnostic and Statistical Manual for Mental Disorders (5th edition) introduced the specifier “with Mixed Features” to the diagnosis of Major Depressive Episode to designate the presence of (hypo) manic symptoms as part of the clinical presentation. This change has led to renewed attention on the operational definition, diagnosis, and treatment of Mixed Depression. Objective: To investigate the diagnostic and therapeutic approaches towards Mixed Depression among a representative sample of Italian psychiatrists. Methods: Between March and April 2021, 342 psychiatrists working in Italian adult mental health services were invited to participate in an anonymous online survey comprising 32 questions designed to investigate clinical and psychopathological approaches regarding the management of mixed depression in daily psychiatric practice. Results: 83.74% of participants reported having performed a diagnosis of mixed depression in the last five years, with the majority of respondents affirming that they had not used any diagnostic tool. Only 7,5% of the surveyed psychiatrists considered the DSM-5 criteria to be fully adequate in the description of this clinical entity. The most used pharmacological approach was combined therapy, in particular antipsychotics plus mood stabilizers. For monotherapy, the preferred drugs were Valproate and Quetiapine. Regarding the conceptualization of mood disorders, 199 of the participants chose the Kraepelinian unitary spectrum view; meanwhile, 101 expressed their preference for the binary model. Conclusion: Our results suggest a prominent position of mixed depression in the context of mood disorders. Univocal operational criteria and additional research on pharmacological treatment are also needed to ensure the correct recognition and management of mixed depression.

Smartphone Psychological Therapy During COVID-19: A Study on the Effectiveness of Five Popular Mental Health Apps for Anxiety and Depression

The aims of this study were to examine the effectiveness of a range of smartphone apps for managing symptoms of anxiety and depression and to assess the utility of a single-case research design for enhancing the evidence base for this mode of treatment delivery. The study was serendipitously impacted by the COVID-19 pandemic, which allowed for effectiveness to be additionally observed in the context of significant community distress. A pilot study was initially conducted using theSuperBetter app to evaluate the proposed methodology, which proved successful with the four finishing participants. In the main study, 39 participants commenced (27 females and 12 males,MAge = 34.04 years,SD = 12.20), with 29 finishing the intervention phase and completing post-intervention measures. At 6-month follow-up, a further three participants could not be contacted. This study used a digitally enhanced, multiple baseline across-individuals single-case research design. Participants were randomly assigned to the following apps:SuperBetter (n = 8),Smiling Mind (n = 7),MoodMission (n = 8),MindShift (n = 8), andDestressify (n = 8). Symptomatology and life functioning were measured at five different time points: pre-baseline/screening, baseline, intervention, 3-week post-intervention, and 6-month follow-up. Detailed individual perceptions and subjective ratings of the apps were also obtained from participants following the study’s completion. Data were analyzed using visual inspection, time-series analysis, and methods of statistical and clinical significance. Positive results were observed for all apps. Overall, more favorable outcomes were achieved by younger participants, those concurrently undertaking psychotherapy and/or psychotropic medication, those with anxiety and mixed anxiety and depression rather than stand-alone depression, and those with a shorter history of mental illness. Outcomes were generally maintained at 6-month follow-up. It was concluded that a diverse range of evidence-based therapies offered via apps can be effective in managing mental health and improving life functioning even during times of significant global unrest and, like all psychotherapies, are influenced by client features. Additionally, this single-case research design is a low-cost/high value means of assessing the effectiveness of mental health apps.Clinical Trial Registration: The study is registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR), which is a primary registry in the World Health Organization Registry Network, registration number ACTRN12619001302145p (http://www.ANZCTR.org.au/ACTRN12619001302145p.aspx).

Investigation of the correlation between mood disorder symptoms and disease activity and functional status in rheumatoid arthritis patients

To investigate the correlation between depressive-anxiety symptoms, mixed features, disease activity, and functional status in patients with rheumatoid arthritis (RA) in the light of the shared underlying etiology in both disorders. The study included 556 patients with RA. RA disease activity was measured using the Disease Activity Score 28-joint count C reactive protein (DAS28-CRP), and the patients were evaluated by a Health Assessment Questionnaire (HAQ). The Hospital Anxiety and Depression Scale (HADS), Mood Disorder Questionnaire (MDQ), and Modified Hypomania Checklist (mHCL) were used to evaluate the mixed depression and bipolarity status of the patients. Of the patients, 430 (77.3%) were female and 126 (22.7%) were male. The median age was 57 years, the median HAQ score was 0.55 points, and the median DAS28-CRP score was 4.1 points. The evaluation of the patients by DAS28-CRP revealed that 58.5% of the patients had moderate and severe disease activity, while only 23.4% of them were in remission. The group using the combination of synthetic disease-modifying anti-rheumatic drugs (sDMARD) and steroid therapy had significantly higher HAD-depression, HAD-anxiety, mHCL, DAS28-CRP, HAQ, and MDQ scores than the group using sDMARD alone. The grouping of the patients based on the DAS28-CRP cut-off scores showed that the patients with moderate and severe disease activity had significantly higher HADS, mHCL, MDQ scores than those in remission and those with mild disease activity (p < 0.001). Disease severity and functional status in RA can be affected by comorbid anxiety-depressive and mixed symptoms. Therefore, clinicians should consider screening the depressive-anxiety and mixed mood symptoms of RA patients. Moreover, patients who use steroid therapy are more susceptible to mood symptoms (anxiety, depression, bipolarity), which should also be considered during the follow-up of patients.

Which mixed depression model? A comparison between DSM-5-defined mixed features and Koukopoulos' criteria.

The criteria of the Diagnostic and Statistical Manual of Mental Disorders 5th edition "with mixed features specifier" (DSM-5 MFS) are considered controversial since they include only typical manic symptoms. By contrast, Koukopoulos developed an alternative model of mixed depression (MxD) focusing primarily on the excitatory component. To compare DSM-5 MFS and Koukopoulos' MxD (KMxD) in terms of prevalence, associated clinical variables, and discriminative capacity for bipolar depression in patients with major depressive episode (MDE). A total of 300 patients with MDE-155 with major depressive disorder and 145 with bipolar disorder (BD)-were recruited. The discriminative capacity of DSM-5 MFS and KMxD criteria for BD was estimated using the area under the curves of receiver operating characteristic (ROC_AUC). The clinical variables associated with these two diagnostic constructs were assessed by performing a logistic regression. A total of 44 and 165 patients met the DSM-5 MFS and KMxD criteria, respectively. The ROC_AUCs and their confidence intervals for BD according to DSM-5 MFS and KMxD were 77.0% (72.0%-82.1%) and 71.9% (66.2%-77.7%), respectively. The optimal thresholds (combining sensitivity and specificity measures) for BD diagnosis were ≥1 (77%/68%) for DSM-5 MFS and ≥3symptoms (78%/66%) for KMxD. However, considering the DSM-5 MFS cut-off (≥3symptoms), the specificity (97%) increased at the expense of sensitivity (26%). KMxD and DSM-5-MFS showed an overlapping discriminative capacity for bipolar depression. The current diagnostic threshold of DSM-5 MFS did not prove to be very inclusive, if compared with the greater diagnostic sensitivity of KMxD, which also yielded better association with clinical variables related to mixedness.

Investigation of the correlation between mood disorder symptoms and disease activity and functional status in rheumatoid arthritis patients.

To investigate the correlation between depressive-anxiety symptoms, mixed features, disease activity, and functional status in patients with rheumatoid arthritis (RA) in the light of the shared underlying etiology in both disorders. The study included 556 patients with RA. RA disease activity was measured using the Disease Activity Score 28-joint count C reactive protein (DAS28-CRP), and the patients were evaluated by a Health Assessment Questionnaire (HAQ). The Hospital Anxiety and Depression Scale (HADS), Mood Disorder Questionnaire (MDQ), and Modified Hypomania Checklist (mHCL) were used to evaluate the mixed depression and bipolarity status of the patients. Of the patients, 430 (77.3%) were female and 126 (22.7%) were male. The median age was 57 years, the median HAQ score was 0.55 points, and the median DAS28-CRP score was 4.1 points. The evaluation of the patients by DAS28-CRP revealed that 58.5% of the patients had moderate and severe disease activity, while only 23.4% of them were in remission. The group using the combination of synthetic disease-modifying anti-rheumatic drugs (sDMARD) and steroid therapy had significantly higher HAD-depression, HADanxiety, mHCL, DAS28-CRP, HAQ, and MDQ scores than the group using sDMARD alone. The grouping of the patients based on the DAS28-CRP cut-off scores showed that the patients with moderate and severe disease activity had significantly higher HADS, mHCL, MDQ scores than those in remission and those with mild disease activity (p < 0.001). Disease severity and functional status in RA can be affected by comorbid anxiety-depressive and mixed symptoms. Therefore, clinicians should consider screening the depressive-anxiety and mixed mood symptoms of RA patients. Moreover, patients who use steroid therapy are more susceptible to mood symptoms (anxiety, depression, bipolarity), which should also be considered during the follow-up of patients.

Bridging the Gap: Investigating the Role of Social Workers in Supporting Metastatic Breast Cancer Patients in Nigeria

ABSTRACT Cancer is a disease common in every country around the globe with high incidences and deaths. Receiving a breast cancer diagnosis is often associated with a death sentence which makes the individual exhibit self-denial attributes, mixed negative emotions, depression, and anxiety. This study investigated the gap in supportive care and the role of social workers in the management of metastatic breast cancer patients in Nigeria. This study employed a qualitative method using Key Informant Interviews (KII). A total of 12 healthcare professionals in the area of medical social work, palliative care, and medical oncology were engaged in collecting the required information. The result revealed that social workers play significant roles in every aspect of the cancer care continuum – diagnosis, treatment, reintegration, or palliative care. Social workers help metastatic breast cancer patients in Nigeria, however, there are growing challenges to their roles. Most unskilled professionals often present themselves as social workers who do not meet professional standards or perform the best practice.

Empirical support for the use and further study of the countertransference construct in the clinical care of patients with bipolar disorder.

We thank Andrew Shaw and colleagues for their recent paper1 inBipolar Disorders, highlightingthat theeffectivetreatment of patients with bipolar disorder requires a good therapeutic alliance,which is related to the clinicians' countertransference reactions and their management. The authorssuggestthat the integration of a psychodynamic approach into the biological paradigm in psychiatry might be helpful to increase countertransference awareness in clinicians, andpotentially improvingdyadic communication,resolution ofalliance ruptures, and treatment adherence. Theyalsomention that although the theoretical literature on countertransference is well developed, no good empirical studies exist that investigate the countertransferential responses experienced by mental health clinicians involved in the care of individualsduring acute phases of bipolar disorder. We would, however, like to add some examples of empirical evidence for the use (and further study) of the countertransference in the clinical care of these patients.

Post-partum psychosis and its association with bipolar disorder in the UK: a case-control study using polygenic risk scores

For more than 150 years, controversy over the status of post-partum psychosis has hindered research and caused considerable confusion for clinicians and women, with potentially negative consequences. We aimed to explore the hypothesis that genetic vulnerability differs between women with first-onset post-partum psychosis and those with bipolar disorder more generally. In this case-control study on first-onset post-partum psychosis and bipolar disorder in the UK, we included 203 women with first-onset post-partum psychosis (defined as a manic, mixed, or psychotic depression episode within 6 weeks of delivery without a psychiatric history) and 1225 parous women with a history of bipolar disorder. Information on women with bipolar disorder was obtained from the Bipolar Disorder Research Network database, and participants were recruited through screening community mental health teams across the UK and via the media and patient support organisations. All were assessed using a semistructured face-to-face psychiatric interview and psychiatric case note review. 2809 women from the general population were recruited via the national UK Blood Services and the 1958 Birth Cohort (UK National Child Development Study) as controls and matched to cases according to genetic ancestry. All self-reported their ethnicity as White and were recruited from across the UK. Polygenic risk scores (PRSs) were generated from discovery genome-wide association studies of schizophrenia, bipolar disorder, and major depression. Logistic regression was used to model the effect of each PRS on diagnosis, and the RRs and ORs presented were adjusted for ten principal components of genetic variation to account for population stratification. 203 women with first-onset post-partum psychosis (median age at interview: 46 years [IQR 37-55]) and 1225 women with bipolar disorder (49 years [41-58]) were recruited between September, 1991, and May, 2013, as well as 2809 controls. Women with first-onset post-partum psychosis had similar bipolar disorder and schizophrenia PRSs to women with bipolar disorder, which were significantly higher than those of controls. When compared with controls, women with first-onset post-partum psychosis had an adjusted relative risk ratio (RR) for bipolar disorder PRSs of 1·71 (95% CI 1·56-1·86, p<0·0001) and for schizophrenia PRSs of 1·82 (1·66-1·97, p<0·0001). The effect sizes were similar when comparing women with bipolar disorder to controls (adjusted RR 1·77 [1·69-1·84], p<0·0001 for bipolar disorder PRSs; 2·00 (1·92-2·08), p<0·0001 for schizophrenia PRSs). Although women with bipolar disorder also had higher major depression PRSs than did controls (1·24 [1·17-1·31], p<0·0001), women with first-onset post-partum psychosis did not differ from controls in their polygenic liability to major depression (0·97 (0·82-1·11), p=0·63). Our study supports the recognition of first-onset post-partum psychosis as a separate nosological entity within the bipolar disorder spectrum both in research and clinical settings. Wellcome Trust and Medical Research Council.

W23. THE POSTPARTUM PSYCHOSIS INTERNATIONAL CONSORTIUM: RESULTS FROM GENOTYPE-PHENOTYPE ANALYSES

For more than 150 years, controversy over the status of post-partum psychosis has hindered research and caused considerable confusion for clinicians and women, with potentially negative consequences. We aimed to explore the hypothesis that genetic vulnerability differs between women with first-onset post-partum psychosis and those with bipolar disorder more generally.In this case-control study on first-onset post-partum psychosis and bipolar disorder in the UK, we included 203 women with first-onset post-partum psychosis (defined as a manic, mixed, or psychotic depression episode within 6 weeks of delivery without a psychiatric history) and 1225 parous women with a history of bipolar disorder. Information on women with bipolar disorder was obtained from the Bipolar Disorder Research Network database, and participants were recruited through screening community mental health teams across the UK and via the media and patient support organisations. All were assessed using a semistructured face-to-face psychiatric interview and psychiatric case note review. 2809 women from the general population were recruited via the national UK Blood Services and the 1958 Birth Cohort (UK National Child Development Study) as controls and matched to cases according to genetic ancestry. All self-reported their ethnicity as White and were recruited from across the UK. Polygenic risk scores (PRSs) were generated from discovery genome-wide association studies of schizophrenia, bipolar disorder, and major depression. Logistic regression was used to model the effect of each PRS on diagnosis, and the RRs and ORs presented were adjusted for ten principal components of genetic variation to account for population stratification.203 women with first-onset post-partum psychosis (median age at interview: 46 years [IQR 37–55]) and 1225 women with bipolar disorder (49 years [41–58]) were recruited between September, 1991, and May, 2013, as well as 2809 controls. Women with first-onset post-partum psychosis had similar bipolar disorder and schizophrenia PRSs to women with bipolar disorder, which were significantly higher than those of controls. When compared with controls, women with first-onset post-partum psychosis had an adjusted relative risk ratio (RR) for bipolar disorder PRSs of 1·71 (95% CI 1·56–1·86, p<0·0001) and for schizophrenia PRSs of 1·82 (1·66–1·97, p<0·0001). The effect sizes were similar when comparing women with bipolar disorder to controls (adjusted RR 1·77 [1·69–1·84], p<0·0001 for bipolar disorder PRSs; 2·00 (1·92–2·08), p<0·0001 for schizophrenia PRSs). Although women with bipolar disorder also had higher major depression PRSs than did controls (1·24 [1·17–1·31], p<0·0001), women with first-onset post-partum psychosis did not differ from controls in their polygenic liability to major depression (0·97 (0·82–1·11), p=0·63).Our study supports the recognition of first-onset post-partum psychosis as a separate nosological entity within the bipolar disorder spectrum both in research and clinical settings.Wellcome Trust and Medical Research Council.

Migraine as a risk factor for mixed symptoms of peripartum depression and anxiety in late pregnancy: A prospective cohort study

BackgroundMigraine has been identified as a risk factor for peripartum depression. However, little is known about the contribution of anxiety to this association or potential changes throughout the peripartum period. MethodsIn a sample of 4,831 women from the Biology, Affect, Stress, Imaging and Cognition cohort in Sweden, participants were asked about history of migraine prior to pregnancy. The participants completed the Edinburgh Postnatal Depression Scale (EPDS) at gestational weeks 17 and 32 and postpartum week 6. Multinomial logistic regression analyses were used to assess associations between migraine and symptoms of depression, anxiety or mixed depression and anxiety, while adjusting for potential confounders. ResultsIn crude estimates, migraine was associated with separate and mixed symptoms of depression and anxiety at most time points. After adjustments, migraine was associated with anxiety at week 17 (adjusted odds ratio: 1.69; 95% confidence interval: 1.11–2.54) and with mixed depression and anxiety at week 32 (adjusted odds ratio: 1.45; 95% confidence interval: 1.06–1.99). None of the other associations remained statistically significant after adjustments. LimitationsMigraine history was self-reported. Symptoms of depression and anxiety were based on the screening tool EPDS and not on clinical diagnoses. ConclusionsThe results demonstrate that migraine may be a risk factor for anxiety in mid- pregnancy and mixed symptoms of peripartum depression and anxiety in late pregnancy. Inflammatory and hormonal factors may underlie the association between migraine, depression and anxiety across the peripartum period.