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Background: Identification of endophenotypes can improve prevention, detection and development of new treatments. We therefore investigated whether aberrant affective cognition constitutes an endophenotype for affective disorders by being present in monozygotic (MZ) twins with unipolar or bipolar disorder in partial remission (i.e. affected) and their unaffected co-twins (i.e. high-risk) relative to twins with no family history of affective disorder (i.e. low-risk). Methods: We conducted an assessor blind cross-sectional study from 2014 to 2017 of MZ twins using Danish population-based registers in recruitment. Twins attended one test session involving neurocognitive testing, clinical ratings and questionnaires. Main outcomes were attention to and recognition of emotional facial expressions, the memory of emotional self-referential words, emotion regulation and coping strategies. Results: Participants were 103 affected, 44 high-risk and 36 low-risk MZ twins. Groups were demographically well-balanced and showed comparable non-affective cognitive performance. We observed no aberrant affective cognition in affected and high-risk relative to low-risk twins. However, high-risk twins displayed attentional avoidance of emotional faces (p s ⩽ 0.009) and more use of task-oriented coping strategies (p = 0.01) compared with affected twins. In contrast did affected twins show more emotion-oriented coping than high- and low-risk twins (p s ⩽ 0.004). Conclusions: Our findings provide no support of aberrant affective cognition as an endophenotype for affective disorders. High-risk twins' attentional avoidance of emotional faces and greater use of task-oriented coping strategies may reflect compensatory mechanisms. [ABSTRACT FROM AUTHOR]

Objective: Affective disorders seem associated with aberrant intestinal microbiota but whether this pattern also occurs in individuals at increased heritable risk is unknown. We investigated associations between gut microbiota profiles and affective disorders by comparing monozygotic (MZ) twins concordant (affected twins with unipolar or bipolar disorder in remission) and discordant to affective disorders (high‐risk) with MZ twins without affective disorders (low‐risk). Methods: Stool samples were collected from 128 MZ twins and the microbiome was profiled using 16S rDNA sequencing of the V3–V4 region. Results: Affected twins had a lower diversity and an absence of a specific operational taxonomical unit (OTU) in comparison with low‐risk twins. The high‐risk twins exhibited the same pattern although the lower diversity was only at a trend level. The OTU belonged to the family Christensenellaceae. The findings were not explained by lifestyle factors (smoking, alcohol consumption, body mass index, or psychotropic medication). Conclusion: Affected twins in remission and high‐risk twins presented aberrant gut microbiota with depletion of a specific OTU. If replicated, this reduced relative sequence absence may together with the globally altered microbiota composition act as a vulnerability marker by accentuating the effect of gene–environment interactions in individuals genetically disposed for an affective disorder. [ABSTRACT FROM AUTHOR]

Objective: Bipolar disorder is associated with impairments in social cognition including the recognition of happy faces. This is accompanied by imbalanced cortico‐limbic response to emotional faces. We found that EPO improved the recognition of happy faces in patients with bipolar disorder. This randomized, controlled, longitudinal fMRI study explores the neuronal underpinnings of this effect. Method: Forty‐four patients with bipolar disorder in full or partial remission were randomized to eight weekly erythropoietin (EPO; 40 000 IU) or saline (NaCl 0.9%) infusions in a double‐blind, parallel‐group design. Participants underwent whole‐brain fMRI at 3T, mood ratings and blood tests at baseline and week 14. During fMRI, participants viewed happy and fearful faces and performed a gender discrimination task. Results: Thirty‐four patients had complete pre‐ and post‐treatment fMRI data (EPO: N = 18, saline: N = 16). Erythropoietin vs. saline increased right superior frontal response to happy vs. fearful faces. This correlated with improved happiness recognition in the EPO group. Erythropoietin also enhanced gender discrimination accuracy for happy faces. These effects were not influenced by medication, mood, red blood cells or blood pressure. Conclusions: Together with previous findings, the present observation suggests that increased dorsal prefrontal attention control is a common mechanism of EPO‐associated improvements across several cognitive domains. [ABSTRACT FROM AUTHOR]

Objective The neurobiological mechanisms mediating an increased risk to develop affective disorders remain poorly understood. In a group of individuals with a family history of major depressive ( MDD) or bipolar disorder ( BD), we investigated the microstructural properties of white matter fiber tracts, that is, cingulum bundle, uncinate fasciculus, anterior limb of the internal capsule, and corpus callosum, that facilitate the communication between brain regions implicated in affective disorders. Method Eighty-nine healthy mono- or dizygotic twins with a co-twin diagnosed with MDD or BD (high-risk) and 57 healthy twins with a co-twin with no familial history of affective disorders (low-risk) were included in a diffusion tensor imaging study. Result The high-risk group showed decreased fractional anisotropy ( FA), a measure of water diffusion directionality, and increased radial diffusivity in the anterior region of corpus callosum compared to the low-risk group. This abnormality was not associated with zygosity or type of depressive disorder of co-twin. Conclusion The observed decreased anterior callosal fiber FA in the high-risk group may be indicative of a compromised interhemispheric communication between left and right frontal regions critically involved in mood regulation. Reduced anterior callosal FA may act as a vulnerability marker for affective disorders in individuals at familial risk. [ABSTRACT FROM AUTHOR]

Objective Erythropoietin ( EPO) improves verbal memory and reverses subfield hippocampal volume loss across depression and bipolar disorder ( BD). This study aimed to investigate with functional magnetic resonance imaging (f MRI) whether these effects were accompanied by functional changes in memory-relevant neuro-circuits in this cohort. Method Eighty-four patients with treatment-resistant unipolar depression who were moderately depressed or BD in remission were randomized to eight weekly EPO (40 000 IU) or saline infusions in a double-blind, parallel-group design. Participants underwent whole-brain f MRI at 3T, mood ratings, and blood tests at baseline and week 14. During f MRI, participants performed a picture encoding task followed by postscan recall. Results Sixty-two patients had complete data ( EPO: N = 32, saline: N = 30). EPO improved picture recall and increased encoding-related activity in dorsolateral prefrontal cortex (dl PFC) and temporo-parietal regions, but not in hippocampus. Recall correlated with activity in the identified dl PFC and temporo-parietal regions at baseline, and change in recall correlated with activity change in these regions from baseline to follow-up across the entire cohort. The effects of EPO were not correlated with change in mood, red blood cells, blood pressure, or medication. Conclusion The findings highlight enhanced encoding-related dl PFC and temporo-parietal activity as key neuronal underpinnings of EPO-associated memory improvement. [ABSTRACT FROM AUTHOR]

BackgroundCognitive dysfunction in depression and bipolar disorder (BD) is insufficiently targeted by available treatments. Erythropoietin (EPO) increases neuroplasticity and may improve cognition in mood disorders, but the neuronal mechanisms of these effects are unknown. This functional magnetic resonance imaging (fMRI) study investigated the effects of EPO on neural circuitry activity during working memory (WM) performance.MethodPatients with treatment-resistant major depression, who were moderately depressed, or with BD in partial remission, were randomized to eight weekly infusions of EPO (40 000 IU) (N = 30) or saline (N = 26) in a double-blind, parallel-group design. Patients underwent fMRI, mood ratings and blood tests at baseline and week 14. During fMRI patients performed an n-back WM task.ResultsEPO improved WM accuracy compared with saline (p = 0.045). Whole-brain analyses revealed that EPO increased WM load-related activity in the right superior frontal gyrus (SFG) compared with saline (p = 0.01). There was also enhanced WM load-related deactivation of the left hippocampus in EPO-treated compared to saline-treated patients (p = 0.03). Across the entire sample, baseline to follow-up changes in WM performance correlated positively with changes in WM-related SFG activity and negatively with hippocampal response (r = 0.28–0.30, p < 0.05). The effects of EPO were not associated with changes in mood or red blood cells (p ⩾0.08).ConclusionsThe present findings associate changes in WM-load related activity in the right SFG and left hippocampus with improved executive function in EPO-treated patients. Clinical trial registration: clinicaltrials.gov: NCT00916552. [ABSTRACT FROM AUTHOR]

Objective: To examine whether a high genetic liability to develop affective disorder is associated with specific personality traits. Method: A cross-sectional, high-risk, case–control study. Through nation-wide registers, healthy monozygotic (MZ) and dizygotic (DZ) twins with (high-risk twins) and without (the control group/low-risk twins) a co-twin history of affective disorder were identified. Personality traits were compared for a total of 211 high-risk and low-risk twins. Results: In univariate analyses, the high-risk twins had a higher level of neuroticism than the control twins ( P = 0.03). In multivariate analyses, a high genetic liability to affective disorder was not significantly associated with neuroticism but correlated to sex, minor psychopathology and recent life events. Conclusion: A high genetic liability to affective disorder showed an association with neuroticism, but the association interacts with other predictors of affective disorder such as female gender, minor psychopathology and recent adversity. [ABSTRACT FROM AUTHOR]

Introduction: Cognitive dysfunction in unipolar depression (UD) and bipolar disorder (BD) may persist into periods of remission and affect psychosocial function. Attention and memory deficits may be more pronounced during remission in BD compared with UD. However, patients’ subjective experience of cognitive difficulties is poorly understood, and it is unclear whether this differs between BD and UD. Aims and objectives: To examine self-reported cognitive function in remitted patients with BD and UD. Methods: Patients with BD (n=54) and UD (n=45) were referred to the outpatient clinic at Department of Psychiatry, Copenhagen University Hospital, following hospital discharge. Affective symptoms and patients’ experience of cognitive symptoms were assessed at their initial consultation at the clinic. Results: Patients in remission experienced mild to moderate impairment of cognitive function with greatest difficulties in motivation, energy, attention and memory. Subjective experience of cognitive function were similar for BD and UD and were predicted by affective symptoms rather than by diagnosis, age, gender or comorbid alcohol misuse. Conclusions: The absence of differences between UD and BD in the subjective experience of cognitive difficulties contrasts with evidence of greater objective cognitive dysfunction in BD. This highlights a potential discord between subjective and objective measures of cognitive function. The impact of affective symptoms on the subjectively experienced cognitive difficulties suggests that they reflect mood symptoms rather than objective cognitive deficits. Further investigation of the relation between objective and subjective measures of cognitive function and the influence of affective symptoms is warranted. [ABSTRACT FROM AUTHOR]

Pregnancy and childbirth are among the strongest risk factors for depression but the neurocognitive mechanisms underlying this enhanced risk are unknown. This study investigated emotional and non-emotional cognition in 57 pregnant women with or without an affective disorder during their third trimester, and the association between cognitive biases and subsequent postpartum depression (PPD). Of the pregnant women, 22 had a diagnosis of unipolar disorder (UD) and seven of bipolar disorder (BD) in full or partial remission, while 28 had no history of affective disorder. We included a control group of 29 healthy non-pregnant women. First, participants were interviewed, completed non-emotional and emotional cognitive tests and lastly filled out questionnaires. The participants were assessed two times after birth: at a home visit shortly after birth, and with a telephone interview to assess PPD in the first six months after birth. Healthy pregnant women rated infant cries less negatively than non-pregnant women, possibly reflecting preparation for motherhood. Pregnant women with UD exhibited a negative bias in ratings of infant cries, whereas pregnant women with BD showed a positive bias in ratings of infant happy faces and recognition of adult facial expressions. Across all pregnant women, more negative ratings of infant cries were associated with enhanced risk of PPD. Negatively biased perception of infant cries during pregnancy may thus signal vulnerability toward PPD. [ABSTRACT FROM AUTHOR]

Background: Abnormalities in affective cognition are putative endophenotypes for bipolar and unipolar disorders but it is unclear whether some abnormalities are disorder-specific. We therefore investigated affective cognition in monozygotic twins at familial risk of bipolar disorder relative to those at risk of unipolar disorder and to low-risk twins.Methods: Seventy monozygotic twins with a co-twin history of bipolar disorder (n = 11), of unipolar disorder (n = 38) or without co-twin history of affective disorder (n = 21) were included. Variables of interest were recognition of and vigilance to emotional faces, emotional reactivity and -regulation in social scenarios and non-affective cognition.Results: Twins at familial risk of bipolar disorder showed increased recognition of low to moderate intensity of happy facial expressions relative to both unipolar disorder high-risk twins and low-risk twins. Bipolar disorder high-risk twins also displayed supraliminal attentional avoidance of happy faces compared with unipolar disorder high-risk twins and greater emotional reactivity in positive and neutral social scenarios and less reactivity in negative social scenarios than low-risk twins. In contrast with our hypothesis, there was no negative bias in unipolar disorder high-risk twins. There were no differences between the groups in demographic characteristics or non-affective cognition.Limitations: The modest sample size limited the statistical power of the study.Conclusions: Increased sensitivity and reactivity to positive social stimuli may be a neurocognitive endophenotype that is specific for bipolar disorder. If replicated in larger samples, this 'positive endophenotype' could potentially aid future diagnostic differentiation between unipolar and bipolar disorder. [ABSTRACT FROM AUTHOR]

B Background: b Patients with mood disorders exhibit abnormalities in emotional cognition (EC) even during periods of remission [1],[2]. Patients allocated in the "emotionally volatile" and "emotionally blunted" clusters were largely diagnosed with bipolar disorder and presented more deficits in neurocognition than the "emotionally preserved" cluster, especially patients in the "emotionally volatile" cluster. The identification of different EC profiles contributes to the growing evidence of EC heterogeneity in mood disorders and highlights a need to develop of tailored interventions focused on the patients' individual necessity. [Extracted from the article]