Projects

Goal 1: Identification of neurocognitive biomarkers of neuropsychiatric conditions

I. VIRDIS – Virtual Reality for Diagnostic Investigation of and Screening for Mental Health Disorders (2024–2027): Funded by the Innovation Fund Denmark. This project aims to develop a VR platform integrated with psychophysiological, eye-tracking and emotional response measures to support diagnostic precision in major depressive disorder, bipolar disorder, psychosis-spectrum disorders, borderline personality disorder, and dissocial personality disorder. Ethics and GDPR approvals have been obtained, VR scenarios – co-developed with patients and clinicians – are being filmed. Recruitment will start in April 2025.

Goal 1: Previous projects

NEAD-Twins – Neuromapping of Endophenotypes for Affective Disorders (2014–2025): Supported by the Lundbeck Foundation and other smaller foundations. This 10-year longitudinal twin study investigates neurocognitive, neuroimaging, and epi-genetic biomarkers of mood disorders to identify predictors of illness onset and relapse. Follow-up assessments completed in the autumn 2024 and data analysis and dissemination are underway.

UBFAL – Emotional bias in monozygotic and dizygotic twins at heritable risk of depression: Negative cognitive bias and aberrant neural processing of emotional faces are trait-marks of depression. Yet it is unclear whether these changes constitute an endophenotype for depression and is also present in healthy individuals with hereditary risk for depression. In the first study of monozygotic twins, we investigated never-depressed twins at high risk of de-pression (indexed by depression in their co-twins) and healthy twins at low risk of depression (no personal or co-twin history of psychiatric disorder) with neurocognitive tests and fMRI. The results revealed different neural response and functional connectivity within fronto-limbic and occipito-parietal regions during emotional face processing and enhanced fear vigilance in healthy high-risk twins. This adds to the growing evidence for abnormalities in the processing of emotional faces as a key endophenotype for depression. In a second study of dizygotic high risk or low risk twins from the same cohort, we observed an unexpected, reduced fear vigilance and lowered recognition of fear and happiness in high risk twins. During face processing in the scanner, high risk dizygotic twins also displayed distinct negative fronto-limbic connectivity and reduced fronto-occipital response to all emotional faces. The findings point to putative neurocognitive and neuronal compensatory mechanisms in dizygotic twins who remain healthy despite their familial risk.

Goal 2: Understanding neurobiological mechanisms of cognitive impair-ment and trajectories

I. TRANSCIN – Transdiagnostic and Diagnosis-Specific Features of Cognitive Impair-ment in Neuropsychiatric Populations (2023–2026): Supported by the Bagger-Sørensen Foundation. This study uses Danish health registries and online cognitive test-ing (N=50,000) as an innovative recruitment strategy to identify individuals with enriched cognitive impairments across autism, ADHD, bipolar disorder, and major depressive disorder (sub-study 1). This targeted approach enables in-depth phenotyping of a focused sample (N=300) through neuroimaging, comprehensive cognitive testing, psychiatric assessments, and blood sampling (sub-study 2). The project establishes a scalable model for studying cognitive impairments and supports future observational and intervention research.

II. PREDICT-10 – Prediction of Cognitive and Brain Trajectories in Bipolar Disorder: A 10-Year Neurobiological Study (2025–2028): With support from the Independent Research Fund Denmark, this long-term longitudinal study integrates neuroimaging, biological, and smartphone-based measures obtained 8-10 years ago with new neuroimaging, biological and clinical measures to identify multilevel biomarkers predicting cognitive and brain changes over time in a large sample (N>500) of individuals with bipolar disorder, relatives, and controls.

Goal 2: Previous projects

BIO-3 – Bipolar Illness Onset study, work package 3: Longitudinal study of a large cohort of newly diagnosed patients with bipolar disorder, their unaffected relatives, and healthy con-trols over a 16-month follow-up period. Results suggest that remitted patients with bipolar disorder and their unaffected relatives show persistent widespread impairments in emotional and non-emotional cognition compared to controls. These trait-related cognitive impairments are associated with (hypo)manic relapse during a 16-month follow-up period, suggesting that cognitive impairments influence the early course in recently diagnosed patients. Moreover, patients exhibit prefrontal hypo-activity during attempts to down-regulate their emotions, which remains stable over a 16-month follow-up and predicts increased likelihood of subsequent relapse.

Goal 3: Neurocognitive screening tools and prophylactic affective cognitive training

I. PACT – Prenatal Affective Cognitive Training to Reduce the Risk of Postpartum De-pression (2022–2025): A randomized controlled trial supported by the Mental Health Services Research Fund investigates the prophylactic effects of affective cog-nitive training in pregnant women at high risk for PPD. The intervention builds on evidence supporting affective cognitive training for depression, integrating cognitive and attention bias modification, mindfulness-based emotion regulation, and working memory training. Partici-pants randomized to PACT undergo individualized computer and virtual reality-based sessions over five weeks.

II. PREPARENT – Internet-Based Digital Tools to Screen for and Prevent Postpartum Depression in Parents-to-Be (2023–2027): With support from the Mental Health Services Research Fund, this study uses online screening to identify cognitive risk factors for PPD and tests the potential prophylactic effects of a novel internet-based affective cognitive training program for high-risk expectant parents. Ethics approval has been secured, and the digital intervention design will be finalised by January 2025. Following this, a pilot study with a small sample will be conducted before scaling up to a national implementation.

III. SYNCARE – Synchrony in Mother-Child Interaction and Child Mental Development in Diverse Family Risk Profiles (2025–2028): This study, supported by the Independent Research Fund Denmark, investigates the long-term effects of maternal PPD risk screening and prenatal affective cognitive training interventions on mother-child interaction and child development.

Goal 3: Previous projects

HEAPAD – Cognitive processing of infant stimuli in pregnant women with and without affective disorders and the association to postpartum depression: Pregnancy and childbirth are among the strongest risk factors for depression, affecting 10-15% of women. Notwith-standing the importance of mothers’ mental health for the early mother-child interactions, there are no available methods to accurately predict who will develop postpartum depression. In a recently completed study, we investigated interpretation of infants’ signals of emotion in pregnant women with and without affective disorders in remission. Healthy pregnant women rated infant cries less negatively than non-pregnant women, which may indicate an increased ability to tolerate infant distress perhaps as a preparation for motherhood. In contrast, preg-nant women with unipolar disorder exhibited a negative bias in ratings of infant cries, which may be a marker of more sensitivity to infant signals of distress. Pregnant women with bipolar disorder showed a positive bias in ratings of infant faces and greater recognition of positive than negative facial expressions. Across all pregnant women, bias in the ratings of infant cry was associated with more risk of postpartum depression. The findings point to putative neu-rocognitive mechanisms involved in risk of postpartum depression.

MIPAD – Mother-infant Interaction, Psychophysiological and neurocognitive responses to infant emotion in mothers with Affective Disorders: For parents with bipolar disorder, there is a 50-60 % risk that the child will develop a psychiatric disorder. Genetic factors play a key role in the intergenerational transmission of psychiatric disorder, but it is unclear how early environmental risk factors interact with genetic vulnerability in this process. Using a multi-disciplinary approach, we demonstrated that symptomatically stable mothers with affective disorders display aberrant psychophysiological and neurocognitive responses to infants’ emotional signals. Healthy mothers showed increased vigilance toward infant stimuli compared with non-mothers, but this ‘maternal vigilance’ was attenuated in mothers with affective dis-orders. Mothers with unipolar disorder expressed more negative facial emotion when listening to infant cry and their attention was more directed towards sad and away from happy infant faces. In contrast, mothers with bipolar disorder expressed less attuned facial expressions while watching infant distress signals and – during fMRI – displayed reduced dorsal prefron-tal response while watching own infants’ faces. Importantly, the decreased maternal vigilance and emotional biases were associated with some difficulties in mother-infant interaction and delays in infant development. The findings have implications for understanding neurocogni-tive changes in mothers that may confer early subtle environmental risk for the infant and, ultimately, contribute to the intergenerational transmission of risk.

Goal 4: Design and testing of novel pro-cognitive interventions

I. CAVIR – Cognitive Assessment and Intervention in Virtual Reality for Patients with Mood or Psychosis Spectrum Disorders (2022–2025): This randomized controlled trial, supported by TrygFonden, concluded in October 2024 with follow-up testing in December 2024. Results revealed the efficacy of VR-based cognitive remediation in improving real-life cognitive and functional outcomes after treatment. The improvements were linked to increased dorsal prefrontal activity during memory encoding, correlating with cognitive gains.

II. ALTIBRAIN – Altitude-Like Hypoxia Cognition Training to Target Brain Erythro-poietin (2022–2027): Supported by the European Research Council. This multidisciplinary translational study explores the impact of low oxygen exposure on neuroplasticity and cognition in humans and mice. Based on our finding that low ambient oxygen upregulates brain EPO, enhancing neuroplasticity and cognition in mice, ALTIBRAIN investigates whether this mechanism can induce similar long-lasting effects across healthy participants and patients with psychiatric conditions. Using neuropsychology, neuroimaging, and neuroscience techniques, we examine whether a 3-week in-termittent low oxygen exposure combined with cognitive training triggers sufficient brain EPO expression to replicate the effects observed with exogenous EPO.

III. EPIC – Epigenetic Priming to Enhance Cognitive Training Across Mice and Humans with Neuropsychiatric Disorders (2025–2029): With support from the Independent Research Fund Denmark, this multidisciplinary, translational study investigates the effects of histone deacetylase inhibitors (HDACi) combined with cognitive training to enhance synaptic plasticity and cognition. Specifically, EPIC explores whether combining a HDACi with cognitive training can produce long-lasting improvements in cognition and neuroplasticity in humans and mice.

IV. BACE – Brain marker for Affective Cognitive Enhancement following targeted training in patients with mood disorders and high-risk relatives: A randomized controlled trial (2025-2028): Funded by the Independent Research Fund Denmark. This trial aims to apply targeted socio-emotional cognitive training in a subgroup of globally impaired patients and relatives to investigate changes in underlying neural activity and associations with illness prognosis over time. This study provides personalized intervention strategies to inform treatment and mitigate the risk of adverse illness course and illness onset.

Goal 4: Previous projects

EPO trials – Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder: There is a need for more effective treatments that aid cognitive functions in depression and bipolar disorder. Erythropoietin (EPO) is involved in neuroplasticity and is a candidate for treatment of cognitive dysfunction and mood symptoms affective disorders. We therefore conducted two parallel randomized controlled clinical phase II trials in treatment-resistant (unipolar) depression and bipolar disorder in remission to exam-ine the effects of 8 weeks of weekly EPO vs. saline infusions on mood and cognition in these groups. Beneficial (mood-independent) effects of EPO were found on cognitive function across both patient groups. In contrast, there was no clear beneficial effect of EPO on the pri-mary measure of mood in treatment-resistant depression (although EPO significantly im-proved self-rated depression and quality of life; tertiary outcome measures in the trial). The findings highlight EPO as a promising candidate treatment to target deficits in neuroplasticity and cognition in affective disorders.

PRETEC-EPO – Prefrontal Target Engagement as a biomarker model for Cognitive im-provement – Erythropoietin: The lack of treatments with solid and enduring pro-cognitive efficacy is related to major methodological challenges in the field, including the absence of a brain-based biomarker model to select among candidate treatments. In our PRETEC-EPO trial, we therefore investigated whether weekly EPO vs. placebo (saline) treatment for 12 weeks can improve cognitive functions in cognitively impaired patients with affective disor-ders as well as the early neuronal changes associated with such effects. No pro-cognitive effects were found on the primary outcome.

REMEDI – Effects of Short-Term Cognitive Remediation on Cognitive Dysfunction in Partially or Fully Remitted Individuals with Bipolar Disorder: Cognitive remediation (CR) is a psychological intervention that aims to improve cognitive function, compensational skills, coping skills and, consequently, psychosocial function. Based on substantial evidence for beneficial effects of CR in patients with schizophrenia, we conducted the first RCT of CR in bipolar disorder. The trial examined whether 12 weeks group-based CR improves cognition in remitted patients with bipolar disorder who experienced moderate to severe cognitive difficulties. No significant beneficial effects were observed on objectively measured cognitive function, suggesting that more intensive, individualized interventions may be necessary.

PRETEC-ABC- Effect of Action-Based Cognitive Remediation on cognitive impairment in patients with remitted bipolar disorder: In this RCT, we investigated the effects of a new intensive 10-week cognitive remediation intervention, Action-Based Cognitive Remediation (ABCR), in bipolar disorder. The intervention involved two weekly group-based training sessions and daily computer training between sessions. The parallel control group involved weekly unstructured group sessions supervised by a therapist. ABCR produced no significant improvement in a global cognition (primary outcome) but a strong improvement in executive functions (secondary outcome) and subjective cognitive functions (tertiary outcome). Importantly, ABCR treatment benefits on executive function was predicted by greater baseline executive dysfunction.

Goal 5: Large-scale initiatives to promote understanding of cognitive health

I. TRANSCIN – Transdiagnostic and Diagnosis-Specific Features of Cognitive Impairment sub-study 1 (2023–2026): Supported by the Bagger-Sørensen Foundation, this large-scale study tests up to 50,000 individuals, including those with neuropsychi-atric and neurodevelopmental conditions and healthy controls. In sub-study 1, we link online cognitive performance data to Danish registry data to identify risk and protective factors for cognitive impairments within and across diagnostic groups (for sub-study 2 aims, see the de-scription under Goal 2).

II. ICARE – Implementing Online Cognitive Assessment in Psychiatric Outpatient Clinics (2024–2027): Funded by the Independent Research Fund Denmark. ICARE integrates ICAT-based assessments into outpatient clinics for mood disorders, analysing data from 400 patients with bipolar or unipolar disorders. It examines patterns of cognitive impairments, their socio-economic impacts, and establishes a scalable framework for digital cognitive screening when systematically integrated in clinical settings.

Both projects leverage registry-based recruitment, innovative sampling strategies, and non-response analyses to ensure data representativeness.

Sidst opdateret: 21. april 2026

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