Publications by authors named "David Andrew Cousins"

7 Publications

  • Page 1 of 1

Lithium effects on Hippocampus volumes in patients with bipolar disorder.

J Affect Disord 2021 Nov 18;294:521-526. Epub 2021 Jul 18.

Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Electronic address:

Background: Lithium is one of the most effective medications for bipolar disorder episode prevention, but its mechanism of action is still largely unknown. The hippocampus is a subcortical cerebral structure involved in the formation of emotional responses, cognition and various primitive functions, altered during affective episodes. Deviations in the anatomy or physiology of the hippocampus would partially explain the symptomatology of bipolar subjects, and restoration may reflect treatment response.

Methods: In this mini review, we summarize the studies which have investigated the effect of lithium intake on the volume of hippocampus, measured using magnetic resonance imaging (MRI). We performed a bibliographic search on PubMed, using the terms terms "hippocampus", "lithium", "bipolar disorder", "volume" and "MRI". Only original studies were considered.

Results: Thirteen studies met the inclusion criteria. Nine studies demonstrated increased total hippocampal volume or hippocampal subfield volumes in BD patients on lithium treatment (Li BD) compared to those not taking lithium (non-Li BD), while four failed to show significant differences between groups. When healthy controls were compared to either the Li subjects or the non-Li ones, the findings were more heterogeneous.

Limitations: Heterogeneity in the methodology and definition of groups limits the comparison of study results.

Conclusions: Lithium may be associated with increased hippocampal volume in BD, potentially due to its putative neurotrophic action, but further research is needed better define the morphological alterations of hippocampus in BD and the longitudinal effects of lithium in the short and long-term.
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November 2021

Quantification of brain proton longitudinal relaxation (T ) in lithium-treated and lithium-naïve patients with bipolar disorder in comparison to healthy controls.

Bipolar Disord 2021 02 2;23(1):41-48. Epub 2019 Dec 2.

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

Background: Proton longitudinal relaxation (T ) is a quantitative MRI-derived tissue parameter sensitive to myelin, macromolecular, iron and water content. There is some evidence to suggest that cortical T is elevated in bipolar disorder and that lithium administration reduces cortical T . However, T has not yet been quantified in separate groups containing lithium-treated patients, lithium-naïve patients, and matched healthy controls.

Methods: Euthymic patients with bipolar disorder receiving lithium (n = 18, BDL) and those on other medications but naïve to lithium (n = 20, BDC) underwent quantitative T mapping alongside healthy controls (n = 18, HC). T was compared between groups within the cortex, white matter and subcortical structures using regions of interest (ROI) derived from the Desikan-Killiany atlas. Effect sizes for each ROI were computed for BDC vs BDL groups and Bipolar Disorder vs HC groups.

Results: No significant differences in T were identified between BDL and BDC groups when corrected for multiple comparisons. Patients with bipolar disorder had significantly higher mean T in a range of ROIs compared to healthy controls, including bilateral motor, somatosensory and superior temporal regions, subcortical structures and white matter.

Conclusions: The higher T values observed in the patients with bipolar disorder may reflect abnormal tissue microstructure. Whilst the precise mechanism remains unknown, these findings may have a basis in differences in myelination, macromolecular content, iron and water content between patients and controls.
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February 2021

White matter microstructural properties in bipolar disorder in relationship to the spatial distribution of lithium in the brain.

J Affect Disord 2019 06 18;253:224-231. Epub 2019 Apr 18.

Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom; Interdisciplinary Computing and Complex BioSystems (ICOS), School of Computing Science, Newcastle University, Newcastle upon Tyne, NE1 5TG, United Kingdom; Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.

Background: Lithium treatment is associated with an increase in magnetic resonance imaging derived measures of white matter integrity, but the relationship between the spatial distribution of brain lithium and white matter integrity is unknown.

Methods: Euthymic patients with bipolar disorder receiving lithium (n = 12) and those on other medications but naïve to lithium (n = 17) underwent diffusion imaging alongside matched healthy controls (n = 16). Generalised fractional anisotropy (gFA) within white matter was compared between groups using a standard space white matter atlas. Lithium-treated patients underwent novel multinuclear lithium magnetic resonance imaging (Li-MRI) to determine the relative lithium concentration across the brain. The relationship between Li-MRI signal intensity and gFA was investigated at the resolution of the Li-MRI sequence in native space.

Results: Lithium-treated bipolar disorder and healthy control groups had higher mean white matter gFA than the bipolar disorder group treated with other medications (t = 2.5, p < 0.05; t = 2.7, p < 0.03, respectively). No differences in gFA were found between patients taking lithium and healthy controls (t = 0.02, p = 1). These effects were seen consistently across most regions in the white matter atlas. In the lithium-treated group, a significant effect of the Li-MRI signal in predicting the gFA (p < 0.01) was identified in voxels containing over 50% white matter.

Limitations: Cross-sectional evaluation of a relatively small cohort.

Conclusions: The higher gFA values observed in the lithium-treated bipolar disorder group suggests that long-term lithium is associated with greater white matter integrity. Our novel analysis supports this further, showing a positive association between white matter gFA and the spatial distribution of lithium.
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June 2019

Sleep Disturbance and the Change from White to Red Lighting at Night on Old Age Psychiatry Wards: A Quality Improvement Project.

Arch Psychiatr Nurs 2018 06 5;32(3):379-383. Epub 2017 Dec 5.

Institute of Neuroscience, Newcastle University, Newcastle upon Tyne NE1 7RU, United Kingdom. Electronic address:

Psychiatric inpatient units often maintain a degree of lighting at night to facilitate the observation of patients, but this has the potential to disrupt sleep. Certain wavelengths of light may be less likely to disturb sleep and if such lighting permitted adequate observations, patient wellbeing may be improved.

Aims And Method: This study explored the effects of changing night-lights from broad-band white to narrow-band red on the amount of sleep observed, 'as required' medication administered and number of falls, in an old age psychiatry inpatient setting. Qualitative data was also gathered with a staff questionnaire. We hypothesised that compared to the use of white lights, red lights would be associated with a greater amount of recorded sleep, lesser use of 'as required' medication and no increase in the number of falls (reflecting comparable safety).

Results: Whilst there were no significant differences in quantitative measures recorded, there were more observations of sleep during the red light period than the white light period (14.1 versus 13.9 times per night) (U=627.5, z=-0.69, p=0.49) and fewer 'as required' medication administrations during the red light period compared to the white light period (3.3 versus 4.8 times per night) (U=640.0, z=0.56, p=0.57). Qualitatively, the staff of the organic assessment unit reported that patients were sleeping better and less agitated at night.

Clinical Implications: Larger and more in-depth studies are required to examine the full effectiveness of using safe, sleep-enhancing lighting on wards at night.
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June 2018

3D Li magnetic resonance imaging of brain lithium distribution in bipolar disorder.

Mol Psychiatry 2018 11 9;23(11):2184-2191. Epub 2018 Feb 9.

Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

Lithium is a major treatment for bipolar disorder and the likelihood of a favourable response may be determined by its distribution in the brain. Lithium can be directly detected by magnetic resonance (MR), but previous Li MR spectroscopy studies have demonstrated that this is challenging compared to conventional H MR imaging due to the MR properties of the lithium nucleus and its low concentration in brain tissue, as dictated by therapeutic dose. We have tested and implemented a highly efficient balanced steady-state free precession Li-MRI method to address these challenges and enable MRI of brain lithium in a short duration scan. We report a 3D Li-MRI acquisition with 25 mm isotropic resolution in an 8-min scan that demonstrates heterogeneity in lithium concentration within the brain in subjects with bipolar disorder. This represents the direct imaging of a pharmaceutical agent in its target organ and notably expands the repertoire of techniques available to investigate the effects of lithium in man.
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November 2018

Acetylcholinesterase inhibitors in treatment-resistant psychotic depression.

Ther Adv Psychopharmacol 2018 Jan 10;8(1):59-61. Epub 2017 Jul 10.

Regional Affective Disorders Service, Northumberland Tyne and Wear NHS Foundation Hospital Trust, Newcastle upon Tyne, UK, and Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.

Dopamine receptor antagonists can be effective in psychotic depression but response is not assured. Visual hallucinations may arise from a dysregulation of brain cholinergic systems and acetylcholinesterase inhibitors (AChEIs) can treat such hallucinations in dementia with Lewy bodies (DLB). AChEIs have been used in schizophrenia with some success but their efficacy and tolerability in psychotic depression is unclear. This striking case illustrates AChEIs specifically targeting multimodal hallucinations in treatment-resistant depression. To our knowledge it is the first case report to do so. It highlights the value of delineating psychopathology when considering novel interventions. This case also shows the idiosyncratic nature of side effects and the importance of pursuing different drugs within class.
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January 2018

Brain networks: foundations and futures in bipolar disorder.

J Ment Health 2010 Apr;19(2):157-67

Department of Psychiatry, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.

Background: Bipolar affective disorder is a common psychiatric illness with an often episodic nature, the neurobiological basis of which remains elusive. Symptom clusters in bipolar disorder can be conceptualized in terms of disordered brain networks, and doing so may aid our understanding of the varied presentations, differing illness courses and treatment responses.

Aims: To review the rationale behind proposed disordered brain network function in bipolar disorder and the evidence of network dysfunction from imaging studies together with an overview of more novel techniques pertinent to this field.

Methods: Medline databases were searched using the terms bipolar disorder, imaging, connectivity and brain networks. Relevant articles were reviewed and bibliographic cross-referencing was used to focus on key areas of interest, supplemented by additional Medline searches as required.

Results: Structural and functional imaging studies support the concept of brain network dysfunction in bipolar disorder. Novel techniques such as diffusion tensor imaging and resting state network analysis can assess such dysfunction more directly, but there are few studies specific to bipolar disorder.

Conclusions: Brain network dysfunction is a useful framework for considering the varied presentations of bipolar disorder. Advanced imaging techniques are increasingly available, with the potential to provide insights into this important area.
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April 2010