Bipolar Disorder: An Integrated Neuroscience and Neuropsychological Review

Bipolar disorder (BD) is a chronic and heterogeneous psychiatric condition with recurrent manic, hypomanic, and depressive episodes, and significant psychosocial dysfunction. Besides mood disturbances, converging evidence shows that cognitive, brain circuit, neurotransmission, inflammation, cellular energy metabolism and synaptic plasticity abnormalities persist. This narrative review synthesises molecular neuroscience, neuroimaging and neuropsychological studies on the possibility of biological changes and their role in cognitive and behavioural symptoms in BD. Dysfunction of prefrontal, limbic, hippocampal, anterior cingulate and associated networks has been suggested to underlie disrupted emotional processing, executive function, memory, attention and processing speed. Neurotransmitter systems such as dopamine, serotonin, glutamate and γ-aminobutyric acid (GABA) do not act alone but instead engage in interactions with intracellular signalling, calcium homeostasis, oxidative stress, mitochondrial function and with the neuroimmune processes. The role of neuroinflammatory and neurotrophic mechanisms in the modulation of neuronal resilience and synaptic plasticity is likely to be further modulated, but findings from biomarkers remains inconsistent depending on mood state, therapy and methodologic issues. However, improved understanding of how these mechanisms work has come from structural and functional neuroimaging, diffusion imaging, electroencephalography, and molecular approaches, but these measures are not yet clinically validated and are not suitable for use as biomarkers in routine clinical diagnosis or treatment selection. Neuropsychological assessment is also important as a complementary assessment to identify cognitive profiles that may remain before and after the acute mood phase and that may be involved in functional disability. The integration of biological and neuropsychological information then may help to inform more personalized assessment and intervention. Longitudinal studies, standardized phenotyping, multimodal studies, use of digital measures, machine learning, and validation of biomarkers in clinically diverse groups should be the focus of future research. In general, a combined neuroscience/neuropsychology approach to the study of BD may be more informative and support the individualized design of treatment plans aimed at mental functioning.