Neurons send and receive information via electrical and chemical processes in the brain. Interneurons are a subset of neurons that are involved in the processing and modulation of information. Glial cells are brain cells that play a role in neurodevelopment, neurotransmission, connectivity, brain metabolism, and the clearance of extracellular ions and neurotransmitters. Astrocytes are the most prevalent glial cell and are primarily involved in neurodevelopment. They also regulate synaptic transmission, mediate glutamate reuptake, and aid in the maintenance of the blood-brain barrier. Oligodendrocytes are glial cells that produce myelin that is used for electrical insulation of nerve axons to ensure rapid impulse conduction. Microglia are glial immune cells that are important for the initiation and control of inflammation in the central nervous system.

What is the evidence for cellular changes in people with bipolar disorder?

Moderate to low quality evidence found no consistent changes in the number, density, or size of neurons, interneurons, or glial cells in people with bipolar disorder compared to people without bipolar disorder.

December 2021

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Pending enough primary studies, we invite reviews on this topic to be conducted. Alternatively we will endeavour to conduct our own review to fill this gap in the Library.

December 2021

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DTI is a specialised imaging technique that uses MRI technology to investigate the movement of water within tissues of interest. It is a powerful imaging method for characterising the integrity of white matter circuitry because it links anatomical and functional neuroimaging.

By applying a magnetic field, the movement (“diffusivity”) of water molecules can be visualised in vivo. The diffusion of water is influenced by the cellular structure of the surrounding tissues, and measures such as fractional anisotropy were derived as an approximate measurement for the freedom of movement. In areas of high structural coherence such as white matter, fractional anisotropy is highest, indicating that water is moving in relatively fixed directions. It is lower in grey matter, and close to zero in cerebrospinal fluid, indicating that water is moving freely. Consequently, changes in fractional anisotropy values are interpreted to be representing alterations in the structural integrity of the regional white matter. However, as alterations in fractional anisotropy cannot be linked directly to specific tissue characteristics such as myelination, other measures including radial diffusivity have been investigated to determine the degree of myelination.

Region-of-interest studies assess white matter integrity in individual brain regions, while voxel-based analyses assess whole brain white matter integrity. Tract-based spatial statistics isolates the central core of white matter tracts with the highest fractional anisotropy and reports significant clusters within that white matter skeleton. Three classes of white matter tracts have been identified. Commissural tracts connect the two hemispheres of the brain, association tracts connect regions within the same hemisphere, and projection tracts connect each region to other parts of the brain or spinal cord.

Understanding neurological structural alterations using DTI in people with bipolar disorder may provide insight into the molecular neurobiology of aberrant neurotransmission, by highlighting brain regions where reduced cellular integrity may contribute to symptom expression.

What is the evidence for DTI findings in people with bipolar disorder?

Moderate quality evidence finds decreased fractional anisotropy and increased radical diffusivity in the right corpus callosum, anterior thalamic radiations, fronto-orbito-polar tract, and superior longitudinal fasciculus of people with bipolar disorder. Fractional anisotropy showed additional reductions in the right interstriatal white matter of patients, and radical diffusivity showed additional increases in the right corticospinal tract of patients. There were also decreases in white matter integrity in relatives of people with bipolar disorder in the right corpus callosum body, left corpus callosum splenium, and the left corticospinal tract.

There were similar decreases in people with bipolar disorder and people with schizophrenia in white matter integrity in the genu of the corpus callosum extending to anterior thalamic radiation/cingulum fibres/inferior fronto-occipital fasciculus, and in left posterior cingulum fibres.

December 2021

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MRI is based on the magnetisation properties of cellular protons. The application of a strong magnetic field causes the protons within cells to shift direction, which will return to their original position over time (“precession”). The rate of precession differs across tissue types (such as grey matter and white matter in the brain), which can be interpreted by specialised programs to represent a 3D image.

What is the evidence for MRI findings in people with bipolar disorder?

Grey matter decreases compared to controls

High quality evidence shows small decreases in hippocampal subfields in people with bipolar disorder. Moderate quality evidence also suggests decreases in bilateral insula, superior temporal gyrus, superior and ventral medial prefrontal cortex, anterior cingulate cortex, left dorsalmedial prefrontal cortex, left ventrolateral prefrontal cortex, and right precentral gyrus. Moderate to low quality evidence suggests decreases in left medial frontal, right inferior frontal, precentral frontal, left inferior longitudinal fasciculus, left insula, superior corona radiate, and the left limbic posterior cingulum.

In people with first-episode bipolar disorder, moderate to high quality evidence suggests small decreases in whole brain grey matter. In youth with bipolar disorder, moderate quality evidence found decreases in the left orbitofrontal cortex, right claustrum, and right dorsolateral prefrontal cortex. In people with bipolar disorder and psychotic symptoms (not necessarily diagnosed with bipolar I disorder), moderate quality evidence suggests decreases in bilateral superior frontal gyri, bilateral insula, bilateral median cingulated/paracingulate gyri, left anterior cingulate/paracingulate gyri, and right precentral gyrus (particularly in females). In people diagnosed with bipolar I disorder, decreases were also found in the right superior temporal gyrus, and the rolandic operculum.

Grey matter increases compared to controls

Moderate quality evidence suggests increases in the cerebellum, bilateral middle frontal gyrus, right middle temporal gyrus, right inferior temporal gyrus, the right middle occipital gyrus, left putamen, and left posterior cingulate cortex of people with bipolar disorder. In people diagnosed with bipolar I disorder, increases were also found in the left precuneus. In relatives of people with bipolar disorder, moderate to high quality evidence suggests small increases in intracerebral volume, with no differences in the thalamus, striatum, amygdala, hippocampus, pituitary, or frontal lobes. Compared to people with bipolar disorder, relatives also show a small increase in grey matter volume.

White matter decreases compared to controls

Moderate to high quality evidence suggests decreases in the posterior corpus callosum extending to the posterior cingulate cortex, with smaller reduced clusters in the left optic radiation and right frontal superior longitudinal tracts. In people with first-episode bipolar disorder, moderate to high quality evidence suggests small decreases in total white matter.

White matter increases compared to controls

Moderate to high quality evidence suggests small increases in the cerebellum and the right lenticular nucleus.

Ventricular changes

Moderate to high quality finds an increased risk of having a cavum septum pellucidum, and increased volume in the lateral and third ventricles.

Compared to people with schizophrenia

Moderate quality evidence suggests fewer grey matter reductions in people with bipolar disorder in the right dorsomedial frontal cortex and the left dorsolateral prefrontal cortex. While grey matter reductions were more extensive in male-dominated schizophrenia samples, there was no effect of gender on the findings in bipolar disorder. Moderate to high quality evidence shows fewer reductions in people with bipolar disorder in the amygdala and in hippocampal regions of the left cornu ammonis (CA)1, left CA2/3, left CA4/dentate gyrus, right presubiculum and right subiculum, with no differences in the left presubiculum or subiculum, or right CA1, CA2/3, or CA4/dentate gyrus.

Compared to people with major depression

Moderate to low quality evidence suggests increased grey matter volume in people with bipolar disorder in the right middle frontal gyrus, left hippocampus, right inferior temporal gyrus, left inferior parietal lobule, and right cerebellar vermis.

Compared to people with borderline personality disorder

Moderate to low quality evidence finds reduced grey matter volume and density in people with bipolar disorder in bilateral medial orbital frontal cortex, right insula, and right thalamus, and increases in the right putamen. In borderline personality disorder, grey matter was reduced in bilateral medial prefrontal cortex, bilateral amygdala, and right parahippocampal gyrus.

Medication effects

Compared to bipolar patients not on lithium treatment, high quality evidence shows those on lithium had small increased global grey matter volume. When comparing either group (lithium treated or lithium free) to controls, there were no differences in global grey matter volume. Lithium-treated patients showed fewer hippocampal reductions than patients treated with other medications.

December 2021

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Minor physical anomalies (MPAs) are subtle anatomical deviations which have little functional or aesthetic impact. MPAs in people with bipolar disorder are highly variable, but may include high palate, low-seated ears, cuspidal ear (ears with angled ridges instead of a round curve at the top of the opening into the ear canal), strabismus (cross-eyes), hypertelorism (increased distance between the eyes) and adherent, or attached ear lobes. They may be traced to events occurring prenatally and may represent risk markers for underlying illness susceptibility. MPAs may be important risk indicators when an individual is already at high risk of developing a mental disorder and when multiple MPAs occur together in one individual.

What is the evidence for minor physical anomalies in people with bipolar disorder?

Moderate quality evidence finds more anomalies in the head and facial region of people with bipolar disorder compared to controls, with no differences in peripheral regions.

December 2021

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Pending enough primary studies, we invite reviews on this topic to be conducted. Alternatively we will endeavour to conduct our own review to fill this gap in the Library.

December 2021

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Optical coherence tomography (OCT) is an imaging technology that assesses the thickness of the peripapillary retinal nerve fibre layer, macular thickness, and volume. It has been used to assess neurologic diseases such as multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease, and more recently, in bipolar disorder.

What is the evidence for OCT in people with bipolar disorder?

Moderate to low quality evidence finds a large reduction in overall peripapillary retinal nerve fibre layer thickness in people with bipolar disorder, particularly in the inferior retinal nerve fibre layers.

December 2021

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Telomeres are protective caps on the ends of chromosomes. They are linked to aging as they shorten with each cell division, and when they reach a critical length the cell stops dividing or dies. Chronic stress has been associated with reduced telomere length, resulting in the recognition of an association between adverse social and environmental influences and accelerated aging. Bipolar disorder has also been associated with adverse environmental influences.

What is the evidence for telomere length in people with bipolar disorder?

Moderate to high quality suggests no differences in telomere length between people with bipolar disorder and controls without a psychiatric disorder.

December 2021

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