In the Journals

Neuropathological correlates of bipolar disorder ‘unlikely’

Results from a systematic review and meta-analysis revealed that the evidence does not support neuropathological correlates of bipolar disorder.

Though this does not rule out the possibility, it is unlikely that a neuropathology exists; however further study remains necessary to confirm or refute these findings, the researchers wrote in Molecular Biology.

“Like other ‘functional’ psychiatric disorders, bipolar disorder lacks any diagnostic neuropathology of the kind which characterizes and defines the dementias, but this does not mean that [bipolar disorder] has no morphological correlates,” Paul J. Harrison, FRCPsych, from the department of psychiatry at University of Oxford and Oxford Health NHS Foundation Trust, England, and colleagues wrote. “To our knowledge, there has been no substantive review covering [bipolar disorder] neuropathology... and there has never been a systematic review.”

To examine which neuropathological findings reported in bipolar disorder are well-established, the investigators conducted a systematic review of the literature and meta-analysis when possible.

Researchers searched more than 5,000 publications and identified 103 relevant data papers. Relative studies measured “visible” neuropathology parameters like density, number, size or shape of cells; cellular constituents; or cytopathological elements in patients with bipolar disorder compared with controls. Studies that identified neuronal and glial populations and that measured the size of a brain structure were also included.

In total, 81 papers were eligible for inclusion. Harrison and colleagues found that most studies relied on a limited number of brain collections and also used small sample sizes, which averaged 12 cases of bipolar disorder and 15 controls. In addition, few studies have tried to closely replicate a previous study, preventing substantial meta-analyses which were limited to two studies each comprising 16 to 36 bipolar disorder cases and 16 to 74 controls. Based on these results, the researchers reported that no neuropathological findings have been established with total certainty.

However, the authors observed several replicated positive findings in bipolar disorder, such as reduced:

  • cortical thickness and glial density in subgenual anterior cingulate cortex;
  • neuronal density in some amygdalar nuclei; and
  • calbindin-positive neuron density in prefrontal cortex.

Though other positive findings have been reported, there was limited or contradictory evidence. Negatively, the study reported that gliosis was not a feature of bipolar disorder and there’s no neuropathological evidence for an inflammatory process in the disorder.

“[Further study] would require research of a much larger scale and scope than has occurred to date, to ensure the results are conclusive, and to allow assessment of potential clinicopathological correlates and subgroupings,” the authors wrote. “This would be a challenging undertaking, but transcriptomic and other molecular studies of psychiatric disorders, including [bipolar disorder], now routinely include many hundreds of brains. Neuropathological research should have similar aspirations.” – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures.

Results from a systematic review and meta-analysis revealed that the evidence does not support neuropathological correlates of bipolar disorder.

Though this does not rule out the possibility, it is unlikely that a neuropathology exists; however further study remains necessary to confirm or refute these findings, the researchers wrote in Molecular Biology.

“Like other ‘functional’ psychiatric disorders, bipolar disorder lacks any diagnostic neuropathology of the kind which characterizes and defines the dementias, but this does not mean that [bipolar disorder] has no morphological correlates,” Paul J. Harrison, FRCPsych, from the department of psychiatry at University of Oxford and Oxford Health NHS Foundation Trust, England, and colleagues wrote. “To our knowledge, there has been no substantive review covering [bipolar disorder] neuropathology... and there has never been a systematic review.”

To examine which neuropathological findings reported in bipolar disorder are well-established, the investigators conducted a systematic review of the literature and meta-analysis when possible.

Researchers searched more than 5,000 publications and identified 103 relevant data papers. Relative studies measured “visible” neuropathology parameters like density, number, size or shape of cells; cellular constituents; or cytopathological elements in patients with bipolar disorder compared with controls. Studies that identified neuronal and glial populations and that measured the size of a brain structure were also included.

In total, 81 papers were eligible for inclusion. Harrison and colleagues found that most studies relied on a limited number of brain collections and also used small sample sizes, which averaged 12 cases of bipolar disorder and 15 controls. In addition, few studies have tried to closely replicate a previous study, preventing substantial meta-analyses which were limited to two studies each comprising 16 to 36 bipolar disorder cases and 16 to 74 controls. Based on these results, the researchers reported that no neuropathological findings have been established with total certainty.

However, the authors observed several replicated positive findings in bipolar disorder, such as reduced:

  • cortical thickness and glial density in subgenual anterior cingulate cortex;
  • neuronal density in some amygdalar nuclei; and
  • calbindin-positive neuron density in prefrontal cortex.

Though other positive findings have been reported, there was limited or contradictory evidence. Negatively, the study reported that gliosis was not a feature of bipolar disorder and there’s no neuropathological evidence for an inflammatory process in the disorder.

“[Further study] would require research of a much larger scale and scope than has occurred to date, to ensure the results are conclusive, and to allow assessment of potential clinicopathological correlates and subgroupings,” the authors wrote. “This would be a challenging undertaking, but transcriptomic and other molecular studies of psychiatric disorders, including [bipolar disorder], now routinely include many hundreds of brains. Neuropathological research should have similar aspirations.” – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures.