Revealing Common Synaptic Pathology in Schizophrenia and Bipolar Disorder
Konopaske GT, Lange N, Coyle JT, Benes FM. Prefrontal cortical dendritic spine pathology in schizophrenia and bipolar disorder. JAMA Psychiatry 2014;71(12):1323-1331. doi: 10.1001/jamapsychiatry.2014.1582.
Background: Previous studies have shown reduced dendritic spine density in the dorsolateral prefrontal cortex (DLPFC) of individuals with schizophrenia, but it was unclear whether this finding is generalizable or also present in bipolar disorder. Both disorders share overlapping features, including psychosis, cognitive deficits and similar neuroanatomical and genetic abnormalities, suggesting potential common neurobiological mechanisms.
Hypothesis: This study hypothesized that dendritic spine loss is present in the DLPFC of individuals with schizophrenia and possibly to an intermediate extent in those with bipolar disorder, reflecting shared but potentially differing pathophysiological processes.
Methods: The authors analyzed post mortem DLPFC tissue (Brodmann area 46) from individuals with schizophrenia (n=14), bipolar disorder (n=9) and controls (n=19). Golgi-stained pyramidal neurons in the deep half of cortical layer III were reconstructed using Neurolucida. Dendritic spine density, number of spines per dendrite and dendrite length were quantified, and potential confounding clinical factors were statistically controlled.
Results: Spine density was significantly reduced by 10.5% in bipolar disorder (p=0.02) and decreased by 6.5% in schizophrenia (p=0.06). The number of spines per dendrite was reduced in both schizophrenia (21.6%, p=0.003) and bipolar disorder (25.8%, p=0.005) compared with controls. Dendrite length was shorter in both schizophrenia (18.3%, p=0.005) and bipolar disorder (18.6%, p=0.005). Other dendritic parameters and somal area did not differ among groups.
Conclusions: This study demonstrated significant dendritic spine loss and reduced dendrite length in the DLPFC of individuals with both schizophrenia and bipolar disorder, suggesting that these conditions share underlying synaptic pathophysiological features.
