Hippocampal role in psychosis bolstered

By Eleanor McDermid, Senior medwireNews Reporter

Reduced hippocampal volumes exist in patients across the psychosis spectrum, shows the latest report from the B-SNIP study.

Volume reductions were present in patients with schizophrenia, schizoaffective disorder and psychotic bipolar disorder, say researcher Matcheri Keshavan (Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA) and colleagues.

“This study firmly establishes the hippocampus as one of the key nodes in the pathway to psychosis”, they write in JAMA Psychiatry. “Understanding the functional consequences and etiological underpinnings of these alterations will likely facilitate better prediction and targeted intervention in psychoses.”

The hippocampal volume reductions were bilateral, with the average volume in the patients ranging from 3897.7 to 3986.1 mm³ in the left hemisphere, compared with 4070.4 mm³ in controls, and from 3947.0 to 3995.6 mm³ versus 4124.6 mm³ in the right hemisphere.

The study included 219 patients with schizophrenia, 142 with schizoaffective disorder, 188 with psychotic bipolar disorder and 337 mentally healthy controls with no personal or immediate family history of psychotic or bipolar disorders.

In addition to the hippocampal volume reductions, the schizophrenia and schizoaffective disorder groups had bilateral reductions in parahippocampal gyrus volume and the schizoaffective disorder patients also had a significant reduction in left entorhinal cortex volume.

Although these surrounding areas were unaffected in psychotic bipolar disorder patients, the observed reductions in hippocampal volume in a large sample “is particularly important and helps address the inconsistent findings in previous [psychotic bipolar disorder] literature”, say the researchers.

For hippocampal subfields, the most marked volume reductions were found in the schizophrenia patients, and schizophrenia and schizoaffective disorder patients had reductions in more subfields than the bipolar disorder patients.

But volumes in the cornu ammonis (CA) 2/3 subfields were bilaterally reduced in all groups of patients, and dentate gyrus volumes were reduced in at least one side in all groups. These areas are thought to be crucial in pattern separation, whereby distinct memories are formed from very similar stimuli, so impaired performance “may result in spurious associations of memories, ultimately manifesting as psychosis”, explains the team.

Consistent with this, the researchers found that smaller hippocampal volumes in patients, but not controls, were associated with poorer verbal declarative memory, assessed with the list-learning measure in the Brief Assessment of Cognition in Schizophrenia. CA 2/3 and dentate gyrus volumes were also associated with declarative memory.

Although modest, these associations “are consistent with the view that psychosis may be related to alterations in a number of nodes of the associative memory network in the hippocampal formation”, concludes the team.

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