Researchers from Harvard Medical School in Boston, MA, investigating the pathophysiology of psychotic disorders have found that patients with these disorders have a reduced brain volume in the hippocampus.

The pathophysiology of psychotic disorders has been studied for more than a hundred years but still remains unclear.

Previous research has suggested that alterations in the medial temporal lobe (MTL), hippocampus, parahippocampal gyrus and entorhinal cortex are indicators of schizophrenia.

The extent to which these alterations are found in patients with other psychotic disorders has been inconclusive, however. In bipolar disorder, for instance, most studies show either little or no change in the MTL.

Some research also found no reduction in the hippocampal volumes of patients with bipolar disorder who were taking lithium.

To investigate this further, the Harvard researchers – who publish their findings in JAMA Psychiatry – conducted a neuroimaging study in healthy volunteers and patients with schizophrenia, schizoaffective disorder and psychotic bipolar disorder.

Consistent with previous research, the MTL appeared reduced in volume in patients with schizophrenia and schizoaffective disorder, but not in patients with psychotic bipolar disorder.

diagram depicting the location of the hippocampus in the brainShare on Pinterest
This study is one of the largest and most technologically sophisticated to analyze the role the hippocampus plays in psychotic disorders.

But the researchers did find volume reductions in the hippocampus across all three groups of patients with psychotic disorders, compared with the healthy volunteers.

Each psychotic disorder also demonstrated hippocampal alterations specific to that condition.

However, although the correlations between psychotic symptoms and reduced volumes in different areas of the hippocampus were statistically significant and consistent with other recent research, the authors admit that the association in their study is still weak.

This could be because there was not much variation in psychotic symptoms in their study participants, as the patients were stable and using antipsychotic medication.

“Yes, the association between hippocampal volume is weak,” study author Dr. Matcheri S. Keshavan told Medical News Today. “It is possible that measures of hippocampal physiology and neurochemistry are more sensitive in detecting relationships to clinical features such as psychosis.”

The researchers also found the reductions in hippocampal volume to be associated with the severity of psychosis, declarative memory and overall cognitive performance.

Different variations may account for different symptoms. For instance, although the hippocampus is involved in encoding new memories – and psychotic disorders are thought to arise from an inability to discriminate between present and past memory experiences – different areas of the hippocampus may play distinct roles in encoding or retrieving memories.

As the patients in this study were mostly medicated with antipsychotics, the authors suggest that future studies should examine the hippocampal alterations in patients before and after beginning treatment with antipsychotics.

Also, this study did not include patients with non-psychotic bipolar disorder, so the researchers are unable to generalize their findings to patients with this condition.

But because this study assessed 549 patients with psychotic disorders (including 188 psychotic bipolar disorder patients) as well as 336 healthy volunteer subjects, the researchers think that the relatively large sample size lends credibility to their findings. They suggest this addresses the previous inconsistencies in smaller studies looking at hippocampal alterations in psychotic bipolar disorder patients.

Also, compared with other research, this study used the most sophisticated technology for analyzing the hippocampus to date.

Explaining why the Harvard study is important, Dr. Keshavan told us:

This study demonstrated the ability to investigate smaller substructures within the hippocampus in a large sample of individuals with a spectrum of psychotic disorders, including schizophrenia and psychotic bipolar disorders. Our observations suggest that changes in the hippocampus, a key brain region related to how we create, store, process and retrieve memories, may not be confined to schizophrenia alone, but are seen across a spectrum of psychotic disorders.”

Recently, Medical News Today reported on a study that suggested frequency of childhood nightmares is linked to an increased risk of psychotic disorders.