An international group of scientists led by researchers from the Johns Hopkins University School of Medicine has discovered structural features of the brain in patients with schizophrenia that is resistant to standard treatment. The work was published in the journal Molecular Psychiatry.
Schizophrenia is a mental disorder with hallucinations, delusions and thought disturbances. Standard antipsychotics block dopamine receptors and help many, but some patients do not receive sufficient relief. This condition is called treatment-resistant schizophrenia. At present, resistance is determined only after several failed courses of different drugs, which can take months or years.
The scientists compared brain scan data from more than 1,200 people from seven centers in six countries. Among them were patients with resistant schizophrenia, patients responding to standard therapy, and healthy volunteers. First a meta-analysis was conducted - the results of independent datasets were combined to identify common trends. Age, sex, race, head size and duration of illness were taken into account.
Patients with resistant schizophrenia were found to have a reduced volume of the hippocampus - a structure deep in the brain that is important for memory and learning. The volume of the putamen, which is involved in learning and motor control, was also smaller, and the surface area of the left superior frontal gyrus, which is associated with thought processes, was reduced.
Then a mega-analysis was conducted: all raw scan data were combined into a single array and data from healthy people were added as a norm. It confirmed the reduction of the hippocampus, putamen and the area of the left superior frontal gyrus. In the hippocampus and superior frontal gyrus a sequence was observed: healthy people had the largest volumes, those responding to treatment had smaller ones, and resistant patients had the smallest. The putamen did not fit this pattern: in resistant patients its size did not differ from healthy people, and in those responding to treatment it was even larger.
The scientists checked whether the differences were related to medication. The dose of antipsychotics did not correlate statistically significantly with hippocampal volume or the area of the superior frontal gyrus. This suggests that the reduction of these areas probably reflects the biology of resistant schizophrenia itself rather than the effect of treatment. Putamen volume correlated weakly with total medication intake, meaning that drugs may have a slight influence on this structure.
The authors note limitations: the sample did not include representatives of African and Latin American populations, and the group of responders may have included people who will develop resistance later. In addition, the identified differences are not yet sufficient for diagnosis: the models could not reliably distinguish resistant patients from the others at the individual level. The scientists believe that in the future brain imaging should be combined with other biological markers, for example genetic or metabolic ones, to create a reliable predictive test.