Progressive losses in gray matter volume and increases in cerebrospinal fluid in the 2 years after a first episode of psychosis in children and adolescents were greater in those eventually diagnosed with schizophrenia or "other" psychoses – but not in those diagnosed with bipolar disorder – compared with healthy controls, results from a prospective, multicenter, 2-year follow-up study show.
Furthermore, the changes in those with schizophrenia were related to markers of poorer prognosis, Dr. Celso Arango and colleagues reported in the January issue of the Archives of General Psychiatry.
The results come from the Child and Adolescent First Episode Psychosis Study (CAFEPS). Participants were 110 patients with an initial episode of psychosis of less than 6 months’ duration and 98 healthy controls who were enrolled at six psychiatric units throughout Spain. Patients and controls were matched for age (mean, 15.5 years and 15.3 years, respectively), sex, and parental socioeconomic status. MRI was performed at baseline and at the 2-year follow-up in 25 patients with schizophrenia, 16 with bipolar disorder, and 20 with "other" psychosis, as well as in 70 healthy controls.
The investigators found that schizophrenia patients, compared with controls, had significantly greater mean losses of whole brain gray matter (–37.1 vs. –14.5 cm3) and greater mean increases of left frontal cerebrospinal fluid volumes (6.7 vs. 2.4 cm3), as well as significantly greater mean losses of gray matter volume in the frontal lobe (–3.3 vs. –0.6 cm3) and in the left parietal lobe (–4.3 vs. –2.2 cm3), reported Dr. Arango of the department of child and adolescent psychiatry at the Hospital General Universitario Gregorio Marañón in Madrid, a member of CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental).
Those with "other" psychoses had significantly greater losses in whole brain gray matter volume (–37.6 vs. –14.5 cm3) and significantly greater loss of gray matter in the frontal lobes (–4.3 vs. –0.6 cm3 for the left, and –4.2 vs. –0.8 cm3 for the right) and left parietal lobes (–5.3 vs. –2.2 cm3), and significantly greater increases in cerebrospinal fluid volume in the frontal lobes (7.1 vs. 2.4 cm3 for the left, and 3.2 vs. 0.8 cm3 for the right), the investigators said (Arch. Gen. Psychiatry 2012;69:16-26).
"Progressive brain changes seem to be more marked in those patients ending with a diagnosis of schizophrenia."
No significant differences were seen in longitudinal volume changes in the bipolar disorder patients, compared with the healthy controls, although the differences that did occur were in the same direction as those that occurred in the other patient subgroups, the investigators noted.
As for associations between volume changes and clinical and outcomes variables, the investigators also noted that "significant correlations were observed between left frontal [gray matter] volume change during follow-up and number of weeks hospitalized and right frontal [cerebrospinal fluid] change, with more weeks hospitalized correlating with greater [gray matter] volume loss and CSF increase in patients with schizophrenia."
A significant association between left frontal CSF volume change during follow-up and left parietal CSF change with mean negative PANSS (Positive and Negative Syndrome Scale) score in patients with schizophrenia also was observed, and left frontal CSF volume change correlated with the mean PANSS total score.
"With regard to clinical improvement, significant correlations were found for the schizophrenia group between the PANSS negative subscale score and PANSS general change score and left temporal [gray matter] loss, with less improvement correlating with larger reductions.
"Associations were also found between frontal right CSF and PANSS general change score and parietal right CSF and PANSS general change score, suggesting that greater CSF volume increase is related to less improvement in general symptoms as measured with PANSS in schizophrenic patients," they wrote.
In the "other" psychoses group, correlations were observed between general and positive and total PANSS change scores, and left parietal CSF loss, suggesting that decreases in CSF volume are associated with less improvement on total score and the presence of positive psychotic symptoms during follow-up.
The findings – which support those from a previous smaller study that also demonstrated that schizophrenia patients with a first episode of psychosis had significant frontal gray matter reductions, compared with healthy controls – suggest a continuum between early-onset and adult-onset psychotic disorders, the investigators said.
Although the underlying mechanisms for brain volume changes in schizophrenia and other psychotic disorder are not yet understood, the findings of this study suggest that one or more active pathophysiologic processes occur in the brains of children and adolescents after a first psychotic episode – particularly in those with schizophrenia, they noted.