What is happening in the brain during schizophrenia?

Location of cortical gray matter changes

Reduction in gray matter volume is most prominent and more widespread in the early phases of schizophrenia

Many neuroimaging studies have confirmed progressive reduction in cortical gray matter volume in schizophrenia, said Professor Antonio Vita, Brescia, Italy. These changes are not widespread but confined to specific areas of the brain. Their location was demonstrated by a meta-analysis and meta-regression carried out by Professor Vita and his colleagues,¹ which showed:

• Reduction in gray matter volume is most prominent and more widespread in the early phases of schizophrenia, affecting frontal, temporal and parietal gray matter⁴
• Reduction in total gray matter volume over time is most noticeable in the left hemisphere and superior temporal regions¹

As schizophrenia progresses, the reduction in gray matter volume is most noticeable in the left hemisphere and superior temporal regions

Among individuals with first-episode schizophrenia, progression of gray matter changes has been shown to be restricted to those with a poor outcome,² noted Professor Vita.

Changes in the brain before transition to psychosis

The changes in the brain precede the transition to psychosis before treatment with antipsychotics, said Professor Lynn DeLisi, Boston, MA, who highlighted a review and meta-analysis of neuroanatomical correlates of clinical high-risk (CHR) for psychosis and potential predictors of transition.

Less cortical gray matter in certain brain regions in individuals who transition to psychosis

Among individuals with CHR for psychosis, transition to psychosis was associated with less cortical gray matter in the right temporal lobe, anterior cingulate and paracingulate.³

Structural magnetic resonance images have also revealed neurobiologically distinct subgroups of patients with schizophrenia, and this has been useful for individualizing interventions,⁴ said Professor DeLisi. But it is not clear what the interventions should be or when they should be applied. The challenge for the next decades is to develop interventions that prevent the progressive brain changes.

Effects of antipsychotic therapy and normal aging on brain volume loss

Higher mean daily antipsychotic intake in patients treated only with second-generation antipsychotics is linked to less progressive gray matter loss

Confounders of excessive brain volume loss during schizophrenia include first-generation vs second-generation antipsychotic therapy and normal aging, said Professor Vita.

Cumulative antipsychotic intake with at least one first-generation antipsychotic is linked to a significantly higher loss of total cortical gray matter volume over time in patients with schizophrenia compared with healthy controls,⁵ he explained.

In contrast, higher mean daily antipsychotic intake in patients treated only with second-generation antipsychotics was linked to less progressive gray matter loss.⁶

Use of second-generation antipsychotics might prevent or slow the progressive brain changes

In terms of brain aging, brain age at the onset of schizophrenia is significantly greater than chronological age (+3.36 years).⁷ This difference between chronological age and schizophrenia brain age is called “schizophrenia brain age gap”, said Professor Vita. It progressively increases during follow-up, but by approximately 5 years after illness onset, the acceleration decreases from 2.5 years/year just after illness onset to about the normal rate (1 year/year).⁷

Interventions that might prevent or slow progressive brain changes in schizophrenia include early intervention, continuity of treatment, prevention of relapses and use of second-generation antipsychotics, concluded Professor Vita.