Brain Deficits Not Evident in Early Psychosis

The characteristic structural and functional brain deficits associated with chronic schizophrenia do not appear to be fully present in early psychosis patients, a report published in the Jan. 15 issue of Biological Psychiatry shows.

The findings suggest that early intervention strategies could delay, reduce, or prevent the development of brain deficits in some patients with early psychosis.

Previous studies have linked dynamic changes to hippocampal volume and neural activation with the transition to psychosis, but have not determined when such changes occur with respect to disease progression, wrote Lisa E. Williams, Ph.D., and her colleagues at Vanderbilt University in Nashville, Tenn. Because of the potential treatment implications, the investigators sought to ascertain whether hippocampal integrity is compromised in the early stage of a psychotic illness.

The investigators compared structural MRI data for 41 early psychosis patients and 34 healthy controls. Functional fMRI data were analyzed for 27 of the early psychosis patients and 30 healthy controls subjects who met memory training criteria. Most of the early psychosis patients had first episode schizophrenia.

The early psychosis and control subjects in both the structural and functional MRI analysis cohorts were similar with respect to age, race, sex, and parental education, the authors wrote. All of the study participants completed a transitive interference task that has been used in the assessment of chronic schizophrenia patients, whereby they learned to identify the winning set of two sets of stimulus pairs drawn from an overlapping sequence and a nonoverlapping set. During the fMRI scan, they were tested on the previously learned conditions and asked to make inferential judgments on new pairings from each condition to evaluate hippocampal activation. With respect to the structural neuroimaging data, a single, blinded rater completed volumetric analysis, manually segmenting the volumes and conducting between-group comparisons of the volumes, which were corrected for individual intracranial volume.

The investigators determined that the early psychosis and control groups did not differ on inference performance or hippocampal volume, and both groups exhibited similar activation of medial temporal regions when judging nonoverlapping pairs, suggesting that "established abnormalities of brain structure and function found in chronic psychosis patients are not fully present in all early psychosis patients," they wrote (Biol. Psychiatry 2012;71:105-13). This result, however, appeared to be specific to those individuals with intact relational memory performance, whereas those who did not meet memory training criteria (25% of the early psychosis group) had smaller hippocampal volumes. This finding supports a link between relational memory and hippocampal integrity. In addition, it indicates that memory deficits and hippocampal volume reductions are present in some early psychosis patients.

The findings are limited by several factors. For example, the training performance criteria needed to test for a selective inference deficit limits the generalizability of the results to all psychotic patients. Another limitation was the short mean duration of illness. "Only 7 of 41 patients had a duration of treated illness greater than 6 months, and this factor was not correlated with inference performance," they stated.

Despite the limitations, the current findings "indicate that hippocampal dysfunction, well established in chronic schizophrenia patients, is not present at the onset of psychosis in all patients with early psychosis, providing an opportunity for clinical intervention."

The investigators disclosed having no relevant financial conflicts of interest.

The characteristic structural and functional brain deficits associated with chronic schizophrenia do not appear to be fully present in early psychosis patients, a report published in the Jan. 15 issue of Biological Psychiatry shows.

The findings suggest that early intervention strategies could delay, reduce, or prevent the development of brain deficits in some patients with early psychosis.

Previous studies have linked dynamic changes to hippocampal volume and neural activation with the transition to psychosis, but have not determined when such changes occur with respect to disease progression, wrote Lisa E. Williams, Ph.D., and her colleagues at Vanderbilt University in Nashville, Tenn. Because of the potential treatment implications, the investigators sought to ascertain whether hippocampal integrity is compromised in the early stage of a psychotic illness.

The investigators compared structural MRI data for 41 early psychosis patients and 34 healthy controls. Functional fMRI data were analyzed for 27 of the early psychosis patients and 30 healthy controls subjects who met memory training criteria. Most of the early psychosis patients had first episode schizophrenia.

The early psychosis and control subjects in both the structural and functional MRI analysis cohorts were similar with respect to age, race, sex, and parental education, the authors wrote. All of the study participants completed a transitive interference task that has been used in the assessment of chronic schizophrenia patients, whereby they learned to identify the winning set of two sets of stimulus pairs drawn from an overlapping sequence and a nonoverlapping set. During the fMRI scan, they were tested on the previously learned conditions and asked to make inferential judgments on new pairings from each condition to evaluate hippocampal activation. With respect to the structural neuroimaging data, a single, blinded rater completed volumetric analysis, manually segmenting the volumes and conducting between-group comparisons of the volumes, which were corrected for individual intracranial volume.

The investigators determined that the early psychosis and control groups did not differ on inference performance or hippocampal volume, and both groups exhibited similar activation of medial temporal regions when judging nonoverlapping pairs, suggesting that "established abnormalities of brain structure and function found in chronic psychosis patients are not fully present in all early psychosis patients," they wrote (Biol. Psychiatry 2012;71:105-13). This result, however, appeared to be specific to those individuals with intact relational memory performance, whereas those who did not meet memory training criteria (25% of the early psychosis group) had smaller hippocampal volumes. This finding supports a link between relational memory and hippocampal integrity. In addition, it indicates that memory deficits and hippocampal volume reductions are present in some early psychosis patients.

The findings are limited by several factors. For example, the training performance criteria needed to test for a selective inference deficit limits the generalizability of the results to all psychotic patients. Another limitation was the short mean duration of illness. "Only 7 of 41 patients had a duration of treated illness greater than 6 months, and this factor was not correlated with inference performance," they stated.

Despite the limitations, the current findings "indicate that hippocampal dysfunction, well established in chronic schizophrenia patients, is not present at the onset of psychosis in all patients with early psychosis, providing an opportunity for clinical intervention."

The investigators disclosed having no relevant financial conflicts of interest.

The characteristic structural and functional brain deficits associated with chronic schizophrenia do not appear to be fully present in early psychosis patients, a report published in the Jan. 15 issue of Biological Psychiatry shows.

The findings suggest that early intervention strategies could delay, reduce, or prevent the development of brain deficits in some patients with early psychosis.

Previous studies have linked dynamic changes to hippocampal volume and neural activation with the transition to psychosis, but have not determined when such changes occur with respect to disease progression, wrote Lisa E. Williams, Ph.D., and her colleagues at Vanderbilt University in Nashville, Tenn. Because of the potential treatment implications, the investigators sought to ascertain whether hippocampal integrity is compromised in the early stage of a psychotic illness.

The investigators compared structural MRI data for 41 early psychosis patients and 34 healthy controls. Functional fMRI data were analyzed for 27 of the early psychosis patients and 30 healthy controls subjects who met memory training criteria. Most of the early psychosis patients had first episode schizophrenia.

The early psychosis and control subjects in both the structural and functional MRI analysis cohorts were similar with respect to age, race, sex, and parental education, the authors wrote. All of the study participants completed a transitive interference task that has been used in the assessment of chronic schizophrenia patients, whereby they learned to identify the winning set of two sets of stimulus pairs drawn from an overlapping sequence and a nonoverlapping set. During the fMRI scan, they were tested on the previously learned conditions and asked to make inferential judgments on new pairings from each condition to evaluate hippocampal activation. With respect to the structural neuroimaging data, a single, blinded rater completed volumetric analysis, manually segmenting the volumes and conducting between-group comparisons of the volumes, which were corrected for individual intracranial volume.

The investigators determined that the early psychosis and control groups did not differ on inference performance or hippocampal volume, and both groups exhibited similar activation of medial temporal regions when judging nonoverlapping pairs, suggesting that "established abnormalities of brain structure and function found in chronic psychosis patients are not fully present in all early psychosis patients," they wrote (Biol. Psychiatry 2012;71:105-13). This result, however, appeared to be specific to those individuals with intact relational memory performance, whereas those who did not meet memory training criteria (25% of the early psychosis group) had smaller hippocampal volumes. This finding supports a link between relational memory and hippocampal integrity. In addition, it indicates that memory deficits and hippocampal volume reductions are present in some early psychosis patients.

The findings are limited by several factors. For example, the training performance criteria needed to test for a selective inference deficit limits the generalizability of the results to all psychotic patients. Another limitation was the short mean duration of illness. "Only 7 of 41 patients had a duration of treated illness greater than 6 months, and this factor was not correlated with inference performance," they stated.

Despite the limitations, the current findings "indicate that hippocampal dysfunction, well established in chronic schizophrenia patients, is not present at the onset of psychosis in all patients with early psychosis, providing an opportunity for clinical intervention."

The investigators disclosed having no relevant financial conflicts of interest.