Biomarkers of vulnerability for schizophrenia identified in youth

Adolescents and young adults with early-onset schizophrenia and those at high clinical risk for schizophrenia share certain patterns of abnormality in the white matter of their brains, according to results from a study that compared brain imaging in those groups along with healthy controls and otherwise healthy heavy users of cannabis.

The study, led by Katherine A. Epstein of the University of Minnesota, Minneapolis, suggests that adolescents with clinical high risk of developing schizophrenia – but not those with heavy cannabis use alone – had abnormalities in the same key brain regions as young people with early-onset schizophrenia (J. Am. Acad. Child Adolesc. Psychiatry 2014;53:362-72).

For their study, Ms. Epstein and her colleagues enrolled 162 participants aged 10-23 years: 55 were diagnosed with early-onset schizophrenia; 55 were age, sex, and handedness-matched healthy controls; 31 were nonpsychotic heavy cannabis users recruited from treatment programs; and 21 were deemed at high risk for developing schizophrenia or a psychotic illness.

Using diffusion tensor imaging, Ms. Epstein and her colleagues found that those in the high-risk and early-onset schizophrenia groups had significant white-matter deficiencies, compared with healthy controls, in the left inferior longitudinal fasciculus and the left inferior fronto-occipital fasciculus – both areas that affect functioning of ventral visual and language streams and whose disruption can produce deficits that affect higher-order cognitive abilities. These groups also saw white-matter deficiencies in the bilateral cortico-spinal tract, compared with healthy controls.

Heavy cannabis users, by contrast, had deficiencies only in the left inferior fronto-occipital fasciculus. The finding that the same areas were altered in both early-onset schizophrenia and clinical high-risk patients was important because the high-risk patients "had lower doses of antipsychotic medication prescribed at time of MRI scan, and less cumulative exposure to antipsychotic medication," Ms. Epstein and her colleagues wrote.

They acknowledged as a limitation of the study that many of the patients were on antipsychotic medications; however, they noted that "the presence of similar abnormalities in [high-risk] participants makes it unlikely that the observed alterations ... are primarily due to antipsychotic medication exposure."

The study was funded by the National Institute of Mental Health. Its corresponding author, Dr. Sanjiv Kumra, also of the University of Minnesota, Minneapolis, disclosed receiving research support from the National Alliance for Research on Schizophrenia and Depression and from Otsuka Pharmaceutical. None of the other study authors reported conflicts of interest.

Adolescents and young adults with early-onset schizophrenia and those at high clinical risk for schizophrenia share certain patterns of abnormality in the white matter of their brains, according to results from a study that compared brain imaging in those groups along with healthy controls and otherwise healthy heavy users of cannabis.

The study, led by Katherine A. Epstein of the University of Minnesota, Minneapolis, suggests that adolescents with clinical high risk of developing schizophrenia – but not those with heavy cannabis use alone – had abnormalities in the same key brain regions as young people with early-onset schizophrenia (J. Am. Acad. Child Adolesc. Psychiatry 2014;53:362-72).

For their study, Ms. Epstein and her colleagues enrolled 162 participants aged 10-23 years: 55 were diagnosed with early-onset schizophrenia; 55 were age, sex, and handedness-matched healthy controls; 31 were nonpsychotic heavy cannabis users recruited from treatment programs; and 21 were deemed at high risk for developing schizophrenia or a psychotic illness.

Using diffusion tensor imaging, Ms. Epstein and her colleagues found that those in the high-risk and early-onset schizophrenia groups had significant white-matter deficiencies, compared with healthy controls, in the left inferior longitudinal fasciculus and the left inferior fronto-occipital fasciculus – both areas that affect functioning of ventral visual and language streams and whose disruption can produce deficits that affect higher-order cognitive abilities. These groups also saw white-matter deficiencies in the bilateral cortico-spinal tract, compared with healthy controls.

Heavy cannabis users, by contrast, had deficiencies only in the left inferior fronto-occipital fasciculus. The finding that the same areas were altered in both early-onset schizophrenia and clinical high-risk patients was important because the high-risk patients "had lower doses of antipsychotic medication prescribed at time of MRI scan, and less cumulative exposure to antipsychotic medication," Ms. Epstein and her colleagues wrote.

They acknowledged as a limitation of the study that many of the patients were on antipsychotic medications; however, they noted that "the presence of similar abnormalities in [high-risk] participants makes it unlikely that the observed alterations ... are primarily due to antipsychotic medication exposure."

The study was funded by the National Institute of Mental Health. Its corresponding author, Dr. Sanjiv Kumra, also of the University of Minnesota, Minneapolis, disclosed receiving research support from the National Alliance for Research on Schizophrenia and Depression and from Otsuka Pharmaceutical. None of the other study authors reported conflicts of interest.

Adolescents and young adults with early-onset schizophrenia and those at high clinical risk for schizophrenia share certain patterns of abnormality in the white matter of their brains, according to results from a study that compared brain imaging in those groups along with healthy controls and otherwise healthy heavy users of cannabis.

The study, led by Katherine A. Epstein of the University of Minnesota, Minneapolis, suggests that adolescents with clinical high risk of developing schizophrenia – but not those with heavy cannabis use alone – had abnormalities in the same key brain regions as young people with early-onset schizophrenia (J. Am. Acad. Child Adolesc. Psychiatry 2014;53:362-72).

For their study, Ms. Epstein and her colleagues enrolled 162 participants aged 10-23 years: 55 were diagnosed with early-onset schizophrenia; 55 were age, sex, and handedness-matched healthy controls; 31 were nonpsychotic heavy cannabis users recruited from treatment programs; and 21 were deemed at high risk for developing schizophrenia or a psychotic illness.

Using diffusion tensor imaging, Ms. Epstein and her colleagues found that those in the high-risk and early-onset schizophrenia groups had significant white-matter deficiencies, compared with healthy controls, in the left inferior longitudinal fasciculus and the left inferior fronto-occipital fasciculus – both areas that affect functioning of ventral visual and language streams and whose disruption can produce deficits that affect higher-order cognitive abilities. These groups also saw white-matter deficiencies in the bilateral cortico-spinal tract, compared with healthy controls.

Heavy cannabis users, by contrast, had deficiencies only in the left inferior fronto-occipital fasciculus. The finding that the same areas were altered in both early-onset schizophrenia and clinical high-risk patients was important because the high-risk patients "had lower doses of antipsychotic medication prescribed at time of MRI scan, and less cumulative exposure to antipsychotic medication," Ms. Epstein and her colleagues wrote.

They acknowledged as a limitation of the study that many of the patients were on antipsychotic medications; however, they noted that "the presence of similar abnormalities in [high-risk] participants makes it unlikely that the observed alterations ... are primarily due to antipsychotic medication exposure."

The study was funded by the National Institute of Mental Health. Its corresponding author, Dr. Sanjiv Kumra, also of the University of Minnesota, Minneapolis, disclosed receiving research support from the National Alliance for Research on Schizophrenia and Depression and from Otsuka Pharmaceutical. None of the other study authors reported conflicts of interest.