Negative Symptoms Increase Cardiovascular Risk in Schizophrenia

cardiovascular system
cardiovascular system
Although various clinical and psychosocial factors were associated with unhealthy lifestyle factors and higher risk for CVD, the strongest associations were with negative symptoms.

In individuals with schizophrenia spectrum disorders, negative symptoms had a strong association with a higher risk for cardiovascular disease (CVD) and factors indicating an unhealthy lifestyle, according to the results of the CHANGE trial published in Schizophrenia Research.

People with severe mental disorders die an average of 15 years earlier than the general population in Western countries. CVD is the most frequent cause of death, and unhealthy eating habits and lack of physical activity are major contributing factors to earlier mortality.

Ane Storch Jakobsen, MD, of the Mental Health Center in Copenhagen, Denmark, and colleagues analyzed data from baseline and 2-year follow-up of 428 individuals with schizophrenia spectrum disorders and abdominal overweight who were enrolled in the CHANGE trial to determine the relationships between clinical and psychosocial factors and established cardiovascular (CV) risk factors. Dependent variables were baseline and follow-up measures of maximal oxygen uptake (VO2max), waist circumference, high-density lipoprotein (HDL), systolic blood pressure, and glycated hemoglobin (HbA1c). Independent variables were baseline values of negative symptoms, positive symptoms, cognition, level of functioning, antipsychotic medication, duration of illness, employment situation, and whether participants had friends.

Negative symptoms demonstrated a negative association with cardiorespiratory fitness, quality of diet, and HDL, and with increasing values of waist circumference, body mass index (BMI), and HbA1c at baseline, as well as poorer cardiorespiratory fitness and larger waist circumference, higher HbA1c, and lower HDL at 2-year follow-up.  

In contrast, better level of functioning and cognitive function correlated positively with cardiorespiratory fitness and HDL and correlated negatively with waist circumference and HbA1c, as well as predicting better fitness, higher HDL, and lower HbA1c at 2-year follow-up.

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Psychotic symptoms and duration of illness were not significantly associated with any outcome, and antipsychotic drugs known to have the worst adverse metabolic effects were positively associated with cholesterol levels, but not with any other outcome. Employment of any kind demonstrated a positive association with cardiorespiratory fitness and a negative association with waist circumference, BMI, and systolic blood pressure. Friendships were negatively associated with waist circumference and positively associated with HDL cholesterol levels; however, none of the 2-year outcomes were predicted by friendship.

The investigators noted that although various clinical and psychosocial factors were associated with less healthy lifestyle factors and higher risk for CVD, the strongest associations were with negative symptoms. They cautioned, however, that bidirectional causality should be considered, and argued that reduction of negative symptoms should be investigated further to reduce the CV morbidity and mortality seen in individuals with schizophrenia spectrum disorders.


Jakobsen AS, Speyer H, Nørgaard HCB, et al. Associations between clinical and psychosocial factors and metabolic and cardiovascular risk factors in overweight patients with schizophrenia spectrum disorders — baseline and two-year findings from the CHANGE trial [published online March 1, 2018]. Schizophrenia Res. doi:10.1016/jschres.2018.02.047