Network analysis was used to examine how densely interconnected individual negative symptom domains are, whether some domains are more central than others, and whether sex influenced network structure. Participants included outpatients with schizophrenia (SZ; n = 201), a bipolar disorder (BD; n = 46) clinical comparison group, and healthy controls (CN; n = 27) who were rated on the Brief Negative Symptom Scale. The mutual information measure was used to construct negative symptom networks. Groups were compared on macroscopic network properties to evaluate overall network connectedness, and microscopic properties to determine which domains were most central. Macroscopic analyses indicated that patients with SZ had a less densely connected negative symptom network than BD or CN groups, and that males with SZ had less densely connected networks than females. Microscopic analyses indicated that alogia and avolition were most central in the SZ group, whereas anhedonia was most central in BD and CN groups. In addition, blunted affect, alogia, and asociality were most central in females with SZ, and alogia and avolition were most central in males with SZ. These findings suggest that negative symptoms may be highly treatment resistant in SZ because they are not very densely connected. Less densely connected networks may make treatments less likely to achieve global reductions in negative symptoms because individual domains function in isolation with little interaction. Sex differences in centralities suggest that the search for pathophysiological mechanisms and targeted treatment development should be focused on different sets of symptoms in males and females.
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