Cluster analysis of cognitive deficits may mark heterogeneity in schizophrenia in terms of outcome and response to treatment

Abstract

Cognitive impairments are central to schizophrenia, but their clinical utility for tagging heterogeneity in lifetime outcome and response to treatment is not conclusive. By exploiting four cognitive domains consistently showing large deficits in studies, we tested whether cluster analysis would define separate subsets of patients and then whether the disease heterogeneity marked by these clusters would be related to lifetime outcome and response to treatment. A total of 112 schizophrenia patients completed a neuropsychological evaluation. The PANSS, GAF-S and GAF-F were rated at the onset and endpoint of the illness trajectory. A blind judgment of the lifetime response to treatment was made. The first cluster presented near-normal cognitive performance. Two other clusters of severely impaired patients were identified: one generally impaired in the four cognitive domains and another selectively impaired in visual episodic memory and processing speed, each relating to a different lifetime evolution of disease and treatment response. Although the two impaired clusters were clinically indistinguishable in symptom severity and functioning at disease onset, patients with selective cognitive impairments demonstrated better improvement at outcome, whereas the generally impaired patients were more likely to be treatment refractory. The findings have implications for the management of patients and for clinical trials since particular combinations of cognitive deficits in patients would influence their treatment response.

Neuro‐ and social‐cognitive clustering highlights distinct profiles in adults with anorexia nervosa

“…Cluster analysis is an explorative, hypothesis‐generating and data driven approach. Thus, analogous to previous studies in the psychosis field, replication studies are required in other well‐defined AN samples of different illness severity (e.g., in‐patients) or stage (e.g., adolescents, or recovered samples), in other ED populations (e.g., bulimia nervosa) and in high risk samples (e.g., offspring of mothers with AN) and in trans‐diagnostic ED samples to assess the robustness and specificity of the cluster solutions found here. Moreover, future studies should examine a broad range of collateral validators (neurobiological, developmental, or clinical) to further assess the meaning of our cluster findings and assess their potential utility in characterizing etiological heterogeneity, predicting longer term outcomes or guiding individual tailoring of treatment.…”

“…This work has suggested that meaningful replicable clusters emerge with associated differences in clinical symptoms, community functioning, treatment response and outcomes. [25][26][27] Analogously, we hypothesize that there will be an ASD-like cluster showing both neuro-and socialcognitive impairment, and that this cluster will have a more severe and chronic form of the illness, together with greater past service utilization and better current treatment adherence.…”

“…Cluster analytic methods have been widely used in the psychosis field to characterize cognitive heterogeneity. This work has suggested that meaningful replicable clusters emerge with associated differences in clinical symptoms, community functioning, treatment response and outcomes …”

Structural brain markers are differentially associated with neurocognitive profiles in socially marginalized people with multimorbid illness.

“…This kind of neurocognitive subtyping is well suited to heterogeneous populations, such as schizophrenia and traumatic brain injury, and has demonstrated considerable clinical utility (Allen & Goldstein, 2013). For example, neurocognitive subtypes identified in schizophrenia were found to differentially predict functional outcomes and lifetime response to treatment (Gilbert et al, 2014). On the other hand, in healthy adults over 80 years old, distinct neurocognitive profiles were useful in validating theoretical models of neurocognitive aging thought to reflect various forms of brain pathology (Gawron et al, 2014).…”

The neuropathology of schizophrenia: new insights from postmortem studies

“…Gilbert et al [6] used alterations in cognitive domains to stratify schizophrenia patients with respect to outcome measures. Patients with selective cognitive impairments demonstrated better improvement at outcome, whereas generally impaired patients were more likely to be A. Schmitt (&) Á P. Falkai Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nußbaumstr.…”