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Neuroimaging the Brain Function of Schizophrenia Patients on Clozapine

Antoinette Richards, Sarah Clark, Stephanie Hare, Wenhao Jiang, Maria Misiura, Dr. Robert Cotes, Dr. David Goldsmith, and Dr. Jessica Turner

Department of Psychology – Georgia State University

References

  1. Freudenreich, O., MD, & McEvoy, J., MD. (n.d.). Guidelines for prescribing clozapine in schizophrenia. Retrieved April 08, 2016, from http://www.uptodate.com/contents/guidelines-for-prescribing-clozapine-in-schizophrenia
  2. Giovagnoli, A. R. (1996). Trail Making Test: Normative values from 287 normal adult controls. Italian Journal Of Neurological Sciences, 17(4), 305-310. doi:10.1007/BF01997792
  3. Nakajima, S., Takeuchi, H., Plitman, E., Fervaha, G., Gerretsen, P., Caravaggio, F., & Graff-Guerrero, A. (2015). Neuroimaging findings in treatment-resistant schizophrenia: A systematic review: Lack of neuroimaging correlates of treatment-resistant schizophrenia. Schizophrenia Research, 164(1-3), 164-175. doi:10.1016/j.schres.2015.01.043
  4. Tombaugh, T. N., Kozak, J., & Rees, L. (1999). Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming. Archives Of Clinical Neuropsychology, 14(2), 167-177. doi:10.1016/S0887-6177(97)00095-4

Current Participant Data (N=5)

Cultural Intersection

Mostly African American Males

Age

Range: 34 – 52 years old

Age of Hospitalization

Range: 17 – 47 years old

Brief Psychiatric Rating Scale (BPRS) Score

Range: 41 – 58

PSYRATS Score

Range: 0 – 35

Animal Fluency

Range: 11 – 30 total

Z-Score Range: -1.18 – 2.62

Trails A

Range: 25 – 72 secs

Z-Score Range: -0.9 – 0.99

Trails B

Range: 41 – 187* secs

Z-Score Range: -0.79 – 0.74

Figure 1. Example Participant T1 image

  • The recruitment goal is about 40 patients who are stable on clozapine through the Grady Behavioral Health Unit (GBHU).
  • Participants attend two separate visits with the researchers. The first visit is conducted at GBHU where the patients are interviewed about demographics, general functioning, cognitive insight, and symptom severity.
  • The second visit is conducted at the Center for Advanced Brain Imaging (CABI).
  • Patients are administered cognitive tests that measure components such as working memory, imagination, verbal fluency, and processing speed. Afterwards, the patients undergo structural and functional magnetic resonance imaging scans.

Method

  • We are in the process of acquiring more participant data for the study.
  • Reported norms for the data presented include:
    • Pre-Severe Clozapine Levels: 250 – 350 mcg/L [1]
    • Trails A: Average = 47.34, SD = 24.96 [2]
    • Trails B: Average = 116.21, SD = 95.80 [2]
    • Animal Fluency: Average = 16.9, SD = 5 [4]

Results

  • This is an exploratory study that will be one of few that investigate differences among participants who respond to clozapine and those who do not.
  • We will be correlating symptom measures, clozapine doses and structural and functional imaging measures.

Discussion

Figure 2. Example Participant DTI tracts

  • Schizophrenia, a complex psychotic disorder, is characterized by positive symptoms, like delusions, hallucinations, and paranoia.
  • Few studies have examined the characteristics of patients who are “treatment resistant,” who do not respond to a broad range of antipsychotics [3].
  • Clozapine is an antipsychotic medication used to treat patients diagnosed with schizophrenia who generally do not respond to other treatments. It is used as a last-resort medication.
  • The relationship between treatment-resistant schizophrenia, clozapine, and brain structure and function warrants more study.
  • We anticipate the patients that have more severe symptoms will show hyperconnectivity between specific regions and show structural differences.

Introduction

Example imaging data types collected during the study.

Figure 3. Example Participant resting fMRI