Oligopeptidases activity in bipolar disorder: Ndel1 and angiotensin I converting enzyme

Abstract

Background: Abnormal activity of two enzymes relevant to neurodevelopment, namely nuclear-distribution element-like 1 (Ndel1) and angiotensin I-converting enzyme (ACE), was reported in individuals with schizophrenia; to our knowledge, these oligopeptidases were never measured in bipolar disorder (BD).

Aims: Evaluate the enzyme activity of Ndel1 and ACE in euthymic individuals with BD type 1 which was compare to healthy control (HC) group.

Methods: Ndel1 and ACE activities were assessed in the serum of individuals with BD type 1 according to DSM-IV criteria (n = 70) and a HC group (n = 34). The possible differences between BD type 1 and HC groups were evaluated using Analysis of Covariance (ANCOVA), and the results were adjusted for age, gender and body mass index.

Results: We observed a positive correlation between Ndel1 activity and the total YMRS score in BD group (p = 0.030) and a positive correlation between ACE activity and Ham-D score (p = 0.047). ANCOVA analysis showed lower Ndel1 activity in BDs compared to HCs. Interestingly, we did not observe between-groups differences in ACE activity, despite the recognized correlation of ACE activity levels with cognitive functions, also described to be worsened in psychiatric patients.

Conclusion: Oligopeptidases, especially Ndel1, which has been strongly correlated with neurodevelopment and brain formation, are potentially a good new target in the study of the neurobiology of BD.

Limitations: The relatively small sample size did not permit to examine the cause-effect relationship of clinical dimensions of BD and the enzymatic activity.

Keywords: ACE; ANCOVA; Analysis of Covariance; Angiotensin I-converting enzyme; BD; BK; BMI; Bipolar disorder; DISC1; DSM-IV; Diagnostic and Statistical Manual of Mental Disorders, 4th edition; Disrupted-in-Schizophrenia 1; Enzyme activity; FEP; FRET; Fluorescence resonance energy transfer; GAF; Global Assessment of Functioning; HCs; HDRS; Hamilton Depression Rating Scale; NT; Ndel1; Nuclear distribution element-like 1; Oligopeptidases; SCID-I; SCZ; SD; SPSS; Statistical Package for Social Sciences; Structured Clinical Interview for DSM-IV-Axis I; YMRS; Young Mania Rating Scale; angiotensin I-converting enzyme; bipolar disorder; body mass index; bradykinin; first episode psychosis; healthy controls; neurotensin; schizophrenia; standard deviation.