ORIGINAL RESEARCH

Left Medial Temporal Cytosolic Choline in Early Onset Depression
Vivek Kusumakar, MD1, Frank P MacMaster, BA2, Larry Gates, PhD3, Sandra J Sparkes, BSc4, Shakeela C Khan, PhD5

Objectives: Previous studies have linked the choline (Cho) resonance seen in proton magnetic resonance spectroscopy (1H-MRS) to major depressive disorder (MDD). We endeavoured to clarify the possible involvement of cytosolic choline in the amygdala (anterior medial temporal region) of juvenile subjects with MDD.
Method:  A total of 11 age- and sex-matched MDD and control pairs aged 14 to 18 years participated in long-echo proton magnetic resonance spectroscopic imaging (1H-MRSI) of the amygdala. Compounds available include N-acetyl-aspartate (NAA), creatine–phosphocreatine (Cr) and choline-containing compounds.
Results:  Subjects with depression demonstrated lower left amygdala Cho–Cr ratios, compared with control subjects (paired t = 2.624, df 10, P = 0.025). Left amygdala NAA–Cr and right amygdala Cho–Cr and NAA–Cr did not differ significantly between subjects with depression and control subjects. In subjects with depression, simple regression revealed a negative trend between left amygdala Cho–Cr and Beck Depression Inventory (BDI) score (F = 3.509, P = 0.098). Right amygdala NAA–Cr and Cho–Cr did not differ significantly.
Conclusion:  Cytosolic choline appears to be involved in the pathophysiology of early-onset MDD, likely secondary to corticosteroid-neuroendocrine-driven changes.

(Can J Psychiatry 2001;46:959–964)

Key Words:  adolescent, amygdala, choline, depression, magnetic resonance spectroscopy


Numerous proton magnetic resonance imaging (1H-MRS) studies have linked cytosolic choline levels to the neuropathology of unipolar major depressive disorder (MDD) and bipolar disorder (BD), although divergent findings have been noted (1–9). The choline resonance (Cho; 3.2ppm) derives most of its signal from phosphocholine and glycerophosphocholine (10,11). This resonance is commonly reported as a ratio with creatine–phosphocreatine (Cr; 3.03ppm) or the putative neuronal marker N-acetyl-aspartate (NAA; 2.02ppm) (12). In a study of adult and elderly subjects with MDD, Charles and others (1) noted a statistically significant elevation in Cho–Cr ratios in a 27cc voxel in the basal ganglia in subjects with MDD, compared with age-matched controls. The Cho–Cr ratios in the subjects with depression dropped significantly after pharmacologic intervention. Similarly, Hamakawa and others (2) found a statistically significant increase in basal ganglia (27cc voxel) Cho–Cr in subjects with BD and an increase in Cho–NAA in subjects with MDD, compared with control subjects. Moore and others (3) noted a significant positive correlation between cingulate (44cc) Cho–Cr and depressive rating scores in a sample of subjects with BD.


Manuscript received August 2001 and accepted October 2001.
1Associate Professor, Psychiatry, Dalhousie University, Halifax, Nova Scotia.
2PhD Candidate, Anatomy and Neurobiology, Psychiatry, Dalhousie University, Halifax, Nova Scotia.
3Assistant Professor, Diagnostic Radiology, Dalhousie University, Halifax, Nova Scotia.
4PhD Candidate, Psychology, Dalhousie University, Halifax, Nova Scotia.
5Assistant Professor, Psychiatry, Dalhousie University, Halifax, Nova Scotia.
Address for correspondence:  Dr V Kusumakar; Maritime Psychiatry, IWK Health Centre, 5850 University Avenue, Halifax, NS B3J 3G9
e-mail: vivek.kusumakar@dal.ca


A reduction in Cho–Cr levels was also associated with antidepressant use in the sample studied by Moore and others (3). In children and adolescents, Steingard and others (4) found a statistically significant increase in orbital prefrontal Cho–Cr (3.8cc voxel), compared with control subjects. In contrast to age- and sex-matched control subjects, Rosenberg and others (5) found a trend for increased choline in a 0.7cc voxel from the left caudate in a treatment-naïve sample of pediatric subjects with MDD.

Despite the abundant evidence of increased choline in several brain regions in subjects with depression, not all adult studies have consistently demonstrated such a pattern in choline levels. Renshaw and others (6) found significantly lower Cho–Cr in the left caudate–putamen (8cc voxel) of subjects with MDD, compared with control subjects. Auer and others (7) did not note any significant difference in choline levels in the cingulate in their study of subjects and control subjects with MDD. More interestingly, Ende and others (8) found a lower hippocampal choline level in MDD subjects, compared with control subjects, and this level rose in response to electroconvulsive therapy. Similarly, Sonawalla and others (9) found an increase in the Cho–Cr ratios in the basal ganglia (8cc voxel) of patients with MDD who responded to fluoxetine treatment.

Clearly, altered choline is a fairly consistent finding in the adult literature. Children and adolescents, however, have been relatively understudied in the neurobiology of