Mohammed T. Abou-Saleh

Principles and Practice of Geriatric Psychiatry.Editors: Professor John R. M. Copeland, Dr Mohammed T. Abou-Saleh and Professor Dan G. BlazerCopyright & 2002 John Wiley & Sons LtdPrint ISBN 0-471-98197-4 Online ISBN 0-470-84641-073Neuro-imagingNeuro-imaging Studies of DepressionMohammed T. Abou-SalehSt George’s Hospital Medical School, London, UKThe use of neuro-imaging techniques in the study of depression hasprovided a major advance in the elucidation of its functional neuroanatomy,metabolic correlates and biochemistry. Structural neuroimagingtechniques, such as computed axial tomography (CT) andmagnetic resonance imaging (MRI) have demonstrated an associationbetween structural brain abnormalities and depression inpatients with unipolar and bipolar disorder 1 . Whilst theseabnormalities are non-specific, there is evidence that volumereduction in the caudate 2 and frontal lobe 3 are specific abnormalitiesin depression, particularly in late-life depression. MRI studieshave consistently shown an increase in the number and/or severityof signal hyperintensities in the white matter in both unipolar andbipolar disorder 4 . Deep white matter lesions have been shown inelderly patients with unipolar depression predominantly in thefrontal lobes and basal ganglia, supporting the notion offrontostriatal dysfunction in depression. These lesions have beenshown to be associated with poor long-term outcome 5 . A recentpopulation-based study of over 1000 elderly people showed thatthose with severe periventricular white matter lesions were three tofive times more likely to have depressive symptoms than those withonly mild or no white matter lesions, whilst those with severesubcortical but not periventricular white matter lesions were morelikely to have had a history of late-onset depression after the age of60 years than those with only mild or no white matter lesions 6 .Severe white matter lesions are thought to represent vascularabnormalities, findings that support the notion that vascularpathology contributes to the aetiology of late-life depression.Functional neuro-imaging techniques have also advanced ourknowledge of the pathophysiology and chemical pathology ofdepression with the introduction of single-photon emissioncomputed tomography (SPECT), positron emission tomography(PET) and magnetic resonance spectroscopy (MRS). Severalstudies have shown an association between depression, lowcerebral blood flow and low metabolic activity. An extensivereview of the literature showed evidence for low cerebral activityin the frontal lobes in unipolar and bipolar depressive patients,with an inverse correlation with increased severity of depressivesymptoms and an association with low activity in basal gangliaand temporal and limbic regions 7 . Low neurostriatal cerebralblood flow was particularly associated with psychomotor slowing 8and an association between hypofrontality and negative symptomsin depressive patients 9 . This abnormality is of special interestin the elderly because of the interface between depression anddementia in this age group.We compared the cerebral perfusion in a group of elderlydepressed patients with that in age matched healthy subjects andAlzheimer’s disease (AD) patients, using SPECT methodologyand hexamethyl propleneamine oxime (HMPAO) as the radioligand10 . The regional cerebral perfusion values of depressedpatients were intermediate between those of the healthy controlsubjects and the AD patients. This is consistent with theintermediate position of the depressed group on other measures,e.g. radioattenuation on CT scan. In addition to the globalimpairment in cerebral perfusion, there are topographicalabnormalities but the cerebral region thus affected is seen tovary in different studies. Sackeim et al. 11 have argued that thetraditional statistical paradigms, concentrating on identifyingspecific brain regions with higher or lower perfusion compared tocontrol subjects, have failed to examine the important issue ofidentifying the abnormal patterning of regional activity, whichwould reflect the activity of functional neural networks. Using anovel scaled subprofile model based on factor analytic technique,they demonstrated topographical abnormalities in the temporoparietalarea, largely consisting of polymodal association cortexwith strong reciprocal connection with the prefrontal polymodalassociation cortex. The study by Baxter et al. 12 on glucosemetabolism using PET strongly suggests that the biologicalsubstrate common to depressive states in different patient groupsis a reduction in glucose metabolism in the left prefrontal cortex.The impairment in cerebral perfusion correlates positively withthe endogenicity score but not necessarily with the severity ofdepressive illness 13 . This is in contrast with studies on cerebralglucose metabolism using PET, reporting a positive correlationbetween the severity of depressive symptoms and glucosemetabolic rate. There are some reports on abnormality in theanteroposterior gradient in cerebral perfusion in depressive illness,but these are not consistent.The temporal sequence of the perfusion abnormality andclinical depression is yet unclear. The impairment in cerebralperfusion improved with clinical recovery, suggesting that thecontinuing impairment can predict chronicity of the course orfrequent relapse of depression. This notion can be examined infurther longitudinal studies.SPECT and PET techniques have also been utilized toinvestigate the chemical pathology of dopamine and serotoninsystems in depression. SPECT studies of D2 receptors showedincreased D2 receptor density in the striatum, reflecting reduceddopamine function 14 , and an association between increased D2receptor binding in the left striatum in the anterior cingulate gyrusand clinical recovery with selective serotonin reuptake inhibitors15 . Studies of the dopamine transport receptors in depressionshowed increased receptor density in the basal ganglia 16 . StudiesPrinciples and Practice of Geriatric Psychiatry, 2nd edn. Edited by J. R. M. Copeland, M. T. Abou-Saleh and D. G. Blazer&2002 John Wiley & Sons, Ltd