Frontal lobe hypoperfusion and depressive symptoms in Alzheimer disease.

BACKGROUND: Depressive symptoms of varying severity are prevalent in up to 63% of Alzheimer disease (AD) patients and often result in greater cognitive decline and increased caregiver burden. The current study aimed to determine the neural correlates of depressive symptoms in a sample of AD patients. METHODS: Using the Cornell Scale for Depression in Dementia, we assessed 56 patients who met criteria for probable AD. Data obtained from Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (SPECT) were analyzed with the use of a magnetic resonance imaging-derived region of interest (ROI) anatomic template before and after atrophy correction and statistical parametric mapping (SPM). The following 4 frontal ROIs were investigated bilaterally: middle frontal gyrus (Brodmann's area [BA] 46), orbitofrontal cortex (BA 11), superior prefrontal (BA 8/9) and anterior cingulate (BA 24/25/32/33). RESULTS: Depressive symptoms were present in 27 of the AD patients (48%). Patients with depressive symptoms showed less perfusion in the right superior and bilateral middle frontal gyri (p < 0.005), left superior frontal (p < 0.05) and anterior cingulate gyri (p < 0.005) before atrophy correction. SPM analyses revealed significantly lower perfusion in bilateral dorsolateral and superior prefrontal cortex of patients with depressive symptoms (right, p < 0.005; left, p < 0.05). SPECT ROI analyses with atrophy correction revealed trends similar to data without atrophy correction but did not reach statistical significance. CONCLUSION: In this study, depressive symptoms in AD patients were associated with relative hypoperfusion in the prefrontal cortex when they were compared with AD patients without depressive symptoms. These findings are consistent with previous reports in studies of primary depression suggesting that these regions are involved in affect and emotional regulation.

A functional neuroimaging study of appetite loss in Alzheimer's disease.

BACKGROUND: Alzheimer's Disease (AD) is frequently associated with changes in appetite. This study investigated the relationship between regional cerebral perfusion and appetite loss in AD. METHODS: 64 patients with possible or probable AD were characterized as being with (n=22) or without (n=44) appetite loss based on the Neuropsychiatric Inventory (NPI) Appetite subscale. 99mTc-ECD SPECT scans were coregistered to a standardized template in Talairach space generating mean ratios of uptake referenced to the cerebellum. Regions of interest (ROIs) included anterior cingulate cortex (ACC), middle mesial temporal cortex (MTC-m), inferior mesial temporal cortex (MTC-i), insula (INS), orbitofrontal cortex (OFC) and thalamus-hypothalamus (THAL). RESULTS: Backward stepwise logistic regression analysis of these ROIs showed hypoperfusion in the L-ACC (p=0.015) and L-OFC (p=0.015), relative sparing of perfusion in the R-ACC (p=0.010), R-OFC (p=0.010) and L-MTC-m (p=0.006), and greater anxiety (p=0.005) independently predicted loss of appetite (chi(2)=22.24, p=0.001, Nagelkerke R(2)=0.41). CONCLUSIONS: Hypoperfusion in the left anterior cingulate and left orbitofrontal cortices, and relative sparing of perfusion in the right anterior cingulate, right orbitofrontal and left middle mesial temporal cortices emerged as predictors of appetite loss in this sample of patients. These findings are consistent with impairments in the extrinsic motivational pathways of eating and impaired reward value of food as components of appetite loss in AD.

Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder.

BACKGROUND: As patients with mood disorders manifest heterogeneity in phenomenology, pathophysiology, etiology, and treatment response, a biological classification of mental disease is urgently needed to advance research. Patient and methodological variability complicates the comparison of neuroimaging study results and limits heuristic model development and a biologically-based diagnostic schema. OBJECTIVE: We have critically reviewed and compared the magnetic resonance neuroimaging literature to determine the degree and directionality of volumetric changes in brain regions putatively implicated in the pathophysiology of major depressive disorder (MDD) versus bipolar disorder (BD). METHODS: A total of 140 published magnetic resonance imaging investigations evaluating subjects with BD or MDD were selected to provide a summary and interpretation of volumetric neuroimaging results in MDD and BD. Further commentary on the pathophysiological implications, and putative cellular and pharmacological mechanisms, is also provided. RESULTS: While whole brain volumes of patients with mood disorders do not differ from those of healthy controls, regional deficits in the frontal lobe, particularly in the anterior cingulate and the orbitofrontal cortex, appear to consistently differentiate subjects with mood disorders from the general population. Preliminary findings also suggest that subcortical structures, particularly the striatum, amygdala, and hippocampus, may be differentially affected in MDD and BD. CONCLUSIONS: Structural neuroimaging studies have consistently identified regional abnormalities in subjects with mood disorders. Future studies should strive to definitively establish the influence of age and medication.

Relationship between regional brain metabolism, illness severity and age in depressed subjects.

We sought to examine the effects of age, depression chronicity, and treatment responsiveness on glucose metabolism in a large well-characterized sample of depressed men and a psychiatrically unaffected control group. The subjects were unmedicated, symptomatic, right-handed males (n=66) who met DSM-IV criteria for a major depressive episode in the context of a major depressive disorder (MDD, n=66) and never depressed, right-handed, healthy control subjects (HC, n=24). Subjects in the MDD group were subsequently classified as responders, or non-responders to a six-week trial of paroxetine monotherapy (20-60 mg). Statistical parametric mapping (SPM) was used to analyze the relationship between age and cerebral glucose metabolism (18-fluorodeoxyglucose positron emission tomography) and the modulation by treatment responsivity and a history of prior depressive episodes. Metabolic activity in the rostral and dorsal anterior cingulate cortex showed a significant negative correlation with age in MDD, but not in HC. Non-response to treatment and previous depressive episodes were associated with a higher degree of age-dependent hypometabolism in the rostral and anterior cingulate cortex. The age-dependent changes documented herein may influence the distinct clinical presentation and treatment response described in older-age depression.

Sexual function during bupropion or paroxetine treatment of major depressive disorder.

OBJECTIVE: The primary objective was to evaluate sexual function (SF) separately in men and women with major depressive disorder (MDD) before and during treatment with bupropion sustained release (SR) or paroxetine. The secondary objectives involved a comparative evaluation of the Sex Effects Scale (Sex FX) and the Investigator-Rated Sexual Desire and Functioning Scale (IRSD-F), as well as a comparison of antidepressant outcomes and an examination of the relation between level of depression and SF over time. METHOD: There were 141 patients (68 women and 73 men) who met DSM-IV criteria for a current major depressive episode. They were randomly assigned to receive bupropion SR (150 to 300 mg daily) or paroxetine (20 to 40 mg daily) under double-blind trial conditions. Patients were assessed at baseline and at 2, 4, 6, and 8 weeks with the 17-item Hamilton Depression Rating Scale (HDRS17), Sex FX, and IRSD-F. RESULTS: Prior to treatment, women reported significantly lower SF on both the Sex FX and IRSD-F scales, compared with men. During treatment, there were no significant drug differences on measures of SF over time for women; however, men who were treated with paroxetine reported a worsening of SF, whereas bupropion SR did not significantly alter SF. Both bupropion SR and paroxetine produced clinically and statistically significant reductions in HDRS17 scores as well as comparable rates of response and remission. There was a statistically significant correlation between the 2 measures of SF at all visits. There was also a significant inverse relation between depression and SF in women, but not in men, irrespective of drug. CONCLUSION: According to the Sex FX scale, a significant difference in antidepressant-related sexual dysfunction was detected in men, but not women, during treatment with bupropion SR or paroxetine.