Dora Kanellopoulos

Problem-Solving Therapy and Supportive Therapy in Older Adults With Major Depression and Executive Dysfunction

OBJECTIVE The purpose of this study was to determine whether problem-solving therapy is an effective treatment in older patients with depression and executive dysfunction, a population likely to be resistant to antidepressant drugs. METHOD Participants were adults age 60 and older with major depression and executive dysfunction. Problem-solving therapy was modified to be accessible to this population. Participants were randomly assigned to 12 weekly sessions of problem-solving therapy or supportive therapy and assessed at weeks 3, 6, 9, and 12. RESULTS Of the 653 individuals referred for this study, 221 met selection criteria and were enrolled in the study. Reduction of depressive symptom severity was comparable for the two treatment groups during the first 6 weeks of treatment, but at weeks 9 and 12 the problem-solving therapy group had a greater reduction in symptom severity, a greater response rate, and a greater remission rate than the supportive therapy group (response rates at week 9: 47.1% and 29.3%; at week 12:56.7% and 34.0%; remission rates at week 9: 37.9% and 21.7%; at week 12: 45.6% and 27.8%). Problem-solving therapy yielded one additional response or remission over supportive therapy for every 4.4-5.6 patients by the end of the trial. CONCLUSIONS These results suggest that problem-solving therapy is effective in reducing depressive symptoms and leading to treatment response and remission in a considerable number of older patients with major depression and executive dysfunction. The clinical value of this finding is that problem-solving therapy may be a treatment alternative in an older patient population likely to be resistant to pharmacotherapy.

Problem-solving therapy and supportive therapy in older adults with major depression and executive dysfunction: effect on disability.

CONTEXT Older patients with depression and executive dysfunction represent a population with significant disability and a high likelihood of failing pharmacotherapy. OBJECTIVES To examine whether problem-solving therapy (PST) reduces disability more than does supportive therapy (ST) in older patients with depression and executive dysfunction and whether this effect is mediated by improvement in depressive symptoms. DESIGN Randomized controlled trial. SETTING Weill Cornell Medical College and University of California at San Francisco. PARTICIPANTS Adults (aged >59 years) with major depression and executive dysfunction recruited between December 2002 and November 2007 and followed up for 36 weeks. Intervention Twelve sessions of PST modified for older depressed adults with executive impairment or ST. Main Outcome Measure Disability as quantified using the 12-item World Health Organization Disability Assessment Schedule II. RESULTS Of 653 individuals referred to this study, 221 met the inclusion criteria and were randomized to receive PST or ST. Both PST and ST led to comparable improvement in disability in the first 6 weeks of treatment, but a more prominent reduction was noted in PST participants at weeks 9 and 12. The difference between PST and ST was greater in patients with greater cognitive impairment and more previous episodes. Reduction in disability paralleled reduction in depressive symptoms. The therapeutic advantage of PST over ST in reducing depression was, in part, due to greater reduction in disability by PST. Although disability increased during the 24 weeks after the end of treatment, the advantage of PST over ST was retained. CONCLUSIONS These results suggest that PST is more effective than ST in reducing disability in older patients with major depression and executive dysfunction, and its benefits were retained after the end of treatment. The clinical value of this finding is that PST may be a treatment alternative in an older patient population likely to be resistant to pharmacotherapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00052091.

WHITE MATTER INTEGRITY PREDICTS STROOP PERFORMANCE IN PATIENTS WITH GERIATRIC DEPRESSION

BACKGROUND This study tested the hypothesis that microstructural white matter abnormalities in frontostriatal-limbic tracts are associated with poor response inhibition on the Stroop task in depressed elders. METHOD Fifty-one elders with major depression participated in a 12-week escitalopram trial. Diffusion tensor imaging was used to determine fractional anisotropy (FA) in white matter regions. Executive function (response inhibition) was assessed with the Stroop task. Voxelwise correlational analysis was used to examine the relationship between Stroop performance and fractional anisotropy. RESULTS Significant associations between FA and Stroop color word interference were evident in multiple frontostriatal-limbic regions, including white matter lateral to the anterior and posterior cingulate cortex and white matter in prefrontal, insular, and parahippocampal regions. CONCLUSIONS These findings suggest that microstructural white matter abnormalities of frontostriatal-limbic networks are associated with executive dysfunction of late-life depression. This observation provides the rationale for examination of specific frontostriatal-limbic pathways in the pathophysiology of geriatric depression.

Functional connectivity in apathy of late-life depression: A preliminary study

BACKGROUND Apathy is common in late-life depression and is associated with disability and poor antidepressant response. This study examined whether resting functional connectivity (FC) of the nucleus accumbens (NAcc) and the dorsal anterior cingulate (dACC) with other structures can distinguish apathetic depressed older patients from non-apathetic depressed patients and normal subjects. METHODS Twenty-six non-demented, non-MCI older adults were studied. Of these, 16 had major depression (7 also had apathy) and 10 had no psychopathology. Resting state fMRI was performed prior to treatment in subjects who were psychotropic-free for at least two weeks. FC was determined by placing seeds in the NAcc and the dACC bilaterally. RESULTS Apathetic depressed patients had lower FC of the NAcc with the amygdala, caudate, putamen, globus pallidus, and thalamus and increased FC with the dorsomedial prefrontal cortex, the superior frontal cortex, and the insula than non-apathetic patients. Further, apathetic patients had lower FC of the dACC with dorsolateral and ventrolateral prefrontal cortices and higher FC with the insula and the orbitofrontal cortex than non-apathetic patients. LIMITATIONS Small number of subjects, lack of random sampling, use of a 1.5T MRI scanner. CONCLUSIONS This preliminary study suggests that FC between the NAcc and the dACC and structures related to reward and related behavioral responses constitute the functional topography of abnormalities characterizing apathy of late life depression. However, replication is needed.

Serotonin transporter polymorphisms, microstructural white matter abnormalities and remission of geriatric depression

OBJECTIVE This study compared microstructural abnormalities in depressed elders and controls and studied the association of the serotonin transporter gene status to white matter abnormalities and to remission of depression. METHODS The subjects were Caucasians with non-psychotic major depression and normal elders. Depressed subjects received escitalopram 10 mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed and voxel-based analysis of fractional anisotropy (FA) was conducted using age and mean diffusivity as covariates. RESULTS Depressed elders (N=27) had lower FA than controls (N=27) in several frontolimbic areas. Depressed elderly S-allele carriers also had lower FA than L homozygotes in frontolimbic brain areas, including the dorsal and rostral anterior cingulate, posterior cingulate, dorsolateral prefrontal and medial prefrontal regions, thalamus, and in other regions. S-allele carriers had a lower remission rate than L homozygotes. LIMITATIONS Small number of subjects, lack of random sampling, fixed antidepressant dose, short follow-up. CONCLUSIONS Lower FA was observed in several frontolimbic and other regions in depressed elders compared to controls. Depressed S-allele carriers had both microstructural white matter abnormalities in frontolimbic networks and a low remission rate. It remains unclear whether the risk for chronicity of geriatric depression in S-allele carriers is mediated by frontolimbic compromise. However, these observations set the stage for studies aiming to identify the relationship of S allele to impairment in specific frontolimbic functions interfering with response of geriatric depression to antidepressants.

Anterior Cingulate Cortical Volumes and Treatment Remission of Geriatric Depression

Structural abnormalities of the anterior cingulate cortex (ACC) may interfere with the interaction of cortical and limbic networks involved in emotional regulation and contribute to chronic depressive syndromes in the elderly. This study examined the relationship of regional anterior cingulate cortical volumes with treatment remission of elderly depressed patients. We hypothesized that patients who failed to remit during a 12‐week controlled treatment trial of escitalopram would exhibit smaller anterior cingulate gray matter volumes than patients who remitted.

Problem solving therapy for the depression-executive dysfunction syndrome of late life

The ‘depression executive dysfunction syndrome’ afflicts a considerable number of depressed elderly patients and may be resistant to conventional pharmacotherapy. Non‐pharmacological approaches addressing their behavioral deficits may reduce disability and experienced stress and improve depression.

BDNF Val66met Polymorphism, White Matter Abnormalities and Remission of Geriatric Depression

OBJECTIVE The polymorphism BDNF val66met of the brain derived neurotrophic factor (BDNF) is common, may increase the risk for depression, and affects BDNF secretion, critical for neuronal survival, plasticity, neurogenesis, and synaptic connectivity. Our objectives were: 1) to test the hypothesis that BDNF(val/met) status influences the remission rate of geriatric depression; 2) to explore whether the relationship between BDNF allelic status to remission is influenced by the presence of microstructural white matter abnormalities. METHOD Non-demented older subjects with major depression had a 2-week placebo period, after which those with a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Fractional anisotropy was determined in specific regions using the Reproducible Object Quantification Scheme (ROQS) software that operates on non-normalized data. RESULTS BDNF(met) carriers were more likely to achieve remission than BDNF(val/val) homozygotes after 12 weeks of treatment with escitalopram 10 mg daily. Microstructural abnormalities in the corpus callosum, left superior corona radiata, and right inferior longitudinal fasciculum were also associated with lower remission rate. However, there were no significant interactions between BDNF(val66met) status and microstructural abnormalities in predicting remission. LIMITATIONS Small number of subjects, focus on a single BDNF polymorphism, fixed antidepressant dose. CONCLUSIONS Depressed older BDNF(met) carriers had a higher remission rate than BDNF(val/val) homozygotes. This effect was not related to microstructural white matter abnormalities, which predicted remission independently. We speculate that the relationship between BDNF(val66met) and remission is due to different effects of BDNF in brain structures related to mood regulation.

Semantic organizational strategy predicts verbal memory and remission rate of geriatric depression

This study tests the hypothesis that the use of semantic organizational strategy during the free‐recall phase of a verbal memory task predicts remission of geriatric depression.

Blood pressure and white matter integrity in geriatric depression

BACKGROUND Cerebrovascular disease may increase vulnerability to geriatric depression, a syndrome often accompanied by frontal-subcortical lesions. High blood pressure is a risk factor for cerebrovascular disease and white matter changes. This study examined whether and in which brain regions blood pressure is associated with compromised white matter integrity in elderly depressed patients. METHODS We studied the association between blood pressure and white matter integrity assessed by diffusion tensor imaging (fractional anisotropy, FA) in 41 older patients with major depression. Correlations between FA and blood pressure, after controlling for age, were examined with a voxelwise analysis. RESULTS Significant associations between FA and blood pressure were detected throughout the anterior cingulate and in multiple frontostriatal and frontotemporal regions. LIMITATIONS This study did not employ a healthy control group. Moreover, the relatively small sample size precluded a comparison of patients with and without hypertension. CONCLUSIONS Compromised frontal-striatal white matter integrity may be the anatomical background through which blood pressure confers vulnerability to depression.