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Electroconvulsive therapy (ECT) is effective for treatment-resistant depression and leads to short-term structural brain changes and decreases in the inflammatory response. However, little is known about how brain structure and inflammation relate to the heterogeneity of treatment response in the months following an index ECT course. A naturalistic six-month study following an index ECT course included 20 subjects with treatment-resistant depression. Upon conclusion of the index ECT course and again after six months, structural magnetic resonance imaging scans and peripheral inflammation measures [interleukin-6 (IL-6), IL-8, tumor necrosis factor (TNF- ), and C-reactive protein] were obtained. Voxel-based morphometry processed with the CAT-12 Toolbox was used to estimate changes in gray matter volume. Between the end of the index ECT course and the end of follow-up, we found four clusters of significant decreases in gray matter volume ( < 0.01, FWE) and no regions of increased volume. Decreased HAM-D scores were significantly related only to reduced IL-8 level. Decreased volume in one cluster, which included the right insula and Brodmann's Area 22, was related to increased HAM-D scores over six months. IL-8 levels did not mediate or moderate the relationship between volumetric change and depression. Six months after an index ECT course, multiple regions of decreased gray matter volume were observed in a naturalistic setting. The independent relations between brain volume and inflammation to depressive symptoms suggest novel explanations of the heterogeneity of longer-term ECT treatment response.

Inflammation plays a role in depression pathophysiology and treatment response, with effects varying by sex and therapeutic modality. Lower levels of interleukin(IL)-8 predict depression response to antidepressant medication and to electroconvulsive therapy (ECT), although ECT effects are specific to females. Whether IL-8 predicts depression response to ketamine and in a sex-specific manner is not known. Here, depressed patients (n = 46; female, n = 17) received open label infusion of ketamine (0.5 mg/kg over 40 min; NCT02165449). Plasma levels of IL-8 were evaluated at baseline and post-treatment. Baseline levels of IL-8 had a trending association with response to ketamine, depending upon sex (responder status × sex interaction: p = 0.096), in which lower baseline levels of IL-8 in females (p = 0.095) but not males (p = 0.96) trended with treatment response. Change in levels of IL-8 from baseline to post-treatment differed significantly by responder status (defined as ≥50% reduction in Hamilton Depression Rating Scale [HAM-D] Score), depending upon sex (responder status × sex × time interaction: F(1,42)=6.68, p = 0.01). In addition, change in IL-8 interacted with sex to predict change in HAM-D score (β = -0.63, p = 0.003); increasing IL-8 was associated with decreasing HAM-D score in females (p = 0.08) whereas the inverse was found in males (p = 0.02). Other inflammatory markers (IL-6, IL-10, tumor necrosis factor-α, C-reactive protein) were explored with no significant relationships identified. Given these preliminary findings, further evaluation of sex differences in the relationship between IL-8 and treatment response is warranted to elucidate mechanisms of response and aid in the development of personalized approaches to depression treatment.

Background There are many prognostic factors for treatment outcome in major depressive disorder (MDD). The predictive power of any single factor, however, is limited. We aimed to develop profiles of antidepressant response and remission based upon hierarchical combinations of baseline clinical and demographic factors. Methods Using data from Level 1 of the Sequenced Treatment Alternatives to Relieve Depression trial (STAR*D), in which 2,876 participants with MDD were treated with citalopram, a signal‐detection analysis was performed to identify hierarchical predictive profiles for patients with different treatment outcome. An automated algorithm was used to determine the optimal predictive variables by evaluating sensitivity, specificity, positive and negative predictive value, and test efficiency. Results Hierarchical combinations of baseline clinical and demographic factors yielded profiles that significantly predicted treatment outcome. In contrast to an overall 47% response rate in STAR*D Level 1, response rates of profiled patient subgroups ranged from 31 to 63%. In contrast to an overall remission rate of 28%, identified subsets of patients had a 12 to 55% probability of remission. The predictors of antidepressant treatment outcome most commonly incorporated into profiles were related to socioeconomic status (e.g., income, education), whereas indicators of depressive symptom type and severity, as well as comorbid clinical conditions, were useful but less powerful predictors. Conclusions Hierarchical profiles of demographic and clinical baseline variables categorized patients according to the likelihood they would benefit from a single antidepressant trial. Socioeconomic factors had greater predictive power than symptoms or other clinical factors, and profiles combining multiple factors were stronger predictors than individual factors alone.

To evaluate deficits of delayed free recall in euthymic older patients with bipolar disorder and relate deficits to resting cerebral metabolism. Two group, between subjects. Outpatient. Participants included 16 older adult (mean age, 58.7 years; SD = 7.5) euthymic outpatients with bipolar disorder (10 Type I and 6 Type II) and 11 healthy comparison subjects (mean age, 58.3 years; SD = 5.2). All participants received resting positron emission tomography with 18flurodeoxyglucose and, within 10 days, delayed free verbal recall testing with the California Verbal Learning Test II. Patients with bipolar disorder, relative to healthy comparison subjects, had significantly poorer delayed free verbal recall. In patients with bipolar disorder, relative to healthy comparison subjects, prefrontal hypometabolism (dorsolateral prefrontal cortex) and paralimbic hypermetabolism (hippocampus, parahippocampal gyrus, and superior temporal gyrus) was associated with recall deficits in patients with bipolar disorder. Prefrontal and limbic metabolism were inversely related. Our findings demonstrate an association between prefrontal hypometabolism and paralimbic hypermetabolism and verbal memory deficits in euthymic older patients with bipolar disorder. Verbal memory deficits may be a clinical consequence of corticolimbic dysregulation in bipolar disorder, even during euthymia. This suggests that such dysregulation and related deficits could be bipolar disorder traits.

Metabolic syndrome is prevalent in older adults and increases the risk of cardiovascular disease. Second-generation antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone) increase the risk of metabolic syndrome and present many challenges for psychiatrists. In this article, we review the relationships between second-generation antipsychotics and metabolic syndrome with a focus on older adults. Because few studies focus exclusively on older adults, we augment this review with relevant findings from younger adults. The differential risk factors of each medication are reviewed, as are recent findings in monitoring and treating metabolic syndrome. Olanzapine and clozapine are more strongly associated with metabolic risks, whereas aripiprazole and ziprasidone are less associated. Although lifestyle modifications can help to reduce some aspects of metabolic syndrome, lifestyle modifications in conjunction with metformin therapy appear to be most effective.

Objectives: To evaluate the impact of external memory devices on the efficacy of a package of internal mnemonic techniques. Participants wrote two types of lists during the study phase: (a) a list of study words and/or (b) a loci list. At recall, participants were not allowed to refer to either of the lists they had written during the study. Design: 2 × 2 factorial with writing study words (“write” or “not write”) and writing down a previously established loci list (“write” or “not write”) manipulated as between-participants variables. Participants: 68 community-dwelling adults 55 years of age and older who wished to improve their memory. Measurements: Free word recall. Results: There were statistically significant effects of writing the loci list, but not of writing the list of study words. Scores were higher when participants wrote the loci lists compared to when they did not. Conclusions: Use of external mnemonics may enhance the efficacy of internal mnemonics, even when the external mnemonic is not used at the time of recall.

Objectives: To describe the Gottfries-Bråne-Steen (GBS) Rating Scale more fully with instruments commonly used for the diagnostic assessment of older patients with cognitive disturbances – the Mini Mental State Examination (MMSE), Hamilton Depression Rating Scale (HDRS), and Global Deterioration Scale (GDS) – and to characterize the specific diagnostic value of the GBS. Design: A multicenter study including patients diagnosed with senile dementia of the Alzheimer type (SDAT; age at onset: > 75 years) and age-matched non-demented subjects. Subjects: One hundred thirty-eight consecutively referred SDAT patients and 116 non-demented age-matched healthy subjects selected from among relatives of the patients. Methods: The MMSE, GBS and HDRS were used for assessing patients and controls. The GDS was utilized for dementia staging. Findings: Principal component analysis carried out on GBS scores yielded three factors explaining 74% of variance: factor 1, general functioning; factor 2, depression, and factor 3, restlessness. The actual composition of these factors was analyzed after computing factor scores for each subject by means of forward selection regressions, each using the MMSE, GDS and HDRS as predictors of scores on a given factor. The best predictors were MMSE and GDS scores for factor 1; HDRS for factor 2, and MMSE for factor 3. A GBS cutoff of 8 (obtained after a quality receiver operating characteristic analysis) best discriminated between demented and non-demented subjects (positive-predictive value: 0.88; negative-predictive value: 0.90). Conclusions: The GBS Rating Scale for dementia can be a useful tool in routine clinical assessment of older subjects with cognitive impairment and distinguishes between demented and non-demented subjects; it gives comprehensive information on functional and psychobehavioral characteristics of demented patients, being composed of factors related to the MMSE and HDRS.

The Geriatric Depression Scale (GDS) is commonly used to measure depression in the elderly. However, there have been no reports of the underlying structure of the GDS. To this end, the GDS was administered to 326 community-dwelling elderly subjects, and the data were subjected to a factor analysis. A five-factor solution was selected and, after a varimax rotation, the factors that emerged could be described as: (1) sad mood, (2) lack of energy, (3) positive mood, (4) agitation, and (5) social withdrawal. This solution accounted for 42.9% of the variance. Knowledge of the factor structure should aid both clinicians and researchers in the interpretation of responses on the GDS.