Faculty Bibliography

Major depressive disorder (MDD) is common. Despite numerous available treatments, many individuals fail to improve clinically. MDD continues to be diagnosed exclusively via behavioral rather than biological methods. Biomarkers-which include measurements of genes, proteins, and patterns of brain activity-may provide an important objective tool for the diagnosis of MDD or in the rational selection of treatments. Proteomic analysis and validation of its results as biomarkers is less explored than other areas of biomarker research in MDD. Mass spectrometry (MS) is a comprehensive, unbiased means of proteomic analysis, which can be complemented by directed protein measurements, such as Western Blotting. Prior studies have focused on MS analysis of several human biomaterials in MDD, including human post-mortem brain, cerebrospinal fluid (CSF), blood components, and urine. Further studies utilizing MS and proteomic analysis in MDD may help solidify and establish biomarkers for use in diagnosis, identification of new treatment targets, and understanding of the disorder. The ultimate goal is the validation of a biomarker or a biomarker signature that facilitates a convenient and inexpensive predictive test for depression treatment response and helps clinicians in the rational selection of next-step treatments.

Individuals with posttraumatic stress disorder (PTSD) experience cognitive impairments and disability in everyday activities. In other neuropsychiatric disorders, impairments in cognition and functional capacity (i.e., the ability to perform everyday tasks) are associated with impairments in real-world functioning, independent of symptom severity. To date, no studies of functional capacity have been conducted in PTSD. Seventy-three women with moderate to severe PTSD underwent assessment with measures of cognition (MATRICS Consensus Cognitive Battery: MCCB), functional capacity (UCSD Performance-Based Skills Assessment-Brief: UPSA-B), PTSD (Clinician-Administered PTSD Scale and PTSD Symptom Scale-Self-report (PSS-SR)), and depression (Montgomery Asberg Depression Rating Scale). Patients also reported their subjective level of disability (Sheehan Disability Scale). Over-reporting of symptom severity was assessed using six validity items embedded within the PSS-SR. Results indicated that on average PTSD patients manifested mild impairments on the functional capacity measure, performing about 1/3 standard deviation below healthy norms, and similar performance on the MCCB. Both clinician-rated and self-rated PTSD symptom severity correlated with self-reported disability but not with functional capacity. Self-reported disability did not correlate with functional capacity or cognition. Greater self-reported disability, depression, and PTSD symptoms all correlated with higher scores on the PSS-SR validity scale. The divergence between objective and subjective measures of disability suggests that individuals' distress, as indexed by symptom validity measures, may be impacting self-reports of disability. Future studies of disability should incorporate objective measures in order to obtain a broad perspective on functioning.

The depression-executive dysfunction syndrome, a late-onset depression of vascular origin with executive dysfunction and psychomotor retardation, has also been described after stroke. We verified whether this syndrome also occurs in nonelderly stroke patients by investigating the association between domains of depressive symptoms with executive functions in 87 first-ever ischemic stroke patients. The retardation domain of the 31-item Hamilton Rating Scale for Depression was associated with decreased performance on verbal fluency (assessed with FAS). The association was maintained for younger patients (aged <60 years) after adjusting for confounders. This result supports the clinical presentation of depression-executive dysfunction syndrome in younger stroke patients. Confirmation of this finding, its neural correlates, and clinical implication deserve further investigation.

OBJECTIVES: The aims of this study were to evaluate correlates and predictors of life functioning and quality of life in bipolar disorder during a comparative effectiveness trial of moderate doses of lithium. METHODS: In the Lithium treatment moderate-dose use study (LiTMUS), 283 symptomatic outpatients with bipolar disorder type I or II were randomized to receive lithium plus "optimal personalized treatment (OPT)", or OPT alone. Participants were assessed using structured diagnostic interviews, clinician-rated blinded assessments, and questionnaires. We employ linear mixed effects models to test the effect of treatment overall and adjunct lithium specifically on quality of life or functioning. Similar models are used to examine the association of baseline demographics and clinical features with quality of life and life functioning. RESULTS: Quality of life and impaired functioning at baseline were associated with lower income, higher depressive severity, and more psychiatric comorbid conditions. Over 6 months, patients in both treatment groups improved in quality of life and life functioning (p-Values<0.0001); without a statistically significant difference between the two treatment groups (p-Values>0.05). Within the lithium group, improvement in quality of life and functioning was not associated with concurrent lithium levels at week 12 or week 24 (p-Values>0.05). Lower baseline depressive severity and younger age of onset predicted less improvement in functioning over 6 months. CONCLUSIONS: Optimized care for bipolar disorder improves overall quality of life and life functioning, with no additional benefit from adjunct moderate doses of lithium. Illness burden and psychosocial stressors were associated with worse quality of life and lower functioning in individuals with bipolar disorder.