Frequency and outcomes of painful physical symptoms in a naturalistic population with major depressive disorder: an analysis of pooled observational studies focusing on subjects aged 65 years and over.

AIMS: To estimate the frequency of painful physical symptoms (PPS) in elderly subjects (≥ 65 years) with major depressive disorder (MDD) in real-world clinical conditions and to establish whether PPS are associated with poor depression outcomes, including more severe depression and worse health-related quality of life (HRQoL). METHODS: Observational studies of MDD that included assessment of PPS and elderly subjects were screened. Measures of PPS were based on the Somatic Symptom Inventory (SSI) or Visual Analogue Scale (VAS). Data from a variety of depressive symptom severity and HRQoL scales were used. Analysis cohorts were based on age [aged ≥ 65 years (elderly) or < 65 years (younger)] and/or PPS status (presence or absence); five subsets were used to examine specific outcomes in matched elderly subjects. RESULTS: Data from seven studies (representing 26 countries) were collated. Of the 11,477 subjects, 14% were aged ≥ 65 years and 71% were classified as having PPS (PPS+). PPS were more frequent in elderly subjects (74% vs. 70% of younger subjects) and were positively associated with being female and Hispanic, and negatively associated with being East Asian in the elderly. The presence of PPS was associated with more severe clinical symptomatology and comparatively poorer HRQoL in elderly subjects. CONCLUSIONS: PPS, although frequent in younger MDD patients, were slightly more frequent in elderly MDD patients and associated with comparatively poorer clinical and functional outcomes. As elderly patients report somatic symptoms more readily than emotional symptoms, physicians should consider depression in addition to physical causes when PPS are present.

Conceptualizing impulsivity and risk taking in bipolar disorder: importance of history of alcohol abuse.

BACKGROUND: Elevated levels of impulsivity and increased risk taking are thought to be core features of both bipolar disorder (BD) and addictive disorders. Given the high rates of comorbid alcohol abuse in BD, alcohol addiction may exacerbate impulsive behavior and risk-taking propensity in BD. Here we examine multiple dimensions of impulsivity and risk taking, using cognitive tasks and self-report measures, in BD patients with and without a history of alcohol abuse. METHODS: Thirty-one BD subjects with a prior history of alcohol abuse or dependence (BD-A), 24 BD subjects with no history of alcohol abuse/dependence (BD-N), and 25 healthy control subjects (HC) were assessed with the Barratt Impulsiveness Scale (BIS) and the computerized Balloon Analogue Risk Task (BART). RESULTS: Both BD groups scored significantly higher than controls on the BIS. In contrast, only the BD-A group showed impaired performance on the BART. BD-A subjects popped significantly more balloons than the BD-N and HC groups. In addition, subjects in the BD-A group failed to adjust their performance after popping balloons. Severity of mood symptomatology was not associated with performance on either task. DISCUSSION: The current study supports a primary role of prior alcohol abuse in risk-taking propensity among patients with bipolar disorder. In addition, findings suggest that impulsivity and risky behavior, as operationalized by self-report and experimental cognitive probes, respectively, are separable constructs that tap distinct aspects of the bipolar phenotype.

Cortical sulci and bipolar disorder.

The width of cortical sulci in bipolar patients (n=19) and healthy controls (n=35) was examined using a novel automated technique involving magnetic resonance imaging. All sulci were wider for bipolar patients than for healthy controls. Bipolar-control differences were largest for the superior and intermediate frontal sulci, smallest for the occipital and cingulate sulci, and intermediate in magnitude for the other sulci (intraparietal, inferior frontal, and central sulci). The results were interpreted in terms of neurodegenerative-illness-related processes, which could produce cortical atrophy and result in wider sulci.

Dissociable mechanisms for memory impairment in bipolar disorder and schizophrenia.

BACKGROUND: Although memory deficits are consistently reported in schizophrenia and bipolar disorder, the mechanisms underlying these impairments are poorly understood. Clarifying the nature and degree of overlap in memory deficits between the two illnesses could help to distinguish brain systems disrupted in these illnesses, and indicate cognitive remediation strategies to improve patient outcomes. METHOD: We examined performance on a non-verbal memory task in clinically stable out-patients with bipolar disorder (n=40), schizophrenia (n=40), and healthy comparison subjects (n=40). This task includes conditions in which distinct mnemonic strategies -- namely, using context to organize familiar stimuli or using holistic representation of novel stimuli -- facilitate performance. RESULT: When compared to a reference condition, bipolar patients had deficits consistent with organizational dysfunction and poor detection of novel information. Although patients with schizophrenia performed worse than the other groups, they were only differentially impaired when organizational demands were significant. Task performance was not correlated with severity of clinical symptomatology. CONCLUSIONS: This pattern of distinct memory impairments implies disturbances in partially overlapping neural systems in bipolar disorder and schizophrenia. Evidence of impairment in detection of novel stimuli that is unique to bipolar disorder suggests that, while the absolute level of cognitive dysfunction is less severe in bipolar disorder as compared to schizophrenia, subtle disruptions in memory are present. These findings can be used to plan targeted cognitive remediation programs by helping patients to capitalize on intact functions and to learn new strategies that they do not employ without training.

Differential working memory impairment in bipolar disorder and schizophrenia: effects of lifetime history of psychosis.

BACKGROUND: Although bipolar disorder and schizophrenia have long been viewed as distinct illnesses, there is growing evidence that these two complex diseases share some common genes, which may manifest as overlapping neuropsychological impairments. Although working memory dysfunction has been proposed to be central to the pathophysiology of schizophrenia, it has received less attention in studies of bipolar disorder. METHOD: We applied measures of working memory to patients with schizophrenia (n = 15), patients with schizoaffective disorder (n = 15), patients with psychotic (n = 11) and non-psychotic (n = 15) bipolar disorder, and demographically matched healthy subjects (n = 32), in order to determine the extent to which these groups show common or unique impairments. RESULTS: While patients with bipolar disorder (with and without psychotic features) and those with schizophrenia/schizoaffective disorder were impaired on backward digit span, only patients with a lifetime history of psychotic features, regardless of diagnosis, were impaired on spatial delayed response task. CONCLUSIONS: Backward digit span performance is comparable in bipolar disorder and schizophrenia, and may be an appropriate endophenotypic marker that cuts across diagnostic categories. In contrast, spatial working memory performance clearly distinguishes non-psychotic bipolar disorder patients from patients with functional psychosis.

Mood disorders - review of structural MRI studies.

BACKGROUND: Mood disorders are related to considerable morbidity and mortality, and although there is little doubt that they are brain-based disorders, their neural correlates still remain elusive. A neuro-anatomic model of mood regulation comprising the prefrontal cortex, amygdala-hippocampus complex, thalamus, basal ganglia, and connections among these areas has been proposed. OBJECTIVE: We reviewed the evidence for regional brain abnormalities in bipolar disorder, and attempted to integrate available findings into a comprehensive pathophysiological model of illness. METHODS: A computerized Medline Ovid search was conducted for the period 1966-2002, and complemented by a manual search of bibliographical references from recent reviews. Articles meeting specified criteria were included. RESULTS: Hyperintense lesions in cortical and subcortical regions are the most consistently reported and widely studied structural abnormalities. Smaller prefrontal cortical volume is a common finding in bipolar disorder and unipolar depression. Enlarged amygdala (in bipolar disorder) and smaller hippocampus (in unipolar depression) have been reported by several groups. Decreased volumes (in unipolar depression) and increased or unaltered volumes (in bipolar disorder) of striatal structures have been reported. CONCLUSIONS: Bipolar and unipolar mood disorders are associated with detectable structural brain abnormalities. The histopathology underlying such anatomical changes remains to be elucidated. To reach more definitive conclusions about neuroanatomical changes that take place during the course of mood disorders, prospective longitudinal studies are needed. Also, integration with functional imaging is necessary in order to elucidate the relevance of identified structural abnormalities.