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Biomedical subjects

Frederick Cassidy

Publications and source records attributed to Frederick Cassidy.

13 recordsLinked to original sources

Cortical white matter microstructural abnormalities in bipolar disorder.

This article reports on preliminary findings describing microstructural abnormalities in the white matter of cortical areas thought to be associated with bipolar disorder. In all, 14 patients with bipolar disorder and 21 nonpsychiatrically ill control subjects underwent MR imaging including a diffusion tensor imaging (DTI) pulse sequence (six directions, b=1000 mm(2)/s). DTI data were analyzed on a workstation using a program that allowed calculation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within the following three white matter fiber tracts bilaterally: the orbital frontal cortex, and the superior and middle frontal gyri. These values were compared across patient groups. The left and right orbital frontal white matter exhibited significantly higher ADC values in bipolar subjects than control subjects on both the left (p=0.028) and right (p=0.011). Microstructural changes in the white matter of the orbital frontal areas as reflected by increased ADC values appear to be associated with bipolar disorder. Further research is needed to better understand the interaction of microstructural changes and bipolar symptoms and whether these changes are specific to bipolar disorder.

Adult↗

Caudate volume measurement in older adults with bipolar disorder.

BACKGROUND: Decreased caudate volumes have been noted in unipolar depressed subjects, especially in the elderly and those with cognitive impairment. No differences have been noted in initial studies of multi-aged bipolar subjects; however, this region has not been examined in older bipolar subjects. METHODS: We examined the caudate nuclei volumes of 36 older bipolar subjects (mean age 58) and 35 older controls (mean age 62) using logistic regression analyses to control for age and gender differences. Differences between late- and early-onset (age-of-onset before age 45) bipolar subjects were also examined, as well as the effect of length of illness. RESULTS: The right caudate was noted to be smaller in older bipolar subjects compared with older controls when controlled for sex and age (p = 0.0448). No differences were noted in overall brain volume nor lateral ventricular volume between the bipolar and control subjects. Late-onset bipolar subjects had a decrease in brain volume (p = 0.035) compared with early-onset bipolar subjects. Late-onset bipolar subjects had a decrease in the right (p = 0.044) and total (p = 0.04) caudate size compared with older controls. CONCLUSIONS: Right caudate volume is decreased in older bipolar subjects compared to controls. Bipolar subjects with late-onset illness have significantly decreased right and total caudate volumes compared to controls. This is affected by neither the length of illness nor the age of onset. Late-onset bipolar subjects have decreased total brain volume compared with early-onset bipolar subjects.

Age of Onset↗

Social support in elderly patients with bipolar disorder.

OBJECTIVE: The role of social support in bipolar disorder is poorly understood. It is known that young and middle-aged patients with impaired social support are more likely to be treatment resistant and have increased hospitalization. However, the role of social support in elderly patients with bipolar disorder has not been studied. Our purpose was to evaluate social support in older adults with bipolar disorder compared with peer controls and younger bipolar patients. In addition, we looked at the role of social support in the age of illness onset. METHODS: We evaluated social support of 29 older subjects with bipolar disorder (age 50 or older) and 56 younger subjects with bipolar disorder using the Duke Social Support Index, comparing them to non-psychiatric, peer controls. Using logistic regression we then examined the relationship of demographic, social support factors, and age of onset. RESULTS: Both older and younger bipolar subjects perceived their social support as inadequate (OR = 14.98; OR = 9.05) compared with similar aged controls. Younger bipolar subjects also had less social interactions than younger controls (OR = 4.63). These findings remained significant when controlled for gender, marital status, race, and education. No significant differences were noted between early-onset and late-onset bipolar subjects. CONCLUSIONS: Older and younger bipolar patients have decreased perceptions of social support than older controls. No effect was found based on the age of illness onset. In addition, younger subjects had less social interactions than peer controls.

Adult↗

An open label trial of C-1073 (mifepristone) for psychotic major depression.

BACKGROUND: The rationale for treating patients with psychotic major depression (PMD) with glucocorticosteroid receptor (GR) antagonists is explained. METHODS: Thirty patients with PMD, with Hamilton Rating Scale for Depression (HAMD-21) scores of 18 or greater, were assigned in an open label trial to receive 50 mg, 600 mg, or 1200 mg of mifepristone for 7 days. RESULTS: All the subjects completed the protocol; there were no dropouts. Side effects were mild and sporadic. Of 19 subjects in the combined 600- and 1200-mg group, 13 had a 30% or greater decline in their Brief Psychiatric Rating Scale (BPRS) scores, compared with 4 of 11 in the 50-mg group. In the 600- and 1200-mg group, 12 of 19 subjects showed a 50% decline in the BPRS positive symptom subscale, a more sensitive index for the symptoms seen in PMD, compared with 3 of 11 in the 50-mg group; 8 of 19 subjects in the 600- and 1200-mg group had a 50% decline in the HAMD-21, compared with 2 of 11 in the 50-mg group. CONCLUSIONS: These results suggest that short term use of GR antagonists may be effective in the treatment of psychotic major depression and that further blinded studies are warranted.

Adult↗

Investigation of Notch3 as a candidate gene for bipolar disorder using brain hyperintensities as an endophenotype.

The purpose of the study was to consider MRI hyperintensities as a potential endophenotype for bipolar disorder (BPD) and to investigate Notch3 (CADASIL) as a candidate gene for BPD. MRI scans were performed on 21 members of a family with a high incidence of BPD. Two-point and multipoint linkage analyses were performed and two exons of Notch3 were investigated with SSCP. Fifteen of 21 family members had MRI hyperintensities, including all bipolar patients and six family members with no affective illness. Two-point linkage analysis yielded negative results for all models. Multipoint linkage analysis yielded negative results except for Model 1a, in which a maximal LOD score was -1.24. A mutation screen of Exons 3 and 4 was negative. Notch3 does not appear to be a candidate gene for BPD in this family.

Adolescent↗

Hypocholesterolemia during mixed manic episodes.

BACKGROUND: An association of relatively low serum cholesterol with both depression and suicide has been reported. Depressive symptoms, including suicidality, are defining features of mixed mania. Few studies have considered differences in cholesterol levels in subjects during mixed bipolar episodes. METHODS: Fasting serum cholesterol levels obtained from 174 subjects evaluated during mixed and pure manic episodes were compared using ANOVA statistics. Sex was included in the analysis and age was used as a covariate. Cholesterol levels in the total manic cohort and in the mixed and pure manic subgroups were compared with national norms. RESULTS: Fasting serum cholesterol levels were lower in the mixed manic subtype compared to the pure manic subtype. As expected, cholesterol levels increased with age. No differences were noted between males and females. Cholesterol levels were lower in both the mixed and pure manic subtypes when compared with national norms. CONCLUSION: Fasting serum cholesterol levels are low in manic patients, especially during mixed bipolar episodes. Cholesterol, which has been reported to be a negative acute phase reactant, may be lower during mixed states as a result of an immune activation.

Adolescent↗

Seasonal variation of mixed and pure episodes of bipolar disorder.

BACKGROUND: Although seasonal patterns of manic episodes have been reported, the seasonal variation of mixed states of bipolar disorder has received little attention. In the current report we address that concern as well as the overall seasonality of manic episodes. METHODS: The seasonal pattern of 304 psychiatric hospital admissions for treatment of mixed or manic bipolar episodes over a 3-year period were analyzed employing two definitions of mixed manic states: DSM-III-R and an ROC derived definition. RESULTS: The frequency of all manic episodes combined peaked in early spring, with a nadir in late fall. Pure manic admissions showed a similar pattern. Mixed manic admissions had a significantly different pattern, with a peak in late summer and a nadir in November. The differences between pure and mixed manic admissions were demonstrated with the use of the ROC definition for mixed states. LIMITATIONS: Effects of medications and medication non-compliance may dampen natural seasonal patterns of episodes. CONCLUSIONS: The different seasonal pattern of mixed and pure manic episodes support the separation of mixed episodes as a distinct clinical subtype.

Adolescent↗

Vascular risk factors in late onset mania.

BACKGROUND: Previous researches have suggested that late onset mania is a distinct subtype associated with medical and neurological disorders. Few studies, however, have focused on vascular risk factors. METHODS: Records of 366 bipolar patients were reviewed and age of first psychiatric hospitalization determined. Late-onset cases were determined empirically from a distribution histogram. Late onset cases were matched to early onset cases and histories of vascular disease/risks and current cholesterol levels compared. RESULTS: The distribution of age of first psychiatric hospitalization was bimodal with an intermode at age 47. Using that threshold, 6.3% of the cohort was classified as having late onset mania. Vascular risks factors were greater and current cholesterol levels higher in the late onset group. CONCLUSIONS: Late onset mania is associated with greater vascular risk factors. The bimodal appearance of age of first psychiatric hospitalization in this study provides further support of late onset mania as a distinct manic subtype with possibly a different, vascular aetiology. Control of these vascular risks may impact on the incidence of late onset mania, as well as on its clinical management.

Adolescent↗

Leukocytosis and hypoalbuminemia in mixed bipolar states: evidence for immune activation.

OBJECTIVE: Although activation of an immune response during major depressive episodes has been reported, less is known about changes during manic and mixed bipolar episodes. METHOD: Albumin and leukocyte levels were compared between subjects in manic and mixed bipolar episodes. Neutrophil, lymphocyte and monocyte levels were compared between the two groups. RESULTS: Albumin levels were lower in mixed manic subjects as opposed to pure manic subjects and in the combined groups levels were lower in females than in males. Leukocyte levels were higher in mixed manic patients compare with pure manic patients. Both neutrophil and monocyte levels were higher in the mixed manic patients but lymphocyte levels were no different. CONCLUSION: Leukocytosis and hypoalbuminemia during mixed manic states suggest immune activation in mixed mania similar to depression. This finding also tends to support the recognition of mixed mania as a distinct bipolar state.

Albumins↗

Smoking and psychosis in patients with bipolar I disorder.

We characterized 67 newly admitted patients in manic or mixed episodes of bipolar I disorder on categorical and continuous measures of smoking and psychosis to test the hypothesis that patients who were smokers would be more likely to demonstrate psychotic features. Smoking did not associate with psychosis in any of our analyses.

Adult↗

Symptom profile consistency in recurrent manic episodes.

Few studies have addressed whether symptom profiles remain consistent between episodes of mania. Those that have done so focused on mood only and adopted the strictly categorical approach. We evaluated 77 subjects during two discrete manic episodes (mean interval, 2 years, 2 weeks). Episodes were characterized on five established symptom factors of mania and on overall severity of classic manic symptoms (i.e., excluding dysphoric symptoms). Pearson correlation coefficients were computed to compare symptom profiles across episodes. Four symptom factors (dysphoria, hedonic activation, psychosis, and irritable aggression) were significantly correlated across episodes, as was manic severity. Psychomotor symptoms were not significantly correlated. Manic symptomatology remains generally similar in bipolar subjects during different episodes. The characterization of manic episodes by the empirical dimensions of symptom factors, as suggested by Kraepelin nearly a century ago, may provide additional information for biological and treatment response studies of manic states that is not captured by categorical subtype diagnosis focused solely on mood symptoms (i.e., mixed v pure manic episodes).

Adolescent↗

Hippocampal volume measurement in older adults with bipolar disorder.

OBJECTIVE: Decreased hippocampal volumes have been noted in unipolar depressed subjects, especially in elderly patients and those with cognitive impairment. Initial studies of mixed-aged bipolar subjects and controls have had conflicting findings, with most noting no difference; however this region has not been examined in older bipolar subjects. METHODS: The authors examined the hippocampal volumes of 36 older bipolar subjects (mean age: 58 years) and 29 older normal-comparison (NC) subjects (mean age: 61), using logistic-regression analyses to control for age and gender. Differences between late- and early-onset (before age 45) bipolar subjects were also examined. RESULTS: The left hippocampus was noted to be enlarged in older bipolar subjects, compared with the older NC group (sex and age controlled). No differences were noted in hippocampal volumes by age at onset nor number of previous episodes. The increase in hippocampal volume may be associated with the use of lithium, but not valproic acid. CONCLUSIONS: Left-hippocampal volume is increased in older bipolar subjects compared with NC subjects. The differences were not explained by age at onset, current mood state, or cognitive status, but may be associated with exposure to lithium. This finding would support previous observations about the neural-plasticity effect of lithium.

Aged↗