Bipolar Disorder: Cassidy F

Ghaemi SN, Bauer M, Cassidy F, Malhi GS, Mitchell P, Phelps J, Vieta E, Youngstrom E, Anonymous00020. · Bipolar Disorder Research Program, Department of Psychiatry, Emory University, Atlanta, GA 30322, USA. · Bipolar Disord. · Pubmed #18199230 No free full text.

Abstract: The Diagnostic Guidelines Task Force of the International Society for Bipolar Disorders (ISBD) presents in this document and this special issue a summary of the current nosological status of bipolar illness, a discussion of possible revisions to current DSM-IV and ICD-10 definitions, an examination of the relevant literature, explication of areas of consensus and dissensus, and proposed definitions that might guide clinicians in the most valid approach to diagnosis of these conditions given the current state of our knowledge.

Cassidy F, Yatham LN, Berk M, Grof P. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. · Bipolar Disord. · Pubmed #18199232 No free full text.

Abstract: OBJECTIVE: To review issues surrounding the diagnosis and validity of bipolar manic states. METHODS: Studies of the manic syndrome and its diagnostic subtypes were reviewed emphasizing historical development, conceptualizations, formal diagnostic proposals, and validation. RESULTS: Definitions delineating mixed and pure manic states derive some validity from external measures. DSM-IV and ICD-10 diagnosis of bipolar mixed states are too rigid and less restrictive definitions can be validated. Anxiety is a symptom often overlooked in diagnosis of manic subtypes and may be relevant to the mixed manic state. The boundary for separation of mixed mania and depression remains unclear. A 'pure' non-psychotic manic state similar to Kraepelin's 'hypomania' has been observed in several independent studies. CONCLUSIONS: Issues surrounding diagnostic subtyping of manic states remain complex and the debates surrounding categorical versus dimensional approaches continue. To the extent that categorical approaches for mixed mania diagnosis are adopted, both DSM-IV and ICD-10 are too rigid. Inclusion of non-specific symptoms in definitions of mixed mania, such as psychomotor agitation, does not facilitate and may hinder the diagnostic separation of pure and mixed mania. The inclusion of a diagnostic seasonal specifier for DSM-IV, which is currently based on seasonal patterns for depression might be expanded to include seasonal patterns for mania. Boundaries between subtypes may be 'fuzzy' rather than crisp, and graded approaches could be considered. With the continued development of new tools, such as imaging and genetics, alternative approaches to diagnosis other than the purely symptom-centric paradigms might be considered.

Cassidy F, Ahearn EP, Carroll BJ. · Duke-Umstead Bipolar Disorders Program, Duke University, Durham, NC 27710, USA. · Bipolar Disord. · Pubmed #11552957 No free full text.

Abstract: BACKGROUND: High rates of substance abuse have been reported in the general population, with males more often affected than females. Although high rates of substance abuse have also been reported in bipolar patients, the relationship between substance abuse and bipolar disorder has not been well characterized. METHODS: Substance abuse histories were obtained in 392 patients hospitalized for manic or mixed episodes of bipolar disorder and rates of current and lifetime abuse calculated. Analyses comparing sex, subtype (manic vs. mixed) and clinical history variables were conducted. RESULTS: Rates of lifetime substance abuse were high for both alcohol (48.5%) and drugs (43.9%). Nearly 60% of the cohort had a history of some lifetime substance abuse. Males had higher rates of abuse than females, but no differences in substance abuse were observed between subjects in manic and mixed bipolar states. Rates of active substance abuse were lower in older age cohorts. Subjects with a comorbid diagnosis of lifetime substance abuse had more psychiatric hospitalizations. CONCLUSIONS: Substance abuse is a major comorbidity in bipolar patients. Although rates decrease in older age groups, substance abuse is still present at clinically important rates in the elderly. Bipolar patients with comorbid substance abuse may have a more severe course. These data underscore the significance of recognition and treatment of substance abuse in bipolar disorder patients.

Beyer JL, Kuchibhatla M, Payne M, Moo-Young M, Cassidy F, MacFall J, Krishnan KR. · Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. · Int J Geriatr Psychiatry. · Pubmed #14758576 No free full text.

Abstract: 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.

Cassidy F, Pieper CF, Carroll BJ. · Duke-Umstead Bipolar Disorders Program, Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27710, USA. · Neuropsychopharmacology. · Pubmed #11522465 links to  free full text

Abstract: Classical descriptions of mania subtypes extend back to Kraepelin; however, in marked contrast to the study of depression subtypes, validation of mania subtypes by multivariate statistical methods has seldom been attempted. We applied Grade of Membership (GOM) analysis to the rated clinical features of 327 inpatients with DSM-III-R mania diagnoses. GOM is a type of latent structure multivariate analysis, which differs from others of this type in making no a priori distributional assumptions about groupings. We obtained 5 GOM Pure Types with good face validity. The major Kraepelinian forms of "hypomania," "acute mania," "delusional mania," and "depressive or anxious mania" were validated. The major new finding is of two mixed mania presentations, each with marked lability of mood. The first of these displayed a dominant mood of severe depression with labile periods of pressured, irritable hostility and paranoia, and the complete absence of euphoria or humor. The second mixed mania Pure Type displayed a true, incongruous mixture of affects: periods of classical manic symptoms with euphoria, elation, humor, grandiosity, psychosis, and psychomotor activation, switching frequently to moderately depressed mood with pressured anxiety and irritability. This multivariate analysis validated classical clinical descriptions of the major subtypes of mania. Two distinct forms of mixed manic episodes were identified. DSM-III-R criteria did not reliably identify either of these two natural groups of mixed bipolar patients. As occurs in depression, this clinical heterogeneity of mania may influence response to drug treatments.

Cassidy F. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3414, Durham, NC 27710, USA. · Bipolar Disord. · Pubmed #19594512 No free full text.

This publication has no abstract.

Cassidy F, Ahearn E, Carroll BJ. · Duke University Medical Center, Durham, NC 27710, United States. · J Affect Disord. · Pubmed #18684512 No free full text.

Abstract: OBJECTIVES: High rates of some depressive symptoms occur in both mixed and pure manic episodes. This study examined whether manic subjects identify these depressive symptoms by self-report consistently with observer ratings, whether dysphoric symptoms are self-rated differently in mixed compared to pure manic episodes, and whether discriminative self-rated dysphoric symptom sets agree with those established by observer ratings. METHODS: Ninety-four inpatients meeting DSM-IV criteria for mania were classified as in pure or mixed episodes. Dysphoric symptoms were evaluated with the Hamilton Depression Rating Scale (HDRS) and the self-rated Carroll Depression Scale (CDS). Total scores and individual symptom scores on the two scales were compared, as were differences between the manic and mixed subtypes. Positive predictive values (PPV) of individual CDS statements for a diagnosis of a mixed bipolar episode were calculated. Those with a PPV of 0.5 or greater were summed across all subjects and the distributions within the bipolar manic and mixed groups inspected. RESULTS: Self-rated depressive symptoms were highly concordant with observer-rated depressive symptoms in mania. Differences were demonstrated between mixed and pure manic subjects based on self-report, and these differences were similar to those observed with HDRS evaluations. A group of 8 dysphoric symptoms discriminated mixed from pure manic episodes on both scales. These symptoms were depressed mood, pathological guilt, suicidal tendency, anhedonia, psychomotor agitation, psychic and somatic anxiety, and general somatic symptoms (fatigue). CONCLUSIONS: Manic patients report depressive symptoms consistently with observer ratings. Self-rated dysphoric symptoms differ significantly between mixed and pure manic episodes. Patient self-rating is another tool which may help in the diagnosis of mixed mania and the recognition of depressive symptoms during manic episodes. LIMITATIONS: The current study included patients who were evaluated during inpatient hospitalization only. The study included only subjects capable and willing to give written informed consent. Generalizability to other bipolar patients is not established.

Beyer JL, Kuchibhatla M, Cassidy F, Krishnan KR. · Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. · Int J Geriatr Psychiatry. · Pubmed #18613269 No free full text.

Abstract: OBJECTIVE: Theories about the impact of stressful life events (SLE) in bipolar disorder have focused on their role early in the disease. Few studies have examined SLE in older bipolar patients. We wanted to assess the impact of SLE in late life bipolar disorder METHODS: We evaluated negative SLE experienced by older bipolar subjects compared with younger bipolar subjects and older controls for number, type, and their association with phase of illness, age of onset, and previous episodes. RESULTS: Both younger and older bipolar subjects have more SLE than similarly aged controls. There was no significant difference in the number of stressors that younger and older bipolar subjects experienced, based on mood state, previous episodes, or age-of-onset. Both older and younger depressed bipolar subjects reported more SLE in the previous 12 months compared with those in a manic state. CONCLUSIONS: Negative SLE are much more prevalent in bipolar patients compared with age-matched controls, and continue to be frequent in later life.

Roche S, Cassidy F, Zhao C, Badger J, Claffey E, Mooney L, Delaney C, Dobrin S, McKeon P. · Smurfit Institute of Genetics, Trinity College, Dublin, Ireland. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #17525977 No free full text.

Abstract: A genome-wide scan in 60 bipolar affective disorder (BPAD) affected sib-pairs (ASPs) identified linkage on chromosome 21 at 21q22 (D21S1446, NPL = 1.42, P = 0.08), a BPAD susceptibility locus supported by multiple studies. Although this linkage only approaches significance, the peak marker is located 12 Kb upstream of S100B, a neurotrophic factor implicated in the pathology of psychiatric disorders, including BPAD and schizophrenia. We hypothesized that the linkage signal at 21q22 may result from pathogenic disease variants within S100B and performed an association analysis of this gene in a collection of 125 BPAD type I trios. S100B single nucleotide polymorphisms (SNPs) rs2839350 (P = 0.022) and rs3788266 (P = 0.031) were significantly associated with BPAD. Since variants within S100B have also been associated with schizophrenia susceptibility, we reanalyzed the data in trios with a history of psychosis, a phenotype in common between the two disorders. SNPs rs2339350 (P = 0.016) and rs3788266 (P = 0.009) were more significantly associated in the psychotic subset. Increased significance was also obtained at the haplotype level. Interestingly, SNP rs3788266 is located within a consensus-binding site for Six-family transcription factors suggesting that this variant may directly affect S100B gene expression. Fine-mapping analyses of 21q22 have previously identified transient receptor potential gene melastatin 2 (TRPM2), which is 2 Mb upstream of S100B, as a possible BPAD susceptibility gene at 21q22. We also performed a family-based association analysis of TRPM2 which did not reveal any evidence for association of this gene with BPAD. Overall, our findings suggest that variants within the S100B gene predispose to a psychotic subtype of BPAD, possibly via alteration of gene expression.

Cassidy F, Zhao C, Badger J, Claffey E, Dobrin S, Roche S, McKeon P. · Smurfit Institute of Genetics, Trinity College, Dublin 2, Ireland. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #17455214 No free full text.

Abstract: Bipolar disorder (BPD) is a complex genetic disorder with cycling symptoms of depression and mania. Despite the extreme complexity of this psychiatric disorder, attempts to localize genes which confer vulnerability to the disorder have had some success. Chromosomal regions including 4p16, 12q24, 18p11, 18q22, and 21q21 have been repeatedly linked to BPD in different populations. Here we present the results of a whole genome scan for linkage to BPD in an Irish population. Our most significant result was at 14q24 which yielded a non-parametric LOD (NPL) score of 3.27 at the D14S588 marker with a nominal P-value of 0.0006 under a narrow (bipolar type I only) model of affection. We previously reported linkage to 14q22-24 in a subset of the families tested in this analysis. We also obtained suggestive evidence for linkage at 4q21, 9p21, 12q24, and 16p13, chromosomal regions that have all been previously linked to BPD. Additionally, we report on a novel approach to linkage analysis, STRUCTURE-Guided Linkage Analysis (SGLA), which is designed to reduce genetic heterogeneity and increase the power to detect linkage. Application of this technique resulted in more highly significant evidence for linkage of BPD to three regions including 16p13, a locus that has been repeatedly linked to numerous psychiatric disorders.

Beyer JL, Taylor WD, MacFall JR, Kuchibhatla M, Payne ME, Provenzale JM, Cassidy F, Krishnan KR. · Department of Psychiatry and Behavioral Science, Duke University Medical Center, Box 3519 DUMC, Durham, NC 27710, USA. · Neuropsychopharmacology. · Pubmed #15988474 links to  free full text

Abstract: 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.

Beyer JL, Kuchibhatla M, Payne ME, Moo-Young M, Cassidy F, Macfall J, Krishnan KR. · Dept. of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. · Am J Geriatr Psychiatry. · Pubmed #15545329 No free full text.

Abstract: 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.

Beyer JL, Kuchibhatla M, Looney C, Engstrom E, Cassidy F, Krishnan KR. · Duke University Medical Center, Department of Psychiatry, Durham, NC 27710, USA. · Bipolar Disord. · Pubmed #12656934 No free full text.

Abstract: 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.

Cassidy F, Ahearn EP, Carroll BJ. · Duke-Umstead Bipolar Disorders Program, Duke University, Durham, NC, USA. · Bipolar Disord. · Pubmed #12519099 No free full text.

Abstract: OBJECTIVES: Associations of both overt thyroid disease as well as subclinical thyroid abnormalities with affective disorders have been well established. Similar associations have been reported with mixed mania and rapid cycling bipolar disorder. We tested for differences in overt and subclinical thyroid disease and subclinical differences in a large series of bipolar patients examined during mixed or pure manic episodes. METHODS: Rates of previously diagnosed thyroid disease were compared by sex, race and manic subtype (mixed versus pure) in 443 patients. Serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations obtained from patients with no clinical thyroid disease collected during manic and mixed bipolar episodes were compared using ANOVA statistics. Race was also included in the model and age was covaried. RESULTS: Rates of thyroid disease, in particular hypothyroidism, were higher in females and white people, and increased with advancing age. No differences were noted between subjects sampled during mixed or pure manic episodes. In patients with no history of thyroid disease, serum TSH and FT4 concentrations did not differ between manic subtypes or between sexes. TSH levels however, were significantly lower in African Americans. CONCLUSIONS: We did not confirm past reports of associations of overt or subclinical thyroid disease with mixed manic episodes. African Americans had significantly lower serum TSH concentrations than white people, while FT4 levels did not differ.

Ahearn EP, Speer MC, Chen YT, Steffens DC, Cassidy F, Van Meter S, Provenzale JM, Weisler RH, Krishnan KR. · Department of Psychiatry, Duke University Medical Center, Durham, North Carolina, USA. · Am J Med Genet. · Pubmed #12210282 No free full text.

Abstract: 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.

Cassidy F, Carroll BJ. · Duke-Umstead Bipolar Disorders Program, Box 3414 Duke University Medical Center, Durham, NC 27710 USA. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #12192467 No free full text.

Abstract: 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.

Cassidy F, Wilson WH, Carroll BJ. · Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA. · Acta Psychiatr Scand. · Pubmed #12086227 No free full text.

Abstract: 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.

Cassidy F, Ahearn EP, Carroll BJ. · Duke-Umstead Bipolar Disorder Program, Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA. · Compr Psychiatry. · Pubmed #11994834 No free full text.

Abstract: 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).

Cassidy F, Carroll BJ. · Duke-Umstead Bipolar Disorders Program, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3414, Durham, NC 27710, USA. · J Affect Disord. · Pubmed #11869779 No free full text.

Abstract: 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.

Cassidy F, Ahearn E, Carroll BJ. · Duke-Umstead Bipolar Disorders Program, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 3414, Durham, NC 27710, USA. · J Affect Disord. · Pubmed #11869766 No free full text.

Abstract: BACKGROUND: Few studies have compared symptom presentations across manic or mixed episodes in manic-depressive patients. METHODS: In the current study we report on symptom presentations of 68 prospectively-evaluated subjects diagnosed with Bipolar Disorder during two discrete manic or mixed episodes. Each episode was categorized using DSM-IIIR criteria for Bipolar Disorder, manic or mixed, as well as a less restrictive definition for manic and mixed states derived from receiver operating characteristic (ROC) analysis of symptoms. RESULTS: The occurrence of mixed bipolar episodes was not random using either the DSM-IIIR or ROC-derived definitions of mixed episodes. LIMITATIONS: Subjects were not all fully medication-free at the time of evaluation which may have altered symptom presentation. The total duration of the study was limited, with the longest inter-episode interval under 6 years. CONCLUSIONS: Although there was variability in mixed symptomatology between episodes, the occurrence of mixed episodes was not random. Manic and mixed episodes tend to recur true to type.

Cassidy F, Carroll BJ. · Duke-Umstead Bipolar Disorders Program, Duke University Medical Center, Durham, NC 27710, USA. · Psychol Med. · Pubmed #11866328 No free full text.

Abstract: 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.

Cassidy F, McEvoy JP, Yang YK, Wilson WH. · Department of Psychiatry, Duke University Medical Center, Durham, NC, USA. · Compr Psychiatry. · Pubmed #11788921 No free full text.

Abstract: 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.

Cassidy F, McEvoy JP, Yang YK, Wilson WH. · John Umstead Hospital, Butner, North Carolina 27509, USA. · J Nerv Ment Dis. · Pubmed #11434641 No free full text.

This publication has no abstract.

Cassidy F, Carroll BJ. · Duke-Umstead Bipolar Disorders Program, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. · Prog Neuropsychopharmacol Biol Psychiatry. · Pubmed #11371003 No free full text.

Abstract: 1. In a previous report the authors compared the frequency of 20 classical and mixed manic signs and symptoms in subjects meeting DSM-III-R criteria for Bipolar Disorder, manic or mixed. In that report, the authors commented that a possible limitation of the study was the diagnosis of mixed and pure mania using DSM-III-R criteria that may be too rigid The authors now address that issue, adopting a ROC-derived definition of mixed mania 2. Three hundred sixty-three subjects meeting DSM-III-R criteria for Bipolar Disorder, manic or mixed, were evaluated by rating 20 signs and symptoms of mania. The frequencies of these signs and symptoms were computed and compared for both mixed and pure subtypes, determined by the ROC-derived definition. 3. Mood lability, dysphoric mood, guilt, anxiety, and suicidality were more frequently observed in the mixed manic group In contrast, euphoria and grandiosity were more frequently observed in the pure manic group. Nonetheless, non-trivial rates of dysphoric mood, irritability and anxiety were still observed in the pure groups, despite the adoption of a less restrictive definition of mixed states. The current results are similar to the results obtained using DSM-III-R criteria for Bipolar Disorder, manic and mixed. Although rates of dysphoric mood, anxiety, lability, guilt and suicidality were lower in the manic group, each of these symptoms may be observed in pure manic episodes, underscoring the importance of recognition and evaluation of these features in formal studies of "pure" as well as mixed manic episodes.

Ahearn EP, Cassidy F, Kelley L, Weisler RH, Carroll BJ. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA. · Compr Psychiatry. · Pubmed #11349237 No free full text.

Abstract: Self-rated scales allow the comparison of subjective mood across the spectrum of manic, depressive, and euthymic states. This study examined the self-reported mood of manic, depressed, and normal subjects using a 23-item research instrument based on the Carroll-Klein model of bipolar disorder. The Multiple Visual Analog Scale (MVAS) measures the following dimensions: consummatory reward (seven items), incentive reward (two items), psychomotor speed (seven items), and central pain (seven items). The MVAS was completed by 31 manic inpatients, 43 depressed inpatients, and 29 normal volunteer subjects. Total scores, average item scores, and total dimension scores were obtained. Subjects also completed a global mood VAS and the Carroll Depression Scale (CDS). Groups were compared by analysis of variance (ANOVA) and post hoc Bonferroni-Dunn methods. In a separate post hoc analysis, the group of manic patients was divided at the median CDS score into "pure" and "dysphoric" manic subgroups. We found excellent congruence of average 23-item total MVAS scores with global VAS and CDS scores. Dimension scores on the MVAS conformed to the predictions of the Carroll-Klein model. Depressed patients differed significantly from both manic and normal subjects on each dimension. MVAS dimension scores of normal subjects did not differ significantly from those of manic patients. On the dimension of central pain, normal subjects had significantly less inhibited scores than the "pure" subgroup of manics. The results confirmed that the dimensions of the Carroll-Klein model are bipolar and orthogonal. By the MVAS technique, the self-reported mood of normal subjects is similar to the self-reported mood of manic patients on all dimensions of the Carroll-Klein model of bipolar disorder. The positive scores of both groups are clearly distinguished from the negative scores of depressed patients. Average MVAS scores of normal subjects approximated the conventional zero score only on the dimension of central pain. Normal subjects exhibit megalothymic (hyperthymia) on most dimensions of subjective mood. The negative MVAS scores of depressed patients are even more deviant from normal than the conventional scoring system would suggest.