Psychomotor performance and monoamine function in bipolar and unipolar affective disorders.

BACKGROUND: Affective disorders are associated with prominent psychomotor abnormalities that may be related to changes in arousal or motivation due to altered catecholamine function. METHODS: We investigated relationships between performance on psychomotor tests of motor speed (reaction time and tapping speed) and visual tracking (trail making and dot placement) and catecholamine system function including cerebrospinal fluid (CSF) or urinary concentrations of catecholamines or their metabolites. Subjects were medicine-free inpatients with unipolar depression or with manic, depressive, or mixed episodes of bipolar disorder, and healthy controls matched by gender and stratified by age. RESULTS: Unipolar and bipolar depressed patients were impaired in motor speed, dexterity, and visual tracking, whereas manic and mixed patients did not differ from controls. Tapping speed correlated positively with CSF 3-methoxy-4-hydroxyphenylglycol in healthy controls and with CSF homovanillic acid in bipolar depressed subjects. Increased catecholamine function correlated with slowing in all other measures for patients with bipolar disorder. Relationships between catecholamines and psychomotor function were weaker in unipolar depressed subjects. Psychomotor function was related to severity of depression in bipolar, but not in unipolar, patients. CONCLUSIONS: These data suggest that catecholamine systems are associated with increased arousal and psychomotor impairment in patients with bipolar disorder. Similar behavioral changes have different neurotransmitter relationships in unipolar disorder.     

Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F 18

Cerebral metabolic rates for glucose were examined in patients with unipolar depression (N = 11), bipolar depression (N = 5), mania (N = 5), bipolar mixed states (N = 3), and in normal controls (N = 9) using positron emission tomography and fluorodeoxyglucose F 18. All subjects were studied supine under ambient room conditions with eyes open. Bipolar depressed and mixed patients had supratentorial whole brain glucose metabolic rates that were significantly lower than those of the other comparison groups. The whole brain metabolic rates for patients with bipolar depression increased going from depression or a mixed state to a euthymic or manic state. Patients with unipolar depression showed a significantly lower ratio of the metabolic rate of the caudate nucleus, divided by that of the hemisphere as a whole, when compared with normal controls and patients with bipolar depression.     

单相抑郁与双相障碍住院患者地塞米松抑制试验的对照研究

目的 通过地塞米松抑制试验(DST)了解单相抑郁和双相障碍患者在不同情绪状态下的下丘脑-垂体-肾上腺轴功能改变情况. 方法对38例单相抑郁住院患者和63例双相障碍住院患者(双相障碍Ⅰ型19例,双相障碍Ⅱ型44例;双相障碍抑郁发作者33例,双相障碍躁狂发作者18例,双相障碍混合发作者12例)进行DST,其中17例单相抑郁、35例双相障碍患者在治疗4周后再次行DST,比较各组DST脱抑制率差异.结果 治疗前,单相抑郁的DST脱抑制率(36.8%)与双相障碍(14.3%)、双相障碍Ⅰ型(10.5%)、双相障碍Ⅱ型(15.9%)以及双相障碍抑郁发作(15.2%)之间比较差异有统计学意义(P<0.05);双相障碍Ⅰ型(10.5%)与双相障碍Ⅱ型(15.9%)之间,双相障碍抑郁发作(15.2%)、双相障碍混合发作(16.7%)和双相障碍躁狂发作(11.1%)两两比较差异均无统计学意义(P>0.05).治疗后,DST脱抑制率在上述各组间差异无统计学意义(P>0.05).治疗后单相抑郁的DST脱抑制率随着病情改善而降低,但较治疗前差异无统计学意义(P>0.05),双相障碍的DST脱抑制率在治疗前后比较差异无统计学意义(P>0.05).结论在疾病期,单相抑郁的DST脱抑制率高于双相障碍;双相障碍的DST脱抑制率与临床分型、发作类型、病情无关.     

Comorbid disorders in hospitalized bipolar adolescents compared with unipolar depressed adolescents

This study examined comorbid psychiatric disorders in adolescents with bipolar disorder. Hospitalized bipolar adolescents (N=10) were compared to hospitalized adolescents with unipolar depression (N=33), and to adolescents with nonaffective psychiatric disorders (N=11). Results showed conduct disorder, attention-deficit hyperactivity disorder, psychosis, and having any DSM-III-R psychoactive substance use disorder were all significantly more common in the bipolar group than the unipolar depressed group. Comorbid anxiety disorder was present in 40–45% of the subjects in the unipolar and bipolar groups, but in none of the control group subjects. This study is supported in part by a grant to Dr. Borchardt from the University of Minnesota Graduate School.     

The presence of antithyroid antibodies in patients with affective and nonaffective psychiatric disorders

We determined the frequency of antithyroglobulin and antimicrosomal antibodies in 173 consecutively admitted psychiatric inpatients. (We found antithyroid antibodies in 8% (5/65) of patients with DSM-III major depression, 13% (4/31) with biploar disorder, and in 0% (0/4) of those with schizoaffective disorder.) The rate of antibody occurrence was unrelated to lithium exposure either within individual diagnostic categories or for the sample as a whole. The overall frequency of positive antithyroid antibody titers in patients with DSM-III affective disorder, 9% (9/99), did not differ from that in patients with nonaffective disorders, 10% (7/68). However, patients with bipolar affective disorder-mixed or bipolar affective disorder-depressed had a higher rate of positive antithyroid antibody titers than other patients. Our findings confirm earlier reports that thyroid disorders may be particularly common in patients with bipolar affective disorder, even in the absence of lithium exposure. However, as antithyroid antibodies also occurred at a relatively high rate in nonaffective disorders, the possible psychiatric effects of autoimmune thyroiditis do not appear to be limited to affective dysregulation.     

Insight into illness in patients with mania,mixed mania,bipolar depression and major depression with psychotic features

Dell'Osso L, Pini S, Cassano GB, Mastrocinque C, Seckinger RA, Saettoni M, Papasogli A, Yale SA, Amador XF. Insight into illness in patients with mania, mixed mania, bipolar depression and major depression with psychotic features. Bipolar Disord 2002: 4: 315–322. © Blackwell Munksgaard 2002 Background: Poor insight into illness is a common feature of bipolar disorder and one that is associated with poor clinical outcome. Empirical studies of illness awareness in this population are relatively scarce with the majority of studies being published over the previous decade. The study reported here sought to replicate previous report findings that bipolar patients frequently show high levels of poor insight into having an illness. We also wanted to examine whether group differences in insight exist among bipolar manic, mixed and unipolar depressed patients with psychotic features. Methods: A cohort of 147 inpatients with DSM‐III‐R bipolar disorder and 30 with unipolar depression with psychotic features, were evaluated in the week prior to discharge using the Structured Clinical Interview for DSM‐III‐R‐Patient Edition (SCID‐P), the Brief Psychiatric Rating Scale (BPRS) and the Scale to assess Unawareness of Mental Disorder (SUMD). Results: Insight into specific aspects of the illness was related to the polarity of mood episode: patients with mania showed significantly poorer insight compared with those with mixed mania, bipolar depression and unipolar depression. A linear regression analysis using SUMD score as the dependent variable and symptoms of mania as the independent variable found that specific manic symptoms did not account for level of insight. Similar results were obtained when the mean insight scores of patients with and without grandiosity were contrasted. Conclusions: We hypothesize that the lack of association between level of insight and total number of manic symptoms or with specific manic symptoms may be related to the persistence of subsyndromal symptoms in patients remitting from a manic episode.     

Menstrual dysfunction prior to onset of psychiatric illness is reported more commonly by women with bipolar disorder than by women with unipolar depression and healthy controls

BACKGROUND: Preliminary reports suggest that menstrual cycle irregularities occur more commonly in women with bipolar disorder and unipolar depression than in the general population. However, it is not always clear whether such abnormalities, reflecting disruption of the hypothalamic-pituitary-gonadal (HPG) axis, are caused by psychotropic treatments or associated with the disorder per se. METHOD: The prevalence of early-onset (within the first 5 postmenarchal years) menstrual cycle dysfunction (menstrual cycle length unpredictable within 10 days or menstrual cycle length<25 days or >35 days) occurring before onset of psychiatric illness was compared between subjects with DSM-IV bipolar disorder participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and subjects with DSM-IV unipolar depression or no psychiatric illness participating in the Harvard Study of Moods and Cycles. Data from the Harvard Study of Moods and Cycles were gathered from September 1995 to September 1997, and data from STEP-BD were gathered from November 1999 to May 2001. RESULTS: Early-onset menstrual cycle dysfunction was reported to have occurred in 101/295 women with bipolar disorder (34.2%), 60/245 women with depression (24.5%), and 134/619 healthy controls (21.7%). Women with bipolar disorder were more likely to have early-onset menstrual cycle dysfunction than healthy controls (chi2=16.58, p<.0001) and depressed women (chi2=6.08, p=.01), while depressed women were not more likely to have early-onset menstrual cycle dysfunction than healthy controls (chi2=0.81, p=.37). CONCLUSIONS: Compared with healthy controls and women with unipolar depression, women with bipolar disorder retrospectively report early-onset menstrual dysfunction more commonly prior to onset of bipolar disorder. Future studies should evaluate potential abnormalities in the hypothalamic-pituitary-gonadal axis that are associated with bipolar disorder.     

Neuropsychologic impairments in bipolar and unipolar mood disorders on the CANTAB neurocognitive battery.

BACKGROUND: Cognitive deficits associated with mood disorders, especially bipolar disorder, have been the focus of limited systematic investigation. METHODS: We tested 35 bipolar (21 in depressed state and 14 in mixed or manic state) and 58 nonbipolar depressed consecutively admitted young adult inpatients and 51 matched healthy individuals on the Cambridge Neuropsychological Test Automated Battery, a computerized neurocognitive battery. RESULTS: The mixed/manic bipolar patients demonstrated robust deficits in episodic and working memory, spatial attention, and problem solving. In contrast, depressed bipolar and nonbipolar patients demonstrated impairments only in episodic memory. CONCLUSIONS: Neuropsychologic findings with the Cambridge Neuropsychological Test Automated Battery indicate widely distributed deficits in cognitive domains subserved by temporal, parietal, and frontostriatal systems in bipolar patients during mixed/manic states of illness. Significant deficits in bipolar and nonbipolar depressed patients were restricted to episodic memory, suggesting a more selective dysfunction in mesial temporal lobe function during episodes of depression. These findings highlight the different cognitive profiles of mania and depression, demonstrate similar patterns of neuropsychologic deficits in bipolar and nonbipolar depression, and point to a need for further research investigating the characteristics, causes, course, and treatment of severe cognitive deficits associated with mixed/manic phases of bipolar disorder.     

Immunoglobulins,autoantibodies and other serum protein fractions in psychiatric disorders

Summary The levels of IgM, IgG and IgA were measured in the serum of 337 psychiatric inpatients (92 patients with bipolar depression, 150 patients with unipolar depression and 95 schizophrenics) and compared to 150 healthy subjects. A significantly higher level of IgM was found in all psychiatric groups compared with the controls, and IgM levels were more elevated in female patients than in male patients for the bipolar and unipolar groups. There were no differences for the other immunoglobulins (IgG, IgA) among the groups studied. In 51 of the patients (17 bipolar, 34 unipolar), other measurements were performed (Greactive protein, antinuclear antibodies, lymphocyte antibodies, thyroid antibodies, complement and the third and fourth factors of complement). The unipolar group showed a significant rise of C-reactive protein values and the presence of antinuclear antibodies. Interestingly all patients with antinuclear antibodies were females. No difference was found between psychiatric patients and controls in lymphocyte antibodies, thyroid antibodies and values of complement.     

Mania associated with electroconvulsive therapy

Of 94 depressed patients given electroconvulsive therapy (ECT), a manic episode developed in 6 (64%). These six patients were equally distributed across three diagnostic categories of depressive illness: primary unipolar depression, bipolar affective disorder, and schizoaffective disorder. Compared with matched controls, the patients who experienced ECT-associated mania had an earlier age of onset and a longer duration of illness. These patients also had more previous psychiatric hospitalizations. Although evidence of a direct causal relationship between the administration of ECT and the development of mania is still lacking, our data suggest that the risk of mania is higher in patients with certain clinical characteristics.     

Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder.

OBJECTIVE: New mood stabilizers are needed that possess efficacy for all phases of bipolar disorder. This study was designed to provide preliminary evidence for the safety and efficacy of a new anticonvulsant, lamotrigine, in adult patients with bipolar disorder who had been inadequately responsive to or intolerant of prior pharmacotherapy. METHOD: A 48-week, open-label, prospective trial was conducted in 75 patients with bipolar I or bipolar II disorder. Lamotrigine was used as adjunctive therapy (N = 60) or monotherapy (N = 15) in patients presenting in depressed, hypomanic, manic, or mixed states. RESULTS: Of the 40 depressed patients included in the efficacy analysis, 48% exhibited a marked response and 20% a moderate response as measured by reductions in 17-item Hamilton Depression Rating Scale scores. Of the 31 with a hypomanic, manic, or mixed state, 81% displayed a marked response and 3% a moderate response on the Mania Rating Scale. From baseline to endpoint, the depressed patients exhibited a 42% decrease in Hamilton depression scale scores, and the patients presenting with hypomania, mania, or a mixed state exhibited a 74% decrease in Mania Rating Scale scores. The most common drug-related adverse events were dizziness, tremor, somnolence, headache, nausea, and rash. Rash was the most common adverse event resulting in drug discontinuation (9% of patients); one patient developed a serious rash and required hospitalization. CONCLUSIONS: These open-label data provide preliminary evidence that lamotrigine may be an effective treatment option for patients with refractory bipolar disorder; however, potential benefits must be weighed against potential side effects, including rash.     

Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study

OBJECTIVES: To determine if bipolar disorder is accurately diagnosed in clinical practice and to assess the effects of antidepressants on the course of bipolar illness. METHOD: Charts of outpatients with affective disorder diagnoses seen in an outpatient clinic during 1 year (N = 85 with bipolar or unipolar disorders) were reviewed. Past diagnostic and treatment information was obtained by patient report and systematic psychiatric history. Bipolar diagnosis was based on DSM-IV criteria using a SCID-based interview. RESULTS: Bipolar disorder was found to be misdiagnosed as unipolar depression in 37% of patients who first see a mental health professional after their first manic/hypomanic episode. Antidepressants were used earlier and more frequently than mood stabilizers, and 23% of this unselected sample experienced a new or worsening rapid-cycling course attributable to antidepressant use. CONCLUSION: These results suggest that bipolar disorder tends be misdiagnosed as unipolar major depressive disorder and that antidepressants seem to be associated with a worsened course of bipolar illness. However, this naturalistic trial was uncontrolled, and more controlled research is required to confirm or refute these findings.     

Clinical predictors of acute response with quetiapine in psychotic mood disorders

BACKGROUND: In controlled studies of patients with schizophrenia, the atypical antipsychotic quetiapine, 300 mg/day, has been shown to be as effective in the treatment of positive and negative symptoms as haloperidol. However, little is known about the efficacy of quetiapine in patients with psychotic mood disorders. The purpose of this study was to assess the efficacy of quetiapine in the treatment of psychotic mood disorders in comparison with nonaffective psychotic disorders and identify clinical factors associated with quetiapine response. METHOD: In a naturalistic setting, by reviewing medical records, we assessed response to quetiapine and factors associated with response to quetiapine in 145 consecutive patients newly treated with the drug at a nonprofit academic psychiatric hospital. These patients had received a discharge diagnosis of bipolar disorder (manic, mixed, or depressive type), major depression with psychotic features, schizophrenia, schizoaffective disorder (bipolar or depressive type), delusional disorder, or psychosis not otherwise specified (NOS) according to DSM-IV criteria. RESULTS: Patients with a diagnosis of bipolar disorder, manic, mixed, or depressed and schizoaffective disorder, bipolar type displayed higher response rates (> 74%) compared with patients with schizophrenia. However, this finding did not achieve statistical significance. A diagnosis of major depression with psychotic features (p = .02) and longer duration of illness (p = .03) were associated with less chance of responding. CONCLUSION: Quetiapine may be a useful alternative or adjunctive treatment for patients with bipolar and schizoaffective disorders.     

Myers Briggs Type Indicator and Tridimensional Personality Questionnaire differences between bipolar patients and unipolar depressed patients

Objectives: The current study was designed to compare personality differences between bipolar patients and unipolar depressed patients, as evaluated on the Myers Briggs Type Indicator (MBTI) and the Tridimensional Personality Questionnaire (TPQ).

Methods: A group of bipolar and a group of unipolar depressed patients filled out the MBTI, the TPQ, the Beck Depression Inventory, and the CAGE questionnaire. The two groups were compared with each other as to responses on the above surveys, and subgroups of bipolar depressed and bipolar patients with manic symptoms were also compared.

Results: Bipolar patients were found to be significantly more extroverted (p=0.004) and less judging (p=0.007) on the MBTI. They were significantly more novelty seeking (p=0.004) and less harm avoidant (p=0.002) on the TPQ. Of the above differences, only the TPQ harm avoidance scale appeared strongly linked to the patients' level of depression.

Conclusion: Significant differences in personality exist between bipolar disorder and unipolar depressed patients.     

Gender differences in the phenomenology of bipolar disorder

OBJECTIVES: To investigate gender differences in the phenomenology of episodes in bipolar disorder as according to ICD-10. METHODS: All patients who got a diagnosis of a manic episode/bipolar disorder in a period from 1994 to 2002 at the first outpatient treatment ever or at the first discharge from psychiatric hospitalization ever in Denmark were identified in a nationwide register. RESULTS: Totally, 682 outpatients and 1037 inpatients got a diagnosis of a manic episode/bipolar disorder at the first contact ever. Significantly more women were treated as outpatients than as inpatients. Women were treated for longer periods as inpatients but not as outpatients. In both settings, the prevalence of depressive versus manic/mixed episodes was similar for men and women and the severity of manic episodes (hypomanic /manic without psychosis/manic with psychosis) and the severity of depressive episodes (mild/moderate/severe without psychosis/severe with psychosis) did not differ between genders. The prevalence of psychotic symptoms at first contact was the same for both genders. Among patients treated in outpatient settings more men than women presented with comorbid substance abuse and among patients treated during hospitalization more women than men presented with mixed episodes. CONCLUSIONS: Besides differences in the prevalence of mixed episodes and comorbid substance abuse few gender differences are found among patients presenting with a manic episode/bipolar disorder at first contact in psychiatric inpatient or outpatient hospital settings.     

The efficacy of ECT in mixed affective states

ECT is efficacious in the treatment of both the depressed and manic phases of bipolar disorder. While ECT is believed to be equally efficacious in the treatment of mixed affective states, to our knowledge there are no empirical studies on this issue. A chart review study was conducted to compare treatment response and clinical course in three groups of patients who received ECT in a general hospital service: bipolar depressed (n = 38), bipolar manic (n = 5), and bipolar mixed (n = 10), diagnosed by DSM-IV criteria. All three groups showed robust response rates, but the number of days of hospitalization was significantly longer in the mixed group (mean 30, SD 19.0 days) compared with the depressed group (mean 19.0, SD 10.9 days, t = 2.4, p < 0.03). There was a trend for the number of ECT treatments to be greater in the mixed compared with the depressed group. These findings indicate that patients with mixed affective states do respond well to a course of ECT, but the longer hospital stays and greater number of ECT treatments suggest that they may be more difficult to treat with ECT than patients with pure bipolar depression or bipolar mania.     

ECT in Unipolar and Bipolar Disorders: A Naturalistic Evaluation of 460 Patients

We compared the efficacy of electroconvulsive therapy (ECT) and numbers of ECTs received by unipolar depressive (n = 368), bipolar depressive (n = 55), and manic patients (n = 37) in a review of records of patients treated in a 12-year period in a university hospital medical center. Both unipolar and bipolar depressive patients received nine treatments, one half more on average than the number of treatments received by manic patients, but the difference was not significant. ECT was equally effective in unipolar and bipolar depression (69.8 and 69.1%, respectively, rated as "markedly improved"), whereas 78.4% of patients with mania had "marked improvement." Both unilateral and bilateral ECTs were equally effective for the three groups. Bipolar depressive and manic patients receiving mixed courses (some unilateral, some bilateral) received more treatments than did those receiving unilateral or bilateral treatments exclusively and tended not to respond as well. We conclude that ECT is an effective treatment for mania, unipolar, and bipolar depression, that unilateral and bilateral treatments are equally effective, and that no significant difference exists in the number of ECTs used to treat these disorders.     

Cholesterol levels in mood disorders: high or low?

Objectives: To assess cholesterol levels in patients with mood disorders.

Methods: All consecutively admitted patients meeting inclusion criteria (n=50) who were hospitalized in an affective disorders unit received assessments of cholesterol levels. Correlations were made with diagnosis using DSM-IV criteria, current mood states, and other clinical and demographic features of illness. Exclusion criteria included current alcohol abuse, medical illnesses that could influence cholesterol levels, eating disorders, and age greater than 70 years.

Results: Cholesterol levels did not differ based on diagnostic status of unipolar depression or bipolar disorder. In the total sample, cholesterol levels were lower in patients with current manic (170.2±38.9, p=0.05) and depressive (182.0±42.0) than in mixed (226.4±43.3) episodes (p=0.05). In subgroups of patients with bipolar disorder, manic episodes (169.9±38.8, n=9) were associated with lower cholesterol levels than depressive (201.0±49.4) or mixed (226.4±44.4) episodes (p=0.02 for comparison of manic and mixed episodes). Body mass index (BMI), age, alcohol use, and gender did not account for these findings.

Conclusions: Cholesterol levels were lower in manic and depressive than in mixed episodes. No differences were found between diagnoses of unipolar or bipolar mood disorders. Cholesterol may be a state rather than a trait function, and may be influenced by the acute mood state.