Diagnostic depressive symptoms of the mixed bipolar episode.

BACKGROUND: There is not yet consensus on the best diagnostic definition of mixed bipolar episodes. Many have suggested the DSM-III-R/-IV definition is too rigid. We propose alternative criteria using data from a large patient cohort. METHODS: We evaluated 237 manic in-patients using DSM-III-R criteria and the Scale for Manic States (SMS). A bimodally distributed factor of dysphoric mood has been reported from the SMS data. We used both the factor and the DSM-III-R classifications to identify candidate depressive symptoms and then developed three candidate depressive symptom sets. Using ROC analysis we determined the optimal threshold number of symptoms in each set and compared the three ROC solutions. The optimal solution was tested against the DSM-III-R classification for crossvalidation. RESULTS: The optimal ROC solution was a set, derived from both the DSM-III-R and the SMS, and the optimal threshold for diagnosis was two or more symptoms. Applying this set iteratively to the DSM-III-R classification produced the identical ROC solution. The prevalence of mixed episodes in the cohort was 13.9% by DSM-III-R, 20.2% by the dysphoria factor and 27.4% by the new ROC solution. CONCLUSIONS: A diagnostic set of six dysphoric symptoms (depressed mood, anhedonia, guilt, suicide, fatigue and anxiety), with a threshold of two symptoms, is proposed for a mixed episode. This new definition has a foundation in clinical data, in the proved diagnostic performance of the qualifying symptoms, and in ROC validation against two previous definitions that each have face validity.

Signs and symptoms of mania in pure and mixed episodes.

BACKGROUND: Debate continues about the diagnosis of mixed mania and the restrictiveness of the DSM-III-R and DSM-IV criteria for Bipolar Disorder, mixed. Although awareness of dysphoric features during mania continues to grow, standard mania rating instruments do not adequately assess mixed states and there is a striking disparity between the dysphoric signs and symptoms emphasized in research studies and the commonly employed DSM criteria. METHODS: Three hundred sixteen inpatients meeting DSM-III-R criteria for Bipolar Disorder, manic or mixed, were evaluated by rating 20 signs and symptoms. The frequencies of these signs and symptoms were computed for both diagnostic subtypes and compared using chi2 statistics and conditional probability parameters. RESULTS: The most frequently noted signs and symptoms in mania are motor activation, accelerated thought process, pressured speech and decreased sleep. Although euphoric mood was present in a large portion of the cohort, irritability, dysphoric mood and mood lability were also prominent in the entire cohort. Dysphoric mood, mood lability, anxiety, guilt, suicidality, and irritability were the only symptoms significantly more common in the mixed group. In contrast, grandiosity, euphoric mood, and pressured speech were significantly more often observed in the pure manic group. Contrary to popular belief, paranoia did not differ significantly between the two groups. Suicidality was present in a non-trivial 7% of the entire cohort, including some subjects who did not meet the criteria for mixed mania. LIMITATIONS: The comparison of mixed and manic episodes requires the appropriate definition of mixed states. In the current report we use the DSM-III-R definition of Bipolar Disorder, mixed, which may be too rigid. CONCLUSIONS: The data underscore that mania is not a purely euphoric state. Substantial rates of dysphoria, lability, anxiety and irritability were noted in the "pure" manic patients, as well as in those who meet the full DSM criteria for Bipolar Disorder, mixed, suggesting, that perhaps a less restrictive definition of mixed states would be more appropriate.

Tryptophan depletion in recently manic patients treated with lithium.

BACKGROUND: Serotonin has been repeatedly implicated in the mechanism of action of lithium against acute mania. Its role, however, has never been directly confirmed. METHODS: We studied recently manic patients successfully treated with lithium using a tryptophan depletion methodology. RESULTS: Patients remained euthymic despite a confirmed decrease in serum tryptophan levels. CONCLUSIONS: These data do not suggest that serotonin plays a critical role in the acute antimanic effect of lithium.

A factor analysis of the signs and symptoms of mania.

BACKGROUND: No adequate factor analyses of signs and symptoms of mania have been reported. From limited past reports, the view has arisen that 2 main symptom clusters (euphoric-grandiose and paranoid-destructive) occur in patients with mania, along with so-called core symptoms of psychomotor pressure. In this view, dysphoric mania is associated with paranoid-destructive symptoms and with psychosis. METHODS: We rated 237 patients with DSM-III-R-defined bipolar disorder, manic (n = 204) or mixed (n = 33), on 15 classic features of mania and 5 features related to dysphoric mood. Principal components factor analysis was applied to the ratings. RESULTS: Five clearly interpretable and clinically relevant factors were identified. The first and strongest factor represented dysphoria in mania, with strong positive loadings for depressed mood, lability, guilt, anxiety, and suicidal thoughts and behaviors and a strong negative loading for euphoric mood. Factors 2 through 5 represented psychomotor acceleration, psychosis, increased hedonic function, and irritable aggression, respectively. The distribution of weighted scores on factor 1 was bimodal, whereas the corresponding distributions of factors 2 through 5 were unimodal. Contrary to all past reports, no general factor denoting overall severity of mania was found. Factors previously proposed by Beigel and Murphy were not confirmed. CONCLUSIONS: Five independent factors representing dysphoric mood, psychomotor pressure, psychosis, increased hedonic function, and irritable aggression were identified. The conventional view of symptom factors in mania was not confirmed. Dysphoric features are statistically salient in patients with mania, and the bimodal distribution of the dysphoria factor is consistent with the possibility that mixed bipolar disorder is a distinct state.

The performance of DSM-III-R major depression criteria in the diagnosis of bipolar mixed states.

Two hundred thirty-seven (237) manic patients diagnosed by DSM-III-R criteria as either purely manic (204) or mixed bipolar (33) were reviewed for analysis of the diagnostic performance of the DSM-III-R criteria required to diagnose the mixed bipolar state. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic efficiency of each of the 9 DSM-III-R criteria for major depression in this cohort. As predicted, four of the major depression criteria had low diagnostic utility, with PPV's less than 0.3. Those items were: weight change; sleep disturbance; psychomotor change; and diminished ability to think or concentrate or indecisiveness. Four symptoms: anhedonia, fatigue, feelings of worthlessness or guilt, and recurrent thoughts of death or suicidal ideation had acceptable utility for the diagnosis of mixed states.

Lack of relapse with tryptophan depletion following successful treatment with ECT.

OBJECTIVE: Although the antidepressant mechanism of ECT is unknown, there are considerable data to support serotonergic involvement. The effects of tryptophan depletion were studied in patients with major depression treated successfully with ECT. METHOD: Five patients who had been successfully treated with ECT for major depression were studied in a randomized, double-blind, crossover design comparing tryptophan depletion to a placebo procedure. RESULTS: No effect of tryptophan depletion on mood symptoms was observed despite more than an 85% decrease in total serum tryptophan. CONCLUSIONS: These data suggest that presynaptic serotonin availability may not be necessary for the acute maintenance of an antidepressant response to ECT.