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Objective: To assess depressive features of a proposed definition of bipolar spectrum disorder (BSD)., Methods: Thirty-six patients with bipolar disorder type I or II were compared to 37 patients with unipolar major depressive disorder through patient interview and chart review., Results: Univariate analysis suggests that 7 of 12 (recurrent major depressive episodes, brief major depressive episodes, atypical depressive symptoms, early age of onset, family history of bipolar disorder, antidepressant tolerance, and antidepressant-induced mania) features of major depressive episodes were more likely to occur in bipolar versus unipolar patients. After adjustment in a multivariable regression model, however, the five most powerful predictors of bipolar disorder were brief major depressive episodes, early age of onset, antidepressant- induced mania, postpartum depression, and atypical depressive symptoms., Conclusions: This preliminary study supports the idea that bipolar disorder is characterized by some depressive features less likely to be found in unipolar depression. Further prospective study needs to be conducted comparing BSD with unipolar depression.

To compare long-term effectiveness and safety of risperidone versus olanzapine as adjunctive maintenance treatments of bipolar disorder. Retrospective observational chart review of 29 outpatients with bipolar or schizoaffective disorder (type I = 15, type II = 3, NOS = 5, schizoaffective = 6) who received risperidone or olanzapine added to lithium or valproate >3 months. Acute indications were depression (n = 8), manic/hypomanic/mixed states (n = 8), rapid cycling (n = 6), other indications (n = 6), and prophylaxis (n = 1). Logistic regression models adjusted for potential confounding factors (i.e., severity of illness, comorbid substance abuse, diagnostic subtype). Overall duration of follow-up was 65.9+/-70.1 weeks. Mild to moderate response was similar in the risperidone and olanzapine groups after adjusting for potential confounders (OR = 0.91, 95% CI [0.05, 16.17]). Somewhat greater adjusted moderate to marked response (OR >3.60, 95% CI [0.31, >42.00]) and longer duration of treatment (HR = 0.52, 95% CI [0.22, 1.22]) occurred in the risperidone group, but were still compatible with the null hypothesis. Weight gain occurred more frequently with olanzapine (57%) than risperidone (13%). EPS was similar, and tardive dyskinesia did not occur. Risperidone and olanzapine appeared to have similar real-world maintenance effectiveness for bipolar disorder, but differed somewhat in side effects.

In interpreting the maintenance literature for bipolar disorder, attention needs to be paid to important methodological issues. In this article, we initially examine the methodological topics that need to be considered, and we then examine the content of the evidence regarding maintenance treatments. Agents used in the long-term treatment of bipolar disorder possess varying degrees of supportive evidence. By consensus, the number of randomized studies and years of clinical experience with lithium mark it as the evidentially strongest long-term agent for bipolar disorder. Recent studies also demonstrate likely long-term benefit with lamotrigine, and possibly olanzapine. Although we possess fewer randomized data, some such evidence exists and, along with clinical experience, supports the likely long-term utility of valproate in the treatment of bipolar disorder as well. Some psychotherapies also may possess adjunctive maintenance efficacy.

The relative misdiagnosis and underdiagnosis of bipolar disorder is due in part to the 'soft' symptoms of bipolarity that characterize patients with non-classical bipolar disorder. While no agreement has been reached on the term for this group of patients, the most common classification used is 'bipolar spectrum', which shifts the emphasis in diagnosis away from polarity and toward other diagnostic validators. In order to recognize and properly treat patients with bipolar disorder, clinicians should focus on careful evaluation of patients with mixed anxiety/depressive symptoms or impulsivity conditions (substance abuse, borderline personality, bulimia, and attention deficit disorder). Furthermore, in the treatment of bipolar disorder, clinicians should also recognize that antidepressants can have a negative effect on patients by increasing the likelihood of more severe rapid cycling. While antidepressants may be useful in particularly difficult cases, emphasis should be placed on mood stabilizers for treatment of the bipolar spectrum.

The 2002 American Psychiatric Association (APA) guidelines for the treatment of bipolar disorder recommended more conservative use of antidepressants. This change in comparison with previous APA guidelines has been criticized, especially from some groups in Europe. The Munich group in particular has published a critique of assumptions underlying the conservative recommendations of the recent APA treatment guidelines. In this paper, we re-examine the argument put forward by the Munich group, and we demonstrate that indeed, conceptually and empirically, there is a strong rationale for a cautious approach to antidepressant use in bipolar disorder, consistent with, and perhaps even more strongly than, the APA guidelines. This rationale is based on support for the following four propositions: (i) The risk of antidepressant induced mood-cycling is high, (ii) Antidepressants have not been shown to definitively prevent completed suicides and reduce mortality, whereas lithium has, (iii) Antidepressants have not been shown to be more effective than mood stabilizers in acute bipolar depression and have been shown to be less effective than mood stabilizers in preventing depressive relapse in bipolar disorder and (iv) Mood stabilizers, especially lithium and lamotrigine, have been shown to be effective in acute and prophylactic treatment of bipolar depressive episodes. We therefore draw three conclusions from this interpretation of the evidence: (i) There are significant risks of mania and long-term worsening of bipolar illness with antidepressants, (ii) Antidepressants should generally be reserved for severe cases of acute bipolar depression and not routinely used in mild to moderate cases and (iii) Antidepressants should be discontinued after recovery from the depressive episode, and maintained only in those who repeatedly relapse after antidepressant discontinuation (a minority we judge to represent only about 15-20% of bipolar depressed patients).

This Commentary summarizes findings from three other papers in this issue with recommendations for evidence-based treatment with lithium, anticonvulsants, antipsychotics, and antidepressants in bipolar disorder. We will also provide a summary of levels of evidence and examine two important methodological issues in assessing drug-induced mania: reliance on significance testing for assessment of side-effects, and limitations of randomized controlled trials (RCTs) for assessing frequency of side-effects. If a study is not specifically powered and designed to assess a side-effect, then no significance testing should be conducted, and side-effects should simply be reported as effect estimates and confidence intervals. Further, RCTs only establish a categorical response to a research question, i.e. whether or not something happens. The frequency of an event (treatment response, side-effects) is often more accurately assessed with observational studies.

Objective: To assess the effectiveness and safety of oxcarbazepine in bipolar disorder., Method: A chart review of naturalistic treatment with oxcarbazepine in 42 outpatients with DSM-IV bipolar disorder (10 males, 32 females; mean +/- SD age = 33.3 +/- 12.4 years; 25 with bipolar disorder type I, 4 with bipolar disorder type II, and 13 with bipolar disorder not otherwise specified) was conducted. Patients had received oxcarbazepine monotherapy or adjunctive therapy between April 2000 and April 2002. Treatment response was defined as a Clinical Global Impressions-Improvement scale score of 1 (marked improvement) or 2 (moderate improvement)., Results: Oxcarbazepine was moderately to markedly effective in 24 subjects (57%). Mixed symptoms were the most common indication (52% [22/42]). The mean oxcarbazepine dose was 1056.6 mg/day, and mean treatment duration was 16.2 weeks. Sedation (17/42, 40%) was the most common side effect, but 16 patients (38%) had no side effects. Twenty-two patients (52%) stopped treatment, mostly due to side effects (12/22). Males were more likely to respond than females (10/10 vs. 14/32, p =.006). Dose, bipolar subtype, indication, past nonresponse to mood stabilizers, concurrent mood stabilizer use, and monotherapy use of oxcarbazepine did not differentially predict response., Conclusion: Oxcarbazepine appeared effective in about one half of patients with bipolar disorder and was well tolerated.

Weanling rats fed a zinc-deficient diet (less than 1 part/10(6)) for 4 weeks develop parakeratotic and hyperplastic buccal epithelium with increased mitotic activity. Normal buccal epithelium contains major keratin polypeptides of 56, 46 and 43 kDa. Four-week zinc-deficient rats lacked the 43 kDa keratin. It appears that the 46 and 43 kDa keratins are related, differing as a result of some post-translation modification. A proteolytic cleavage of the 46 kDa keratin to the 43 kDa species is the most likely mechanism. The findings point to a decrease of keratinolytic enzyme activity in the zinc-deficient rats.

Thirteen cases of pleomorphic adenoma were studied by both immunohistochemical and other histochemical methods. The exocrine cells and myoepithelial cells appear to produce similar cell products as their normal salivary gland counterparts. Keratin was found in both exocrine cells and myoepithelial cells. CEA, secretory component, and lactoferrin were detected only in the tumor exocrine cells with adenoid differentiation. S-100 protein, ferritin, fibronectin, laminin and elastin were detected only in the myoepithelial cells. The residual sugars glucosyl, mannosyl, galactosyl and fucosyl were identified in both cell types, in variably detectable amounts.

One case of myoepithelioma was studied by immunohistochemical and histochemical methods to identify the cell products of this tumor. The myoepithelioma had two cell types: plasmacytoid cells and spindle cells. The tumor myoepithelial cells produced the same cell products as did the normal myoepithelial cells but in variable amounts, possibly related to stages of differentiation. As no exocrine cell products could be identified in this neoplasm, it is considered a "true" myoepithelioma.

Spectrin binds to a population of high-affinity sites on the exposed surface of inverted vesicles prepared from human red blood cell ghost membranes. Optimal spectrin binding requires the presence of monovalent salts but does not require calcium or magnesium. The band 2 subunit of spectrin, prepared in SDS, can also bind to vesicles, but isolated band 1 is inactive. Pre-incubation of inverted vesicles with antibodies directed against the cytoplasmic segment of band 3 or against bands 4.1-4.2 inhibits the binding of spectrin to the same vesicles. Antibodies against the cytoplasmic portion of glycophorin A have no effect. These results suggest that spectrin binds to a protein acceptor on the cytoplasmic surface of the red cell membrane which is close to the cytoplasmic segments of bands 3 and 4.1 and/or 4.2.