The prognostic role of perceived criticism, medication adherence and family knowledge in bipolar disorders.

BACKGROUND: In schizophrenia, high levels of critical comments by significant others are associated with early relapse, especially if medication adherence is sub-optimal. Levels of criticism may be influenced by family knowledge about both the disorder and its treatment. No study has explored whether this combination factors influence outcome in adults with bipolar disorders. METHODS: Medication adherence was assessed in 81 individuals with bipolar disorder of whom 75 rated perceived criticism by an identified 'significant other' as well as their own perceived sensitivity. 33 (of the 75) had a close family member who agreed to completed an assessment of their knowledge and understanding of bipolar disorders. Psychiatric admissions were then recorded prospectively over 12 months. RESULTS: Perceived criticism and medication adherence were significant predictors of admission. In the patient-family member dyads (n=33), the odds ratio (OR) for admission was 3.3 (95% confidence intervals 1.3-8.6) in individuals with low levels of medication adherence, high perceived criticism, and a family member with poor knowledge and understanding. LIMITATIONS: The small sub-sample of patient-family member dyads means those findings require replication. Sensitivity to criticism by professional caregivers may not equate to that by relatives. CONCLUSIONS: Perceived criticism may be a simple but robust clinical predictor of relapse in mood disorders. High levels of perceived criticism, poor understanding of bipolar disorder by a significant other, and sub-optimal treatment adherence are risk factors for hospitalization in adults with bipolar disorders that are potentially modifiable through the use of strategic psychosocial interventions.

Gene expression changes in female zebrafish (Danio rerio) brain in response to acute exposure to methylmercury.

Methylmercury (MeHg) is a potent neurotoxicant and endocrine disruptor that accumulates in aquatic systems. Previous studies have shown suppression of hormone levels in both male and female fish, suggesting effects on gonadotropin regulation in the brain. The gene expression profile in adult female zebrafish whole brain induced by acute (96 h) MeHg exposure was investigated. Fish were exposed by injection to 0 or 0.5 µg MeHg/g. Gene expression changes in the brain were examined using a 22,000-feature zebrafish microarray. At a significance level of p < 0.01, 79 genes were up-regulated and 76 genes were down-regulated in response to MeHg exposure. Individual genes exhibiting altered expression in response to MeHg exposure implicate effects on glutathione metabolism in the mechanism of MeHg neurotoxicity. Gene ontology (GO) terms significantly enriched among altered genes included protein folding, cell redox homeostasis, and steroid biosynthetic process. The most affected biological functions were related to nervous system development and function, as well as lipid metabolism and molecular transport. These results support the involvement of oxidative stress and effects on protein structure in the mechanism of action of MeHg in the female brain. Future studies will compare the gene expression profile induced in response to MeHg with that induced by other toxicants and will investigate responsive genes as potential biomarkers of MeHg exposure.

Determinants of social functioning in bipolar disorder.

BACKGROUND: Evidence indicates that social outcomes in bipolar disorders (BP) are poorer than previously assumed. This study explores determinants of the quality and quantity of social activity. METHODS: Seventy-seven subjects with BP completed self-report and observer-rated questionnaires assessing demographic and clinical factors, personality and social functioning. RESULTS: Quality of functioning and spectrum of activity were found to be independent. The best determinants of the quality of functioning, accounting for 33% of the variance, were premorbid neuroticism and the current level of depressive symptoms. Only 30% of subjects were active in all social domains, and the quantity of social activity was largely explained by social circumstances, namely, living with someone else and later age of illness onset. CONCLUSIONS: The implications of these findings are discussed in this paper. We suggest that future studies need to differentiate between factors associated with the quality of functioning as compared with the quantity of social activity.

Cognitive styles in individuals with bipolar disorders.

BACKGROUND: Published studies of emotional processing and cognitive style in bipolar disorders tend to have small sample sizes or use non-clinical samples. Larger clinically representative studies are needed. METHOD: Self-esteem, dysfunctional attitudes and personality style were compared in unipolar (N=16) and bipolar disorder (N=77); and then investigated in the different phases of bipolar disorder (remitted=26; depressed=38; hypomanic=13). One-year outcome was assessed in 36 bipolar subjects. RESULTS: Unipolar subjects and bipolar subjects differed significantly in their mean levels of negative self-esteem (unipolar=15.5; bipolar=12.7; P<0.05). Bipolar subjects with hypomania reported mean levels of dysfunctional beliefs that were higher than individuals in remission but lower than depressed subjects (remitted=136.7; depressed=153.8; hypomanic=144.8; P<0.05). Hypomanic subjects recorded the highest levels of negative as well as positive self-esteem. In the exploratory analysis of outcome, negative self-esteem (Exp [B] 1.91; 95% CI 1.11 to 3.32; P<0.05) was the most robust predictor of relapse. CONCLUSIONS: There are similarities in the cognitive style of individuals with unipolar as compared to bipolar disorders. Cognitive style in hypomania represents a phase between remission and depression rather than the polar opposite of depression. The implications of these findings are considered for psychological and neural network models.

Do clinicians understand why individuals stop taking lithium?

BACKGROUND: Previous research highlights that, over a 2-year period, up to 50% of individuals receiving lithium prophylaxis are non-adherent with medication against medical advice. The main reasons identified by clinicians only partially reflect the reasons given by patients. METHODS: Seventy-two subjects who were identified from biochemistry laboratory data as receiving lithium for an affective disorder and who gave written informed consent, completed the 'Reasons for Stopping Medication' questionnaire. Forty-one clinicians involved in treating these 72 patients also completed the same questionnaire. Ratings on the 'Reasons for Stopping Medication' questionnaire were compared between adherent and non-adherent patients and between patients and their clinicians. RESULTS: Adherent (n=39) and previously non-adherent patients (n=33) showed a high level of concordance in their rank ordering of reasons for considering stopping taking lithium (Kendall's W=0.059; P=0.001), with 'bothered by the idea that moods were controlled by medication', 'bothered by the idea of a chronic illness' and 'felt depressed' being the most commonly endorsed items. Clinicians and patients views showed low levels of concordance (Kendall's W=0.019; P=0.32). Clinicians identified 'missing highs', and 'felt well, saw no need to take medication' as the most likely reasons for non-adherence. The differences in the primary reasons for stopping lithium identified by clinicians and patients were statistically significant (chi(2)=61.1; df 40, P=0.005). CONCLUSIONS: Patients' reasons for stopping lithium appear to be influenced by concerns about what having an affective disorder and taking medication says about them. Clinicians are not fully aware of the main reasons patients would stop prophylactic treatment.

Self-reported adherence to treatment with mood stabilizers, plasma levels, and psychiatric hospitalization.

OBJECTIVE: The authors explored the relationship of adherence to treatment with mood stabilizers (lithium, carbamazepine, and sodium valproate) and plasma levels of these drugs to future psychiatric hospitalizations. METHOD: They prospectively followed 98 patients with mood disorders who were prescribed mood stabilizers. These patients participated in an initial interview and completed a questionnaire regarding their adherence to the medications. Data on their plasma levels of these drugs were taken from assays done in the 3 months before the interview. RESULTS: Six of the 98 patients were not classified as to medication adherence or plasma levels. Twenty-nine (32%) of the remaining patients reported partial adherence to the medication regimen, and 33 (36%) had an index plasma level that was suboptimal. At 18 months, rates of admission to a psychiatric hospital were significantly higher in the 16 partially adherent patients with subtherapeutic plasma levels (N=13, 81%) than in the 46 adherent patients with therapeutic plasma levels (N=4, 9%). However, hospital admission was also more likely in partially adherent patients with therapeutic plasma levels than in adherent patients with subtherapeutic plasma levels. CONCLUSIONS: Adherence to medication regimens may be a proxy measure of other healthy behaviors.

Nonadherence with mood stabilizers: prevalence and predictors.

BACKGROUND: The prevalence of nonadherence with mood stabilizers ranges from about 18% to 52%. Only 1% of publications on mood stabilizers address this issue. This study aimed to explore the prevalence and predictors of nonadherence in a cohort of individuals with affective disorders receiving long-term treatment with mood stabilizers. METHOD: Subjects receiving lithium, carbamazepine, and/or valproate were identified from biochemistry laboratory data. Ninety-eight of these subjects had major depressive disorder (N = 20) or bipolar disorder (N = 78) (DSM-IV) and gave informed consent to participate in a structured clinical interview to assess their medication adherence and the factors that influenced it. RESULTS: Just under 50% of subjects (46/98) acknowledged some degree of medication nonadherence in the previous 2 years, and 32% (29/92) reported only partial adherence in the last month (missing 30% or more of their prescribed medication). Backward stepwise logistic regression demonstrated that partially adherent subjects were best distinguished from adherent subjects by a more frequent past history of nonadherence, denial of severity of illness, and greater duration of being prescribed a mood stabilizer. CONCLUSION: Rates of mood stabilizer nonadherence are high. Attitudes and behaviors are better predictors of nonadherence than side effects from medication. Clinicians need to inquire routinely about problems with adherence.

Metacognitive awareness and prevention of relapse in depression: empirical evidence.

Metacognitive awareness is a cognitive set in which negative thoughts/feelings are experienced as mental events, rather than as the self. The authors hypothesized that (a) reduced metacognitive awareness would be associated with vulnerability to depression and (b) cognitive therapy (CT) and mindfulness-based CT (MBCT) would reduce depressive relapse by increasing metacognitive awareness. They found (a) accessibility of metacognitive sets to depressive cues was less in a vulnerable group (residually depressed patients) than in nondepressed controls; (b) accessibility of metacognitive sets predicted relapse in residually depressed patients; (c) where CT reduced relapse in residually depressed patients, it increased accessibility of metacognitive sets; and (d) where MBCT reduced relapse in recovered depressed patients, it increased accessibility of metacognitive sets. CT and MBCT may reduce relapse by changing relationships to negative thoughts rather than by changing belief in thought content.