A double blind randomized clinical trial of buprenorphine augmentation for treatment of psychotic symptoms in opioid addicted bipolar patients.

OBJECTIVE: To assess the efficacy of buprenorphine augmentation in treatment of psychotic symptoms in bipolar disorder type I. DESIGN: Bipolar type I patients with manic or depressive episodes and psychotic feature and with opioid dependency comorbidity were randomly included and allocated. Both groups of buprenorphine (4 or 6 mg/d) and placebo were also treated with enough dosages of sodium valproate and risperidone. Psychosis as primary outcome and depressive and manic symptoms as secondary outcome were assessed at baseline and after 1 and 2 weeks. Data were analyzed through t test and repeated measure ANOVA. RESULTS: Twenty-four patients remained in each group. Both groups displayed significant reduction in psychotic, depressive, and manic symptoms during the 2 weeks of study, although there was not any significant difference between them. CONCLUSIONS: Buprenorphine did not add any efficacy to usual treatment of psychotic episodes of bipolar, although did not aggravate psychiatric symptoms.

A case of skew deviation and downbeat Nystagmus induced by Lithium.

BACKGROUND: Lithium salts have been commonly used for prophylaxis and treatment of bipolar disorder and have numerous side effects. However, there has been no report of skew deviation and downbeat nystagmus associated with lithium. Herein, we report the first case of lithium-induced skew deviation and downbeat nystagmus. CASE PRESENTATION: A 39 years-old woman presented with intermittent vertical diplopia and dizziness within 1-2 months. Ophthalmologic examination revealed downbeat nystagmus and 6 prism diopters of right hypertropia. Funduscopic examination showed mild incyclotorsion on right eye. However, ductions and versions were within normal range. Other neurological examinations were also normal. She had a history of bipolar disorder treated with daily 600-900 mg of lithium for past 6 years, and 2 months before the first visit, daily dose of lithium was increased to 1200 mg. We referred the patients to psychiatrist. Although the serum level of lithium was within the normal therapeutic range, her daily dose of lithium was reduced to 600 mg and then stopped. 6 days after cessation of lithium, down beat nystagmus and right hypertropia were completely resolved and symptoms did not recur over a year. CONCLUSION: Even within a normal therapeutic range, downbeat nystagmus and skew deviation can occur as side effect of lithium. Dehydration may contribute to the neurotoxicity of lithium.

Sexual dimorphism in up-regulation of suppressors of cytokine signaling genes in patients with bipolar disorder.

BACKGROUND: Proteins encoded by Suppressors of cytokine signaling (SOCS) genes have critical roles in the regulation of immune responses. Meanwhile, several lines of evidence support the presence of immune dysfunction in bipolar disorder (BD) patients. METHODS: In the present study, we assessed expression levels of SOCS1-3 and SOCS5 genes in peripheral blood of patients with BD and healthy subjects. RESULTS: All SOCS genes were up-regulated in patients compared with healthy subjects. However, when comparing patients with sex-matched controls, the significant differences were observed only in the male subjects except for SOCS5 which was up-regulated in both male and female patients compared with the corresponding control subjects. Significant pairwise correlations were found between expression levels of genes in both patients and controls. Based on the area under curve values, SOCS5 had the best performance in the differentiation of disease status in study participants (AUC = 0.92). Combination of four genes increased the specificity of tests and resulted in diagnostic power of 0.93. CONCLUSION: Taken together, these data suggest a role for SOCS genes in the pathogenesis of BD especially in the male subjects. Moreover, peripheral expression levels of SOCS genes might be used as a subsection of a panel of diagnostic biomarkers in BD.

Psychosocial Implications of Tardive Dyskinesia in Patients With Mood Disorders Versus Schizophrenia.

Dopamine receptor blocking agents-including antipsychotics-can produce tardive dyskinesia (TD). First-generation antipsychotics were effective in treating schizophrenia and severe forms of bipolar disorder; however, they were associated with substantial extrapyramidal effects, especially at high doses. Second-generation antipsychotics are effective and produce fewer adverse movement effects; nevertheless, the risk for TD was not eliminated. Tardive dyskinesia can be distressing to patients with good insight into their illness and the movements, especially if they are working and in relationships, and should be treated to improve psychosocial outcomes. In patients with poor insight into their illness and lack of awareness of their TD symptoms, clinicians should treat TD if it causes severe impairment.

Statistical methods for testing X chromosome variant associations: application to sex-specific characteristics of bipolar disorder.

BACKGROUND: Bipolar disorder (BD) affects both sexes, but important sex differences exist with respect to its symptoms and comorbidities. For example, rapid cycling (RC) is more prevalent in females, and alcohol use disorder (AUD) is more prevalent in males. We hypothesize that X chromosome variants may be associated with sex-specific characteristics of BD. Few studies have explored the role of the X chromosome in BD, which is complicated by X chromosome inactivation (XCI). This process achieves "dosage compensation" for many X chromosome genes by silencing one of the two copies in females, and most statistical methods either ignore that XCI occurs or falsely assume that one copy is inactivated at all loci. We introduce new statistical methods that do not make these assumptions. METHODS: We investigated this hypothesis in 1001 BD patients from the Genetic Association Information Network (GAIN) and 957 BD patients from the Mayo Clinic Bipolar Disorder Biobank. We examined the association of over 14,000 X chromosome single nucleotide polymorphisms (SNPs) with sex-associated BD traits using two statistical approaches that account for whether a SNP may be undergoing or escaping XCI. In the "XCI-informed approach," we fit a sex-adjusted logistic regression model assuming additive genetic effects where we coded the SNP either assuming one copy is expressed or two copies are expressed based on prior knowledge about which regions are inactivated. In the "XCI-robust approach," we fit a logistic regression model with sex, SNP, and SNP-sex interaction effects that is flexible to whether the region is inactivated or escaping XCI. RESULTS: Using the "XCI-informed approach," which considers only the main effect of SNP and does not allow the SNP effect to differ by sex, no significant associations were identified for any of the phenotypes. Using the "XCI-robust approach," intergenic SNP rs5932307 was associated with BD (P = 8.3 × 10-8), with a stronger effect in females (odds ratio in males (ORM) = 1.13, odds ratio in females for a change of two allele copies (ORW2) = 3.86). CONCLUSION: X chromosome association studies should employ methods which account for its unique biology. Future work is needed to validate the identified associations with BD, to formally assess the performance of both approaches under different true genetic architectures, and to apply these approaches to study sex differences in other conditions.

Hepatic gene expression explains primary drug toxicity in bipolar disorder.

In bipolar disorder (BPD), long-term psychotropic drug treatment is often necessary to prevent relapse or recurrence. Nevertheless, adverse drug effects including disturbances in hepatic metabolism are observed and still poorly understood. Here, the association between hepatic gene expression and histopathological changes of the liver was investigated. By the use of microarrays (Affymetrix U133 plus2.0), a genome-wide expression study was performed on BPD patients with psychotropic drug treatment (n = 29) compared to unaffected controls (n = 20) and validated by quantitative real-time PCR. WebGestalt was used to identify over-represented functional pathways of the Reactome database. Association analyses between histopathological changes and differentially expressed genes comprised in the over-represented functional pathways were performed using regression analyses, from which feature-expression heatmaps were drawn. The majority of identified genes were underexpressed and involved in energy supply, metabolism of lipids and proteins, and the innate immune system. Positive associations were found for genes involved in all pathways and degenerative changes. The strongest negative association was observed between genes involved in energy supply and hepatic activity, as well as inflammation. In summary, we found a possible association between gene expression involved in various biological pathways and histopathological changes of the liver in BPD. Further, we found support for the probable primary toxic effect of psychotropic drugs on hepatic injury in BPD. Even if the safety of psychotropic drugs improves, adverse effects especially on hepatic function should not be underestimated.

CACNA1C polymorphism and brain cortical structure in bipolar disorder

Background: The CACNA1C gene encodes the 1C subunit of L-type voltage-gated calcium channels and has been associated with several psychiatric syndromes ­ including bipolar disorder ­ in several genome-wide association studies. Experimental and clinical studies have reported changes with respect to behaviour and biomarkers in risk allele carriers, corroborating the essential role of the CACNA1C gene in neurons, during development and in the mature brain. However, the association of this gene with regional cortical thickness has not been evaluated in patients with bipolar disorder. Methods: Using magnetic resonance imaging, we measured the average cortical thickness of 68 brain regions in 87 patients genotyped for the single-nucleotide polymorphism rs1006737 in CACNA1C. Results: We found associations with the mean thickness of several cortical areas: the left lateral orbitofrontal and rostral anterior cingulate cortices, as well as other parts of the frontal and parietal cortices. Limitations: This cross-sectional cohort study could not fully differentiate correlation from causation. Conclusion: The CACNA1C polymorphism rs1006737 is associated with the mean thickness of cortical brain areas that have been shown to be altered in bipolar disorder.

The impact of familial risk and early life adversity on emotion and reward processing networks in youth at-risk for bipolar disorder.

A recently developed risk calculator for bipolar disorder (BD) accounts for clinical and parental psychopathology. Yet, it is understood that both familial predisposition and early life adversity contribute to the development of BD. How the interplay between these two factors influence emotion and reward processing networks in youth at risk for BD remains unclear. In this exploratory analysis, offspring of BD parents performed emotion and reward processing tasks while undergoing a fMRI scan. Risk calculator score was used to assess risk for developing BD in the next 5 years. Environmental risk was tabulated using the Stressful Life Events Schedule (SLES). Emotion and reward processing networks were investigated for genetic and/or environment interactions. Interaction effects were found between risk calculator scores, negative SLES score and activity in right amygdala and bilateral fusiform gyri during the emotion processing task, as well as activity in the fronto-, striatal, and parietal regions during the reward processing task. Our findings are preliminary; however, they support the unique and interactive contributions of both familial and environmental risk factors on emotion and reward processing within OBP. They also identify potential neural targets to guide development of interventions for youth at greatest risk for psychiatric disorders.

Postpartum psychosis in bipolar disorder: no evidence of association with personality traits, cognitive style or affective temperaments.

BACKGROUND: Bipolar disorder has been associated with several personality traits, cognitive styles and affective temperaments. Women who have bipolar disorder are at increased risk of experiencing postpartum psychosis, however little research has investigated these traits and temperaments in relation to postpartum psychosis. The aim of this study is to establish whether aspects of personality, cognitive style and affective temperament that have been associated with bipolar disorder also confer vulnerability to postpartum psychosis over and above their known association with bipolar disorder. METHODS: Personality traits (neuroticism, extraversion, schizotypy and impulsivity), cognitive styles (low self-esteem and dysfunctional attitudes) and affective temperaments (including cyclothymic and depressive temperaments) were compared between two groups of parous women with DSM-IV bipolar I disorder: i) 284 with a lifetime history of postpartum psychosis within 6 weeks of delivery (PP group), ii) 268 without any history of mood episodes with onset during pregnancy or within 6 months of delivery (no perinatal mood episode, No PME group). RESULTS: After controlling for current mood state, and key demographic, clinical and pregnancy-related variables, there were no statistically significant differences between the PP and No PME groups on any of the personality, cognitive style or affective temperament measures. CONCLUSIONS: Personality traits, cognitive styles and affective temperaments previously shown to be associated with bipolar disorder in general were not specifically associated with the occurrence of postpartum psychosis. These factors may not be relevant for predicting risk of postpartum psychosis in women with bipolar disorder.

Use of ecological momentary assessment to detect variability in mood, sleep and stress in bipolar disorder.

OBJECTIVE: Our aim was to study within-person variability in mood, cognition, energy, and impulsivity measured in an Ecological Momentary Assessment paradigm in bipolar disorder by using modern statistical techniques. Exploratory analyses tested the relationship between bipolar disorder symptoms and hours of sleep, and levels of pain, social and task-based stress. We report an analysis of data from a two-arm, parallel group study (bipolar disorder group N = 10 and healthy control group N = 10, with 70% completion rate of 14-day surveys). Surveys of bipolar disorder symptoms, social stressors and sleep hours were completed on a smartphone at unexpected times in an Ecological Momentary Assessment paradigm twice a day. Multi-level models adjusted for potential subject heterogeneity were adopted to test the difference between the bipolar disorder and health control groups. RESULTS: Within-person variability of mood, energy, speed of thoughts, impulsivity, pain and perception of skill of tasks was significantly higher in the bipolar disorder group compared to health controls. Elevated bipolar disorder symptom domains in the evening were associated with reduced sleep time that night. Stressors were associated with worsening of bipolar disorder symptoms. Detection of symptoms when an individual is experiencing difficulty allows personalized, focused interventions.

Exposure to household pet cats and dogs in childhood and risk of subsequent diagnosis of schizophrenia or bipolar disorder.

BACKGROUND: Serious psychiatric disorders such as schizophrenia and bipolar disorder have been associated with environmental exposures in early life. Contact with household pets such as cats and dogs can serve as a source of environmental exposure during these time periods. METHODS: We investigated the relationship between exposure to a household pet cat or dog during the first 12 years of life and having a subsequent diagnosis of schizophrenia or bipolar disorder. These studies were performed in a cohort of 396 individuals with schizophrenia, 381 with bipolar disorder, and 594 controls. The hazards of developing schizophrenia or bipolar disorder associated with first exposure to a household pet cat or dog were calculated using Cox Proportional Hazard and multivariate logistic regression models including socio-demographic covariates. RESULTS: We found that exposure to a household pet dog was associated with a significantly decreased hazard of having a subsequent diagnosis of schizophrenia (Hazard Ratio .75, p < .002) Furthermore, a significant decreased relative risk of schizophrenia was detected following exposure at birth and during the first years of life. There was no significant relationship between household exposure to a pet dog and bipolar disorder. There were no significant associations between exposure to a household pet cat and subsequent risk of either a schizophrenia or bipolar disorder diagnosis. However, there were trends towards an increased risk of both disorders at defined periods of exposure. CONCLUSIONS: Exposure to household pets during infancy and childhood may be associated with altered rates of development of psychiatric disorders in later life.

Sodium valproate induced acute pancreatitis in a bipolar disorder patient: a case report.

BACKGROUND: Sodium valproate is one of the most widely used antiepileptics and mood stabilizers. However, this drug may induce acute pancreatitis. Few cases have been reported so far, mainly on the pediatric patients who underwent antiepileptic treatment. Hereby, we present a case of bipolar disorder with sodium valproate-induced acute pancreatitis. CASE PRESENTATION: The patient is a 54-year-old Chinese male. He was diagnosed with bipolar disorder for more than 39 years. Since the first onset of the disease, he had several relapses. The patient had had sodium valproate to stabilize mood swings for a year before the occurrence of acute pancreatitis. But he did vomit once during the inpatient care period. Then he was referred to another hospital following a notably high level of amylase. The results of computed tomography demonstrated an increased pancreatic volume and swollen peripancreatic fat tissue. As a result, the patient was diagnosed with acute pancreatitis. Unlike other cases reported in literatures, the high amylase level did not revert to normal after the withdrawal of medications. The patient was discharged from hospital with a high level of amylase, and was placed under follow-up observations. CONCLUSION: Acute pancreatitis is considered as one of the idiosyncratic adverse reactions to antiepileptic drugs. Previous reports were mainly on the pediatric patients with increased propensity to idiosyncratic drug effects, or the adult chronic renal failure patients with sodium valproate-induced pancreatitis due to the retention of intermediate metabolites in their bodies. In this study, even though our patient exhibited no high risk of developing pancreatitis, he was treated for drug-induced acute pancreatitis in three hospitals. As rare as drug-induced acute pancreatitis can be, it should not be overlooked, Moreover, the mechanism of how sodium valproate induces acute pancreatitis remains unknown. Therefore, physicians need to consider the medical history of patients before prescribing this medication.

Pharmacological and behavioural interventions to promote smoking cessation in adults with schizophrenia and bipolar disorders: a systematic review and meta-analysis of randomised trials.

OBJECTIVE: Smoking in people with serious mental illness is a major public health problem and contributes to significant levels of morbidity and mortality. The aim of the review was to systematically examine the efficacy of methods used to aid smoking cessation in people with serious mental illness. METHOD: A systematic review and meta-analysis of randomised controlled trials to compare the effectiveness and safety of pharmacological and behavioural programmes for smoking cessation in people with serious mental illness. Electronic databases were searched for trials to July 2018. We used the Cochrane Collaboration's tool for assessing the risk of bias. RESULTS: Twenty-eight randomised controlled trials were identified. Varenicline increased the likelihood of smoking cessation at both 3 months (risk ratio (RR) 3.56, 95% CI 1.82 to 6.96, p=0.0002) and at 6 months (RR 3.69, 95% CI 1.08 to 12.60, p=0.04). Bupropion was effective at 3 months (RR 3.96, 95% CI 1.86 to 8.40, p=0.0003), especially at a dose of 300 mg/day, but there was no evidence of effect at 6 months (RR 2.22, 95% CI 0.52 to 9.47, p=0.28). In one small study, nicotine therapy proved effective at increasing smoking cessation up to a period of 3 months. Bupropion used in conjunction with nicotine replacement therapy showed more effect than single use. Behavioural and bespoke interventions showed little overall benefit. Side effects were found to be low. CONCLUSION: The new information of this review was the effectiveness of varenicline for smoking cessation at both 3 and 6 months and the lack of evidence to support the use of both bupropion and nicotine products for sustained abstinence longer than 3 months. Overall, the review found relatively few studies in this population.

Genetic Advance in Depressive Disorder.

Major depressive disorder (MDD) and bipolar disorder (BPD) are both chronic, severe mood disorder with high misdiagnosis rate, leading to substantial health and economic burdens to patients around the world. There is a high misdiagnosis rate of bipolar depression (BD) just based on symptomology in depressed patients whose previous manic or mixed episodes have not been well recognized. Therefore, it is important for psychiatrists to identify these two major psychiatric disorders. Recently, with the accumulation of clinical sample sizes and the advances of methodology and technology, certain progress in the genetics of major depression and bipolar disorder has been made. This article reviews the candidate genes for MDD and BD, genetic variation loci, chromosome structural variation, new technologies, and new methods.

Case of significantly delayed divalproex-induced thrombocytopaenia.

We describe a 48-year-old male patient on long-term divalproex treatment for bipolar disorder who developed grade II thrombocytopaenia after approximately 18 years of therapy. Abrupt cessation of divalproex led to immediate platelet level reconstitution.

Rapid cycling bipolar disorder is associated with antithyroid antibodies, instead of thyroid dysfunction.

BACKGROUND: Conclusions regarding the association between antithyroid antibodies or thyroid dysfunction and rapid cycling bipolar disorder (RCBD) have been conflicting. Previous studies suggest that the impact of antithyroid antibodies on mental wellbeing seems to be independent of thyroid function. Here, we investigated their independent association with RCBD in a large, well-defined population of bipolar disorder (BD). METHODS: Fast serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid Stimulating Hormone (TSH), TPO-abs and Tg-abs were simultaneously measured in 352 patients with BD. Clinical features of BD were collected through semi-structural interview conducted by trained interviewers with background of psychiatric education. RESULTS: Neither hypothyroidism nor hyperthyroidism was significantly associated with RCBD. Both TPO-abs and Tg-abs were significantly related to RCBD, even after controlling for gender, age, marriage status, education, antidepressants treatment, comorbidity of thyroid diseases, and thyroid function (serum levels of FT3, FT4 and TSH). Although TPO-abs and Tg-abs were highly correlated with each other, binary logistic regression with forward LR selected TPO-abs, instead of Tg-abs, to be associated with RCBD. TPO-abs was significantly, independently of Tg-abs, associated with hyperthyroidism, while Tg-abs was marginally significantly related to hypothyroidism at the presence of TPO-abs. CONCLUSION: TPO-abs might be treated as a biomarker of RCBD. Further exploring the underlying mechanism might help understand the nature of RCBD and find out new treatment target for it.

Air Pollution (Particulate Matter) Exposure and Associations with Depression, Anxiety, Bipolar, Psychosis and Suicide Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: Particulate air pollution's physical health effects are well known, but associations between particulate matter (PM) exposure and mental illness have not yet been established. However, there is increasing interest in emerging evidence supporting a possible etiological link. OBJECTIVES: This systematic review aims to provide a comprehensive overview and synthesis of the epidemiological literature to date by investigating quantitative associations between PM and multiple adverse mental health outcomes (depression, anxiety, bipolar disorder, psychosis, or suicide). METHODS: We undertook a systematic review and meta-analysis. We searched Medline, PsycINFO, and EMBASE from January 1974 to September 2017 for English-language human observational studies reporting quantitative associations between exposure to PM <1.0µm in aerodynamic diameter (ultrafine particles) and PM <2.5 and <10µm in aerodynamic diameter (PM2.5 and PM10, respectively) and the above psychiatric outcomes. We extracted data, appraised study quality using a published quality assessment tool, summarized methodological approaches, and conducted meta-analyses where appropriate. RESULTS: Of 1,826 citations identified, 22 met our overall inclusion criteria, and we included 9 in our primary meta-analyses. In our meta-analysis of associations between long-term (>6 months) PM2.5 exposure and depression (n=5 studies), the pooled odds ratio was 1.102 per 10-µg/m3 PM2.5 increase (95% CI: 1.023, 1.189; I2=0.00%). Two of the included studies investigating associations between long-term PM2.5 exposure and anxiety also reported statistically significant positive associations, and we found a statistically significant association between short-term PM10 exposure and suicide in meta-analysis at a 0-2 d cumulative exposure lag. DISCUSSION: Our findings support the hypothesis of an association between long-term PM2.5 exposure and depression, as well as supporting hypotheses of possible associations between long-term PM2.5 exposure and anxiety and between short-term PM10 exposure and suicide. The limited literature and methodological challenges in this field, including heterogeneous outcome definitions, exposure assessment, and residual confounding, suggest further high-quality studies are warranted to investigate potentially causal associations between air pollution and poor mental health. https://doi.org/10.1289/EHP4595.

Feasibility and Acceptability of a Lifestyle Intervention For Individuals With Bipolar Disorder.

Individuals with bipolar disorder are at greater risk for cardiovascular disease and are less likely to adhere to lifestyle interventions than the general population. To decrease cardiovascular risk and improve adherence to lifestyle interventions, we developed the Nutrition Exercise and Wellness Treatment (NEW Tx). NEW Tx is an 18-session, 20-week cognitive behavioral therapy-based treatment comprising 3 modules: Nutrition, Exercise, and Wellness. To evaluate the feasibility and acceptability of this intervention as well as predictors of treatment satisfaction and expectations, 38 adult outpatients with bipolar disorder were randomized to either NEW Tx or a waitlist control condition. There was no statistically significant difference in dropout rates between the groups (26.3% in NEW Tx, 31.6% in the control condition). In the NEW Tx condition, participants attended a mean of 66.7% of sessions and reported moderate to high satisfaction. There were no study-related adverse events. We also found that expectations, but not perceived credibility (or believability), of NEW Tx (as measured by the Credibility/Expectancy Questionnaire) at baseline predicted treatment satisfaction (as measured by the Care Satisfaction Questionnaire) posttreatment. Manic symptoms at baseline predicted treatment satisfaction, and marital status predicted one's expectations of lifestyle interventions. Data suggest that NEW Tx is a feasible and acceptable intervention for individuals with bipolar disorder and that further research is warranted to explore potential moderators of treatment expectations and credibility in this clinical population.

Commentary on "Synchrony Between Bipolar Mood Cycles and Lunar Tidal Cycles Ended After Initiation of Light Treatment and Treatment of Hypothyroidism".

According to a recent report, mood cycles in a group of patients with rapid cycling bipolar disorder oscillated in synchrony with lunar gravimetric tides. Mood switches in a 67-year-old woman with rapid cycling bipolar II disorder on lithium maintenance treatment were assessed with a χ periodogram and a χ analysis of the mood switches in relation to the lunar tidal cycle. During a period when she was treated with nortriptyline and her thyroid-stimulating hormone levels were elevated, her mood switches had a significant (P<0.05) 29- to 30-day periodicity, and the χ analysis showed that the switches were distributed nonrandomly in relation to the spring-neap lunar tidal cycle (P<0.0001); 14 of 15 switches occurred within 2 days of the spring tides. After nortriptyline was discontinued, thyroid-stimulating hormone levels were normalized with treatment with levothyroxine, and consistent bright light treatment was started, the synchrony between mood cycles and lunar cycles disappeared, and rapid cycling eventually stopped. The possibility that lunar mood cycling is sometimes contingent on antidepressant treatment, decreased thyroid function, and certain types of light-dark cycles needs to be considered in future research on lunar tidal influences on the course of bipolar illness.

Synchrony Between Bipolar Mood Cycles and Lunar Tidal Cycles Ended After Initiation of Light Treatment and Treatment of Hypothyroidism.

According to a recent report, mood cycles in a group of patients with rapid cycling bipolar disorder oscillated in synchrony with lunar gravimetric tides. Mood switches in a 67-year-old woman with rapid cycling bipolar II disorder on lithium maintenance treatment were assessed with a χ periodogram and a χ analysis of the mood switches in relation to the lunar tidal cycle. During a period when she was treated with nortriptyline and her thyroid-stimulating hormone levels were elevated, her mood switches had a significant (P<0.05) 29- to 30-day periodicity, and the χ analysis showed that the switches were distributed nonrandomly in relation to the spring-neap lunar tidal cycle (P<0.0001); 14 of 15 switches occurred within 2 days of the spring tides. After nortriptyline was discontinued, thyroid-stimulating hormone levels were normalized with treatment with levothyroxine, and consistent bright light treatment was started, the synchrony between mood cycles and lunar cycles disappeared, and rapid cycling eventually stopped. The possibility that lunar mood cycling is sometimes contingent on antidepressant treatment, decreased thyroid function, and certain types of light-dark cycles needs to be considered in future research on lunar tidal influences on the course of bipolar illness.