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International Review of Psychosis & Bipolarity

Athens, Greece, 9-12 May 2014

Chair: Prof Konstantinos Fountoulakis

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Most Recent Articles Published on Psychosis and Bipolarity:

Related Articles

[Amélie, a case of alternating suffering].

Soins Psychiatr. 2012 Sep-Oct;(282):26-9

Authors: Caldarola Y, Bonnemains C

The expression of melancholic suffering undermines nursing teams. Torn between the desire to care and the feeling of powerlessness, the team itself suffers. Through the clinical case of Amélie, her history and her responses, the nurses have had to adopt strategies and tools in order to preserve themselves and to be able to continue to provide quality care.

PMID: 23050359 [PubMed - indexed for MEDLINE]

Cognitive vulnerability to bipolar disorder in offspring of parents with bipolar disorder.

Br J Clin Psychol. 2014 Apr 21;

Authors: Pavlickova H, Turnbull O, Bentall RP

BACKGROUND: Bipolar disorder is a highly heritable illness, with a positive family history robustly predictive of its onset. It follows that studying biological children of parents with bipolar disorder may provide information about developmental pathways to the disorder. Moreover, such studies may serve as a useful test of theories that attribute a causal role in the development of mood disorders to psychological processes.
METHOD: Psychological style (including self-esteem, coping style with depression, domain-specific risk-taking, sensation-seeking, sensitivity to reward and punishment, and hypomanic personality and cognition) was assessed in 30 offspring of bipolar parents and 30 children of well parents. Parents of both child groups completed identical assessments.
RESULTS: Although expected differences between parents with bipolar disorder and well parents were detected (such as low self-esteem, increased rumination, high sensitivity to reward and punishment), offspring of bipolar parents were, as a group, not significantly different from well offspring, apart from a modest trend towards lower adaptive coping. When divided into affected and non-affected subgroups, both groups of index children showed lower novelty-seeking. Only affected index children showed lower self-esteem, increased rumination, sensitivity to punishment, and hypomanic cognitions. Notably, these processes were associated with symptoms of depression.
CONCLUSION: Psychological abnormalities in index offspring were associated with having met diagnostic criteria for psychiatric illnesses and the presence of mood symptoms, rather than preceding them. Implications of the present findings for our understanding of the development of bipolar disorder, as well as for informing early interventions, are discussed.
PRACTITIONER POINTS: Decreased active coping and seeking for novel stimuli might be one of first psychological indications relevant to the future development of mood disorders. Psychological abnormalities typical for individuals with mood disorders were present only in already affected offspring of parents with bipolar disorder.
LIMITATIONS OF THE STUDY: This was a cross-sectional study; longitudinal design would greatly enhance our understanding of the association between psychological processes and symptoms. The sample size in this study was modest.

PMID: 24749716 [PubMed - as supplied by publisher]

Baclofen-Induced Manic Symptoms: Case Report and Systematic Review.

Psychosomatics. 2014 Feb 15;

Authors: Geoffroy PA, Auffret M, Deheul S, Bordet R, Cottencin O, Rolland B

BACKGROUND: The gamma-aminobutyric acid type B receptor agonist baclofen is approved for spasticity and is used off-label for diverse types of addictive disorders, notably alcohol dependence. Baclofen may induce numerous neuropsychiatric adverse drug reactions, including behavioral disinhibition. However, this precise adverse drug reaction has never been assessed using either a validated causality algorithm or a scale for manic symptoms.
METHODS: We report a case of a 49-year-old male patient who exhibited de novo mania during treatment with baclofen for alcohol dependence. Symptoms were evaluated using the Young Mania Rating Scale, and the causality of baclofen was determined using the Naranjo algorithm. This case was also compared with other cases of baclofen-induced mania through a systematic literature review.
RESULTS: Mr. X, taking 180mg/d of baclofen, presented with mania and scored 24 of 44 on the Young Mania Rating Scale, and the imputability of baclofen was "probable" using the Naranjo algorithm (8 of 13). In addition, 4 other cases of baclofen-induced mania were reported in the literature; 3 cases had a bipolar I disorder history. Baclofen-induced manic symptoms occurred mostly during the dose-escalation phase.
CONCLUSION: Baclofen-induced manic symptoms may appear in patients with or without bipolar disorder. Particular attention is required during the dose-increase phase and in patients with a history of mood disorders.

PMID: 24751117 [PubMed - as supplied by publisher]

Beyond a single index of mania symptoms: Structure and validity of subdimensions.

J Affect Disord. 2014 Jun;161:8-15

Authors: Ruggero CJ, Kotov R, Watson D, Kilmer JN, Perlman G, Liu K

BACKGROUND: DSM-5 portrays mania as unitary despite evidence of distinct symptom clusters. Studies investigating the structure of mania have been inconsistent, in part because many relied on instruments not designed for this question. The present work used a clinical interview designed for structural analysis in order to identify and validate subdimensions specific to mania symptoms.
METHODS: Psychiatric outpatients (N=422) and undergraduates with a history of mental health treatment (N=306) were interviewed with a comprehensive measure of mood and anxiety that included 24 manic symptoms. Patients completed additional measures of symptoms and functioning, and a semi-structured diagnostic interview.
RESULTS: A 4-factor model of mania replicated across independent samples and was superior in fit to competing models, including the unidimensional model implied whenever researchers or clinicians use only a total score for mania. The factors were only moderately correlated, and three of the four ("Irritability" was the exception) showed a strong criterion, convergent and discriminant validity, suggesting they are specific to mania. Subdimensions showed distinct and meaningful associations with functioning.
LIMITATIONS: Symptoms of psychosis and depression are important features of manic episodes, but were not included in the present study since they lack specificity to mania.
CONCLUSIONS: Mania is multifaceted. At least three subdimensions specific to mania were identified ("Euphoric Activation," "Hyperactive Cognition" and "Reckless Overconfidence"). Use of subdimensions, in addition to overall mania severity, may enhance the ability of studies to detect meaningful biological correlates of bipolar disorder. Moreover, their different associations with functioning suggest assessing subdimensions has clinical utility as well.

PMID: 24751301 [PubMed - in process]

Effect of adjunctive benzodiazepines on clinical outcomes in lithium- or quetiapine-treated outpatients with bipolar I or II disorder: Results from the Bipolar CHOICE trial.

J Affect Disord. 2014 Jun;161:30-5

Authors: Bobo WV, Reilly-Harrington NA, Ketter TA, Brody BD, Kinrys G, Kemp DE, Shelton RC, McElroy SL, Sylvia LG, Kocsis JH, McInnis MG, Friedman ES, Singh V, Tohen M, Bowden CL, Deckersbach T, Calabrese JR, Thase ME, Nierenberg AA, Rabideau DJ, Schoenfeld DA, Faraone SV, Kamali M

BACKGROUND: Little is known about the longer-term effects of adjunctive benzodiazepines on symptom response during treatment in patients with bipolar disorders.
METHODS: The study sample consisted of 482 patients with bipolar I or II disorder enrolled in a 6-month, randomized, multi-site comparison of lithium- and quetiapine-based treatment. Changes in clinical measures (BISS total and subscales, CGI-BP, and CGI-Efficacy Index) were compared between participants who did and did not receive benzodiazepine treatment at baseline or during follow-up. Selected outcomes were also compared between patients who did and did not initiate benzodiazepines during follow-up using stabilized inverse probability weighted analyses.
RESULTS: Significant improvement in all outcome measures occurred within each benzodiazepine exposure group. Benzodiazepine users (at baseline or during follow-up) experienced significantly less improvement in BISS total, BISS irritability, and CGI-BP scores than did benzodiazepine non-users. There were no significant differences in these measures between patients who did and did not initiate benzodiazepines during follow-up in the weighted analyses. There was no significant effect of benzodiazepine use on any outcome measure in patients with comorbid anxiety or substance use disorders.
LIMITATIONS: This is a secondary analysis of data from a randomized effectiveness trial that was not designed to address differential treatment response according to benzodiazepine use.
CONCLUSIONS: Adjunctive benzodiazepines may not significantly affect clinical outcome in lithium- or quetiapine-treated patients with bipolar I or II disorder over 6 months, after controlling for potential confounding factors.

PMID: 24751304 [PubMed - in process]

Stressful life events in bipolar I and II disorder: Cause or consequence of mood symptoms?

J Affect Disord. 2014 Jun;161:55-64

Authors: Koenders MA, Giltay EJ, Spijker AT, Hoencamp E, Spinhoven P, Elzinga BM

BACKGROUND: Life events are assumed to be triggers for new mood episodes in bipolar disorder (BD). However whether life events may also be a result of previous mood episodes is rather unclear.
METHOD: 173 bipolar outpatients (BD I and II) were assessed every three months for two years. Life events were assessed by Paykel?s self-report questionnaire. Both monthly functional impairment due to manic or depressive symptomatology and mood symptoms were assessed.
RESULTS: Negative life events were significantly associated with both subsequent severity of mania and depressive symptoms and functional impairment, whereas positive life events only preceded functional impairment due to manic symptoms and mania severity. These associations were significantly stronger in BD I patients compared to BD II patients. For the opposite temporal direction (life events as a result of mood/functional impairment), we found that mania symptoms preceded the occurrence of positive life events and depressive symptoms preceded negative life events.
LIMITATIONS: The use of a self-report questionnaire for the assessment of life events makes it difficult to determine whether life events are cause or consequence of mood symptoms. Second, the results can only be generalized to relatively stable bipolar outpatients, as the number of severely depressed as well as severely manic patients was low.
CONCLUSIONS: Life events appear to precede the occurrence of mood symptoms and functional impairment, and this association is stronger in BD I patients. Mood symptoms also precede the occurrence of life event, but no differences were found between BD I and II patients.

PMID: 24751308 [PubMed - in process]

An investigation into the relationship between first-degree relatives of bipolar affective disorder and (idiopathic) epilepsy in a sub-Saharan African population.

J Affect Disord. 2014 Jun;161:84-6

Authors: Jidda MS, Wakil MA, Ibrahim AW, Mohammed AO

OBJECTIVE: Phenomenological, neuro-biological and pharmacological investigations linked bipolar affective disorders with epilepsy. Similarly, a large community-based epidemiological study of epileptic patients reported that 12% of the participants had bipolar symptoms, a rate 7× higher than in control. Bipolar and epileptic disorders are epiphenomena of an underlying genetic susceptibility. This study aimed to determine the relationship between first-degree relatives of bipolar and epileptic patients in a sub-Saharan African population.
METHOD: In this case-control study, we used a socio-demographic and clinical variables questionnaire to assess random convenient samples of 50 control, 40 and 60 first-degree relatives of bipolar and epileptic patients, respectively at Federal Neuro-psychiatric Hospital (FNPH), Maiduguri. Relatives of epileptic patients and the control completed the mood disorder questionnaire (MDQ). Two consultant psychiatrists made the diagnosis of epilepsy using the ILAE criteria, in relatives of bipolar patients and the control. Participants in both groups had no EEG. We analysed the data obtained, using EPI-info 7 to report averages and associations between categorical variables with Chi-square test, and analysis of variance (ANOVA) for parametric data(statistical significance set at p=0.5, two-tailed).
RESULTS: The rate of epilepsy among relatives of bipolar disorder compared with control was 15.2% vs. 2.0% (?(2)=46.08, p<0.001), and that of bipolar among relatives of epileptics compared with control was 14.5% vs. 2.1% (?(2)=31.2, p<0.001). Educational status showed significant relationship across two groups (?(2)=24.19, p=0.0001). Using ANOVA, age showed significant relationship among relatives of bipolar and epileptic patients (F=5.769, p=0.0039).
CONCLUSION: Despite its limitations, this preliminary study contributes to literature on the relationship between epilepsy and bipolar affective disorder in sub-Saharan Africa.

PMID: 24751312 [PubMed - in process]

Association between family history of mood disorders and clinical characteristics of bipolar disorder: Results from the Brazilian bipolar research network.

J Affect Disord. 2014 Jun;161:104-8

Authors: Berutti M, Nery FG, Sato R, Scippa A, Kapczinski F, Lafer B

OBJECTIVES: To compare clinical characteristics of bipolar disorder (BD) in patients with and without a family history of mood disorders (FHMD) in a large sample from the Brazilian Research Network of Bipolar Disorders.
METHODS: Four-hundred eighty-eight DSM-IV BD patients participating in the Brazilian Research Network of Bipolar Disorders were included. Participants were divided between those with FHMD (n=230) and without FHMD (n=258). We compared these two groups on demographic and clinical variables and performed a logistic regression to identify which variables were most strongly associated with positive family history of mood disorders.
RESULTS: BD patients with FHMD presented with significantly higher lifetime prevalence of any anxiety disorder, obsessive-compulsive disorder, social phobia, substance abuse, and were more likely to present history of suicide attempts, family history of suicide attempts and suicide, and more psychiatric hospitalizations than BD patients without FHMD. Logistic regression showed that the variables most strongly associated with a positive FHMD were any comorbid anxiety disorder, comorbid substance abuse, and family history of suicide.
LIMITATIONS: Cross-sectional study and verification of FHMD by indirect information.
CONCLUSION: BD patients with FHMD differ from BD patients without FHMD in rates of comorbid anxiety disorder and substance abuse, number of hospitalizations and suicide attempts. As FHMD is routinely assessed in clinical practice, these findings may help to identify patients at risk for particular manifestations of BD and may point to a common, genetically determined neurobiological substrate that increases the risk of conditions such as comorbidities and suicidality in BD patients.

PMID: 24751316 [PubMed - in process]

Association of affective temperaments measured by TEMPS-A with cognitive deficits in patients with bipolar disorder.

J Affect Disord. 2014 Jun;161:109-15

Authors: Xu G, Lu W, Ouyang H, Dang Y, Guo Y, Miao G, Bessonov D, Akiskal KK, Akiskal HS, Lin K

BACKGROUND: Affective temperaments such as cyclothymia, which may be the fundamental substrates for bipolar disorder and bipolar II in particular, have been reported to be associated with abnormalities in the regions that are related to cognitive deficits in bipolar disorder. However, few studies have examined the effects of affective temperaments on neuropsychological performance in individuals with bipolar disorder.
METHOD: In a six-week prospective study, we administered Chinese version of TEMPS-A (Temperament Evaluation of Memphis, Pisa, San Diego-Autoquestionnair) to 93 patients with bipolar I depression, 135 patients with bipolar II depression, and 101 healthy controls. Cognitive function was assessed with a battery of neuropsychological tasks, including attention, processing speed, set shifting, planning, verbal working memory, verbal fluency, and visual spatial memory. Mixed-effects statistical models were used to assess the effects of affective temperaments on cognitive function.
RESULTS: Bipolar patients with hyperthymic temperament showed greater cognitive deficits in set shifting (p=0.05) and verbal working memory (p=0.026) than did bipolar patients with non-predominant temperaments (predominant temperament was defined as one standard deviation above the mean). The differences in estimated marginal means were -0.624 (95% CI, -1.25 to 0) and -0.429 (95% CI, -0.81 to -0.05), respectively. Significant temperament X bipolar subtype interaction effects were observed for set shifting (Wald X(2)=18.161, p<0.001), planning (Wald X(2)=7.906, p=0.048), and visual spatial memory (Wald X(2)=16.418, p=0.001).
LIMITATION: The anxious temperament was not evaluated.
CONCLUSION: Our data suggest that hyperthymic temperament may be associated with cognitive deficits in some specific domains in bipolar disorder; and that the effect of temperaments may be different across subtypes of bipolar disorder.

PMID: 24751317 [PubMed - in process]

Predictive value of baseline resistance in early response to antidepressants.

J Affect Disord. 2014 Jun;161:127-35

Authors: Icick R, Millet E, Curis E, Bellivier F, Lépine JP

BACKGROUND: Major Depressive Disorder (MDD) is the 3rd source for burden worldwide according to the World Health Organization (WHO). This comes partly from unsatisfactory response rates after usual treatment, highlighting the need for early indicators such as early improvement of depressive symptoms to adapt treatment strategies, especially for severe inpatients. Thus our objective was to assess the predictive value of baseline partial resistance in early antidepressant response (EAR), hypothesizing that previous treatment failures would decrease the probability of early response.
METHODS: We included 122 consecutive inpatients with current unipolar MDE. The Mini-Neuropsychiatric Interview was used to ascertain DSM-IV diagnoses of MDD as well as psychiatric comorbidities, and to exclude patients with a history of bipolar disorder. A specifically designed questionnaire was used to collect data on previous treatment trials for the current episode so as to generate scores on the five existing methods for quantifying treatment resistance. We prospectively assessed EAR, defined as a 50% decrease in MADRS after 14 days of steady regimen of antidepressant.
RESULTS: In the per protocol sample (N=76), multivariate analyses showed that psychotic features at baseline remained an independent predictor of absence of EAR (p<.01), unlike baseline partial resistance, which may rather be associated with a lack of any improvement.
LIMITATIONS: Lack of data about further response and non-randomized treatment allocation.
CONCLUSION: Available methods for quantifying treatment resistance are heterogeneous and do not predict short-term response among severely depressed inpatients, despite potential usefulness in predicting a lack of early improvement.

PMID: 24751320 [PubMed - in process]

Contributions of the social environment to first-onset and recurrent mania.

Mol Psychiatry. 2014 Apr 22;

Authors: Gilman SE, Ni MY, Dunn EC, Breslau J, McLaughlin KA, Smoller JW, Perlis RH

In treated cohorts, individuals with bipolar disorder are more likely to report childhood adversities and recent stressors than individuals without bipolar disorder; similarly, in registry-based studies, childhood adversities are more common among individuals who later become hospitalized for bipolar disorder. Because these types of studies rely on treatment-seeking samples or hospital diagnoses, they leave unresolved the question of whether or not social experiences are involved in the etiology of bipolar disorder. We investigated the role of childhood adversities and adulthood stressors in liability for bipolar disorder using data from the National Epidemiologic Survey on Alcohol and Related Conditions (n=33?375). We analyzed risk for initial-onset and recurrent DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) manic episodes during the study's 3-year follow-up period. Childhood physical abuse and sexual maltreatment were associated with significantly higher risks of both first-onset mania (odds ratio (OR) for abuse: 2.23; 95% confidence interval (CI)=1.71, 2.91; OR for maltreatment: 2.10; CI=1.55, 2.83) and recurrent mania (OR for abuse: 1.55; CI=1.00, 2.40; OR for maltreatment: 1.60; CI=1.00, 2.55). In addition, past-year stressors in the domains of interpersonal instability and financial hardship were associated with a significantly higher risk of incident and recurrent mania. Exposure to childhood adversity potentiated the effects of recent stressors on adult mania. Our findings demonstrate a role of social experiences in the initial onset of bipolar disorder, as well as in its prospective course, and are consistent with etiologic models of bipolar disorder that implicate deficits in developmentally established stress-response pathways.Molecular Psychiatry advance online publication, 22 April 2014; doi:10.1038/mp.2014.36.

PMID: 24751965 [PubMed - as supplied by publisher]

Comparative modeling and virtual screening for the identification of novel inhibitors for myo-inositol-1-phosphate synthase.

Mol Biol Rep. 2014 Apr 22;

Authors: Azam SS, Sarfaraz S, Abro A

Myo-inositol-1-phosphate (MIP) synthase is a key enzyme in the myo-inositol biosynthesis pathway. Disruption of the inositol signaling pathway is associated with bipolar disorders. Previous work suggested that MIP synthase could be an attractive target for the development of anti-bipolar drugs. Inhibition of this enzyme could possibly help in reducing the risk of a disease in patients. With this objective, three dimensional structure of the protein was modeled followed by the active site prediction. For the first time, computational studies were carried out to obtain structural insights into the interactive behavior of this enzyme with ligands. Virtual screening was carried out using FILTER, ROCS and EON modules of the OpenEye scientific software. Natural products from the ZINC database were used for the screening process. Resulting compounds were docked into active site of the target protein using FRED (Fast Rigid Exhaustive Docking) and GOLD (Genetic Optimization for Ligand Docking) docking programs. The analysis indicated extensive hydrogen bonding network and hydrophobic interactions which play a significant role in ligand binding. Four compounds are shortlisted and their binding assay analysis is underway.

PMID: 24752405 [PubMed - as supplied by publisher]

Bipolar Disorder Symptoms in Patients Seeking Bariatric Surgery.

Obes Surg. 2014 Apr 22;

Authors: Grothe KB, Mundi MS, Himes SM, Sarr MG, Clark MM, Geske JR, Kalsy SA, Frye MA

BACKGROUND: Mood disorders are common among patients seeking bariatric surgery although little data exist regarding the prevalence of bipolar symptoms in this population and how they influence surgical outcomes. Our aim was to describe baseline rates of bipolar symptoms and their relationship to psychological factors and completing surgery in a sample of adults seeking bariatric surgery at an academic medical center.
METHODS: We retrospectively reviewed the relationship of bipolar symptoms to demographic characteristics, baseline weight, psychological factors, and bariatric surgery completion.
RESULTS: Nine hundred thirty-five patients completed the preoperative psychological evaluation. Six percent of the preoperative sample screened positive for symptoms of bipolar disorder. Patients with bipolar symptoms endorsed more robust psychopathology, trauma history, and problematic eating behaviors than patients without bipolar symptoms. Twenty-two percent of the patients with bipolar symptoms underwent bariatric surgery (n?=?12), yet only 13 % were denied bariatric surgery for psychiatric reasons, suggesting that other variables may influence the completion of bariatric surgery for these patients.
CONCLUSION: Prevalence rates of bipolar symptoms may be greater in patients seeking bariatric surgery compared with the general population, and few patients with bipolar symptoms actually undergo bariatric surgery. Psychological factors differentiate patients with bipolar symptoms who undergo bariatric surgery vs those who do not.

PMID: 24752620 [PubMed - as supplied by publisher]

Barrett's esophagus in anorexia nervosa: A case report.

Int J Eat Disord. 2014 Apr 22;

Authors: Pacciardi B, Cargioli C, Mauri M

Barrett's esophagus (BE) is a metaplastic lesion that may result from long-lasting gastroesophageal reflux and it is an established precursor of esophageal adenocarcinoma. There are reports of an increased prevalence of BE, and eventually esophageal adenocarcinoma, in patients with eating disorders characterized by purging behaviors like those with bulimia nervosa (BN). Among patients with eating disorders, those affected by anorexia nervosa binging purging subtype (ANBP), are behaviorally very similar to those with BN, but to our knowledge there are no data in literature about BE in patients with ANBP. We present the case of a 37-year-old female with a 20-year history of ANBP in comorbidity with bipolar disorder, who developed a BE requiring multi-specialistic intervention. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014).

PMID: 24753136 [PubMed - as supplied by publisher]

Blood-cerebrospinal fluid barrier dysfunction in patients with bipolar disorder in relation to antipsychotic treatment.

Psychiatry Res. 2014 Apr 5;

Authors: Zetterberg H, Jakobsson J, Redsäter M, Andreasson U, Pålsson E, Ekman CJ, Sellgren C, Johansson AG, Blennow K, Landén M

Blood-cerebrospinal barrier (BCB) dysfunction has previously been shown in subjects with schizophrenia and depressed patients with attempted suicide. Bipolar disorder (BPD) shares clinical features with both these disorders, but it is unknown if the integrity of the BCB is altered also in BPD. To assess if BCB function in BPD we surveyed 134 mood-stabilized BPD patients and 86 healthy controls. Serum and cerebrospinal fluid (CSF) samples were collected and analyzed for albumin concentration by immunonephelometry. CSF/serum albumin ratio, an established measure of BCB function, was significantly elevated in BPD patients as compared to controls. After stratifying patients according to diagnostic subtype, BPD I patients had the highest CSF/serum albumin ratios. Moreover, BPD patients on antipsychotic treatment had higher CSF/serum albumin ratio than BPD patients on other treatments. When excluding BPD patients on antipsychotic treatment the difference in CSF/serum albumin ratio between the BPD and control groups disappeared. In conclusion, antipsychotic treatment in BPD is associated with elevated CSF/serum albumin ratio, tentatively as a sign of impaired BCB function. Whether this elevation is caused by antipsychotic treatment or is associated with a certain subtype of BPD, requiring antipsychotic treatment, remains to be determined.

PMID: 24745469 [PubMed - as supplied by publisher]

Safety and Tolerability of Inhaled Loxapine in Subjects with Asthma and Chronic Obstructive Pulmonary Disease-Two Randomized Controlled Trials.

J Aerosol Med Pulm Drug Deliv. 2014 Apr 18;

Authors: Gross N, Greos LS, Meltzer EO, Spangenthal S, Fishman RS, Spyker DA, Cassella JV

Abstract Background: Loxapine, a first-generation antipsychotic, delivered with a novel inhalation delivery device developed for the acute treatment of agitation in patients with schizophrenia or bipolar disorder was evaluated in subjects with asthma or chronic obstructive pulmonary disease (COPD). Methods: Separate randomized, double-blind, parallel-arm, placebo-controlled trials compared two administrations of inhaled loxapine (10?mg) 10?hr apart with placebo in 52 subjects with asthma and in 53 subjects with COPD. A thermally-generated drug aerosol of loxapine was delivered to the deep lung for rapid systemic absorption. Controller medications were continued throughout the study, but quick-relief bronchodilators were withheld from 6-8?hr before through 34?hr after dose 1, unless indicated as rescue. Results: All airway adverse events (AEs) were of mild or moderate severity. Symptomatic bronchospasm occurred in 53.8% of subjects with asthma after inhaled loxapine and 11.5% after placebo; and in 19.2% of COPD subjects after inhaled loxapine and 11.1% after placebo. Subjects required inhaled albuterol as follows: asthma: 53.8% after inhaled loxapine and 11.5% after placebo; and COPD: 23.1% after inhaled loxapine and 14.8% after placebo. Respiratory signs/symptoms requiring treatment responded to rescue bronchodilator [forced expiratory volume in 1?sec (FEV1) return to within 10% of baseline] within 1?hr in 11 of 15 events in asthma subjects and four of seven events in COPD subjects, the remainder by the last spirometry. Conclusions: In subjects with either asthma or COPD, FEV1 decline and bronchospasm can occur following inhaled loxapine, but more frequently in asthmatic subjects. Most subjects with bronchospasm responded to rescue bronchodilator within 1?hr. No treatment-related serious AE occurred. Although inhaled loxapine is contraindicated in patients with active airways disease per the current approved US labeling, these studies demonstrated that rescue bronchodilator mitigated the symptomatic bronchospasms that may occur in case of inadvertent use.

PMID: 24745666 [PubMed - as supplied by publisher]

Sleep complaints and memory in psychotropic drug-free euthymic patients with bipolar disorder.

J Formos Med Assoc. 2014 May;113(5):298-302

Authors: Wang CH, Chen KC, Hsu WY, Lee IH, Chiu NY, Chen PS, Yang YK

BACKGROUND/PURPOSE: Few studies have been conducted examining the genuine sleep condition and memory in patients with euthymic bipolar disorder. Thus we evaluated sleep complaints and memory functions in psychotropic drug-free euthymic patients with bipolar disorder.
METHODS: Twenty-two psychotropic drug-free euthymic patients with bipolar disorder and 44 healthy controls matched by age and sex were recruited and assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Wechsler Memory Scale-Revised (WMS-R).
RESULTS: The quality of sleep and memory function of the euthymic patients with bipolar disorder were significantly poorer than those of the controls. Both years of education and the hypnotic use sub-item of the PSQI were significantly correlated with visual memory index of the WMS-R.
CONCLUSION: Sleep complaints management is important in euthymic patients with bipolar disorder.

PMID: 24746115 [PubMed - in process]

Vascular Mortality in Participants of a Bipolar Genomics Study.

Psychosomatics. 2014 Feb 6;

Authors: Fiedorowicz JG, Jancic D, Potash JB, Butcher B, Coryell WH

BACKGROUND: In prior work, we identified a relationship between symptom burden and vascular outcomes in bipolar disorder.
OBJECTIVE: We sought to replicate these findings using a readily accessible measure of mood disorder chronicity and vascular mortality.
METHODS: We conducted a mortality assessment using the National Death Index for 1716 participants with bipolar I disorder from the National Institute of Mental Health Genetics Initiative Bipolar Disorder Consortium. We assessed the relationship between the duration of the most severe depressive and manic episodes and time to vascular mortality (cardiovascular or cerebrovascular) using Cox proportional hazards models, adjusting for potentially confounding variables.
RESULTS: Mortality was assessed a mean for 7 years following study intake, at which time 58 participants died, 18 of vascular causes. These participants had depression for much longer than their counterparts did (Wilcoxon rank sum Z = 2.30, p = 0.02) and the duration of the longest depressive episode in years was significantly associated with time to vascular mortality in models (hazard ratio = 1.16, 95% confidence interval: 1.02-1.33, p = 0.02), which controlled for age, gender, vascular disease equivalents, and vascular disease risk factors. The duration of longest mania was not related to vascular mortality.
CONCLUSION: The duration of the most severe depression is independently predictive of vascular mortality, lending further support to the idea that mood disorders hasten vascular mortality in a dose-dependent fashion. Further study of the relevant mechanisms by which mood disorders may hasten vascular disease and of integrated treatments for mood and cardiovascular risk factors is warranted.

PMID: 24746452 [PubMed - as supplied by publisher]

Prevalence and clinical correlates of alcohol use disorders among bipolar disorder patients: Results from the Brazilian Bipolar Research Network.

Compr Psychiatry. 2014 Feb 25;

Authors: Nery FG, Miranda-Scippa A, Nery-Fernandes F, Kapczinski F, Lafer B

OBJECTIVES: To investigate prevalence rates and clinical correlates of alcohol use disorders (AUD) among bipolar disorder (BD) patients in a large sample from the Brazilian Bipolar Research Network.
METHODS: Four hundred and eighty-three DSM-IV BD patients, divided according to the presence or absence of a lifetime AUD diagnosis (BD-AUD vs. BD-nonAUD), were included. Demographic and clinical characteristics of these two groups were compared. Logistic regression was performed to identify which characteristics were most strongly associated with a lifetime AUD diagnosis.
RESULTS: Nearly 23% presented a lifetime AUD diagnosis. BD-AUD patients were more likely to be male, to present rapid cycling, post-traumatic stress disorder (PTSD), anorexia, other substance use disorders (SUD), family history of SUD, any substance misuse during the first mood episode, history of psychosis, suicide attempts, and younger age at onset of illness than BD-nonAUD patients. Logistic regression showed that the variables most strongly associated with a lifetime AUD diagnosis were SUD (non-alcohol), any substance misuse during the first mood episode, PTSD, male gender, suicide attempt, family history of SUD, and younger age at onset of BD.
CONCLUSIONS: BD-AUD patients begin their mood disorder earlier and present more suicidal behaviors than BD-nonAUD patients. Personal and family history of SUD may be good predictors of comorbid AUD among BD patients. These variables are easily assessed in the clinical setting and may help to identify a particularly severe subgroup of BD patients.

PMID: 24746528 [PubMed - as supplied by publisher]

The Hypomania Checklist (HCL) - Systematic review of its properties to screen for bipolar disorders.

Compr Psychiatry. 2014 Mar 21;

Authors: Meyer TD, Schrader J, Ridley M, Lex C

OBJECTIVE: Bipolar disorders (BDs) are often not recognised with potentially drastic consequences for the individuals and their families. In clinical practice self-reports can be used to screen to enhance recognition. We therefore present a systematic review of the screening properties for the Hypomania Checklist (HCL-32).
METHODS: A systematic literature search was conducted to identify all relevant studies looking at the screening properties of the HCL-32 in adults.
RESULTS: Out of 196 papers 21 papers reported data on 22 independent samples. We narratively reviewed these studies. Weighted estimated Sensitivity was 80% regardless of whether a BD diagnosis was compared to unipolar depression or any other non-bipolar diagnosis. Specificity indicated that the HCL-32 was better when comparing BD to unipolar depression (65.3%) than to any other diagnostic category (57.3%). Fewer studies provided estimates for predictive powers, leading to less reliable overall estimates for these indicators.
CONCLUSIONS: Despite some limitations, using the HCL-32 as a first screening in patients seeking help for depression can be recommended, but should never be used on its own for diagnosing. Future research should examine whether screening properties can be improved by developing an algorithm incorporating the negative consequences reported for different areas in the HCL-32.

PMID: 24746530 [PubMed - as supplied by publisher]

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BMJ Case Rep. 2013;2013

Authors: Alchakaki A, Kabach M, Alraiyes AH, Alraies MC

PMID: 24049089 [PubMed - indexed for MEDLINE]

Related Articles

Bipolar disorder, not so rare diagnosis: subtypes of different degrees of severity, diagnosis, therapy.

Rev Med Chir Soc Med Nat Iasi. 2014 Jan-Mar;118(1):111-5

Authors: Amih?esei IC

Bipolar disorder is manifesting as a mood disorder, typically showing episodes of mania, alternating with depressive episodes. The subtypes are including bipolar I disorder (one or several manic episodes) and bipolar II disorder (hypomanic episodes and one or several major depressive episodes). Nevertheless, sub-threshold diagnosis criteria may include another 5.1, up to 6.4% of the population as having a bipolar spectrum disorder diagnosis. Anyone who received the diagnosis is not considered cured afterwards (just in remission). Diagnosis is considering the symptoms of mania, hypomania and depression. Therapy is based on lithium, anticonvulsants, for the manic symptoms, lamotrigine for the depressive episodes and antipsychotics. Under medication, most of the affected subjects are living a normal life; to a certain degree, medication may also prevent the relapses.

PMID: 24741786 [PubMed - in process]

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Psychosocial Functioning in Depressive Patients: A Comparative Study between Major Depressive Disorder and Bipolar Affective Disorder.

Depress Res Treat. 2014;2014:302741

Authors: Mehta S, Mittal PK, Swami MK

Introduction. Major depressive disorder (MDD) and bipolar affective disorder (BAD) are among the leading causes of disability. These are often associated with widespread impairments in all domains of functioning including relational, occupational, and social. The main aim of the study was to examine and compare nature and extent of psychosocial impairment of patients with MDD and BAD during depressive phase. Methodology. 96 patients (48 in MDD group and 48 in BAD group) were included in the study. Patients were recruited in depressive phase (moderate to severe depression). Patients having age outside 18-45 years, psychotic symptoms, mental retardation, and current comorbid medical or axis-1 psychiatric disorder were excluded. Psychosocial functioning was assessed using Range of Impaired Functioning Tool (LIFE-RIFT). Results. Domains of work, interpersonal relationship, life satisfaction, and recreation were all affected in both groups, but the groups showed significant difference in global psychosocial functioning score only (P = 0.031) with BAD group showing more severe impairment. Conclusion. Bipolar depression causes higher global psychosocial impairment than unipolar depression.

PMID: 24744917 [PubMed]

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Distinctive trajectory groups of mental health functioning among assertive community treatment clients: an application of growth mixture modelling analysis.

Can J Psychiatry. 2013 Dec;58(12):670-8

Authors: Wilk P, Vingilis E, Bishop JE, He W, Braun J, Forchuk C, Seeley J, Mitchell B

OBJECTIVE: Assertive community treatment (ACT) studies that have used conventional, statistical growth modelling methods have not examined different trajectories of outcomes or covariates that could influence different trajectories, even though heterogeneity in outcomes has been established in other research on severe mental illness. The purpose of our study was to examine the general trend in mental health functioning of ACT clients over a 2-year follow-up time period, to discover groups of ACT clients with distinctive longitudinal trajectories of mental health functioning, and to examine if some of the key sociodemographic and illness-related factors influence group membership.
METHOD: A 2-year, prospective, within-subjects study of 216 ACT clients within southern Ontario, collected functional outcome data at baseline and 12 and 24 months using the Colorado Client Assessment Record. Baseline covariates included sex, primary diagnosis, number of comorbidities, hospitalization history, and duration of illness. Growth mixture modelling (GMM) was used to examine trajectories.
RESULTS: Clinical staff assessments of ACT clients showed a statistically significant improvement in functioning and 84% achieved successful community tenure. GMM analysis identified 2 classes of ACT clients: class 1 (79.63% of clients) experienced lower and stable overall functioning, and class 2 (20.37%) showed a better baseline functioning score and improvement in the overall functioning over time. Class membership was predicted by the number of comorbidities and diagnosis.
CONCLUSIONS: Our study suggests general stability in overall functioning for the sampled ACT clients over 2 years, but significant heterogeneity in trajectories of functioning.

PMID: 24331286 [PubMed - indexed for MEDLINE]

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Changes in mindfulness following repetitive transcranial magnetic stimulation for mood disorders.

Can J Psychiatry. 2013 Dec;58(12):687-91

Authors: Leong K, Chan P, Grabovac A, Wilkins-Ho M, Perri M

OBJECTIVE: Mindfulness practices are associated with changes in different cortical regions, including the dorsolateral prefrontal cortices (DLPFCs). Our study sought to examine how an index course of repetitive transcranial magnetic stimulation (rTMS) over the DLPFC improved components of mindfulness as assessed by Baer's Five Facet Mindfulness Questionnaire (FFMQ) and the Experience Questionnaire (EQ).
METHOD: Our preliminary study is a retrospective chart review of 32 patients who had undergone an index course of rTMS for major depressive episode between 2009 and 2012. The following information was collected prior to rTMS: patient demographics, diagnosis, and age of onset of primary diagnosis. The following information was collected prior to and after rTMS: 21-item Hamilton Rating Scale for Depression (HRSD) scores, Patient-Health Questionnaire (PHQ-9) scores, Generalized Anxiety Disorder 7-item (GAD-7) scale scores, FFMQ scores, and EQ scores.
RESULTS: Following rTMS, results showed statistically significant decreases in HRSD, PHQ-9, and GAD-7 scores. There was significant improvement in the nonreactivity to inner experience subscale of the BFFMQ and in the decentring subscale of the EQ. Subgroup analysis between patients who did not improve on the HRSD by 50% or more following rTMS and those who did revealed no baseline difference in mindfulness. There was significant improvement in the decentring subscale of the EQ in both subgroups.
CONCLUSIONS: Our study provides preliminary data that rTMS may be associated with improvement in some components of mindfulness, independently of changes in depression.

PMID: 24331288 [PubMed - indexed for MEDLINE]

Formulary restrictions on atypical antipsychotics: impact on costs for patients with schizophrenia and bipolar disorder in Medicaid.

Am J Manag Care. 2014;20(2):e52-60

Authors: Seabury SA, Goldman DP, Kalsekar I, Sheehan JJ, Laubmeier K, Lakdawalla DN

Objectives: To measure the impact of state Medicaid formulary policies on costs for patients with schizophrenia and bipolar disorder. Study Design: Retrospective analysis of medical and pharmacy claims for patients diagnosed with schizophrenia or bipolar disorder in 24 state Medicaid programs. Methods: We combined information on formulary restrictions in Medicaid with the medical and pharmacy claims of 117,908 patients with schizophrenia and 170,596 patients with bipolar disorder in Medicaid who were single-eligible, and newly prescribed a second-generation antipsychotic from 2001 to 2008. We tested the impact of formulary restrictions on the medical costs and utilization of patients in the 12 months after the index prescription. To capture social costs in addition to medical expenditures in Medicaid, we estimated the incremental costs of incarcerating patients with schizophrenia and bipolar disorder associated with formulary restrictions. Results: Patients with schizophrenia subject to formulary restrictions were more likely to be hospitalized (odds ratio 1.13, P <.001), had 23% higher inpatient costs (P <.001), and 16% higher total costs (P <.001). Similar effects were observed for patients with bipolar disorder. Our estimates suggest restrictive formulary policies in Medicaid increased the number of prisoners by 9920 and incarceration costs by $362 million nationwide in 2008. Conclusions: Applying formulary restrictions to atypical antipsychotics is associated with higher total medical expenditures for patients with schizophrenia and bipolar disorder in Medicaid. Combined with the other social costs such as an increase in incarceration rates, these formulary restrictions could increase state costs by $1 billion annually, enough to offset any savings in pharmacy costs.

PMID: 24738555 [PubMed - in process]

Lithium and autophagy.

ACS Chem Neurosci. 2014 Apr 16;

Authors: Motoi Y, Shimada K, Ishiguro K, Hattori N

Lithium, a drug used to treat bipolar disorders, has a variety of neuroprotective mechanisms, including autophagy regulation, in various neuropsychiatric conditions. In neurodegenerative diseases, lithium enhances aggregate-prone protein, including mutated huntingtin, phosphorylated tau, and ?-synuclein, and causes damaged mitochondria to degrade, while in a mouse model of cerebral ischemia and Alzheimer's disease, autophagy downregulation by lithium is observed. The signaling pathway of lithium as an autophagy enhancer might be associated with the mammalian target of rapamycin (mTOR)-independent pathway, which is involved in myo-inositol-1,4,5-triphosphate (IP3) in Huntington's disease and Parkinson's disease. However, the mTOR-dependent pathway might be involved in inhibiting glycogen synthase kinase-3?(GSK-3?) in other diseases. Lithium's autophagy-enhancing property may contribute to the therapeutic benefit of patients with neuropsychiatric disorders.

PMID: 24738557 [PubMed - as supplied by publisher]

Cannabis use in first-treatment bipolar I disorder: relations to clinical characteristics.

Early Interv Psychiatry. 2014 Apr 17;

Authors: Kvitland LR, Melle I, Aminoff SR, Lagerberg TV, Andreassen OA, Ringen PA

AIMS: The aim of this study was to investigate the associations between recent cannabis use, current symptomatology and age at onset of first manic, depressive and psychotic episodes in a large sample with first-treatment bipolar I disorder (BD I).
METHODS: One hundred one patients with first-treatment Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) bipolar I disorder were included as part of the Thematically Organized Psychosis study. The Structural Clinical Interview for DSM-IV was used for DSM-IV diagnosis and identification of episodes of illness. Earlier suicide attempts were recorded. Manic, depressive and psychotic symptoms were rated using the Young Mania Rating Scale, Inventory of Depressive Symptoms and Positive and Negative Syndrome Scale correspondingly. Cannabis use within the six last months was recorded.
RESULTS: After controlling for confounders, recent cannabis use was significantly associated with lower age at onset of first manic and psychotic episode, but not with onset of first depressive episode (both P?<?0.05). Recent use was also associated with more lifetime suicide attempts (P?<?0.01). No group differences were found on symptom levels.
CONCLUSIONS: The present study confirms earlier findings of an association between cannabis use and a lower age at onset. Recent cannabis use was also associated with more lifetime suicide attempts. The current findings suggest that recent cannabis use is associated with a more severe course of illness in the early phase of BD I.

PMID: 24739233 [PubMed - as supplied by publisher]

Reliability and Validity the Brief Problem Monitor, an Abbreviated Form of the Child Behavior Checklist.

Psychiatry Clin Neurosci. 2014 Apr 16;

Authors: Piper BJ, Gray HM, Raber J, Birkett MA

AIM: The parent form of the 113 item Child Behavior Checklist (CBCL) is widely utilized by child psychiatrists and psychologists. This report examines the reliability and validity of a recently developed abbreviated version of the CBCL, the Brief Problem Monitor (BPM).
METHODS: Caregivers (N=567) completed the CBCL online and the 19 BPM items were examined separately.
RESULTS: Internal consistency of the BPM was high (Cronbach's alpha=0.91) and satisfactory for the Internalizing (0.78), Externalizing (0.86), and Attention (0.87) scales. High correlations between the CBCL and BPM were identified for the total score (r=0.95) as well as the Internalizing (0.86), Externalizing (0.93), and Attention (0.97) scales. The BPM and scales were sensitive and identified significantly higher behavioral and emotional problems among children whose caregiver reported a psychiatric diagnosis of Attention Deficit Hyperactivity Disorder, bipolar, depression, anxiety, developmental disabilities, or Autism Spectrum Disorders relative to a comparison group that had not been diagnosed with these disorders. BPM ratings also differed by the socioeconomic status and education of the caregiver. Mothers with higher annual incomes rated their children as having 38.8% fewer total problems (Cohen's d=0.62) as well as 42.8% lower Internalizing (d=0.53), 44.1% less Externalizing (d=0.62), and 30.9% decreased Attention (d=0.39). A similar pattern was evident for maternal education (d=0.30 to 0.65).
CONCLUSION: Overall, these findings provide strong psychometric support for the BPM although the differences based on the characteristics of the parent indicates that additional information from other sources (e.g., teachers) should be obtained to complement parental reports.

PMID: 24735087 [PubMed - as supplied by publisher]

A comparison of decision making in patients with bipolar i disorder and schizophrenia.

Schizophr Res. 2014 Apr 12;

Authors: Martino DJ, Strejilevich SA

PMID: 24735784 [PubMed - as supplied by publisher]

Page Last Updated : 09-08-2013


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