Managing psychosis in a renal transplant recipient with bipolar affective disorder and allograft rejection.
Nephrology (Carlton). 2015 Mar;20 Suppl 1:2-5
Authors: Dave V, Mulley W, Kanellis J, Summers S
Management of mental health issues in the post-transplant setting can be difficult given the potential for medication related neurotoxicity. The lack of established guidelines in this area further compounds this difficulty. The current report details the course of patient with stable bipolar affective disorder prior to renal transplantation, who developed de novo psychosis post-transplantation as an adverse effect of her tacrolimus therapy. The patient was unable to take her usual oral immunosuppressants due to the severity of her psychosis and she eventually required alemtuzumab parenterally as rescue therapy from rejection. This case highlights the diagnostic and therapeutic challenges when dealing with transplant recipients with significant psychosis.
PMID: 25807849 [PubMed - in process]
Mitochondrial Dysfunction in the Pathophysiology of Bipolar Disorder: Effects of Pharmacotherapy.
Mini Rev Med Chem. 2015 Mar 24;
Authors: Callaly E, Walder K, Morris G, Maes M, Debnath M, Berk M
Bipolar disorder is a common, chronic and complex mental illness. Bipolar disorder is frequently comorbid with primary mitochondrial and metabolic disorders, and studies have implicated mitochondrial dysfunction in its pathophysiology. In the brains of people with bipolar disorder, high-energy phosphates are decreased, lactate is elevated and pH decreased, which together suggest a shift toward glycolysis for energy production. Furthermore, oxidative stress is increased, and calcium signalling dysregulated. Additionally, there is downregulation of the expression of mitochondrial complexes, especially complex I. The therapeutic effects of some bipolar disorder drugs have recently been shown to be related to these mechanisms. In this review we will evaluate current research on the interactions between mitochondrial dysfunction and bipolar disorder pathology. We will then appraise the current literature describing the effects of bipolar disorder drugs on mitochondrial function, and discuss ramifications for future research.
PMID: 25807948 [PubMed - as supplied by publisher]
Association involving serotonin transporter gene linked polymorphic region and bipolar disorder type 1 in Iranian population.
Asia Pac Psychiatry. 2015 Mar 23;
Authors: Ghadiri M, Nourmohammadi I, Fasihi Ramandi M, Moazen Zadeh E
INTRODUCTION: Serotonin transporter gene linked polymorphic region, also called 5HTTLPR, is a candidate in the genetics of bipolar disorder; however, the results of previous association studies are inconsistent. Several explanations have been proposed for that inconsistency; among them are the existing differences both in the genetic basis of bipolar disorder subtypes and the genetic backgrounds of the studied populations. We aimed to investigate the association of 5HTTLPR with bipolar disorder type I (BP-1) in Iranian population.
METHODS: In this case-control study, 146 patients with BP-1 and 165 controls were recruited. The patients were selected through the Structured Clinical Interview for Diagnostic and?Statistical?Manual of?Mental?Disorders, 4th edition. It was required that the patients do not have any present history of general medical conditions, substance abuse, and concurrent major psychiatric disorders. The polymorphism was evaluated by blood sampling and subsequent DNA extraction, polymerase chain reaction, and agarose gel electrophoresis. Chi-square test was used for analyzing allelic and genotype frequencies and two-tailed P values were obtained.
RESULTS: The S allele was significantly more frequent in the BP-1 patients compared with the controls (P?=?0.02, S allele odds ratio?=?1.5, confidence interval 95%?=?1.06-2.11).
DISCUSSION: Our statistically significant results suggest that the role of 5HTTLPR in the pathogenesis of BP-1 needs to be clarified by further scrutiny in Iranian population and other populations of Near East.
PMID: 25808404 [PubMed - as supplied by publisher]
Peripapillary retinal nerve fiber layer thickness in bipolar disorder.
Graefes Arch Clin Exp Ophthalmol. 2015 Mar 26;
Authors: Mehraban A, Samimi SM, Entezari M, Seifi MH, Nazari M, Yaseri M
BACKGROUND: To compare peripapillary retinal nerve fiber layer thickness (RNFLT) between patients with bipolar disorder and a control group by optical coherence tomography (OCT).
METHODS: This prospective comparative case series included 60 eyes of 30 patients with bipolar disorder and 60 eyes of 30 age-matched healthy control subjects. Using OCT, peripapillary RNFLT of the 4 quadrants and the mean of them was compared between the two groups. Variables such as age of onset, duration, smoking, psychosis, mania and depression episodes in the case group and their relationships with RNFLT were evaluated by OCT.
RESULTS: Mean RNFLT was 99?±?8 in the case group, significantly less than the106?±?8 m? in the control group (p?=?0.001). The inferior, superior, and nasal quadrants in the case and control groups showed significant difference in RNFLT (p?<?0.001) (p?=?0.040) (p?=?0.005); however, the temporal quadrant was not reduced significantly, compared to the control value (p?=?0.907). Moreover, the only variable showing significant relation with RNFLT was duration of bipolar disorder (p?=?0.040).
CONCLUSION: Reduction of peripapilary RNFLT occurs in patients with bipolar disorder, and is related to the duration of disease. RNFLT can be a beneficial value for studying neurodegenerative changes over time towards detecting the severity and duration of disorder.
PMID: 25808660 [PubMed - as supplied by publisher]
Lithium treatment and hippocampal subfields and amygdala volumes in bipolar disorder.
Bipolar Disord. 2015 Mar 24;
Authors: Hartberg CB, Jørgensen KN, Haukvik UK, Westlye LT, Melle I, Andreassen OA, Agartz I
OBJECTIVES: Results from magnetic resonance imaging (MRI) studies are heterogeneous with regard to hippocampal and amygdala volume alterations in bipolar disorder (BD). Lithium treatment may influence both structures. It is unknown if lithium treatment has distinct effects on hippocampal subfield volumes and if subfield volumes change over the course of illness in BD.
METHODS: MRI scans were obtained for 34 lithium-treated patients with BD (Li+), 147 patients with BD who were not treated with lithium (Non-Li), and 300 healthy controls. Hippocampal total and subfield volumes and amygdala volumes were automatically estimated using Freesurfer. General linear models were used to investigate volume differences between groups and the effects of illness course and lithium treatment.
RESULTS: The Non-Li BD group displayed significantly smaller bilateral cornu ammonis (CA) 2/3 and CA4/dentate gyrus (DG) subfields, total hippocampal volumes, right CA1 and right subiculum subfields, and left amygdala volume compared to healthy controls. There were no differences between the Li+ BD and either the Non-Li BD or the healthy control groups. In patients with numerous affective episodes, Non-Li BD patients had smaller left CA1 and CA2/3 volumes compared to Li+ BD patients and healthy controls. There were positive associations between lithium treatment duration and left amygdala volume.
CONCLUSIONS: Hippocampal subfield and amygdala volumes were reduced in Non-Li BD patients compared to healthy controls, whereas the Li+ BD volumes were no different from those in Non-Li BD patients or healthy controls. Over the course of BD, lithium treatment might counteract reductions specifically in the left CA1 and CA2/3 hippocampal subfields and amygdala volumes, in accordance with the suggested neuroprotective effects of lithium.
PMID: 25809287 [PubMed - as supplied by publisher]
Schizotypy-do not worry, it is not all worrisome.
Schizophr Bull. 2015 Mar;41 Suppl 2:S436-43
Authors: Mohr C, Claridge G
A long-standing tradition in personality research in psychology, and nowadays increasingly in psychiatry, is that psychotic and psychotic-like thoughts are considered common experiences in the general population. Given their widespread occurrence, such experiences cannot merely reflect pathological functioning. Moreover, reflecting the multi-dimensionality of schizotypy, some dimensions might be informative for healthy functioning while others less so. Here, we explored these possibilities by reviewing research that links schizotypy to favorable functioning such as subjective wellbeing, cognitive functioning (major focus on creativity), and personality correlates. This research highlights the existence of healthy people with psychotic-like traits who mainly experience positive schizotypy (but also affective features mapping onto bipolar disorder). These individuals seem to benefit from a healthy way to organize their thoughts and experiences, that is, they employ an adaptive cognitive framework to explain and integrate their unusual experiences. We conclude that, instead of focusing only on the pathological, future studies should explore the behavioral, genetic, imaging, and psychopharmacological correlates that define the healthy expression of psychotic-like traits. Such studies would inform on protective or compensatory mechanisms of psychosis-risk and could usefully inform us on the evolutionary advantages of the psychosis dimension.
PMID: 25810058 [PubMed - in process]
Factor structure and reliability of the Italian adaptation of the Hypomania Check List-32, second revision (HCL-32-R2).
J Affect Disord. 2015 Mar 10;178:112-120
Authors: Fornaro M, De Berardis D, Mazza M, Pino M, Favaretto E, Bedani F, Wieser C, Indelicato L, Paternò VF, Lo Monaco F, Dugo F, Ventriglio A, Mungo S, Selle V, Valchera A, Elassy M, Martinotti G, De Bartolomeis A, Iasevoli F, Tomasetti C, Avvisati L, Tartaglione S, Perna G, Cattaneo CI, Consoli G, Romano A, Del Debbio A, Martino M, D?Angelo E, De Pasquale C, Koshy AS, Angst J
OBJECTIVE: To assess the psychometric properties of the Italian adaptation of the Hypomania-Check-List 32-item, second revision (HCL-32-R2) for the detection of bipolarity in major depressive disorder (MDD) treatment-seeking outpatients.
METHODS: A back-to-back Italian adaption of the "Bipolar Disorders: Improving Diagnosis, Guidance, and Education" English module of the HCL-32-R2 was administered between March 2013 and October 2014 across twelve collaborating sites in Italy. Diagnostic and Statistical Manual Fourth edition (DSM-IV) diagnoses were made adopting the mini-international neuropsychiatric interview, using bipolar disorder (BD) patients as controls.
RESULTS: In our sample (n=441, of whom, BD-I=68; BD-II=117; MDD=256), using a cut-off of 14 allowed the HCL-32-R2 to discriminate DSM-IV-defined MDD patients between "true unipolar" (HCL-32-R2(-)) and "sub-threshold bipolar depression" (HCL-32-R2(+)) with sensitivity=89% and specificity=79%. Area under the curve was .888; positive and negative predictive values were 75.34% and 90.99% respectively. Owing to clinical interpretability considerations and consistency with previous adaptations of the HCL-32, a two-factor solution (F1="hyperactive/elated" vs. F2="irritable/distractible/impulsive") was preferred using exploratory and confirmatory factor analyses, whereas items n.33 ("I gamble more") and n.34 ("I eat more") introduced in the R2 version of the scale slightly loaded onto F2 and F1 respectively. Cronbach?s ?=.88 for F1 and .71 for F2.
LIMITATIONS: No cross-validation with any additional validated screening tool; treatment-seeking outpatient sample; recall bias; no systematic evaluation of eventual medical/psychiatric comorbidities, current/lifetime pharmacological history, neither record of severity of current MDE.
CONCLUSIONS: Our results seem to indicate fair accuracy of HCL-32 as a screening instrument for BD, though replication studies are warranted.
PMID: 25805403 [PubMed - as supplied by publisher]
Risks for Nonaffective Psychotic Disorder and Bipolar Disorder in Young People With Autism Spectrum Disorder: A Population-Based Study.
JAMA Psychiatry. 2015 Mar 25;
Authors: Selten JP, Lundberg M, Rai D, Magnusson C
Importance: Whether individuals with autism spectrum disorder (ASD) are at increased risk for nonaffective psychotic disorder (NAPD) or bipolar disorder (BD) is unknown.
Objective: To test whether the risks for NAPD and BD in individuals with ASD are increased and whether these risks are higher than those of their siblings not diagnosed as having ASD.
Design, Setting, and Participants: We performed a nested case-control study of all individuals 17 years or younger who ever resided in Stockholm County, Sweden, from January 1, 2001, through December 31, 2011 (Stockholm Youth Cohort). We included cohort members ever diagnosed as having ASD (n?=?9062) and their full siblings never diagnosed as having ASD. Each case was matched with 10 control individuals of the same sex born during the same month and year. Using Swedish registers, cases, siblings, and controls were followed up until December 31, 2011. By then, the oldest individuals had reached the age of 27 years.
Exposures: Autism spectrum disorder, registered before age 16 or 28 years. We distinguished between ASD with and without intellectual disability (ID).
Main Outcomes and Measures: We calculated odds ratios (ORs) for NAPD and BD adjusted for age, sex, population density of place of birth, personal or parental history of migration, hearing impairment, parental age, parental income, parental educational level, and parental history of psychiatric disorder.
Results: The adjusted ORs for NAPD and BD for cases with non-ID ASD registered before age 16 years were 5.6 (95% CI, 3.3-8.5) and 5.8 (95% CI, 3.9-8.7), respectively; the adjusted ORs for cases with ID ASD were 3.5 (95% CI, 2.0-6.0) and 1.8 (95% CI, 0.8-4.1). The adjusted ORs for NAPD and BD in cases with non-ID ASD registered before age 28 years were 12.3 (95% CI, 9.5-15.9) and 8.5 (95% CI, 6.5-11.2), respectively; for cases with ID ASD, these ORs were 6.4 (95% CI, 4.2-9.8) and 2.0 (95% CI, 1.0-3.9), respectively. The ORs for NAPD and BD for the nonautistic full siblings of cases for whom ASD was registered before age 16 years, adjusted for hearing loss, were 1.8 (95% CI, 1.1-2.7) and 1.7 (95% CI, 1.1-2.6), respectively.
Conclusions and Relevance: A diagnosis of ASD is associated with a substantially increased risk for NAPD and BD. This finding contributes to our understanding of these disorders and has implications for the management of ASD.
PMID: 25806797 [PubMed - as supplied by publisher]
Development of mania with carbamazepine for treatment of seizure disorder in a 7-year-old boy.
J Clin Psychiatry. 2015 Jan;76(1):e117-8
Authors: Malas NM, Ortiz-Aguayo R, Meyer V
PMID: 25650677 [PubMed - indexed for MEDLINE]
60 years of advances in neuropsychopharmacology for improving brain health, renewed hope for progress.
Eur Neuropsychopharmacol. 2015 Feb 7;
Authors: Millan MJ, Goodwin GM, Meyer-Lindenberg A, Ogren SO
Pharmacotherapy is effective in helping many patients suffering from psychiatric and neurological disorders, and both psychotherapeutic and stimulation-based techniques likewise have important roles to play in their treatment. However, therapeutic progress has recently been slow. Future success for improving the control and prevention of brain disorders will depend upon deeper insights into their causes and pathophysiological substrates. It will also necessitate new and more rigorous methods for identifying, validating, developing and clinically deploying new treatments. A field of Research and Development (R and D) that remains critical to this endeavour is Neuropsychopharmacology which transformed the lives of patients by introducing pharmacological treatments for psychiatric disorder some 60 years ago. For about half of this time, the European College of Neuropsychopharmacology (ECNP) has fostered efforts to enhance our understanding of the brain, and to improve the management of psychiatric disorders. Further, together with partners in academia and industry, and in discussions with regulators and patients, the ECNP is implicated in new initiatives to achieve this goal. This is then an opportune moment to survey the field, to analyse what we have learned from the achievements and failures of the past, and to identify major challenges for the future. It is also important to highlight strategies that are being put in place in the quest for more effective treatment of brain disorders: from experimental research and drug discovery to clinical development and collaborative ventures for reinforcing "R and D". The present article sets the scene, then introduces and interlinks the eight articles that comprise this Special Volume of European Neuropsychopharmacology. A broad-based suite of themes is covered embracing: the past, present and future of "R and D" for psychiatric disorders; complementary contributions of genetics and epigenetics; efforts to improve the treatment of depression, neurodevelopmental and neurodegenerative disorders; and advances in the analysis and neuroimaging of cellular and cerebral circuits.
PMID: 25799919 [PubMed - as supplied by publisher]
Distinguishing bipolar II depression from unipolar major depressive disorder: Differences in heart rate variability.
World J Biol Psychiatry. 2015 Mar 24;:1-10
Authors: Chang HA, Chang CC, Kuo TB, Huang SY
OBJECTIVES: Bipolar II (BPII) depression is commonly misdiagnosed as unipolar depression (UD); however, an objective and reliable tool to differentiate between these disorders is lacking. Whether cardiac autonomic function can be used as a biomarker to distinguish BPII from UD is unknown.
METHODS: We recruited 116 and 591 physically healthy patients with BPII depression and UD, respectively, and 421 healthy volunteers aged 20-65 years. Interviewer and self-reported measures of depression/anxiety severity were obtained. Cardiac autonomic function was evaluated by heart rate variability (HRV) and frequency-domain indices of HRV.
RESULTS: Patients with BPII depression exhibited significantly lower mean R-R intervals, variance (total HRV), low frequency (LF)-HRV, and high frequency (HF)-HRV but higher LF/HF ratio compared to those with UD. The significant differences remained after adjusting for age. Compared to the controls, the patients with BPII depression showed cardiac sympathetic excitation with reciprocal vagal impairment, whereas the UD patients showed only vagal impairment. Depression severity independently contributed to decreased HRV and vagal tone in both the patients with BPII depression and UD, but increased sympathetic tone only in those with BPII depression.
CONCLUSIONS: HRV may aid in the differential diagnosis of BPII depression and UD as an adjunct to diagnostic interviews.
PMID: 25800950 [PubMed - as supplied by publisher]
NCAN Cross-Disorder Risk Variant is Associated with Limbic Gray Matter Deficits in Healthy Subjects and Major Depression.
Neuropsychopharmacology. 2015 Mar 24;
Authors: Dannlowski U, Kugel H, Grotegerd D, Redlich R, Suchy J, Opel N, Suslow T, Konrad C, Ohrmann P, Bauer J, Kircher T, Krug A, Jansen A, Baune BT, Heindel W, Domschke K, Forstner A, Nöthen MM, Treutlein J, Arolt V, Hohoff C, Rietschel M, Witt SH
Genome-wide association studies have reported an association between NCAN rs1064395 genotype and bipolar disorder. This association was later extended to schizophrenia and major depression. However, the neurobiological underpinnings of these associations are poorly understood. NCAN is implicated in neuronal plasticity and expressed in subcortical brain areas, such as the amygdala and hippocampus, which are critically involved in dysfunctional emotion processing and -regulation across diagnostic boundaries. We hypothesized that the NCAN risk variant is associated with reduced gray matter volumes in these areas. Gray matter structure was assessed by voxel-based morphometry on structural MRI-data in two independent German samples (healthy subjects, n=512; depressed inpatients, n=171). All participants were genotyped for NCAN rs1064395. Hippocampal and amygdala region-of-interest analyses were performed within each sample. Additionally, whole-brain data from the combined sample were analyzed. Risk (A)-allele carriers showed reduced amygdala and hippocampal gray matter volumes in both cohorts with a remarkable spatial overlap. In the combined sample, genotype effects observed for the amygdala and hippocampus survived correction for entire brain volume. Further effects were also observed in the left orbitofrontal cortex and the cerebellum/fusiform gyrus. We conclude that NCAN genotype is associated with limbic gray matter alterations in healthy and depressed subjects in brain areas implicated in emotion perception and -regulation. The present data suggest that NCAN forms susceptibility to neuro-structural deficits in the amygdala, hippocampus, and prefrontal areas independent of disease, which might lead to disorder onset in the presence of other genetic or environmental risk factors.Neuropsychopharmacology accepted article preview online, 24 March 2015. doi:10.1038/npp.2015.86.
PMID: 25801500 [PubMed - as supplied by publisher]
A meta-analysis investigating the prevalence and moderators of migraines among people with bipolar disorder.
J Affect Disord. 2015 Mar 9;178:88-97
Authors: Fornaro M, Stubbs B
BACKGROUND: Uncertainty exists regarding the prevalence and moderators of migraine comorbidity among people with bipolar disorder (BD). We conducted a meta-analysis and meta-regression to investigate the prevalence and moderators of migraine among people with BD.
METHOD: Two authors independently searched major electronic databases from inception till 02/2015. Articles were included that reported the prevalence of migraine in people with BD with or without a control group. A random effects meta-analysis and exploratory meta-regression were conducted.
RESULTS: Fourteen studies were included encompassing 3976 individuals with BD (mean age 35.5 years, SD 7.6, 29% male). The overall pooled prevalence of migraine was 34.8% (95% CI=25.54-44.69). The prevalence of migraine was higher among people with BD-II (54.17%, 95% CI=31.52-75.95, n=742) compared to BD-I (32.7%, 95% CI=18.16-49.19, n=2138, z=3.97, p<0.0001). The prevalence of migraine was 33.9% (95% CI=26.02-42.44), 39.5% (95% CI=18.81-62.39) and 47.11% (95% CI=22.24-72.77) in North America, Europe and South America respectively. The prevalence of migraine was higher when classified according to recognized criteria at 47.91% (95% CI=32.51-63.5) compared to non-recognized criteria (20.0%, 95% CI=12.44-29.06, z=-8.40, p<0.0001). Meta regression suggests mean age may be a potential moderator.
CONCLUSION: Migraine is common and burdensome among people with BD. People with BD-II appear to be particularly affected. Nonetheless, future research is required to better understand these relationships, with a special emphasis toward the course specifiers of comorbid migraine cases of either BD-I vs. BD-II.
PMID: 25801521 [PubMed - as supplied by publisher]
The bipolar II disorder personality traits, a true syndrome?
J Affect Disord. 2015 Mar 9;178:107-111
Authors: Gudmundsson E
BACKGROUND: The author was struck by the similarities and commonality of complaints, aside from mood swings, made by Bipolar II patients and started registrating these complaints. This registrational work eventually led to the development of The Bipolar II Syndome Checklist. The aim of this work was to understand how widely the Bipolar II disorder affects the personality, and what disturbing personality traits are the most common? Deliberately, no attempt was made to diagnose psychiatric comorbidities, in the hope that one would get a clearer view of what symptoms, if any, could be considered a natural part of the Bipolar II Disorder. As far as the author knows this is a novel approach.
METHOD: 105 Bipolar II patients completed the Bipolar II Syndrome Checklist. The answers to the 44 questions on the list are presented in tables.
RESULTS: Symptoms like anxiety, low self esteem, paranoia, extreme hurtfulness, migraine, Post Partum Depression, obsessive traits, alcoholism in the family are amongst the findings which will be presented in greater detail.
LIMITATIONS: No control group. Bipolar I patients excluded. The Bipolar II Syndrome Checklist has not been systematically validated.
CONCLUSIONS: The results show that Bipolar II Disorder causes multiple symptoms so commonly that it may be justified to describe it as a syndrome, The Bipolar II Syndrome. Also these disturbances commonly lie in families of Bipolar II patients and are in all likelihood, greatly underdiagnosed. The clinical relevance of this study lies in increasing our knowledge and understanding of the nature of the Bipolar II Disorder, which in all probability will increase the diagnostic and treatment accuracy, since clinicians are more likely to scan for other symptoms needing treatment.
PMID: 25801523 [PubMed - as supplied by publisher]
The epidemiology of common mental disorders from age 20 to 50: results from the prospective Zurich cohort Study.
Epidemiol Psychiatr Sci. 2015 Mar 24;:1-9
Authors: Angst J, Paksarian D, Cui L, Merikangas KR, Hengartner MP, Ajdacic-Gross V, Rössler W
BACKGROUND: There are only a small number of prospective studies that have systematically evaluated standardised diagnostic criteria for mental disorder for more than a decade. The aim of this study is to present the approximated overall and sex-specific cumulative incidence of mental disorder in the Zurich cohort study, a prospective cohort study of 18-19 years olds from the canton of Zurich, Switzerland, who were followed through age 50.
METHOD: A stratified sample of 591 participants were interviewed with the Structured Psychopathological Interview and Rating of the Social Consequences of Psychological Disturbances for Epidemiology, a semi-structured interview that uses a bottom-up approach to assess the past-year presence of 15 psychiatric syndromes. Seven interview waves took place between 1979 and 2008. Approximated cumulative incidence was estimated using Kaplan-Meier methods.
RESULTS: Rates of mental disorder were considerably higher than those generally reported in cross-sectional surveys. We found rates ranging from 32.5% for major depressive disorder to 1.2% for Bipolar I disorder. The cumulative probability of experiencing any of the mental disorders assessed by age 50 was 73.9%, the highest reported to date. We also found that rates differed by sex for most disorders, with females generally reporting higher rates of mood, anxiety and phobic disorder, and males reporting higher rates of substance- and alcohol-related disorders.
CONCLUSIONS: These findings confirm those of other long-term prospective studies that indicate the nearly universal nature of disturbances of emotion and behaviour across the life span. Greater community awareness of the normative nature of these experiences is warranted. An important area of future research is study long-term course and stability to determine who among those with such disturbances suffer from chronic disabling mental disorders. Such longitudinal studies may aid in directing services and intervention efforts where they are most needed.
PMID: 25802979 [PubMed - as supplied by publisher]
Minor contribution of biliary excretion in lithium elimination in rats.
Drug Metabol Personal Ther. 2015 Mar 1;30(1):65-67
Authors: Uwai Y, Kawasaki T, Nabekura T
BACKGROUND: Lithium, which is often used for the treatment of bipolar disorders, is mainly recovered into urine after being orally administered. Due to the fact that it is completely absorbed via the gastrointestinal tract, it remains unknown whether biliary excretion is involved in the lithium disposition. In this study, we examined biliary excretion of lithium in rats and compared these with renal excretion.
MATERIALS AND METHODS: After the injection of lithium chloride to femoral vein, plasma levels and excretion into urine and bile of lithium were evaluated.
RESULTS: After its intravenous administration as a bolus, the plasma concentration of lithium decreased time-dependently. Until 60 min, 6.47% and 0.694% of injected lithium were excreted into urine and bile, respectively. The biliary clearance of lithium was calculated to be 0.0779 mL/min/kg, and this was 11.3% of the renal clearance.
CONCLUSIONS: These findings suggest the low ability of the liver to eliminate lithium from plasma in comparison with the kidney in rats.
PMID: 25803094 [PubMed - as supplied by publisher]
Sex differences in mania phenotype and ethanol consumption in the lateral hypothalamic kindled rat model.
Transl Psychiatry. 2015;5:e534
Authors: Abulseoud OA, Gawad NA, Mohamed K, Vadnie C, Camsari UM, Karpyak V, Frye MA, Choi DS
Sex differences have been observed in mania phenotypes in humans. However the mechanisms underlying this difference are poorly understood. Activating the lateral hypothalamus is implicated in manic-like behaviors in rodents. Using newly established lateral hypothalamus kindled (LHK) rat mania model, we investigated sex differences of manic-like behaviors and its correlation with voluntary ethanol intake. We stimulated the lateral hypothalamus bilaterally in the male and female Wistar rats over five consecutive days. We recorded and quantified kindling-induced behaviors for each individual animal. We also assessed ethanol consumption using a two-bottle choice ethanol drinking as well as circadian locomotor activity counts daily throughout the experiment. We found notable sex differences in several aspects of manic-like behaviors during kindling. Males exhibited a significantly increased locomotor activity during the light phase, and reduced rest interval. On the other hand, females displayed significantly higher ethanol consumption and more frequent rearing behavior. However, no sex differences were present in the duration of sexual, feeding or grooming behaviors or in dark-phase activity counts. The excessive alcohol intake in LHK female rats is reminiscent of clinically reported sex differences in bipolar patients while the other phenotypic sex differences such as rearing and locomotor activity are less clearly described in clinical studies. Overall, our results lend further evidence for the validity of the LHK rat as a useful model to study brain region-specific molecular changes during mania and its correlation with alcohol use disorders.
PMID: 25803497 [PubMed - as supplied by publisher]
Long-term morbidity in bipolar-I, bipolar-II, and unipolar major depressive disorders.
J Affect Disord. 2015 Mar 3;178:71-78
Authors: Forte A, Baldessarini RJ, Tondo L, Vázquez GH, Pompili M, Girardi P
BACKGROUND: Long-term symptomatic status in persons with major depressive and bipolar disorders treated clinically is not well established, although mood disorders are leading causes of disability worldwide.
AIMS: To pool data on long-term morbidity, by type and as a proportion of time-at-risk, based on published studies and previously unreported data.
METHODS: We carried out systematic, computerized literature searches for information on percentage of time in specific morbid states in persons treated clinically and diagnosed with recurrent major depressive or bipolar I or II disorders, and incorporated new data from one of our centers.
RESULTS: We analyzed data from 25 samples involving 2479 unipolar depressive and 3936 bipolar disorder subjects (total N=6415) treated clinically for 9.4 years. Proportions of time ill were surprisingly and similarly high across diagnoses: unipolar depressive (46.0%), bipolar I (43.7%), and bipolar II (43.2%) disorders, and morbidity was predominantly depressive: unipolar (100%), bipolar-II (81.2%), bipolar-I (69.6%). Percent-time-ill did not differ between UP and BD subjects, but declined significantly with longer exposure times.
CONCLUSIONS: The findings indicate that depressive components of all major affective disorders accounted for 86% of the 43-46% of time in affective morbidity that occurred despite availability of effective treatments. These results encourage redoubled efforts to improve treatments for depression and adherence to their long-term use.
PMID: 25797049 [PubMed - as supplied by publisher]
Serotonin levels in the dorsal raphe nuclei of both chipmunks and mice are enhanced by long photoperiod, but brain dopamine level response to photoperiod is species-specific.
Neurosci Lett. 2015 Mar 19;
Authors: Goda R, Otsuka T, Iwamoto A, Kawai M, Shibata S, Furuse M, Yasuo S
Seasonal affective disorder (SAD) is a subtype of major depressive or bipolar disorders associated with the shortened photoperiod in winter. This depressive disorder is integrally tied to the seasonal regulation of the brain's serotonergic system. Recently, we found that C57BL/6J mice subjected to a forced-swim test exhibited immobility, a photoperiod-dependent depression-associated behavior, and suppression of brain serotonin levels. However, mice are nocturnal animals, and it is unclear whether the brain serotonergic system responds similarly to photoperiod in nocturnal and diurnal species. This study compared the responses of brain serotonergic and dopaminergic systems to photoperiod in diurnal chipmunks and nocturnal C57BL/6J mice. In both species, serotonin levels in the dorsal raphe nuclei were higher under long-day conditions than short-day conditions, suggesting a similarity in the photoperiod responses of the serotonergic systems. However, photoperiod affected dopamine levels in various brain regions differently in the two species. Some chipmunk brain regions exhibited stronger photoperiod-induced changes in dopamine levels than those of C57BL/6J mice, and the direction of the changes in the hypothalamus was opposite. In conclusion, photoperiod may regulate the brain serotonergic system through similar mechanisms, regardless of whether the animals are diurnal or nocturnal, but photoperiod-dependent regulation of brain dopamine is species-specific.
PMID: 25797183 [PubMed - as supplied by publisher]
Hallucinations and inhibitory functioning in healthy young adults with high and low levels of hypomanic personality traits.
Cogn Neuropsychiatry. 2015 May;20(3):254-269
Authors: Badcock JC, Mahfouda S, Maybery MT
INTRODUCTION: Hallucinations in schizophrenia and hallucination proneness in healthy young adults are associated with a common cognitive mechanism, namely impaired inhibitory control. Hallucinatory-like experiences also seem related to hypomanic symptoms in non-clinical participants; however, the mechanisms involved are unknown. We sought to examine self-reported hallucinatory/anomalous perceptual experiences in students selected for high versus low levels of hypomanic personality traits, and whether hypomania is characterised by deficient inhibitory control.
METHOD: Undergraduate students with either high (n = 26) or low (n = 28) scores on the Hypomanic Personality Scale-Revised (HPS-20) were compared on: (1) the Launay Slade Hallucination Scale-Revised (LSHS-R), a measure of hallucination proneness, (2) the Cardiff Anomalous Perceptions Scale (CAPS) and (3) the Inhibition of Currently Irrelevant Memories (ICIM) task, an index of intentional inhibition.
RESULTS: The high HPS group had higher total scores, as well as higher frequency (on CAPS only), intrusiveness and distress (CAPS) scores compared to the low HPS group. They also produced significantly more false alarms on the second run of the ICIM task than the low hypomania traits group.
CONCLUSIONS: Frequent, intrusive and distressing perceptual anomalies and proneness to hallucinations tend to occur in healthy individuals with hypomanic personality traits and may be associated with transient difficulties with inhibitory control. Inhibitory control may be a cognitive marker of vulnerability to hallucinations across diagnostic boundaries.
PMID: 25798816 [PubMed - as supplied by publisher]
A Comparison of Mental Health Diagnoses Treated via Interactive Video and Face to Face in the Veterans Healthcare Administration.
Telemed J E Health. 2015 Mar 23;
Authors: Grubbs KM, Fortney JC, Dean T, Williams JS, Godleski L
OBJECTIVE: This study compares the mental health diagnoses of encounters delivered face to face and via interactive video in the Veterans Healthcare Administration (VHA).
MATERIALS AND METHODS: We compiled 1 year of national-level VHA administrative data for Fiscal Year 2012 (FY12). Mental health encounters were those with both a VHA Mental Health Stop Code and a Mental Health Diagnosis (n=11,906,114). Interactive video encounters were identified as those with a Mental Health Stop Code, paired with a VHA Telehealth Secondary Stop Code. Primary diagnoses were grouped into posttraumatic stress disorder (PTSD), depression, anxiety, bipolar disorder, psychosis, drug use, alcohol use, and other.
RESULTS: In FY12, 1.5% of all mental health encounters were delivered via interactive video. Compared with face-to-face encounters, a larger percentage of interactive video encounters was for PTSD, depression, and anxiety, whereas a smaller percentage was for alcohol use, drug use, or psychosis.
CONCLUSIONS: Providers and patients may feel more comfortable treating depression and anxiety disorders than substance use or psychosis via interactive video.
PMID: 25799233 [PubMed - as supplied by publisher]
Attentional Capture by Emotional Scenes across Episodes in Bipolar Disorder: Evidence from a Free-Viewing Task.
Biol Psychol. 2015 Mar 18;
Authors: García-Blanco A, Salmerón L, Perea M
We examined whether the initial orienting, subsequent engagement, and overall allocation of attention are determined exogenously (i.e., by the affective valence of the stimulus) or endogenously (i.e., by the participant's mood) in the manic, depressive and euthymic episodes of bipolar disorder (BD). Participants were asked to compare the affective valence of two pictures (happy/threatening/neutral [emotional] vs. neutral [control]) while their eye movements were recorded in a free-viewing task. Results revealed that the initial orienting was exogenously captured by emotional images relative to control images. Importantly, engagement and overall allocation were endogenously captured by threatening images relative to neutral images in BD patients, regardless of their episode-this effect did not occur in a group of healthy controls. The threat-related bias in BD, which occurs even at the early stages of information processing (i.e. attentional engagement), may reflect a vulnerability marker.
PMID: 25796341 [PubMed - as supplied by publisher]
Evaluation of TrkB and BDNF transcripts in prefrontal cortex, hippocampus and striatum from subjects with schizophrenia, bipolar disorder and major depressive disorder.
Neurobiol Dis. 2015 Mar 18;
Authors: Reinhart V, Bove SE, Volfson D, Lewis DA, Kleiman RJ, Lanz TA
Brain-derived neurotrophic factor (BDNF) signaling is integral to a range of neural functions, including synaptic plasticity, and exhibits activity-dependent regulation of expression. As altered BDNF signaling has been implicated in multiple psychiatric diseases, here we report a quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis of mRNAs encoding TrkB, total BDNF and the four most abundant BDNF transcripts (I, IIc, IV and VI) in post-mortem tissue from matched tetrads of subjects with schizophrenia, bipolar disorder or major depressive disorder (MDD) and healthy comparison subjects. In all three regions examined, dorsolateral prefrontal cortex (DLPFC), associative striatum and hippocampus, total BDNF mRNA levels did not differ in any disease state. In DLPFC, BDNF IIc was significantly lower in schizophrenia relative to healthy comparison subjects. In hippocampus, BDNF I, IIc and VI were lower in subjects with both schizophrenia and bipolar disorder relative to comparison subjects. In striatum, TrkB mRNA was lower in bipolar disorder and MDD, while BDNF IIc was elevated in MDD, relative to comparison subjects. These data highlight potential alterations in BDNF signaling in the corticohippocampal circuit in schizophrenia, and within the striatum in mood disorders. Novel therapies aimed at improving BDNF-TrkB signaling may therefore have potential to impact on a range of psychiatric disorders.
PMID: 25796564 [PubMed - as supplied by publisher]
Quantitative Measures of Craniofacial Dysmorphology in a Family Study of Schizophrenia and Bipolar Illness.
Schizophr Bull. 2015 Mar 20;
Authors: Deutsch CK, Levy DL, Price SF, Bodkin JA, Boling L, Coleman MJ, Johnson F, Lerbinger J, Matthysse S, Holzman PS
Several laboratories, including ours, have reported an overrepresentation of craniofacial (CF) anomalies in schizophrenia (SZ). How might this dysmorphology arise in a brain-based disorder? Because the brain and face derive from shared embryologic primordia and morphogenetic forces, maldevelopmental processes may result in both CF and brain dysmorphology. Our approach is 2-pronged. First, we have employed, for the first time in the study of psychiatric disorders, objective measures of CF morphology that utilize an extensive normative database, permitting computation of standardized scores for each subject. Second, we have rendered these findings biologically interpretable by adopting principles of embryology in the analysis of dysmorphology. Dependent measures in this investigation focused on derivatives of specific embryonic primordia and were contrasted among probands with psychotic disorders, their first-degree relatives, and normal controls (NC). Subject groups included patients with a diagnosis of SZ (N = 39) or bipolar (BP) disorder with psychotic features (N = 32), their clinically unaffected relatives (N = 82 and N = 41, respectively), and NC (N = 95) subjects. Anomalies involving derivatives of frontonasal and mandibular embryonic primordia showed a clear association with psychotic illness, as well as familial aggregation in relatives in both diagnostic groups. In contrast, one class of CF anomalies emerged only among SZ probands and their first-degree relatives: dysmorphology arising along the junction of the frontonasal and maxillary prominence derivatives, manifested as marked asymmetries. This class was not overrepresented among the BP patients nor among their relatives, indicating that this dysmorphology appears to be specific to SZ and not a generalized feature of psychosis. We discuss these findings in light of embryologic models that relate brain regions to specific CF areas.
PMID: 25795453 [PubMed - as supplied by publisher]
Cluster analysis reveals abnormal hippocampal neurometabolic profiles in young people with mood disorders.
Eur Neuropsychopharmacol. 2015 Mar 5;
Authors: Hermens DF, Naismith SL, Chitty KM, Lee RS, Tickell A, Duffy SL, Paquola C, White D, Hickie IB, Lagopoulos J
While numerous studies have employed magnetic resonance spectroscopy (MRS) to determine in vivo neurometabolite levels associated with mood disorders the findings in both unipolar depression and bipolar disorder have been mixed. Data-driven studies may shed new light on this literature by identifying distinct subgroups of patients who may benefit from different treatment strategies. The objective of the present study was to utilize hierarchical cluster analysis in order to generate new hypotheses with respect to neurometabolic profiling of mood disorder. Participants were 165 young persons (18-30 yrs) with a mood disorder and 40 healthy controls. Neurometabolite levels were recorded via proton-MRS ((1)H MRS). The ratios (relative to creatine) of glutamate (GLU), N-acetyl aspartate (NAA) and myo-inositol (MI) measured within the hippocampus. Self-reported and clinician rated symptoms as well as cognition were also measured. The unipolar depression (N=90) and bipolar disorder (N=75) groups did not significantly differ (from each other or controls) in their levels of GLU, NAA or MI. Cluster analyses derived four subgroups of patients who were distinguished by all three metabolites. There was a pattern of positive association between NAA and GLU, whereby clusters were abnormally increased (clusters 1, 2) or normal (cluster 4) or abnormally decreased (cluster 3) in these neurometabolites. These findings suggest that there are neurometabolic abnormalities in subgroups of young people with mood disorder, which may occur despite diagnostic similarities. Such evidence highlights that the underlying neurobiology of mood disorder is complex and MRS may have unique utility in delineating underlying neurobiology and targeting treatment strategies.
PMID: 25795519 [PubMed - as supplied by publisher]
Development of screening inventories for bipolar disorder at workplace: A diagnostic accuracy study.
J Affect Disord. 2015 Mar 9;178:32-38
Authors: Imamura K, Kawakami N, Naganuma Y, Igarashi Y
BACKGROUND: This study aimed to develop a new instrument for bipolar disorder screening, the Workplace Bipolar Inventory (WBI), and examine its efficiency as compared with Mood Disorder Questionnaire (MDQ) and Bipolar Spectrum Diagnostic Scale (BSDS) among workers on leave of the absence due to their mental health problems.
METHODS: Participants were recruited at a psychiatric outpatient clinic for return-to-work in Tokyo, Japan, during September to November 2009. 81 outpatients were recruited, 55 of whom (68%) agreed to participate in this study. Participants answered questionnaires including WBI, MDQ, BSDS, and demographic factors. Their diagnostic information according to the international statistical classification of diseases and related health problems 10th revision (ICD-10) was obtained from their attending psychiatrists. The WBI is a new self-rating 39-item questionnaire which developed with input from occupational mental health specialists and an analysis of WHO Composite International Diagnostic Interview (CIDI) items. The WBI contains 3 subtype scales: WBI-A (5 items), WBI-AB4 (9 items), and WBI-AB (39 items).
RESULTS: Reliability of these scales was moderate. In the AUC of these scales, BSDS was the best of them (0.83). In the optimal cut-off point of these scales, WBI-AB4 showed good efficiency of screening (sensitivity=0.78, specificity=0.75). Both MDQ and BSDS had high specificity, while low in sensitivity.
LIMITATIONS: The well validated diagnostic method (i.e., the structured clinical interview for DSM-IV [SCID] or CIDI) was not applied in this study.
CONCLUSIONS: The WBI, especially WBI-AB4 would be a useful workplace screening tool for workers with bipolar disorder.
PMID: 25795533 [PubMed - as supplied by publisher]
Online mindfulness-based intervention for late-stage bipolar disorder: pilot evidence for feasibility and effectiveness.
J Affect Disord. 2015 Mar 5;178:46-51
Authors: Murray G, Leitan ND, Berk M, Thomas N, Michalak E, Berk L, Johnson SL, Jones S, Perich T, Allen NB, Kyrios M
OBJECTIVES: People in the late stage of bipolar disorder (BD) experience elevated relapse rates and poorer quality of life (QoL) compared with those in the early stages. Existing psychological interventions also appear less effective in this group. To address this need, we developed a new online mindfulness-based intervention targeting quality of life (QoL) in late stage BD. Here, we report on an open pilot trial of ORBIT (online, recovery-focused, bipolar individual therapy).
METHODS: Inclusion criteria were: self-reported primary diagnosis of BD, six or more episodes of BD, under the care of a medical practitioner, access to the internet, proficient in English, 18-65 years of age. Primary outcome was change (baseline - post-treatment) on the Brief QoL.BD (Michalak and Murray, 2010). Secondary outcomes were depression, anxiety, and stress measured on the DASS scales (Lovibond and Lovibond, 1993).
RESULTS: Twenty-six people consented to participate (Age M=46.6 years, SD=12.9, and 75% female). Ten participants were lost to follow-up (38.5% attrition). Statistically significant improvement in QoL was found for the completers, t(15)=2.88, 95% CI:.89-5.98, p=.011, (Cohen?s dz=.72, partial ?(2)=.36), and the intent-to-treat sample t(25)=2.65, 95% CI:.47-3.76, (Cohen?s dz=.52; partial ?(2)=.22). A non-significant trend towards improvement was found on the DASS anxiety scale (p=.06) in both completer and intent-to-treat samples, but change on depression and stress did not approach significance.
LIMITATIONS: This was an open trial with no comparison group, so measured improvements may not be due to specific elements of the intervention. Structured diagnostic assessments were not conducted, and interpretation of effectiveness was limited by substantial attrition.
CONCLUSION: Online delivery of mindfulness-based psychological therapy for late stage BD appears feasible and effective, and ORBIT warrants full development. Modifications suggested by the pilot study include increasing the 3 weeks duration of the intervention, adding cautions about the impact of extended meditations, and addition of coaching support/monitoring to optimise engagement.
PMID: 25795535 [PubMed - as supplied by publisher]
A Nation-Wide Study on the Percentage of Schizophrenia and Bipolar Disorder Patients Who Earn Minimum Wage or Above.
Schizophr Bull. 2015 Mar 20;
Authors: Davidson M, Kapara O, Goldberg S, Yoffe R, Noy S, Weiser M
OBJECTIVE: Although it is undisputable that patients with severe mental illness have impaired ability to work, the extent of this is unclear. This is a nation-wide, cross-sectional survey of patients who have been hospitalized with severe mental illness earning minimum wage or above.
METHOD: Data from the Israeli Psychiatric Hospitalization Case Registry were linked with nation-wide data from the National Insurance Institute (the equivalent of US Social Security) on personal income. Hospitalization data were obtained on all consecutive admissions to any psychiatric hospital in the country between 1990-2008 with a diagnosis of schizophrenia, other nonaffective psychotic disorders, or bipolar disorder (N = 35 673). Earning minimum wage or more was defined as earning at least 1000 USD/month, which was equivalent to minimum wage in Israel in December 2010.
RESULTS: The percentages of patients with only 1 admission who were earning minimum wage or above in December 2010 were as follows: 10.6% of patients with a diagnosis of schizophrenia; 21.6% of patients with a diagnosis of nonaffective psychotic disorders; and 24.2% of patients with bipolar disorder. The percentages of patients with multiple admissions who were earning minimum wage or above were as follows: 5.8% of patients with schizophrenia; 11.2% of patients with nonaffective psychotic disorders; and 19.9% of patients with bipolar disorder.
CONCLUSIONS: Despite potential confounders, the results indicate that patients with schizophrenia, nonaffective psychotic disorders, or bipolar disorder have a poor employment outcome, even if they have only been admitted once. These results emphasize the importance of improving interventions to re-integrate these individuals into the work force.
PMID: 25796051 [PubMed - as supplied by publisher]
[Ida Buchmann - "love brings..." in the Gugging Gallery].
Authors: Feilacher J
PMID: 25428528 [PubMed - indexed for MEDLINE]
Collaborative care for patients with bipolar disorder: randomised controlled trial.
Br J Psychiatry. 2015 Mar 19;
Authors: van der Voort TY, van Meijel B, Goossens PJ, Hoogendoorn AW, Draisma S, Beekman A, Kupka RW
Background A substantial number of people with bipolar disorder show a suboptimal response to treatment. Aims To study the effectiveness of a collaborative care programme on symptoms and medication adherence in patients with bipolar disorder, compared with care as usual. Method A two-armed, cluster randomised clinical trial was carried out in 16 out-patient mental health clinics in The Netherlands, in which 138 patients were randomised. Patient outcomes included duration and severity of symptoms and medication adherence, and were measured at baseline, 6 months and 12 months. Collaborative care comprised contracting, psychoeducation, problem-solving treatment, systematic relapse prevention and monitoring of outcomes. Mental health nurses functioned as care managers in this programme. The trial was registered with The Netherlands Trial Registry (NTR2600). Results Collaborative care had a significant and clinically relevant effect on number of months with depressive symptoms, both at 6 months (z = -2.6, P = 0.01, d = 0.5) and at 12 months (z = -3.1, P = 0.002, d = 0.7), as well as on severity of depressive symptoms at 12 months (z = -2.9, P = 0.004, d = 0.4). There was no effect on symptoms of mania or on treatment adherence. Conclusions When compared with treatment as usual, collaborative care substantially reduced the time participants with bipolar disorder experienced depressive symptoms. Also, depressive symptom severity decreased significantly. As persistent depressive symptoms are difficult to treat and contribute to both disability and impaired quality of life in bipolar disorder, collaborative care may be an important form of treatment for people with this disorder.
PMID: 25792695 [PubMed - as supplied by publisher]