Authors: De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM, Koch C, McLachlan R, New M, Rebar R, Singer F, Vinik A, Weickert MO
Thyroid hormones are essential for brain maturation, and for brain function throughout life. In adults, thyroid diseases can lead to various clinical manifestations (1, 2). For example, hypothyroidism causes lethargy, hyporeflexia and poor motor coordination. Subclinical hypothyroidism is often associated with memory impairment. Hypothyroidism is also associated to bipolar affective disorders, depression, or loss of cognitive functions, especially in the elderly (3). Hyperthyroidism causes anxiety, irritability, and hyperreflexia. Both, hypothyroidism or hyperthyroidism can lead to mood disorders, dementia, confusion, and personality changes. Most of these disorders are usually reversible with proper treatment, indicating that thyroid hormone alterations of adult onset do not leave permanent structural defects. The actions of thyroid hormone during development are different, in the sense that they are required to perform certain actions during specific time windows. Thyroid hormone deficiency, even of short duration may lead to irreversible brain damage, the consequences of which depend on the specific timing of onset and duration of thyroid hormone deficiency (4-8). The rat has been the most widely used animal model in the sudy of thyroid physiology and in the actions of thyroid hormone in brain, and the use of gene knock out and knock in mice is providing new insights. When the results of animal studies are extrapolated to the human, it is important to realize that the timing of development in relation to birth among mammals presents substantial differences, even if the sequence of events is similar (9-11). Most brain growth occurs after birth in man and in rodents, but rats and mice are born with a less developed thyroid axis than humans. As a useful reference ?the newborn rat may be compared with a human fetus in the second trimester of pregnancy, and the newborn human baby to a 6-10 day old rat? (12).
The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup: Posttraumatic stress disorder enters the age of large-scale genomic collaboration.
Neuropsychopharmacology. 2015 Apr 23;
Authors: Logue MW, Amstadter AB, Baker DG, Duncan L, Koenen KC, Liberzon I, Miller MW, Morey RA, Nievergelt CM, Ressler KJ, Smith AK, Smoller JW, Stein MB, Sumner JA, Uddin M
The development of posttraumatic stress disorder (PTSD) is influenced by genetic factors. Although there have been some replicated candidates, the identification of risk variants for PTSD has lagged behind genetic research of other psychiatric disorders such as schizophrenia, autism and bipolar disorder. Psychiatric genetics has moved beyond examination of specific candidate genes in favor of the genome-wide association study (GWAS) strategy of very large numbers of samples, which allows for the discovery of previously unsuspected genes and molecular pathways. The successes of genetic studies of schizophrenia and bipolar disorder have been aided by the formation of a large-scale GWAS consortium: the Psychiatric Genomics Consortium (PGC). In contrast, only a handful of GWAS of PTSD have appeared in the literature to date. Here we describe the formation of a group dedicated to large-scale study of PTSD genetics: the PGC-PTSD. The PGC-PTSD faces challenges related to the contingency on trauma exposure and the large degree of ancestral genetic diversity within and across participating studies. Using the PGC analysis pipeline supplemented by analyses tailored to address these challenges, we anticipate that our first large-scale GWAS of PTSD will comprise over 10?000 cases and 30?000 trauma-exposed controls. Following in the footsteps of our PGC forerunners, this collaboration-of a scope that is unprecedented in the field of traumatic stress-will lead the search for replicable genetic associations and new insights into the biological underpinnings of PTSD.Neuropsychopharmacology accepted article preview online, 23 April 2015. doi:10.1038/npp.2015.118.
PMID: 25904361 [PubMed - as supplied by publisher]
Brain Structure in Neuropsychologically Defined Subgroups of Schizophrenia and Psychotic Bipolar Disorder.
Schizophr Bull. 2015 Apr 22;
Authors: Woodward ND, Heckers S
BACKGROUND: Neuropsychological impairment is heterogeneous in psychosis. The association of intracranial volume (ICV) and total brain volume (TBV) with cognition suggests brain structure abnormalities in psychosis will covary with the severity of cognitive impairment. We tested the following hypotheses: (1) brain structure abnormalities will be more extensive in neuropsychologically impaired psychosis patients; (2) psychosis patients with premorbid cognitive limitations will show evidence of hypoplasia (ie, smaller ICV); and (3) psychosis patients with evidence of cognitive decline will demonstrate atrophy (ie, smaller TBV, but normal ICV).
METHODS: One hundred thirty-one individuals with psychosis and 97 healthy subjects underwent structural magnetic resonance imaging and neuropsychological testing. Patients were divided into neuropsychologically normal and impaired groups. Impaired patients were further subdivided into deteriorated and compromised groups if estimated premorbid intellect was average or below average, respectively. ICV and TBV were compared across groups. Localized brain volumes were qualitatively examined using voxel-based morphometry.
RESULTS: Compared to healthy subjects, neuropsychologically impaired patients exhibited smaller TBV, reduced grey matter volume in frontal, temporal, and subcortical brain regions, and widespread white matter volume loss. Neuropsychologically compromised patients had smaller ICV relative to healthy subjects, and neuropsychologically normal and deteriorated patient groups, but relatively normal TBV. Deteriorated patients exhibited smaller TBV compared to healthy subjects, but relatively normal ICV. Unexpectedly, TBV, adjusted for ICV, was reduced in neuropsychologically normal patients.
CONCLUSIONS: Patients with long-standing cognitive limitations exhibit evidence of early cerebral hypoplasia, whereas neuropsychologically normal and deteriorated patients show evidence of brain tissue loss consistent with progression or later cerebral dysmaturation.
PMID: 25904725 [PubMed - as supplied by publisher]
Bipolar disorder comorbid with alcohol use disorder: focus on neurocognitive correlates.
Front Physiol. 2015;6:108
Authors: Balanzá-Martínez V, Crespo-Facorro B, González-Pinto A, Vieta E
Bipolar disorder (BD) and alcohol use disorders (AUDs) are usually comorbid, and both have been associated with significant neurocognitive impairment. Patients with the BD-AUD comorbidity (dual diagnosis) may have more severe neurocognitive deficits than those with a single diagnosis, but there is paucity of research in this area. To explore this hypothesis more thoroughly, we carried out a systematic literature review through January 2015. Eight studies have examined the effect of AUDs on the neurocognitive functioning of BD patients. Most studies found that BD patients with current or past history of comorbid AUDs show more severe impairments, especially in verbal memory and executive cognition, than their non-dual counterparts. Greater neurocognitive dysfunction is another facet of this severe comorbid presentation. Implications for clinical practice and research are discussed. Specifically, the application of holistic approaches, such as clinical staging and systems biology, may open new avenues of discoveries related to the BD-AUD comorbidity.
PMID: 25904869 [PubMed]
ZNF804A Transcriptional Networks in Differentiating Neurons Derived from Induced Pluripotent Stem Cells of Human Origin.
PLoS One. 2015;10(4):e0124597
Authors: Chen J, Lin M, Hrabovsky A, Pedrosa E, Dean J, Jain S, Zheng D, Lachman HM
ZNF804A (Zinc Finger Protein 804A) has been identified as a candidate gene for schizophrenia (SZ), autism spectrum disorders (ASD), and bipolar disorder (BD) in replicated genome wide association studies (GWAS) and by copy number variation (CNV) analysis. Although its function has not been well-characterized, ZNF804A contains a C2H2-type zinc-finger domain, suggesting that it has DNA binding properties, and consequently, a role in regulating gene expression. To further explore the role of ZNF804A on gene expression and its downstream targets, we used a gene knockdown (KD) approach to reduce its expression in neural progenitor cells (NPCs) derived from induced pluripotent stem cells (iPSCs). KD was accomplished by RNA interference (RNAi) using lentiviral particles containing shRNAs that target ZNF804A mRNA. Stable transduced NPC lines were generated after puromycin selection. A control cell line expressing a random (scrambled) shRNA was also generated. Neuronal differentiation was induced, RNA was harvested after 14 days and transcriptome analysis was carried out using RNA-seq. 1815 genes were found to be differentially expressed at a nominally significant level (p<0.05); 809 decreased in expression in the KD samples, while 1106 increased. Of these, 370 achieved genome wide significance (FDR<0.05); 125 were lower in the KD samples, 245 were higher. Pathway analysis showed that genes involved in interferon-signaling were enriched among those that were down-regulated in the KD samples. Correspondingly, ZNF804A KD was found to affect interferon-alpha 2 (IFNA2)-mediated gene expression. The findings suggest that ZNF804A may affect a differentiating neuron's response to inflammatory cytokines, which is consistent with models of SZ and ASD that support a role for infectious disease, and/or autoimmunity in a subgroup of patients.
PMID: 25905630 [PubMed - as supplied by publisher]
Value of subthalamic nucleus local field potentials recordings in predicting stimulation parameters for deep brain stimulation in Parkinson's disease.
J Neurol Neurosurg Psychiatry. 2010 Aug;81(8):885-9
Authors: Yoshida F, Martinez-Torres I, Pogosyan A, Holl E, Petersen E, Chen CC, Foltynie T, Limousin P, Zrinzo LU, Hariz MI, Brown P
OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can be a highly effective treatment for Parkinson's disease. However, therapeutic efficacy can be limited by inconsistent targeting of this nucleus. It was shown previously that an increase in local field potential (LFP) power over the beta frequency band may provide intraoperative confirmation of STN targeting. Whether the depth of this focal increase also helps predict the depth and voltage chosen for chronic stimulation is tested here.
METHODS: LFPs were recorded from the contacts of 57 DBS electrodes as the latter were advanced in 2 mm steps from above to below the intended surgical target point in STN.
RESULTS: A spectral peak in the bipolar LFP was recorded in the 11-35 Hz band at the lowest contact pair that underwent a steep but focal change during electrode descent in all but three sides. The depth of the initial intraoperative step increase in beta correlated with the depth of the contact independently chosen for chronic DBS (Spearman's rho=0.35, p=0.01). In addition, the absolute difference between the depths of the initial increase in beta and the contact chosen for chronic DBS correlated with the voltage used for chronic stimulation (rho=0.322, p=0.017). Thus more voltage had to be employed if a depth was selected for chronic stimulation that differed from that of the beta generator.
CONCLUSIONS: Online spectral analysis of LFPs recorded from the DBS electrode may help identify the optimal therapeutic target in the STN region for DBS.
PMID: 20466699 [PubMed - indexed for MEDLINE]
Allelic imbalance associated with the schizophrenia risk SNP rs1344706 indicates a cis-acting variant in ZNF804A.
Schizophr Res. 2014 Mar;153(1-3):243-5
Authors: Guella I, Vawter MP
PMID: 24462263 [PubMed - indexed for MEDLINE]
Manic episode induced by steroid (fluorometholone) eye drops in an elderly patient.
Psychiatry Clin Neurosci. 2014 Aug;68(8):652-3
Authors: Kumagai R, Ichimiya Y
PMID: 24649914 [PubMed - indexed for MEDLINE]
Aggravation of hypertriglyceridemia and acute pancreatitis in a bipolar patient treated with quetiapine.
Yonsei Med J. 2014 May;55(3):831-3
Authors: Liou LS, Hung YJ, Hsieh CH, Hsiao FC
Pancreatitis is a very rare adverse effect of quetiapine treatment, with only 5 cases of quetiapine-associated pancreatitis reported in the English literature to date. Herein, we report one patient who developed severe hypertriglyceridemia (>1000 mg/dL) after quetiapine administration, resulting in acute pancreatitis. An analysis of the underlying pathogenic mechanisms and a review of relevant literature are also presented. Clinicians should be aware of the potentially life-threatening metabolic disturbances and/or pancreatitis associated with quetiapine therapy.
PMID: 24719155 [PubMed - indexed for MEDLINE]
Preclinical modeling of primal emotional affects (Seeking, Panic and Play): gateways to the development of new treatments for depression.
Authors: Panksepp J, Yovell Y
Mammalian brains contain at least 7 primal emotional systems--Seeking, Rage, Fear, Lust, Care, Panic and Play (capitalization reflects a proposed primary-process terminology, to minimize semantic confusions and mereological fallacies). These systems help organisms feel affectively balanced (e.g. euthymic) and unbalanced (e.g. depressive, irritable, manic), providing novel insights for understanding human psychopathologies. Three systems are especially important for understanding depression: The separation distress (Panic) system mediates the psychic pain of separation distress (i.e. excessive sadness and grief), which can be counteracted by minimizing Panic arousals (as with low-dose opioids). Depressive dysphoria also arises from reduced brain reward-seeking and related play urges (namely diminished enthusiasm (Seeking) and joyful exuberance (Play) which promote sustained amotivational states). We describe how an understanding of these fundamental emotional circuits can promote the development of novel antidepressive therapeutics--(i) low-dose buprenorphine to counteract depression and suicidal ideation emanating from too much psychic pain (Panic overarousal), (ii) direct stimulation of the Seeking system to counteract amotivational dysphoria, and (iii) the discovery and initial clinical testing of social-joy-promoting molecules derived from the analysis of the Play system.
PMID: 25341411 [PubMed - indexed for MEDLINE]
Characterization of lithium coordination sites with magic-angle spinning NMR.
J Magn Reson. 2015 Feb 14;254:131-138
Authors: Haimovich A, Goldbourt A
Lithium, in the form of lithium carbonate, is one of the most common drugs for bipolar disorder. Lithium is also considered to have an effect on many other cellular processes hence it possesses additional therapeutic as well as side effects. In order to quantitatively characterize the binding mode of lithium, it is required to identify the interacting species and measure their distances from the metal center. Here we use magic-angle spinning (MAS) solid-state NMR to study the binding site of lithium in complex with glycine and water (LiGlyW). Such a compound is a good enzyme mimetic since lithium is four-coordinated to one water molecule and three carboxylic groups. Distance measurements to carbons are performed using a 2D transferred echo double resonance (TEDOR) MAS solid-state NMR experiment, and water binding is probed by heteronuclear high-resolution proton-lithium and proton-carbon correlation (wPMLG-HETCOR) experiments. Both HETCOR experiments separate the main complex from impurities and non-specifically bound lithium species, demonstrating the sensitivity of the method to probe the species in the binding site. Optimizations of the TEDOR pulse scheme in the case of a quadrupolar nucleus with a small quadrupole coupling constant show that it is most efficient when pulses are positioned on the spin-1/2 (carbon-13) nucleus. Since the intensity of the TEDOR signal is not normalized, careful data analysis that considers both intensity and dipolar oscillations has to be performed. Nevertheless we show that accurate distances can be extracted for both carbons of the bound glycine and that these distances are consistent with the X-ray data and with lithium in a tetrahedral environment. The lithium environment in the complex is very similar to the binding site in inositol monophosphatase, an enzyme associated with bipolar disorder and the putative target for lithium therapy. A 2D TEDOR experiment applied to the bacterial SuhB gene product of this enzyme was designed to probe direct correlations between lithium, the enzyme inhibitor, and the closest carboxyl carbons of the binding site. At this point, the chemical shift of the bound carboxyl groups in this 29kDa enzyme could be determined.
PMID: 25899290 [PubMed - as supplied by publisher]
Bipolar disorder with comorbid attention-deficit and hyperactivity disorder. Main clinical features and clues for an accurate diagnosis.
Acta Psychiatr Scand. 2015 Apr 20;
Authors: Torres I, Gómez N, Colom F, Jiménez E, Bosch R, Bonnín CM, Martínez-Aran A, Casas M, Vieta E, Ramos-Quiroga JA, Goikolea JM
OBJECTIVE: To study the prevalence of attention-deficit and hyperactivity disorder (ADHD) in adult patients with bipolar disorder (BD) and identify differential clinical features for a better diagnosis.
METHOD: A total of 163 euthymic bipolar out-patients were screened for ADHD with the ASRS.V1 and the WURS at a BD Unit. Patients with a positive screening were assessed with the CAADID, at an ADHD unit. Sociodemographic and clinical features of the groups with and without ADHD were compared.
RESULTS: Lifetime prevalence of comorbid ADHD was 17.9% (10.5% for adult ADHD and 7.4% for childhood ADHD). The BD + ADHD group showed more suicidal behaviour although less severe. Comorbidity was also more common, especially regarding substance use disorders. Nevertheless, these patients did not show more affective episodes or hospitalizations and suffered more atypical but less melancholic depression. However, they required more treatment with psychotherapy and valproate. One-third of positive screenings at the ASRS were false; a severe course of BD was the hallmark of this subgroup.
CONCLUSION: Adult patients with BD and ADHD show differential clinical features, but not a more severe course of BD. Comorbidity with substance abuse is a big issue, deserving special clinical attention. Better screening tools are necessary to avoid overdiagnosis of comorbid ADHD in BD.
PMID: 25900393 [PubMed - as supplied by publisher]
Subjective experience of coercion in psychiatric care: a study comparing the attitudes of patients and healthy volunteers towards coercive methods and their justification.
Eur Arch Psychiatry Clin Neurosci. 2015 Apr 22;
Authors: Mielau J, Altunbay J, Gallinat J, Heinz A, Bermpohl F, Lehmann A, Montag C
Under certain conditions, coercive interventions in psychotic patients can help to regain insight and alleviate symptoms, but can also traumatize subjects. This study explored attitudes towards psychiatric coercive interventions in healthy individuals and persons suffering from schizophrenia, schizoaffective or bipolar disorder. The impact of personal history of coercive treatment on preferences concerning clinical management of patients unable to consent was investigated. Six case vignettes depicting scenarios of ethical dilemmas and demanding decisions in favour of or against coercive interventions were presented to 60 healthy volunteers and 90 patients. Structured interviews focusing on experienced coercion were performed in conjunction with the Coercion Experience Scale and the Admission Experience Survey. Symptom severity, psychosocial functioning and insight into illness were assessed as influencing variables. Student's t tests compared patients' and controls' judgments, followed by regression analyses to define the predictive value of symptoms and measures of coercion on judgments regarding the total patient sample and patients with experience of fixation. Patients and non-psychiatric controls showed no significant difference in their attitudes towards involuntary admission and forced medication. Conversely, patients more than controls significantly disapproved of mechanical restraint. Subjective experience of coercive interventions played an important role for the justification of treatment against an individual's "natural will". Factors influencing judgments on coercion were overall functioning and personal experience of treatment effectiveness and fairness. Qualitative and quantitative aspects of perceived coercion, in addition to insight into illness, predicted judgments of previously fixated patients. Results underline the importance of the quality of practical implementation and care, if coercive interventions cannot be avoided.
PMID: 25900468 [PubMed - as supplied by publisher]
Classification and neurobiological concepts of mania, bipolar disorder and major depression.
Eur Arch Psychiatry Clin Neurosci. 2015 Apr 22;
Authors: Schmitt A, Falkai P
PMID: 25900469 [PubMed - as supplied by publisher]
Increased cardiometabolic dysfunction in first-degree relatives of patients with psychotic disorders.
Schizophr Res. 2015 Apr 18;
Authors: Mothi SS, Tandon N, Padmanabhan J, Mathew IT, Clementz B, Tamminga C, Pearlson G, Sweeney J, Keshavan MS
INTRODUCTION: Elevated prevalence of comorbid cardio-vascular and metabolic dysfunction (CMD) is consistently reported in patients with severe psychotic disorders such as schizophrenia (SZ), schizoaffective (SZA) and bipolar disorder (BP-P). Since both psychosis and CMD are substantively heritable in nature, we attempted to investigate the occurrence of CMD disorders in first-degree relatives of probands with psychosis.
METHODS: Our sample included 861 probands with a diagnosis of SZ (n=354), SZA (n=212) and BP-P (n=295), 776 first-degree relatives of probands and 416 healthy controls. Logistic regression was used to compare prevalence of any CMD disorders (diabetes, hypertension, hyperlipidemia or coronary artery disease) across groups. Post hoc tests of independence checked for CMD prevalence across psychosis diagnosis (SZ, SZA and BP-P), both in relatives of probands and within probands themselves.
RESULTS: After controlling for potential confounders, first-degree relatives with (p<0.001) and without (p=0.03) Axis I non-psychotic or Axis- II cluster disorders were at a significant risk for CMD compared to controls. No significant difference (p=0.42) was observed in prevalence of CMD between relatives of SZ, SZA and BP-P, or between psychosis diagnoses for probands (p=0.25).
DISCUSSION: Prevalence of CMD was increased in the first-degree relatives of psychosis subjects. This finding suggests the possibility of overlapping genetic contributions to CMD and psychosis. Increased somatic disease burden in relatives of psychotic disorder probands points to need for early detection and preventive efforts in this population.
PMID: 25900543 [PubMed - as supplied by publisher]
Conducting qualitative research in mental health: Thematic and content analyses.
Aust N Z J Psychiatry. 2015 Apr 21;
Authors: Crowe M, Inder M, Porter R
OBJECTIVE: The objective of this paper is to describe two methods of qualitative analysis - thematic analysis and content analysis - and to examine their use in a mental health context.
METHOD: A description of the processes of thematic analysis and content analysis is provided. These processes are then illustrated by conducting two analyses of the same qualitative data. Transcripts of qualitative interviews are analysed using each method to illustrate these processes.
RESULTS: The illustration of the processes highlights the different outcomes from the same set of data.
CONCLUSION: Thematic and content analyses are qualitative methods that serve different research purposes. Thematic analysis provides an interpretation of participants' meanings, while content analysis is a direct representation of participants' responses. These methods provide two ways of understanding meanings and experiences and provide important knowledge in a mental health context.
PMID: 25900973 [PubMed - as supplied by publisher]
Rapid-onset adult respiratory distress syndrome after activated charcoal aspiration. A pitch-black tale of a potential to kill.
Am J Respir Crit Care Med. 2015 Feb 1;191(3):344-5
Authors: De Weerdt A, Snoeckx A, Germonpré P, Jorens PG
PMID: 25635491 [PubMed - indexed for MEDLINE]
Voxel-Based Meta-Analytical Evidence of Structural Disconnectivity in Major Depression and Bipolar Disorder.
Biol Psychiatry. 2015 Mar 12;
Authors: Wise T, Radua J, Nortje G, Cleare AJ, Young AH, Arnone D
BACKGROUND: Identification of white matter microstructure differences and similarities between major depression and bipolar disorder is a necessary step to better understand the underlying brain abnormalities in affective disorders and target more effective treatments. However, research has not yet yielded robust conclusions. We report here a meta-analysis of diffusion tensor imaging studies in these conditions.
METHODS: A comprehensive literature search was conducted up to 2014 to identify studies comparing fractional anisotropy (FA) between patients and control subjects. Results were combined to identify white matter abnormalities in major depression (736 patients vs. 668 control subjects) and bipolar disorder (536 patients vs. 489 control subjects). Effect size comparison and conjunction analysis allowed identification of similarities and differences between the disorders.
RESULTS: A significant decrease in FA in the genu of the corpus callosum characterized both conditions. The comparison between unipolar and bipolar disorders revealed a greater decrease in FA in the left posterior cingulum in bipolar disorder. Studies that adopted tract-based spatial statistics methodology showed more pronounced reductions in these regions compared with voxel-based analyses.
CONCLUSIONS: Major depression and bipolar disorder are characterized by abnormalities in white matter tracts of the genu of the corpus callosum that connect the two hemispheres of the prefrontal cortex implicated in mood regulation. Bipolar disorder was associated with reduced white matter integrity in the left posterior cingulum, which may contribute to cognitive impairment described in this condition. Tract-based spatial statistics may be a more sensitive technique to detect white matter abnormalities in these regions compared with voxel-based analyses.
PMID: 25891219 [PubMed - as supplied by publisher]
Damage-associated molecular patterns and immune activation in bipolar disorder.
Acta Psychiatr Scand. 2015 Apr 16;
Authors: Stertz L, Fries GR, Rosa AR, Kauer-Sant'anna M, Ferrari P, Paz AV, Green C, Cunha ÂB, Dal-Pizzol F, Gottfried C, Kapczinski F
OBJECTIVE: Immune activation in bipolar disorder (BD) has been frequently reported. Damage-associated molecular patterns (DAMPs) are key players in the immune activation reaction. The aim of this study was to assess DAMP levels in drug-free patients with BD during acute episodes.
METHOD: Serum levels of a predetermined set of DAMPs were assessed in drug-free patients with BD (n = 20) during an acute mood episode. We also included two control groups: healthy subjects, used as a negative control (n = 20); and patients with sepsis, used as a positive control for severe immune activation (n = 20).
RESULTS: Multivariate analysis using generalized linear mixed model indicated that all DAMPs differed as a function of group membership after controlling for age and addressing multiplicity (P < 0.0006 for all comparisons). Follow-up analyses showed higher levels in BD subjects of circulating cell-free (ccf) nuclear (n)DNA (P = 0.02), HSP70 (P = 0.03) and HSP90? (P = 0.02) as compared to healthy subjects. Also, patients with BD showed lower levels of ccf nDNA (P = 0.04), HSP60 (P = 0.03), HSP70 (P = 0.01), and HSP90? (P = 0.002) as compared to patients with sepsis and higher levels of ccf mitochondrial DNA (P < 0.0001).
CONCLUSION: The present findings may be linked to the inflammatory activity previously described among patients with BD and may help in the development of more targeted and personalized treatments for patients under acute episodes of BD.
PMID: 25891376 [PubMed - as supplied by publisher]
Synthetic and Natural Inhibitors of Phospholipases A2: Their Importance for Understanding and Treatment of Neurological Disorders.
ACS Chem Neurosci. 2015 Apr 18;
Authors: Ong WY, Farooqui T, Kokotos G, Farooqui AA
Phospholipases A2 (PLA2) are a diverse group of enzymes that hydrolyze membrane phospholipids into arachidonic acid and lysophospholipids. Arachidonic acid is metabolized to eicosanoids (prostaglandins, leukotrienes, thromboxanes) and lysophospholipids are converted to platelet-activating factors. These lipid mediators play critical roles in the initiation, maintenance and modulation of neuroinflammation and oxidative stress. Neurological disorders including excitotoxicity; traumatic nerve and brain injury; cerebral ischemia; Alzheimer's disease; Parkinson's disease; multiple sclerosis; experimental allergic encephalitis; pain; depression; bipolar disorder; schizophrenia and autism are characterized by oxidative stress, inflammatory reactions, alterations in phospholipid metabolism, accumulation of lipid peroxides, and increased activities of PLA2 isoforms. Several old and new synthetic inhibitors of PLA2, including fatty acid trifluoromethyl ketones; methyl arachidonyl fluorophosphonate; bromoenol lactone; indole-based inhibitors; pyrrolidine-based inhibitors; amide inhibitors, 2-oxoamides; 1,3-disubstituted propan-2-ones and polyfluoroalkyl ketones; as well as phytochemical based PLA2 inhibitors including curcumin, Ginkgo biloba and Centella Asiatica extracts have been discovered, and used for the treatment of neurological disorders in cell culture and animal model systems. The purpose of this review is to summarize information on selective and potent synthetic inhibitors of PLA2 as well as several PLA2 inhibitors from plants, for treatment of oxidative stress and neuroinflammation associated with the pathogenesis of neurological disorders.
PMID: 25891385 [PubMed - as supplied by publisher]
[Mental Disorder and Partnership: the Influence and Potential Burden of Affective Disorders on the Quality of Partnerships].
Psychiatr Prax. 2015 Apr 17;
Authors: Wieser E, Richter-Schmiedinger T, Glückler C, Schmidt A, Volkert J, Reif A, Kornhuber J, Biermann T
Aim: The aim of the present study was to explore the connection between affective disorders and various aspects of the quality of relationships and their impact on partnerships. Methods: In a multi-centric study, we used questionnaires to compare three groups of couples: 23 patients suffering from major depression and their partners, 32 patients with a bipolar disorder and their partners, and 49 healthy couples serving as controls. Results: Regardless of the type of affective disorders, stability of the relationship, felt happiness and other measures of quality of partnership were significantly impaired in couples with an affected partner. Partners of patients experience a higher emotional strain in every day life compared to healthy controls. There was a trend showing that bipolar disorder leads to a greater burden and a higher conflict potential than depression. Discussion: The present study deals with stabile partnerships in daily life, including severely disabled patients needing in-patient treatment. Taking into account the health status of their partners, we discuss various aspects of happiness, conflict potentials as well as impact on the quality of relationships.
PMID: 25891886 [PubMed - as supplied by publisher]
Increased risk of hyperlipidemia in patients with bipolar disorder: a population-based study.
Gen Hosp Psychiatry. 2015 Apr 8;
Authors: Hsu JH, Chien IC, Lin CH
OBJECTIVE: We conducted this nationwide study to examine the epidemiology of hyperlipidemia among Taiwanese patients with bipolar disorder.
METHODS: We used a random sample of 766,427 subjects who were ?18 years old in 2005. Subjects with at least one primary diagnosis of bipolar disorder were identified. Individuals with a primary or secondary diagnosis of hyperlipidemia or medication treatment for hyperlipidemia were also identified. We compared the prevalence of hyperlipidemia in patients with bipolar disorder with the general population in 2005. Furthermore, we investigated this cohort from 2006 to 2010 to detect the incident cases of hyperlipidemia.
RESULTS: The prevalence of hyperlipidemia in patients with bipolar disorder was higher than that of the general population [13.5% vs. 7.9%; odds ratio, 1.75; 95% confidence interval (CI), 1.52-2.02] in 2005. The average annual incidence of hyperlipidemia in patients with bipolar disorder was also higher than that of the general population (4.37% vs. 2.55%; risk ratio, 1.66; 95% CI, 1.47-1.87) from 2006 to 2010.
CONCLUSIONS: Patients with bipolar disorder had a higher prevalence and incidence of hyperlipidemia compared with the general population. Patients with bipolar disorder coexisting hypertension exhibited a higher likelihood of hyperlipidemia.
PMID: 25892153 [PubMed - as supplied by publisher]
Differentiating risk for mania and borderline personality disorder: The nature of goal regulation and impulsivity.
Psychiatry Res. 2015 Feb 7;
Authors: Fulford D, Eisner LR, Johnson SL
Researchers and clinicians have long noted the overlap among features and high comorbidity of bipolar disorder and borderline personality disorder. The shared features of impulsivity and labile mood in both disorders make them challenging to distinguish. We tested the hypothesis that variables related to goal dysregulation would be uniquely related to risk for mania, while emotion-relevant impulsivity would be related to risk for both disorders. We administered a broad range of measures related to goal regulation traits and impulsivity to 214 undergraduates. Findings confirmed that risk for mania, but not for borderline personality disorder, was related to higher sensitivity to reward and intense pursuit of goals. In contrast, borderline personality disorder symptoms related more strongly than did mania risk with threat sensitivity and with impulsivity in the context of negative affect. Results highlight potential differences and commonalities in mania risk versus borderline personality disorder risk.
PMID: 25892256 [PubMed - as supplied by publisher]
Is childhood cat ownership a risk factor for schizophrenia later in life?
Schizophr Res. 2015 Apr 17;
Authors: Fuller Torrey E, Simmons W, Yolken RH
Two previous studies suggested that childhood cat ownership is a possible risk factor for later developing schizophrenia or other serious mental illness. We therefore used an earlier, large NAMI questionnaire to try and replicate this finding. The results were the same, suggesting that cat ownership in childhood is significantly more common in families in which the child later becomes seriously mentally ill. If true, an explanatory mechanism may be Toxoplasma gondii. We urge our colleagues to try and replicate these findings to clarify whether childhood cat ownership is truly a risk factor for later schizophrenia.
PMID: 25892720 [PubMed - as supplied by publisher]
Cognitive Styles in Mood Disorders: Discriminative Ability of Unipolar and Bipolar Cognitive Profiles.
Int J Cogn Ther. 2015 Mar;8(1):35-60
Authors: Shapero BG, Stange JP, Goldstein KE, Black CL, Molz AR, Hamlat EJ, Black SK, Boccia AS, Abramson LY, Alloy LB
Although previous research has identified cognitive styles that distinguish individuals with bipolar disorder (BD), individuals with major depressive disorder (MDD), and individuals without mood disorders from one another, findings have been inconsistent. The current study included 381 participants classified into a BD group, a MDD group, and a no mood disorder group. To differentiate between these groups, this study evaluated cognitive styles with a battery of traditional and more recently-developed measures. Receiver operating characteristics (ROC) analyses were used to determine the discriminate ability of variables with significant between group differences. Results supported that BD and MDD may be characterized by distinct cognitive styles. Given work showing that interventions for MDD may not be effective at treating BD, it is important to directly compare individuals with these disorders. By clarifying the overlapping and divergent cognitive styles characterizing BD and MDD, research can not only improve diagnostic validity, but also provide more efficacious and effective interventions.
PMID: 25893033 [PubMed - as supplied by publisher]
Improving the Recognition of Borderline Personality Disorder in a Bipolar World.
J Pers Disord. 2015 Apr 20;:1-16
Authors: Zimmerman M
Both bipolar disorder and borderline personality disorder (BPD) are serious mental health disorders resulting in significant psychosocial morbidity, reduced health-related quality of life, and excess mortality. Yet research on BPD has received much less funding from the National Institute of Health (NIH) than has bipolar disorder during the past 25 years. Why hasn't the level of NIH research funding for BPD been commensurate with the level of psychosocial morbidity, mortality, and health expenditures associated with the disorder? In the present article, the author illustrates how the bipolar disorder research community has done a superior job of "marketing" their disorder. Studies of underdiagnosis, screening, diagnostic spectra, and economics are reviewed for both bipolar disorder and BPD. Researchers of bipolar disorder have conducted multiple studies highlighting the problem with underdiagnosis, developed and promoted several screening scales, published numerous studies of the operating characteristics of these screening measures, attempted to broaden the definition of bipolar disorder by advancing the concept of the bipolar spectrum, and repeatedly demonstrated the economic costs and public health significance of bipolar disorder. In contrast, researchers of BPD have almost completely ignored each of these four issues and research efforts. Although BPD is as frequent as (if not more frequent than) bipolar disorder, as impairing as (if not more impairing than) bipolar disorder, and as lethal as (if not more lethal than) bipolar disorder, it has received less than one-tenth the level of funding from the NIH and has been the focus of many fewer publications in the most prestigious psychiatric journals. The researchers of BPD should consider adopting the strategy taken by researchers of bipolar disorder before the diagnosis is eliminated in a future iteration of the DSM or the ICD.
PMID: 25893554 [PubMed - as supplied by publisher]
Predicting Psychosis Across Diagnostic Boundaries: Behavioral and Computational Modeling Evidence for Impaired Reinforcement Learning in Schizophrenia and Bipolar Disorder With a History of Psychosis.
J Abnorm Psychol. 2015 Apr 20;
Authors: Strauss GP, Thaler NS, Matveeva TM, Vogel SJ, Sutton GP, Lee BG, Allen DN
There is increasing evidence that schizophrenia (SZ) and bipolar disorder (BD) share a number of cognitive, neurobiological, and genetic markers. Shared features may be most prevalent among SZ and BD with a history of psychosis. This study extended this literature by examining reinforcement learning (RL) performance in individuals with SZ (n = 29), BD with a history of psychosis (BD+; n = 24), BD without a history of psychosis (BD-; n = 23), and healthy controls (HC; n = 24). RL was assessed through a probabilistic stimulus selection task with acquisition and test phases. Computational modeling evaluated competing accounts of the data. Each participant's trial-by-trial decision-making behavior was fit to 3 computational models of RL: (a) a standard actor-critic model simulating pure basal ganglia-dependent learning, (b) a pure Q-learning model simulating action selection as a function of learned expected reward value, and (c) a hybrid model where an actor-critic is "augmented" by a Q-learning component, meant to capture the top-down influence of orbitofrontal cortex value representations on the striatum. The SZ group demonstrated greater reinforcement learning impairments at acquisition and test phases than the BD+, BD-, and HC groups. The BD+ and BD- groups displayed comparable performance at acquisition and test phases. Collapsing across diagnostic categories, greater severity of current psychosis was associated with poorer acquisition of the most rewarding stimuli as well as poor go/no-go learning at test. Model fits revealed that reinforcement learning in SZ was best characterized by a pure actor-critic model where learning is driven by prediction error signaling alone. In contrast, BD-, BD+, and HC were best fit by a hybrid model where prediction errors are influenced by top-down expected value representations that guide decision making. These findings suggest that abnormalities in the reward system are more prominent in SZ than BD; however, current psychotic symptoms may be associated with reinforcement learning deficits regardless of a Diagnostic and Statistical Manual of Mental Disorders (5th Edition; American Psychiatric Association, 2013) diagnosis. (PsycINFO Database Record
PMID: 25894442 [PubMed - as supplied by publisher]
Effects of Mood Stabilizers on Brain Energy Metabolism in Mice Submitted to an Animal Model of Mania Induced by Paradoxical Sleep Deprivation.
Neurochem Res. 2015 Apr 17;
Authors: Streck EL, Scaini G, Jeremias GC, Rezin GT, Gonçalves CL, Ferreira GK, Réus GZ, Resende WR, Valvassori SS, Kapczinski F, Andersen ML, Quevedo J
There is a body of evidence suggesting that mitochondrial dysfunction is involved in bipolar disorder (BD) pathogenesis. Studies suggest that abnormalities in circadian cycles are involved in the pathophysiology of affective disorders; paradoxical sleep deprivation (PSD) induces hyperlocomotion in mice. Thus, the present study aims to investigate the effects of lithium (Li) and valproate (VPA) in an animal model of mania induced by PSD for 96 h. PSD increased exploratory activity, and mood stabilizers prevented PSD-induced behavioral effects. PSD also induced a significant decrease in the activity of complex II-III in hippocampus and striatum; complex IV activity was decreased in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex. Additionally, VPA administration was able to prevent PSD-induced inhibition of complex II-III and IV activities in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex, whereas Li administration prevented PSD-induced inhibition only in prefrontal cortex and hippocampus. Regarding the enzymes of Krebs cycle, only citrate synthase activity was increased by PSD in prefrontal cortex. We also found a similar effect in creatine kinase, an important enzyme that acts in the buffering of ATP levels in brain; its activity was increased in prefrontal cortex, hippocampus and cerebral cortex. These results are consistent with the connection of mitochondrial dysfunction and hyperactivity in BD and suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.
PMID: 25894682 [PubMed - as supplied by publisher]
Alterations of Glucocorticoid Receptor Gene Methylation in Externalizing Disorders During Childhood and Adolescence.
Behav Genet. 2015 Apr 18;
Authors: Heinrich A, Buchmann AF, Zohsel K, Dukal H, Frank J, Treutlein J, Nieratschker V, Witt SH, Brandeis D, Schmidt MH, Esser G, Banaschewski T, Laucht M, Rietschel M
Epigenetic modulations are a hypothesized link between environmental factors and the development of psychiatric disorders. Research has suggested that patients with depression or bipolar disorder exhibit higher methylation levels in the glucocorticoid receptor gene NR3C1. We aimed to investigate whether NR3C1 methylation changes are similarly associated with externalizing disorders such as aggressive behavior and conduct disorder. NR3C1 exon 1F methylation was analyzed in young adults with a lifetime diagnosis of an externalizing disorder (N = 68) or a depressive disorder (N = 27) and healthy controls (N = 124) from the Mannheim Study of Children at Risk. The externalizing disorders group had significantly lower NR3C1 methylation levels than the lifetime depressive disorder group (p = 0.009) and healthy controls (p = 0.001) This report of lower methylation levels in NR3C1 in externalizing disorders may indicate a mechanism through which the differential development of externalizing disorders as opposed to depressive disorders might occur.
PMID: 25894927 [PubMed - as supplied by publisher]
Treatment delay is associated with more episodes and more severe illness staging progression in patients with bipolar disorder.
Psychiatry Res. 2015 Apr 9;
Authors: Goi PD, Vianna-Sulzbach M, Silveira L, Grande I, Chendo I, Sodré LA, Ceresér KM, Rosa AR, Kunz M, Kauer-Sant?Anna M, Massuda R, Kapczinski F, Gama CS
PMID: 25895487 [PubMed - as supplied by publisher]