Psychiatr Hung. 2016;31(1):1
Authors: Tamás T, Sándor F
PMID: 27294227 [PubMed - indexed for MEDLINE]
Neurodevelopmental Disorders or Early Death in Siblings of Children With Cerebral Palsy.
Pediatrics. 2016 Jul 21;
Authors: Tollånes MC, Wilcox AJ, Stoltenberg C, Lie RT, Moster D
OBJECTIVES: To explore the presence of shared underlying causes of cerebral palsy (CP) and other neurodevelopmental disorders, by examining risks of other disorders in siblings of children with CP.
METHODS: We used Norwegian national registries to identify 1.4 million pairs of full siblings (singletons) and 28?000 sets of twins born from 1967 to 2006, identify stillbirths and neonatal deaths, and find individuals with CP, epilepsy, intellectual disability, autism spectrum disorders, attention-deficit/hyperactivity disorder, blindness, deafness, schizophrenia, and bipolar disorder. Associations between CP in 1 sibling and neurodevelopmental disorders or early death in other siblings were estimated using logistic regression models.
RESULTS: There were 5707 neonatal survivors (beyond 28 days) with CP (2.5/1000). These children had substantial comorbidity (eg, 29% had epilepsy). Singleton siblings of (singleton) children with CP had increased risks of neurodevelopmental problems, including epilepsy (odds ratio [OR], 1.8 [95% confidence interval (CI), 1.5-2.5]), intellectual disability (OR, 2.3 [95% CI, 1.8-2.9]), autism spectrum disorders (OR, 1.6 [95% CI, 1.1-2.2]), attention-deficit/hyperactivity disorder (OR 1.3 [95% CI, 1.1-1.6]), blindness (OR 2.4 [95% CI, 1.1-5.4]), and schizophrenia (OR 2.0 [95% CI, 1.2-3.2]). There was no increase in risk of bipolar disorder (OR 1.0 [95% CI, 0.6-1.6]). Families with children with CP also had increased risk of losing another child in the perinatal period (stillbirth OR, 1.8 [95% CI, 1.5- 2.3]; neonatal death OR, 1.7 [95% CI, 1.3-2.2]). Associations were stronger within sets of twins.
CONCLUSIONS: Siblings of a child with CP were at increased risk for a variety of other neurodevelopmental morbidities, as well as early death, indicating the presence of shared underlying causes.
PMID: 27443356 [PubMed - as supplied by publisher]
Interaction between dorsal hippocampal NMDA receptors and lithium on spatial learning consolidation in rats.
Brain Res Bull. 2016 Jul 18;
Authors: Parsaeia L, Torkaman-Boutorabi A, Asadi F, Zarrindast MR
Previous investigations have shown that NMDA receptors play an important role in learning and memory process. Lithium is a primary drug for management and prophylaxis of bipolar disorder. It can regulate signal transduction pathways in several regions of the brain and alter the function of several neurotransmitter systems involved in memory processes. The present study aimed to test the interaction of NMDA glutamatergic system of the CA1 region of dorsal hippocampus and lithium on spatial learning. Spatial memory was assessed in Morris water maze task by a single training session of eight trials followed by a probe trial and visible test 24h later. All drugs were injected into CA1 regions, 5min after training. Our data indicated that post- training administration of lithium (20?g/rat, intra-CA1) significantly impaired memory consolidation. Intra- CA1administration of NMDA, a glutamate receptor agonist (0.001 and 0.01?g/rat) showed spatial learning facilitation. Infusion of D-AP5, a glutamate receptor antagonist (0.05 and 0.1?g/rat) showed impairment of spatial memory. Our data also indicated that post- training administration of ineffective dose of NMDA (0.0001?g/rat) significantly decreased amnesia induced by lithium in spatial memory consolidation. In addition, post-training intra-CA1 injection of ineffective dose of D-AP5 (0.01?g/rat) could significantly increase lithium induced amnesia. It seems probable that signaling cascades of NMDA receptors that regulates synaptic plasticity are targets of anti-manic agents such as lithium. Our results suggest that NMDA receptors of the dorsal hippocampus may be involved in lithium-induced spatial learning impairment in the MWM task.
PMID: 27444123 [PubMed - as supplied by publisher]
Unmet needs of bipolar disorder patients.
Neuropsychiatr Dis Treat. 2016;12:1561-70
Authors: Hajda M, Prasko J, Latalova K, Hruby R, Ociskova M, Holubova M, Kamaradova D, Mainerova B
BACKGROUND: Bipolar disorder (BD) is a serious mental illness with adverse impact on the lives of the patients and their caregivers. BD is associated with many limitations in personal and interpersonal functioning and restricts the patients' ability to use their potential capabilities fully. Bipolar patients long to live meaningful lives, but this goal is hard to achieve for those with poor insight. With progress and humanization of society, the issue of patients' needs became an important topic. The objective of the paper is to provide the up-to-date data on the unmet needs of BD patients and their caregivers.
METHODS: A systematic computerized examination of MEDLINE publications from 1970 to 2015, via the keywords "bipolar disorder", "mania", "bipolar depression", and "unmet needs", was performed.
RESULTS: Patients' needs may differ in various stages of the disorder and may have different origin and goals. Thus, we divided them into five groups relating to their nature: those connected with symptoms, treatment, quality of life, family, and pharmacotherapy. We suggested several implications of these needs for pharmacotherapy and psychotherapy.
CONCLUSION: Trying to follow patients' needs may be a crucial point in the treatment of BD patients. However, many needs remain unmet due to both medical and social factors.
PMID: 27445475 [PubMed]
Unraveling Executive Functioning in Dual Diagnosis.
Front Psychol. 2016;7:979
Authors: Duijkers JC, Vissers CT, Egger JI
In mental health, the term dual-diagnosis is used for the co-occurrence of Substance Use Disorder (SUD) with another mental disorder. These co-occurring disorders can have a shared cause, and can cause/intensify each other's expression. Forming a threat to health and society, dual-diagnosis is associated with relapses in addiction-related behavior and a destructive lifestyle. This is due to a persistent failure to control impulses and the maintaining of inadequate self-regulatory behavior in daily life. Thus, several aspects of executive functioning like inhibitory, shifting and updating processes seem impaired in dual-diagnosis. Executive (dys-)function is currently even seen as a shared underlying key component of most mental disorders. However, the number of studies on diverse aspects of executive functioning in dual-diagnosis is limited. In the present review, a systematic overview of various aspects of executive functioning in dual-diagnosis is presented, striving for a prototypical profile of patients with dual-diagnosis. Looking at empirical results, inhibitory and shifting processes appear to be impaired for SUD combined with schizophrenia, bipolar disorder or cluster B personality disorders. Studies involving updating process tasks for dual-diagnosis were limited. More research that zooms in to the full diversity of these executive functions is needed in order to strengthen these findings. Detailed insight in the profile of strengths and weaknesses that underlies one's behavior and is related to diagnostic classifications, can lead to tailor-made assessment and indications for treatment, pointing out which aspects need attention and/or training in one's self-regulative abilities.
PMID: 27445939 [PubMed]
Opposite Interplay between PPAR Gamma and Canonical Wnt/Beta-Catenin Pathway in Amyotrophic Lateral Sclerosis.
Front Neurol. 2016;7:100
Authors: Lecarpentier Y, Vallée A
The opposite interplay between peroxisome proliferator-activated receptor gamma (PPAR gamma) and Wnt/beta-catenin signaling has led to the categorization of neurodegenerative diseases (NDs) as either NDs in which PPAR gamma is downregulated while the canonical Wnt/beta-catenin pathway is upregulated [amyotrophic lateral sclerosis (ALS), Parkinson's disease, Huntington's disease, multiple sclerosis, Friedreich's ataxia] or NDs in which PPAR gamma is upregulated while the canonical Wnt/beta-catenin signaling is downregulated (bipolar disorder, schizophrenia, Alzheimer's disease). ALS, a common adult-onset debilitating ND, is characterized by a chronic and progressive degeneration of upper and lower motor neurons resulting in muscular atrophy, paralysis, and ultimately death. The intent of this review is to provide an analysis of the integration of these two opposed systems, i.e., canonical Wnt/beta-catenin and PPAR gamma, in ALS. Understanding this integration may aid in the development of novel ALS therapies. Although the canonical Wnt/beta-catenin pathway is upregulated in ALS, riluzole, an enhancer of the canonical Wnt signaling, is classically prescribed in this disease in humans. However, studies carried out on ALS transgenic mice have shown beneficial effects after treatment by PPAR gamma agonists partly due to their anti-inflammatory effects.
PMID: 27445967 [PubMed]
Protein Kinase A and Anxiety-Related Behaviors: A Mini-Review.
Front Endocrinol (Lausanne). 2016;7:83
Authors: Keil MF, Briassoulis G, Stratakis CA, Wu TJ
This review focuses on the anxiety related to cyclic AMP/protein kinase A (PKA) signaling pathway that regulates stress responses. PKA regulates an array of diverse signals that interact with various neurotransmitter systems associated with alertness, mood, and acute and social anxiety-like states. Recent mouse studies support the involvement of the PKA pathway in common neuropsychiatric disorders characterized by heightened activation of the amygdala. The amygdala is critical for adaptive responses leading to fear learning and aberrant fear memory and its heightened activation is widely thought to underpin various anxiety disorders. Stress-induced plasticity within the amygdala is involved in the transition from normal vigilance responses to emotional reactivity, fear over-generalization, and deficits in fear inhibition resulting in pathological anxiety and conditions, such as panic and depression. Human studies of PKA signaling defects also report an increased incidence of psychiatric disorders, including anxiety, depression, bipolar disorder, learning disorders, and attention deficit hyperactivity disorder. We speculate that the PKA system is uniquely suited for selective, molecularly targeted intervention that may be proven effective in anxiolytic therapy.
PMID: 27445986 [PubMed]
Elevated Level of Serum Carcinoembryonic Antigen (CEA) and Search for a Malignancy: A Case Report.
Authors: Asad-Ur-Rahman F, Saif MW
Carcinoembryonic antigen (CEA) has been shown to be associated with tumor burden in patients with colorectal cancer. However, it is also elevated to a significant degree in a number of other malignant and non-malignant conditions. We report a case of reversible CEA elevation in a patient using lithium for bipolar disorder. A 58-year-old female with a longstanding smoking history and a past medical history of chronic obstructive pulmonary disease (COPD), bipolar illness, hypothyroidism, and obesity was found to have an elevated CEA level of 11.2 ng/ml (normal level <5 ng/ml) in the workup for postmenopausal bleeding. Her history was not positive for malignancy of colorectum, ovaries, thyroid, or breast. She underwent a large number of imaging and endoscopic studies to evaluate for colorectal, breast, ovarian, and lung cancer; however, it did not reveal any evidence of malignancy. Upon review of her medications, she reported that she had recently started lithium for her bipolar illness. We followed up her CEA level while her dose of lithium was reduced from 450 to 300 mg per day. Her CEA level decreased from 25 mg/dl to 6.1 mg/dl and remained stable over the course of the next eight months. Our case is the first case report that identifies lithium as a potential cause of reversible CEA elevation. The underlying mechanism is yet to be elucidated, but it underscores the importance of investigating the medications as part of the workup.
PMID: 27446768 [PubMed]
Potential Roles of Adropin in Central Nervous System: Review of Current Literature.
Front Mol Biosci. 2016;3:25
Authors: Shahjouei S, Ansari S, Pourmotabbed T, Zand R
Adropin is a 4.9 kDa peptide that is important for maintenance of metabolic and non-metabolic homeostasis. It regulates glucose and fatty acid metabolism and is involved in endothelial cell function and endothelial nitric oxide (NO) synthase bioactivity as well as physical activity and motor coordination. Adropin is expressed in many tissues and organs including central nervous system (CNS). This peptide plays a crucial role in the development of various CNS disorders such as stroke, schizophrenia, bipolar disorder as well as Alzheimer's, Parkinson's, and Huntington's diseases. In this comprehensive review, the potential roles of adropin in cellular signaling pathways that lead to pathogenesis and/or treatment of CNS disorders will be discussed.
PMID: 27446928 [PubMed]
Anxiety symptoms in a major mood and schizophrenia spectrum disorders.
Eur Psychiatry. 2016 Jul 19;37:1-7
Authors: Karpov B, Joffe G, Aaltonen K, Suvisaari J, Baryshnikov I, Näätänen P, Koivisto M, Melartin T, Oksanen J, Suominen K, Heikkinen M, Paunio T, Isometsä E
BACKGROUND: Comorbid anxiety symptoms and disorders are present in many psychiatric disorders, but methodological variations render comparisons of their frequency and intensity difficult. Furthermore, whether risk factors for comorbid anxiety symptoms are similar in patients with mood disorders and schizophrenia spectrum disorders remains unclear.
METHODS: The Overall Anxiety Severity and Impairment Scale (OASIS) was used to measure anxiety symptoms in psychiatric care patients with schizophrenia or schizoaffective disorder (SSA, n=113), bipolar disorder (BD, n=99), or depressive disorder (DD, n=188) in the Helsinki University Psychiatric Consortium Study. Bivariate correlations and multivariate linear regression models were used to examine associations of depressive symptoms, neuroticism, early psychological trauma and distress, self-efficacy, symptoms of borderline personality disorder, and attachment style with anxiety symptoms in the three diagnostic groups.
RESULTS: Frequent or constant anxiety was reported by 40.2% of SSA, 51.5% of BD, and 55.6% of DD patients; it was described as severe or extreme by 43.8%, 41.4%, and 41.2% of these patients, respectively. SSA patients were significantly less anxious (P=0.010) and less often avoided anxiety-provoking situations (P=0.009) than the other patients. In regression analyses, OASIS was associated with high neuroticism, symptoms of depression and borderline personality disorder and low self-efficacy in all patients, and with early trauma in patients with mood disorders.
CONCLUSIONS: Comorbid anxiety symptoms are ubiquitous among psychiatric patients with mood or schizophrenia spectrum disorders, and in almost half of them, reportedly severe. Anxiety symptoms appear to be strongly related to both concurrent depressive symptoms and personality characteristics, regardless of principal diagnosis.
PMID: 27447101 [PubMed - as supplied by publisher]
The T Allele of MTHFR c.C677T and Its Synergism with G (Val 158) Allele of COMT c.G472A Polymorphism Are Associated with the Risk of Bipolar I Disorder.
Genet Test Mol Biomarkers. 2016 Jul 22;
Authors: Rahimi Z, Kakabaraee K, Garavand A, Rahimi Z
AIMS: The aims of the present study were to investigate the association between methylenetetrahydrofolate reductase (MTHFR) c.C677T (p.A222V) and catechol-O-methyltransferase (COMT) c.G472A (p.V158M) polymorphisms and their synergism with respect to bipolar I disorder (BID).
METHODS: Within an ethnic Kurdish population from Western Iran the MTHFR c.C677T and COMT c.G472A polymorphisms were studied in 150 patients with BID and 149 gender- and age-matched healthy individuals using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
RESULTS: In the presence of MTHFR 677T allele and MTHFR TT genotype, the risk of BID was 1.44 times (p?=?0.046) and 1.81-fold (p?=?0.029), respectively. The frequency of COMT 472G allele compared to the A allele in cases and controls was not significant (p?=?0.078); however there was a synergism between the presence of MTHFR 677T and COMT 472G alleles that increased the risk of BID by 2.58-fold (p?=?0.003).
CONCLUSIONS: Our findings indicate that the presence of the lower activity allele of MTHFR (677T) increased the risk of BID. In addition, the concomitant presence of the MTHFR 677T allele with the COMT 472G allele was associated with increased susceptibility to BID in our population.
PMID: 27447284 [PubMed - as supplied by publisher]
Structural and Functional Brain Correlates of Cognitive Impairment in Euthymic Patients with Bipolar Disorder.
PLoS One. 2016;11(7):e0158867
Authors: Alonso-Lana S, Goikolea JM, Bonnin CM, Sarró S, Segura B, Amann BL, Monté GC, Moro N, Fernandez-Corcuera P, Maristany T, Salvador R, Vieta E, Pomarol-Clotet E, McKenna PJ
INTRODUCTION: Cognitive impairment in the euthymic phase is a well-established finding in bipolar disorder. However, its brain structural and/or functional correlates are uncertain.
METHODS: Thirty-three euthymic bipolar patients with preserved memory and executive function and 28 euthymic bipolar patients with significant memory and/or executive impairment, as defined using two test batteries, the Rivermead Behavioural Memory Test (RBMT) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS), plus 28 healthy controls underwent structural MRI using voxel-based morphometry (VBM). Twenty-seven of the cognitively preserved patients, 23 of the cognitively impaired patients and 28 controls also underwent fMRI during performance of the n-back working memory task.
RESULTS: No clusters of grey or white matter volume difference were found between the two patient groups. During n-back performance, the cognitively impaired patients showed hypoactivation compared to the cognitively preserved patients in a circumscribed region in the right dorsolateral prefrontal cortex. Both patient groups showed failure of de-activation in the medial frontal cortex compared to the healthy controls.
CONCLUSIONS: Cognitive impairment in euthymic bipolar patients appears from this study to be unrelated to structural brain abnormality, but there was some evidence for an association with altered prefrontal function.
PMID: 27448153 [PubMed - as supplied by publisher]
[Treatment of psychiatric disorders during pregnancy and the breast feeding : Psychotherapy and other nondrug therapies].
Nervenarzt. 2016 Jul 22;
Authors: Kittel-Schneider S, Reif A
The majority of women suffering from psychiatric disorders in pregnancy and the breast feeding prefer psychotherapy and other nonpharmacological treatment over psychopharmacological treatment although the risk of malformations and postnatal complications in children exposed to psychopharmacological drugs must be regarded as acceptable in moderate to severely ill patients. Data are lacking, but several psychotherapeutic and biological treatments as well as noninvasive brain stimulation procedures have been investigated to treat depressive episodes and anxiety disorders in pregnancy and the breast feeding. In mild to moderate depressive episodes different psychotherapy treatments and counseling are significantly more effective in reducing depressive symptoms than no treatment.The same seems to be true for anxiety disorders; however, studies on this are sparse. Treatment by telephone and internet also seems to improve symptoms, which is of interest especially in the less flexible group of breast feeding women and for the development of future health care structures. Noninvasive stimulation treatment has been shown to be an effective nonpharmacological therapeutic option. Data for other recent noninvasive brain stimulation treatments and biological treatments as well as exercise therapy are sparse. In severe and delusional cases as well as treatment-resistant depressive episodes, electroconvulsive therapy should be considered in pregnant women. Because several patients prefer nonpharmacological therapy during this period, those should be applied if available and feasible. Regarding nonpharmacological treatment of obsessive-compulsive disorder, bipolar disorder and schizophrenia during pregnancy and the breast feeding, no recommendation can currently be given.
PMID: 27448177 [PubMed - as supplied by publisher]
Outcome of cognitive-behavioral therapy for relatives of people with severe mental disorders.
Psicothema. 2016 Aug;28(3):227-34
Authors: Polo-López R, Salaberria K, Cruz-Sáez MS, Echeburua E
BACKGROUND: Over the past 20 years, research shows that families of people affected by severe mental illness (schizophrenia, bipolar disorder, and addiction) may suffer emotional distress and lack of self-esteem.
AIMS: In this study, long-term effectiveness of a cognitive-behavioral treatment designed for relatives of people with severe mental illness was evaluated.
METHOD: A total of 30 relatives living with a person affected by a severe mental disorder received 10 sessions of tailored cognitive-behavioral therapy.
RESULTS: The study shows that the treatment was effective for the reduction of depression-anxiety symptoms, as well as for negative emotions and psychological distress.
CONCLUSIONS: This psychological support program has shown to be effective as a treatment for the relatives of people with serious mental health problems both in the posttreatment and in the 12-month follow-up.
PMID: 27448253 [PubMed - in process]
Clinical assessment of psychotic and mood disorder symptoms for risk of future violence.
CNS Spectr. 2014 Oct;19(5):468-73
Authors: Scott CL, Resnick PJ
This article reviews important components to consider when evaluating the relationship of psychotic and mood disorder symptoms to violence. Particular attention is given to assessing persecutory delusions and command auditory hallucinations. Clinical implications of research findings to evaluating violence risk in psychiatric patients are reviewed.
PMID: 27358936 [PubMed - indexed for MEDLINE]
Lithium and differential reversal of abnormalities in neurons from bipolar patients.
Neuroscientist. 2016 Apr;22(2):106
PMID: 27433560 [PubMed - indexed for MEDLINE]
[The German research network for mental disorders].
Nervenarzt. 2016 Jul 20;
Authors: Bauer M, Banaschewski T, Heinz A, Kamp-Becker I, Meyer-Lindenberg A, Padberg F, Rapp MA, Rupprecht R, Schneider F, Schulze TG, Wittchen HU
Mental disorders are among the greatest medical and social challenges facing us. They can occur at all stages of life and are among the most important commonly occurring diseases. In Germany 28?% of the population suffer from a mental disorder every year, while the lifetime risk of suffering from a mental disorder is almost 50?%. Mental disorders cause great suffering for those affected and their social network. Quantitatively speaking, they can be considered to be among those diseases creating the greatest burden for society due to reduced productivity, absence from work and premature retirement. The Federal Ministry of Education and Research is funding a new research network from 2015 to 2019 with up to 35 million euros to investigate mental disorders in order to devise and develop better therapeutic measures and strategies for this population by means of basic and translational clinical research. This is the result of a competitive call for research proposals entitled research network for mental diseases. It is a nationwide network of nine consortia with up to ten psychiatric and clinical psychology partner institutions from largely university-based research facilities for adults and/or children and adolescents. Furthermore, three cross-consortia platform projects will seek to identify shared causes of diseases and new diagnostic modalities for anxiety disorders, attention deficit hyperactivity disorders (ADHS), autism, bipolar disorders, depression, schizophrenia and psychotic disorders as well as substance-related and addictive disorders. The spectrum of therapeutic approaches to be examined ranges from innovative pharmacological and psychotherapeutic treatment to novel brain stimulation procedures. In light of the enormous burden such diseases represent for society as a whole, a sustainable improvement in the financial support for those researching mental disorders seems essential. This network aims to become a nucleus for long overdue and sustained support for a German center for mental disorders.
PMID: 27439991 [PubMed - as supplied by publisher]
Cross-phenotype Polygenic Risk Score Analysis of Persistent Post-Concussive Symptoms in U.S. Army Soldiers with Deployment-acquired Traumatic Brain Injury.
J Neurotrauma. 2016 Jul 20;
Authors: Polimanti R, Chen CY, Ursano RJ, Heeringa SG, Jain S, Kessler RC, Nock MK, Smoller J, Sun X, Gelernter J, Stein MB
Traumatic brain injury (TBI) contributes to the increased rates of suicide and post-traumatic stress disorder in military personnel and veterans; and it is also associated with the risk of neurodegenerative and psychiatric disorders. A cross-phenotype high-resolution polygenic risk score (PRS) analysis of persistent post-concussive symptoms (PCS) was conducted in 845 U.S. Army soldiers who sustained TBI during their deployment. We used a prospective longitudinal survey of three Brigade Combat Teams to assess deployment-acquired TBI and persistent physical, cognitive, and emotional PCS. PRS were derived from summary statistics of large genome-wide association studies of Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, and major depressive disorder; and for years of schooling, college completion, childhood intelligence, infant head circumference (IHC), and adult intracranial volume. Although our study had more than 95% of statistical power to detect moderate-to-large effect sizes, no association was observed with neurodegenerative and psychiatric disorders, suggesting that persistent PCS does not share genetic components with these traits to a moderate-to-large degree. We observed a significant finding: subjects with high IHC PRS recovered better from cognitive/emotional persistent PCS than the other individuals (R2= 1.11%; p=3.37*10-3). Enrichment analysis identified two significant Gene Ontology (GO) terms related to this result: GO:0050839~Cell adhesion molecule binding (p=8.9*10-6) and GO:0050905~Neuromuscular process (p=9.8*10-5). In summary, our study indicated that the genetic predisposition to persistent PCS after TBI does not have substantial overlap with neurodegenerative and psychiatric diseases; but mechanisms related to early brain growth may be involved.
PMID: 27439997 [PubMed - as supplied by publisher]
Whether lithium inhibits glycogen synthase kinase (GSK)-3? activity in vivo in humans is still an open question.
Bipolar Disord. 2016 Jul 21;
Authors: Agam G, Azab AN
PMID: 27440170 [PubMed - as supplied by publisher]
Anxiety Symptoms in Psychotic Disorders: Results from the Second Australian National Mental Health Survey.
Clin Schizophr Relat Psychoses. 2016;10(2):93-100
Authors: Bosanac P, Mancuso SG, Castle DJ
BACKGROUND: The prevalence of anxiety symptoms among Australians with psychotic disorders was examined as part of the Survey of High Impact Psychosis (SHIP).
METHODS: A two-phase design was used. Of 7,955 people who were screened positive for psychosis and eligible, there were 1,825 participants (18-34 years and 35-64 years) interviewed. Data were collected on symptomatology, substance use, cognitive ability, functioning, disability, physical health, mental health service utilization, medication use, education, employment and housing. Anxiety symptomatology was divided into generalized anxiety, panic, phobic, social anxiety and obsessive-compulsive symptoms.
RESULTS: The most common ICD-10 diagnoses were schizophrenia or schizoaffective disorder (63.0%) and bipolar (mania) disorder (17.5%). Overall, 59.8% (n=1,092) of participants reported experiencing anxiety symptoms in the previous twelve months. Female gender was highly associated with all domains of anxiety. Smoking was significantly associated with all domains of anxiety, except generalized anxiety. The presence of any depressive symptoms in the previous twelve months was significantly associated with all anxiety symptoms. Medication side effects were associated with phobic and obsessive-compulsive symptoms. Social dysfunction was associated with social anxiety, and less so for obsessive-compulsive symptoms.
CONCLUSIONS: Anxiety symptoms are common in people with psychotic disorders. Appropriate screening and treatment should be a clinical priority.
PMID: 27440210 [PubMed - in process]
Cariprazine for the Treatment of Schizophrenia: A Review of this Dopamine D3-Preferring D3/D2 Receptor Partial Agonist.
Clin Schizophr Relat Psychoses. 2016;10(2):109-19
Authors: Citrome L
Cariprazine is an antipsychotic medication and received approval by the U.S. Food and Drug Administration for the treatment of schizophrenia in September 2015. Cariprazine is a dopamine D3 and D2 receptor partial agonist, with a preference for the D3 receptor. Cariprazine is also a partial agonist at the serotonin 5-HT1A receptor and acts as an antagonist at 5-HT2B and 5-HT2A receptors. The recommended dose range of cariprazine for the treatment of schizophrenia is 1.5-6 mg/d; the starting dose of 1.5 mg/d is potentially therapeutic. Cariprazine is administered once daily and is primarily metabolized in the liver through the CYP3A4 enzyme system and, to a lesser extent, by CYP2D6. There are two active metabolites of note, desmethyl-cariprazine and didesmethyl-cariprazine; the latter's half-life is substantially longer than that for cariprazine and systemic exposure to didesmethyl-cariprazine is several times higher than that for cariprazine. Three positive, 6-week, Phase 2/3, randomized controlled trials in acute schizophrenia demonstrated superiority of cariprazine over placebo. Pooled responder rates were 31% for cariprazine 1.5-6 mg/d vs. 21% for placebo, resulting in a number needed to treat (NNT) of 10. In a 26-72 week, randomized withdrawal study, significantly fewer patients relapsed in the cariprazine group compared with placebo (24.8% vs. 47.5%), resulting in an NNT of 5. The most commonly encountered adverse events (incidence ?5% and at least twice the rate of placebo) are extrapyramidal symptoms (number needed to harm [NNH] 15 for cariprazine 1.5-3 mg/d vs. placebo and NNH 10 for 4.5-6 mg/d vs. placebo) and akathisia (NNH 20 for 1.5-3 mg/d vs. placebo and NNH 12 for 4.5-6 mg/d vs. placebo). Short-term weight gain appears small (approximately 8% of patients receiving cariprazine 1.5-6 mg/d gained ?7% body weight from baseline, compared with 5% for those randomized to placebo, resulting in an NNH of 34). Cariprazine is associated with no clinically meaningful alterations in metabolic variables, prolactin, or the ECG QT interval. Cariprazine is also approved for the acute treatment of manic or mixed episodes associated with bipolar I disorder. Clinical trials are ongoing in patients with acute bipolar I depression and as adjunctive treatment to antidepressant therapy in patients with major depressive disorder.
PMID: 27440212 [PubMed - in process]
Preliminary assessment of pre-morbid DNA methylation in individuals at high genetic risk of mood disorders.
Bipolar Disord. 2016 Jul 21;
Authors: Walker RM, Sussmann JE, Whalley HC, Ryan NM, Porteous DJ, McIntosh AM, Evans KL
OBJECTIVES: Accumulating evidence implicates altered DNA methylation in psychiatric disorders, including bipolar disorder (BD) and major depressive disorder (MDD). It is not clear, however, whether these changes are causative or result from illness progression or treatment. To disentangle these possibilities we profiled genome-wide DNA methylation in well, unrelated individuals at high familial risk of mood disorder. DNA methylation was compared between individuals who subsequently developed BD or MDD [ill later (IL)] and those who remained well [well later (WL)].
METHODS: DNA methylation profiles were obtained from whole-blood samples from 22 IL and 23 WL individuals using the Infinium HumanMethylation450 BeadChip. Differential methylation was assessed on a single-locus and regional basis. Pathway analysis was performed to assess enrichment for particular biological processes amongst nominally significantly differentially methylated loci.
RESULTS: Although no locus withstood correction for multiple testing, uncorrected P-values provided suggestive evidence for altered methylation at sites within genes previously implicated in neuropsychiatric conditions, such as Transcription Factor 4 (TCF4) and Interleukin 1 Receptor Accessory Protein-Like 1 ([IL1RAPL1]; P?3.11×10(-5) ). Pathway analysis revealed significant enrichment for several neurologically relevant pathways and functions, including Nervous System Development and Function and Behavior; these findings withstood multiple testing correction (q?0.05). Analysis of differentially methylated regions identified several within the major histocompatibility complex (P?.000 479), a region previously implicated in schizophrenia and BD.
CONCLUSIONS: Our data provide provisional evidence for the involvement of altered whole-blood DNA methylation in neurologically relevant genes in the aetiology of mood disorders. These findings are convergent with the findings of genome-wide association studies.
PMID: 27440233 [PubMed - as supplied by publisher]
Multibody cofactor and substrate molecular recognition in the myo-inositol monophosphatase enzyme.
Sci Rep. 2016;6:30275
Authors: Ferruz N, Tresadern G, Pineda-Lucena A, De Fabritiis G
Molecular recognition is rarely a two-body protein-ligand problem, as it often involves the dynamic interplay of multiple molecules that together control the binding process. Myo-inositol monophosphatase (IMPase), a drug target for bipolar disorder, depends on 3 Mg(2+) ions as cofactor for its catalytic activity. Although the crystallographic pose of the pre-catalytic complex is well characterized, the binding process by which substrate, cofactor and protein cooperate is essentially unknown. Here, we have characterized cofactor and substrate cooperative binding by means of large-scale molecular dynamics. Our study showed the first and second Mg(2+) ions identify the binding pocket with fast kinetics whereas the third ion presents a much higher energy barrier. Substrate binding can occur in cooperation with cofactor, or alone to a binary or ternary cofactor-IMPase complex, although the last scenario occurs several orders of magnitude faster. Our atomic description of the three-body mechanism offers a particularly challenging example of pathway reconstruction, and may prove particularly useful in realistic contexts where water, ions, cofactors or other entities cooperate and modulate the binding process.
PMID: 27440438 [PubMed - in process]
Medical and Psychosocial Barriers to Weight Management in Older Veterans With and Without Serious Mental Illness.
Psychol Serv. 2016 Jul 21;
Authors: Muralidharan A, Klingaman EA, Prior SJ, Molinari V, Goldberg RW
Older adults with serious mental illness (SMI) are an understudied population with complex care needs and high rates of obesity/overweight. Little is known about the experiences of older adults with SMI with weight management. The present study is an observational study of veterans ages 55 and over with a body mass index in the overweight or obese range, comparing Veterans with schizophrenia or bipolar disorder (n = 9044) to their same-age peers with no mental health disorders (n = 71156), on their responses to a questionnaire assessment of medical and psychosocial factors related to weight management. Responses to the questionnaire between August, 2005 and May, 2013 were used to examine the following: demographics, clinical characteristics, medical barriers to weight management, current weight loss plan, reliability of social support, reasons for being overweight, and weight loss barriers. Physical health concerns were highly prevalent in both groups. Veterans in the SMI group endorsed more medical issues and were significantly more likely to endorse experiences that indicated that their medical conditions were poorly controlled (e.g., shortness of breath). Veterans in the SMI group were more likely to endorse many barriers to healthy eating and physical activity, across medical, psychological, social, and environmental domains. Even within a sample at medically high-risk for complications related to obesity and metabolic syndrome, older veterans with SMI and overweight/obesity experience more challenges with weight management than their same-age peers with overweight/obesity and no mental health disorders. Weight management interventions for this population should take a multifaceted approach. (PsycINFO Database Record
PMID: 27441416 [PubMed - as supplied by publisher]
Do current national and international guidelines have specific recommendations for older adults with bipolar disorder? A brief report.
Int J Geriatr Psychiatry. 2016 Jul 21;
Authors: Dols A, Kessing LV, Strejilevich SA, Rej S, Tsai SY, Gildengers AG, Almeida OP, Shulman KI, Sajatovic M, International Society for Bipolar Disorders Task Force for Older Adults with Bipolar Disorder
OBJECTIVE: Older adults with bipolar disorder (OABD) are a growing segment of patients with bipolar disorder (BD) for which specific guidelines are warranted. Although, OABD are frequently excluded from randomized controlled trials due to their age or somatic comorbidity, more treatment data from a variety of sources have become available in recent years. It is expected that at least some of this emerging information on OABD would be incorporated into treatment guidelines available to clinicians around the world.
METHODS: The International Society of Bipolar Disorders OABD task force compiled and compared recommendations from current national and international guidelines that specifically address geriatric or older individuals with BD (from year 2005 onwards).
RESULTS: There were 34 guidelines, representing six continents and 19 countries. The majority of guidelines had no separate section on OABD. General principles for treating OABD with medication are recommended to be similar to those for younger adults, with special caution for side effects due to somatic comorbidity and concomitant medications. Therapeutic lithium serum levels are suggested to be lower but recommendations are very general and mostly not informed by specific research evidence.
CONCLUSIONS: There is a lack of emphasis of OABD-specific issues in existing guidelines. Given the substantial clinical heterogeneity in BD across the life span, along with the rapidly expanding population of older individuals worldwide, and limited mental health workforce with geriatric expertise, it is critical that additional effort and resources be devoted to studying treatment interventions specific to OABD and that treatment guidelines reflect research findings. Copyright © 2016 John Wiley & Sons, Ltd.
PMID: 27442023 [PubMed - as supplied by publisher]
Screening for bipolar disorders: A public health issue.
J Affect Disord. 2016 Jun 21;205:139-143
Authors: Carta MG, Angst J
INTRODUCTION: Bipolar disorder (BD) is a public health issue; it is one of the leading causes of disability and its late diagnosis heightens the impact of the condition. Screening tools for early detection could be extremely useful.
METHODS: Narrative review on screening of BD.
RESULTS: Screening questionnaires have high sensitivity but relatively low specificity if DSM diagnoses are taken as the "gold standard". Critics maintain that an excess of false positives makes such tools unnecessary for identifying cases and of little use in screening studies consisting of two phases. However, "positive" screening was frequently homogeneous with BD in terms of gender, age, level of distress, low social functioning and employment rate, comorbidity with alcohol and substance abuse, heavy recourse to health care, use of mood stabilizers and antidepressants, risk of suicide attempts, and high recurrence of depressive episodes. While none of these components is pathognomonic of BD, their co-occurrence could identify subthreshold "cases". The studies reviewed found positivity at screening to be associated with impaired quality of life, even without BD and independently of comorbidity. Patients with a neurological disease and positive at screening show homogenous brain lesions, different from those of patients screening negative.
CONCLUSIONS: The results are coherent with the hypothesis that positivity identifies a bipolar spectrum of clinical and public health interest, including sub-threshold bipolar cases, which do not fulfil the diagnostic criteria for BD.
PMID: 27442457 [PubMed - as supplied by publisher]
Preliminary investigation of the relationships between sleep duration, reward circuitry function, and mood dysregulation in youth offspring of parents with bipolar disorder.
J Affect Disord. 2016 Jul 1;205:144-153
Authors: Soehner AM, Bertocci MA, Manelis A, Bebko G, Ladouceur CD, Graur S, Monk K, Bonar LK, Hickey MB, Axelson D, Goldstein BI, Goldstein TR, Birmaher B, Phillips ML
BACKGROUND: Altered reward circuitry function is observed in individuals with bipolar disorder (BD) and their unaffected offspring (OBP). While OBP are at elevated risk for BD, modifiable risk factors that may exacerbate neural vulnerabilities in OBP remain under-characterized. As sleep loss is strongly linked to mania in BD, this study tested associations between sleep duration, reward circuitry function, and mood dysregulation in OBP.
METHODS: Two groups of youth unaffected with BD (9-17yr) completed a number-guessing fMRI reward paradigm: 25 OBP and 21 age-sex-IQ-matched offspring of control parents with non-BD psychopathology (OCP), to differentiate risk for BD from risk for psychopathology more broadly. Regressions tested effects of group status, self-reported past-week sleep duration, and their interaction on neural activity and bilateral ventral striatum (VS) functional connectivity to win>control. Correlations with parent-reported mood dysregulation were assessed.
RESULTS: Group effects were observed for right posterior insula activity (OCP>OBP) and VS-left posterior insula connectivity (OBP>OCP). Group(?)sleep duration interactions were observed for left dorsal anterior-mid-cingulate (daMCC) activity and VS-left anterior insula/ventrolateral prefrontal cortex (VLPFC) connectivity. Specifically, sleep duration and daMCC activity were positively related in OBP, but negatively related in OCP and sleep duration and VS-left anterior insula/VLPFC connectivity were negatively related in OBP, but positively in OCP. Additionally, increased VS-left posterior insula connectivity and VS-left anterior insula/VLPFC connectivity were associated with greater mood dysregulation in OBP only.
LIMITATIONS: Cross-sectional design and small sample size.
CONCLUSIONS: Altered reward-related VS-insula connectivity could represent a neural pathway underpinning mood dysregulation in OBP, and may be modulated by shortened sleep duration.
PMID: 27442458 [PubMed - as supplied by publisher]
Prevalence of Circadian Rhythm Sleep-Wake Disorders and Associated Factors in Euthymic Patients with Bipolar Disorder.
PLoS One. 2016;11(7):e0159578
Authors: Takaesu Y, Inoue Y, Murakoshi A, Komada Y, Otsuka A, Futenma K, Inoue T
Recent studies have suggested that there are certain pathophysiological relationships between bipolar disorder (BD) and circadian rhythm dysfunction. However, apparently no studies have clarified the prevalence of circadian rhythm sleep-wake disorders (CRSWD) in patients with BD. This study was set out to investigate the prevalence of CRSWD and associated factors in patients with BD. One hundred four euthymic BD outpatients participated in this study. The subjects were asked to answer questionnaires including demographic variables, clinical course of BD, and family history of psychiatric disorders and suicide. Severity of BD was assessed by the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. CRSWD was diagnosed by clinical interview, together with sleep logs, according to the International Classification of Sleep Disorders, third edition (ICSD-3). Thirty-five subjects (32.4%) met the criteria for CRSWD. The age at the time of investigation and that at the onset of BD were both lower in the CRSWD group than in the non-CRSWD group. The rates of family history of psychiatric disorders and suicide in the CRSWD group were higher than those in the non-CRSWD group. Multiple logistic regression analysis revealed that the presence of CRSWD was significantly associated with younger onset age of BD and family history of suicide. The prevalence of CRSWD could be quite high in BD patients. Younger onset age of BD and family history of suicide were associated with presence of CRSWD in BD patients.
PMID: 27442503 [PubMed - as supplied by publisher]
Soluble Intracellular Adhesion Molecule-1 in Patients with Unipolar or Bipolar Affective Disorders: Results from a Pilot Trial.
Neuropsychobiology. 2016 Jul 22;74(1):8-14
Authors: Schaefer M, Sarkar S, Schwarz M, Friebe A
BACKGROUND: Immunological and vascular markers may play a role in the pathophysiology of mood disorders and mood changes.
AIM: To test whether the cell adhesion molecule soluble intracellular adhesion molecule-1 (sICAM-1) may serve as a biomarker for patients with unipolar or bipolar affective disorders when compared to a healthy control group, and whether sICAM-1 blood levels change during different mood states.
METHODS: sICAM-1 serum concentrations were compared between 20 healthy controls and 48 patients with affective disorders (unipolar, bipolar II and bipolar I disorder) during different mood states (euthymic mood state, depression or mania).
RESULTS: When compared to healthy controls, patients with affective disorders had significantly higher sICAM-1 levels during the euthymic state (p = 0.015). Differences became more pronounced during depression (p = 0.013). When unipolar and bipolar patients were analyzed separately, unipolar patients significantly differed from controls during the euthymic and depressive mood state, while bipolar II patients showed a trend towards higher sICAM-1 levels during depression. Patients with bipolar I disorders had significantly higher sICAM-1 levels during manic states when compared to controls (p = 0.007).
CONCLUSIONS: sICAM-1 elevation in unipolar and bipolar patients, independent of mood changes, might support the hypothesis of chronic immune activation and endothelial dysfunction in patients with affective disorders.
PMID: 27442531 [PubMed - as supplied by publisher]
Uric acid levels in subjects with bipolar disorder: A comparative meta-analysis.
J Psychiatr Res. 2016 Jul 9;81:133-139
Authors: Bartoli F, Crocamo C, Mazza MG, Clerici M, Carrà G
Previous research has hypothesised increased uric acid levels, possibly because of an amplified purinergic metabolism and a reduced adenosine activity, in subjects with bipolar disorder. This systematic review and meta-analysis aimed at estimating if individuals with bipolar disorder had uric acid levels higher than both healthy controls and subjects with major depression (trait marker hypothesis). It also tested if uric acid levels could differ in different phases of bipolar disorder (state marker hypothesis). Meta-analyses were carried out generating pooled standardized mean differences (SMDs), using random-effects models. Heterogeneity between studies was estimated using the I(2) index. Relevant sensitivity and meta-regression analyses were conducted. We searched main Electronic Databases, identifying twelve studies that met our inclusion criteria. Meta-analyses showed increased uric acid levels in individuals with bipolar disorder as compared with both healthy controls (SMD = 0.65, p < 0.001, I(2) = 82.9%) and those with major depression (SMD = 0.46, p < 0.001; I(2) = 68.7%). However, meta-regression analyses confirmed this association only as compared with healthy controls. Finally, though uric acid levels were higher in manic/mixed phases as compared with depressive ones (SMD = 0.34; p = 0.04, I(2) = 58.8%), a sensitivity analysis did not confirm the association. In sum, our meta-analysis shows that subjects with bipolar disorder have uric acid levels higher than healthy controls. The potential role of factors that might clarify the nature of this association deserves additional research.
PMID: 27442964 [PubMed - as supplied by publisher]