Altered apolipoprotein C expression in association with cognition impairments and hippocampus volume in schizophrenia and bipolar disorder.
Eur Arch Psychiatry Clin Neurosci. 2016 Aug 22;
Authors: Knöchel C, Kniep J, Cooper JD, Stäblein M, Wenzler S, Sarlon J, Prvulovic D, Linden DE, Bahn S, Stocki P, Ozcan S, Alves G, Carvalho AF, Reif A, Oertel-Knöchel V
Proteomic analyses facilitate the interpretation of molecular biomarker probes which are very helpful in diagnosing schizophrenia (SZ). In the current study, we attempt to test whether potential differences in plasma protein expressions in SZ and bipolar disorder (BD) are associated with cognitive deficits and their underlying brain structures. Forty-two plasma proteins of 29 SZ patients, 25 BD patients and 93 non-clinical controls were quantified and analysed using multiple reaction monitoring-based triple quadrupole mass spectrometry approach. We also computed group comparisons of protein expressions between patients and controls, and between SZ and BD patients, as well. Potential associations of protein levels with cognitive functioning (psychomotor speed, executive functioning, crystallised intelligence) as well as underlying brain volume in the hippocampus were explored, using bivariate correlation analyses. The main finding of this study was that apolipoprotein expression differed between patients and controls and that these alterations in both disease groups were putatively related to cognitive impairments as well as to hippocampus volumes. However, none of the protein level differences were related to clinical symptom severity. In summary, altered apolipoprotein expression in BD and SZ was linked to cognitive decline and underlying morphological changes in both disorders. Our results suggest that the detection of molecular patterns in association with cognitive performance and its underlying brain morphology is of great importance for understanding of the pathological mechanisms of SZ and BD, as well as for supporting the diagnosis and treatment of both disorders.
PMID: 27549216 [PubMed - as supplied by publisher]
An Open-Label Feasibility Trial of Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Major Depressive Episodes.
Acta Med Okayama. 2016 Aug;70(4):307-11
Authors: Fujiwara M, Inagaki M, Higuchi Y, Uchitomi Y, Terada S, Kodama M, Kishi Y, Yamada N
Repetitive transcranial magnetic stimulation (rTMS) has been reported to be a new treatment option for treatment-resistant depression. In Japan, there has been limited research into its feasibility, efficacy, and tolerability. We have launched a trial of rTMS for treating medication-resistant major depressive disorder and bipolar depression. We are investigating low-frequency rTMS to the right dorsolateral prefrontal cortex and traditional high-frequency rTMS to the left dorsolateral prefrontal cortex, in 20 patients. The primary outcome of the study is the treatment completion rate. This study will provide new data on the usefulness of rTMS for treatment-resistant depression in Japan.
PMID: 27549679 [PubMed - in process]
Tolerability and Safety Profile of Cariprazine in Treating Psychotic Disorders, Bipolar Disorder and Major Depressive Disorder: A Systematic Review with Meta-Analysis of Randomized Controlled Trials.
CNS Drugs. 2016 Aug 22;
Authors: Lao KS, He Y, Wong IC, Besag FM, Chan EW
BACKGROUND: Cariprazine is a novel antipsychotic agent recently approved for treating schizophrenia and bipolar mania in the USA. The sample sizes of published randomized controlled trials (RCTs) of the drug are small; previous meta-analyses included few RCTs and did not specifically investigate the tolerability/safety profile of cariprazine.
OBJECTIVE: Our objective was to conduct a meta-analysis of published RCTs to systematically review the tolerability and safety of cariprazine versus placebo.
METHODS: We searched the clinical trial registers (the metaRegister of controlled trials, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform) and electronic databases (PubMed, Embase, PsycINFO and Cochrane library) up to June 2016 to identify phase II/III RCTs of cariprazine in patients with schizophrenia, bipolar disorder or major depressive disorder. We conducted a meta-analysis to investigate outcomes, including risks of discontinuation due to adverse events (AEs), extrapyramidal side effects (EPS) or related events, metabolic syndrome and cardiovascular-related events.
RESULTS: We included nine RCTs, with a total of 4324 subjects. The risk of discontinuation due to AEs for cariprazine was similar to that for placebo (risk ratio [RR] 1.13, 95 % confidence interval [CI] 0.77-1.66). Cariprazine was associated with higher risks of EPS-related events than was placebo, including risk of akathisia (RR 3.92, 95 % CI 2.83-5.43), tremor (RR 2.41, 95 % CI 1.53-3.79) and restlessness (RR 2.17, 95 % CI 1.38-3.40). The cariprazine treatment group was more likely to have clinically significant weight gain (RR 1.68, 95 % CI 1.12-2.52). No statistically significant differences in results were found in other metabolic parameters or cardiovascular-related events.
CONCLUSION: There was a statistically significant higher risk of EPS-related AEs and a slight increase in mean body weight with cariprazine. There were no statistically significant effects on prolactin level or cardiovascular parameters. EPSs were the main short-term adverse reactions reported in the limited number of patients studied. Further clinical and post-marketing pharmacovigilance studies are needed to investigate the long-term safety of cariprazine.
PMID: 27550371 [PubMed - as supplied by publisher]
Involuntary admissions in Italy: the impact of seasonality.
Int J Psychiatry Clin Pract. 2016 Aug 23;:1-7
Authors: Aguglia A, Moncalvo M, Solia F, Maina G
OBJECTIVE: The aim of this study is to assess the prevalence of involuntary admissions with regard to seasonality and clinical associated features, in a sample of patients admitted to a psychiatric unit in a period of 24 months.
METHODS: All subjects consecutively admitted to the Psychiatric Inpatient Unit of the San Luigi Gonzaga Hospital, Orbassano (University of Turin, Italy) from September 2013 to August 2015 were recruited. Socio-demographic and clinical characteristics were collected.
RESULTS: Seven hundred and thirty admissions in psychiatric ward were recognized. The prevalence of involuntary admission was 15.4%. Patients with involuntary hospitalizations showed a higher education level, a higher prevalence of admission in spring/summer with a significant peak in June, a longer duration of hospitalization and a lower suicide ideation. Among involuntary admissions, physical restraint and suicide attempts were more prevalent during spring compared to the other seasons.
CONCLUSIONS: Seasonality has an important role in the psychopathology of psychiatric disorders, particularly in bipolar and related disorder, and may represent an influencing factor in hospital admissions and hospitalizations. Seasonal pattern must be considered while managing diagnosis and treatment of mental disorders, with regard to prevention and psychoeducation of patients.
PMID: 27551753 [PubMed - as supplied by publisher]
Transdiagnostic impairment of cognitive control in mental illness.
J Psychiatr Res. 2016 Aug 5;83:37-46
Authors: McTeague LM, Goodkind MS, Etkin A
Intact cognitive control or executive function has characteristic patterns in both behavior and functional neurocircuitry. Functional neuroimaging studies have shown that a frontal-cingulate-parietal-insular (i.e., "multiple demand") network forms a common functional substrate undergirding successful adaptation to diverse cognitive processing demands. Separate work on intact neurocognitive performance implicates a higher order factor that largely explains performance across domains and may reflect trait cognitive control capacity. In the current review we highlight findings from respective psychiatric disorders (i.e., psychotic, bipolar and unipolar depressive, anxiety, and substance use disorders) suggesting that cognitive control perturbations amidst psychopathology are most pronounced within these common brain and behavioral indices of adaptive cognitive functioning and moreover, are evident across disorders (i.e., transdiagnostically). Specifically, within each of the disorder classes impairments are consistent in the multiple demand network across a wide range of cognitive tasks. While severity varies between disorders, broad as opposed to domain-specific impairments consistently emerge in neurocognitive performance. Accumulating findings have revealed that phenotypically diverse psychiatric disorders share a common factor or vulnerability to dysfunction that is in turn related to broad neurocognitive deficits. Furthermore, we have observed that regions of the multiple demand network, which overlap with the salience network (dorsal anterior cingulate and bilateral anterior insula) are characterized by reduced gray matter transdiagnostically and predict weaker neurocognitive performance. In summary, transdiagnostic (as opposed to disorder-specific) patterns of symptomatic distress and neurocognitive performance deficits, concurrent with parallel anomalies of brain structure and function may largely contribute to the real-world socio-occupational impairment common across disorders.
PMID: 27552532 [PubMed - as supplied by publisher]
Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder: A meta-analysis study.
J Psychiatr Res. 2016 Aug 5;83:47-53
Authors: Rocha RB, Dondossola ER, Grande AJ, Colonetti T, Ceretta LB, Passos IC, Quevedo J, da Rosa MI
OBJECTIVE: We performed a systematic review and meta-analysis to estimate brain-derived neurotrophic factor (BDNF) level in patients with major depressive disorder (MDD) after electroconvulsive therapy (ECT).
METHOD: A comprehensive search of the Cochrane Library, MEDLINE, LILACS, Grey literature, and EMBASE was performed for papers published from January 1990 to April 2016. The following key terms were searched: "major depressive disorder", "unipolar depression", "brain-derived neurotrophic factor", and "electroconvulsive therapy".
RESULTS: A total of 252 citations were identified by the search strategy, and nine studies met the inclusion criteria of the meta-analysis. BDNF levels were increased among patients with MDD after ECT (P value = 0.006). The standardized mean difference was 0.56 (95% CI: 0.17-0.96). Additionally, we found significant heterogeneity between studies (I(2) = 73%).
CONCLUSION: Our findings suggest a potential role of BDNF as a marker of treatment response after ECT in patients with MDD.
PMID: 27552533 [PubMed - as supplied by publisher]
Inclusion/exclusion criteria in late life depression antidepressant efficacy trials.
Int J Geriatr Psychiatry. 2016 Aug 22;
Authors: Zimmerman M, Multach MD, Clark HL, Walsh E, Rosenstein LK, Gazarian D
OBJECTIVE: The generalizability of antidepressant efficacy trials (AETs) has been questioned. No studies have examined the inclusion/exclusion criteria used in placebo-controlled studies of late life depression and compared them to the criteria used in non-late life AETs.
METHOD: We conducted a comprehensive literature review of placebo-controlled AETs published from January, 1995 through December, 2014. We compared the inclusion/exclusion criteria used in the 18 studies of late life depression to those used in non-late life depression.
RESULTS: There were nine inclusion/exclusion criteria that were used in more than half of the late life depression AETs: minimum severity on a symptom severity scale (100.0%), significant suicidal ideation (77.8%), psychotic features during the current episode of depression or history of a psychotic disorder (94.4%), history of bipolar disorder (77.8%), diagnosis of alcohol or drug abuse or dependence (83.3%), presence of a comorbid nondepressive, nonsubstance use Axis I disorder (55.6%), episode duration too short (66.7%), and an insufficient score on a cognitive screen (88.3%) or the presence of a cognitive disorder (55.6%). There were some differences between the late life and non-late life depression studies-use of a screening measure of cognitive functioning, presence of a cognitive disorder such as dementia, and the minimum depression severity cutoff score required at baseline.
CONCLUSIONS: The inclusion/exclusion criteria in AETs of late life depression were generally similar to the criteria used in non-late life depression AETs. Copyright © 2016 John Wiley & Sons, Ltd.
PMID: 27546477 [PubMed - as supplied by publisher]
Verbal Violence Experiences of Adults With Serious Mental Illnesses.
Psychiatr Rehabil J. 2016 Aug 22;
Authors: Karni-Vizer N, Salzer MS
Trauma experienced by individuals with serious mental illnesses extends beyond physical and sexual abuse. This is among the first studies to examine verbal violence, both spoken and written words, experienced by individuals with serious mental illnesses. Fifty individuals diagnosed with a schizophrenia-spectrum, bipolar, or major depressive disorder were recruited from community-based mental health agencies and reported on their experiences with 8 types of verbal violence identified in the literature, or related written comments, including: belittling, insulting, name-calling, teasing/embarrassing, threatening, cursing, or yelling. They also reported on the frequency of such events and the perpetrators. 82% of participants reported at least 1 type of verbal violence in their lifetime and 66% reported an incident in the past year. The most common experiences were being called names, belittled, and insulted, teased, or embarrassed in front of others. Top perpetrators were friends and parents. Verbal violence is a common experience with potentially devastating effects on mental health and well-being, sense of safety, and recovery and community participation among adults with serious mental illnesses. It is plausible that such comments deserve being recognized as "violence" on par with physical and sexual assaults, although further research would be useful to expand our knowledge about their effects on health, wellness, and community inclusion. New interventions that prevent, lessen, and eliminate such violence, may also be advisable. (PsycINFO Database Record
PMID: 27547854 [PubMed - as supplied by publisher]
Sensorimotor Control Impairment in Young Adults With Idiopathic Scoliosis Compared With Healthy Controls.
J Manipulative Physiol Ther. 2016 Aug 17;
Authors: Pialasse JP, Mercier P, Descarreaux M, Simoneau M
OBJECTIVE: It has been hypothesized that the impaired sensorimotor control observed in adolescents with idiopathic scoliosis (IS) may be related more to the onset of scoliosis than to the maturation of sensory systems or sensorimotor control mechanisms. The objective of this study was to assess sensorimotor control in adults diagnosed with IS in adolescence versus healthy controls.
METHODS: The study included 20 young adults 20 to 24 years of age (10 healthy controls and 10 diagnosed with adolescent IS but not treated for it). Binaural bipolar galvanic vestibular stimulation (GVS) was delivered to assess sensorimotor control. Vertical forces under each foot and upper body kinematics along the frontal plane were measured before GVS (2-second window), during GVS (2-second window), immediately after the cessation of GVS (1-second window), and during the following 2 seconds. Balance control was assessed by calculating the root mean square values of vertical forces and upper body kinematics.
RESULTS: Compared with healthy controls, the IS group showed greater body sway upon GVS; the amplitude of this sway was even greater immediately after the cessation of GVS-an outcome requiring sensorimotor control.
CONCLUSION: Compared with normal controls, adults who had been diagnosed with IS in adolescence showed altered balance control immediately following GVS. This finding suggests that dysfunctional sensorimotor control may be related to the onset of scoliosis rather than to a transient suboptimal development of the sensory systems or sensorimotor control mechanisms.
PMID: 27544925 [PubMed - as supplied by publisher]
Early ERP modulation during mood adjectives processing in patients with affective disorders.
Neurosci Lett. 2016 Aug 16;
Authors: Grzybowski SJ, Wyczesany M
Attentional bias is considered a key feature in mood disorders, and yet little is known of its neural correlates within the early stream of information processing in manic and depressed patients. The study aimed to capture and detail attentional bias during emotional word processing in patients within the first 500ms of stimulus exposition. 28 mood adjectives (14 positive and 14 negative) were used as stimuli. We expected differences in adjective encoding between groups during lexico-semantic analysis based on varying attentional resource allocation. Differences were evidenced within the first 100ms after stimulus onset with higher amplitudes for both patient groups than controls, possibly indicating more automatic attention allocation to stimuli during sensory analysis stages. Between 200-290ms after the words' onset, a specific valence mood-word mismatch was registered which approached significance, with higher responses evoked to negative than positive words in manic patients, and the opposite pattern of activity observed in depressed patients, suggesting cognitive bias based on mood incongruence during the lexico-semantic analysis stage. There was also a lateralized pattern of activity, with higher amplitudes over the right hemisphere posteriorly, and higher over the left frontally in the patient groups, especially in the manic individuals. The study points to attentional bias based on mood incongruence processing during crucial stages of meaning encoding within the early stream of information processing.
PMID: 27542343 [PubMed - as supplied by publisher]
Gene-specific DNA methylation may mediate atypical antipsychotic-induced insulin resistance.
Bipolar Disord. 2016 Aug 20;
Authors: Burghardt KJ, Goodrich JM, Dolinoy DC, Ellingrod VL
OBJECTIVES: Atypical antipsychotics (AAPs) carry a significant risk of cardiometabolic side effects, including insulin resistance. It is thought that the insulin resistance resulting from the use of AAPs may be associated with changes in DNA methylation. We aimed to identify and validate a candidate gene associated with AAP-induced insulin resistance by using a multi-step approach that included an epigenome-wide association study (EWAS) and validation with site-specific methylation and metabolomics data.
METHODS: Subjects with bipolar disorder treated with AAPs or lithium monotherapy were recruited for a cross-sectional visit to analyze peripheral blood DNA methylation and insulin resistance. Epigenome-wide DNA methylation was analyzed in a discovery sample (n = 48) using the Illumina 450K BeadChip. Validation analyses of the epigenome-wide findings occurred in a separate sample (n = 72) using site-specific methylation with pyrosequencing and untargeted metabolomics data. Regression analyses were conducted controlling for known confounders in all analyses and a mediation analysis was performed to investigate if AAP-induced insulin resistance occurs through changes in DNA methylation.
RESULTS: A differentially methylated probe associated with insulin resistance was discovered and validated in the fatty acyl CoA reductase 2 (FAR2) gene of chromosome 12. Functional associations of this DNA methylation site with untargeted phospholipid-related metabolites were also detected. Our results identified a mediating effect of this FAR2 methylation site on AAP-induced insulin resistance.
CONCLUSIONS: Going forward, prospective, longitudinal studies assessing comprehensive changes in FAR2 DNA methylation, expression, and lipid metabolism before and after AAP treatment are required to assess its potential role in the development of insulin resistance.
PMID: 27542345 [PubMed - as supplied by publisher]
Suicidal Behavior in Mood Disorders: Response to Pharmacological Treatment.
Curr Psychiatry Rep. 2016 Sep;18(9):88
Authors: Tondo L, Baldessarini RJ
Suicidal behavior is strongly associated with depression, especially if accompanied by behavioral activation, dysphoria, or agitation. It may respond to some treatments, but the design of scientifically sound, ethical trials to test for therapeutic effects on suicidal behavior is highly challenging. In bipolar disorder, and possibly also unipolar major depression, an underprescribed medical intervention with substantial evidence of preventive effects on suicidal behavior is long-term treatment with lithium. It is unclear whether this effect is specifically antisuicidal or reflects beneficial effects of lithium on depression, mood instability, and perhaps aggression and impulsivity. Antisuicidal effects of anticonvulsant mood stabilizers (carbamazepine, lamotrigine, valproate) appear to be less than with lithium. Further evaluation is needed for potential antisuicidal effects of atypical antipsychotics with growing evidence of efficacy in depression, particularly acute bipolar depression, while generally lacking risk of inducing agitation, mania, or mood instability. Short-term and long-term value and safety of antidepressants are relatively secure for unipolar depression but uncertain and poorly tested for bipolar depression; their effects on suicidal risk in unipolar depression may be age-dependent. Sedative anxiolytics are virtually unstudied as regards suicidal risks. Adequate management of suicidal risks in mood disorder patients requires comprehensive, clinically skillful monitoring and timely interventions.
PMID: 27542851 [PubMed - as supplied by publisher]
Advanced Circadian Phase in Mania and Delayed Circadian Phase in Mixed Mania and Depression Returned to Normal after Treatment of Bipolar Disorder.
EBioMedicine. 2016 Aug 13;
Authors: Moon JH, Cho CH, Son GH, Geum D, Chung S, Kim H, Kang SG, Park YM, Yoon HK, Kim L, Jee HJ, An H, Kripke DF, Lee HJ
Disturbances in circadian rhythms have been suggested as a possible cause of bipolar disorder (BD). Included in this study were 31 mood episodes of 26 BD patients, and 18 controls. Circadian rhythms of BD were evaluated at admission, at 2-week intervals during hospitalization, and at discharge. All participants wore wrist actigraphs during the studies. Saliva and buccal cells were obtained at 8:00, 11:00, 15:00, 19:00, and 23:00 for two consecutive days. Collected saliva and buccal cells were used for analysis of the cortisol and gene circadian rhythm, respectively. Circadian rhythms had different phases during acute mood episodes of BD compared to recovered states. In 23 acute manic episodes, circadian phases were ~7hour advanced (equivalent to ~17hour delayed). Phases of 21 out of these 23 cases returned to normal by ~7hour delay along with treatment, but two out of 23 cases returned to normal by ~17hour advance. In three cases of mixed manic episodes, the phases were ~6-7hour delayed. For five cases of depressive episodes, circadian rhythms phases were ~4-5hour delayed. After treatment, circadian phases resembled those of healthy controls. Circadian misalignment due to circadian rhythm phase shifts might be a pathophysiological mechanism of BD.
PMID: 27543154 [PubMed - as supplied by publisher]
The Prevalence of Bipolar Disorders and Association With Quality of Life in a Cohort of Patients With Multiple Sclerosis.
J Neuropsychiatry Clin Neurosci. 2016 Aug 19;:appineuropsych15120403
Authors: Jun-O'Connell AH, Butala A, Morales IB, Henninger N, Deligiannidis KM, Byatt N, Ionete C
Clinical observations of mood instability in multiple sclerosis (MS) have led to the hypothesis that bipolar disorder (BD) may be more prevalent in persons with MS than in the general population. This cross-sectional study assesses the prevalence of BD among patients with MS using standardized psychiatric diagnostic interviews and evaluates quality of life. This study demonstrates a higher prevalence of BD in patients with MS compared with the general population. It also reveals the negative impact of BD on quality of life, raises the concern that BD can occur before the onset of neurological symptoms in MS, and suggests that, in some cases, BD may delay diagnosis of MS.
PMID: 27539374 [PubMed - as supplied by publisher]
Antidepressant Action on Mitochondrial Dysfunction in Psychiatric Disorders.
Drug Dev Res. 2016 Aug 19;
Authors: Adzic M, Brkic Z, Bulajic S, Mitic M, Radojcic MB
Preclinical Research Mitochondria are cell organelles crucial to the production of cellular energy. Several lines of evidence have indicated that mitochondrial dysfunction could be related to the pathophysiology of CNS diseases including bipolar disorder, major depressive disorder, and schizophrenia. These changes include impaired energy metabolism in the brain, co-morbidity with mitochondrial diseases, the effects of psychotropics on mitochondrial function, increased mitochondrial DNA (mtDNA) deletion in the brain, and association with mtDNA polymorphisms. Additionally, psychotropic drug treatments can alter energy metabolism and may affect mitochondrial processes. This review focuses on recent findings regarding the effects of antidepressants on mitochondrial processes in psychiatric disorders. Drug Dev Res, 2016. © 2016 Wiley Periodicals, Inc.
PMID: 27539538 [PubMed - as supplied by publisher]
The Psychiatric Inclusion and Exclusion Criteria in Placebo-Controlled Monotherapy Trials of Bipolar Depression: An Analysis of Studies of the Past 20 Years.
CNS Drugs. 2016 Aug 19;
Authors: Zimmerman M, Holst CG, Clark HL, Multach M, Walsh E, Rosenstein LK, Gazarian D
BACKGROUND: Concerns about the generalizability of pharmacotherapy efficacy trials to "real-world" patients have been raised for more than 40 years. Almost all of this literature has focused on treatment studies of major depressive disorder (MDD).
OBJECTIVE: The aim of the study was to review the psychiatric inclusion and exclusion criteria used in placebo-controlled trials that assessed the efficacy of medications for bipolar depression (bipolar disorder efficacy trials [BDETs]) and compare the criteria used in BDETs with those used in efficacy trials of antidepressants to treat MDD (antidepressant efficacy trials [AETs]).
METHODS: We searched the MEDLINE, Embase, and PsycINFO databases for articles published from January 1995 through December 2014. We identified 170 placebo-controlled AETs and 22 BDETs published during these 20 years. Two of the authors independently reviewed each article and completed a pre-specified information extraction form listing the psychiatric inclusion and exclusion criteria used in the study.
RESULTS: Six inclusion/exclusion criteria were used in at least half of the BDETs: minimum severity on a depression symptom severity scale, significant suicidal ideation, diagnosis of alcohol or drug use disorder, presence of a comorbid nondepressive, nonsubstance use Axis I disorder, current episode of depression being too long, and absence of current manic symptoms. BDETs were significantly less likely than AETs to exclude patients with a history of psychotic features/disorders, borderline personality disorder, and post-traumatic stress disorder and more likely to exclude individuals who scored too low on the first item of the Hamilton Depression Rating Scale. Nearly two-thirds of the BDETs placed an upper limit on the duration of the current depressive episode, three times higher than the rate in the AETs. There was no difference on other variables between the AETs and BDETs.
CONCLUSIONS: Similar to treatment studies of nonbipolar MDD, the treatment studies of bipolar depression frequently excluded patients with comorbid psychiatric and substance use disorders and insufficient severity of depressive symptoms as rated on standardized scales. These findings indicate that concerns about the generalizability of data from trials of recently approved medications for the treatment of bipolar depression are as relevant as the concerns that have been raised about studies of antidepressants for nonbipolar depression.
PMID: 27541608 [PubMed - as supplied by publisher]
The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion.
Neuropathol Appl Neurobiol. 2015 Dec;41(7):941-51
Authors: Moskovitz J, Walss-Bass C, Cruz DA, Thompson PM, Hairston J, Bortolato M
AIMS: The enzyme catechol-O-methyltransferase (COMT) plays a primary role in the metabolism of catecholamine neurotransmitters and is implicated in the modulation of cognitive and emotional responses. The best characterized single nucleotide polymorphism (SNP) of the COMT gene consists of a valine (Val)-to-methionine (Met) substitution at codon 108/158. The Met-containing variant confers a marked reduction in COMT catalytic activity. We recently showed that the activity of recombinant COMT is positively regulated by the enzyme Met sulphoxide reductase (MSR), which counters the oxidation of Met residues of proteins. The current study was designed to assess whether brain COMT activity may be correlated to MSR in an allele-dependent fashion.
METHODS: COMT and MSR activities were measured from post-mortem samples of prefrontal cortices, striata and cerebella of 32 subjects by using catechol and dabsyl-Met sulphoxide as substrates, respectively. Allelic discrimination of COMT Val(108/185) Met?SNP was performed using the Taqman 5'nuclease assay.
RESULTS: Our studies revealed that, in homozygous carriers of Met, but not Val alleles, the activity of COMT and MSR was significantly correlated throughout all tested brain regions.
CONCLUSION: These results suggest that the reduced enzymatic activity of Met-containing COMT may be secondary to Met sulphoxidation and point to MSR as a key molecular determinant for the modulation of COMT activity.
PMID: 25640985 [PubMed - indexed for MEDLINE]
Cognitive reserve lessens the burden of white matter lesions on executive functions in bipolar disorder.
Psychol Med. 2016 Aug 18;:1-10
Authors: Rolstad S, Abé C, Olsson E, Eckerström C, Landén M
BACKGROUND: The concept of cognitive reserve (CR) hypothesizes that intellectually stimulating activities provide resilience against brain pathology/disease. Whereas brain abnormalities and cognitive impairment are frequently reported in bipolar disorder (BD), it is unknown whether the impact of brain alterations can be lessened by higher CR in BD.
METHOD: We tested if higher CR would reduce the influence of total volumes of deep white matter hypointensities (WMH), ventricular cerebrospinal fluid (CSF), and prefrontal cortex on memory, executive, and attention/speed functions in patients with BD (n = 75). Linear regression models with interaction terms for CR and brain volumes were applied to directly test if CR reduces the influence of brain pathology on cognitive domains.
RESULTS: CR reduced the influence of total volumes of deep WMH (? = -0.38, Q = 0.003) and ventricular CSF (? = -41, Q = 006) on executive functions.
CONCLUSIONS: The interactions between CR and total volumes of deep WMH/ventricular CSF appear to account for executive functioning in BD. The results suggest that the concept of CR is applicable in BD. Higher reserve capacity in BD alters the relationship between brain pathology and clinical presentation.
PMID: 27534695 [PubMed - as supplied by publisher]
A case of lithium intoxication induced by an antihypertensive angiotensin 1 subtype-specific angiotensin II receptor blocker in an elderly patient with bipolar disorder and hypertension.
Nihon Ronen Igakkai Zasshi. 2016;53(3):244-9
Authors: Hayashi Y, Nishida S, Takekoshi A, Murakami M, Yamada M, Kimura A, Suzuki A, Inuzuka T
Lithium carbonate is considered to be a first-line treatment for bipolar disorder; however, this drug has a narrow therapeutic window, and lithium intoxication is commonly induced by various drugs interaction and situations. We herein report a case of lithium intoxication induced by the administration of an antihypertensive agent targeting the angiotensin 1 (AT1) subtype of the angiotensin II receptor in a 65-year-old woman with a 40-year history of bipolar disorder type 1, and 1-year history of essential hypertension. Her bipolar disorder had been well-controlled with 600 mg/day of lithium carbonate for more than 10 years. She was later diagnosed with hypertension and the AT1 receptor blocker, azilsartan was thereafter administrated on a daily basis. After 3 weeks of azilsartan administration, she presented with progressive action tremor and showed a gradual deterioration of her physical state. Four months after the start of azilsartan administration, she presented with alternating episodes of diarrhea and constipation. Two weeks before admission to our hospital, she presented with mild consciousness disturbances, myoclonus, truncal ataxia, and appetite loss. She was diagnosed to have lithium intoxication based on an elevated serum lithium concentration of 3.28 mEq/l.It is therefore important to evaluate the serum lithium concentration after the administration of antihypertensive agents, and consider lithium-antihypertensive agent interactions when selecting antihypertensive agents in elderly patients receiving long-term lithium carbonate treatment.
PMID: 27535187 [PubMed - in process]
Increased Serum Levels of Oxytocin in 'Treatment Resistant Depression in Adolescents (TRDIA)' Group.
PLoS One. 2016;11(8):e0160767
Authors: Sasaki T, Hashimoto K, Oda Y, Ishima T, Yakita M, Kurata T, Kunou M, Takahashi J, Kamata Y, Kimura A, Niitsu T, Komatsu H, Hasegawa T, Shiina A, Hashimoto T, Kanahara N, Shimizu E, Iyo M
OBJECTIVE: 'Treatment-resistant depression' is depression that does not respond to an adequate regimen of evidence-based treatment. Treatment-resistant depression frequently becomes chronic. Children with treatment-resistant depression might also develop bipolar disorder (BD). The objective of this study was to determine whether serum levels of oxytocin (OXT) in treatment-resistant depression in adolescents (TRDIA) differ from non-treatment-resistant depression in adolescents (non-TRDIA) or controls. We also investigated the relationships between serum OXT levels and the clinical symptoms, severity, and familial histories of adolescent depressive patients.
METHODS: We measured serum OXT levels: TRDIA (n = 10), non-TRDIA (n = 27), and age- and sex- matched, neurotypical controls (n = 25). Patients were evaluated using the Children's Depression Rating Scale-Revised (CDRS-R) and the Depression Self-Rating Scale for Children-Japanese Version (DSRS-C-J). The patients were also assessed retrospectively using the following variables: familial history of major depressive disorder and BD (1st degree or 2nd degree), history of disruptive mood dysregulation disorder, recurrent depressive disorder (RDD), history of antidepressant activation.
RESULTS: Serum levels of OXT among the TRDIA and non-TRDIA patients and controls differed significantly. Interestingly, the rates of a family history of BD (1st or 2nd degree), RDD and a history of antidepressant activation in our TRDIA group were significantly higher than those of the non-TRDIA group.
CONCLUSIONS: Serum levels of OXT may play a role in the pathophysiology of TRDIA.
PMID: 27536785 [PubMed - as supplied by publisher]
A meta-analysis and systematic review of the comorbidity between irritable bowel syndrome and bipolar disorder.
Medicine (Baltimore). 2016 Aug;95(33):e4617
Authors: Tseng PT, Zeng BS, Chen YW, Wu MK, Wu CK, Lin PY
Irritable bowel syndrome (IBS) and bipolar disorder (BD) are 2 distinct diseases but may share a similar pathophysiology. However, the comorbidity rate of these 2 diseases is unclear. Also, the current practice guidelines suggest prescribing antidepressants to IBS patients. However, this practice may increase the risk of phase-shift to manic episodes in IBS patients comorbid with BD.This study aimed to determine the relationship between IBS and BD through a meta-analysis.Electronic research through PubMed, Medline, ScienceDirect online, ClinicalTrials.gov, and additional resources.The inclusion criteria were studies investigating the prevalence rate of BD in subjects with IBS and control subjects; and articles on clinical trials on humans.Data from included studies were pooled by a random effects model, and possible confounding variables were examined by meta-regression and subgroup analysis.The current study consists of a total of 177,117 IBS patients and 192,092 control subjects extracted from 6 included studies. The prevalence rate of BD was significantly higher in the IBS patients than in the controls (odds ratio = 2.48, 95% confidence interval: 2.35-2.61, P?<?0.001). However, the significance persists only in studies from database research, but not from primary studies. In addition, there was no significant association between the prevalence rate of BD in IBS and several clinical variables, including age, female proportion, prevalence of comorbid diabetes, or hypertension.The total number of included studies is small. Moreover, apparently different results from database research and primary research limit the generalization of our findings to a broad population. Also, we could only perform meta-regression on limited clinical variables.Our results support a significantly higher prevalence rate of BD in IBS patients than in controls. Clinicians should be cautious about the risk of phase-shift to manic episodes when prescribing antidepressants in IBS patients under current practice guidelines.
PMID: 27537599 [PubMed - as supplied by publisher]
Contrasting Emotion Processing and Executive Functioning in Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder.
Behav Neurosci. 2016 Aug 18;
Authors: Soncin S, Brien DC, Coe BC, Marin A, Munoz DP
Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) are highly comorbid and share executive function and emotion processing deficits, complicating diagnoses despite distinct clinical features. We compared performance on an oculomotor task that assessed these processes to capture subtle differences between ADHD and BD. The interaction between emotion processing and executive functioning may be informative because, although these processes overlap anatomically, certain regions that are compromised in each network are different in ADHD and BD. Adults, aged 18-62, with ADHD ( = 22), BD ( = 20), and healthy controls ( = 21) performed an interleaved pro- and antisaccade task (looking toward vs. looking away from a visual target, respectively). Task irrelevant emotional faces (fear, happy, sad, neutral) were presented on a subset of trials either before or with the target. The ADHD group made more direction errors (looked in the wrong direction) than controls. Presentation of negatively valenced (fear, sad) and ambiguous (neutral) emotional faces increased saccadic reaction time in BD only compared to controls, whereas longer presentation of sad faces modestly increased group differences. The antisaccade task differentiated ADHD from controls. Emotional processing further impaired processing speed in BD. We propose that the dorsolateral prefrontal cortex is critical in both processing systems, but the inhibitory signal this region generates is impacted by dysfunction in the emotion processing network, possibly at the orbitofrontal cortex, in BD. These results suggest there are differences in how emotion processing and executive functioning interact, which could be utilized to improve diagnostic specificity. (PsycINFO Database Record
PMID: 27537826 [PubMed - as supplied by publisher]
The prevalence of thyroid disorders among sexual and violent offenders and their co-occurrence with psychological symptoms.
Int J Prison Health. 2009;5(1):25-38
Authors: Langevin R, Langevin M, Curnoe S, Bain J
The prevalence of thyroid abnormalities among 831 sexual, violent, and non-violent non-sex offenders was found to be greater than found in the general population. Thyroid abnormalities were most common among violent offenders and among sex offenders who victimized children. Thyroid disorders were associated with psychotic diagnoses, delusions, mania, suicidal thoughts, and showed a trend to more suicide attempts. These disorders were undiagnosed in 49.1% of the cases prior to the present clinical assessment. Of these, 59.3% faced their first criminal charges, and the undiagnosed thyroid abnormalities may be important in the offenders' treatment and may be possible legal mitigating factors in some offenses. Results indicate that a routine endocrine evaluation with blood tests would be a valuable addition to the assessment of violent and sexual offenders.
PMID: 25758927 [PubMed - indexed for MEDLINE]
Is age of onset associated with severity, prognosis, and clinical features in bipolar disorder? A meta-analytic review.
Bipolar Disord. 2016 Aug 17;
Authors: Joslyn C, Hawes DJ, Hunt C, Mitchell PB
OBJECTIVES: To identify clinical characteristics and adverse outcomes associated with an earlier age of onset of bipolar disorder.
METHODS: A comprehensive search yielded 15 empirical papers comparing clinical presentation and outcomes in individuals with bipolar disorder grouped according to age of onset (total N=7370). The following variables were examined to determine odds ratios (ORs) and 95% confidence intervals (CIs): presence of Axis I comorbidity, rapid cycling, psychotic symptoms, mixed episodes (DSM-IV), lifetime suicide attempts, lifetime alcohol and substance abuse, symptom severity, and treatment delay.
RESULTS: Early age of onset was found to be associated with longer delay to treatment (Hedges' g=0.39, P=.001), greater severity of depression (Hedges' g=0.42, P<.001), and higher levels of comorbid anxiety (OR=2.34, P<.001) and substance use (OR=1.80, P<.001). Surprisingly, no association was found between early age of onset and clinical characteristics such as psychotic symptoms or mixed episodes as defined by DSM-IV.
CONCLUSIONS: Earlier age of onset of bipolar disorder is associated with factors that can negatively impact long-term outcomes such as increased comorbidity. However, no association was found between early onset and indicators of severity or treatment resistance such as psychotic symptoms. Clinical features found to have the strongest relationship with early age of onset were those potentially amenable to pharmacological and psychological treatment. Results highlight the importance of early identification and provide potential areas of focus for the development of early intervention in bipolar disorder.
PMID: 27530107 [PubMed - as supplied by publisher]
Opportunities for translational research in the epigenetics of mood disorders: a comment to the review by Robert M. Post.
Bipolar Disord. 2016 Aug 17;
Authors: Malhi GS, Outhred T
PMID: 27530207 [PubMed - as supplied by publisher]
Distinct behavioral and immunoendocrine parameters during crack cocaine abstinence in women reporting childhood abuse and neglect.
Drug Alcohol Depend. 2016 Aug 11;
Authors: Levandowski ML, Viola TW, Prado CH, Wieck A, Bauer ME, Brietzke E, Grassi-Oliveira R
AIM: To assess plasma levels of cortisol and cytokines between cocaine-dependent women with and without childhood maltreatment (CM) history during cocaine detoxification treatment.
METHOD: We assessed immunoendocrine and clinical parameters of 108 crack cocaine female users during 3 weeks of inpatient detoxification treatment, and 24 healthy women to obtain reference values. Women with (CM+, n=53) or without (CM-, n=55) CM history were identified answering the Childhood Trauma Questionnaire (CTQ). Blood samples and clinical assessment were collected before lunch during the first, second and third week post-treatment admission. Flow cytometry was used to assess TNF-?, IFN-?, IL-2, IL-4, IL-6, IL-10, IL-17A plasma levels and ELISA assay was used to measure plasma cortisol levels.
RESULTS: At baseline, lower Th1 and Th17-related cytokines levels and higher Th2 cytokines levels were observed in crack cocaine users compared with reference values. Cytokines levels of cocaine dependents gradually became closer to reference values along detoxification treatment. However, when CM+ and CM- groups were compared, increased levels of IL-6, IL-4 and TNF-? across time were observed in CM+ group only. Additionally, a Th1/Th2 immune imbalance was observed within CM+ group, which was negatively correlated with the severity of the crack withdrawal. Finally, loading trauma exposure severity, immunoendocrine and clinical parameters in factor analysis, we identified three clusters of observed variables during detoxification: (1) systemic immunity and trauma exposure, (2) pro-inflammatory immunity and (3) behavior CONCLUSION: Our results suggest the existence of an immunological phenotype variant associated with CM exposure during crack cocaine detoxification of women.
PMID: 27530287 [PubMed - as supplied by publisher]
nArgBP2 as a hub molecule in the etiology of various neuropsychiatric disorders.
BMB Rep. 2016 Aug 17;
Authors: Lee SE, Chang S
Recent studies have strongly implicated postsynaptic scaffolding proteins such as SAPAP3 or Shank3 in the pathogenesis of various mood disorders, including autism spectrum disorder, bipolar disorder (BD), and obsessive-compulsive disorders. Neural Abelson-related gene-binding protein 2 (nArgBP2) was originally identified as a protein that interacts with SAPAP3 and Shank3. Recent study shows that the genetic deletion of nArgBP2 in mice leads to manic/bipolar-like behavior resembling symptoms of BD. However, the function of nArgBP2 at synapse, or its connection with the synaptic dysfunctions, is completely unknown. This study provides compelling evidence that nArgBP2 regulates the spine morphogenesis through the activation of Rac1/WAVE/PAK/cofilin pathway, and that its ablation causes a robust and selective inhibition of excitatory synapse formation, by controlling actin dynamics. Our results revealed the underlying mechanism for the synaptic dysfunction caused by nArgBP2 downregulation that associates with analogous human BD. Moreover, since nArgBP2 interacts with key proteins involved in various neuropsychiatric disorders, our finding implies that nArgBP2 could function as a hub linking various etiological factors of different mood disorders.
PMID: 27530683 [PubMed - as supplied by publisher]
Challenges and developments in research of the early stages of bipolar disorder.
Rev Bras Psiquiatr. 2016 Aug 11;:0
Authors: Brietzke E, Rosa AR, Pedrini M, Noto MN, Kapczinski F, Scott J
Recently, attention in the field of bipolar disorder (BD) has focused on prevention, including early detection and intervention, as these strategies have the potential to delay, lessen the severity, or even prevent full-blown episodes of BD. Although knowledge of the neurobiology of BD has advanced substantially in the last two decades, most research was conducted with chronic patients. The objective of this paper is to comprehensively review the literature regarding the early stages of BD, to explore recent discoveries on the neurobiology of these stages, and to discuss implications for research and clinical care. The following databases were searched: PubMed, PsycINFO, Cochrane Library, and SciELO. Articles published in English from inception to December 2015 were retrieved. Several research approaches were used, including examination of offspring studies, retrospective studies, prospective studies of clinical high-risk populations, and exploration of the progression after the first manic episode. Investigations with neuroimaging, cognition assessments, and biomarkers provide promising (although not definitive) evidence of alterations in the neural substrate during the at-risk stage. Research on BD should be expanded to encompass at-risk states and aligned with recent methodological progress in neuroscience.
PMID: 27533022 [PubMed - as supplied by publisher]
Monitoring fluid intake in mental health patients.
Nurs Stand. 2016 Aug 17;30(51):36
Authors: Taylor D
During my second year of nurse training, I had a clinical placement on an acute male psychiatric ward with around 20 male patients. They had a variety of mental health conditions, including depression, bipolar affective disorder and schizophrenia.
PMID: 27533410 [PubMed - as supplied by publisher]
'What is to be done?'.
Aust N Z J Psychiatry. 2015 Nov;49(11):953-4
Authors: Henderson S
PMID: 26508798 [PubMed - indexed for MEDLINE]