Ten-year outcomes in first episode psychotic major depression patients compared with schizophrenia and bipolar patients.
Schizophr Res. 2016 May 25;
Authors: Heslin M, Lappin JM, Donoghue K, Lomas B, Reininghaus U, Onyejiaka A, Croudace T, Jones PB, Murray RM, Fearon P, Doody GA, Dazzan P, Craig TJ, Morgan C
We aimed to investigate long-term outcomes in psychotic major depression patients compared to schizophrenia and bipolar/manic psychosis patients, in an incidence sample, while accounting for diagnostic change. Based on Aetiology and Ethnicity in Schizophrenia and Other Psychoses (ÆSOP and ÆSOP-10), a first episode psychosis cohort was followed-up 10years after first presentation. The Schedules for Clinical Assessment in Neuropsychiatry, WHO Life Chart and Global Assessment of Functioning were used to assess clinical, social and service use outcomes. Seventy-two PMD patients, 218 schizophrenia patients and 70 psychotic bipolar disorder/mania patients were identified at baseline. Differences in outcome between PMD and bipolar patients based on baseline and lifetime diagnosis were minimal. Differences in clinical, social and service use outcomes between PMD and schizophrenia were more substantial with PMD patients showing better outcomes on most variables. However, there was some weak evidence (albeit not quite statistically significant at p<0.05) based on lifetime diagnoses that PMD patients were more likely to attempt suicide (OR 2.31, CI 0.98-5.42, p0.055) and self-harm (OR 2.34, CI 0.97-5.68, p0.060). PMD patients have better social and service use outcomes compared to people with schizophrenia, but may be more likely to attempt suicide or self-harm. This unique profile is important for clinicians to consider in any risk assessment.
PMID: 27236408 [PubMed - as supplied by publisher]
Commentary on "Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial".
Bipolar Disord. 2016 May 27;
Authors: Wirz-Justice A, Terman M
PMID: 27233225 [PubMed - as supplied by publisher]
Acute risk factors for suicide attempts and death: prospective findings from the STEP-BD study.
Bipolar Disord. 2016 May 27;
Authors: Ballard ED, Vande Voort JL, Luckenbaugh DA, Machado-Vieira R, Tohen M, Zarate CA
OBJECTIVES: Suicide is unfortunately common in psychiatric practice, but difficult to predict. The present study sought to assess which clinical symptoms increase in the months before suicidal behavior in a sample of psychiatric outpatients with bipolar disorder.
METHODS: Data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial were used. A total of 103 participants who attempted suicide or died by suicide during the trial were included; a 15% random sample of the remaining participants (n = 427) was used as a comparison sample. Linear mixed models in the six months before suicidal behavior were conducted for each of five proposed acute risk factors for suicidal behavior. Participants were assessed using the Clinical Monitoring Form (CMF) at each visit for the following potential acute risk factors for suicidal behavior: suicidal ideation, loss of interest, anxiety, psychomotor agitation, and high-risk behavior.
RESULTS: Each of the five symptoms was elevated overall in individuals who engaged in suicidal behavior (p < 0.05). The severity of both suicidal ideation and loss of interest significantly increased in the months before suicidal behavior (p < 0.001). Anxiety demonstrated comparable effect sizes across multiple models. Psychomotor agitation and high-risk behavior were not significantly elevated before suicidal behavior.
CONCLUSIONS: Suicidal ideation, loss of interest and, to a lesser extent, anxiety may represent acute suicide risk factors up to four months before suicidal behavior in outpatients with bipolar disorder. Further investigation of these potential acute risk factors in prospective analyses is warranted.
PMID: 27233466 [PubMed - as supplied by publisher]
Differences in cognitive impairment between schizophrenia and bipolar disorder: Considering the role of heterogeneity.
Psychiatry Clin Neurosci. 2016 May 28;
Authors: Bora E
Schizophrenia is associated with significant cognitive impairment. Bipolar disorder (BP) also presents?with cognitive?deficits that are similar to,?albeit less severe?than those reported in schizophrenia. There has been controversy over whether selective deficits in social cognition or developmental trajectory of cognitive deficits can distinguish schizophrenia from BP. Also, available studies have not generally considered the potential effect of cognitive heterogeneity within both disorders on between-group differences. Current review examines the evidence on the specificity of social cognitive deficits and early neurocognitive impairment to schizophrenia and explores the overall outcome of studies investigating within and cross-diagnosis cognitive heterogeneity in schizophrenia and BP. Current evidence does not support the specificity of social cognitive impairment to schizophrenia. Available studies also suggest that cognitive impairment in premorbid and early stages is evident not only in schizophrenia but also many patients in BP. Both schizophrenia and BP have a number of cognitive subgroups including severe impairment, good functioning and one or more selective or modest impairment clusters. While both disorders are represented in each cognitive subgroup, there are significant cross-diagnostic differences regarding prevalences of individuals belonging to the severe impairment and good functioning subgroups. The individuals with schizophrenia are much more likely to exhibit severe cognitive impairment than individuals with BP and opposite true for having good cognitive functioning. Further identification of neurobiological and genetic characteristics of cognitive subgroups in major psychoses can improve the validity of diagnostic systems and can advance the development of personalized management approaches including cognitive remediation.
PMID: 27233969 [PubMed - as supplied by publisher]
Facial emotion recognition in euthymic patients with bipolar disorder and their unaffected first-degree relatives.
Compr Psychiatry. 2016 Jul;68:18-23
Authors: de Brito Ferreira Fernandes F, Gigante AD, Berutti M, Amaral JA, de Almeida KM, de Almeida Rocca CC, Lafer B, Nery FG
BACKGROUND: Facial emotion recognition (FER) is an important task associated with social cognition because facial expression is a significant source of non-verbal information that guides interpersonal relationships. Increasing evidence suggests that bipolar disorder (BD) patients present deficits in FER and these deficits may be present in individuals at high genetic risk for BD. The aim of this study was to evaluate the occurrence of FER deficits in euthymic BD patients, their first-degree relatives, and healthy controls (HC) and to consider if these deficits might be regarded as an endophenotype candidate for BD.
METHODS: We studied 23 patients with DSM-IV BD type I, 22 first-degree relatives of these patients, and 27 HC. We used the Penn Emotion Recognition Tests to evaluate tasks of FER, emotion discrimination, and emotional acuity. Patients were recruited from outpatient facilities at the Institute of Psychiatry of the University of Sao Paulo Medical School, or from the community through media advertisements, had to be euthymic, with age above 18years old and a diagnosis of DSM-IV BD type I.
RESULTS: Euthymic BD patients presented significantly fewer correct responses for fear, and significantly increased time to response to recognize happy faces when compared with HC, but not when compared with first-degree relatives. First-degree relatives did not significantly differ from HC on any of the emotion recognition tasks.
CONCLUSION: Our results suggest that deficits in FER are present in euthymic patients, but not in subjects at high genetic risk for BD. Thus, we have not found evidence to consider FER as an endophenotype candidate for BD.
PMID: 27234178 [PubMed - in process]
Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder.
Compr Psychiatry. 2016 Jul;68:34-9
Authors: Bumb JM, Enning F, Mueller JK, van der List T, Rohleder C, Findeisen P, Noelte I, Schwarz E, Leweke FM
BACKGROUND: Melatonin, which plays an important role for regulation of circadian rhythms and the sleep/wake cycle has been linked to the pathophysiology of major depressive and bipolar disorder. Here we investigated melatonin levels in cerebrospinal fluid (CSF) and serum of depression and bipolar patients to elucidate potential differences and commonalities in melatonin alterations across the two disorders.
METHODS: Using enzyme-linked immunosorbent assays, CSF and serum melatonin levels were measured in 108 subjects (27 healthy volunteers, 44 depressed and 37 bipolar patients). Covariate adjusted multiple regression analysis was used to investigate group differences in melatonin levels.
RESULTS: In CSF, melatonin levels were significantly decreased in bipolar (P<0.001), but not major depressive disorder. In serum, we observed a significant melatonin decrease in major depressive (P=0.003), but not bipolar disorder. No associations were found between serum and CSF melatonin levels or between melatonin and measures of symptom severity or sleep disruptions in either condition.
CONCLUSION: This study suggests the presence of differential, body fluid specific alterations of melatonin levels in bipolar and major depressive disorder. Further, longitudinal studies are required to explore the disease phase dependency of melatonin alterations and to mechanistically explore the causes and consequences of site-specific alterations.
PMID: 27234180 [PubMed - in process]
Study of positive and negative feedback sensitivity in psychosis using the Wisconsin Card Sorting Test.
Compr Psychiatry. 2016 Jul;68:119-28
Authors: Farreny A, Del Rey-Mejías Á, Escartin G, Usall J, Tous N, Haro JM, Ochoa S
BACKGROUND: Schizophrenia involves marked motivational and learning deficits that may reflect abnormalities in reward processing. The purpose of this study was to examine positive and negative feedback sensitivity in schizophrenia using computational modeling derived from the Wisconsin Card Sorting Test (WCST). We also aimed to explore feedback sensitivity in a sample with bipolar disorder.
METHODS: Eighty-three individuals with schizophrenia and 27 with bipolar disorder were included. Demographic, clinical and cognitive outcomes, together with the WCST, were considered in both samples. Computational modeling was performed using the R syntax to calculate 3 parameters based on trial-by-trial execution on the WCST: reward sensitivity (R), punishment sensitivity (P), and choice consistency (D). The associations between outcome variables and the parameters were investigated.
RESULTS: Positive and negative sensitivity showed deficits, but P parameter was clearly diminished in schizophrenia. Cognitive variables, age, and symptoms were associated with R, P, and D parameters in schizophrenia. The sample with bipolar disorder would show cognitive deficits and feedback abnormalities to a lesser extent than individuals with schizophrenia.
CONCLUSION: Negative feedback sensitivity demonstrated greater deficit in both samples. Idiosyncratic cognitive requirements in the WCST might introduce confusion when supposing model-free reinforcement learning. Negative symptoms of schizophrenia were related to lower feedback sensitivity and less goal-directed patterns of choice.
PMID: 27234192 [PubMed - in process]
High Frequency Electrical Stimulation of Lateral Habenula Reduces Voluntary Ethanol Consumption in Rats.
Int J Neuropsychopharmacol. 2016 May 27;
Authors: Li J, Zuo W, Fu R, Xie G, Kaur A, Bekker A, Ye JH
BACKGROUND: Development of new strategies that can effectively prevent and/or treat alcohol use disorders is of paramount importance, because the currently available treatments are inadequate. Increasing evidence indicates that the lateral habenula (LHb) plays an important role in aversion, drug abuse, and depression. In light of the success of high-frequency stimulation (HFS) of the LHb in improving helplessness behavior in rodents, we assessed the effects of LHb HFS on ethanol-drinking behavior in rats.
METHODS: We trained rats to drink ethanol under an intermittent access two-bottle choice procedure. We used c-Fos immunohistochemistry and electrophysiological approaches to examine LHb activity. We applied a HFS protocol that has proven effective for reducing helplessness behavior in rats via a bipolar electrode implanted into the LHb.
RESULTS: c-Fos protein expression and the frequency of both spontaneous action potential firings and spontaneous excitatory postsynaptic currents were higher in LHb neurons of ethanol-withdrawn rats compared to their ethanol-naïve counterparts. HFS to the LHb produced long-term reduction of intake and preference for ethanol, without altering locomotor activity. Conversely, low-frequency electrical stimulation to the LHb or HFS applied to the nearby nucleus did not affect drinking behavior.
CONCLUSIONS: Our results suggest that withdrawal from chronic ethanol exposure increases glutamate release and the activity of LHb neurons, and that functional inhibition of the LHb via HFS reduces ethanol consumption. Thus, LHb HFS could be a potential new therapeutic option for alcoholics.
PMID: 27234303 [PubMed - as supplied by publisher]
In vitro protective efficacy of Lithium chloride against Mycoplasma hyopneumoniae infection.
Res Vet Sci. 2016 Jun;106:93-6
Authors: Ishag HZ, Wu YZ, Liu MJ, Xiong QY, Feng ZX, Yang RS, Shao GQ
Mycoplasma hyopneumoniae (M. hyopneumoniae) infection affects the swine industry. Lithium chloride (LiCl), is a drug used to treat bipolar disorder and has also shown activity against bacterial and viral infections. Herein, we evaluated the antibacterial activity of LiCl on PK-15 cells infected with M. hyopneumoniae. Incubation of LiCl (40mM) with cells for 24h, did not significantly affect the cell viability. The qRT-PCR showed ~80% reduction in M. hyopneumoniae genome when LiCl added post-infection. A direct effect of LiCl on bacteria was also observed. However, treatment of cells with LiCl prior infection, does not protect against the infection. Anti-bacterial activity of LiCl was further confirmed by IFA, which demonstrated a reduction in the bacterial protein. With 40mM LiCI, the apoptotic cell death, production of nitric oxide and superoxide anion induced by M. hyopneumoniae, were prevented by ~80%, 60% and 58% respectively. Moreover, caspase-3 activity was also reduced (82%) in cells treated with 40mM LiCl. LiCl showed activity against various strains of M. hyopneumoniae examined in our study. Collectively, our data showed that LiCl inhibited the infection of M. hyopneumoniae through anti-apoptotic mechanism.
PMID: 27234543 [PubMed - in process]
Curcumin in depressive disorders: an overview of potential mechanisms, preclinical and clinical findings.
Eur J Pharmacol. 2016 May 24;
Authors: Kaufmann FN, Gazal M, Bastos C, Kaster MP, Ghisleni G
Considering the high prevalence of psychiatric disorders, its social burden and the limitations of currently available treatments, alternative therapeutic approaches targeting different biological pathways have been investigated. Curcumin is a natural compound with multi-faceted pharmacological properties, interacting with several neurotransmitter systems and intracellular signaling pathways involved in mood regulation. Also, curcumin has anti-inflammatory, antioxidant and neurotrophic effects, suggesting a strong potential to manage conditions associated with neurodegeneration, such as psychiatric disorders. Most literature data focused on the potential of curcumin to counteract behavioral and neurochemical alterations in preclinical models of depression. The findings still need to be further explored and clinical reports share some controversial results that might be associated with its low systemic bioavailability following oral administration. Other psychiatric disorders also have neurochemical alterations similar to those found in depression, including neurotoxicity, oxidative stress and neuroinflammation. Despite the limited number of reports, preclinical models investigated the potential role for curcumin in anxiety, bipolar disorder, post-traumatic stress disorder and autism spectrum disorders. Here, we will summarize the cellular targets of curcumin relevant to psychiatric disorders and its effects in preclinical and clinical studies with depression, anxiety disorders and other psychiatric related conditions.
PMID: 27235294 [PubMed - as supplied by publisher]
Physical activity and sedentary behavior in people with bipolar disorder: A systematic review and meta-analysis.
J Affect Disord. 2016 May 14;201:145-152
Authors: Vancampfort D, Firth J, Schuch F, Rosenbaum S, De Hert M, Mugisha J, Probst M, Stubbs B
BACKGROUND: Mortality rates are approximately two to three times higher in people with bipolar disorder (BD) than in general population. Lack of physical activity (PA) and sedentary behavior (SB) are independent risk factors for cardiovascular disease and premature mortality.
AIMS: We conducted a meta-analysis to investigate PA and SB levels and its predictors in BD.
METHODS: Major electronic databases were searched from inception till 02/2016 for articles measuring PA and SB with a self-report questionnaire (SRQ) or objective measure (e.g. accelerometer) in BD. A random effects meta-analysis and meta-regression analysis were conducted.
RESULTS: Six studies were eligible including 279 (129?) people with BD (mean age=43.9 years; range: 32.0-51.5 years). The trim and fill analysis demonstrated people with BD spent in total 210.1min (95%CI=146.3-273.9min) per day being physically active and 613.3min (95%CI=389.9-836.6min) during waking hours being sedentary. No significant difference in total PA per day was observed between people with BD and controls (g=-0.62, 95% CI=-1.55 to 0.31, I(2)=88.5%, n BD =82, n controls =86). Objective measures of PA recorded significantly lower levels (P=0.03) compared to self-report PA. Meta-regression demonstrated that older age and a higher body mass index predicted lower PA levels.
LIMITATIONS: Only a limited number of studies were identified assessing SB in people with BD.
CONCLUSIONS: Adults with BD engage in high levels of sedentary behavior during waking hours. Given that sedentary behavior is an independent predictor of cardiovascular disease, future lifestyle interventions specifically targeting the prevention of sedentary behavior are warranted.
PMID: 27235817 [PubMed - as supplied by publisher]
Sitting time, physical fitness impairments and metabolic abnormalities in people with bipolar disorder: An exploratory study.
Psychiatry Res. 2016 May 21;242:7-12
Authors: Vancampfort D, Sienaert P, Wyckaert S, De Hert M, Stubbs B, Probst M
A sedentary lifestyle is an independent risk factor for cardiovascular disease and mortality. Little is known however about sedentary behavior in people with bipolar disorder (BD). The primary aim of this study was to explore associations between sitting time (as a proxy for a sedentary lifestyle) and physical fitness and metabolic parameters in BD. A secondary aim was to investigate associations between psychiatric symptoms, psychotropic medication use and sitting time. Thirty-nine (21?) participants (43.7±12.4 years) completed a full metabolic screening, the sitting time item of the International Physical Activity Questionnaire, the Quick Inventory of Depressive Symptomatology self-report and the Hypomania Checklist-32. Additionally participants performed the Eurofit-test battery and 6-min walk test. The mean time spent sitting per day for the entire sample was 7.0±3.0h. A higher body mass index, worse physical fitness and higher antipsychotic medication dose were identified as independent predictors of higher levels of sitting behavior. The model explained 76.5% of the variability in the sitting time. Given that a sedentary lifestyle is an independent predictor of cardiovascular disease, future interventions specifically targeting time spend sitting are warranted in BD, with a particular emphasis on those with high body mass index and low fitness levels.
PMID: 27235986 [PubMed - as supplied by publisher]
BDNF Val66Met Polymorphism and Bipolar Disorder in European Populations: A Risk Association in Case-Control, Family-based and GWAS Studies.
Neurosci Biobehav Rev. 2016 May 25;
Authors: Li M, Chang H, Xiao X
Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animal models and may be implicated in the etiology of mood-related phenotypes. A functional polymorphism (Val66Met) in the BDNF gene was demonstrated to influence BDNF secretion and function, as well as mood and cognitive related phenotypes. However, previous genetic association studies of Val66Met polymorphism in the clinical risk of mood disorders have been complicated, possibly due to phenotypic diversity, underpowered statistical association or ancestry-specific effects. Here, we collected mood phenotypic and genetic data in over 90,000 individuals from diverse ethnic groups and conducted a systematic meta-analysis. The results showed that the Val66Met polymorphism was significantly associated with BPD in Europeans (Pmeta=0.0029, OR=1.136), but not in Asians (Pmeta=0.443). Also, it appears that the risk for MDD conferred by BDNF is waning, as the Val66Met variant was not associated with MDD in either European or Asian samples (Pmeta>0.5).
PMID: 27236043 [PubMed - as supplied by publisher]
Contemporary Treatment Approaches to Major Depression and Bipolar Disorders.
Nurs Clin North Am. 2016 Jun;51(2):335-51
Authors: John RL, Antai-Otong D
Mood disorders have a high incidence of coexisting psychiatric, substance use, and physical disorders. When these disorders are unrecognized and left untreated, patients are likely to have a reduced life expectancy and experience impaired functional and psychosocial deficits and poor quality of life. Psychiatric nurses are poised to address the needs of these patients through various approaches. Although the ideal approach for mood disorders continues to be researched, there is a compilation of data showing that integrated models of treatment that reflect person-centered, strength, and recovery-based principles produce positive clinical outcomes.
PMID: 27229286 [PubMed - in process]
Whole-gene sequencing investigation of SAT1 in attempted suicide.
Am J Med Genet B Neuropsychiatr Genet. 2016 May 27;
Authors: Monson ET, de Klerk K, Gaynor SC, Wagner AH, Breen ME, Parsons M, Casavant TL, Zandi PP, Potash JB, Willour VL
Suicidal behavior imposes a tremendous cost, with current US estimates reporting approximately 1.3 million suicide attempts and more than 40,000 suicide deaths each year. Several recent research efforts have identified an association between suicidal behavior and the expression level of the spermidine/spermine N1-acetyltransferase 1 (SAT1) gene. To date, several SAT1 genetic variants have been inconsistently associated with altered gene expression and/or directly with suicidal behavior. To clarify the role SAT1 genetic variation plays in suicidal behavior risk, we present a whole-gene sequencing effort of SAT1 in 476 bipolar disorder subjects with a history of suicide attempt and 473 subjects with bipolar disorder but no suicide attempts. Agilent SureSelect target enrichment was used to sequence all exons, introns, promoter regions, and putative regulatory regions identified from the ENCODE project within 10?kb of SAT1. Individual variant, haplotype, and collapsing variant tests were performed. Our results identified no variant or assessed region of SAT1 that showed a significant association with attempted suicide, nor did any assessment show evidence for replication of previously reported associations. Overall, no evidence for SAT1 sequence variation contributing to the risk for attempted suicide could be identified. It is possible that past associations of SAT1 expression with suicidal behavior arise from variation not captured in this study, or that causal variants in the region are too rare to be detected within our sample. Larger sample sizes and broader sequencing efforts will likely be required to identify the source of SAT1 expression level associations with suicidal behavior. © 2016 Wiley Periodicals, Inc.
PMID: 27229768 [PubMed - as supplied by publisher]
Treatment-seeking patients with binge-eating disorder in the Swedish national registers: clinical course and psychiatric comorbidity.
BMC Psychiatry. 2016;16:163
Authors: Welch E, Jangmo A, Thornton LM, Norring C, von Hausswolff-Juhlin Y, Herman BK, Pawaskar M, Larsson H, Bulik CM
BACKGROUND: We linked extensive longitudinal data from the Swedish national eating disorders quality registers and patient registers to explore clinical characteristics at diagnosis, diagnostic flux, psychiatric comorbidity, and suicide attempts in 850 individuals diagnosed with binge-eating disorder (BED).
METHOD: Cases were all individuals who met criteria for BED in the quality registers (N?=?850). We identified 10 controls for each identified case from the Multi-Generation Register matched on sex, and year, month, and county of birth. We evaluated characteristics of individuals with BED at evaluation and explored diagnostic flux across eating disorders presentations between evaluation and one-year follow-up. We applied conditional logistic regression models to assess the association of BED with each comorbid psychiatric disorder and with suicide attempts and explored whether risk for depression and suicide were differentially elevated in individuals with BED with or without comorbid obesity.
RESULTS: BED shows considerable diagnostic flux with other eating disorders over time, carries high psychiatric comorbidity burden with other eating disorders (OR 85.8; 95 % CI: 61.6, 119.4), major depressive disorder (OR 7.6; 95 % CI: 6.2, 9.3), bipolar disorder (OR 7.5; 95 % CI: 4.8, 11.9), anxiety disorders (OR 5.2; 95 % CI: 4.2, 6.4), and post-traumatic stress disorder (OR 4.3; 95 % CI: 3.2, 5.7) and is associated with elevated risk for suicide attempts (OR 1.8; 95 % CI: 1.2, 2.7). Depression and suicide attempt risk were elevated in individuals with BED with and without comorbid obesity.
CONCLUSIONS: Considerable flux occurs across BED and other eating disorder diagnoses. The high psychiatric comorbidity and suicide risk underscore the severity and clinical complexity of BED.
PMID: 27230675 [PubMed - in process]
Antimanic Treatment With Tamoxifen Affects Brain Chemistry: A Double-Blind, Placebo-Controlled Proton Magnetic Resonance Spectroscopy Study.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2016 Mar;1(2):125-131
Authors: Yildiz A, Aydin B, Gökmen N, Yurt A, Cohen B, Keskinoglu P, Öngür D, Renshaw P
BACKGROUND: The antimanic efficacy of a protein kinase C (PKC) inhibitor, tamoxifen, has been tested in several clinical trials, all reporting positive results. However, mechanisms underlying the observed clinical effects requires further confirmation through studies of biological markers.
METHODS: We investigated the effect of tamoxifen versus placebo on brain metabolites via a proton ((1)H) magnetic resonance spectroscopy (MRS) study. Forty-eight adult bipolar I manic patients (mean Young Mania Rating Scale (YMRS) score of 37.8±5.8) were scanned at baseline and following 3 weeks of double-blind treatment. We hypothesized that manic symptom alleviation would improve the levels of markers associated with brain energy metabolism (creatine plus phosphocreatine [total creatine; tCr]) and neuronal viability (N-acetylaspartate [NAA]).
RESULTS: The YMRS scores decreased from 38.6±4.5 to 20.0±11.1 in the tamoxifen group and increased from 37.0±6.8 to 43.1±7.8 in the placebo group (p<0.001). (1)H MRS measurements revealed a 5.5±13.8% increase in the dorsomedial prefrontal cortex (DMPFC) tCr levels in the tamoxifen group and a 5.3±13.1% decrease in tCr in the placebo group (p=0.027). A significant correlation between the YMRS score change and tCr percent change was observed in the whole group (Spearman ?=0.341, p=0.029). Both tCr and NAA levels in the responder group were increased by 9.4±15.2% and 6.1±11.7%, whereas levels in the non-responder group were decreased by 2.1±13.2% and 6.5±10.5%, respectively (p<0.05).
CONCLUSIONS: Tamoxifen effectively treated mania while it also increased brain tCr levels, consistent with involvement of both excessive PKC activation and impaired brain energy metabolism in the development of bipolar mania.
CLINICAL TRIAL REGISTRATION: Registry name: ClinicalTrials.gov URL: https://clinicaltrials.gov/ct2/show/NCT00411203?term=NCT00411203&rank=1 Registration number: NCT00411203.
PMID: 27231722 [PubMed - as supplied by publisher]
Are obstetrical complications really involved in the etiology and course of schizophrenia and mood disorders?
Psychiatry Res. 2016 May 11;241:297-301
Authors: Buoli M, Bertino V, Caldiroli A, Dobrea C, Serati M, Ciappolino V, Altamura AC
The impact of stressful experiences during gestation or early life, leading to increased psychiatric disorders susceptibility, is currently well described in literature, however, few data are available on the association between obstetrical complications and later development of specific diagnoses or clinical features (e.g. psychotic symptoms). Aim of the present paper was to evaluate obstetrical complications frequency in different psychiatric diagnoses and their association with clinical features. Three hundred and eighty-eight patients with a diagnosis of schizophrenia, bipolar disorder or major depressive disorder were compared in terms of clinical presentation according to the presence, type and severity of obstetrical complications. Seventeen percent of the total sample (N=65) had history of at least one obstetrical complication. Patients with a history of at least one obstetrical complication result in an earlier age of onset (F=3.93, p=0.04) and a current higher GAF score (F=6.46, p=0.01). Lewis-Murray scale score was directly correlated with GAF scores (t=2.9, p=0.004) and inversely correlated with age at onset (t=-2.77, p=0.006). Obstetrical complications are frequently registered in patients with schizophrenia or mood disorders. In our sample, they appear to have an anticipatory effect on illness onset, but they seem not to be associated with a specific psychiatric diagnosis.
PMID: 27232550 [PubMed - as supplied by publisher]
Personality and the long-term outcome of first-episode depression: a prospective 5-year follow-up study.
J Clin Psychiatry. 2016 May 10;
Authors: Bukh JD, Andersen PK, Kessing LV
OBJECTIVE: To determine the impact of the personality traits neuroticism and extraversion as well as comorbid personality disorders on the rate of remission, recurrence, and conversion to bipolar disorder after the first lifetime episode of depression.
METHODS: A total of 301 inpatients or outpatients aged 18-70 years with a validated diagnosis of a single depressive episode according to ICD-10 were assessed by the Structured Clinical Interview for DSM-IV Axis II Personality Disorders and the Eysenck Personality Questionnaire from 2005 through 2007. At 5-year follow-up, 262 patients were reassessed by means of the Life Chart Method and diagnostic interviews from 2011 through 2013. Cox regression analyses were used to estimate the effect of personality factors on the rates of remission, recurrence, and conversion to bipolar disorder, respectively.
RESULTS: A comorbid cluster C personality disorder decreased the rate of remission by 30% (HR = 0.7; 95% CI, 0.5-0.9; P = .02) and increased the rate of recurrence after remission of the first depression by 80% (HR = 1.8; 95% CI, 1.0-3.0; P = .04). A higher neuroticism score at baseline decreased the rate of remission by 20% for each increase of 1 SD (HR = 0.8; 95% CI, 0.7-0.9; P = .002), and a higher level of extraversion increased the rate of conversion to bipolar disorder by 60% for each increase of 1 SD (HR = 1.6; 95% CI, 1.0-2.5; P = .05).
CONCLUSIONS: Comorbidity of cluster C personality disorders and the level of neuroticism and extraversion have significant impact on the long-term prognosis of depression. The identified predictors of the course of illness should guide patients and clinicians for individualized tailored treatment of comorbid conditions in depression.
PMID: 27232945 [PubMed - as supplied by publisher]
Mental, Neurological, and Substance Use Disorders: Disease Control Priorities, Third Edition (Volume 4)
Book. 2016 03 14
Authors: Patel V, Chisholm D, Dua T, Laxminarayan R, Medina-Mora ME
This volume of the third edition of the Disease Control Priorities (DCP) project addresses mental, neurological, and substance use (MNS) disorders. MNS disorders are a heterogeneous range of disorders that owe their origin to a complex array of genetic, biological, psychological, and social factors. Although many health systems deliver care for these disorders through separate channels, with an emphasis on specialist services in hospitals, the disorders have been grouped together in this volume to guide policy makers, particularly in low-resource settings, as they prioritize essential health care packages and delivery platforms (box 1.1). MNS disorders are grouped together because they share several important characteristics, notably: They all owe their symptoms and impairments to some degree of brain dysfunction. Social determinants play an important role in the etiology and symptom expression for many of these disorders (box 1.2). The disorders frequently co-occur in the same individual. Their impact on families and society is profound. They are strongly associated with stigma and discrimination. They often observe a chronic or relapsing course. They all share a pitifully inadequate response from health care systems in all countries, particularly in low- and middle-income countries (LMICs). Our grouping of MNS disorders is also consistent with programs intended to address their health burden, exemplified by the Mental Health Gap Action Programme (mhGAP) (WHO 2008), and with the goals of the third edition of Disease Control Priorities (DCP3) of synthesizing evidence and making recommendations across diverse health conditions. As we emphasize in this volume, these shared characteristics shape the response of countries in addressing the burden of MNS disorders. For example, a strong case is made for an integrated public health response to these conditions in all countries, but particularly in LMICs because of the paucity of specialist services in these settings. Such services have been the hallmark of the health system response to these conditions in high-income countries (HICs). DCP1 had only addressed a few MNS disorders: psychosis and bipolar disorder. DCP2 had focused on the cost-effectiveness of specific interventions for burdensome disorders, organized separately for mental disorders, neurological disorders, alcohol use disorders, illicit drug use disorders, and learning and developmental disabilities. In this third edition, we have considered interventions for five groups of disorders?adult mental disorders, child mental and developmental disorders, neurological disorders, alcohol use disorder, and illicit drug use such as opioid dependence?and suicide and self-harm-health outcomes strongly associated with MNS disorders. Within each group, we have prioritized conditions associated with high burden for which there is evidence in support of interventions that are cost-effective and scalable. Inevitably, such an approach does not address a significant number of conditions, for example, multiple sclerosis as a neurological disorder and anorexia nervosa as an adult mental disorder. However, the recommendations in this volume, particularly regarding the delivery of packages for care, could be extended to other conditions not expressly addressed. In addition, some important MNS disorders or concerns are covered in companion volumes of DCP3, notably, nicotine dependence, early childhood development, neurological infections, and stroke. This volume addresses four overall questions and themes (box 1.3): First, we address the question of why MNS disorders deserve prioritization by pointing to and reviewing the health and economic burden of disease attributable to MNS disorders. We build on the 2010 estimates of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD 2010) in two important ways: by examining trends in the burden over time, and by estimating the additional mortality attributable to these disorders. Second, we address the question of what by reviewing the evidence on the effectiveness of specific interventions for the prevention and treatment of a selection of MNS disorders. Third, we consider how and where these interventions can be appropriately implemented across a range of service delivery platforms. Fourth, we address the question of how much by examining the cost of scaling up cost-effective interventions and the case for enhanced service coverage and financial protection for MNS disorders. This chapter also considers how some countries have attempted to incorporate this body of evidence into scaled-up programs for MNS disorders. The chapter discusses lessons on barriers and strategies for how these will need to be addressed for successful scaling-up. The primary focus of the volume?and DCP3 as a whole?is on LMICs. We include HICs in the section on global disease burden, and we draw liberally on the concentration of available evidence on intervention effectiveness from these countries.
Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia.
Eur Psychiatry. 2015 Jun;30(4):486-91
Authors: Cheah SY, Lawford BR, Young RM, Morris CP, Voisey J
BACKGROUND: Dystrobrevin binding protein 1 (DTNBP1) is a schizophrenia susceptibility gene involved with neurotransmission regulation (especially dopamine and glutamate) and neurodevelopment. The gene is known to be associated with cognitive deficit phenotypes within schizophrenia. In our previous studies, DTNBP1 was found associated not only with schizophrenia but with other psychiatric disorders including psychotic depression, post-traumatic stress disorder, nicotine dependence and opiate dependence. These findings suggest that DNTBP1 may be involved in pathways that lead to multiple psychiatric phenotypes. In this study, we explored the association between DTNBP1 SNPs (single nucleotide polymorphisms) and multiple psychiatric phenotypes included in the Diagnostic Interview of Psychosis (DIP).
METHODS: Five DTNBP1 SNPs, rs17470454, rs1997679, rs4236167, rs9370822 and rs9370823, were genotyped in 235 schizophrenia subjects screened for various phenotypes in the domains of depression, mania, hallucinations, delusions, subjective thought disorder, behaviour and affect, and speech disorder. SNP-phenotype association was determined with ANOVA under general, dominant/recessive and over-dominance models.
RESULTS: Post hoc tests determined that SNP rs1997679 was associated with visual hallucination; SNP rs4236167 was associated with general auditory hallucination as well as specific features including non-verbal, abusive and third-person form auditory hallucinations; and SNP rs9370822 was associated with visual and olfactory hallucinations. SNPs that survived correction for multiple testing were rs4236167 for third-person and abusive form auditory hallucinations; and rs9370822 for olfactory hallucinations.
CONCLUSION: These data suggest that DTNBP1 is likely to play a role in development of auditory related, visual and olfactory hallucinations which is consistent with evidence of DTNBP1 activity in the auditory processing regions, in visual processing and in the regulation of glutamate and dopamine activity.
PMID: 25697573 [PubMed - indexed for MEDLINE]
Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial.
Bipolar Disord. 2016 May;18(3):221-32
Authors: Henriksen TE, Skrede S, Fasmer OB, Schoeyen H, Leskauskaite I, Bjørke-Bertheussen J, Assmus J, Hamre B, Grønli J, Lund A
OBJECTIVES: The discovery of the blue lightsensitive retinal photoreceptor responsible for signaling daytime to the brain suggested that light to the circadian system could be inhibited by using blue-blocking orange tinted glasses. Blue-blocking (BB) glasses are a potential treatment option for bipolar mania. We examined the effectiveness of BB glasses in hospitalized patients with bipolar disorder in a manic state.
METHODS: In a single-blinded, randomized, placebo-controlled trial (RCT), eligible patients (with bipolar mania; age 18-70 years) were recruited from five clinics in Norway. Patients were assigned to BB glasses or placebo (clear glasses) from 6 p.m. to 8 a.m. for 7 days, in addition to treatment as usual. Symptoms were assessed daily by use of the Young Mania Rating Scale (YMRS). Motor activity was assessed by actigraphy, and compared to data from a healthy control group. Wearing glasses for one evening/night qualified for inclusion in the intention-to-treat analysis.
RESULTS: From February 2012 to February 2015, 32 patients were enrolled. Eight patients dropped out and one was excluded, resulting in 12 patients in the BB group and 11 patients in the placebo group. The mean decline in YMRS score was 14.1 [95% confidence interval (CI): 9.7-18.5] in the BB group, and 1.7 (95% CI: -4.0 to 7.4) in the placebo group, yielding an effect size of 1.86 (Cohen's d). In the BB group, one patient reported headache and two patients experienced easily reversible depressive symptoms.
CONCLUSIONS: This RCT shows that BB glasses are effective and feasible as add-on treatment for bipolar mania.
PMID: 27226262 [PubMed - in process]
Diagnostic shift in patients diagnosed with schizoaffective disorder: a systematic review and meta-analysis of rediagnosis studies.
Bipolar Disord. 2016 May;18(3):233-46
Authors: Santelmann H, Franklin J, Bußhoff J, Baethge C
OBJECTIVES: The diagnosis of schizoaffective disorder (SAD) is well established in clinical practice but is heavily disputed on theoretical grounds. We analyzed the extent and direction of diagnostic shift in SAD patients.
METHODS: We searched Medline, Embase, and PsycINFO systematically for all studies documenting two diagnostic assessments at different points in time (rediagnosis studies) and used meta-analytic methods to quantify diagnostic shift. Multiple prespecified and post-hoc subgroup analyses (e.g., rater blinding) and meta-regressions (e.g., year of publication) were carried out.
RESULTS: We included 31 studies out of 4,415 articles screened: 27 studies on the shift from and 23 studies on the shift to SAD (median time span was two years). A total of 36% of patients with a diagnosis of SAD at first assessment switch, many to schizophrenia (19%), 14% to affective disorders, and 6% to other disorders. Among patients diagnosed with SAD at second assessment, 55% had received a different diagnosis at first assessment, a large portion of whom had been initially diagnosed with affective disorder (24%), schizophrenia (18%), and other disorders (12%).
CONCLUSIONS: Diagnostic shift in SAD patients is substantial. Psychiatrists need to reassess the diagnosis during the course of the illness and to adjust treatment. Slightly more diagnoses of SAD are changed to schizophrenia than to affective disorders, and among patients rediagnosed with SAD, fewer have been diagnosed with schizophrenia than with affective disorders. Thus, at the diagnostic level, there seems to be a slight trend toward schizophrenia during the course of functional psychoses.
PMID: 27226263 [PubMed - in process]
Hypothyroidism risk compared among nine common bipolar disorder therapies in a large US cohort.
Bipolar Disord. 2016 May;18(3):247-60
Authors: Lambert CG, Mazurie AJ, Lauve NR, Hurwitz NG, Young SS, Obenchain RL, Hengartner NW, Perkins DJ, Tohen M, Kerner B
OBJECTIVES: Thyroid abnormalities in patients with bipolar disorder (BD) have been linked to lithium treatment for decades, yet other drugs have been less well studied. Our objective was to compare hypothyroidism risk for lithium versus the anticonvulsants and second-generation antipsychotics commonly prescribed for BD.
METHODS: Administrative claims data on 24,574 patients with BD were analyzed with competing risk survival analysis. Inclusion criteria were (i) one year of no prior hypothyroid diagnosis nor BD drug treatment, (ii) followed by at least one thyroid test during BD monotherapy on lithium carbonate, mood-stabilizing anticonvulsants (lamotrigine, valproate, oxcarbazepine, or carbamazepine) or antipsychotics (aripiprazole, olanzapine, risperidone, or quetiapine). The outcome was cumulative incidence of hypothyroidism per drug, in the presence of the competing risk of ending monotherapy, adjusted for age, sex, physician visits, and thyroid tests.
RESULTS: Adjusting for covariates, the four-year cumulative risk of hypothyroidism for lithium (8.8%) was 1.39-fold that of the lowest risk therapy, oxcarbazepine (6.3%). Lithium was non-statistically significantly different from quetiapine. While lithium conferred a higher risk when compared to all other treatments combined as a group, hypothyroidism risk error bars overlapped for all drugs. Treatment (p = 3.86e-3), age (p = 6.91e-10), sex (p = 3.93e-7), and thyroid testing (p = 2.79e-87) affected risk. Patients taking lithium were tested for hypothyroidism 2.26-3.05 times more frequently than those on other treatments.
CONCLUSIONS: Thyroid abnormalities occur frequently in patients with BD regardless of treatment. Therefore, patients should be regularly tested for clinical or subclinical thyroid abnormalities on all therapies and treated as indicated to prevent adverse effects of hormone imbalances on mood.
PMID: 27226264 [PubMed - in process]
Sex differences in mortality among patients admitted with affective disorders in North Norway: a 33-year prospective register study.
Bipolar Disord. 2016 May;18(3):272-81
Authors: Høye A, Nesvåg R, Reichborn-Kjennerud T, Jacobsen BK
OBJECTIVE: Previous studies from North Norway showed significantly increased mortality in patients with schizophrenia and personality disorder. The aim of the present study was to investigate total and cause-specific mortality in inpatients with affective disorder in a 33-year follow-up cohort, with a specific focus on sex differences.
METHODS: Based on a hospital case register covering all admissions to psychiatric hospital in the two northernmost counties in Norway from 1980 to 2012, 790 men and 866 women with major depressive disorder and 331 men and 514 women with bipolar disorder were included. The cohort was linked to the Norwegian Cause of Death Registry. The relative mortality in men compared to women was tested using Cox regression with attained age as the time variable. The standardized mortality ratio (SMR) of the patients when compared to the general population in Norway was calculated.
RESULTS: Patients with affective disorders had twice the mortality of the general Norwegian population [SMR = 2.1, 95% confidence interval (CI): 1.9-2.3]. For major depressive disorder, the SMR for total mortality was higher among men (2.6, 95% CI: 2.2-3.0) than women (1.8, 95% CI: 1.5-2.1). For bipolar disorder, no difference was seen between men and women. The SMR for suicide among women showed an increasing trend throughout the period 1980-1990: 20.0 (95% CI: 10.4-38.4); 1991-2001: 27.0 (95% CI: 15.7-46.2); 2002-2012: 40.4 (95% CI: 23.0-71.2).
CONCLUSIONS: The substantially increased mortality in patients with affective disorders in Norway has been persistent over a period of 33 years, despite extensive reforms in psychiatric health care. Indications of increasing SMR for suicide in women call for further research.
PMID: 27226265 [PubMed - in process]
nArgBP2 regulates excitatory synapse formation by controlling dendritic spine morphology.
Proc Natl Acad Sci U S A. 2016 May 25;
Authors: Lee SE, Kim Y, Han JK, Park H, Lee U, Na M, Jeong S, Chung C, Cestra G, Chang S
Neural Abelson-related gene-binding protein 2 (nArgBP2) was originally identified as a protein that directly interacts with synapse-associated protein 90/postsynaptic density protein 95-associated protein 3 (SAPAP3), a postsynaptic scaffolding protein critical for the assembly of glutamatergic synapses. Although genetic deletion of nArgBP2 in mice leads to manic/bipolar-like behaviors resembling many aspects of symptoms in patients with bipolar disorder, the actual function of nArgBP2 at the synapse is completely unknown. Here, we found that the knockdown (KD) of nArgBP2 by specific small hairpin RNAs (shRNAs) resulted in a dramatic change in dendritic spine morphology. Reintroducing shRNA-resistant nArgBP2 reversed these defects. In particular, nArgBP2 KD impaired spine-synapse formation such that excitatory synapses terminated mostly at dendritic shafts instead of spine heads in spiny neurons, although inhibitory synapse formation was not affected. nArgBP2 KD further caused a marked increase of actin cytoskeleton dynamics in spines, which was associated with increased Wiskott-Aldrich syndrome protein-family verprolin homologous protein 1 (WAVE1)/p21-activated kinase (PAK) phosphorylation and reduced activity of cofilin. These effects of nArgBP2 KD in spines were rescued by inhibiting PAK or activating cofilin combined with sequestration of WAVE. Together, our results suggest that nArgBP2 functions to regulate spine morphogenesis and subsequent spine-synapse formation at glutamatergic synapses. They also raise the possibility that the aberrant regulation of synaptic actin filaments caused by reduced nArgBP2 expression may contribute to the manifestation of the synaptic dysfunction observed in manic/bipolar disorder.
PMID: 27226294 [PubMed - as supplied by publisher]
Cortical Thickness of Functionally Defined Visual Areas in Schizophrenia and Bipolar Disorder.
Cereb Cortex. 2016 May 25;
Authors: Reavis EA, Lee J, Wynn JK, Engel SA, Jimenez AM, Green MF
Patients with schizophrenia show specific abnormalities in visual perception, and patients with bipolar disorder may have related perceptual deficits. During tasks that highlight perceptual dysfunction, patients with schizophrenia show abnormal activity in visual brain areas, including the lateral occipital complex (LOC) and early retinotopic cortex. It is unclear whether the anatomical structure of those visual areas is atypical in schizophrenia and bipolar disorder. In members of those two patient groups and healthy controls, we localized LOC and early retinotopic cortex individually for each participant using functional magnetic resonance imaging (MRI), then measured the thickness of those regions of interest using structural MRI scans. In both regions, patients with schizophrenia had the thinnest cortex, controls had the thickest cortex, and bipolar patients had intermediate cortical thickness. A control region, motor cortex, did not show this pattern of group differences. The thickness of each visual region of interest was significantly correlated with performance on a visual object masking task, but only in schizophrenia patients. These findings suggest an anatomical substrate for visual processing abnormalities that have been found with both neural and behavioral measures in schizophrenia and other severe mental illnesses.
PMID: 27226446 [PubMed - as supplied by publisher]
Inflammatory cytokines and nuclear factor-kappa B activation in adolescents with bipolar and major depressive disorders.
Psychiatry Res. 2016 May 7;241:315-322
Authors: Miklowitz DJ, Portnoff LC, Armstrong CC, Keenan-Miller D, Breen EC, Muscatell KA, Eisenberger NI, Irwin MR
Adults with bipolar disorder (BD) and major depressive disorder (MDD) have higher circulating levels of proinflammatory cytokines than healthy controls. However, it is not known whether pediatric-onset patients with BD or MDD show increases in levels of inflammation or activation of nuclear factor kappa B (NF-?B), a key transcription factor in inflammatory signaling. Circulating levels of inflammatory cytokines, as well as spontaneous and stimulated levels of activated NF-?B in total peripheral blood mononuclear cells, monocytes and lymphocytes were measured in adolescents with BD (n=18), MDD (n=13), or no psychiatric history (n=20). Participants had a range of mood symptoms at time of testing. Adolescents with BD had significantly higher spontaneous levels of NF-?B in peripheral blood mononuclear cells, monocyte and lymphocyte populations, and higher plasma levels of IL-1? than healthy controls. Following stimulation with recombinant human TNF-?, participants with BD and MDD both had greater increases in NF-?B in monocytes than controls. Further, greater stimulated increases of NF-?B in monocytes were associated with the current severity of depressive symptoms. The results are limited by the small sample and cross-sectional design. Interventions that target early immunological dysregulation should be examined in relation to long-term outcomes in youth with bipolar and depressive disorders.
CLINICAL TRIAL REGISTRATION INFORMATION: Early Intervention for Youth at Risk for Bipolar Disorder, https://clinicaltrials.gov/ct2/show/NCT01483391.
PMID: 27227701 [PubMed - as supplied by publisher]
[Guideline-adherent psychiatric psychotherapeutic treatment of bipolar disorders : Which resources are needed?]
Nervenarzt. 2016 May 24;
Authors: Pfennig A, Conell J, Ritter P, Ritter D, Severus E, Meyer TD, Hautzinger M, Wolff J, Godemann F, Reif A, Bauer M
In this article the guideline-adherent psychiatric psychotherapeutic treatment of patients with bipolar disorders is outlined and the required resources are estimated. Based on the core recommendations of the S3 guidelines for diagnostics and treatment of bipolar disorders published in 2012, inpatient treatment needs in hours per week and per patient are determined for both manic and bipolar depressive episodes. The resulting staffing requirements are estimated on this basis. In summary, for guideline-adherent inpatient psychiatric psychotherapeutic treatment the additional needs regarding the physician/psychotherapeutic domain add up to 44 min per patient and week during a manic episode and 88 min for patients with bipolar depression when compared to current psychiatry staffing regulations.
PMID: 27220643 [PubMed - as supplied by publisher]
Polymorphisms of BDNF and CACNA1C are not associated with cognitive functioning in bipolar disorder or healthy controls.
Cogn Neuropsychiatry. 2016 May 25;:1-8
Authors: Rolstad S, Sellgren Majkowitz C, Joas E, Ekman CJ, Pålsson E, Landén M
INTRODUCTION: The cause of cognitive dysfunction in bipolar disorder (BD) is not well understood. BDNF and CACNA1C are two susceptibility genes for the disorder that have also been reported to be associated with cognitive deficits in the disorder, but the studies have been small and with conflicting results. We therefore attempted to replicate an association between cognitive dysfunction with the most commonly studied single nucleotide polymorphisms rs6265 and rs1006737.
METHODS: Regression models with five aggregated cognitive domains derived from a comprehensive test battery and IQ score were run using directly genotyped risk variants of SNPs rs6265 and rs1006737 as predictors with covariates as appropriate. Models were performed in a clinical sample of Swedish patients with BD (N?=?114) and sex- and age-matched population controls (N?=?104).
RESULTS: No significant associations (regardless of correction for multiple testing) between the BDNF and CACNA1C risk variants and cognitive functioning were found in either patients or controls.
CONCLUSIONS: Our results do not support that the common genetic risk variants in rs6265 and rs1006737 are associated with cognitive dysfunction.
PMID: 27221213 [PubMed - as supplied by publisher]