Most Recent Articles Published on Bipolar Disorder:

Brain Cortical Thickness and Surface Area Correlates of Neurocognitive Performance in Patients with Schizophrenia, Bipolar Disorder, and Healthy Adults.

J Int Neuropsychol Soc. 2011 Oct 3;:1-14

Authors: Hartberg CB, Sundet K, Rimol LM, Haukvik UK, Lange EH, Nesvåg R, Dale AM, Melle I, Andreassen OA, Agartz I

Abstract
Relationships between cortical brain structure and neurocognitive functioning have been reported in schizophrenia, but findings are inconclusive, and only a few studies in bipolar disorder have addressed this issue. This is the first study to directly compare relationships between cortical thickness and surface area with neurocognitive functioning in patients with schizophrenia (n = 117) and bipolar disorder (n = 121) and healthy controls (n = 192). MRI scans were obtained, and regional cortical thickness and surface area measurements were analyzed for relationships with test scores from 6 neurocognitive domains. In the combined sample, cortical thickness in the right rostral anterior cingulate was inversely related to working memory, and cortical surface area in four frontal and temporal regions were positively related to neurocognitive functioning. A positive relationship between left transverse temporal thickness and processing speed was specific to schizophrenia. A negative relationship between right temporal pole thickness and working memory was specific to bipolar disorder. In conclusion, significant cortical structure/function relationships were found in a large sample of healthy controls and patients with schizophrenia or bipolar disorder. The differences that were found between schizophrenia and bipolar may indicate differential relationship patterns in the two disorders, which may be of relevance for understanding the underlying pathophysiology. (JINS, 2011, 17, 1-14).

PMID: 22013998 [PubMed - as supplied by publisher]

Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: cohort study.

Br J Psychiatry. 2011 Oct 20;

Authors: Li CT, Bai YM, Huang YL, Chen YS, Chen TJ, Cheng JY, Su TP

Abstract
BACKGROUND: People with major depressive disorder who fail to respond to adequate trials of antidepressant treatment may harbour hidden bipolar disorder. AIMS: We aimed to compare the rates of a change in diagnosis to bipolar disorder among people with major depressive disorder with stratified responses to antidepressants during an 8-year follow-up period. METHOD: Information on individuals with major depressive disorder identified during 2000 (cohort 2000, n = 1485) and 2003 (cohort 2003, n = 2459) were collected from a nationally representative cohort of 1 000 000 health service users in Taiwan. Participants responding well to antidepressants were compared with those showing poor responses to adequate trials of antidepressants. RESULTS: In 7.6-12.1% of those with a diagnosis of unipolar major depressive disorder this diagnosis was subsequently changed to bipolar disorder, with a mean time to change of 1.89-2.98 years. Difficult-to-treat participants presented higher rates of change to a bipolar diagnosis (25.6% in cohort 2000; 26.6% in cohort 2003) than easy-to-treat participants (8.8-8.9% in cohort 2000; 6.8-8.6% in cohort 2003; P<0.0001). Regression analysis showed that the variable most strongly associated with the change in diagnosis was antidepressant use history. The difficult-to-treat participants were associated most with diagnostic changing (cohort 2000: odds ratio (OR) = 1.88 (95% CI 1.12-3.16); cohort 2003: OR = 4.94 (95% CI 2.81-8.68)). CONCLUSIONS: This is the first large-scale study to report an association between antidepressant response history and subsequent change in diagnosis from major depressive disorder to bipolar disorder. Our findings support the view that a history of poor response to antidepressants in unipolar depression could be a useful predictor for bipolar diathesis.

PMID: 22016435 [PubMed - as supplied by publisher]

Spotlight on severe premenstrual syndrome and bipolar disorder: a frequent tragic confusion.

Climacteric. 2011 Oct;14(5):602

Authors: Studd J

PMID: 22016893 [PubMed - in process]

The Possible Involvement of Glycogen Synthase Kinase-3 (GSK-3) in Diabetes, Cancer and Central Nervous System Diseases.

Curr Pharm Des. 2011 Jul 7;

Authors: Amar S, Belmaker RH, Agam G

Glycogen synthase kinase (GSK) is a key enzyme in multiple cell processes. Since many pharmacological compounds that have effects on common metabolic pathways may have uses in many different diseases, we review here the possible involvement of glycogen synthase kinase 3 in diabetes, cancer and CNS diseases. Moreover, diabetes has recently been strongly linked to CNS diseases such as schizophrenia and bipolar illness. GSK is both directly and indirectly inhibited by lithium, a key compound for treatment of bipolar disorder. Several antipsychotic drugs also affect the GSK3 mediated pathways and postmortem study of brain in schizophrenia led to reports of alterations of GSK3 activity or mRNA message. However, other reports are contradictory. Development of GSK3 inhibitors for CNS diseases is complicated by the importance of GSK3 in glucose metabolism and pancreas function and the possible effect of GSK3 inhibition to be oncogenic. Further development of GSK inhibitors for clinical trials should be approached with caution.

PMID: 21736545 [PubMed - as supplied by publisher]

Annual cost of managing bipolar disorder to the UK healthcare system.

J Affect Disord. 2011 Jul 5;

Authors: Young AH, Rigney U, Shaw S, Emmas C, Thompson JM

INTRODUCTION:: Bipolar disorder is a common illness characterized by recurrent episodes of pathological disturbances of mood. The aim of this study was to estimate the annual cost associated with bipolar disorder to the UK healthcare system (National Health Service). METHODS:: A retrospective observational study was conducted. Primary care resource use was estimated using the IMS Disease Analyzer, a nationally representative sample of general practitioner (GP) practices. Two sources of data from the NHS Information Centre were used to assess resource use in secondary care and in outpatient and community mental health. The number of bed days and day attendances for patients hospitalized was obtained from the Hospital Episode Statistics (HES). This was supplemented with Mental Health Minimum Dataset (MHMDS) to quantify outpatient and community mental health face-to-face contacts. Resource use was examined between 01 April 2007 and 31 March 2008. RESULTS:: The annual NHS cost of bipolar disorder was estimated to be £342million at 2009/2010 prices. Hospitalizations accounted for 60%, outpatient and community mental health 26.7%, and medication in primary care 7.4% of the overall direct costs of care. LIMITATIONS:: This study may be confounded by the absence of a control group. This study was limited to an assessment of direct healthcare costs only, not the wider societal cost of bipolar disorder. CONCLUSIONS:: The direct medical cost of managing bipolar disorder in the UK healthcare system is considerable. Therapeutic strategies that optimize community-based management, prevention of recurrence and hospitalization could reduce the economic burden of this illness.

PMID: 21737141 [PubMed - as supplied by publisher]

The impact of brief depressive episodes on the outcome of bipolar disorder and major depressive disorder: A 1-year prospective study.

J Affect Disord. 2011 Jul 5;

Authors: Altamura AC, Buoli M, Dell'osso B, Albano A, Serati M, Colombo F, Pozzoli S, Angst J

BACKGROUND: Brief depressive episodes (BDEs) cause psychosocial impairment and increased risk of suicide, worsening the outcome and long-term course of affective disorders. The aim of this naturalistic observational study was to assess the frequency of BDEs and very brief depressive episodes (VBDEs) and their impact on clinical outcome in a sample of patients with major depressive disorder (MDD) and bipolar disorder (BD). METHOD: Seventy patients with a diagnosis of MDD or BD were followed up and monthly visited for a period of 12months, assessing the eventual occurrence of BDEs and/or VBDEs. Clinical and demographic variables of the total sample and of the groups divided according to the presence of BDEs or VBDEs were collected and compared by one-way ANOVAs. Hamilton Depression Rating Scale 21 items (HDRS), Young Mania Rating Scale (YMRS), Clinical Global Impression (severity of illness) (CGIs) and the Short Form Health Survey (SF-36-item 1) were administered at baseline and logistic regression was performed to evaluate whether baseline scores were predictive of the onset of BDEs or VBDEs. RESULTS: BDEs (88.6% of the total sample), VBDEs (44.3% of the total sample) and BDEs+VBDEs (40.0% of the total sample) were found to occur frequently across the sample. BDE patients showed more death thoughts during major depressive episodes (?(2)=4.14, df=1, p=0.04, Phi=0.24) compared to patients without BDEs. Indeed VBDE patients showed a higher rate of hospitalization (?(2)=5.71, df=1, p=0.031, phi=0.29), a more frequent prescription of a combined treatment (?(2)=13.07, df=7, p=0.03, phi=0.43) and higher scores at SF-36 item 1 (F=6.65, p=0.01) compared to patients without VBDEs. Finally, higher SF-36 item 1 scores were found to be predictive of VBDEs (odds ratio=2.81, p=0.03). DISCUSSION: Major depressives, either unipolar or bipolar, with BDEs or VBDEs showed a worse outcome, represented by a more severe psychopathology and higher rates of hospitalization. VBDEs were predicted by a negative subjective general health perception. Studies with larger samples and longer follow-up are warranted to confirm the results of the present study.

PMID: 21737143 [PubMed - as supplied by publisher]

Genome-Wide Association of Bipolar Disorder Suggests an Enrichment of Replicable Associations in Regions near Genes.

PLoS Genet. 2011 Jun;7(6):e1002134

Authors: Smith EN, Koller DL, Panganiban C, Szelinger S, Zhang P, Badner JA, Barrett TB, Berrettini WH, Bloss CS, Byerley W, Coryell W, Edenberg HJ, Foroud T, Gershon ES, Greenwood TA, Guo Y, Hipolito M, Keating BJ, Lawson WB, Liu C, Mahon PB, McInnis MG, McMahon FJ, McKinney R, Murray SS, Nievergelt CM, Nurnberger JI, Nwulia EA, Potash JB, Rice J, Schulze TG, Scheftner WA, Shilling PD, Zandi PP, Zöllner S, Craig DW, Schork NJ, Kelsoe JR

Although a highly heritable and disabling disease, bipolar disorder's (BD) genetic variants have been challenging to identify. We present new genotype data for 1,190 cases and 401 controls and perform a genome-wide association study including additional samples for a total of 2,191 cases and 1,434 controls. We do not detect genome-wide significant associations for individual loci; however, across all SNPs, we show an association between the power to detect effects calculated from a previous genome-wide association study and evidence for replication (P?=?1.5×10(-7)). To demonstrate that this result is not likely to be a false positive, we analyze replication rates in a large meta-analysis of height and show that, in a large enough study, associations replicate as a function of power, approaching a linear relationship. Within BD, SNPs near exons exhibit a greater probability of replication, supporting an enrichment of reproducible associations near functional regions of genes. These results indicate that there is likely common genetic variation associated with BD near exons (±10 kb) that could be identified in larger studies and, further, provide a framework for assessing the potential for replication when combining results from multiple studies.

PMID: 21738484 [PubMed - in process]

Duration of untreated psychosis and pathways to care in patients with first-episode psychosis in Iran.

Early Interv Psychiatry. 2009 May;3(2):131-6

Authors: Sharifi V, Kermani-Ranjbar T, Amini H, Alaghband-rad J, Salesian N, Seddigh A

This is the first study on the duration of untreated psychosis and pathways to care among patients with first-episode psychosis in Iran as a developing country.

PMID: 21352186 [PubMed - indexed for MEDLINE]

Cognitive efficacy of quetiapine and olanzapine in early-onset first-episode psychosis.

Schizophr Bull. 2011 Mar;37(2):405-15

Authors: Robles O, Zabala A, Bombín I, Parellada M, Moreno D, Ruiz-Sancho A, Arango C

The primary purpose of this study was to compare changes in cognition in early-onset psychosis after 6-months treatment with quetiapine or olanzapine. This is a randomized, single-blind, 6-month study in 50 adolescents with a diagnosis of early-onset psychosis. Patients were randomized to quetiapine (n = 24) or olanzapine (n =26). A thorough neuropsychological battery was administered at baseline and after 6-month treatment. Out of the total sample included in the study, 32 patients completed at least 6-months treatment with the assigned medication (quetiapine, n =16; olanzapine, n = 16). No changes were observed in cognitive performance after 6-month treatment with quetiapine or olanzapine. Although some trends toward cognitive improvement were observed for the olanzapine group after 6-month treatment, neither group showed statistically significant gains. Furthermore, there was no evidence of any differential efficacy of olanzapine or quetiapine on cognitive improvement in this sample of adolescents with psychosis.

PMID: 19706697 [PubMed - indexed for MEDLINE]

Lamotrigine blocks NMDA receptor-initiated arachidonic acid signalling in rat brain: implications for its efficacy in bipolar disorder.

Int J Neuropsychopharmacol. 2011 Jun 28;:1-13

Authors: Ramadan E, Basselin M, Rao JS, Chang L, Chen M, Ma K, Rapoport SI

An up-regulated brain arachidonic acid (AA) cascade and a hyperglutamatergic state characterize bipolar disorder (BD). Lamotrigine (LTG), a mood stabilizer approved for treating BD, is reported to interfere with glutamatergic neurotransmission involving N-methyl-d-aspartate receptors (NMDARs). NMDARs allow extracellular calcium into the cell, thereby stimulating calcium-dependent cytosolic phospholipase A2 (cPLA2) to release AA from membrane phospholipid. We hypothesized that LTG, like other approved mood stabilizers, would reduce NMDAR-mediated AA signalling in rat brain. An acute subconvulsant dose of NMDA (25 mg/kg) or saline was administered intraperitoneally to unanaesthetized rats that had been treated p.o. daily for 42 d with vehicle or a therapeutically relevant dose of LTG (10 mg/kg.d). Regional brain AA incorporation coefficients k* and rates Jin, and AA signals, were measured using quantitative autoradiography after intravenous [1-14C]AA infusion, as were other AA cascade markers. In chronic vehicle-treated rats, acute NMDA compared to saline increased k* and Jin in widespread regions of the brain, as well as prostaglandin (PG)E2 and thromboxane B2 concentrations. Chronic LTG treatment compared to vehicle reduced brain cyclooxygenase (COX) activity, PGE2 concentration, and DNA-binding activity of the COX-2 transcription factor, NF-?B. Pretreatment with chronic LTG blocked the acute NMDA effects on AA cascade markers. In summary, chronic LTG like other mood stabilizers blocks NMDA-mediated signalling involving the AA metabolic cascade. Since markers of the AA cascade and of NMDAR signalling are up-regulated in the post-mortem BD brain, mood stabilizers generally may be effective in BD by dampening NMDAR signalling and the AA cascade.

PMID: 21733229 [PubMed - as supplied by publisher]

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials.

Int J Neuropsychopharmacol. 2011 Jun 22;:1-21

Authors: Vieta E, Günther O, Locklear J, Ekman M, Miltenburger C, Chatterton ML, Aström M, Paulsson B

The purpose of this meta-analysis was to examine the efficacy of maintenance treatments for bipolar disorder. Placebo-controlled or active comparator bipolar maintenance clinical trials of ?6 months' duration with at least 15 patients/treatment group were identified using Medline, EMBASE, clinicaltrials.gov, and Cochrane databases (1993 to July 2010). The main outcome measure was relative risk for relapse for patients in remission. Twenty trials (5364 patients) were identified. Overall, lithium and quetiapine were the most studied agents (eight and five trials, respectively). The majority of studies included patients who had previously responded to treatment for an acute episode. All interventions, with the exception of perphenazine+mood stabilizer, showed a relative risk for manic/mixed or depressive relapse below 1.0, although there was variation in the statistical significance of the findings vs. placebo. No monotherapy was associated with a significantly reduced risk for both manic/mixed and depressed relapse. Of the combination treatments, only quetiapine+lithium/divalproex, was associated with a significantly reduced risk vs. comparator (placebo+lithium/valproate) for relapse at both the manic/mixed and depressed poles of bipolar illness. Limitations for the analysis include differences in study durations and definitions of relapse. In conclusion, available maintenance therapies show considerable variation in efficacy. The efficacy of lithium and divalproex has been confirmed, but newer therapies, such as a number of atypical antipsychotics were also shown to be effective in bipolar disorder. Efficacy of all maintenance interventions needs to be balanced against the safety and tolerability profiles of individual agents.

PMID: 21733231 [PubMed - as supplied by publisher]

Mouse strain differences in phencyclidine-induced behavioural changes.

Int J Neuropsychopharmacol. 2011 Jun 9;:1-13

Authors: Mouri A, Koseki T, Narusawa S, Niwa M, Mamiya T, Kano SI, Sawa A, Nabeshima T

Administration of phencyclidine (PCP) is acknowledged to generate a model of psychosis in animals. With the identification of genetic susceptibility factors for schizophrenia and bipolar disorder, great efforts have been made to generate genetic animal models for major mental illnesses. As these disorders are multifactorial, comparisons among drug-induced (non-genetic) and genetic models are becoming an important issue in biological psychiatry. A major barrier is that the standard mouse strain used in the generation of genetic models is C57BL/6, whereas almost all studies with PCP-induced models have utilized other strains. To fill this technical gap, we systematically compared the behavioural changes upon PCP administration in different mouse strains, including C57BL/6N, C57BL/6J, ddY, and ICR. We observed strain differences in PCP-induced hyperlocomotion and enhanced immobility in the forced swim test (ddY>>C57BL/6N and 6J>ICR). In contrast, there was no strain difference in the impairment of recognition memory in the novel object recognition memory test after withdrawal of chronic PCP administration. This study provides practical guidance for comparing genetic with PCP-induced models of psychosis in C57BL/6. Furthermore, such strain differences may provide a clue to the biological mechanisms underlying PCP-induced endophenotypes possibly relevant to major mental illnesses.

PMID: 21733237 [PubMed - as supplied by publisher]

Prefrontal cortex glutathione S-transferase levels in patients with bipolar disorder, major depression and schizophrenia.

Int J Neuropsychopharmacol. 2011 May 9;:1-6

Authors: Gawryluk JW, Wang JF, Andreazza AC, Shao L, Yatham LN, Young LT

Antioxidant defence systems have received increasing attention in the pathophysiology of psychiatric disorders, including: bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). Recently, we reported decreased glutathione (GSH) levels in post-mortem prefrontal cortex from patients with BD, MDD, and SCZ. To explore this further, we evaluated the levels of two glutathione S-transferase (GST) isoforms via immunoblotting: GST Pi and GST Mu. GST Pi levels were not affected in any of the patients groups vs. controls. GST Mu levels were significantly decreased in patients with MDD and SCZ but not BD. Compared to controls, GST Mu levels were not different in BD patients who had been treated with mood stabilizers at the time of death but were significantly lower in those not taking mood stabilizers at the time of death. These data suggest that GST Mu may be a target for mood stabilizers.

PMID: 21733244 [PubMed - as supplied by publisher]

Estimates of the treated prevalence of bipolar disorders by mental health services in the general population: comparison of results from administrative and health survey data.

Chronic Dis Inj Can. 2011 Jun;31(3):129-34

Authors: Bulloch AG, Currie S, Guyn L, Williams JV, Lavorato DH, Patten SB

Informed provision of population mental health services requires accurate estimates of disease burden.

PMID: 21733350 [PubMed - in process]

In bipolar disorder beyond 10 weeks of treatment, the term antidepressants is a misnomer.

J Clin Psychiatry. 2011 Jun;72(6):871

Authors: Sparhawk R

PMID: 21733484 [PubMed - in process]

A Rare Case of Acute Respiratory Distress Syndrome Secondary to Acute Lithium Intoxication.

Am J Ther. 2011 Jun 25;

Authors: Kansagra AJ, Yang E, Nambiar S, Patel PS, Karetzky MS

Lithium carbonate is a widely administered antimanic drug used for the treatment of bipolar disorder, schizoaffective disorder, and depression. Despite the established clinical efficacy of lithium, its usage must be approached with caution due to its narrow therapeutic index. Lithium poisoning results in multisystem toxicity, and characteristic clinical manifestations are directly correlated to serum lithium concentration. We describe a rather rare but fatal side effect of lithium: acute respiratory distress syndrome (ARDS) in a 46-year-old female on lithium for the treatment of bipolar disease. She was referred for generalized weakness, found in hemodynamic compromise, and had laboratory data significant for a lithium level of 3.3 mmole/L, needing emergent hemodialysis. Subsequently, she developed hypoxic respiratory failure requiring intubation. Her chest x-rays showed new bilateral pulmonary edema, the computed tomography scan showed extensive alveolar consolidation and V/Q scan of low probability for pulmonary embolism. She underwent 3 dialysis sessions and supportive care and was able to be extubated in 5 days. To our knowledge, 4 cases of ARDS after the onset of lithium toxicity have been documented. All patients presented with altered mental status at serum lithium levels ranging from 3.8 to 4.9 mmole/L and cardiogenic etiologies in addition to other likely causes of ARDS were ruled out in each case. The patients were treated with saline hydration (50%) or hemodialysis (50%), indicating that hemodialysis may be a permissive factor in lithium-associated ARDS development rather than a required component. Taken together, we believe that lithium is a likely culprit in the initiation of ARDS and propose the addition of ARDS to the family of clinical manifestations of severe lithium toxicity.

PMID: 21734531 [PubMed - as supplied by publisher]

Lithium and valproate modulate antioxidant enzymes and prevent ouabain-induced oxidative damage in an animal model of mania.

J Psychiatr Res. 2011 Feb;45(2):162-8

Authors: Jornada LK, Valvassori SS, Steckert AV, Moretti M, Mina F, Ferreira CL, Arent CO, Dal-Pizzol F, Quevedo J

In this study, we assessed the oxidative stress parameters in rats submitted to an animal model of mania induced by ouabain (OUA), which included the use of lithium (Li) and valproate (VPA). Li and VPA treatment reversed and prevented the OUA-induced damage in these structures, however, this effect varies depending on the brain region and treatment regimen. Moreover, the activity of the antioxidant enzymes, namely, superoxide dismutase (SOD) and catalase (CAT) was found to be increased and decreased, respectively, in the brain of OUA-administered rats. Li and VPA modulated SOD and CAT activities in OUA-subjected rats in both experimental models. Our results support the notion that Li and VPA exert antioxidant-like properties in the brain of rats submitted to animal model of mania induced by ouabain.

PMID: 20627318 [PubMed - indexed for MEDLINE]

Effects of 3 different stimulus intensities of ultrabrief stimuli in right unilateral electroconvulsive therapy in major depression: a randomized, double-blind pilot study.

J Psychiatr Res. 2011 Feb;45(2):174-8

Authors: Quante A, Luborzewski A, Brakemeier EL, Merkl A, Danker-Hopfe H, Bajbouj M

Efficacy and cognitive outcome of ECT is depending on electrode placement, pulse width and electrical dosage. Several studies showed that high-dosage right unilateral ECT (RULECT) had a better antidepressant effects than low-dosage RULECT and less cognitive side effect than bilateral stimulation. In this prospective, randomized, double-blind trial, we examined the efficacy and cognitive side effects of RULECT with three different (high dose) stimulus intensities (4×, 7× and 10× above the seizure threshold (ST)).

PMID: 20728093 [PubMed - indexed for MEDLINE]

Abstract thinking: environmental modification, development, and psychopathology.

J Am Acad Child Adolesc Psychiatry. 2010 Dec;49(12):1180

Authors: Stringaris A

PMID: 21093765 [PubMed - indexed for MEDLINE]

[First episode of mood disorders: an opportunity for early intervention in bipolar disorders].

Encephale. 2010 Mar;36 Suppl 3:S71-6

Authors: Conus P

While early intervention strategies have been developed for psychotic disorders, affective psychoses and bipolar disorders have been neglected by this movement. However, when considering that outcome of bipolar disorders is often not as favorable as previously thought and that delay between illness onset and introduction of an adequate treatment is often very long, such developments seem clearly justified. In this paper we briefly review arguments supporting early intervention in bipolar disorders, the practical and theoretical obstacles that still need to be overcome, the strategies that may already now contribute to decrease treatment delay, and we describe current state of research regarding identification of the prodromal phase of bipolar disorders.

PMID: 21095396 [PubMed - indexed for MEDLINE]

Program evaluation of a community crisis stabilization program.

Arch Psychiatr Nurs. 2010 Dec;24(6):387-96

Authors: Boyer DE, Kane C

The purpose of this program evaluation was to evaluate the outcomes of treatment for participants in a community crisis stabilization (CCS) program. This CCS incorporated a patient-centered and wellness model of treatment. A descriptive study was conducted to assess change in psychological symptoms and quality of life of participants from admission to discharge. The sample (n = 42) was evaluated on admission and at discharge with four measurements: the Brief Symptoms Inventory (BSI), the Revised 24-Item Behavior and Symptom Identification Scale (BASIS-24), the Brief Psychiatric Rating Scale (BPRS), and the World Health Organization Quality of Life Scale-Brief Measure (WHOQOL-BREF). Changes in total scores on the BSI (t = 6.263, P < .001), the BASIS-24 (t = 6.964, P < .001), the BPRS (t = 4.638, P < .001), and the WHOQOL-BREF (t = 6.574, P < .001) demonstrated improvement at discharge.

PMID: 21111293 [PubMed - indexed for MEDLINE]

Detection of overreported psychopathology with the MMPI-2-RF [corrected] validity scales.

Psychol Assess. 2010 Dec;22(4):757-67

Authors: Sellbom M, Bagby RM

We examined the utility of the validity scales on the recently released Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2 RF; Ben-Porath & Tellegen, 2008) to detect overreported psychopathology. This set of validity scales includes a newly developed scale and revised versions of the original MMPI-2 validity scales. We used an analogue, experimental simulation in which MMPI-2 RF responses (derived from archived MMPI-2 protocols) of undergraduate students instructed to overreport psychopathology (in either a coached or noncoached condition) were compared with those of psychiatric inpatients who completed the MMPI-2 under standardized instructions. The MMPI-2 RF validity scale Infrequent Psychopathology Responses best differentiated the simulation groups from the sample of patients, regardless of experimental condition. No other validity scale added consistent incremental predictive utility to Infrequent Psychopathology Responses in distinguishing the simulation groups from the sample of patients. Classification accuracy statistics confirmed the recommended cut scores in the MMPI-2 RF manual (Ben-Porath & Tellegen, 2008).

PMID: 21133544 [PubMed - indexed for MEDLINE]

Diagnostic validity of the Eppendorf Schizophrenia Inventory (ESI): a self-report screen for ultrahigh risk and acute psychosis.

Psychol Assess. 2010 Dec;22(4):935-44

Authors: Niessen MA, Dingemans PM, van de Fliert R, Becker HE, Nieman DH, Linszen D

Providers of mental health services need tools to screen for acute psychosis and ultrahigh risk (UHR) for transition to psychosis in help-seeking individuals. In this study, the Eppendorf Schizophrenia Inventory (ESI) was examined as a screening tool and for its ability to correctly predict diagnostic group membership (e.g., help seeking, mild psychiatric complaints, highly symptomatic mood or anxiety disorder, UHR, acute psychosis). Diagnostic evaluation with established instruments was used for diagnosis in 3 research samples. UHR status was assessed with the Structured Interview for Prodromal Symptoms/Scale of Prodromal Symptoms (Miller et al., 1999) and the Bonn Scale for the Assessment of Basic Symptoms Prediction list (Gross, Huber, Klosterkötter, & Linz, 1987; Klosterkötter, Hellmich, Steinmeyer, & Schulze-Lutter, 2001). This study showed that members of different diagnostic groups rate themselves significantly differently on the ESI and its subscales. A new subscale was constructed, the UHR-Psychosis scale, that showed good utility in detecting individuals with interview-diagnosed UHR status and acute psychosis. The scale is also sensitive to the threshold between UHR and acute psychosis. Practical applications of the ESI include use as a diagnostic tool within various settings.

PMID: 21133552 [PubMed - indexed for MEDLINE]

Overlapping clusters of gray matter deficits in paranoid schizophrenia and psychotic bipolar mania with family history.

Neurosci Lett. 2011 Feb 4;489(2):94-8

Authors: Cui L, Li M, Deng W, Guo W, Ma X, Huang C, Jiang L, Wang Y, Collier DA, Gong Q, Li T

The purpose of this study was to assess volumetric abnormalities of gray matter throughout the entire brain in patients with paranoid schizophrenia or with bipolar mania compared with control groups. We obtained weighted 3D T1 magnetic resonance images from 23 patients with paranoid schizophrenia, 24 patients with psychotic bipolar mania, and 36 healthy controls. Gray matter volume differences were assessed using optimized volumetric voxel-based morphometry (VBM). Both paranoid schizophrenia and bipolar mania group showed reduction of gray matter volume in the superior temporal gyrus (STG) (Brodmann Area, BA 22 areas), and the inferior parietal lobule, and enlargement of putamen, although different sides of the inferior parietal lobule and putamen were affected in the groups. Our findings showed the presence of overlapping clusters of gray matter deficits in paranoid-type schizophrenia and psychotic bipolar mania. The overlap in gray matter pathology between the two disorders may be attributed to risk factors common to both disorders.

PMID: 21138758 [PubMed - indexed for MEDLINE]

Mania and depression. Mixed, not stirred.

J Affect Disord. 2011 Apr 21;

Authors: Pacchiarotti I, Mazzarini L, Kotzalidis GD, Valentí M, Nivoli AM, Sani G, Torrent C, Murru A, Sanchez-Moreno J, Patrizi B, Girardi P, Vieta E, Colom F

OBJECTIVE: Current criteria for mixed bipolar episode do not allow an adequate understanding of a vast majority of bipolar patients with mixed (hypo) manic-depressive features, keeping the qualification of "mixed episodes" for bipolar type I only. This study was aimed to test the existence of a bipolar-mixed continuum by comparing the characteristics of three groups classified according to patterns of past and current manic or mixed episodes. METHOD: 134 bipolar I inpatients were divided according to their pattern of excitatory "mixed-like" episodes in three groups: 1) lifetime history of purely manic episodes without mixed features (PMA); 2) lifetime history of both manic and mixed episodes (MIX) and 3) lifetime history exclusively of mixed, but not manic, episodes (PMIX). Differences in clinical and demographic characteristics were analyzed by using chi-square head-to-head for categorical data, one-way ANOVA for continuous variables and Tukey's post-hoc comparison. Logistic regression was used to control for data validity. RESULTS: PMIX had higher rates of depressive predominant polarity and less lifetime history of psychotic symptoms, and had received more antidepressants both lifetime and during 6months prior to index episode. PMIX had more suicide attempts and Axis I comorbidity than PMA. DISCUSSION: PMIX is likely to have a higher risk for suicide and higher rates of comorbidities; current DSM-IV-TR criteria are not fit for correctly classifying these patients and this may affect treatment appropriateness. The concept of "mixicity" should be extended beyond bipolar I disorder to other bipolar disorder subtypes.

PMID: 21514674 [PubMed - as supplied by publisher]

Transgenic mice overexpressing the extracellular domain of NCAM are impaired in working memory and cortical plasticity.

Neurobiol Dis. 2011 Apr 16;

Authors: Brennaman LH, Kochlamazashvili G, Stoenica L, Nonneman RJ, Moy SS, Schachner M, Dityatev A, Maness PF

The neural cell adhesion molecule, NCAM, is a pivotal regulator of neural development, with key roles in axonal and dendritic growth and synaptic plasticity. Alterations in NCAM expression or proteolytic cleavage have been linked to human neuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer's disease, and may contribute to cognitive dysfunction. We have generated mice overexpressing the NCAM extracellular (EC) proteolytic cleavage fragment which has been reported to be increased in schizophrenic versus normal brains. These mice show impaired GABAergic innervation and reduced number of apical dendritic spines on pyramidal neurons in the prefrontal cortex (PFC). Here, these NCAM-EC transgenic mice were subjected to behavioral tasks and electrophysiological measurements to determine the impact of structural abnormalities in the PFC on synaptic and cognitive functions. NCAM-EC mice exhibited impaired working memory in a delayed non-match-to-sample task, which requires PFC function, but showed no differences in anxiety, olfactory abilities, or sociability. Transgenic mice displayed impaired long- and short-term potentiation in the PFC but normal synaptic plasticity in the hippocampus, suggesting that the abnormal synaptic innervation in NCAM-EC mice impairs PFC plasticity and alters working memory. These findings may have implications for cognitive dysfunctions observed in neuropsychiatric disorders.

PMID: 21515372 [PubMed - as supplied by publisher]

Cerebral Asymmetry in Schizophrenia.

Neuroscientist. 2011 Apr 25;

Authors: Oertel-Knöchel V, Linden DE

The hemispheres of the human brain are anatomically and functionally asymmetric, and many cognitive and motor functions such as language and handedness are lateralized. This review examines anatomical, psychological, and physiological approaches to the understanding of separate hemispheric functions and their integration. The concept of hemispheric laterality plays a central role in current neuropsychological and pathophysiological models of schizophrenia. Reduced hemispheric asymmetry has also been reported for other mental disorders, for example, bipolar disorder. Recent research reflects an increasing interest in the molecular and population genetics of laterality and its potential link with animal models of schizophrenia. The authors review the principles of laterality and brain asymmetry and discuss the evidence for changes in asymmetry in schizophrenia and other mental disorders.

PMID: 21518811 [PubMed - as supplied by publisher]

The impact of the CACNA1C gene polymorphism on frontolimbic function in bipolar disorder.

Mol Psychiatry. 2011 Apr 26;

Authors: Jogia J, Ruberto G, Lelli-Chiesa G, Vassos E, Maierú M, Tatarelli R, Girardi P, Collier D, Frangou S

PMID: 21519340 [PubMed - as supplied by publisher]

Sensitivity to stress among the offspring of parents with bipolar disorder: a study of daytime cortisol levels.

Psychol Med. 2011 Apr 28;:1-11

Authors: Ostiguy CS, Ellenbogen MA, Walker CD, Walker EF, Hodgins S

BACKGROUND: It is well known that the hypothalamic-pituitary-adrenal (HPA) axis is compromised in major depression and bipolar disorder. There is increasing evidence that subtle HPA abnormalities, such as elevated cortisol levels, precede the development of an affective disorder. Interpersonal stress is also associated with the development of affective disorders. The present study sought to determine whether interpersonal chronic and episodic stress moderated the relationship between cortisol levels in the natural environment and risk status, defined as having a parent with bipolar disorder.MethodSixty-two offspring of parents with bipolar disorder (OBD) and 60 offspring with no family history of affective disorders (OFH-), aged 19.48 years (s.d.=3.38, range 14-28), completed interviews assessing mental disorders and chronic and episodic stress, and provided saliva samples over 3 days. RESULTS: Regression analyses revealed that the OBD who experienced high interpersonal chronic stress displayed a larger cortisol rise following awakening than the OBD reporting low interpersonal chronic stress. The same relationship was also found for levels of non-interpersonal chronic stress. The OBD who reported experiencing severe interpersonal episodic stress exhibited higher levels of daytime cortisol than the OBD reporting interpersonal episodic stress of mild severity. Importantly, none of the above relationships were detected in the OFH-. Each of the interactions between family history of affective disorders and stress remained after controlling for age, gender and offspring lifetime affective disorders and current non-affective disorders. CONCLUSIONS: A biological sensitivity to stress may underlie the susceptibility to affective disorders among the OBD.

PMID: 21524333 [PubMed - as supplied by publisher]

Impaired Limbic Gamma Oscillatory Synchrony during Anxiety-Related Behavior in a Genetic Mouse Model of Bipolar Mania.

J Neurosci. 2011 Apr 27;31(17):6449-6456

Authors: Dzirasa K, McGarity DL, Bhattacharya A, Kumar S, Takahashi JS, Dunson D, McClung CA, Nicolelis MA

Alterations in anxiety-related processing are observed across many neuropsychiatric disorders, including bipolar disorder. Though polymorphisms in a number of circadian genes confer risk for this disorder, little is known about how changes in circadian gene function disrupt brain circuits critical for anxiety-related processing. Here we characterize neurophysiological activity simultaneously across five limbic brain areas (nucleus accumbens, amygdala, prelimbic cortex, ventral hippocampus, and ventral tegmental area) as wild-type (WT) mice and mice with a mutation in the circadian gene, CLOCK (Clock-?19 mice) perform an elevated zero maze task. In WT mice, basal limbic gamma oscillatory synchrony observed before task performance predicted future anxiety-related behaviors. Additionally, dynamic changes in limbic gamma oscillatory synchrony were observed based on the position of WT mice in the zero maze. Clock-?19 mice, which displayed an increased propensity to enter the open section of the elevated maze, showed profound deficits in these anxiety-related circuit processes. Thus, our findings link the anxiety-related behavioral deficits observed in Clock-?19 mice with dysfunctional gamma oscillatory tuning across limbic circuits and suggest that alterations in limbic oscillatory circuit function induced by circadian gene polymorphisms may contribute to the behavioral manifestations seen in bipolar mania.

PMID: 21525286 [PubMed - as supplied by publisher]

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