'Emerging Biology of PDE10A'
Curr Pharm Des. 2014 Aug 26;
Authors: S Wilson L, Brandon NJ
Cyclic AMP and cyclic GMP are essential second messengers that regulate multiple signaling pathways in virtually all cell types. Their accumulation in cells is finely regulated by cyclic nucleotide phosphodiesterases (PDEs), the only enzymes that can degrade these signaling molecules and thus provide exquisite control over intracellular signaling processes. One PDE family, PDE10A, is highly enriched in the brain and its unique expression profile in specific brain regions of interest, in particular to antipsychotic treatment, has made it an attractive therapeutic target for the treatment of schizophrenia. However, after a Phase II trial failure of a selective PDE10A inhibitor for the treatment of schizophrenia, it has encouraged the field to reexamine the role of this enzyme in the brain, and the possible CNS disorders in which PDE10A inhibition could be therapeutic. We will review the localization of PDE10A, both within the brain and the neuron and discuss how its role in regulating cAMP and cGMP accumulation modulates intracellular signaling pathways. Since this cellular signaling has best been documented in the striatum, we will focus our discussion of PDE10A in the context of disorders that affect the basal ganglia, including psychiatric disorders such as bipolar disorder and autism spectrum disorders and the movement disorders, including Parkinson's disease and Huntington's disease.
PMID: 25159072 [PubMed - as supplied by publisher]
Mood Stabilizers and Antipsychotics for Acute Mania: A Systematic Review and Meta-Analysis of Combination/Augmentation Therapy Versus Monotherapy.
CNS Drugs. 2014 Aug 27;
Authors: Ogawa Y, Tajika A, Takeshima N, Hayasaka Y, Furukawa TA
BACKGROUND: Pharmacotherapy remains the mainstay of treatment for acute bipolar mania, but there are many choices, including mood stabilizers (MSs) and antipsychotics (APs).
OBJECTIVE: To provide an up-to-date and comprehensive review of the efficacy, acceptability and adverse effects of MSs and APs as combination or augmentation therapy versus monotherapy with either drug class for the treatment of acute mania.
DATA SOURCES: The Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, Scopus, and clinical trial databases were searched for articles published between the inception of the databases and July 1, 2014. The following keywords were used: [bipolar disorder, mania, manic, mixed bipolar, schizoaffective] combined with the names of MSs and APs. The reference lists of all the identified randomized controlled trials (RCTs), articles that cited the identified trials, and recent systematic reviews were also checked.
STUDY SELECTION: Double-blind RCTs comparing MS and AP as combination or augmentation therapy with either monotherapy during the acute phase treatment of mania were included in the present study. The electronic search yielded 6,445 potential articles in September 2013 and 264 new references in an updated search performed in July 2014. Finally, 19 RCTs were considered eligible for our meta-analyses: MS plus AP combination or augmentation therapy was compared with MS monotherapy in 14 trials (n = 3,651) and with AP monotherapy in 6 trials (n = 606) [one study compared combination therapy versus both MS monotherapy and AP monotherapy].
DATA EXTRACTION: The primary outcomes were the mean change scores on validated rating scales for mania and all-cause discontinuation at 3 weeks. The secondary outcomes included response, remission, the mean change scores for depression, dropouts due to adverse events and to inefficacy, and adverse events at 3 weeks and mean change scores on validated rating scales at 1 week. Using random-effects models, standardized mean difference (SMD), risk ratio (RR) and numbers needed to treat with their 95 % confidence intervals (CIs) were calculated.
RESULTS: Most patients included in trials comparing combination/augmentation therapy versus MS monotherapy had prior treatment with an MS, while more than 70 % of participants in trials comparing combination/augmentation therapy versus AP monotherapy had not been on medications or were washed out from their previous medication before randomization. MS plus AP combination/augmentation therapy was more effective than MS monotherapy in terms of change in scores on mania rating scales at 3 weeks (SMD -0.26; 95 % CI -0.36 to -0.15) and at 1 week (SMD -0.17, -0.29 to -0.04). MS plus AP combination/augmentation therapy was more effective than AP monotherapy at 3 weeks (SMD -0.31, -0.50 to -0.12), but not at 1 week (SMD -0.22, -0.84 to 0.40). No significant differences were seen between the combination/augmentation therapy and either monotherapy group in study withdrawal for any reason (MS + AP vs. MS monotherapy: RR 0.99, 0.88-1.12; MS + AP vs. AP monotherapy: RR 0.70, 0.47-1.04) or adverse events (MS + AP vs. MS monotherapy: RR 1.39, 0.97-1.99; MS + AP vs. AP monotherapy: RR 0.62, 0.27-1.40). The combination/augmentation therapy was associated with more side effects, especially with somnolence, while it did not increase treatment-emergent depression.
CONCLUSIONS: Combining MS and AP is more efficacious and more burdensome than, but overall as acceptable as, the continuation of MS or AP monotherapy, when either monotherapy has not been successful. There is currently no robust evidence to judge whether MS and AP combination therapy is more efficacious than MS monotherapy as the initial therapy for acutely manic patients without prior medication.
PMID: 25160685 [PubMed - as supplied by publisher]
The Impact of Psychopharmacology on Contemporary Psychiatry.
Can J Psychiatry. 2014 Aug 1;59(8):401-405
Authors: Baldessarini RJ
PMID: 25161063 [PubMed - as supplied by publisher]
Expression of ZNF804A in Human Brain and Alterations in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder: A Novel Transcript Fetally Regulated by the Psychosis Risk Variant rs1344706.
JAMA Psychiatry. 2014 Aug 27;
Authors: Tao R, Cousijn H, Jaffe AE, Burnet PW, Edwards F, Eastwood SL, Shin JH, Lane TA, Walker MA, Maher BJ, Weinberger DR, Harrison PJ, Hyde TM, Kleinman JE
Importance: The single-nucleotide polymorphism rs1344706 in the zinc finger protein 804A gene (ZNF804A) shows genome-wide association with schizophrenia and bipolar disorder. Little is known regarding the expression of ZNF804A and the functionality of rs1344706.
Objectives: To characterize ZNF804A expression in human brain and to investigate how it changes across the life span and how it is affected by rs1344706, schizophrenia, bipolar disorder, and major depressive disorder.
Design, Setting, and Participants: Molecular and immunochemical methods were used to study ZNF804A messenger RNA (mRNA) and ZNF804A protein, respectively. ZNF804A transcripts were investigated using next-generation sequencing and polymerase chain reaction-based methods, and ZNF804A protein was investigated using Western blots and immunohistochemistry. Samples of dorsolateral prefrontal cortex and inferior parietal lobe tissue were interrogated from 697 participants between 14 weeks' gestational age and age 85 years, including patients with schizophrenia, bipolar disorder, or major depressive disorder.
Main Outcomes and Measures: Quantitative measurements of ZNF804A mRNA and immunoreactivity, and the effect of diagnosis and rs1344706 genotype.
Results: ZNF804A was expressed across the life span, with highest expression prenatally. An abundant and developmentally regulated truncated ZNF804A transcript was identified, missing exons 1 and 2 (ZNF804AE3E4) and predicted to encode a protein lacking the zinc finger domain. rs1344706 influenced expression of ZNF804AE3E4 mRNA in fetal brain (P?=?.02). In contrast, full-length ZNF804A showed no association with genotype (P?>?.05). ZNF804AE3E4 mRNA expression was decreased in patients with schizophrenia (P?=?.006) and increased in those with major depressive disorder (P?<?.001), and there was a genotype-by-diagnosis interaction in bipolar disorder (P?=?.002). ZNF804A immunoreactivity was detected in fetal and adult human cerebral cortex. It was localized primarily to pyramidal neurons, with cytoplasmic as well as dendritic and nuclear staining. No differences in ZNF804A-immunoreactive neurons were seen in schizophrenia or related to rs1344706 (P?>?.05).
Conclusions and Relevance: rs1344706 influences the expression of ZNF804AE3E4, a novel splice variant. The effect is limited to fetal brain and to this isoform. It may be part of the mechanism by which allelic variation in ZNF804A affects risk of psychosis. ZNF804A is translated in human brain, where its functions may extend beyond its predicted role as a transcription factor.
PMID: 25162540 [PubMed - as supplied by publisher]
MAOA and mechanisms of panic disorder revisited: from bench to molecular psychotherapy.
Mol Psychiatry. 2014 Jan;19(1):122-8
Authors: Reif A, Richter J, Straube B, Höfler M, Lueken U, Gloster AT, Weber H, Domschke K, Fehm L, Ströhle A, Jansen A, Gerlach A, Pyka M, Reinhardt I, Konrad C, Wittmann A, Pfleiderer B, Alpers GW, Pauli P, Lang T, Arolt V, Wittchen HU, Hamm A, Kircher T, Deckert J
Panic disorder with agoraphobia (PD/AG) is a prevalent mental disorder featuring a substantial complex genetic component. At present, only a few established risk genes exist. Among these, the gene encoding monoamine oxidase A (MAOA) is noteworthy given that genetic variation has been demonstrated to influence gene expression and monoamine levels. Long alleles of the MAOA-uVNTR promoter polymorphism are associated with PD/AG and correspond with increased enzyme activity. Here, we have thus investigated the impact of MAOA-uVNTR on therapy response, behavioral avoidance and brain activity in fear conditioning in a large controlled and randomized multicenter study on cognitive behavioral therapy (CBT) in PD/AG. The study consisted of 369 PD/AG patients, and genetic information was available for 283 patients. Carriers of the risk allele had significantly worse outcome as measured by the Hamilton Anxiety scale (46% responders vs 67%, P=0.017). This was accompanied by elevated heart rate and increased fear during an anxiety-provoking situation, that is, the behavioral avoidance task. All but one panic attack that happened during this task occurred in risk allele carriers and, furthermore, risk allele carriers did not habituate to the situation during repetitive exposure. Finally, functional neuroimaging during a classical fear conditioning paradigm evidenced that the protective allele is associated with increased activation of the anterior cingulate cortex upon presentation of the CS+ during acquisition of fear. Further differentiation between high- and low-risk subjects after treatment was observed in the inferior parietal lobes, suggesting differential brain activation patterns upon CBT. Taken together, we established that a genetic risk factor for PD/AG is associated with worse response to CBT and identify potential underlying neural mechanisms. These findings might govern how psychotherapy can include genetic information to tailor individualized treatment approaches.
PMID: 23319006 [PubMed - indexed for MEDLINE]
Employment program for patients with severe mental illness in Malaysia: a 3-month outcome.
Compr Psychiatry. 2014 Jan;55 Suppl 1:S38-45
Authors: Wan Kasim SH, Midin M, Abu Bakar AK, Sidi H, Nik Jaafar NR, Das S
OBJECTIVE: This study aimed to examine the rate and predictive factors of successful employment at 3 months upon enrolment into an employment program among patients with severe mental illness (SMI).
METHODS: A cross-sectional study using universal sampling technique was conducted on patients with SMI who completed a 3-month period of being employed at Hospital Permai, Malaysia. A total of 147 patients were approached and 126 were finally included in the statistical analyses. Successful employment was defined as the ability to work 40 or more hours per month. Factors significantly associated with successful employment from bivariate analyses were entered into a multiple logistic regression analysis to identify predictors of successful employment.
RESULTS: The rate of successful employment at 3 months was 68.3% (n=81). Significant factors associated with successful employment from bivariate analyses were having past history of working, good family support, less number of psychiatric admissions, good compliance to medicine, good interest in work, living in hostel, being motivated to work, satisfied with the job or salary, getting a preferred job, being in competitive or supported employment and having higher than median scores of PANNS on the positive, negative and general psychopathology. Significant predictors of employment, from a logistic regression model were having good past history of working (p<0.021; OR 6.12; [95% CI 2.1-11.9]) and getting a preferred job (p<0.032; [OR 4.021; 95% CI 1.83-12.1]).
CONCLUSION: Results showed a high employment rate among patients with SMI. Good past history of working and getting a preferred job were significant predictors of successful employment.
PMID: 23602390 [PubMed - indexed for MEDLINE]
Topiramate use does not reduce flares of inflammatory bowel disease.
Dig Dis Sci. 2014 Jul;59(7):1535-43
Authors: Crockett SD, Schectman R, Stürmer T, Kappelman MD
BACKGROUND: Additional medications are needed for inflammatory bowel disease (IBD) as existing therapies are incompletely effective and can be costly and toxic. Preclinical studies suggest that topiramate (an anticonvulsant) may have disease-modifying properties in IBD, but its efficacy in humans is unknown.
AIM: To evaluate whether topiramate use is associated with clinical benefit in IBD patients.
METHODS: We conducted a retrospective cohort study using administrative claims data from the MarketScan databases. Persons with IBD were identified between 2000 and 2010. New users of topiramate were compared with users of other anticonvulsant and anti-migraine medications. The primary outcome was a new prescription for an oral steroid (?14 days). Secondary outcomes included initiation of biologic agents, abdominal surgery, and hospitalization. Cox proportional hazard modeling was used to adjust for potential confounders.
RESULTS: We identified 773 new users of topiramate and 958 users of comparator drugs. After adjusting for potential confounders, topiramate use was not associated with the primary outcome of steroid prescriptions [hazard ratio (HR) 1.14, 95 % confidence interval (CI) 0.74, 1.73]. Results did not differ significantly by IBD subtype. There was no difference between topiramate users and users of comparator drugs with respect to post-exposure initiation of biologic agents (HR 0.93, 95 % CI 0.39, 2.19), abdominal surgery (HR 1.04, 95 % CI 0.17, 6.41), or hospitalization (HR 0.86, 95 % CI 0.62, 1.19).
CONCLUSION: In this large U.S. administrative claims study, topiramate use was not associated with markers of IBD flares. These results cast doubt on whether topiramate may be an effective adjunct to current IBD therapy.
PMID: 24504592 [PubMed - indexed for MEDLINE]
The Effect of Clozapine on Premature Mortality: An Assessment of Clinical Monitoring and Other Potential Confounders.
Schizophr Bull. 2014 Aug 25;
Authors: Hayes RD, Downs J, Chang CK, Jackson RG, Shetty H, Broadbent M, Hotopf M, Stewart R
Clozapine can cause severe adverse effects yet it is associated with reduced mortality risk. We test the hypothesis this association is due to increased clinical monitoring and investigate risk of premature mortality from natural causes. We identified 14 754 individuals (879 deaths) with serious mental illness (SMI) including schizophrenia, schizoaffective and bipolar disorders aged ? 15 years in a large specialist mental healthcare case register linked to national mortality tracing. In this cohort study we modeled the effect of clozapine on mortality over a 5-year period (2007-2011) using Cox regression. Individuals prescribed clozapine had more severe psychopathology and poorer functional status. Many of the exposures associated with clozapine use were themselves risk factors for increased mortality. However, we identified a strong association between being prescribed clozapine and lower mortality which persisted after controlling for a broad range of potential confounders including clinical monitoring and markers of disease severity (adjusted hazard ratio 0.4; 95% CI 0.2-0.7; p = .001). This association remained after restricting the sample to those with a diagnosis of schizophrenia or those taking antipsychotics and after using propensity scores to reduce the impact of confounding by indication. Among individuals with SMI, those prescribed clozapine had a reduced risk of mortality due to both natural and unnatural causes. We found no evidence to indicate that lower mortality associated with clozapine in SMI was due to increased clinical monitoring or confounding factors. This is the first study to report an association between clozapine and reduced risk of mortality from natural causes.
PMID: 25154620 [PubMed - as supplied by publisher]
DSM-5 reviewed from different angles: goal attainment, rationality, use of evidence, consequences-part 2: bipolar disorders, schizophrenia spectrum disorders, anxiety disorders, obsessive-compulsive disorders, trauma- and stressor-related disorders, personality disorders, substance-related and addictive disorders, neurocognitive disorders.
Eur Arch Psychiatry Clin Neurosci. 2014 Aug 26;
Authors: Möller HJ, Bandelow B, Bauer M, Hampel H, Herpertz SC, Soyka M, Barnikol UB, Lista S, Severus E, Maier W
Part 1 of this paper discussed several more general aspects of Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and offered a detailed, paradigmatic analysis of changes made to the chapter on depressive disorders. This second part focusses on several other disorders, including bipolar and schizophrenia spectrum disorders. The respective changes and their possible consequences are discussed under consideration of traditional psychiatric classification, particularly from the perspective of European traditions and on the basis of a PubMed search and review papers. The general conclusion is that even seemingly small changes such as the introduction of the mixed feature specifier can have far-reaching consequences. Contrary to the original plans, DSM-5 has not radically changed to become a primarily dimensional diagnostic system but has preserved the categorical system for most disorders. The ambivalence of the respective decision-making becomes apparent from the last minute decision to change the classification of personality disorders from dimensional back to categorical. The advantages and disadvantages of the different approaches are discussed in this context. In DSM-5, only the chapter on addictive disorders has a somewhat dimensional structure. Also in contrast to the original intentions, DSM-5 has not used a more neurobiological approach to disorders by including biological markers to increase the objectivity of psychiatric diagnoses. Even in the most advanced field in terms of biomarkers, the neurocognitive disorders, the primarily symptom-based, descriptive approach has been preserved and the well-known amyloid-related and other biomarkers are not included. This is because, even after so many years of biomarker research, the results are still not considered to be robust enough to use in clinical practice.
PMID: 25155875 [PubMed - as supplied by publisher]
Are confusional arousals pathological?
Neurology. 2014 Aug 26;83(9):834-41
Authors: Ohayon MM, Mahowald MW, Leger D
OBJECTIVE: The objective of this study was to determine the extent that confusional arousals (CAs) are associated with mental disorders and psychotropic medications.
METHODS: Cross-sectional study conducted with a representative sample of 19,136 noninstitutionalized individuals of the US general population aged 18 years or older. The study was performed using the Sleep-EVAL expert system and investigated sleeping habits; health; and sleep, mental, and medical conditions (DSM-IV-TR, ICSD-II, ICD-10).
RESULTS: A total of 15.2% (95% confidence interval 14.6%-15.8%) (n = 2,421) of the sample reported episodes of CAs in the previous year; 8.6% had complete or partial amnesia of the episodes and 14.8% had CAs and nocturnal wandering episodes. Eighty-four percent of CAs were associated with sleep/mental disorders or psychotropic drugs. Sleep disorders were present for 70.8% of CAs. Individuals with a circadian rhythm sleep disorder or a long sleep duration (?9 hours) were at higher risk of CAs. Mental disorders were observed in 37.4% of CAs. The highest odds were observed in individuals with bipolar disorders or panic disorder. Use of psychotropic medication was reported by 31.3% of CAs: mainly antidepressant medications. After eliminating possible causes and associated conditions, only 0.9% of the sample had CA disorder.
CONCLUSIONS: CAs are highly prevalent in the general population. They are often reported allegedly as a consequence of the treatment of sleep disorders. For the majority of subjects experiencing CAs, no medications were used, but among those who were using medications, antidepressants were most common. Sleep and/or mental disorders were important factors for CAs independent of the use of any medication.
PMID: 25156346 [PubMed - in process]
Evidence for cognitive subgroups in bipolar disorder and the influence of subclinical depression and sleep disturbances.
Eur Neuropsychopharmacol. 2014 Aug 15;
Authors: Volkert J, Kopf J, Kazmaier J, Glaser F, Zierhut KC, Schiele MA, Kittel-Schneider S, Reif A
Recent research in bipolar disorder (BD) points to the relevance and persistence of cognitive deficits even in euthymia. Up to now, the mechanisms behind why some bipolar patients (BP) do not reach their former level of cognitive performance and psychosocial functioning while others remit completely, are not understood. In this study we aimed to identify a "cognitive deficit" vs. "non-deficit" subgroup within BD by using an extensive neuropsychological test battery. The test performance of 70 euthymic outpatients (BD-I and II, recruited as a sample of convenience from our bipolar disorder programme) was compared to 70 matched, healthy controls (HC). Furthermore, we investigated the association between demographic/clinical variables and the cognitive performance of BP. As expected, our sample of euthymic BP performed significantly worse than HC in psychomotor speed, divided attention, working memory, verbal memory, word fluency and problem solving. However, 41.4% of the patients did not have any neurocognitive deficits at all, and whether or not a patient belonged to the non-deficit group was not influenced by disease severity. Instead, our results demonstrate that patients suffering from persistent sleep disturbances and sub-threshold depressive symptomatology show more severe cognitive dysfunctions. In addition, antipsychotic treatment and comorbid anxiety disorder were associated with cognitive deficits. In sum, these results suggest that a major part of cognitive impairment is due to current symptomatology, especially sleep disorder and sub-syndromal depression. Rigorous treatment of these symptoms thus might well improve cognitive deficits and, as a consequence, overall functioning in BD.
PMID: 25156468 [PubMed - as supplied by publisher]
The hypomanic personality scale: A measure of personality and/or bipolar symptoms?
Psychiatry Res. 2014 Jul 28;
Authors: Parker G, Fletcher K, McCraw S, Hong M
The Hypomanic Personality Scale (HPS) was designed to measure a predispositional personality style to bipolar disorder. Its properties have largely been assessed in non-clinical samples. We undertook a number of analyses to determine if it is likely to be a measure of actual personality style or is confounded by items capturing hypomanic/manic mood symptoms. A total of 112 bipolar and 164 unipolar patients completed the measure. Several principal components analyses were undertaken and associations were examined between HPS items and scores on a measure designed to identify bipolar disorder - the Mood Swings Questionnaire (MSQ). Principal components analyses generated a similar set of four factors in both the unipolar and bipolar sample sub-sets and congruent with previous analyses undertaken in non-clinical samples, suggesting identification of normative dimensions that underpin hypomanic and manic mood states. A number of HPS items correlated highly with the MSQ. Results suggest that HPS is unlikely to simply be a measure of personality style and appears strongly confounded by hypomanic/manic mood symptoms. The measure may therefore - in its current form - be inappropriate for at-risk research seeking to determine the capacity of personality style to predict onset of a bipolar disorder.
PMID: 25156658 [PubMed - as supplied by publisher]
Collaborative Care for Adolescents With Depression in Primary Care: A Randomized Clinical Trial.
JAMA. 2014 Aug 27;312(8):809-816
Authors: Richardson LP, Ludman E, McCauley E, Lindenbaum J, Larison C, Zhou C, Clarke G, Brent D, Katon W
Importance: Up to 20% of adolescents experience an episode of major depression by age 18 years yet few receive evidence-based treatments for their depression.
Objective: To determine whether a collaborative care intervention for adolescents with depression improves depressive outcomes compared with usual care.
Design: Randomized trial with blinded outcome assessment conducted between April 2010 and April 2013.
Setting: Nine primary care clinics in the Group Health system in Washington State.
Participants: Adolescents (aged 13-17 years) who screened positive for depression (Patient Health Questionnaire 9-item [PHQ-9] score ?10) on 2 occasions or who screened positive and met criteria for major depression, spoke English, and had telephone access were recruited. Exclusions included alcohol/drug misuse, suicidal plan or recent attempt, bipolar disorder, developmental delay, and seeing a psychiatrist.
Interventions: Twelve-month collaborative care intervention including an initial in-person engagement session and regular follow-up by master's-level clinicians. Usual care control youth received depression screening results and could access mental health services through Group Health.
Main Outcomes and Measures: The primary outcome was change in depressive symptoms on a modified version of the Child Depression Rating Scale-Revised (CDRS-R; score range, 14-94) from baseline to 12 months. Secondary outcomes included change in Columbia Impairment Scale score (CIS), depression response (?50% decrease on the CDRS-R), and remission (PHQ-9 score <5).
Results: Intervention youth (n?=?50), compared with those randomized to receive usual care (n?=?51), had greater decreases in CDRS-R scores such that by 12 months intervention youth had a mean score of 27.5 (95% CI, 23.8-31.1) compared with 34.6 (95% CI, 30.6-38.6) in control youth (overall intervention effect: F2,747.3?=?7.24, P?<?.001). Both intervention and control youth experienced improvement on the CIS with no significant differences between groups. At 12 months, intervention youth were more likely than control youth to achieve depression response (67.6% vs 38.6%, OR?=?3.3, 95% CI, 1.4-8.2; P?=?.009) and remission (50.4% vs 20.7%, OR?=?3.9, 95% CI, 1.5-10.6; P?=?.007).
Conclusions and Relevance: Among adolescents with depression seen in primary care, a collaborative care intervention resulted in greater improvement in depressive symptoms at 12 months than usual care. These findings suggest that mental health services for adolescents with depression can be integrated into primary care.
Trial Registration: clinicaltrials.gov Identifier: NCT01140464.
PMID: 25157724 [PubMed - as supplied by publisher]
Label-free, live optical imaging of reprogrammed bipolar disorder patient-derived cells reveals a functional correlate of lithium responsiveness.
Transl Psychiatry. 2014;4:e428
Authors: Wang JL, Shamah SM, Sun AX, Waldman ID, Haggarty SJ, Perlis RH
Development of novel treatments and diagnostic tools for psychiatric illness has been hindered by the absence of cellular models of disease. With the advent of cellular reprogramming, it may be possible to recapitulate the disease biology of psychiatric disorders using patient skin cells transdifferentiated to neurons. However, efficiently identifying and characterizing relevant neuronal phenotypes in the absence of well-defined pathophysiology remains a challenge. In this study, we collected fibroblast samples from patients with bipolar 1 disorder, characterized by their lithium response (n=12), and healthy control subjects (n=6). We identified a cellular phenotype in reprogrammed neurons using a label-free imaging assay based on a nanostructured photonic crystal biosensor and found that an optical measure of cell adhesion was associated with clinical response to lithium treatment. This cellular phenotype may represent a useful biomarker to evaluate drug response and screen for novel therapeutics.
PMID: 25158003 [PubMed - as supplied by publisher]
Antidepressant efficacy of high and low frequency rTMS at 110% of motor threshold versus sham stimulation over left prefrontal cortex.
Brain Stimul. 2014 Jan-Feb;7(1):36-41
Authors: Speer AM, Wassermann EM, Benson BE, Herscovitch P, Post RM
BACKGROUND: While the efficacy of repetitive transcranial magnetic stimulation (rTMS) at 10 Hz over the left prefrontal cortex has been repeatedly demonstrated, it is not clear that the optimal parameters for the treatment of depression have been adequately elucidated.
OBJECTIVES: We sought to assess the antidepressant effectiveness of high and low frequency at a higher intensity rTMS compared to sham in patients with moderately treatment resistant depression.
METHOD: The authors conducted a three-week, double-blind, randomized, sham-controlled study of 24 acutely depressed patients given either active 20 Hz (n = 8) or 1 Hz (n = 8) rTMS (at 110% of motor threshold [MT]) or sham treatments (n = 8) over the left prefrontal cortex. Hamilton Depression ratings were analyzed by ANOVA.
RESULTS: Patients on both frequencies showed greater improvement than on sham, which was associated with minor increases in depression. During open continuation to allow 7 weeks of active treatment in all individuals, additional improvement was observed.
CONCLUSIONS: The results seen here using 110% of MT for 3 weeks were more robust than those of previous studies of 1-Hz or 20-Hz rTMS for 2 weeks (at 80% and 100% of MT). The results also raise the possibility that both high and low frequency rTMS over left prefrontal cortex (and not just low frequency over the right prefrontal cortex) exert antidepressant effects, but further work is required to assess what parameters may be most effective in general and for a given individual.
PMID: 23928104 [PubMed - indexed for MEDLINE]
Anti-anhedonic effect of deep brain stimulation of the prefrontal cortex and the dopaminergic reward system in a genetic rat model of depression: an intracranial self-stimulation paradigm study.
Brain Stimul. 2014 Jan-Feb;7(1):21-8
Authors: Rea E, Rummel J, Schmidt TT, Hadar R, Heinz A, Mathé AA, Winter C
BACKGROUND: One of the two core symptoms of major depression (MD), whether uni- or bipolar, is the inability to experience pleasure, suggested to be triggered by dysregulation within the brain reward system. In recent years, deep brain stimulation (DBS) has evolved as a potential tool to modulate pathological neural activity; stimulation of the subgenual cingulate (Cg25) has been shown to reduce depressive symptoms, including anhedonia. In rodents, the ventromedial prefrontal cortex (vmPFC) is likely to represent the correlate of Cg25 and accordingly, stimulation of vmPFC reduces anhedonia-like behavior in rats.
OBJECTIVE/HYPOTHESIS: The present study addresses the question of whether the anti-anhedonic effect of vmPFC-DBS is mediated by the brain reward system.
METHODS: Rats of the Flinders Sensitive Line (FSL), a validated genetic animal model of depression, and its controls, the Flinders Resistant Line (FRL), were stimulated in the vmPFC and tested in the forced swim test (FST), sucrose consumption test (SCT) and the intracranial self-stimulation (ICSS) paradigm. The curve-shift paradigm of ICSS was used in combination with vmPFC-DBS, d-amphetamine and fluoxetine to quantify reward-facilitating or -attenuating treatment effects.
RESULTS: Our findings support anti-depressive efficacy of vmPFC-DBS with respect to despair- and anhedonia-like behavior, as shown in the FST and SCT, respectively. However, DBS did not elicit reward-facilitating or reward-attenuating effects on ICSS behavior.
CONCLUSION: These data suggest that it is unlikely that the anti-anhedonic effect of vmPFC-DBS depends on the mesolimbic dopaminergic reward system.
PMID: 24139146 [PubMed - indexed for MEDLINE]
Case managers' perceptions of consumer work readiness and association with pursuit of employment.
Psychiatr Serv. 2013 Dec 1;64(12):1267-9
Authors: Goscha R, Kondrat DC, Manthey TJ
OBJECTIVE The purpose of this study was to determine whether case managers' perceptions of consumers' work readiness-in the areas of the individual consumer's hygiene, social skills, medication adherence, psychiatric symptoms, and substance use-influence pursuit of employment. METHODS A cross-sectional survey study design was used to assess the role of staff perceptions in consumers' pursuit of employment. A hierarchical generalized linear model with a logit link function was used to analyze data from 1,556 consumers nested within data for 113 case manager caseloads. RESULTS Case managers' perception of work readiness was significantly associated with pursuit of employment. CONCLUSIONS The clients of case managers with less stringent criteria for pursuing employment were more likely to take positive steps toward employment.
PMID: 24292732 [PubMed - indexed for MEDLINE]
Pregnancy outcome following in utero exposure to lithium: a prospective, comparative, observational study.
Am J Psychiatry. 2014 Jul 1;171(7):785-94
Authors: Diav-Citrin O, Shechtman S, Tahover E, Finkel-Pekarsky V, Arnon J, Kennedy D, Erebara A, Einarson A, Ornoy A
OBJECTIVE: The authors conducted a prospective, comparative observational study to evaluate the risk of major anomalies following exposure to lithium during pregnancy.
METHOD: A total of 183 lithium-exposed pregnancies of women who contacted the Israeli Teratology Information Service were followed up (90.2% in the first trimester) and compared with 72 disease-matched and 748 nonteratogenic-exposed pregnancies.
RESULTS: There were significantly more miscarriages (adjusted odds ratio=1.94, 95% CI=1.08-3.48) and elective terminations of pregnancy (17/183 [9.3%] compared with 15/748 [2.0%]) in the lithium-exposed group compared with the nonteratogenic exposure group. The rate of major congenital anomalies after exclusion of genetic or cytogenetic anomalies was not significantly different between the three groups (lithium-exposed in the first trimester: 8/123 [6.5%]; bipolar: 2/61 [3.3%]; nonteratogenic: 19/711 [2.7%]). Cardiovascular anomalies occurred more frequently in the lithium group exposed during the first trimester when compared with the nonteratogenic exposure group (5/123 [4.1%] compared with 4/711 [0.6%]) but not after excluding anomalies that spontaneously resolved (3/123 [2.4%] compared with 2/711 [0.3%]). Ebstein's anomaly was diagnosed in one lithium-exposed fetus and in two retrospective lithium cases that were not included because contact with the information service was made after the prenatal diagnosis by ultrasound. The rate of noncardiovascular anomalies was not significantly different between the groups. The rate of preterm deliveries was higher in the lithium group compared with the nonteratogenic exposure group (18/131 [13.7%] compared with 41/683 [6.0%]).
CONCLUSIONS: Lithium treatment in pregnancy is associated with a higher rate of cardiovascular anomalies. Women who are treated with lithium during organogenesis should undergo fetal echocardiography and level-2 ultrasound.
PMID: 24781368 [PubMed - indexed for MEDLINE]
Lithium during pregnancy.
Am J Psychiatry. 2014 Jul 1;171(7):712-5
Authors: Bergink V, Kushner SA
PMID: 24980165 [PubMed - indexed for MEDLINE]
An analysis of moderate sedation protocols used in dental specialty programs: a retrospective observational study.
J Endod. 2014 Sep;40(9):1327-31
Authors: Setty M, Montagnese TA, Baur D, Aminoshariae A, Mickel A
INTRODUCTION: Pain and anxiety control is critical in dental practice. Moderate sedation is a useful adjunct in managing a variety of conditions that make it difficult or impossible for some people to undergo certain dental procedures. The purpose of this study was to analyze the sedation protocols used in 3 dental specialty programs at the Case Western Reserve University School of Dental Medicine, Cleveland, OH.
METHODS: A retrospective analysis was performed using dental school records of patients receiving moderate sedation in the graduate endodontic, periodontic, and oral surgery programs from January 1, 2010, to December 31, 2012. Information was gathered and the data compiled regarding the reasons for sedation, age, sex, pertinent medical conditions, American Society of Anesthesiologists physical status classifications, routes of administration, drugs, dosages, failures, complications, and other information that was recorded.
RESULTS: The reasons for the use of moderate sedation were anxiety (54%), local anesthesia failures (15%), fear of needles (15%), severe gag reflex (8%), and claustrophobia with the rubber dam (8%). The most common medical conditions were hypertension (17%), asthma (15%), and bipolar disorder (8%). Most patients were classified as American Society of Anesthesiologists class II. More women (63.1%) were treated than men (36.9%). The mean age was 45 years. Monitoring and drugs varied among the programs. The most common tooth treated in the endodontic program was the mandibular molar.
CONCLUSIONS: There are differences in the moderate sedation protocols used in the endodontic, periodontic, and oral surgery programs regarding monitoring, drugs used, and record keeping.
PMID: 25146012 [PubMed - in process]
Current Neural and Behavioral Dimensional Constructs across Mood Disorders.
Curr Behav Neurosci Rep. 2014 Sep 1;1(3):144-153
Authors: Langenecker SA, Jacobs RH, Passarotti AM
Our understanding of the underlying neurobiology for mood disorders is still limited. We present an integrated model for conceptualizing and understanding mood disorders drawing upon a broad literature pertinent to mood disorders. The integrated model of emotion processing and regulation incorporates the linguistic constructs of the Research Domain Criteria (RDoC) initiative. In particular, we focus on the Positive Valence domain/circuit (PVC), highlighting recent reward research and the Negative Valence domain/circuit (NVC), highlighting rumination. Furthermore, we also illustrate the Cognitive Control and Problem Solving (CCaPS) circuit, which is heavily involved in emotion regulation, as well as the default mode network (DMN) and interactions between circuits. We conclude by proposing methods for addressing challenges in the developmental study of mood disorders including using high-risk design that incorporates risk for many disorders.
PMID: 25147755 [PubMed - as supplied by publisher]
Characterization and evaluation of self-nanoemulsifying sustained-release pellet formulation of ziprasidone with enhanced bioavailability and no food effect.
Drug Deliv. 2014 Aug 22;:1-10
Authors: Miao Y, Chen G, Ren L, Pingkai O
Abstract The purpose of this work was to develop self-nanomulsifying drug delivery systems (SNEDDS) in sustained-release pellets of ziprasidone to enhance the oral bioavailability and overcome the food effect of ziprasidone. Preformulation studies including screening of excipients for solubility and pseudo-ternary phase diagrams suggested the suitability of Capmul MCM as oil phase, Labrasol as surfactant, and PEG 400 as co-surfactant for preparation of self-nanoemulsifying formulations. Preliminary composition of the SNEDDS formulations were selected from the pseudo-ternary phase diagrams. The prepared ziprasidone-SNEDDS formulations were characterized for self-emulsification time, effect of pH and robustness to dilution, droplet size analysis and zeta potential. The optimized ziprasidone-SNEDDS were used to prepare ziprasidone-SNEDDS sustained-release pellets via extrusion-spheronization method. The pellets were characterized for SEM, particle size, droplet size distribution and zeta potential. In vitro drug release studies indicated the ziprsidone-SNEDDS sustained-release pellets showed sustained release profiles with 90% released within 10?h. The ziprsidone-SNEDDS sustained-release pellets were administered to fasted and fed beagle dogs and their pharmacokinetics were compared to commercial formulation of Zeldox as a control. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolonged actions and enhanced bioavailability with no food effect was achieved simultaneously in ziprsidone-SNEDDS sustained-release pellets compared with Zeldox in fed state. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.
PMID: 25148542 [PubMed - as supplied by publisher]
Diabetes and psychiatric illness in the total population of Stockholm.
J Psychosom Res. 2014 Sep;77(3):169-73
Authors: Wändell P, Ljunggren G, Wahlström L, Carlsson AC
OBJECTIVE: Concomitant psychiatric disorders in people with diabetes affect morbidity and mortality. We aimed to study psychiatric morbidity in people with diabetes and the general population using administrative health care data in Stockholm County.
METHODS: The study population included all living persons who resided in Stockholm County, Sweden, on January 1, 2011 (N=2,058,408). Subjects with a diagnosis of diabetes were identified with data from all consultations in primary health care, specialist outpatient care and inpatient care during the time span 2009-2013. As outcome, information was obtained on all consultations due to any psychiatric diagnosis as well as, specifically, schizophrenia, bipolar disorders, depression, and anxiety disorders, in 2011-2013. Analyses were performed by age group and gender. Age-adjusted odds ratios (ORs) with 95% confidence intervals (95% CI) for women and men with diabetes, using individuals without diabetes as referents, were calculated.
RESULTS: Age-adjusted OR for all psychiatric diagnoses among people with diabetes was 1.296 (95% CI 1.267-1.326) for women and 1.399 (95% CI 1.368-1.432) for men. The greatest excess risk was found for schizophrenia, with OR 3.439 (95% CI 3.057-3.868) in women and 2.787 (95% CI 2.514-3.089) in men, with ORs between 1.276 (95% CI 1.227-1.327) and 1.714 (95% CI 1.540-1.905) for the remaining diagnoses.
CONCLUSION: The prevalence of psychiatric disorders is elevated in people with diabetes, which calls for preventive action to be taken to minimize suffering and costs to society.
PMID: 25149026 [PubMed - in process]
Valproic acid increases NO production via SH-PTP1-CDK5-eNOS-Ser(116) signaling cascade in endothelial cells and mice.
Free Radic Biol Med. 2014 Aug 19;
Authors: Cho DH, Park JH, Joo Lee E, Jong Won K, Lee SH, Kim YH, Hwang S, Ja Kwon K, Young Shin C, Song KH, Jo I, Han SH
Valproic acid (VPA) with inhibitory activity of histone deacetylase has been used in the treatment of epilepsy and bipolar disorder that are associated with cerebrovascular dysfunction. Because nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a role in maintenance of vascular function, NO is likely to mediate VPA's drug effect, but its effect on NO production remains controversial. We investigated whether and how VPA regulates NO production in bovine aortic endothelial cells (BAEC) and mice. VPA increased NO production in BAEC, which was accompanied by decrease in phosphorylations of eNOS at serine 116 (eNOS-Ser(116)) and cyclin-dependent kinase 5 at tyrosine 15 (CDK5-Tyr(15)). Ectopic expression of p25, a CDK5 activator, restored the VPA-inhibited eNOS-Ser(116) phosphorylation. In silico analysis revealed that the CDK5-Tyr(15) residue might be a substrate for SH2 domain-containing protein tyrosine phosphatase 1 (SH-PTP1), and CDK5 actually interacted with SH-PTP1. VPA increased SH-PTP1 expression and its activity. Stibogluconate, a specific SH-PTP1 inhibitor, reversed the VPA-inhibited phosphorylations of CDK5-Tyr(15) and eNOS-Ser(116). Knockdown of SH-PTP1 using small interfering RNA also reversed all the observed VPA's effects. Finally, both serum NO level and acetylcholine-induced aortic relaxation increased in the VPA-medicated male mice. These increases were accompanied by increased SH-PTP1 expression and decreased phosphorylations of CDK5-Tyr(15) and eNOS-Ser(116) in mouse aortas. In conclusion, VPA increases NO production by inhibiting CDK5-Tyr(15)-eNOS-Ser(116) phosphorylation axis; this process is mediated by SH-PTP1. VPA may be useful in the treatment of NO-related cerebrocardiovascular diseases.
PMID: 25150199 [PubMed - as supplied by publisher]
Investigation of the Montreal Cognitive Assessment (MoCA) as a cognitive screener in severe mental illness.
Psychiatry Res. 2014 Aug 8;
Authors: Musso MW, Cohen AS, Auster TL, McGovern JE
This study examined the Montreal Cognitive Assessment (MoCA) as a neurocognitive screener and its relationship with functional outcomes in a sample of outpatients diagnosed with severe mental illness (SMI). The MoCA, Brief Assessment of Cognition in Schizophrenia (BACS), UCSD Performance-Based Skills Assessment Test-2 (UPSA-2), and Global Assessment of Functioning (GAF) were administered to 28 SMI patients and 18 non-psychiatric controls. Patients obtained significantly lower scores on the MoCA, BACS, UPSA-2, and GAF compared to non-patients. The cutoff score <26 of the MoCA resulted in favorable sensitivity (89%) but lower specificity (61%) in classification of SMI patients. The MoCA was significantly correlated with UPSA scores but not GAF scores, whereas the BACS was not significantly correlated with UPSA or GAF scores. When entered into hierarchical regression analyses, the MoCA accounted for significant variance in UPSA scores above variance accounted for by the BACS. Both the MoCA and the BACS contributed unique variance in GAF scores. Overall, the MoCA demonstrated high sensitivity as a cognitive screener in SMI. Moreover, MoCA scores were related to performance-based measures of functional capacity.
PMID: 25150920 [PubMed - as supplied by publisher]
Fixed dose-combination products in psychiatry: Systematic review and meta-analysis.
J Psychopharmacol. 2014 Aug 22;
Authors: Farooq S, Singh SP
Despite highly prevalent use of drug combinations in psychiatry, combination products are not commonly available. We aimed to systematically review the evidence for the use and efficacy of combination products in the practice of psychiatry. Systematic search of major data bases yielded nine double-blind randomized controlled trials, which generated 15 comparisons of combination products against a single therapeutic agent, that included a placebo. All these studies included 2827 participants: 976 in their combination products arms and 1851 patients in the comparator arms. The number of combination products were identified, but all except two studies tested only one combination drug (e.g. olanzapine and fluoxetine (OFC)). All combined formulations were significantly superior to a single agent, with standardized mean distance (SMD) of - 0.29 (confidence interval (CI) = - 0.43, - 0 .14; p < 0.001) in improving depression. In the subgroup analysis, the OFC combination was significantly superior to a single therapeutic agent for bipolar depression (SMD = - 0.32; CI = - 0.45, - 0.19; p < 0.001) and for treatment-resistant depression (SMD = - 0.29; CI = - 0.49, - 0.08; p < 0.005), but not for borderline personality nor major depressive disorder (MDD). The evidence in general medicine suggests that combination products can offer significant advantage in improving efficacy and treatment adherence; but in psychiatry, research and development in fixed-dose combinations has been limited.
PMID: 25151108 [PubMed - as supplied by publisher]
Affective temperaments and neurocognitive functioning in bipolar disorder.
J Affect Disord. 2014 Aug 5;169C:51-56
Authors: Russo M, Mahon K, Shanahan M, Ramjas E, Solon C, Braga RJ, Burdick KE
BACKGROUND: There is evidence that patients with bipolar disorder (BD) score higher on affective temperament ratings compared to healthy controls (HCs). Moreover, unaffected relatives demonstrate similar patterns as BD patients suggesting that such temperaments are related to the genetic risk for BD and may serve as endophenotypes for the disorder. It is unknown whether affective temperaments are associated with other core features of BD, such as impairments in neurocognition. This study examined the relationship between affective temperaments and neurocognition in patients with BD and in HCs.
METHODS: Temperaments were evaluated using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego, Auto-questionnaire version (TEMPS-A) in 64 patients with BD and 109 HCs. Neurocognitive functioning was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Correlational analyses between temperaments and cognition were conducted in BD and HC subjects.
RESULTS: Data suggest that affective temperaments and neurocognition are correlated. In BD higher ratings of cyclothymia and irritability were associated with better processing speed, working memory, reasoning and problem-solving. In the HC group, increased irritability was related to worse performance on measures of attention and social cognition.
LIMITATIONS: Lack of functional outcome measures to evaluate the impact of temperaments and cognition on psychosocial functioning. It would be useful to test these findings on unaffected relatives of BD patients.
CONCLUSIONS: Cyclothymic and irritable temperaments are correlated with specific aspects of neurocognition in BD. This study is among the few exploring the dimensional relationship between temperaments and cognition in BD, and provides preliminary evidence for future studies investigating the neural and genetic mechanisms underlying the association between these variables.
PMID: 25151191 [PubMed - as supplied by publisher]
Abnormal deactivation of the inferior frontal gyrus during implicit emotion processing in youth with bipolar disorder: Attenuated by medication.
J Psychiatr Res. 2014 Aug 8;
Authors: M Hafeman D, Bebko G, Bertocci MA, Fournier JC, Bonar L, Perlman SB, Travis M, Gill MK, Diwadkar VA, Sunshine JL, Holland SK, Kowatch RA, Birmaher B, Axelson D, Horwitz SM, Arnold LE, Fristad MA, Frazier TW, Youngstrom EA, Findling RL, Drevets W, Phillips ML
Previous neuroimaging studies of youth with bipolar disorder (BD) have identified abnormalities in emotion regulation circuitry. Using data from the Longitudinal Assessment of Manic Symptoms Cohort (a clinical sample recruited for behavioral and emotional dysregulation), we examined the impact of BD and medication on activation in these regions. Functional neuroimaging data were obtained from 15 youth with BD who currently were unmedicated with a mood stabilizer or antipsychotic (U-BD), 19 youth with medicated BD (M-BD), a non-bipolar clinical sample with high rates of disruptive behavioral disorders (non-BD, n = 59), and 29 healthy controls (HC) while they were shown task-irrelevant morphing emotional faces and shapes. Whole brain analysis was used to identify clusters that showed differential activation to emotion vs. shapes across group. To assess pair-wise comparisons and potential confounders, mean activation data were extracted only from clusters within regions previously implicated in emotion regulation (including amygdala and ventral prefrontal regions). A cluster in the right inferior frontal gyrus (IFG) showed group differences to emotion vs. shapes (159 voxels, corrected p < .05). Within this cluster, U-BD youth showed decreased activation relative to HC (p = .007) and non-BD (p = .004) youth. M-BD also showed decreased activation in this cluster relative to HC and non-BD youth, but these differences were attenuated. Results were specific to negative emotions, and not found with happy faces. IFG findings were not explained by other medications (e.g. stimulants) or diagnoses. Compared to both HC and a non-BD sample, U-BD is associated with abnormally decreased right IFG activation to negative emotions.
PMID: 25151338 [PubMed - as supplied by publisher]
Association study of TPH2 polymorphisms and bipolar disorder in the Han Chinese population.
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Aug 21;
Authors: Chen S, Huang X, Yu T, Li X, Cao Y, Li X, Xu F, Yang F, Jesse FF, Xu M, Li W, He L, He G
OBJECTIVE: Bipolar disorder (BPD) is a serious and common mental disorder with high heritability. The serotonergic system is known to be implicated in the etiology of the disorder. Tryptophan hydroxylase isoform-2 (TPH2), which controls the synthesis of serotonin in the brain, has been suggested as a candidate gene for BDP. The aim of this study was to examine the association between the polymorphisms in TPH2 and BPD.
METHODS: We conducted a case-control study by genotyping six SNPs (rs10784941, rs1386494, rs2171363, rs4760816, rs1386486, and rs1872824) in 506 bipolar patients and 507 controls of Chinese Han origin.
RESULTS: rs10784941 was not in the Hardy-Weinberg equilibrium and therefore excluded from further analysis. Rs1386486 and rs1872824 showed statistically significant differences between cases and controls in genotype frequencies (rs1386486: p=0.043351; rs1872824: p=0.016563), but no association in allele frequencies. Strong LD was found among rs1386494, rs2171363 and rs4760816, but no positive association with BPD was found for haplotypes.
CONCLUSION: Our results indicate that in the Han Chinese population TPH2 may be a potential susceptibility gene for bipolar disorder. Further studies are needed to validate this association.
PMID: 25152196 [PubMed - as supplied by publisher]
The course of neuropsychological impairment and brain structure abnormalities in psychotic disorders.
Neurosci Res. 2014 Aug 21;
Authors: Woodward ND
Neuropsychological impairment and abnormalities in brain structure are commonly observed in psychotic disorders, including schizophrenia and bipolar disorder. Shared deficits in neuropsychological functioning and abnormalities in brain structure suggest overlapping neuropathology between schizophrenia and bipolar disorder which has important implications for psychiatric nosology, treatment, and our understanding of the etiology of psychotic illnesses. However, the emergence and trajectory of brain dysfunction in psychotic disorders is less well understood. Differences in the course and progression of neuropsychological impairment and brain abnormalities among psychotic disorders may point to unique neuropathological processes. This article reviews the course of neuropsychological impairment and brain structure abnormalities in schizophrenia and bipolar disorder.
PMID: 25152315 [PubMed - as supplied by publisher]