Structural brain alterations in bipolar disorder II: A combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) study

Background

Brain structural changes have been described in bipolar disorder (BP), but usually studies focused on both I and II subtypes indiscriminately and investigated changes in either brain volume or white matter (WM) integrity. We used combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) analysis to track changes in the grey matter (GM) and WM in the brains of patients affected by BPII, as compared to healthy controls.

Methods

Using VBM and DTI, we scanned 20 DSM-IV-TR BPII patients in their euthymic phase and 21 healthy, age- and gender-matched volunteers with no psychiatric history.

Results

VBM showed decreases in GM of BPII patients, compared to controls, which were diffuse in nature and most prominent in the right middle frontal gyrus and in the right superior temporal gurus. DTI showed significant and widespread FA reduction in BPII patients in all major WM tracts, including cortico-cortical association tracts.

Limitations

The small sample size limits the generalisability of our findings.

Conclusions

Reduced GM volumes and WM integrity changes in BPII patients are not prominent like those previously reported in bipolar disorder type-I and involve cortical structures and their related association tracts.     

Systematic review and voxel-based meta-analysis of diffusion tensor imaging studies in bipolar disorder

Background

Diffusion tensor imaging (DTI) studies have shown changes in the microstructure of white matter in bipolar disorder. Studies suggest both localised, predominantly fronto-limbic, as well as more widespread changes in white matter, but with some apparent inconsistency. A meta-analysis of white matter alterations in adults with bipolar disorder was undertaken.

Method

Whole-brain DTI studies comparing adults with bipolar disorder to healthy controls on fractional anisotropy (FA) were retrieved using searches of MEDLINE and EMBASE from between 2003 and December 2012. White-matter tract involvement was collated and quantified. Clusters of significantly altered FA were meta-analysed using effect-size signed differential mapping (ES-SDM).

Results

Ten VBA studies (252 patients and 256 controls) and five TBSS studies (138 patients and 98 controls) met inclusion criteria. Sixty-one clusters of significantly different FA between bipolar disorder and healthy controls were identified. Analysis of white-matter tracts indicated that all major classes of tracts are implicated. ES-SDM meta-analysis of VBA studies revealed three significant clusters of decreased FA in bipolar disorder (a right posterior temporoparietal cluster and two left cingulate clusters). Findings limited to the Bipolar Type I papers were more robust.

Limitations

Voxel-based studies do not accurately identify tracts, and our ES-SDM analysis used only published peak voxels rather than raw DTI data.

Conclusions

There is consistent data indicating widespread white matter involvement with decreased white matter FA demonstrated in three disparate areas in bipolar disorder. White matter alterations are not limited to anterior fronto-limbic pathways in bipolar disorder.     

Improvements in white matter micro-structural integrity of right uncinate fasciculus and left fronto-occipital fasciculus of remitted first-episode medication-naïve panic disorder patients

Objective:

We designed this study to investigate neural correlates of white matter micro-structural integrity of remitted patients with first-episode, medication-naïve and very late-onset panic disorder

Method:

Twenty-one remitted patients with panic disorder completed treatment course with treatment of escitalopram (dose range around 10–15 mg/d). Twenty-one healthy controls were also enrolled into this study. Patients and controls all received 3-Tesla magnetic resonance imaging diffusion tensor imaging scanning at baseline and 6th week. We utilized FDT (FMRIB's Diffusion Toolbox v2.0) function of FSL (FMRIB Software Library) to calculate fractional anisotropy (FA). We compared FA values of patients and controls at baseline and 6th week to estimate the changes of FA of remitted patient group and inter-scan bias of controls. FA outputs of remitted patients and controls were compared by independent t test.

Results:

We found increased FA in some regions of right uncinate fasciculus and left fronoto-occipital fasciculus after remission in patient group (corrected p<0.05). Reduced FA of other regions of right uncinate fasciculus was still observed in remitted patients when they were compared to the control group.

Conclusion:

Subtle changes of white matter micro-structural integrity after remission might represent neural correlates of treatment effects for first-episode, medication-naïve and very late-onset panic disorder.     

Long-chain omega-3 fatty acid intake is associated positively with corticolimbic gray matter volume in healthy adults

Background

In animals, dendritic arborization and levels of brain derived neurotrophic factor are positively associated with intake of the omega-3 fatty acids. Here, we test whether omega-3 fatty acid intake in humans varies with individual differences in gray matter volume, an in vivo, systems-level index of neuronal integrity.

Methods

Fifty-five healthy adults completed two 24 h dietary recall interviews. Intake of long-chain omega-3 fatty acids was categorized by tertiles. Regional gray matter volumes in a putative emotional brain circuitry comprised of the anterior cingulate cortex (ACC), amygdala and hippocampus were calculated using optimized voxel-based morphometry on high-resolution structural magnetic resonance images.

Results

Region of interest analyses revealed positive associations between reported dietary omega-3 intake and gray matter volume in the subgenual ACC, the right hippocampus and the right amygdala, adjusted for total gray matter volume of brain. Unconstrained whole-brain analyses confirmed that higher intake of omega-3 fatty acids was selectively associated with increased greater gray matter volume in these and not other regions.

Conclusions

Higher reported consumption of the long-chain omega-3 fatty acids is associated with greater gray matter volume in nodes of a corticolimbic circuitry supporting emotional arousal and regulation. Such associations may mediate previously observed effects of omega-3 fatty acids on memory, mood and affect regulation.     

Time course of recovery showing initial prefrontal cortex changes at 16 weeks,extending to subcortical changes by 3 years in pediatric bipolar disorder

Objective

Activation changes at the interface of affective and cognitive systems are examined over a 3 year period in pediatric bipolar disorder (PBD).

Methods

Thirteen participants with PBD and 10 healthy controls (HC) matched on demographics and IQ were scanned at baseline, at 16 weeks, and after 3 years. All patients received pharmacotherapy based on a medication algorithm. A pediatric affective color matching paradigm was used to probe cognitive processing under emotional challenge.

Results

At baseline, in response to emotional vs. neutral words, patients with PBD showed greater activation than HC in the right dorsal lateral prefrontal cortex (DLPFC) and amygdala, ventral lateral prefrontal cortex (VLPFC), bilateral anterior cingulate cortex (ACC), and ventral striatum. Increased activation in DLPFC in the PBD group normalized by 16 weeks. By 3 years, normalization was observed in VLPFC, ACC, amygdala, and striatum.

Limitations

Small sample size renders the present findings preliminary.

Conclusions

Greater activation in fronto-striatal and fronto-limbic circuits were observed in unmedicated patients with PBD. Present findings suggest the possibility that DLPFC is most malleable to pharmacological intervention with systematic pharmacotherapy leading to immediate response, which extended to amygdalostriatal and ventral cortical regions at 3 years. The seminal observation from this study is the prolonged length of recovery time in the normalization of subcortical activity along with their interfacing cortical regions. Findings from this proof of concept study need to be replicated in a larger sample.     

Posterior cerebellar vermal deficits in bipolar disorder

Background

Based on growing evidence of the crucial role of the cerebellum in emotional regulation, we sought to identify cerebellar structural deficits in a large sample of patients with bipolar disorder (BD).

Methods

Cerebellar gray matter density was examined in 49 BD patients (24 medication-naive and 25 medication-treated) and 50 carefully matched healthy individuals, using voxel-based morphometry with a high-resolution spatially unbiased atlas template of the human cerebellum. This recently developed methodology is specifically optimized for the assessment of cerebellar structures. We further explored whether antimanic treatment could attenuate cerebellar structural deficits.

Results

BD patients showed a greater reduction in gray matter density of the posterior cerebellar regions, including the bilateral vermi and the right crus relative to healthy individuals (corrected p<.05). A stepwise linear reduction in gray matter density was observed in bilateral vermal regions between healthy individuals, medication-treated, and medication-naive BD patients. Furthermore, positive correlations of longer duration of illness with bilateral vermal gray matter deficits were observed only in medication-naive BD patients, but not in patients with medication history.

Limitations

This study adopted a cross-sectional design. The automatic intensity-normalization method for the measurement of cerebellar gray matter density may have a limitation in providing detailed anatomical information at a cerebellar folia level.

Conclusions

The current findings suggest that BD-related deficits in the posterior cerebellar regions, which appear to progress over the course of illness, could potentially be ameliorated by proper treatment with mood stabilizers.     

DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia

Background

DISC1 is considered a susceptibility gene for schizophrenia and schizoaffective disorder, but little is known regarding the potential mechanisms through which it may confer increased risk. Given that DISC1 plays a role in cerebral cortex development, polymorphisms in this gene may have relevance for neurobiological models of schizophrenia that have implicated cortical deficits in its pathophysiology.

Methods

We investigated whether the DISC1 leu607phe polymorphism was associated with prefrontal gray matter volumes using magnetic resonance imaging in a cohort of patients with schizophrenia (N = 19) and healthy volunteers (N = 25) and positive and negative symptoms in 200 patients with schizophrenia.

Results

Among patients and healthy volunteers, phe carriers (N = 11) had significantly less gray matter in the superior frontal gyrus and anterior cingulate gyrus compared to leu/leu homozygotes (N = 33). Further, among patients left superior frontal gyrus gray matter volume was significantly negatively correlated with severity of hallucinations. In addition, patients who were phe carriers (N = 144) had significantly greater severity of positive symptoms (hallucinations) compared to patients who were leu/leu homozygotes (N = 56).

Discussion

These findings implicate DISC1 in variation of prefrontal cortical volume and positive symptoms, thus providing a potential mechanism through which DISC1 may confer increased risk for schizophrenia or schizoaffective disorder.     

Diffusion tensor MR imaging characteristics of cerebral white matter development in fetal pigs

Background

The purpose of this study was to investigate the anisotropic features of fetal pig cerebral white matter (WM) development by magnetic resonance diffusion tensor imaging, and to evaluate the developmental status of cerebral WM in different anatomical sites at different times.

Methods

Fetal pigs were divided into three groups according to gestational age: E69 (n?=?8), E85 (n?=?11), and E114 (n?=?6). All pigs were subjected to conventional magnetic resonance imaging (MRI) and diffusion tensor imaging using a GE Signa 3.0 T MRI system (GE Healthcare, Sunnyvale, CA, USA). Fractional anisotropy (FA) was measured in deep WM structures and peripheral WM regions. After the MRI scans,the animals were sacrificed and pathology sections were prepared for hematoxylin & eosin (HE) staining and luxol fast blue (LFB) staining. Data were statistically analyzed with SPSS version 16.0 (SPSS, Chicago, IL, USA). A P-value?<?0.05 was considered statistically significant. Mean FA values for each subject region of interest (ROI), and deep and peripheral WM at different gestational ages were calculated, respectively, and were plotted against gestational age with linear correlation statistical analyses. The differences of data were analyzed with univariate ANOVA analyses.

Results

There were no significant differences in FAs between the right and left hemispheres. Differences were observed between peripheral WM and deep WM in fetal brains. A significant FA growth with increased gestational age was found when comparing E85 group and E114 group. There was no difference in the FA value of deep WM between the E69 group and E85 group. The HE staining and LFB staining of fetal cerebral WM showed that the development from the E69 group to the E85 group, and the E85 group to the E114 group corresponded with myelin gliosis and myelination, respectively.

Conclusions

FA values can be used to quantify anisotropy of the different cerebral WM areas. FA values did not change significantly between 1/2 way and 3/4 of the way through gestation but was then increased dramatically at term, which could be explained by myelin gliosis and myelination ,respectively.

     

DSM-5 mixed specifier for manic episodes: Evaluating the effect of depressive features on severity and treatment outcome using asenapine clinical trial data

Background

To describe the frequency of mixed specifier as proposed in DSM-5 in bipolar I patients with manic episodes, and to evaluate the effect of mixed specifier on symptom severity and treatment outcome.

Methods

This post-hoc analysis used proxies for DSM-5 mixed features specifier by using MADRS or PANSS items.

Results

Of the 960 patients analysed, 34%, 18% and 4.3% of patients, respectively, had ≥3 depressive features with mild (score ≥1 for MADRS items and ≥2 for PANSS item), moderate (score ≥2 MADRS, ≥3 PANSS) and severe (score ≥3 MADRS, ≥4 PANSS) symptoms. In patients with ≥3 depressive features and independent of treatment: MADRS remission (score ≤12) rate decreased with increasing severity (61–43%) and YMRS remission (score ≤12) was similar for mild and moderate patients (36–37%), but higher for severe (54%). In asenapine-treated patients, the MADRS remission rate was stable regardless of baseline depressive symptom severity (range 64–67%), whereas remission decreased with increasing severity with olanzapine (63–38%) and placebo (49–25%). Reduction in YMRS was significantly greater for asenapine compared with placebo at day 2 across the 3 severity cut-offs and continued to decrease throughout the treatment period. The difference between olanzapine and placebo was statistically significant in mild and moderate patients.

Limitations

Results are from post-hoc analyses.

Conclusions

These analyses support the validity of proposed DSM-5 criteria. They confirm that depressive features are frequent in bipolar patients with manic episodes. With increasing baseline severity of depressive features, treatment outcome was poorer with olanzapine and placebo, but remained stable with asenapine.     

Identification of cortical activation and white matter architecture according to short-term motor learning in the human brain: functional MRI and diffusion tensor tractography study

Objectives

The purpose of this study was to examine whether two weeks of short-term motor training led to changes of cortical activation patterns and white matter integrity in cortical and subcortical structures according to motor skill acquisition, using functional MRI (fMRI) and diffusion tensor image (DTI).

Methods

We enrolled twenty healthy volunteers, who were randomly assigned to training and control groups. The training group was trained with a serial reaction time (SRT) task, one hour a day for 10 days within two weeks, whereas the control group had no training. Movement accuracy (MA) and movement time (MT) were tested twice before and after training, while fMRI was scanned during SRT task. Immediately after these tests, DTI was conducted.

Results

The training group showed significant differences in the increase of MA and the reduction of MT, compared with control group. The activated volume of cortices related to motor function was gradually decreased in the training group, according to motor skill acquisition. DTI analysis showed no significant differences between pre- and post-tests in both groups.

Conclusions

Our findings indicated that short-term motor training led to cortical activation patterns of the cerebral cortex according to implicit motor learning. However, changes of white matter integrity were not observed. It seems that short-term motor training may not be enough to change white matter architectures, due to lack of the training period.     

Diffusion Tensor Imaging of Heterotopia: Changes of Fractional Anisotropy during Radial Migration of Neurons

Purpose

Diffusion tensor imaging provides better understanding of pathophysiology of congenital anomalies, involving central nervous system. This study was aimed to specify the pathogenetic mechanism of heterotopia, proved by diffusion tensor imaging, and establish new findings of heterotopia on fractional anisotropy maps.

Materials and Methods

Diffusion-weighted imaging data from 11 patients (M : F = 7 : 4, aged from 1 to 22 years, mean = 12.3 years) who visited the epilepsy clinic and received a routine seizure protocol MRI exam were retrospectively analyzed. Fractional anisotropy (FA) maps were generated from diffusion tensor imaging of 11 patients with heterotopia. Regions of interests (ROI) were placed in cerebral cortex, heterotopic gray matter and deep gray matter, including putamen. ANOVA analysis was performed for comparison of different gray matter tissues.

Results

Heterotopic gray matter showed signal intensities similar to normal gray matter on T1 and T2 weighted MRI. The measured FA of heterotopic gray matter was higher than that of cortical gray matter (0.236 ± 0.011 vs. 0.169 ± 0.015, p < 0.01, one way ANOVA), and slightly lower than that of deep gray matter (0.236 ± 0.011 vs. 0.259 ± 0.016, p < 0.01).

Conclusion

Increased FA of heterotopic gray matter suggests arrested neuron during radial migration and provides better understanding of neurodevelopment.     

Relationship between the clinical global impression of severity for schizoaffective disorder scale and established mood scales for mania and depression

Background

This analysis explored the relationship between ratings on HAM-D-17 or YMRS and those on the depressive or manic subscale of CGI-S for schizoaffective disorder (CGI-S-SCA).

Methods

This post hoc analysis used the database (N=614) from two 6-week, randomized, placebo-controlled studies of paliperidone ER versus placebo in symptomatic subjects with schizoaffective disorder assessed using HAM-D-17, YMRS, and CGI-S-SCA scales. Parametric and nonparametric regression models explored the relationships between ratings on YMRS and HAM-D-17 and on depressive and manic domains of the CGI-S-SCA from baseline to the 6-week end point. A clinically meaningful improvement was defined as a change of 1 point in the CGI-S-SCA score. No adjustment was made for multiplicity.

Results

Multiple linear regression models suggested that a 1-point change in the depressive domain of CGI-S-SCA corresponded to an average 3.6-point (SE=0.2) change in HAM-D-17 score. Similarly, a 1-point change in the manic domain of CGI-S-SCA corresponded to an average 5.8-point (SE=0.2) change in YMRS score. Results were confirmed using local and cumulative logistic regression models in addition to equipercentile linking.

Limitations

Lack of subjects scoring over the complete range of possible scores may limit broad application of the analyses.

Conclusion

Clinically meaningful score changes in depressive and manic domains of CGI-S-SCA corresponded to approximately 4- and 6-point score changes on HAM-D-17 and YMRS, respectively, in symptomatic subjects with schizoaffective disorder.     

Clinical subtypes of severe bipolar mixed states

Objective

The aim of the present study was to identify different clinical subtypes in severe, treatment resistant bipolar mixed state (MS).

Method

The sample comprised 202 Bipolar I patients currently in MS referred for an Electro-convulsive Therapy (ECT) trial and evaluated in the first week of hospitalization and one week after the ECT course. Principal component factor analysis (PCA) followed by Varimax rotation was performed on 21 non-overlapping items selected from Hamilton rating-scale for depression (HAMD) and from Young mania rating-scale (YMRS) at baseline evaluation. Cluster subtypes derived from the factor scores were compared in clinical variables and final HAMD, YMRS, Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores.

Results

The principal-component analysis extracted 6 interpretable factors explaining 55.9% of the total variance. Cluster analysis identified four groups, including respectively 63 (31.2%) subjects with Agitated-Irritable Mixed-Depression, 59 (29.2%) with Psychotic Mixed-Mania, 17 (8.5%) with Anxious-Irritable-Psychotic Mixed-Mania, and 63 (31.2%) with Retarded-Psychotic Mixed-Depression. The four clusters were statistically distinct and did not show significant overlap in the main symptomatological presentation. Cluster subtypes reported differences in number of past mood episodes, duration of the current episode, suicide attempts, lifetime comorbidity with panic and eating disorders, baseline and final rating-scale scores and rate of remission after ECT trial.

Conclusions

Our study indicates that, at least in severe treatment resistant MS, multiple depressive and manic subtypes can be observed with substantial differences in terms of clinical presentation, course, associated comorbidities and treatment response.     

Reduced Brain Gray Matter Concentration in Patients With Obstructive Sleep Apnea Syndrome

Study Objectives:

To investigate differences in brain gray matter concentrations or volumes in patients with obstructive sleep apnea syndrome (OSA) and healthy volunteers.

Designs:

Optimized voxel-based morphometry, an automated processing technique for MRI, was used to characterize structural differences in gray matter in newly diagnosed male patients.

Setting:

University hospital

Patients and Participants:

The study consisted of 36 male OSA and 31 non-apneic male healthy volunteers matched for age (mean age, 44.8 years).

Interventions:

Using the t-test, gray matter differences were identified. The statistical significance level was set to a false discovery rate P < 0.05 with an extent threshold of k_E > 200 voxels.

Measurements and Results:

The mean apnea-hypopnea index (AHI) of patients was 52.5/ h. On visual inspection of MRI, no structural abnormalities were observed. Compared to healthy volunteers, the gray matter concentrations of OSA patients were significantly decreased in the left gyrus rectus, bilateral superior frontal gyri, left precentral gyrus, bilateral frontomarginal gyri, bilateral anterior cingulate gyri, right insular gyrus, bilateral caudate nuclei, bilateral thalami, bilateral amygdalo-hippocampi, bilateral inferior temporal gyri, and bilateral quadrangular and biventer lobules in the cerebellum (false discovery rate P < 0.05). Gray matter volume was not different between OSA patients and healthy volunteers.

Conclusions:

The brain gray matter deficits may suggest that memory impairment, affective and cardiovascular disturbances, executive dysfunctions, and dysregulation of autonomic and respiratory control frequently found in OSA patients might be related to morphological differences in the brain gray matter areas.

Citation:

Joo EY; Tae WS; Lee MJ; Kang JW; Park HS; Lee JY; Suh M; Hong SB. Reduced brain gray matter concentration in patients with obstructive sleep apnea syndrome. SLEEP 2010;33(2):235-241.     

Cognitive functions and cognitive styles in young euthymic patients with bipolar I disorder

Background

Recent evidences suggest that bipolar disorder patients do not return to premorbid functioning levels during the inter-episode periods. Cognitive deficits may impair patients working and functioning status and may also have negative impact on other aspects of thinking.

Objectives

To assess the prevalence of cognitive dysfunction in patients with bipolar disorder in euthymic state and to explore any evident cognitive style problems.

Method

Case-control naturalistic study 60 patients with bipolar I disorder in euthymic state according to DSM-IV were recruited and subdivided into two groups each contains of 30 patients; (Group BPM) euthymic patients with recent manic episode, and Group BPD euthymic patients with recent depressive episode. Both groups were further compared with control group (Group C) consisted of 30 frequency matched healthy volunteers. Groups were subjected to the following: 1-clinical psychiatric examination, 2-Hamilton Depression Scale (HAMD-17) and Bech–Rafaelsen Melancholia Scale (MES) for patients’ group (BPD), 3-Young Mania Rating Scale (YMRS) and Bech–Rafaelsen Mania Scale (MAS) for patients’ group (BPM), 4-assessment of euthymic state of mood included both MAS and MES, 5-MMSE, MTS and CDT were performed to assess cognitive functions, 6-cognitive styles evaluation included Fear of Failure, Hopelessness Scale, (the Social Dysfunction and Aggression Scale SDAS-9 and Arabic Anger Scale.

Results

Definite cognitive function impairment and different patterns of cognitive style were detected in case groups. MMSE, MTS and CDT scores were statistically significant. Fear of Failure Scale Scores were higher in BPM; 16 (53.33%) reported severe intensity compared to 16 (53.33%) of BPD Group reporting moderate intensity and 30 (100%) of the control group reporting only mild intensity of fear of failure with statistically significant differences. Although patients were in euthymic state; Hopelessness Scale discriminated between those with affective disorders and controls and other scores for hostility SADS-9 and Arabic Anger Scale. Moreover, measures of cognitive styles showed differences among patients of the case groups who joined psychotherapy program in their management (28) compared to those who did not (32).

Limitation

Cognitive impact of psychotropic drugs could not be eliminated since the current study is naturalistic study.

Conclusions

Those with BAD in euthymic state suffer from cognitive dysfunction and some aspects of cognitive styles that may negatively interfere with their performance. Psychotherapeutic programs should consider these findings in their approaches for better impact on patients’ quality of life and overall treatment outcome.     

White Matter Differences Predict Cognitive Vulnerability to Sleep Deprivation

Objectives:

In other disciplines, white matter (WM) differences have been linked to cognitive impairments. This study sets out to clarify whether similar microstructural differences in WM tracts predict a person''s cognitive vulnerability to the effects of total sleep deprivation (TSD).

Design:

Participants completed a simple visual-motor task both before and after 24 h of TSD. Using a median split on the percent change in accuracy from pre-TSD to post-TSD, participants were separated into susceptibility groups. A diffusion tensor MR imaging (DTI) scan was acquired from each participant, and fractional anisotropy (FA) was calculated, examined across the brain, and compared between susceptibility groups.

Setting:

University of Texas at Austin.

Participants:

Thirty-two West Point cadets (9 females, 23 males) between 19 and 25 years of age.

Results:

Participant susceptibility to TSD was correlated with lower FA values in multiple regions of white matter, including the genu of corpus callosum and ascending and longitudinal white matter pathways. Significantly higher FA values in those less vulnerable to TSD, indicating increased neural connectivity and WM organization, may moderate the cognitive effects of sleep deprivation.

Conclusions:

Differences in distributed WM pathways reflect, and may contribute to, a person''s ability to function effectively when sleep deprived. The widespread nature of this effect supports previous views that TSD has a global effect on brain functioning.

Citation:

Rocklage M; Williams V; Pacheco J; Schnyer DM. TitleTitleTitle. SLEEP 2009;32(8):1100-1103.     

First controlled treatment trial of bipolar II hypomania with mixed symptoms: Quetiapine versus placebo

Objectives

To compare the efficacy and safety of adjunctive quetiapine (QTP) versus placebo (PBO) for patients with bipolar II disorder (BDII) currently experiencing mixed hypomanic symptoms in a 2-site, randomized, placebo-controlled, double-blind, 8-week investigation.

Methods

Participants included 55 adults (age 18–65 years) who met criteria for BDII on the Structured Clinical Interview for DSM-IV-TR (SCID). Entrance criteria included a stable medication regimen for ≥2 weeks and hypomania with mixed symptoms (>12 on the Young Mania Rating Scale [YMRS] and >15 on the Montgomery Asberg Depression Rating Scale [MADRS] at two consecutive visits 1–3 days apart). Participants were randomly assigned to receive adjunctive quetiapine (n=30) or placebo (n=25).

Results

Adjunctive quetiapine demonstrated significantly greater improvement than placebo in Clinical Global Impression for Bipolar Disorder Overall Severity scores (F(1)=10.12, p=.002) and MADRS scores (F(1)=6.93, p=.0138), but no significant differences were observed for YMRS scores (F(1)=3.68, p=.069). Side effects of quetiapine were consistent with those observed in previous clinical trials, with sedation/somnolence being the most common, occurring in 53.3% with QTP and 20.0% with PBO.

Conclusions

While QTP was significantly more effective than PBO for overall and depressive symptoms of BDII, there was no significant difference between groups in reducing symptoms of hypomania. Hypomania improved across both groups throughout the study.     

Cognitive–linguistic deficits in euthymic elderly patients with bipolar disorder

Background

There is increasing evidence that bipolar disorder is also associated with neuropsychological impairments persisting during euthymia, thus representing a trait-like feature of the disease. Language and speech abnormalities are also present in bipolar disorder, especially in verbal fluency and verbal memory. However, there is a lack of studies in the literature investigating different levels of linguistic processing (phonological, syntactical, and semantic) in a single cohort of euthymic bipolar patients. Based on previous findings of pervasive language impairment in euthymic elderly bipolar patients, the aim of this study was to comprise a more thorough investigation on the subject.

Methods

We studied 19 euthymic bipolar patients aged 60 and above, and 20 cognitively healthy subjects using the Arizona Battery for Communication Disorders of Dementia (ABCD) and the Test for Reception of Grammar Version 2 (TROG-2) in order to assess the phonological, syntactic, and semantic domains of language.

Results

Bipolar patients performed poorer than controls in Linguistic Expression (p=0.011), in Linguistic Comprehension (Following Commands; p=0.025 and Reading Comprehension of Sentences; p=0.007), and in the TROG-2 (p=0.006).

Limitations

The small sample comprising only elderly patients; the lack of statistical power to analyze the potential effect of individual medications on the cognitive performance.

Conclusions

Our data demonstrate that linguistic impairment is present in euthymic bipolar patients, affecting mostly syntactic and lexical–semantic abilities, both in comprehension and production of language. These deficits are interrelated with other cognitive skills also known to be affected in bipolar disorder, such as executive functions and episodic memory.     

Development and validation of a screening questionnaire for present or past (hypo)manic episodes based on DSM-IV-TR criteria

Background

We developed a self-reported questionnaire, the Manic Episode Screening Questionnaire (MES), based on the eight diagnostic criteria items of DSM-IV-TR (hypo)manic episodes. This study was designed to determine the optimal screening methods to identify bipolar disorders among mood disorder patients of a psychiatric specialty clinic.

Methods

In 95 mood disorder patients, we assessed the operational characteristics of the MES as a screening and diagnostic instrument using a DSM-IV-TR diagnosis by a trained psychiatrist as a reference standard. The reference criteria were bipolar disorders. MES was used with two methods: the diagnostic algorithm and the one-question method (question #1 only). The diagnostic algorithm was regarded as fulfilled if the answers to question #1 and three or more of questions #2 to #8 were “yes”, corresponding to the DSM-IV-TR (hypo)manic episode criteria. In different subjects, the test-retest reliability of the MES was examined.

Results

The two methods of the MES showed high specificity (0.93–0.94), high positive predictive value (0.81–0.83) and high negative predictive value (0.88–0.90), but the sensitivity scored lower (0.68–0.75). The test-retest reliability was moderate: 0.75 for the diagnostic algorithm and 0.68 for the one-question method.

Limitations

This study includes a small number of bipolar I patients. The findings might not be generalized to patients outside of this patient population.

Conclusions

The MES is useful for the screening and diagnosis of bipolar disorders among mood disorder patients in psychiatric specialty clinics. The one-question method of the MES is more convenient to use than prior questionnaires and is here recommended.     

The association of chronic kidney disease with brain lesions on MRI or CT: a systematic review

Background and purpose

This review reports on the association between chronic kidney disease (CKD) established with glomerular filtration rate (GFR) and brain lesions established with MRI or CT.

Methods

Literature was searched combining synonyms of kidney function, brain lesions and terms for the definitions thereof, and MRI or CT. This resulted in 1507 articles, of which 20 were finally included.

Results

Cross-sectional studies found an association between GFR and white matter lesions (WML) with 7 out of 11 associations significant (odds ratios (OR) GFR, continuous variable: 0.84–0.89 per 10 ml/min/1.73 m²). Most significant results were found in studies including subjects from the general population. GFR was associated with silent cerebral infarcts (SCI) with 9 out of 12 associations significant (OR GFR, continuous variable: 0.96–0.99 per ml/min/1.73 m²). Brain atrophy was reported significant 4 out of 5 associations (OR GFR, continuous variable: 0.64 per 10 ml/min/1.73 m²). Additionally, 2 follow up studies were included. One established that serum creatinine at baseline is a significant predictor of the presence of SCI; the other that the presence of SCI at baseline is a significant predictor of a decrease in GFR.

Conclusion

The results from this review show that CKD is associated with brain lesions. These brain lesions include WML, SCI and brain atrophy. This finding is of clinical importance because these brain lesions are predictive of stroke, cognitive decline and dementia. Additional follow up studies should be performed to better understand the causative pathway and to establish whether screening and preventive programs are beneficial.