Executive functioning and theory of mind in euthymic bipolar disorder

Objectives:  To examine the nature of executive deficits in euthymic patients with bipolar disorder (BD).
Methods:  Fifteen euthymic BD patients and 13 controls were administered a battery of executive tasks including verbal fluency, Stroop, Theory of Mind (ToM) tests and selected subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Self-report and clinician ratings of mood and social and occupational functioning were also obtained.
Results:  There were no significant differences between BD patients and controls on the primary measures of the following executive tasks: verbal fluency, attentional set-shifting, problem solving or planning. On secondary measures of speed, BD patients were slower to complete the first trial of the Stroop task (p = 0.001). Patients with BD committed more errors across all secondary measures. Patients performed poorly when compared with controls on tests of verbal ToM (p = 0.02), and although they performed non-verbal ToM tasks at a level comparable to controls (p = 0.60), they were slower to initiate a response (p = 0.006). ToM was not significantly correlated with any measure of social and occupational functioning; however it correlated with the achievement scores of the CANTAB Stockings of Cambridge task (Pearson's r  = 0.68, p < 0.01).
Conclusions:  Deficits found in euthymic bipolar patients suggest fronto-subcortical pathway dysfunction. This is consistent with other neuropsychological and neuroimaging research that points to a trait deficit in BD. Further investigation is necessary perhaps using more real-world tests.     

Differences in outcome of DSM-IV bipolar I and II disorders

Objectives:  To investigate whether the course of bipolar disorder (BD) type II is more depressive than that of BD I, and, if so, to explore the underlying factors that cause this difference.
Methods:  In a prospective, naturalistic study of 191 secondary care psychiatric in- and outpatients diagnosed in an acute phase of BD I or II, 160 patients (85.1%) were followed for 18 months. Using a life chart, the exact timing of symptom states in follow-up was examined. Differences between BD I (n = 75) and II (n = 85) in duration of index phase and episode, time to full remission and recurrence, and time in any mood episode were investigated.
Results:  Patients with BD II spent a higher proportion of time ill (47.5% versus 37.7%; p = 0.02) and in depressive symptom states (58.0% versus 41.7%; p = 0.003) than BD I patients. This was a result of the higher proportion (61.7% versus 48.6%; p = 0.03) and mean number (1.69 versus 1.11; p = 0.006) of depressive illness phases in BD II, rather than of differences in the duration of depressive phases. Type of index phase strongly predicted the outcome. In linear regression models, both BD II and type of index phase predicted more time spent in depressive symptom states.
Conclusions:  In medium-term follow-up, BD II patients spend about 40% more time in depressive symptom states than BD I patients because a higher proportion of BD II patients have depressive phases and the frequency of these is higher. Differences in type of index phase may markedly confound differences in outcome between BD I and II.     

Can body mass index help predict outcome in patients with bipolar disorder?

Objective:  Several studies have reported higher prevalence of obesity in patients suffering from bipolar disorder (BD). To study the relation of elevated body mass index (BMI) in patients with BD more closely, we investigated differences in sociodemographic, clinical, and medical characteristics with respect to BMI, with the hypothesis that BMI is related to prognosis and outcome.
Methods:  We measured the BMI of 276 subjects of a tertiary care sample from the Maritime Bipolar Registry. Subjects were 16 to 83 years old, with psychiatric diagnoses of bipolar I disorder (n = 186), bipolar II disorder (n = 85), and BD not otherwise specified (n = 5). The registry included basic demographic data and details of the clinical presentation. We first examined the variables showing a significant association with BMI; subsequently, we modeled the relationship between BMI and psychiatric outcome using structural equation analysis.
Results:  The prevalence of obesity in our sample was 39.1%. We found higher BMI in subjects with a chronic course (p < 0.001) and longer duration of illness (p = 0.02), lower scores on the Global Assessment of Functioning Scale (p = 0.02), and on disability (p = 0.002). Overweight patients had more frequent comorbid subthreshold social (p = 0.02) and generalized anxiety disorders (p = 0.05), diabetes mellitus type II (p < 0.001), and hypertension (p = 0.001). Subjects who achieved complete remission of symptoms on lithium showed significantly lower BMI (p = 0.01).
Conclusions:  Our findings suggest that BMI is associated with the prognosis and outcome of BD. Whether this association is causal remains to be determined.     

The longitudinal course of cognition in older adults with bipolar disorder

Objectives:  Epidemiological studies suggest that elders with bipolar disorder (BD) may be at increased risk for dementia compared to the general population. We sought to investigate whether older adults with BD would present with more cognitive dysfunction than expected for their age and education, and whether they would experience a more rapid cognitive decline over three-year prospective follow-up.
Methods:  Thirty-three subjects age ≥ 50, mean (SD) age 69.7 (7.9) years, with BD I (n = 28) and II (n = 5) had neuropsychological examination at baseline and longitudinally over three years. All subjects were administered the Dementia Rating Scale (DRS) when euthymic. Thirty-six mentally healthy comparators ('controls'), equated on age and education, were selected from ongoing studies in our research center examining the longitudinal relationship between late-life mood disorders and cognitive function.
Results:  Compared to mentally healthy comparators, subjects with BD performed significantly worse on the DRS at baseline [mean (SD) 135.2 (4.7); n = 33 versus 139.5 (3.3); n = 36], and over follow-up [131.9 (7.7); n = 14 versus 139.1 (3.4); n = 22]. There was a group-by-time interaction between the subjects with BD and the controls [group × time: F (1,64) = 5.07, p = 0.028].
Conclusions:  In our study, older adults with BD had more cognitive dysfunction and more rapid cognitive decline than expected given their age and education. Cognitive dysfunction and accelerated cognitive decline may lead to decreased independence, with increased reliance on family and community supports, and potential placement in assisted-living facilities.     

Gender influences the detection of spatial working memory deficits in bipolar disorder

Objective:  Despite evidence that gender may influence neurocognitive functioning, few studies have examined its effects in bipolar disorder (BD) a priori . The aim of this study was to examine how gender influences executive-type functions, which are potentially useful as endophenotypes for BD.
Methods:  The performance of 26 euthymic patients (12 males, 14 females) with DSM-IV BD (20 BD type I and six BD type II) was compared to that of 26 controls (12 males, 14 females) on tests of executive function. Controls were matched to patients on an individual basis for sex, age and premorbid IQ. Tests assessed spatial working memory (SWM), planning, attentional set-shifting and verbal fluency.
Results:  Overall, patients showed deficits in SWM strategy (p < 0.001) and made more SWM errors relative to controls (p < 0.001). These deficits were more apparent in male-only comparisons (both p < 0.001) than in female-only comparisons (both p < 0.05). When examined in isolation, male controls were significantly better at performing the SWM task than female controls (both p < 0.05). This pattern was not observed in the patient cohort: male patients had poorer strategy scores than female patients (p < 0.05), but made a similar number of SWM errors.
Conclusions:  These findings provide evidence that gender can influence the detection of SWM deficits in the euthymic phase of BD, as the sex-related disequilibrium in SWM identified in healthy controls was disrupted in BD.     

Retrospective age at onset of bipolar disorder and outcome during two-year follow-up: results from the STEP-BD study

Objective:  Symptoms of bipolar disorder are increasingly recognized among children and adolescents, but little is known about the course of bipolar disorder among adults who experience childhood onset of symptoms.
Methods:  We examined prospective outcomes during up to two years of naturalistic treatment among 3,658 adult bipolar I and II outpatients participating in a multicenter clinical effectiveness study, the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Age at illness onset was identified retrospectively by clinician assessment at study entry.
Results:  Compared to patients with onset of mood symptoms after age 18 years (n = 1,187), those with onset before age 13 years (n = 1,068) experienced earlier recurrence of mood episodes after initial remission, fewer days of euthymia, and greater impairment in functioning and quality of life over the two-year follow-up. Outcomes for those with onset between age 13 and 18 years (n = 1,403) were generally intermediate between these two groups.
Conclusion:  Consistent with previous reports in smaller cohorts, adults with retrospectively obtained early-onset bipolar disorder appear to be at greater risk for recurrence, chronicity of mood symptoms, and functional impairment during prospective observation.     

Trauma exposure and posttraumatic stress disorder among primary care patients with bipolar spectrum disorder

Objective:  To examine relationships between exposure to trauma, bipolar spectrum disorder (BD) and posttraumatic stress disorder (PTSD) in a sample of primary care patients.
Methods:  A systematic sample (n = 977) of adult primary care patients from an urban general medicine practice were interviewed with measures including the Mood Disorders Questionnaire, the PTSD Checklist–Civilian Version, and the Medical Outcomes Study 12-Item Short Form Health Survey.
Results:  Compared with patients who screened negative for BD (n = 881), those who screened positive (n = 96) were 2.6 times [95% confidence interval (CI): 1.6–4.2] as likely to report physical or sexual assault, and 2.9 times (95% CI: 1.6–5.1) as likely to screen positive for current PTSD. Among those screening positive for BD, comorbid PTSD was associated with significantly worse social functioning. These results controlled for selected background characteristics, current major depressive episode, and current alcohol/drug use disorder.
Conclusion:  In an urban general medicine setting, trauma exposure was related to BD, and the frequency of PTSD among patients with BD appears to be common and clinically significant. These results suggest an unmet need for mental health care in this specific population and are especially important in view of available treatments for BD and PTSD.     

Polarity at illness onset in bipolar I disorder and clinical course of illness

Objectives:  Studies have suggested that episode polarity at illness onset in bipolar disorder may be predictive of some aspects of lifetime clinical characteristics. We here examine this possibility in a large, well-characterized sample of patients with bipolar I disorder.
Methods:  We assessed polarity at onset in patients with bipolar I disorder (N = 553) recruited as part of our ongoing studies of affective disorders. Lifetime clinical characteristics of illness were compared in patients who had a depressive episode at first illness onset (n = 343) and patients who had a manic episode at first illness onset (n = 210).
Results:  Several lifetime clinical features differed between patients according to the polarity of their onset episode of illness. A logistic regression analysis showed that the lifetime clinical features significantly associated with a depressive episode at illness onset in our sample were: an earlier age at illness onset; a predominantly depressive polarity during the lifetime; more frequent and more severe depressive episodes; and less prominent lifetime psychotic features.
Conclusions:  Knowledge of pole of onset may help the clinician in providing prognostic information and management advice to an individual with bipolar disorder.     

Norepinephrine and serotonin imbalance in the locus coeruleus in bipolar disorder

Objectives:  Abnormalities in norepinephrine (NE) and serotonin (5-HT) are implicated in bipolar disorder (BD). We examined 5-HT input and NE neurons in the locus coeruleus (LC, the NE nucleus that innervates the forebrain) in BD by quantifying immunoreactivity (IR) for tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the biosynthetic enzymes for NE and 5-HT, respectively.
Methods:  Six suicides with BD were compared to matched normal controls and unipolar major depression suicides, using immunocytochemistry with computer-assisted quantification of immunoreactivity.
Results:  Depressed bipolar suicides had 26.7 ± 1.3% of LC area occupied by the TH immunoreactive (TH-IR) process, while controls had 50.7 ± 8% (p = 0.002) and unipolar depressed suicides had 50.3 ± 2.5% (p = 0.003). In bipolars, these processes did not stain as darkly (1.9 ± 0.5 × background) as controls (2.9 ± 0.9 × background; p = 0.01) or unipolars (2.9 ± 0.6 × background; p = 0.002). Bipolar suicides also had less TPH-IR processes in the LC (11.7 ± 10%) compared with controls (32.8 ± 8.8%; p = 0.01) or unipolar suicides (30.3 ± 8%; p = 0.02). The TPH-IR intensity did not differ between groups.
Conclusions:  We found less TH-IR and TPH-IR in the LC in depressed bipolar suicides, but not unipolar suicides, suggesting that both NE and 5-HT activity is lower in BD. Studies during manic or euthymic states will determine whether these changes are mood state dependent.     

Functional impairment as a predictor of short-term symptom course in bipolar I disorder

Objectives:  Most prior research has focused on functional impairment as a consequence, rather than a predictor, of mood symptoms in bipolar disorder (BD). Yet the majority of this research has been cross-sectional, thus limiting conclusions regarding directionality of effects. Indeed, just as functional impairment may represent an important outcome of BD, it may also serve as a risk factor for future affective symptoms or episodes. Thus, the primary aim of this study was to evaluate functional impairment as a predictor of mood symptoms in BD.
Methods:  Ninety-two patients with bipolar I disorder, recruited from hospital settings, were administered the Modified Hamilton Rating Scale for Depression, Bech–Rafaelson Mania Scale, and UCLA Social Attainment Survey (SAS) at baseline and at four-month follow-up.
Results:  Overall, patients evidenced a moderate level of functional impairment at both time points. Whereas baseline functional impairment was not associated with subsequent manic symptoms, baseline functional impairment was significantly predictive of depressive symptom levels at four-month follow-up. When individual SAS subscales were evaluated, impaired romantic relationship functioning and activity involvement were each significantly predictive of subsequent depressive symptoms, whereas baseline peer functioning was not.
Conclusions:  The study results suggest that functional impairment may be predictive of subsequent depressive, but not manic, symptoms over a relatively short-term follow-up period. Future studies that evaluate illness course over longer follow-up periods would be useful to further clarify the potential bidirectional relationship between depression and functional impairment in BD.     

A preliminary functional magnetic resonance imaging study of prefrontal-amygdalar activation changes in adolescents with bipolar depression treated with lamotrigine

Objectives:  Hypotheses regarding mood dysregulation in bipolar disorder (BD) have centered on limbic overactivity with relative prefrontal underactivity during mood episodes. Therefore, we hypothesized that adolescents with bipolar depression successfully treated with lamotrigine would show decreases in amygdalar activation, and increases in prefrontal activation.
Methods:  Eight adolescents with BD underwent functional magnetic resonance imaging (fMRI) at baseline and after eight weeks of lamotrigine treatment. Blocks of negatively and neutrally valenced emotional pictures were presented during scanning, and subjects were asked to rate how each picture made them feel. Activation in bilateral amygdalae and dorsolateral prefrontal cortices (DLPFC) for negative minus neutral pictures was correlated with Children's Depression Rating Scale (CDRS) scores.
Results:  Mean (SD) CDRS scores decreased significantly, from 53.0 (10.6) at baseline to 26.3 (5.3) at Week 8. This clinical improvement was correlated with decreased right amygdalar activation ( r  = 0.91, p = 0.002). At Week 8, but not baseline, CDRS score was positively correlated with bilateral amygdalar activation ( r  = 0.85, p = 0.007). DLPFC activation was not correlated with change in CDRS score.
Conclusions:  These preliminary results indicate that adolescents with BD treated with lamotrigine demonstrated less amygdalar activation when viewing negative stimuli as depressive symptoms improved. Larger controlled studies are needed to confirm these findings.     

Subsyndromal symptoms assessed in longitudinal, prospective follow-up of a cohort of patients with bipolar disorder

Background: Many patients with bipolar disorder (BD) do not regain full function following an acute illness episode, but the extent to which this impairment is the result of persistent symptoms has not been well established. This study examined factors associated with persistent subsyndromal symptoms in a well characterized group of BD patients who were prospectively followed for an average of 3 years.
Methods: Detailed life charting data from 138 patients with BD were reviewed. Patients were categorized into euthymic, subsyndromal or syndromal groups according to the clinical state during their most recent year of follow-up. The three groups were then examined with respect to comorbidity, function and treatment received.
Results: Patients with subsyndromal symptoms had high rates of comorbid anxiety disorders, and were more likely to have increased rates of eating disorders as well. Patients with subsyndromal symptoms had lower global assessment of function (GAF) scores than euthymic patients, and had as many clinic contacts and medication trials as patients with full episodes of illness.
Conclusions: Persistent subsyndromal symptoms in BD patients are associated with high rates of comorbidity that is important to recognize and treat in order to optimize mood and functioning.     

Oxcarbazepine add-on in the treatment of refractory bipolar disorder

Objective:  To assess the effectiveness and safety of oxcarbazepine (OXC) in bipolar disorder (BD) and related conditions.
Methods:  We reviewed medical records of patients given OXC treatment between March 2003 and March 2005 at the University of British Columbia Hospital. Response to treatment was assessed retrospectively using the Clinical Global Impression of Severity (CGI-S), and the Clinical Global Impression of Improvement (CGI-I) scales.
Results:  OXC was prescribed to 15 patients with bipolar I (n = 12), bipolar II (n = 2) and schizoaffective (n = 1) disorder who presented with depression (n = 9), mania (n = 3), hypomania (n = 1), or mixed state (n = 2). Six patients had Axis II diagnoses and 10 patients had a family history of mood disorders. Psychiatric co-morbidity was found in four patients. The mean daily dose of OXC was 775 ± 556.11 mg/day and the mean duration of follow-up was 31.60 ± 41.51 weeks. The OXC add-on led to a significant reduction in symptoms as indicated by reduction in CGI-S scores at 1 and 2 months. Nine of 12 patients at 1 month and seven of 14 at 1 or 2 months were much or very much improved on CGI-I scale. One patient (7%) developed hyponatremia. Six patients (40%) experienced no side effects and three patients (20%) stopped the medication because of side effects.
Conclusion:  OXC was effective and well-tolerated in refractory BD and schizoaffective disorder. These preliminary data are promising but controlled studies are needed to confirm its efficacy in refractory BD.     

Functional polymorphism of the glucocorticoid receptor gene associates with mania and hypomania in bipolar disorder

Objectives:  In affective disorders, dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is a frequently observed phenomenon. Subtle changes in glucocorticoid receptor (GR) functioning caused by polymorphisms of the GR gene ( NR3C1 ) may be at the base of the altered reaction of the HPA axis to stress and subsequently related to the development and course of affective disorders. The aim of our study is to evaluate associations between GR gene polymorphisms and bipolar disorder (BD).
Methods:  In this study, 245 patients with BD were interviewed to confirm diagnosis and BD subtype. Data on medication use and sociodemographic details were also collected. The control group consisted of 532 healthy blood donors, from which data on sex and age were collected. To perform genotyping, blood was collected from all patients and healthy controls.
Results:  A trend was found for a protective effect of the exon 9β polymorphism (p = 0.14) and the TthIII I polymorphism (p < 0.05) on the manifestation of the disease. These effects were significantly influenced by male gender for both polymorphisms. Patients with BD and the A/G variant in exon 9β had significantly fewer manic and hypomanic episodes than noncarriers (p < 0.05). No further associations were found with the other investigated GR gene polymorphisms and BD. These findings were not corrected for multiple comparisons.
Conclusions:  We conclude that the exon 9β polymorphism and the TthIII I polymorphism of the GR gene may be associated with a protective effect on the clinical manifestation and course in patients with BD. Furthermore, no associations were found between the other studied GR gene polymorphisms and this disease.     

Do positive emotions predict symptomatic change in bipolar disorder?

Objectives:  Bipolar disorder is associated with positive emotion disturbance, though it is less clear which specific positive emotions are affected.
Methods:  The present study examined differences among distinct positive emotions in recovered bipolar disorder (BD) patients (n = 55) and nonclinical controls (NC) (n = 32) and whether they prospectively predicted symptom severity in patients with BD. At baseline, participants completed self-report measures of several distinct trait positive emotions. Structured assessments of diagnosis and current mood symptoms were obtained for BD participants. At a six-month follow-up, a subset of BD participants' (n = 39) symptoms were reassessed.
Results:  BD participants reported lower joy, compassion, love, awe, and contentment compared to NC participants. BD and NC participants did not differ in pride or amusement. For BD participants, after controlling for baseline symptom severity, joy and amusement predicted increased mania severity, and compassion predicted decreased mania severity at the six-month follow-up. Furthermore, amusement predicted increased depression severity and pride predicted decreased severity of depression. Awe, love, and contentment did not predict symptom severity.
Conclusions:  These results are consistent with a growing literature highlighting the importance of positive emotion in the course of bipolar disorder.     

Prospective predictors of suicide and suicide attempts in 1,556 patients with bipolar disorders followed for up to 2 years

Objectives:  Bipolar disorders are associated with high rates of suicide attempts (SAs) and completions. Several factors have been reported to be associated with suicide in persons with bipolar disorder, but most studies to date have been retrospective and have not utilized multivariate statistics to account for the redundant prediction among variables submitted for analysis.
Methods:  This study examined the association between baseline clinical and demographic variables and subsequent SAs and completions through 2 years of follow-up of participants in the Systematic Treatment Enhancement Program for Bipolar Disorder using a pattern-mixture model.
Results:  Of the sample with complete data (n = 1,556), 57 patients (3.66%) experienced an SA or completion (CS). Several variables predicted suicidality (SA + CS) in this data set when considered alone, but after controlling for redundant prediction from other baseline characteristics, only history of suicide [odds ratio (OR) = 4.52, p < 0.0001] and percent days depressed in the past year (OR = 1.16, p = 0.036) were significantly associated with SAs and completions. A secondary analysis included a greater number of variables but a smaller sample size (n = 1,014). In the secondary analyses, only prior SAs predicted prospective suicidality (OR = 3.87, p = 0.0029).
Conclusions:  These results indicate that patients with bipolar disorder who present with a history of SAs are over four times as likely to have a subsequent SA or completion. Further studies are needed to evaluate and prevent future attempts in this high-risk cohort.     

A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states

Objective:  Asenapine is approved for bipolar disorder and schizophrenia. This was a 3-week, randomized, double-blind, placebo-controlled trial of asenapine for treating acute bipolar mania.
Methods:  After a single-blind placebo run-in period, adults (n = 488) experiencing manic or mixed episodes were randomized to flexible-dose sublingual asenapine (10 mg BID on day 1; 5 or 10 mg BID thereafter; n = 194), placebo (n = 104), or oral olanzapine (15 mg BID on day 1; 5–20 mg QD thereafter; n = 191). Primary efficacy, change in Young Mania Rating Scale (YMRS) total score from baseline to day 21, was assessed using analysis of covariance with last observation carried forward [(LOCF); primary analysis]. A mixed model for repeated measures [(MMRM); prespecified secondary analysis] was also used to assess efficacy. Tolerability and safety assessments included adverse events, physical examinations, extrapyramidal symptom ratings, and laboratory values.
Results:  Mean daily dosages were asenapine 18.2 mg and olanzapine 15.8 mg. Significantly greater least squares (LS) mean ± SE changes in YMRS scores were observed on day 2 with asenapine (−3.0 ± 0.4) and olanzapine (−3.4 ± 0.4) versus placebo (−1.5 ± 0.5, both p < 0.01) and were maintained until day 21 (−10.8 ± 0.8 with asenapine, −12.6 ± 0.8 with olanzapine; both p ≤ 0.0001 versus placebo, −5.5 ± 1.1) with LOCF. The results of MMRM analyses were consistent with those of LOCF. Asenapine had a modest impact on weight and metabolic measures.
Conclusions:  These results indicate that asenapine is rapidly acting, efficacious, and well tolerated for patients with bipolar I disorder experiencing an acute manic episode.     

Pilot sample of very early onset bipolar disorder in a military population moderates the association of negative life events and non-fatal suicide attempt

Objective:  To examine the moderating effects of very early onset diagnostic status (≤ 13 years) upon the association between life events and non-fatal suicide attempt.
Methods:  Measures of negative life events, suicidal ideation and current suicide attempt were administered to 298 military-based young adults at entry to treatment for suicidality. Current and lifetime diagnoses were assigned using the Diagnostic Interview Schedule. The predictive ability of negative life events for non-fatal suicide attempt was examined separately for the total sample and for those with retrospectively determined histories of very early onset bipolar disorder (VEOBPD; n = 16), very early onset major depressive disorder (VEOMDD; n = 21) and very early onset anxiety disorder (VEOANX; n = 53).
Results:  Negative life events and suicide attempt were significantly and positively associated among those with no history of VEOBPD (OR = 1.30, 95% CI = 1.02–1.65, p < 0.05), including those with VEOMDD and VEOANX. Consistent with expectation, VEOBPD moderated the association between negative life events and suicide attempt (OR = 0.88, 95% CI = 0.78–0.99, p < 0.05), such that negative life events were non-significantly and negatively associated with the presence of a suicide attempt (OR = 0.21, 95% CI = 0.04–1.02, p = 0.09) among patients with a history of VEOBPD.
Conclusions:  Despite similar rates of suicide attempt among all diagnostic groups, life stress did not contribute to attempt among those with VEOBPD. These findings are consistent with the severity and chronicity of VEOBPD. Potential explanations of these findings include a scarring effect on coping skills and increased sensitization to life stress.     

Sexually dimorphic features of vermis morphology in bipolar disorder

Objectives:  The cerebellar vermis is increasingly implicated in bipolar disorder (BD). In this study, we investigated vermis morphology in BD using a quantitative volumetric analysis.
Methods:  Volumes for total vermis and vermis subregions V1 (lobules I–V), V2 (lobules VI–VII), and V3 (lobules VIII–X) were calculated using high-resolution structural magnetic resonance imaging obtained from 44 individuals with BD (25 females and 19 males) and 43 healthy comparison (HC) subjects (26 females and 17 males). Total vermis volumes were compared between the BD and HC groups. Potential effects of vermis subregions and clinical features were explored.
Results:  Total vermis volumes were significantly larger in the BD group than in the HC group (p = 0.02). There was a significant group-by-sex interaction (p = 0.02). Total vermis volumes were significantly larger in males with BD than HC males (p = 0.004); vermis volumes did not differ significantly between females with and without BD (p = 0.95). Subregion analyses showed a trend-level interaction between diagnosis and subregion (p = 0.07) in which subregion V1 volumes were significantly larger in BD participants (p = 0.001), with differences primarily driven by males (p = 0.001).
Conclusions:  Our findings demonstrate increases in cerebellar vermis volumes in males with BD. These findings support the presence of structural alterations in the cerebellar vermis in BD and furthermore the influence of sex on such changes.     

An initial report of a new biological marker for bipolar disorder: P85 evoked brain potential

Objectives:  Progress toward understanding the neurobiological and genetic underpinnings of bipolar disorder has been limited by the scarcity of potential biological markers that predict its occurrence. A measure of the integrity of brain inhibitory function, sensory gating, measured using the amplitude of the evoked potential at 50 ms to the first of two paired clicks divided by the response to the second, has been characterized as a biological marker for schizophrenia. Currently, no such biological marker exists for bipolar disorder. The goal of this research was to determine how gating of an auditory brain potential at 85 ms (P85), not previously examined in sensory gating studies, differentiated control and patient groups.
Methods:  P50 and P85 auditory evoked potentials were collected from individuals diagnosed with schizoaffective disorder (n = 45), paranoid schizophrenia (n = 66), and bipolar I disorder (n = 42) using DSM-IV criteria and the Structured Clinical Interview for DSM-IV; and from 56 healthy controls.
Results:  The P85 gating ratio was significantly larger in the bipolar disorder group compared to each of the other groups ( F _3,204 = 5.47, p = 0.001, and post-hoc tests). The P50 gating ratio was significantly larger for the schizoaffective group than for the control group ( F _3,204 = 2.81, p = 0.040), but did not differ from the ratio for the schizophrenia, paranoid type (p = 0.08) and bipolar groups.
Conclusions:  The previously unstudied P85 gating ratio may provide a new marker specific to bipolar disorder. The findings will promote further studies to investigate the unique contribution of this measure as an endophenotype.