Hippocampal cingulum white matter increases over time in young people at high genetic risk for bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a strongly familial psychiatric disorder associated with white matter (WM) brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about WM trajectories in those at increased genetic risk. METHODS: Diffusion magnetic resonance imaging (dMRI) data were acquired at baseline and after two years in 91 unaffected individuals with a first-degree relative with bipolar disorder (HR), and 85 individuals with no family history of mental illness (CON). All participants were aged between 12 and 30 years at baseline. We examined longitudinal change in Fractional Anisotropy (FA) using tract-based spatial statistics (TBSS). RESULTS: Compared to the CON group, HR participants showed a significant increase in FA in the right cingulum (hippocampus) (CGH) over a two-year period (p < .05, FDR corrected). This effect was more pronounced in HR individuals without a lifetime diagnosis of a mood disorder than those with a mood disorder. LIMITATIONS: While our study is well powered to achieve the primary objectives, our sub-group analyses were under powered. CONCLUSIONS: In one of the very few longitudinal neuroimaging studies of young people at high risk for BD, this study reports novel evidence of atypical white matter development in HR individuals in a key cortico-limbic tract involved in emotion regulation. Our findings also suggest that this different white matter developmental trajectory may be stronger in HR individuals without affective psychopathology. As such, increases in FA in the right CGH of HR participants may be a biomarker of resilience to mood disorders.

Accelerated cortical thinning and volume reduction over time in young people at high genetic risk for bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a familial psychiatric disorder associated with frontotemporal and subcortical brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about structural brain trajectories in those at risk. METHOD: Neuroimaging was conducted at baseline and at 2-year follow-up interval in 90 high-risk individuals with a first-degree BD relative (HR), and 56 participants with no family history of mental illness who could have non-BD diagnoses. All 146 subjects were aged 12-30 years at baseline. We examined longitudinal change in gray and white matter volume, cortical thickness, and surface area in the frontotemporal cortex and subcortical regions. RESULTS: Compared to controls, HR participants showed accelerated cortical thinning and volume reduction in right lateralised frontal regions, including the inferior frontal gyrus, lateral orbitofrontal cortex, frontal pole and rostral middle frontal gyrus. Independent of time, the HR group had greater cortical thickness in the left caudal anterior cingulate cortex, larger volume in the right medial orbitofrontal cortex and greater area of right accumbens, compared to controls. This pattern was evident even in those without the new onset of psychopathology during the inter-scan interval. CONCLUSIONS: This study suggests that differences previously observed in BD are developing prior to the onset of the disorder. The pattern of pathological acceleration of cortical thinning is likely consistent with a disturbance of molecular mechanisms responsible for normal cortical thinning. We also demonstrate that neuroanatomical differences in HR individuals may be progressive in some regions and stable in others.

A prospective study of pre-employment psychological testing amongst police recruits.

BACKGROUND: Pre-employment psychological screening to detect psychological vulnerability is common amongst emergency service organizations worldwide, yet the evidence for its ability to predict poor mental health outcomes is limited with published studies looking at post-recruitment research data rather than data collected by the organizations themselves. AIMS: The present study sought to investigate the ability of pre-employment screening to predict later psychological injury-related absenteeism amongst police officers. METHODS: A nested case-control study using prospective data was conducted. One hundred and fifty police officers with a liability-accepted psychological injury were matched to a control group of 150 psychologically healthy officers. Conditional logistic regression was used to examine associations between Minnesota Multiphasic Personality Inventory-2 (MMPI-2) scales measuring factors research has shown to predict psychological injury (Neuroticism, Psychoticism, Introversion, Disconstraint and Aggressiveness) and psychopathology (Depression, Anxiety and post-traumatic stress disorder [PTSD]) with subsequent psychological injury. RESULTS: Contrary to expectations, we were unable to demonstrate any association between validated pre-employment measures of personality and psychopathology with mental health outcomes amongst newly recruited police officers over a 7-year follow-up. CONCLUSIONS: Other measures may be better able to predict future mental health problems in police recruits.

The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders.

Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.

Structural dysconnectivity of key cognitive and emotional hubs in young people at high genetic risk for bipolar disorder.

Emerging evidence suggests that psychiatric disorders are associated with disturbances in structural brain networks. Little is known, however, about brain networks in those at high risk (HR) of bipolar disorder (BD), with such disturbances carrying substantial predictive and etiological value. Whole-brain tractography was performed on diffusion-weighted images acquired from 84 unaffected HR individuals with at least one first-degree relative with BD, 38 young patients with BD and 96 matched controls (CNs) with no family history of mental illness. We studied structural connectivity differences between these groups, with a focus on highly connected hubs and networks involving emotional centres. HR participants showed lower structural connectivity in two lateralised sub-networks centred on bilateral inferior frontal gyri and left insular cortex, as well as increased connectivity in a right lateralised limbic sub-network compared with CN subjects. BD was associated with weaker connectivity in a small right-sided sub-network involving connections between fronto-temporal and temporal areas. Although these sub-networks preferentially involved structural hubs, the integrity of the highly connected structural backbone was preserved in both groups. Weaker structural brain networks involving key emotional centres occur in young people at genetic risk of BD and those with established BD. In contrast to other psychiatric disorders such as schizophrenia, the structural core of the brain remains intact, despite the local involvement of network hubs. These results add to our understanding of the neurobiological correlates of BD and provide predictions for outcomes in young people at high genetic risk for BD.

Prevalence of current anxiety disorders in people with bipolar disorder during euthymia: a meta-analysis.

BACKGROUND: Anxiety disorders are highly prevalent in people with bipolar disorder, but it is not clear how many have anxiety disorders even at times when they are free of major mood episodes. We aimed to establish what proportion of euthymic individuals with bipolar disorder meet diagnostic criteria for anxiety disorders. METHOD: We performed a random-effects meta-analysis of prevalence rates of current DSM-III- and DSM-IV-defined anxiety disorders (panic disorder, agoraphobia, social anxiety disorder, generalized anxiety disorder, specific phobia, obsessive-compulsive disorder, post-traumatic stress disorder, and anxiety disorder not otherwise specified) in euthymic adults with bipolar disorder in studies published by 31 December 2015. RESULTS: Across 10 samples with 2120 individuals with bipolar disorder, 34.7% met diagnostic criteria for one or more anxiety disorders during euthymia [95% confidence interval (CI) 23.9-45.5%]. Direct comparison of 189 euthymic individuals with bipolar disorder and 17 109 population controls across three studies showed a 4.6-fold increase (risk ratio 4.60, 95% CI 2.37-8.92, p < 0.001) in prevalence of anxiety disorders in those with bipolar disorder. CONCLUSIONS: These findings suggest that anxiety disorders are common in people with bipolar disorder even when their mood is adequately controlled. Euthymic people with bipolar disorder should be routinely assessed for anxiety disorders and anxiety-focused treatment should be initiated if indicated.

Are there subtypes of bipolar depression?

OBJECTIVE: To investigate for subtypes of bipolar depression using latent class analysis (LCA). METHOD: Participants were recruited through a bipolar disorder (BD) clinic. LCA was undertaken using: (i) symptoms reported on the SCID-IV for the most severe lifetime depressive episode; (ii) lifetime illness features such as age at first depressive and hypo/manic episodes; and (iii) family history of BD and unipolar depression. To explore the validity of any demonstrated 'classes', clinical, demographic and treatment correlates were investigated. RESULTS: A total of 243 BD subjects (170 with BD-I and 73 with BD-II) were included. For the combined sample, we found two robust LCA solutions, with two and three classes respectively. There were no consistent solutions when the BD-I and BD-II samples were considered separately. Subjects in class 2 of the three-class solution (characterised by anxiety, insomnia, reduced appetite/weight loss, irritability, psychomotor retardation, suicidal ideation, guilt, worthlessness and evening worsening) were significantly more likely to be in receipt of government financial support, suggesting a particularly malign pattern of symptoms. CONCLUSION: Our study suggests the existence of two or three distinct classes of bipolar depression and a strong association with functional outcome.

Interhemispheric white matter integrity in young people with bipolar disorder and at high genetic risk.

BACKGROUND: White matter (WM) impairments have been reported in patients with bipolar disorder (BD) and those at high familial risk of developing BD. However, the distribution of these impairments has not been well characterized. Few studies have examined WM integrity in young people early in the course of illness and in individuals at familial risk who have not yet passed the peak age of onset. METHOD: WM integrity was examined in 63 BD subjects, 150 high-risk (HR) individuals and 111 participants with no family history of mental illness (CON). All subjects were aged 12 to 30 years. RESULTS: This young BD group had significantly lower fractional anisotropy within the genu of the corpus callosum (CC) compared with the CON and HR groups. Moreover, the abnormality in the genu of the CC was also present in HR participants with recurrent major depressive disorder (MDD) (n = 16) compared with CON participants. CONCLUSIONS: Our findings provide important validation of interhemispheric abnormalities in BD patients. The novel finding in HR subjects with recurrent MDD - a group at particular risk of future hypo/manic episodes - suggests that this may potentially represent a trait marker for BD, though this will need to be confirmed in longitudinal follow-up studies.

Abnormalities in left inferior frontal gyral thickness and parahippocampal gyral volume in young people at high genetic risk for bipolar disorder.

BACKGROUND: Fronto-limbic structural brain abnormalities have been reported in patients with bipolar disorder (BD), but findings in individuals at increased genetic risk of developing BD have been inconsistent. We conducted a study in adolescents and young adults (12-30 years) comparing measures of fronto-limbic cortical and subcortical brain structure between individuals at increased familial risk of BD (at risk; AR), subjects with BD and controls (CON). We separately examined cortical volume, thickness and surface area as these have distinct neurodevelopmental origins and thus may reflect differential effects of genetic risk. METHOD: We compared fronto-limbic measures of grey and white matter volume, cortical thickness and surface area in 72 unaffected-risk individuals with at least one first-degree relative with bipolar disorder (AR), 38 BD subjects and 72 participants with no family history of mental illness (CON). RESULTS: The AR group had significantly reduced cortical thickness in the left pars orbitalis of the inferior frontal gyrus (IFG) compared with the CON group, and significantly increased left parahippocampal gyral volume compared with those with BD. CONCLUSIONS: The finding of reduced cortical thickness of the left pars orbitalis in AR subjects is consistent with other evidence supporting the IFG as a key region associated with genetic liability for BD. The greater volume of the left parahippocampal gyrus in those at high risk is in line with some prior reports of regional increases in grey matter volume in at-risk subjects. Assessing multiple complementary morphometric measures may assist in the better understanding of abnormal developmental processes in BD.

Placebo-controlled pilot trial testing dose titration and intravenous, intramuscular and subcutaneous routes for ketamine in depression.

OBJECTIVE: This pilot study assessed the feasibility, efficacy and safety of an individual dose-titration approach, and of the intravenous (IV), intramuscular (IM) and subcutaneous (SC) routes for treating depression with ketamine. METHOD: Fifteen treatment-refractory depressed participants received ketamine or midazolam (control treatment) in a multiple crossover, double-blind study. Ketamine was administered by IV (n = 4), IM (n = 5) or SC (n = 6) injection. Dose titration commenced at 0.1 mg/kg, increasing by 0.1 mg/kg up to 0.5 mg/kg, given in separate treatment sessions separated by ≥1 week, with one placebo control treatment randomly inserted. Mood, psychotomimetic and hemodynamic effects were assessed and plasma ketamine concentrations assayed. RESULTS: Twelve participants achieved response and remission criteria, achieved at doses as low as 0.1 mg/kg. All three routes of administration resulted in comparable antidepressant effects. Fewest adverse effects were noted with the SC route. Antidepressant response, adverse effects and ketamine concentrations were dose-related. CONCLUSION: Antidepressant response occurred at a range of doses and at <0.5 mg/kg. The dose-titration approach is a practical method for optimizing the efficacy - side-effects trade-off on an individual patient basis. This pilot study provides preliminary evidence for SC injection as a practical, feasible and efficacious treatment approach.

Neuropsychological and social cognitive function in young people at genetic risk of bipolar disorder.

BACKGROUND: Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives. METHOD: Neurocognitive and social cognitive ability was examined in 99 young people (age range 16-30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD. RESULTS: Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs. CONCLUSIONS: Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.

Workplace interventions for common mental disorders: a systematic meta-review.

Depression and anxiety disorders are the leading cause of sickness absence and long-term work incapacity in most developed countries. The present study aimed to carry out a systematic meta-review examining the effectiveness of workplace mental health interventions, defined as any intervention that a workplace may either initiate or facilitate that aims to prevent, treat or rehabilitate a worker with a diagnosis of depression, anxiety or both. Relevant reviews were identified via a detailed systematic search of academic and grey literature databases. All articles were subjected to a rigorous quality appraisal using the AMSTAR assessment. Of the 5179 articles identified, 140 studies met the inclusion criteria, of which 20 were deemed to be of moderate or high quality. Together, these reviews analysed 481 primary research studies. Moderate evidence was identified for two primary prevention interventions; enhancing employee control and promoting physical activity. Stronger evidence was found for CBT-based stress management although less evidence was found for other secondary prevention interventions, such as counselling. Strong evidence was also found against the routine use of debriefing following trauma. Tertiary interventions with a specific focus on work, such as exposure therapy and CBT-based and problem-focused return-to-work programmes, had a strong evidence base for improving symptomology and a moderate evidence base for improving occupational outcomes. Overall, these findings demonstrate there are empirically supported interventions that workplaces can utilize to aid in the prevention of common mental illness as well as facilitating the recovery of employees diagnosed with depression and/or anxiety.

Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder.

Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.

Confirmatory test of two factors and four subtypes of bipolar disorder based on lifetime psychiatric co-morbidity.

BACKGROUND: The first aim was to use confirmatory factor analysis (CFA) to test a hypothesis that two factors (internalizing and externalizing) account for lifetime co-morbid DSM-IV diagnoses among adults with bipolar I (BPI) disorder. The second aim was to use confirmatory latent class analysis (CLCA) to test the hypothesis that four clinical subtypes are detectible: pure BPI; BPI plus internalizing disorders only; BPI plus externalizing disorders only; and BPI plus internalizing and externalizing disorders. METHOD: A cohort of 699 multiplex BPI families was studied, ascertained and assessed (1998-2003) by the National Institute of Mental Health Genetics Initiative Bipolar Consortium: 1156 with BPI disorder (504 adult probands; 594 first-degree relatives; and 58 more distant relatives) and 563 first-degree relatives without BPI. Best-estimate consensus DSM-IV diagnoses were based on structured interviews, family history and medical records. MPLUS software was used for CFA and CLCA. RESULTS: The two-factor CFA model fit the data very well, and could not be improved by adding or removing paths. The four-class CLCA model fit better than exploratory LCA models or post-hoc-modified CLCA models. The two factors and four classes were associated with distinctive clinical course and severity variables, adjusted for proband gender. Co-morbidity, especially more than one internalizing and/or externalizing disorder, was associated with a more severe and complicated course of illness. The four classes demonstrated significant familial aggregation, adjusted for gender and age of relatives. CONCLUSIONS: The BPI two-factor and four-cluster hypotheses demonstrated substantial confirmatory support. These models may be useful for subtyping BPI disorders, predicting course of illness and refining the phenotype in genetic studies.

The duration of undiagnosed bipolar disorder: effect on outcomes and treatment response.

INTRODUCTION: There are commonly long delays between the onset of bipolar disorder (BP), seeking of treatment and acquiring a bipolar disorder diagnosis. Whether a longer duration of undiagnosed bipolar disorder (DUBP) leads to an inferior treatment response is unclear in the literature. METHOD: We conducted two studies with independent samples of BP patients who had received a first-time diagnosis of BP - first investigating whether DUBP was related to clinical and social outcomes at the time of assessment (n=173) and, second, whether response to mood stabiliser medication was affected by DUBP when assessed three months following assessment and intervention (n=64). RESULTS: Participants׳ mean DUBP was 18-20 years (from the onset of mood episodes). After controlling for age, a longer DUBP was associated with employment difficulties, whereas a shorter DUBP was associated with a history of engaging in self-harm behaviours, as well as a reduced likelihood of experiencing social costs as consequence of the mood disorder. The majority of study variables were statistically unrelated to DUBP. In a multivariate analysis, age was the only predictor variable to make a significant contribution to the DUBP (33%). Across the 3-month intervention period, participants improved significantly on all but one outcome measure. The participants׳ likelihood to improve, become worse or experience minimal/no change over the study period was not significantly related to the DUBP. LIMITATIONS: Self-reporting poses a risk to measurement precision. Being a naturalistic observation, no specific dose of medication was prescribed. The small sample of BP I patients provided insufficient statistical power to undertake meaningful separate analyses of the BP I and BP II participants. CONCLUSION: Early detection and intervention remains important for helping to reduce morbidity and risks associated with untreated BP. However, the variation in DUBP was mostly a function of age and did not substantially affect clinical status at assessment, or lead to an inferior response to mood stabilising medication.

A meta-analysis of the risk of major affective disorder in relatives of individuals affected by major depressive disorder or bipolar disorder.

BACKGROUND: To conduct a meta-analysis to estimate the incidence of major depressive disorder (MDD) and bipolar disorder (BD) in first-degree relatives (FDRs) of probands affected by MDD or BD. The risk for MDD in FDR of BD probands and vice versa is also investigated. METHODS: A systematic review of case-control and cohort studies, which were published between 1977 and 2012; reported relative risks (RR) or odd ratios (OR) or equivalent raw data; made an explicit distinction between MDD and BD; used operational diagnostic criteria; and reported systematic proband recruitment and ascertainment of relatives. Studies were obtained by electronic MEDLINE and EMBASE searches and hand-searching. Estimates were derived from pooled data using random effects methods. RESULTS: Of an initial sample of 241 articles, 22 were eligible for inclusion. For FDRs of one proband with MDD compared to healthy control probands, estimates for MDD were OR=2.14 (95% CI 1.72-2.67), increasing to OR=3.23 (95% CI 2.11-4.94) for two MDD probands. For FDRs of one BD proband compared to healthy control probands, estimates for BD were OR=7.92 (95% CI 2.45-25.61), and OR=6.58 (95% CI 2.64-16.43) for FDRs of two BD probands. CONCLUSIONS: These findings support previously published data indicating strong familiality for both MDD and BD. Data will be useful in providing individuals with a family history of MDD or BPD with tailored risk estimates.

Bipolar disorder in a national survey using the World Mental Health Version of the Composite International Diagnostic Interview: the impact of differing diagnostic algorithms.

OBJECTIVE: The World Mental Health Version of the Composite International Diagnostic Interview (WMH-CIDI) DSM-IV bipolar disorder diagnostic algorithms were recalibrated in about 2006 following evidence of over-diagnosis of bipolar I disorder. There have been no reports of the impact of this recalibration on epidemiological findings. METHOD: Data were taken from the 2007 Australian National Survey of Mental Health and Wellbeing. Findings for cases identified by the recalibrated bipolar disorder definition were contrasted against those identified by the un-recalibrated definition. RESULTS: The 12-month prevalence of recalibrated bipolar disorder and un-recalibrated bipolar disorder were 0.9% and 1.7% respectively. The un-recalibrated bipolar disorder group was younger and more likely to have never married than the recalibrated bipolar disorder group. They were also more likely to have a comorbid alcohol use disorder, substance use disorder and asthma or arthritis. While they were more likely to have at least severe interference in at least one of the Sheehan Scale domains of functioning, they were less likely to have made a suicide attempt. Similarly, they were less likely to have consulted a psychiatrist. CONCLUSION: It is not possible to be certain about the nature of these differences. Some may be artifactual (reflecting greater statistical power to detect differences with the larger un-recalibrated bipolar disorder defined sample), while others may be indicative of the inclusion of a clinically distinct subpopulation with the un-recalibrated bipolar disorder definition, thereby producing a more heterogeneous sample. These findings indicate the need for clarity in the diagnostic algorithm used in epidemiological reports on bipolar disorder using the World Mental Health Version of the Composite International Diagnostic Interview.

A randomized controlled trial of mindfulness-based cognitive therapy for bipolar disorder.

OBJECTIVE: To compare the efficacy of mindfulness-based cognitive therapy (MBCT) plus treatment as usual (TAU) to TAU alone for patients with bipolar disorder over a 12-month follow-up period. METHOD: Participants with a DSM-IV diagnosis of bipolar disorder were randomly allocated to either MBCT plus TAU or TAU alone. Primary outcome measures were time to recurrence of a DSM-IV major depressive, hypomanic or manic episode; the Montgomery-Åsberg Depression Rating Scale (MADRS); and Young Mania Rating Scale (YMRS). Secondary outcome measures were number of recurrences, the Depression Anxiety Stress Scales (DASS), and the State Trait Anxiety Inventory (STAI). RESULTS: Ninety-five participants with bipolar disorder were recruited to the study (MBCT = 48; TAU = 47). Intention-to-treat (ITT) analysis found no significant differences between the groups on either time to first recurrence of a mood episode or total number of recurrences over the 12-month period. Furthermore, there were no significant between-group differences on the MADRS or YMRS scales. A significant between-group difference was found in STAI - state anxiety scores. There was a significant treatment by time interaction for the DAS - achievement subscale. CONCLUSION: While MBCT did not lead to significant reductions in time to depressive or hypo/manic relapse, total number of episodes, or mood symptom severity at 12-month follow-up, there was some evidence for an effect on anxiety symptoms. This finding suggests a potential role of MBCT in reducing anxiety comorbid with bipolar disorder.

Lack of cortico-limbic coupling in bipolar disorder and schizophrenia during emotion regulation.

Bipolar disorder (BD) and schizophrenia (Sz) share dysfunction in prefrontal inhibitory brain systems, yet exhibit distinct forms of affective disturbance. We aimed to distinguish these disorders on the basis of differential activation in cortico-limbic pathways during voluntary emotion regulation. Patients with DSM-IV diagnosed Sz (12) or BD-I (13) and 15 healthy control (HC) participants performed a well-established emotion regulation task while undergoing functional magnetic resonance imaging. The task required participants to voluntarily upregulate or downregulate their subjective affect while viewing emotionally negative images or maintain their affective response as a comparison condition. In BD, abnormal overactivity (hyperactivation) occurred in the right ventrolateral prefrontal cortex (VLPFC) during up- and downregulation of negative affect, relative to HC. Among Sz, prefrontal hypoactivation of the right VLPFC occurred during downregulation (opposite to BD), whereas upregulation elicited hyperactivity in the right VLPFC similar to BD. Amygdala activity was significantly related to subjective negative affect in HC and BD, but not Sz. Furthermore, amygdala activity was inversely coupled with the activity in the left PFC during downregulation in HC (r=-0.76), while such coupling did not occur in BD or Sz. These preliminary results indicate that differential cortico-limbic activation can distinguish the clinical groups in line with affective disturbance: BD is characterized by ineffective cortical control over limbic regions during emotion regulation, while Sz is characterized by an apparent failure to engage cortical (hypofrontality) and limbic regions during downregulation.