Volume and shape analysis of subcortical brain structures and ventricles in euthymic bipolar I disorder.

Previous structural magnetic resonance imaging (S-MRI) studies of bipolar disorder have reported variable morphological changes in subcortical brain structures and ventricles. This study aimed to establish trait-related subcortical volumetric and shape abnormalities in a large, homogeneous sample of prospectively confirmed euthymic bipolar I disorder (BD-I) patients (n=60), compared with healthy volunteers (n=60). Participants were individually matched for age and gender. Volume and shape metrics were derived from manually segmented S-MR images for the hippocampus, amygdala, caudate nucleus, and lateral ventricles. Group differences were analysed, controlling for age, gender and intracranial volume. BD-I patients displayed significantly smaller left hippocampal volumes and significantly larger left lateral ventricle volumes compared with controls. Shape analysis revealed an area of contraction in the anterior head and medial border of the left hippocampus, as well as expansion in the right hippocampal tail medially, in patients compared with controls. There were no significant associations between volume or shape variation and lithium status or duration of use. A reduction in the head of the left hippocampus in BD-I patients is interesting, given this region's link to verbal memory. Shape analysis of lateral ventricular changes in patients indicated that these are not regionally specific.

Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment.

Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity.

General practitioners' opinions and attitudes towards medical assessment of fitness to drive of older adults in Ireland.

OBJECTIVE: The study sought to assess opinions and attitudes of general practitioners (GPs) in Ireland towards fitness to drive (FTD) assessment in people older than 65 years old as well as to gather information on current assessment practices. METHOD: A postal-based cross-sectional survey was carried out with 603 GP practices randomly selected using the Irish College of General Practitioners database. RESULTS: Response rate was 42.6%. The prevalence of GPs not confident in assessing FTD was less than 15% with 81% reporting the need for more education on assessing FTD, and 82% identifying that mandatory reporting of unsafe drivers posed a conflict of interest. Only 37% of GPs always/often used the Irish Road Safety Authority handbook when assessing FTD with 14% not aware of its existence. Of responders, 89% were of the opinion that a clinical assessment tool would be of benefit in assessing FTD. CONCLUSION: Our study highlights the need for education and training for Irish GPs on FTD assessment in the older people patient population.

White matter differences in euthymic bipolar I disorder: a combined magnetic resonance imaging and diffusion tensor imaging voxel-based study.

OBJECTIVES: A broad range of subtle and markedly heterogenous neuroanatomical abnormalities of grey matter and white matter have been reported in bipolar disorder. Euthymic bipolar disorder patients represent a clinically homogenous group in which to identify trait-based biomarkers of bipolar disorder. In this study, we sought to clarify the nature and extent of neuroanatomical differences in a large, clinically homogeneous group of euthymic bipolar disorder patients. METHODS: Structural magnetic resonance imaging (sMRI) was obtained for 60 patients with prospectively confirmed euthymic bipolar I disorder and 60 individually age- and gender-matched healthy volunteers. High angular resolution diffusion tensor imaging (DTI) scans were obtained for a subset of this sample comprising 35 patients and 43 controls. Voxel-based analysis of both sMRI and DTI data sets was performed. RESULTS: Bipolar disorder patients displayed global reductions in white matter volume and fractional anisotropy reductions in the corpus callosum, posterior cingulum, and prefrontal white matter compared with controls. There were corresponding increases in radial diffusivity in the callosal splenium in patients compared with controls. No significant group differences were detected in grey matter. In patients, lithium was associated with a bilateral increase in grey matter volume in the temporal lobes, but not with any DTI parameter. CONCLUSIONS: Euthymic bipolar I disorder is characterized by both diffuse global white matter deficits and potential regional disorganization in interhemispheric and longitudinal tracts, while grey matter appears to be preserved.

Limbic and callosal white matter changes in euthymic bipolar I disorder: an advanced diffusion magnetic resonance imaging tractography study.

BACKGROUND: White matter microstructural changes detected using diffusion tensor imaging have been reported in bipolar disorder. However, findings are heterogeneous, which may be related to the use of analysis techniques that cannot adequately model crossing fibers in the brain. We therefore sought to identify altered diffusion anisotropy and diffusivity changes using an improved high angular resolution fiber-tracking technique. METHODS: Diffusion magnetic resonance imaging data was obtained from 35 prospectively confirmed euthymic bipolar disorder type 1 patients (age 22-59) and 43 control subjects (age 22-59) drawn from a sample of 120 age- and gender-matched demographically similar case-control pairs. Tractography using a constrained spherical deconvolution approach to account for crossing fibers was implemented. Changes in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity between patient and control groups in subdivisions of the corpus callosum, cingulum, and fornix were measured as indicators of trait differences in white matter microstructural organization in bipolar disorder. RESULTS: Patients had significantly reduced fractional anisotropy and increased mean diffusivity and radial diffusivity in all divisions of the corpus callosum, left fornix, and subgenual cingulum compared with control subjects. Axial diffusivity was increased in the fornix bilaterally and right dorsal-anterior cingulum. CONCLUSIONS: By using an improved fiber-tracking method in a clinically homogeneous population, we were able to localize trait diffusivity changes to specific subdivisions of limbic fiber pathways, including the fornix. Our findings extend previous reports of altered limbic system microstructural disorganization as a trait feature of bipolar disorder.

Identification of common variants associated with human hippocampal and intracranial volumes.

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).

Psychiatric illness and driving: Irish psychiatrists' documentation practices.

OBJECTIVE: Psychiatric illness and the use of psychotropic medication are recognised as factors that may impair driving ability. Clinicians in the UK have a legal duty to advise patients on the effects of illness and prescribed medication on driving ability. Although clinicians in Ireland have no equivalent legal obligations, good medical practice suggests that doctors should be aware of whether patients are active drivers, and issue appropriate advice, supported by adequate documentation in clinical notes. METHOD: The initial phase of the study analysed 44 outpatient records and 48 discharge records to ascertain the level of documentation regarding driving status, and advice given to patients regarding the effect of illness or medication on driving ability. The second phase involved distribution of an anonymous questionnaire to 18 psychiatrists employed in the acute psychiatric unit setting. RESULTS: Although there was minimal documentation regarding the potential effect of illness on driving ability, more than 50% of case notes revealed documented advice to patients regarding side-effects of medication and driving ability. Over 50% of case notes contained advice about medication compliance, but none contained cautionary advice about operating machinery. All psychiatrists admitted not being aware of the driving status of every patient they reviewed. Over 50% admitted to advising patients of the effect of illness or medication on driving ability, but fewer reported documenting this advice on every occasion. All psychiatrists reported that they would benefit from training in this area. CONCLUSION: This study suggests that there is underdocumentation of advice given to patients regarding the effect of their symptoms or medication on driving ability. Clinicians need to improve their awareness of patients' driving status, in addition to receiving training on what their responsibilities are in this regard.