Corpus callosum changes in euthymic bipolar affective disorder.

BACKGROUND: Changes in corpus callosum area and thickness have been reported in bipolar disorder. Imaging and limited neuropathological data suggest possible abnormalities in myelination and/or glial function. AIMS: To compare corpus callosum area, thickness and magnetic resonance imaging (MRI) T1 signal intensity in patients with bipolar disorder and healthy controls. METHOD: A total of 48 patients with euthymic bipolar disorder and 46 healthy controls underwent MRI analysis of callosal midsagittal area, callosal thickness and T1 signal intensity. RESULTS: The bipolar group had smaller overall and subregional callosal areas and correspondingly reduced callosal width than the control group. Age correlated negatively with callosal area in the control group but not in the bipolar group. Signal intensity was higher in women than in men in both groups. Signal intensity was reduced in women, but not in men, in the bipolar group. CONCLUSIONS: Observed differences probably relate to diagnosis rather than mood state and bipolar disorder appears to result in morphometric change that overrides changes seen in normal ageing. Intensity changes are consistent with possible altered myelination or glial function. A gender-dependent factor appears to operate and to interact with diagnosis.

Pituitary volume and third ventricle width in euthymic patients with bipolar disorder.

BACKGROUND: Many of the clinical and neuroendocrine features of bipolar disorder involve hypothalamic structures. Although current neuroimaging techniques inadequately resolve the structural components of the hypothalamus, evidence of derangement can be sought by examining the adjacent third ventricle and the functionally related pituitary. AIMS: To investigate the structure and function of the hypothalamic-pituitary-adrenal axis in euthymic patients with bipolar disorder. METHOD: Euthymic adult patients with bipolar disorder (n=49) were compared with matched normal control subjects (n=47). Pituitary volume and third ventricle width were assessed on MRI scans. Basal salivary cortisol levels were measured. RESULTS: The width of the third ventricle in patients with bipolar disorder exceeded that of controls (mean +/- SD (in mm): 3.87 +/- 1.96 versus 2.56 +/- 1.34; d=0.76, ANOVA F=12.7, p=0.001), with the greatest differences found in males. Third ventricle width increased with age across the groups (F=16.97, p<0.001). Pituitary volumes did not differ between patients and controls (mean +/- SD (in mm(3)): 632 +/- 176 versus 679 +/- 159). Overall, females had larger pituitaries than males (703 +/- 160 versus 595 +/- 161; d=0.67, F=9.65, p=0.003; all subjects), but female patients had smaller pituitaries compared to female controls (637 +/- 178 versus 756 +/- 126; d=0.65, F=5.04, p=0.03). No difference was found in a comparable analysis of males. Pituitary volume did not differ between patients prescribed and not prescribed antipsychotic drugs. Basal salivary cortisol levels did not differ between patients and controls. CONCLUSIONS: In euthymic patients with normal basal cortisol levels, pituitary volume and third ventricle width were found to differ from normal controls. These differences were related to gender, may be important in the pathogenesis of bipolar disorder and could link the vegetative and endocrine abnormalities seen in this condition. Such findings may reflect a trait abnormality or be a consequence of previous episodes.

Comparison of short and long versions of the Prudhoe Cognitive Function Test and the K-BIT in participants with intellectual impairment.

The Prudhoe Cognitive Function Test (PCFT) directly measures the cognitive abilities of people with intellectual impairment. This study examined the relationship between this instrument and the Kaufman Brief Intelligence Test (K-BIT) and two shorter versions of the same scale. High correlations between the verbal and performance sections of the K-BIT and the Long PCFT were found with correlation coefficients of 0.85 and 0.78, respectively. Extremely high correlations between the Short versions of the PCFT and the Long version were obtained at 0.97 for Form A and 0.98 for Form B, illustrating that both Short forms and the Long form are essentially interchangeable. The PCFT is a reliable and robust schedule in the assessment of cognitive function in this population.

White matter microstructural abnormalities in euthymic bipolar disorder.

BACKGROUND: Abnormal diffusion parameters are reported in specific brain regions and white matter tracts in bipolar disorder. AIMS: To investigate whether these abnormalities are generalised, and thus evident in large regions of white matter. METHOD: Diffusion parameters were measured at several regions in the corpus callosum and in deep/periventricular white matter in 28 currently euthymic patients with bipolar disorder and controls. White matter hyperintensity loads were assessed. RESULTS: Comparing the whole data-sets using the sign test, in the group with bipolar disorder, mean diffusivity was greater at all 15 sites (P<0.001) and fractional anisotropy was reduced at 13 (P<0.01). The effect of diagnosis was significant for callosal mean diffusivity and fractional anisotropy and for deep/periventricular mean diffusivity (MANCOVA). Comparing individual regions (Mann-Whitney U-test), prefrontal and periventricular mean diffusivity were significantly increased; callosal and occipital fractional anisotropy were significantly reduced. Former substance use and lithium were possible confounding factors. Periventricular white matter hyperintensities were associated with significantly increased periventricular mean diffusivity in individuals with bipolar disorder. CONCLUSIONS: Generalised white matter microstructural abnormalities may exist in bipolar disorder, possibly exacerbated by past substance use and ameliorated by lithium.

Soft neurological signs do not increase with age in euthymic bipolar subjects.

BACKGROUND: Soft neurological signs (SNS) are found to be in excess in bipolar disorder (BD). This paper explores changes in SNS with ageing to ascertain whether BD is associated with a progressive neurological decline or a relatively fixed, persistent deficit. METHODS: 53 euthymic BD subjects and controls, aged 15-55 years, were for examined for the presence of SNS which were rated using a modified Kolakowska battery. RESULTS: In controls, SNS scores increased slowly and significantly with age whereas in BD subjects high scores occurred throughout the age range and were not age dependent. This confirms and extends an earlier, smaller, study which is reanalysed. LIMITATIONS: The study design was cross-sectional whereas a longitudinal study would better reveal changes in soft signs with ageing. CONCLUSIONS: The studies suggest strongly that BD is accompanied by a significant neurobiological deficit which may progress only minimally with increasing age.

Magnetic resonance imaging abnormalities in young euthymic patients with bipolar affective disorder.

Temporal lobe and limbic structures may be abnormal in bipolar disorder. T2-weighted magnetic resonance imaging (MRI) scans frequently show deep white matter lesions. MRI was performed on 50 young (19-39 years) euthymic patients with bipolar disorder and 26 controls. Mean temporal lobe volumes were reduced in patients (right, 9.42 cm3; left, 6.33 cm3) but this could not but this could not be ascribed to a specific structure. Deep white matter lesions were present in 5 patients but no controls raising questions of their aetiological significance.

A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder.

BACKGROUND: A number of studies have reported evidence of cognitive deficits in euthymic bipolar patients. Qualitative reviews of the literature have indicated impairments in executive functions and declarative memory are most consistently reported. However, not all primary studies conducted to date have had sufficient power to detect statistically significant differences and there have been few attempts to quantify the magnitude of impairments. This review aims to combine data from available studies to identify the profile of neuropsychological deficits in euthymic bipolar patients and quantify their magnitude. METHOD: Systematic literature review and meta-analysis. RESULTS: Large effect sizes (d>or=0.8) were noted for aspects of executive function (category fluency, mental manipulation) and verbal learning. Medium effect sizes (0.5

Neuropsychological dysfunction, soft neurological signs and social disability in euthymic patients with bipolar disorder.

BACKGROUND: Neurocognitive deficits exist in euthymic patients with bipolar disorder, but relationships between symptoms, psychosocial and neurological factors remain uncertain. AIMS: To measure neurocognitive function in bipolar disorder and explore links to sub-syndromal mood symptoms, soft neurological signs and psychosocial impairment. METHOD: Attention, memory and executive function were tested in 37 euthymic patients with bipolar disorder and 37 controls. Psychosocial functioning, soft neurological signs and residual mood symptoms were assessed. RESULTS: Performances on tests reflecting executive function and verbal memory (but not attention) were significantly poorer in the bipolar disorder group. Sub-syndromal mood symptoms produced small cognitive effects, predominantly on verbal memory. Soft neurological signs, especially frontal signs, were marked; some patients showed marked social disability which correlated strongly with soft neurological signs but weakly with executive dysfunction, which was linked to illness episodes. CONCLUSIONS: Cognitive dysfunction, social dysfunction and soft signs occur in euthymic patients with bipolar disorder and may represent trait deficits.

Does quetiapine have mood altering properties?

We present a series of three cases who developed manic symptoms on introduction of quetiapine to their medication regime. All were male, with long-standing psychotic illnesses (schizophrenia/schizoaffective disorder), relatively well maintained on medication until their deterioration which prompted a review of their medication. The dose range of prescribed quetiapine was 300-800 mg daily. Two patients had previously received antidepressants without displaying manic symptoms. The mania subsided on withdrawal of quetiapine in two patients. The third patient continued on quetiapine but with the addition of zuclopenthixol depot. Sodium valproate was prescribed to the other two patients, and quetiapine was discontinued. These cases indicate that a side-effect of quetiapine may be mood elevation. An ability to elevate mood while controlling psychoses would be helpful in the treatment of post-psychotic and bipolar depression. Its clinical importance in the control of manic episodes, for which atypical antipsychotics are used increasingly, is uncertain.