Increased pituitary volume in patients with established bipolar affective disorder

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been demonstrated in bipolar disorder (BD), but previous magnetic resonance imaging (MRI) studies of pituitary gland volume in BD have reported variable findings. In this MRI study we investigated pituitary volume in 26 patients with established bipolar I disorder (8 males and 18 females, mean age = 38.4 years) and 24 matched controls (7 males and 17 females, mean age = 38.7 years). The BD patients had a significantly larger pituitary volume as compared with controls, but there was no association between pituitary volume and illness duration, number of manic/depressive episodes, daily medication dosage, family history, or clinical subtype (i.e., psychotic and nonpsychotic). Pituitary volume was larger in females than in males for both groups. These results support previous neuroendocrine findings that implicate HPA axis dysfunction in the core pathophysiological process of BD.     

Changes in gray matter volume in patients with bipolar disorder.

BACKGROUND: Several lines of evidence suggest the presence of neurofunctional abnormalities in patients with bipolar disorder. These functional abnormalities may stem from structural pathology in these or connected brain regions. Previous studies have generally used a region of interest (ROI) approach to study morphologic changes in bipolar disorder with inconsistent findings among research groups, which may reflect differences in how ROIs are defined. Voxel based morphometry (VBM) allows a more exploratory analysis without the necessity for predefined anatomic boundaries. In this study we utilized VBM to compare gray matter volume between groups of bipolar and healthy subjects. METHODS: Thirty-two patients with bipolar disorder and 27 healthy subjects participated in structural magnetic resonance imaging (MRI) scans. MRI images were segmented, normalized to a standard stereotactic space, and compared on a voxel-by-voxel basis using statistical parametric mapping. RESULTS: Bipolar subjects showed increased gray matter in several regions including portions of anterior cingulate, ventral prefrontal cortex, fusiform gyrus and parts of the primary and supplementary motor cortex. Bipolar subjects showed decreased gray matter volume in superior parietal lobule. CONCLUSIONS: These data support suggestions that neurofunctional deficits are related to structural brain abnormalities in patients with bipolar disorder. The increased gray matter observed in several regions suggests that some affected areas may demonstrate volumetric expansion, at least in some patient populations.     

Decreased N-acetylaspartate in children with familial bipolar disorder.

BACKGROUND: Relatively low levels of brain N-acetylaspartate, as measured by magnetic resonance spectroscopy, may indicate decreased neuronal density or viability. Dorsolateral prefrontal levels of N-acetylaspartate have been reported to be decreased in adults with bipolar disorder. We used proton magnetic resonance spectroscopy to investigate dorsolateral prefrontal N-acetylaspartate levels in children with familial bipolar disorder. METHODS: Subjects were 15 children and adolescents with bipolar disorder, who each had at least one parent with bipolar disorder, and 11 healthy controls. Mean age was 12.6 years for subjects and controls. Subjects were allowed to continue current medications. Proton magnetic resonance spectroscopy at 3-Tesla was used to study 8 cm(3) voxels placed in left and right dorsolateral prefrontal cortex. RESULTS: Bipolar subjects had lower N-acetylaspartate/Creatine ratios only in the right dorsolateral prefrontal cortex (p <.02). No differences in myoinositol or choline levels were found. CONCLUSIONS: Children and adolescents with bipolar disorder may have decreased dorsolateral prefrontal N-acetylaspartate, similar to adults with BD, indicating a common neuropathophysiology. Longitudinal studies of at-risk children before the onset and during the early course of bipolar disorder are needed to determine the role of prefrontal N-acetylaspartate as a possible risk marker and/or indication of early bipolar illness progression.     

Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder.

BACKGROUND: N-acetyl aspartate (NAA) is an amino acid present in high concentrations in neurons and is thus a putative neuronal marker. In vivo proton magnetic resonance spectroscopy ((1)H MRS) studies have shown lower NAA concentrations in patients with various neurodegenerative disorders, suggesting decreased neuronal number, size, or function. Dorsolateral prefrontal (DLPF) NAA has not been extensively assessed in bipolar disorder patients, but it could be decreased in view of consistent reports of decreased DLPF cerebral blood flow and metabolism in mood disorders. We measured DLPF NAA in patients with bipolar disorder and healthy control subjects using in vivo (1)H MRS. METHODS: We obtained ratios of NAA, choline, and myoinositol (mI) to creatine-phosphocreatine (Cr-PCr) in bilateral DLPF 8-mL voxels of 20 bipolar patients (10 Bipolar I, 10 Bipolar II) and 20 age- and gender-matched healthy control subjects using (1)H MRS. RESULTS: DLPF NAA/Cr-PCr ratios were lower on the right hemisphere (p<.03) and the left hemisphere (p<.003) in bipolar disorder patients compared with healthy control subjects. CONCLUSIONS: These preliminary data suggest that bipolar disorder patients have decreased DLPF NAA/Cr-PCr. This finding could represent decreased neuronal density or neuronal dysfunction in the DLPF region.     

Hippocampal volume measurement in older adults with bipolar disorder.

OBJECTIVE: Decreased hippocampal volumes have been noted in unipolar depressed subjects, especially in elderly patients and those with cognitive impairment. Initial studies of mixed-aged bipolar subjects and controls have had conflicting findings, with most noting no difference; however this region has not been examined in older bipolar subjects. METHODS: The authors examined the hippocampal volumes of 36 older bipolar subjects (mean age: 58 years) and 29 older normal-comparison (NC) subjects (mean age: 61), using logistic-regression analyses to control for age and gender. Differences between late- and early-onset (before age 45) bipolar subjects were also examined. RESULTS: The left hippocampus was noted to be enlarged in older bipolar subjects, compared with the older NC group (sex and age controlled). No differences were noted in hippocampal volumes by age at onset nor number of previous episodes. The increase in hippocampal volume may be associated with the use of lithium, but not valproic acid. CONCLUSIONS: Left-hippocampal volume is increased in older bipolar subjects compared with NC subjects. The differences were not explained by age at onset, current mood state, or cognitive status, but may be associated with exposure to lithium. This finding would support previous observations about the neural-plasticity effect of lithium.     

Smaller pituitary volume in adult patients with obsessive–compulsive disorder

Aims:  Another structure in the obsessive–compulsive disorder (OCD) circuit may be the pituitary gland because of the fact that limbic–hypothalamic–pituitary–adrenal (LHPA) axis abnormality has been reported in patients with OCD. There has been only one prior study, however, concerning pituitary volumetry, in which the sample was a pediatric group. The purpose of the present study was therefore to investigate this in an adult OCD patient group using magnetic resonance imaging (MRI).
Methods:  Pituitary volume was measured in 23 OCD patients and the same number of healthy control subjects. Volumetric measurements were made on T1-weighted coronal MRI, with 2.40-mm-thick slices, at 1.5 T, and were done blindly.
Results:  A statistically significantly smaller pituitary volume was found in OCD patients compared to healthy controls (age and intracranial volume as covariates). With regard to gender and diagnosis, there was a significant difference in pituitary gland volume ( F  = 4.18, P  < 0.05). In addition, post-hoc analysis indicated near-significant difference in men with OCD as compared with women with OCD ( P  = 0.07) and significant difference between control men and control women ( F  = 10.96, P  < 0.001).
Conclusions:  Taking into consideration that the prior study found decreases in pituitary volume in pediatric patients with OCD as compared with healthy control subjects, future large MRI studies should investigate pituitary size longitudinally, with a careful characterization of hypothalamo-pituitary-adrenal (HPA) function in conjunction with anatomic MRI evaluation.     

Pituitary volume in unaffected relatives of patients with schizophrenia and bipolar disorder

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity has been demonstrated in both schizophrenia and bipolar disorder, but the mechanisms underlying this abnormality are still unclear. Enlarged pituitary volume has been recently reported in patients with first episode psychosis and been interpreted as a consequence of an increased activation of the HPA axis. The aim of this study was to assess the contribution of familial liability to pituitary volume in schizophrenia and bipolar disorder. Pituitary volume may be an indirect measure of HPA axis activity. METHODS: MRI brain scans and measurements of pituitary volumes were obtained for 183 subjects: 26 patients with established schizophrenia or schizoaffective disorder, 44 of their unaffected first-degree relatives (22 familial schizophrenia, 22 non-familial schizophrenia), 29 patients with established bipolar disorder, 38 of their unaffected first-degree relatives, and 46 healthy comparison subjects. RESULTS: We found a significantly larger pituitary volume (effect size=0.7) in unaffected relatives of patients with schizophrenia compared with controls (p=0.002); the pituitary was even larger in relatives of patients with familial schizophrenia (effect size=0.8, p=0.005). We did not find a significant difference in pituitary volume when comparing the relatives of bipolar patients with controls. Among patients, those with schizophrenia who were receiving prolactin-elevating antipsychotics had an increased pituitary volume compared with controls (effect size=1.0, p=0.006). CONCLUSIONS: These results suggest that the larger pituitary volume previously reported in first episode schizophrenia could be partly due to a genetic susceptibility to over-activate the HPA axis.     

Decreased plasma prolactin release in euthymic lithium-treated women with bipolar disorder

In order to evaluate the effect of treatment with citalopram (CIT) and lithium (Li) on hormone levels in women with bipolar disorder, morning plasma prolactin (PRL) and cortisol (CORT) were measured in 14 nonmedicated depressed patients, 13 depressed patients responding to CIT treatment, 17 euthymic patients on long-term Li treatment, and 11 healthy controls. Plasma PRL values in the Li group were significantly lower than those of the three other groups, suggesting a net inhibitory impact of augmentative effects of Li on dopaminergic activity and serotonergic neurotransmission in the central nervous system. Plasma CORT values in nonmedicated depressed patients were significantly higher than those of healthy controls, indicating hyperactivity of the hypothalamic-pituitary-adrenal system in depression, which appears to be a state-dependent phenomenon, and is normalized upon successful treatment with Li and CIT.     

Caudate volume measurement in older adults with bipolar disorder

BACKGROUND: Decreased caudate volumes have been noted in unipolar depressed subjects, especially in the elderly and those with cognitive impairment. No differences have been noted in initial studies of multi-aged bipolar subjects; however, this region has not been examined in older bipolar subjects. METHODS: We examined the caudate nuclei volumes of 36 older bipolar subjects (mean age 58) and 35 older controls (mean age 62) using logistic regression analyses to control for age and gender differences. Differences between late- and early-onset (age-of-onset before age 45) bipolar subjects were also examined, as well as the effect of length of illness. RESULTS: The right caudate was noted to be smaller in older bipolar subjects compared with older controls when controlled for sex and age (p = 0.0448). No differences were noted in overall brain volume nor lateral ventricular volume between the bipolar and control subjects. Late-onset bipolar subjects had a decrease in brain volume (p = 0.035) compared with early-onset bipolar subjects. Late-onset bipolar subjects had a decrease in the right (p = 0.044) and total (p = 0.04) caudate size compared with older controls. CONCLUSIONS: Right caudate volume is decreased in older bipolar subjects compared to controls. Bipolar subjects with late-onset illness have significantly decreased right and total caudate volumes compared to controls. This is affected by neither the length of illness nor the age of onset. Late-onset bipolar subjects have decreased total brain volume compared with early-onset bipolar subjects.     

Increased right amygdala volume in lithium‐treated patients with bipolar I disorder

Usher J, Menzel P, Schneider‐Axmann T, Kemmer C, Reith W, Falkai P, Gruber O, Scherk H. Increased right amygdala volume in lithium‐treated patients with bipolar I disorder. Objective: The amygdala plays a major role in processing emotional stimuli. Fourteen studies using structural magnetic resonance imaging (MRI) have examined the amygdala volume in paediatric and adult patients with bipolar disorder (BD) compared with healthy controls (HC) and reported inconsistent findings. Lithium has been found to increase grey matter volume, and first evidence points towards an effect on regional brain volume such as the amygdala. Method: We examined the amygdala volume of euthymic patients with BD treated with lithium (n = 15), without lithium (n = 24) and HC (n = 41) using structural MRI. Results: Patients treated with lithium exhibited in comparison to HC a larger right absolute (+17.9%, P = 0.015) and relative (+18%, P = 0.017) amygdala volume. There was no significant difference in amygdala volume between patients without lithium treatment and HC. Conclusion: Lithium appears to have a sustained effect on a central core region of emotional processing and should therefore be considered in studies examining BD.     

Decreased thyroid function in Korean women with bipolar disorder receiving valproic acid

We report here two adult female patients with bipolar disorder who developed abnormal thyroid function after short-or long-term administration of valproic acid (VPA). The first patient developed sick euthyroid syndrome (relative to her pretreatment thyroid levels) after only 2 months of treatment with VPA and quetiapine. The second patient, who had no pretreatment medical history including thyroid disease, developed hypothyroidism after several years of treatment with VPA and quetiapine.     

Adult bipolar disorder is continuous with pediatric bipolar disorder.

Considerable debate exists regarding the continuity of bipolar disorder (BD) in children and adolescents. Do affected children continue to have BD as adults? Are pediatric forms of BD distinct from adult forms of the disorder? Here, I argue that, in fact, strictly defined BD I and II in children and adolescents is continuous with adult BD. First, if we take developmental differences into account, children and adults share similar symptoms, since they are both diagnosed according to DSM-IV criteria. Next, retrospective studies indicate that 50% to 66% of adults with BD had onset of their disorder before age 19 years. Early prospective data indicate that adolescents with BD progress to become young adults with BD. Further, family studies of pediatric BD probands find high rates of BD in adult relatives, and pediatric offspring of parents with BD have elevated rates of BD, compared with control subjects. Finally, biological characteristics of pediatric BD (such as treatment response, neurobiology, and genetics) are either shared with adults having BD or fit logically into developmental models of BD. Thus, while not conclusive, a preponderance of data support the hypothesis that pediatric BD is continuous with adult BD. Prospective studies incorporating phenomenological and biological assessment are needed to decisively address this issue.     

Neurological abnormalities in patients with bipolar disorder

A test for agraphaesthesia and the face-hand test were administered to 75 DSM-III bipolar disorder patients. Twenty-five patients (33.3%) had abnormal findings on these tests. Abnormal findings were limited to the group of 54 patients with a history of long-term neuroleptic exposure. There was a strong correlation between the duration of cumulative neuroleptic exposure and the presence of abnormalities. In the group with long-term neuroleptic exposure, family history of affective disorders was negatively correlated with the presence of abnormalities. It appears that long-term neuroleptic exposure may be a contributory causal factor in the development of abnormal neurological signs in bipolar patients. A tendency toward more left-hand errors suggesting hemispheric integration dysfunction was noted in the patients exposed to long-term neuroleptics.     

稳定期双相障碍Ⅰ型患者执行功能及其影响因素研究

目的探讨稳定期双相障碍Ⅰ型患者的执行功能损害及其影响因素。方法纳入115例稳定期双相障碍Ⅰ型患者和115名正常对照,采用言语流畅性测验(动物)、威斯康星卡片分类测验(Wisconsin Card SortingTest,WSCT)、汉诺塔(Tower of Hanoi,TOH)评定执行功能,比较组间的差异及分析患者执行功能的影响因素。结果①患者组言语流畅总数、WSCT(分类数、总错误数和持续错误数)、TOH(总分、平均执行时间)成绩均较正常对照差,差异有统计学意义(P<0.05)。②进一步分层分析,有和无精神病性症状患者组在言语流畅总数、WSCT(分类数、总错误数和持续错误数)和TOH平均执行时间成绩均较对照组差,且前者的TOH总分也较对照组差,上述差异有统计学意义(P<0.05)。无精神病性症状组TOH平均计划时间均长于有精神病性症状组和正常对照组,差异有统计学意义(P<0.05)。③相关分析显示,患者组WSCT各项指标均与发病年龄相关,言语流畅测验和TOH的各指标均分别与汉密尔顿抑郁量表评分、Young躁狂量表评分或病期相关,上述相关均有统计学意义(P<0.05)但相关均不强。未发现稳定时间长短与任何执行功能指标相关(P>0.05)。结论稳定期双相障碍Ⅰ型患者存在明显的执行功能损害,其中WSCT指标独立于临床症状。     

Reduced left hemispheric white matter volume in twins with bipolar I disorder.

BACKGROUND: Although the heritability of bipolar I disorder (BPI) is high, few magnetic resonance imaging (MRI) studies of siblings of bipolar patients exist. We performed MRI brain scans on a nationwide sample of twins with BPI, as well as on their co-twins and a demographically balanced sample of control twin subjects, to detect any structural alterations related to the disorder and to the increased genetic risk. METHODS: The National Hospital Discharge Register, National Population Register, and Finnish Twin Cohorts were used to identify bipolar twins. Structured diagnostic interviews and MRI scans were obtained for 24 twins with BPI, 15 healthy co-twins, and 27 control twin subjects. RESULTS: Patients and co-twins showed a significant decrease in left hemispheric white matter volume. The disparity in patients was -16.1 cm(3) (95% confidence interval [CI] -26.6, -5.6) and in co-twins -11.3 cm(3) (95% CI -22.1, -0.4) compared with control twin subjects. No gray matter decrease was seen in patients or co-twins. CONCLUSIONS: The results of this first large-scale MRI study of twins with BPI, their co-twins, and appropriate control twin subjects, suggest that alterations of the left hemisphere white matter in BPI may reflect genetic factors predisposing to the disorder.     

Smoking and psychosis in patients with bipolar I disorder.

We characterized 67 newly admitted patients in manic or mixed episodes of bipolar I disorder on categorical and continuous measures of smoking and psychosis to test the hypothesis that patients who were smokers would be more likely to demonstrate psychotic features. Smoking did not associate with psychosis in any of our analyses.     

Thalamic volumes in patients with bipolar disorder

There are several hypotheses on functional neuronal networks that modulate mood states and which might form the neuroanatomical basis of bipolar disorder. The thalamus has been reported to be a key structure within the circuits that modulate mood states and might thus play an important role within the aetiology of the bipolar affective disorder. Nevertheless, structural brain imaging studies on the thalamus volume of bipolar patients have shown heterogeneous results. Using structural MRI scanning, we compared the thalamus volume of 41 euthymic bipolar patients to the thalamus volume of 41 well-matched healthy controls. Taking the concomitant medication as a co-variable within the patient group, the analysis of variance revealed a significantly smaller relative volume of the right thalamus in patients not treated with lithium when compared with healthy controls. In contrast, there are no significant differences concerning the thalamus volume between all euthymic bipolar patients and healthy controls. The study only shows findings of a transverse section. No longitudinal analysis was performed. More detailed information on patients’ pharmacological histories could not be obtained. In conclusion, this result may be interpreted as an indication of the impact of the thalamus in the pathogenesis of the bipolar I disorder and emphasises the need for further longitudinal studies in bipolar patients with special attention paid to the concomitant medication, in particular to the role of lithium.