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Biomedical subjects

Roberto B Sassi

Publications and source records attributed to Roberto B Sassi.

At least 19 recordsLinked to original sources

Smaller cingulate volumes in unipolar depressed patients.

BACKGROUND: The anterior cingulate cortex is a key structure in brain networks involved in mood regulation. Abnormalities in this brain region are possibly implicated in the pathophysiology of depression. This anatomical magnetic resonance imaging (MRI) study compared cingulate cortex volumes in unipolar depressed patients and age- and gender-matched healthy control subjects. METHODS: Thirty-one unmedicated DSM-IV unipolar patients (24 female, aged 39.2 +/- 11.9 years [mean +/- SD]) and 31 healthy control subjects (24 female, aged 36.7 +/- 10.7 years) were studied in a 1.5-T GE Signa magnet (General Electric Medical Systems, Milwaukee, Wisconsin). Cingulate volumes were compared by analysis of covariance with intracranial volume as the covariate. RESULTS: The unipolar patients had significantly smaller anterior and posterior cingulate volumes bilaterally compared with healthy control subjects. When patients were divided into currently depressed (n = 21) and remitted (n = 10) subgroups, currently depressed patients had significantly smaller anterior and posterior cingulate volumes bilaterally compared with healthy control subjects, whereas remitted patients had significantly smaller left anterior cingulate volumes compared with healthy individuals. CONCLUSIONS: Gray matter abnormalities in the cingulate cortex are implicated in the pathophysiology of unipolar depression. Smaller cingulate volumes in currently depressed patients support the hypothesis that cingulate cortex abnormalities are state dependent, whereas changes in left anterior cingulate might be trait related.

Adolescent↗

MRI study of thalamus volumes in juvenile patients with bipolar disorder.

In vivo imaging studies suggest functional abnormalities of the thalamus in adult patients with bipolar disorder, but the presence of anatomical abnormalities is controversial. Our objective in this study was to compare the thalamus volumes of children and adolescents with bipolar disorder versus healthy controls to determine whether any morphological abnormalities exist early in illness course. We studied 16 patients with bipolar disorder according to DSM-IV criteria (mean age+/-SD=15.5+/-3.4 years) and 21 healthy control subjects (mean age+/-SD=16.9+/-3.8 years). Blinded examiners measured thalamic gray matter volumes with a semiautomated technique. Analysis of covariance, with age, gender, and intracranial brain volume as covariates, revealed no significant differences in left and right thalamic volumes between patients with bipolar disorder and healthy controls. Our findings indicate there are no significant differences in thalamus size between children and adolescents with bipolar disorder and healthy comparison subjects, in contrast to available findings for schizophrenia and first-break psychosis. Any differences in thalamus size that may exist between patients with bipolar disorder and healthy controls must amount to small effect sizes.

Adolescent↗

MRI study of corpus callosum in children and adolescents with bipolar disorder.

This structural magnetic resonance imaging study examined the length, areas, and circularity of the corpus callosum (CC) in 16 children and adolescents with bipolar disorder and 21 healthy controls. Bipolar disorder patients had lower circularity of the CC splenium compared with healthy controls. No significant differences in CC length or area were observed, suggesting that reported CC abnormalities appear late in the course of bipolar disorder.

Adolescent↗

Structural brain changes in bipolar disorder using deformation field morphometry.

The objective of this study was to investigate anatomical brain abnormalities in adult bipolar patients using a deformation field morphometry technique. Our sample consisted of 32 right-handed bipolar I patients (men/women=16/16) and 32 right-handed, age and gender matched healthy controls. Deformation field morphometry analysis was performed on three-dimensional spoiled gradient recalled acquisition images. We found gender-specific structural differences between bipolar patients and healthy individuals. Bipolar men had significantly larger lateral ventricles (especially pronounced in the left hemisphere) and smaller left dorsolateral prefrontal cortex than healthy male controls. Our results are complementary to the findings of functional imaging and post-mortem studies that demonstrate abnormalities in the dorsolateral prefrontal cortex in bipolar patients.

Adolescent↗

1H Magnetic resonance spectroscopy study of dorsolateral prefrontal cortex in unipolar mood disorder patients.

Neuroimaging and postmortem studies have suggested the involvement of the dorsolateral prefrontal cortex (DLPFC) in the pathophysioloy of unipolar disorder. We examined with in vivo 1H magnetic resonance spectroscopy (MRS) the levels of specific metabolites in the DLPFC of adult unipolar patients and the role of illness chronicity on DLPFC abnormalities. Nineteen unmedicated unipolar mood disorder patients and 19 age- and gender-matched healthy controls underwent a short echo-time 1H MRS examination localized to an 8-cm3 single voxel placed in the left DLPFC. There were no significant differences in metabolite levels, including N-acetylaspartate (NAA), phosphocreatine plus creatine (PCr+Cr) and choline-containing-compounds (GPC+PC), between the two groups. However, NAA/PCr+Cr ratios were significantly lower in the chronic than in the less chronically ill patients and healthy controls. The low levels of NAA/PCr+Cr ratios in the left DLPFC of unipolar patients who had been more chronically ill suggest a potential role for illness chronicity in neuronal abnormalities in the DLPFC in unipolar disorder. This could possibly be accounted for by neurodegenerative processes arising with the progression of the illness. Future 1H MRS investigations should longitudinally examine the role of illness chronicity on DLPFC abnormalities and their relationship with the symptoms of unipolar disorder.

Adult↗

Subgenual prefrontal cortex of child and adolescent bipolar patients: a morphometric magnetic resonance imaging study.

The subgenual prefrontal cortex (SGPFC) plays an important role in emotional processing. We carried out a magnetic resonance imaging (MRI) study comparing the volume of the SGPFC in child and adolescent bipolar patients and healthy controls. The sample consisted of 15 children and adolescents who met DSM-IV criteria for bipolar disorder (mean age +/- S.D.=15.5 +/- 3.5 years) and 21 healthy adolescents (mean age +/- S.D.=16.9 +/- 3.8 years). MR images were obtained with a 1.5 T GE Signa Imaging System with Signa 5.4.3 software. SGPFC volumes were measured with the semi-automated software MedX (Sensor Systems, Sterling, VA, USA). ANCOVA was performed to compare SGPFC volumes between groups, using age, gender and intra-cranial volume (ICV) as covariates. The volumes (mean +/- S.D.) of the right and left SGPFC for bipolar patients were 291.27 +/- 88.70 mm(3) and 284.86 +/- 83.98 mm(3), respectively. For healthy controls, the right and left SGPFC volumes were 284.95 +/- 73.33 mm(3) and 307.55 +/- 73.67 mm(3), respectively. There were no statistically significant differences between groups regarding right or left SGPFC volumes. We found no evidence of volumetric abnormalities in the SGPFC of bipolar children and adolescents.

Adolescent↗

1H magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in bipolar disorder patients.

BACKGROUND: Magnetic resonance spectroscopy studies (MRS) reported abnormally low levels of N-acetylaspartate (NAA, a marker of neuronal integrity) in dorsolateral prefrontal cortex (DLPFC) of adult bipolar patients, suggesting possible neuronal dysfunction. Furthermore, recent MRS reports suggested possible lithium-induced increase in NAA levels in bipolar patients. We examined with in vivo (1)H MRS NAA levels in the DLPFC of adult bipolar patients. METHODS: Ten DSM-IV bipolar disorder patients (6 lithium-treated, 4 drug-free) and 32 healthy controls underwent a short echo-time 1H MRS session, which localized an 8 cm3 single-voxel in the left DLPFC using a STEAM sequence. RESULTS: No significant differences between the two groups were found for NAA, choline-containing molecules (GPC+PC), or phosphocreatine plus creatine (PCr+Cr) (Student t-test, p > 0.05). Nonetheless, NAA/PCr+Cr ratios were significantly increased in lithium-treated bipolar subjects compared to unmedicated patients and healthy controls (Mann-Whitney U-test, p < 0.05). LIMITATIONS: Relatively small sample size may have reduced the statistical power of our analyses and the utilization of a single-voxel approach did not allow for the examination of other cortical brain areas. CONCLUSIONS: This study did not find abnormally reduced levels of NAA in left DLPFC of adult bipolar patients, in a sample of patients who were mostly on medications. However, elevated NAA/PCr+Cr ratios were shown in lithium-treated bipolar patients. Longitudinal 1H MRS studies should further examine NAA levels in prefrontal cortex regions in untreated bipolar patients before and after mood stabilizing treatment.

Adult↗

Developmental abnormalities in striatum in young bipolar patients: a preliminary study.

OBJECTIVES: Anatomical abnormalities in the basal ganglia of adult mood disorder patients have been reported. To investigate whether these abnormalities are present early in illness course, we compared the volume of striatal structures in young bipolar patients and healthy controls. METHODS: Brain magnetic resonance images of 15 children and adolescents who met DSM-IV criteria for bipolar disorders and 21 healthy controls were obtained. Measurements were performed manually, by trained evaluators, who were blind to subjects' diagnosis. The volumes of caudate and putamen were compared in patients and controls. RESULTS: The volumes of striatal structures were not significantly different in patients and controls (ANCOVA, p > 0.05). However, we found a significant inverse relationship between age and the volumes of left caudate (r = -0.72, p < 0.01), right caudate (r = -0.66, p = 0.02) and left putamen (r = -0.71, p = 0.01) in bipolar patients, not present in healthy controls. CONCLUSIONS: Abnormalities in striatal development may be involved in the pathophysiology of bipolar disorder.

Adolescent↗

Reduced NAA levels in the dorsolateral prefrontal cortex of young bipolar patients.

OBJECTIVE: Converging evidence implicates prefrontal circuits in the pathophysiology of bipolar disorder. Proton spectroscopy studies performed in adult bipolar patients assessing prefrontal regions have suggested decreased levels of N-acetylaspartate (NAA), a putative marker of neuronal integrity. In order to examine whether such abnormalities would also be found in younger patients, a 1H spectroscopy study was conducted that focused on the dorsolateral prefrontal cortex of children and adolescents with bipolar disorder. METHOD: The authors examined the levels of NAA, creatine plus phosphocreatine, and choline-containing molecules in the left dorsolateral prefrontal cortex of 14 bipolar disorder patients (mean age=15.5 years, SD=3, eight female) and 18 healthy comparison subjects (mean age=17.3, SD=3.7, seven female) using short echo time, single-voxel in vivo 1H spectroscopy. Absolute metabolite levels were determined using the water signal as an internal reference. RESULTS: Bipolar patients presented significantly lower NAA levels and a significant inverse correlation between choline-containing molecules and number of previous affective episodes. No differences were found for other metabolites. CONCLUSIONS: These findings suggest that young bipolar patients have decreased NAA levels in the dorsolateral prefrontal cortex, similar to what was previously reported in adult patients. Such changes may reflect an underdevelopment of dendritic arborizations and synaptic connections. These neuronal abnormalities in the dorsolateral prefrontal cortex of bipolar disorder youth are unlikely to represent long-term degenerative processes, at least in the subgroup of patients where the illness had relatively early onset.

Adolescent↗

Cingulate cortex anatomical abnormalities in children and adolescents with bipolar disorder.

OBJECTIVE: In vivo imaging studies have suggested anatomical and functional abnormalities in the anterior cingulate in adults with mood disorders. This anatomical magnetic resonance imaging study examined the cingulate cortex in children and adolescents with bipolar disorder and matched healthy comparison subjects. METHOD: Sixteen patients (mean age=15.5 years, SD=3.4) with DSM-IV bipolar disorder and 21 matched healthy comparison subjects (mean age=16.9 years, SD=3.8) were studied. Three-dimensional gradient echo imaging was performed (TR=25 msec, TE=5 msec, slice thickness=1.5 mm) in a 1.5-T GE Signa magnet. Cingulate volumes were compared by using analysis of covariance, with age and intracranial volume as covariates. RESULTS: The patients with bipolar disorder had significantly smaller mean volumes relative to the healthy subjects in the left anterior cingulate (mean=2.49 cm(3 [SD=0.28] versus 3.60 cm3 [SD=0.12], respectively), left posterior cingulate (2.53 cm3 [SD=0.32] versus 2.89 cm3 [SD=0.09]), and right posterior cingulate (2.19 cm3 [SD=0.13] versus 2.28 cm3 [SD=0.08]). No significant between-group difference was found for the right anterior cingulate (2.64 cm3 [SD=0.21] versus 2.71 cm3 [SD=0.10]). CONCLUSIONS: The findings indicate smaller cingulate volumes in children and adolescents with bipolar disorder, suggesting that such abnormalities may be present early in the illness course.

Adolescent↗

Anatomical MRI study of corpus callosum in unipolar depression.

Previous studies have suggested abnormal cerebral lateralization in major depressive disorder (MDD). Few controlled MRI studies have investigated the corpus callosum (CC), the largest commissura connecting the two cerebral hemispheres, in MDD. This study investigated anatomical abnormalities in the CC and its subdivisions in MDD patients. Twenty-two unmedicated MDD patients and 39 healthy subjects underwent brain magnetic resonance imaging (MRI). Measurements of the CC and its sub-regions were performed with a semi-automated software (NIH Image, version 1.62). ANCOVA with age, gender, and intra-cranial volume (ICV) as covariates showed no significant differences in CC measurements between patients and controls (df=1,56; p>0.05). However, patients with familial MDD had a significantly larger middle genu area (F(1,45)=4.252; p=0.045) compared to healthy controls, and significantly larger middle genu (F(1,13)=5.366; p=0.037), anterior splenium (F(1,13)=6.27; p=0.026), and middle splenium areas (F(1,13)=4.706; p=0.049) compared to patients with non-familial MDD. Although preliminary, our findings suggest that anatomical abnormalities in CC may be restricted to patients with familial MDD, with possible enlargement of CC in this particular sub-group. The possible role of callosal abnormalities in the pathogenesis of mood disorders should be further examined.

Adolescent↗

Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression.

Morphometric MRI studies suggest decreased hippocampal volumes in currently depressed patients, with conflicting findings for the amygdala. We studied these temporal lobe structures and superior temporal gyrus (STG) in patients with current and remitted major depression. We scanned 31 unmedicated depressed patients (21 currently depressed, 10 remitted) and 31 matched healthy controls with a 3D SPGR sequence in a 1.5 Tesla GE Signa Imaging System. There was a trend towards smaller left amygdala volumes in all depressed patients compared with healthy controls. We found significantly smaller hippocampal volumes bilaterally in currently depressed patients than in remitted patients. Furthermore, we found a statistically significant inverse correlation between length of illness and left hippocampus volumes and right superior temporal gyrus volumes. Our finding of smaller hippocampi in currently depressed patients is consistent with the hypothesis that hypercortisolism could result in hippocampal neurotoxicity in major depression. A smaller hippocampal size may be more characteristic of the depressive state and not be present in remitted patients.

Adolescent↗

Reduced left anterior cingulate volumes in untreated bipolar patients.

BACKGROUND: Functional and morphologic abnormalities of the cingulate cortex have been reported in mood disorder patients. To examine the involvement of anatomic abnormalities of the cingulate in bipolar disorder, we measured the volumes of this structure in untreated and lithium-treated bipolar patients and healthy control subjects, using magnetic resonance imaging (MRI). METHODS: The volumes of gray matter at the right and left anterior and posterior cingulate cortices were measured in 11 bipolar patients not taking any psychotropic medications (aged 38 +/- 11 years, 5 women), 16 bipolar patients treated with lithium monotherapy (aged 33 +/- 11 years, 7 women), and 39 healthy control subjects (aged 37 +/- 10 years, 14 women). Volumetric measurements were made with T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5T, and were done blindly. RESULTS: Using analysis of covariance with age and intracranial volume as covariates, we found that untreated bipolar patients had decreased left anterior cingulate volumes compared with healthy control subjects [2.4 +/-.3 cm3 and 2.9 +/-.6 cm3, respectively; F(1,58) = 6.4, p =.042] and compared with lithium-treated patients [3.3 +/-.5 cm3; F(1,58) = 11.7, p =.003]. The cingulate volumes in lithium-treated patients were not significantly different from those of healthy control subjects. CONCLUSIONS: Our findings indicate that anatomic abnormalities in left anterior cingulate are present in bipolar patients. Furthermore, our results suggest that lithium treatment might influence cingulate volumes in bipolar patients, which could possibly reflect postulated neuroprotective effects of lithium.

Adult↗

Abnormal left superior temporal gyrus volumes in children and adolescents with bipolar disorder: a magnetic resonance imaging study.

Abnormalities in left superior temporal gyrus (STG) have been reported in adult bipolar patients. However, it is not known whether such abnormalities are already present early in the course of this illness. Magnetic resonance imaging (MRI) morphometric analysis of STG was performed in 16 DSM-IV children and adolescents with bipolar disorder (mean age+/-SD 15.5+/-3.4 years) and 21 healthy controls (mean age+/-SD 16.9+/-3.8 years). Subjects underwent a 3D spoiled gradient recalled acquisition MRI examination. Using analysis of covariance with age, gender and intra-cranial brain volume as covariates, we found significantly smaller left total STG volumes in bipolar patients (12.5+/-1.5 cm(3)) compared with healthy controls (13.6+/-2.5 cm(3)) (F=4.45, d.f.=1, 32, P=0.04). This difference was accounted for by significantly smaller left and right STG white matter volumes in bipolar patients. Decreased white matter connections may be the core of abnormalities in STG, which is an important region for speech, language and communication, and could possibly underlie neurocognitive deficits present in bipolar patients.

Adolescent↗

Anatomic evaluation of the orbitofrontal cortex in major depressive disorder.

BACKGROUND: The orbitofrontal cortex (OFC) plays a major role in neuropsychologic functioning including exteroceptive and interoceptive information coding, reward-guided behavior, impulse control, and mood regulation. This study examined the OFC and its subdivisions in patients with MDD and matched healthy control subjects. METHODS: Magnetic resonance imaging (MRI) was performed on 31 unmedicated MDD and 34 control subjects matched for age, gender, and race. Gray matter volumes of the OFC and its lateral and medial subdivisions were measured blindly. RESULTS: The MDD patients had smaller gray matter volumes in right medial [two-way analysis of covariance F(1,60) = 4.285; p =.043] and left lateral OFC [F(1,60) = 4.252; p =.044]. Left lateral OFC volume correlated negatively with age in patients but not in control subjects. Male, but not female patients exhibited smaller left and right medial OFC volumes compared with healthy control subjects of the same gender. CONCLUSIONS: These findings suggest that patients with MDD have reduced OFC gray matter volumes. Although this reduction might be important in understanding the pathophysiology of MDD, its functional and psychopathologic consequences are as yet unclear. Future studies examining the relationship between specific symptomatic dimensions of MDD and OFC volumes could be especially informative.

Adult↗

Normal pituitary volumes in children and adolescents with bipolar disorder: a magnetic resonance imaging study.

The volume of the pituitary gland in adults with bipolar disorder has previously been reported to be smaller than that of healthy controls. Such abnormalities would be consistent with the HPA dysfunction reported in this illness. We conducted a study of children and adolescents with bipolar disorder to determine whether size abnormalities in the pituitary gland are already present early in illness course. Magnetic resonance imaging (MRI) morphometric analysis of the pituitary gland was carried out in 16 DSM-IV children and adolescents with bipolar disorder (mean age+/-sd=15.5+/-3.4 years) and 21 healthy controls (mean age+/-sd=16.9+/-3.8 years). Subjects underwent a 1.5 T MRI, with 3-D Spoiled Gradient Recalled (SPGR) acquisition. There was no statistically significant difference between pituitary gland volumes of bipolar patients compared to healthy controls (ANCOVA, age, gender, and ICV as covariates; F=1.77, df=1,32, P=.19). There was a statistically significant direct relationship between age and pituitary gland volume in both groups (r=.59, df=17, P=.007 for healthy controls; r=.61, df=12, P=.008 for bipolar patients). No evidence of size abnormalities in the pituitary gland was found in child and adolescent bipolar patients, contrary to reports involving adult bipolar patients. This suggests that anatomical abnormalities in this structure may develop later in illness course as a result of continued HPA dysfunction.

Adolescent↗

1H MRS study of dorsolateral prefrontal cortex in healthy individuals before and after lithium administration.

The mechanism of action of lithium is still largely unknown. However, recent animal and human studies suggested the possible neuroprotective effects of this medication. In particular, a recent magnetic resonance spectroscopy (MRS) study showed the increase of cortical brain levels of N-acetyl-aspartate (NAA), a putative marker of neuronal integrity/functioning, in both bipolar patients and normal controls after 4 weeks of lithium administration. We investigated the effects of lithium on NAA levels in a sample of healthy individuals using in vivo 1H MRS in dorsolateral prefrontal cortex (DLPFC), a region likely implicated in the pathophysiology of bipolar disorder. In vivo short echo-time 1H-MRS measurements of 8 cm3 single voxels placed bilaterally in the DLPFC were conducted at baseline and after 4 weeks of lithium administration on 12 healthy individuals (mean age+/-SD = 25.0+/-9.8 years; six males). After lithium administration, no significant differences in NAA, phosphocreatine plus creatine, glycerophosphocholine plus phosphocholine (or choline-containing molecules), and myo-inositol absolute levels or ratios were found in DLPFC (paired t-tests, p > 0.05). Contrary to prior MRS reports in bipolar patients, we found that lithium administration did not significantly increase NAA levels in the DLPFC of healthy individuals. Future longitudinal studies will be needed to further investigate whether chronic lithium treatment increases NAA levels in other brain regions in healthy individuals, and whether it promotes changes in these levels in specific brain regions in bipolar patients.

Adolescent↗

Magnetic resonance imaging study of corpus callosum abnormalities in patients with bipolar disorder.

BACKGROUND: This study was conducted to further examine the hypothesis of abnormalities in size of corpus callosum in subjects with bipolar disorder. METHODS: Sixteen right-handed DSM-IV bipolar I patients and 27 right-handed healthy control subjects were studied. A 1.5-T GE Signa magnet was used, and three-dimensional gradient echo imaging (spoiled gradient recall acquisition) was conducted. Area measurements of corpus callosum were obtained blindly, with a semi-automated software, by a well-trained rater. RESULTS: Right-handed bipolar I patients had significantly smaller total corpus callosum, genu, posterior body, and isthmus areas compared with right-handed healthy control subjects (analysis of covariance with age, gender, and intracranial volume as covariates, p <.05). Partial correlation analyses, controlled for intracranial volumes, found a significant inverse relationship between age and total callosal, genu, anterior body, isthmus, and circularity in healthy control subjects (p <.05) but not in bipolar patients (p >.05). CONCLUSIONS: Smaller callosal areas may lead to altered inter-hemispheric communication and be involved in the pathophysiology and cognitive impairment found in bipolar disorder.

Adult↗