Acioly L.T. Lacerda

Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder

Our knowledge about the neurobiology of suicide is limited. It has been proposed that suicidal behavior generally requires biological abnormalities concomitant with the personality trait of impulsivity/aggression, besides an acute psychiatric illness or psychosocial stressor. We investigated fronto-limbic anatomical brain abnormalities in suicidal and non-suicidal adult female patients with unipolar depression. Our sample consisted of seven suicidal unipolar patients, 10 non-suicidal unipolar patients and 17 healthy female comparison subjects. The criterion for suicidality was one or more documented lifetime suicide attempts. A 1.5T GE Signa Imaging System running version Signa 5.4.3 software was used to acquire the magnetic resonance imaging images. All anatomical structures were measured blindly, with the subjects’ identities and group assignments masked. We used analysis of covariance with age and intracranial volume as covariates and the Tukey–Kramer procedure to compare suicidal patients, non-suicidal patients and healthy comparison subjects. Suicidal patients had smaller right and left orbitofrontal cortex gray matter volumes compared with healthy comparison subjects. Suicidal patients had larger right amygdala volumes than non-suicidal patients. Abnormalities in the orbitofrontal cortex and amygdala in suicidal patients may impair decision-making and predispose these patients to act more impulsively and to attempt suicide.

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.

Cannabis use before age 15 and subsequent executive functioning

BACKGROUND Many studies have suggested that adolescence is a period of particular vulnerability to neurocognitive effects associated with substance misuse. However, few large studies have measured differences in cognitive performance between chronic cannabis users who started in early adolescence (before age 15) with those who started later. AIMS To examine the executive functioning of individuals who started chronic cannabis use before age 15 compared with those who started chronic cannabis use after 15 and controls. METHOD We evaluated the performance of 104 chronic cannabis users (49 early-onset users and 55 late-onset users) and 44 controls who undertook neuropsychological tasks, with a focus on executive functioning. Comparisons involving neuropsychological measures were performed using generalised linear model analysis of variance (ANOVA). RESULTS The early-onset group showed significantly poorer performance compared with the controls and the late-onset group on tasks assessing sustained attention, impulse control and executive functioning. CONCLUSIONS Early-onset chronic cannabis users exhibited poorer cognitive performance than controls and late-onset users in executive functioning. Chronic cannabis use, when started before age 15, may have more deleterious effects on neurocognitive functioning.

Elevated thalamic and prefrontal regional cerebral blood flow in obsessive-compulsive disorder: a SPECT study

Functional neuroimaging studies have pointed to a possible role of cerebral circuits involving the prefrontal and anterior cingulate cortices, the striatum, and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Regional cerebral blood flow (rCBF) of 16 drug-free Brazilian patients with OCD and 17 healthy subjects matched for age, gender, handedness and level of education was measured with [99m-Tc] HMPAO single photon emission computed tomography. Analysis of covariance identified four regions of interest with significantly higher rCBF: the right superior and inferior frontal cortex and the right and left thalamus. Positive correlations between symptom severity measured by Clinical Global Impression scores and rCBF were found in the right and left inferior frontal lobes and in the right basal ganglia. Compulsive behavior was inversely correlated with rCBF in the right thalamus, and duration of illness correlated positively with rCBF in the right and left superior frontal lobes and with the right thalamus. The findings of this SPECT study conducted in Brazil are in agreement with prior studies and provide additional support for the involvement of prefrontal-subcortical circuits in the pathophysiology of OCD. Furthermore, the study suggests that similar brain mechanisms appear to be involved cross-culturally.

Neuropsychological performance and regional cerebral blood flow in obsessive-compulsive disorder.

Convergent findings from neuropsychological and neuroimaging studies have suggested that neural dysfunction in frontal-subcortical circuits may play a central role in the pathophysiology of obsessive-compulsive disorder (OCD). To further examine the relationship between these two sets of findings we investigated both neuropsychological functions and regional cerebral blood flow (rCBF) in a combined study. Fourteen unmedicated patients fulfilling DSM-IV criteria for OCD and 14 healthy controls matched for age, gender, handedness, and education were assessed on neuropsychological tests that included Trail Making Test (TMT), Rey Complex Figure Test (RCF) (copy and 5-min recall), Verbal Fluency Test (VFT), and Wisconsin Card Sorting Test (WCST). rCBF was studied with 99 mTc-hexamethyl-propyleneamine-oxime (HMPAO) single photon emission computed tomography (SPECT). Patients performed more poorly than controls (P<.05) on RCF (copy), VFT, and WCST (perseverative errors). Spearmans correlations indicated that severity of OCD correlated inversely with performance on the RCF (copy and recall scores) and positively with rCBF in the right thalamus. Positive correlations were observed between nonperseverative errors (WCST) and rCBF in frontal areas and anterior cingulate. Perseverative errors (WCST) correlated negatively with rCBF in the right thalamus. These findings are consistent with most previously published studies and suggest neural dysfunctions in the frontal-subcortical circuits probably more pronounced in the right hemisphere. They also extend the existing research, showing associations between deficits in cortical-subcortical circuitry and performance on neuropsychological tests of controlled attention and visuospatial functions.

Morphology of the orbitofrontal cortex in first-episode schizophrenia: Relationship with negative symptomatology

Different studies have documented OFC abnormalities in schizophrenia, but it is unclear if they are present at disease onset or are a consequence of disease process and/or drug exposure. The evaluation of first-episode, drug-naïve subjects allows us to clarify this issue. Magnetic resonance imaging was performed on 43 first-episode, antipsychotic-naïve schizophrenia patients and 53 healthy comparison subjects matched for age, gender, race, and handedness. Gray matter OFC volumes were measured blind to the diagnoses. As compared to controls, patients had greater volumes in left total OFC (p=0.048) and left lateral OFC (p=0.037). Severity of negative symptoms (anhedonia, flattened affect, and alogia) positively correlated with both the left lateral (Spearmans, rho=0.37, p=0.019; rho=0.317, p=0.041; r=0.307, p=0.048, respectively) and the left total OFC (Spearmans, rho=0.384, p=0.014; rho=0.349, p=0.023; rho=0.309, p=0.047, respectively). The present results suggest that first-episode, antipsychotic-naïve schizophrenia subjects exhibit increased OFC volumes that correlate with negative symptoms severity. The OFC, through extensive and complex interconnections with several brain structures with putative role in pathophysiology of schizophrenia including amygdala, hippocampus, thalamus, DLPFC, and superior temporal lobe, may mediate schizophrenia symptoms such as blunting of emotional affect and impaired social functioning. Although the specific neuropathological mechanisms underlying structural abnormalities of the OFC remain unclear, increased OFC volumes might be related to deviations in neuronal migration and/or pruning. Future follow-up studies examining high-risk individuals who subsequently develop schizophrenia at different stages of disease could be especially instructive.

Neurostructural imaging findings in children with post-traumatic stress disorder: brief review.

Child maltreatment has been associated with different psychiatric disorders. Studies on both animals and humans have suggested that some brain areas would be directly affected by severe psychological trauma. The pathophsysiology of post‐traumatic stress disorder (PTSD) appears to be related to a complex interaction involving genetic and environmental factors. Advanced neuroimaging techniques have been used to investigate neurofunctional and neurostructural abnormalities in children, adolescents, and adults with PTSD. This review examined structural brain imaging studies that were performed in abused and traumatized children, and discusses the possible biological mechanisms involved in the pathophysiology of PTSD, the implications and future directions for magnetic resonance imaging (MRI) studies. Published reports in refereed journals were reviewed by searching Medline and examining references of the articles related to structural neuroimaging of PTSD. Structural MRI studies have been performed in adults and children to evaluate the volumetric brain alterations in the PTSD population. In contrast with studies involving adults, in which hippocampus volumetric reduction was the most consistent finding, studies involving children and adolescents with PTSD have demonstrated smaller medial and posterior portions of the corpus callosum.

Measurement of the orbitofrontal cortex: a validation study of a new method

The orbital frontal cortex (OFC) plays a critical role in the pathophysiology of several neuropsychiatric disorders. Few morphometric neuroimaging studies have examined the OFC using different methodologies and have reported discrepant values. Substantial variability in gyri and sulci across individuals as well as unclear landmarks underline the difficulties in obtaining accurate and reliable measurements. We propose a new geometrical method for measuring the OFC taking into account individual brain variability. The OFC was defined by using the intercommissural line and the inferior edge of the frontal lobe as the main landmarks. The medial and lateral subdivisions of OFC were also separately measured using the olfactory sulcus as the boundary to distinguish between them. After resampling and refitting, 10 scans were independently traced by two trained researchers using BRAINS software. Talairach coordinates were identified on each scan from the OFC and surrounding adjacent brain regions to assess the validity of this method. Brain regions were assigned using Talairach Daemon system. OFC volumes were comparable with those previously reported. Sensitivity and specificity for OFC gray matter were 87.6 and 84.8%, respectively. Intraclass coefficients (ICCs) for gray, white, and total OFC were 0.995, 0.994, and 0.997, respectively. ICCs for OFC medial and lateral subdivisions ranged between 0.996 and 0.998. This method appears to be a valid method for measuring the OFC with excellent reliability. This uncomplicated approach is easy to apply and has the potential to be a valuable alternative to the previously published methods.

Magnetic resonance imaging study of the orbitofrontal cortex in autism

The orbitofrontal cortex is involved in multiple psychologic functions, such as emotional and cognitive processing, learning, and social behavior. These functions are variably impaired in individuals with autism. The present study examined the size of the orbitofrontal cortex, and its medial and lateral subdivisions, using magnetic resonance imaging (MRI) scans obtained from 40 non—mentally retarded individuals with autism and 41 healthy controls. No differences were observed between the two groups on any of the orbitofrontal cortex measurements. However, when compared with controls, a smaller right lateral orbitofrontal cortex was observed in children and adolescents with autism, whereas a larger right lateral orbitofrontal cortex was found in adult patients. Interestingly, a positive relationship was found in the patient group between circumscribed interests and all orbitofrontal cortex structures. The present study suggests the absence of global volumetric abnormalities in the orbitofrontal cortex in autism and indicates that the functional disturbances in this structure might not be related to anatomic alterations. (J Child Neurol 2006;21:866—871; DOI 10.2310/ 7010.2006.00199).

The validity and reliability of the portuguese versions of three tools used to diagnose delirium in critically ill patients

OBJECTIVES: The objectives of this study are to compare the sensitivity and specificity of three diagnostic tools for delirium (the Intensive Care Delirium Screening Checklist, the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet) in a mixed population of critically ill patients, and to validate the Brazilian Portuguese Confusion Assessment Method for Intensive Care Units. METHODS: The study was conducted in four intensive care units in Brazil. Patients were screened for delirium by a psychiatrist or neurologist using the Diagnostic and Statistical Manual of Mental Disorders. Patients were subsequently screened by an intensivist using Portuguese translations of the three tools. RESULTS: One hundred and nineteen patients were evaluated and 38.6% were diagnosed with delirium by the reference rater. The Confusion Assessment Method for Intensive Care Units had a sensitivity of 72.5% and a specificity of 96.2%; the Confusion Assessment Method for Intensive Care Units Flowsheet had a sensitivity of 72.5% and a specificity of 96.2%; the Intensive Care Delirium Screening Checklist had a sensitivity of 96.0% and a specificity of 72.4%. There was strong agreement between the Confusion Assessment Method for Intensive Care Units and the Confusion Assessment Method for Intensive Care Units Flowsheet (kappa coefficient = 0.96). CONCLUSION: All three instruments are effective diagnostic tools in critically ill intensive care unit patients. In addition, the Brazilian Portuguese version of the Confusion Assessment Method for Intensive Care Units is a valid and reliable instrument for the assessment of delirium among critically ill patients.