Environmental stress alters genetic regulation of novelty seeking in vervet monkeys.

Considerable attention has been paid to identifying genetic influences and gene-environment interactions that increase vulnerability to environmental stressors, with promising but inconsistent results. A nonhuman primate model is presented here that allows assessment of genetic influences in response to a stressful life event for a behavioural trait with relevance for psychopathology. Genetic and environmental influences on free-choice novelty seeking behaviour were assessed in a pedigreed colony of vervet monkeys before and after relocation from a low stress to a higher stress environment. Heritability of novelty seeking scores, and genetic correlations within and between environments were conducted using variance components analysis. The results showed that novelty seeking was markedly inhibited in the higher stress environment, with effects persisting across a 2-year period for adults but not for juveniles. There were significant genetic contributions to novelty seeking scores in each year (h(2) = 0.35-0.43), with high genetic correlations within each environment (rhoG > 0.80) and a lower genetic correlation (rhoG = 0.35, non-significant) between environments. There were also significant genetic contributions to individual change scores from before to after the move (h(2) = 0.48). These results indicate that genetic regulation of novelty seeking was modified by the level of environmental stress, and they support a role for gene-environment interactions in a behavioural trait with relevance for mental health.

Fetal and maternal factors associated with infant mortality in vervet monkeys.

BACKGROUND: Causes of infant death remain unknown in significant proportions of human and non-human primate pregnancies. METHODS: A closed breeding colony with high rates of infant mortality had pregnancies assessed (n=153) by fetal measurements and maternal characteristics. Infant outcome was classified as neonatal death (stillborn or died <48 hours from birth), postnatal death (died 2-30 days) or surviving (alive after 30 days). RESULTS: Fetal size did not predict outcome. Poor maternal glycemic control and low social ranking increased odds for adverse outcome (OR=3.72, P=0.01 and 2.27, P=0.04, respectively). Male sex was over-represented in stillbirths (P=0.04), and many were macrosomic, but size did not associate with maternal glycemic control measured as glycated hemoglobin A1c. Postnatally dead infants were smaller (P<0.01), which associated with behavioral factors and glycemic control. CONCLUSIONS: Fetal growth estimates predicted gestational age but not fetal outcome. Maternal social status and metabolic health, particularly glycemic control, increased risks of adverse pregnancy outcome.

Clinicopathologic characterization of naturally occurring diabetes mellitus in vervet monkeys.

Diabetes mellitus (DM) is a group of chronic metabolic diseases characterized by persistent fasting hyperglycemia, and it can be of either polygenic or monogenic origin. Animal models have played an important role in elucidating the pathophysiology of the polygenic Type 1 and type 2 DM forms; however, useful animal models of the monogenic forms do not exist. The authors describe 4 cases of naturally occurring DM in vervet monkeys (Chlorocebus aethiops sabaeus), 1 of which has clinicopathologic findings consistent with type 2 DM, including persistent hyperglycemia, hypertriglyceridemia, islet amyloidosis, and reduced islet insulin immunostaining. In contrast, the 3 remaining animals have clinicopathologic similarities to a monogenic form of the disease, including a lack of islet amyloidosis and hypertriglyceridemia, as well as normal islet insulin immunostaining. In addition, pedigree analysis conducted on one of these animals is consistent with either an autosomal dominant or mitochondrial inheritance pattern, which supports a monogenic form of DM. The authors thus hypothesize that a naturally occurring monogenic form of diabetes may occur in vervet monkeys, making them a potential animal model for future studies.

Architectonic distribution of the serotonin transporter within the orbitofrontal cortex of the vervet monkey.

To elucidate the organization of the serotoninergic innervation within the orbitofrontal cortex (OFC), serotonin transporter (SERT) density was quantified by autoradiography using [(3)H]cyanoimipramine binding. In six adult vervet monkeys, 15 architectonic areas were delineated according to cytoarchitectonic (Nissl), myeloarchitectonic (Gallyas) and chemoarchitectonic (acetylcholinesterase) criteria to assess SERT distribution at two levels of organization: cortical area and cortical type. For cortical type, the 15 areas were evenly divided into three different categories primarily based upon the degree of granularization of layer IV: agranular, dysgranular, and granular. Within agranular and dysgranular, but not granular cortical types, SERT density was area-specific and progressively decreased in a medial to lateral gradient. Across cortical types, SERT density decreased in a caudal to rostral gradient: agranular>dysgranular>granular. A similar caudal to rostral gradient was seen when serotonin content was measured (using high performance liquid chromatography) in areas representative of each cortical type. Collectively, these results suggest that the serotoninergic innervation is organized according to both cortical type and area, and is thus structured to differentially modulate information processing within the OFC.

Brain metabolic changes associated with symptom factor improvement in major depressive disorder.

BACKGROUND: Symptoms of major depressive disorder (MDD) have been linked to regional brain function through imaging studies of symptom provocation in normal control subjects and baseline studies of subjects with MDD. We examined associations between change in depressive symptom factors and change in regional brain metabolism from before to after treatment of MDD. METHODS: Thirty-nine outpatients with MDD underwent 18F-fluorodeoxyglucose positron emission tomography scanning before and after treatment with either paroxetine or interpersonal psychotherapy. Associations were determined between changes in regional brain metabolism and changes in four Hamilton Depression Rating Scale factors (anxiety/somatization [ANX], psychomotor retardation [PR], cognitive disturbance [COGN], and sleep disturbance) and two corresponding Profile of Mood States subscales (tension [TENS] and fatigue [FATIG]). RESULTS: Improvement in ANX, PR, TENS, and FATIG factors was associated with decreasing ventral frontal lobe metabolism. Improvement in ANX and TENS was also associated with decreasing ventral anterior cingulate gyrus (AC) and anterior insula activity, whereas improvement in PR was associated with increasing dorsal AC activity. COGN improvement was associated with increasing dorsolateral prefrontal cortex metabolism. CONCLUSIONS: Brain regions that show significant relationships with symptom provocation in normal control subjects have similar relationships with MDD symptoms as they improve with treatment.

Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings.

BACKGROUND: In functional brain imaging studies of major depressive disorder (MDD), regional abnormalities have been most commonly found in prefrontal cortex, anterior cingulate gyrus, and temporal lobe. We examined baseline regional metabolic abnormalities and metabolic changes from pretreatment to posttreatment in subjects with MDD. We also performed a preliminary comparison of regional changes with 2 distinct forms of treatment (paroxetine and interpersonal psychotherapy). METHODS: Twenty-four subjects with unipolar MDD and 16 normal control subjects underwent resting F 18 ((18)F) fluorodeoxyglucose positron emission tomography scanning before and after 12 weeks. Between scans, subjects with MDD were treated with either paroxetine or interpersonal psychotherapy (based on patient preference), while controls underwent no treatment. RESULTS: At baseline, subjects with MDD had higher normalized metabolism than controls in the prefrontal cortex (and caudate and thalamus), and lower metabolism in the temporal lobe. With treatment, subjects with MDD had metabolic changes in the direction of normalization in these regions. After treatment, paroxetine-treated subjects had a greater mean decrease in Hamilton Depression Rating Scale score (61.4%) than did subjects treated with interpersonal psychotherapy (38.0%), but both subgroups showed decreases in normalized prefrontal cortex (paroxetine-treated bilaterally and interpersonal psychotherapy-treated on the right) and left anterior cingulate gyrus metabolism, and increases in normalized left temporal lobe metabolism. CONCLUSIONS: Subjects with MDD had regional brain metabolic abnormalities at baseline that tended to normalize with treatment. Regional metabolic changes appeared similar with the 2 forms of treatment. These results should be interpreted with caution because of study limitations (small sample size, lack of random assignment to treatment groups, and differential treatment response between treatment subgroups).

Posttraumatic stress and depressive reactions among Nicaraguan adolescents after hurricane Mitch.

OBJECTIVE: This study determined the severity of posttraumatic stress and depressive reactions among Nicaraguan adolescents after Hurricane Mitch and the relationship of these reactions to objective and subjective features of hurricane exposure, death of a family member, forced relocation, and thoughts of revenge. METHOD: Six months after the hurricane, 158 adolescents from three differentially exposed cities were evaluated by using a hurricane exposure questionnaire, the Child Posttraumatic Stress Disorder Reaction Index, and the Depression Self-Rating SCALE: RESULTS: Severe levels of posttraumatic stress and depressive reactions were found among adolescents in the two most heavily affected cities. Severity of posttraumatic stress and depressive reactions and features of objective hurricane-related experiences followed a "dose-of-exposure" pattern that was congruent with the rates of death and destruction across cities. Level of impact (city), objective and subjective features, and thoughts of revenge accounted for 68% of the variance in severity of posttraumatic stress reaction. Severity of posttraumatic stress reaction, death of a family member, and sex accounted for 59% of the variance in severity of depression. CONCLUSIONS: After a category 5 hurricane, adolescents in heavily affected areas with extreme objective and subjective hurricane-related traumatic features of exposure experience severe and chronic posttraumatic stress and comorbid depressive reactions. The recovery of the severely affected Nicaraguan adolescents is vital to the social and economic recovery of a country ravaged by years of political violence and poverty. These findings strongly indicate the need to incorporate public mental health approaches, including systematic screening and trauma/grief-focused interventions, within a comprehensive disaster recovery program.

Individual differences in response to a stranger: social impulsivity as a dimension of temperament in vervet monkeys (Cercopithecus aethiops sabaeus).

Social impulsivity in response to a stranger was assessed in male vervet monkeys (Cercopithecus aethiops sabaeus) using the Intruder Challenge Test. Vervets (N = 128, ages 3-18 years) were presented with an unfamiliar adult male at the periphery of the home enclosure. An index of impulsivity reflecting variation in the tendency to rapidly approach, engage, and challenge the intruder was derived from factor analysis of behavioral responses. Scale reliability (alpha = .84) and test-retest consistency (intraclass correlation = .83) were high, indicating that this index reliably and efficiently measures a stable aspect of temperament from impulsive to inhibited. Impulsivity scores peaked at age 4, when vervet males typically emigrate from the natal group. The highest ranking males in each group were more likely to score in the moderate range, whereas lower ranking males were more likely to score in the highest (impulsive) or lowest (inhibited) quartiles.

Menstrual cycle-related brain metabolite changes using 1H magnetic resonance spectroscopy in premenopausal women: a pilot study.

Proton magnetic resonance spectroscopy (1H-MRS) was used to assess neurochemical brain changes across the menstrual cycle in five women with premenstrual dysphoric disorder (PMDD) and six control subjects. Women with PMDD and control subjects were scanned on days 8 and 26 within one menstrual cycle (i.e. at times of complete absence and height of PMDD symptoms, respectively). The point resolved spectroscopic sequence (PRESS) was used to localize a voxel of 8 ml in the medial frontal gray matter and in the occipito-parietal white matter. The ratio of N-acetyl-aspartate to creatine in the region of the medial prefrontal cortex and the cingulate gyrus declined significantly from the follicular to the luteal phase in both groups of subjects. The menstrual phase-dependent significant increase in the ratio of choline to creatine was observed in the parietal white matter. The myo-inositol/creatine ratio exhibited a trend toward higher levels in the PMDD patients in the luteal phase of the menstrual cycle. Differences between PMDD and control subjects were not statistically significant. Menstrual cycle phase-dependent changes in ovarian hormonal concentrations may influence the neurochemistry of brain activity in premenopausal women.

Social impulsivity inversely associated with CSF 5-HIAA and fluoxetine exposure in vervet monkeys.

Animal and human research suggests that the central serotonin system is involved in the inhibition of impulsive behavior. Two studies were designed to assess this relationship in male vervet monkeys (Cercopithecus aethiops sabaeus) using a standardized test of impulsivity in a social context: the Intruder Challenge. In the first study, an index of impulsivity in response to an unfamiliar adult male intruder (including latency to approach and aggressive and assertive interactions) was inversely correlated with levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in cisternal cerebrospinal fluid (r = -0.33, p <.01, n = 138). The approach, but not aggressive, component of the Impulsivity Index was the primary contributor to this relationship (partial r = -0.27, p <.01). The second experiment compared responses to the Intruder Challenge after 9 weeks of daily treatment with fluoxetine (2 mg/kg, i.m.) or vehicle. Fluoxetine-treated subjects (n = 6) had significantly lower Impulsivity Index scores than controls (n = 12). The results from these two investigations provide evidence for serotonergic influences on social impulsivity.

Activities of daily living in Alzheimer's disease: neuropsychiatric, cognitive, and medical illness influences.

Using a retrospective data analysis, the authors investigated the relationships between instrumental activities of daily living (IADLs) and neuropsychiatric symptoms, cognitive impairment, and medical illness burden in patients with Alzheimer's disease (AD). One hundred forty-three patients fulfilling the clinical criteria for probable or possible AD in an outpatient clinic were assessed for IADLs, neuropsychiatric symptoms, cognitive impairment, and medical illness burden with the Functional Activities Questionnaire (FAQ), Neuropsychiatric Inventory (NPI), Mini-Mental State Exam (MMSE), and Cumulative Illness Rating Scale-Geriatric (CIRS-G). Both MMSE and NPI scores related significantly to IADLs as measured by the FAQ. Several psychiatric symptoms were correlated significantly with IADLs. FAQ scores had no correlation with CIRS-G. Neuropsychiatric findings also were associated significantly with MMSE and had a weak correlation with CIRS-G scores. IADLs changed with cognition and neuropsychiatric disturbances in AD. Medical illness burden had little influence on functional status and a limited impact on neuropsychiatric symptoms.

Prospective study of posttraumatic stress, anxiety, and depressive reactions after earthquake and political violence.

OBJECTIVE: The authors sought to assess the severity and longitudinal course of posttraumatic stress, anxiety, and depressive reactions among two groups of adults differentially exposed to severe and mild earthquake trauma and a third group exposed to severe violence. They also examined interrelationships among these reactions and predictors of outcome and compared posttraumatic stress disorder (PTSD) symptom category profile and course between those exposed to earthquake and those exposed to violence. METHOD: Seventy-eight non-treatment-seeking subjects were assessed with self-report instruments approximately 1.5 and 4.5 years after the 1988 Spitak earthquake in Armenia and the 1988 pogroms against Armenians in Azerbaijan. RESULTS: The two groups that had been exposed to severe trauma (earthquake or violence) had high initial and follow-up PTSD scores that did not remit over the 3-year interval. Overall, depressive symptoms subsided. Posttraumatic stress, anxiety, and depressive reactions were highly intercorrelated within and across both time intervals. No significant differences in PTSD severity, profile, or course were seen between subjects exposed to severe earthquake trauma versus those exposed to severe violence. CONCLUSIONS: After exposure to severe trauma, either an earthquake or violence, adults are at high risk of developing severe and chronic posttraumatic stress reactions that are associated with chronic anxiety and depressive reactions. Clinical evaluation and therapeutic intervention should include specific attention to these reactions. Early mental health intervention is recommended to prevent their chronicity.

Personality changes in adult subjects with major depressive disorder or obsessive-compulsive disorder treated with paroxetine.

BACKGROUND: Human and animal studies point to 3 dimensions of personality that change during pharmacotherapy with a selective serotonin reuptake inhibitor (SSRI). Specifically, harm avoidance has been found to decrease, social dominance has been found to increase, and hostility in social situations has been found to decrease with SSRI treatment. We sought to determine personality changes in subjects with either major depressive disorder (MDD) or obsessive-compulsive disorder (OCD) treated with paroxetine. We also sought to determine whether or not these personality changes were associated with disease state (MDD vs. OCD) or treatment response (responders vs. nonresponders). METHOD: Thirty-seven subjects diagnosed with either MDD or OCD (according to DSM-IV criteria) completed the Cattell 16 Personality Factor Inventory (16-PF) before and after treatment with paroxetine. Treatment response was defined as a Clinical Global Impressions-Improvement rating of "much" or "very much" improved and a drop in Hamilton Rating Scale for Depression score of at least 50% for MDD or Yale-Brown Obsessive Compulsive Scale score of at least 30% for OCD. RESULTS: No significant differences were found between subjects with MDD and OCD in personality change with treatment. In the whole group, treatment responders had a greater decrease than nonresponders in 16-PF factors relating to harm avoidance. An increase in social dominance factors and a decrease in factors relating to hostility in social situations were found, but these changes were not significantly different between responders and nonresponders. CONCLUSION: These findings indicate that certain personality dimensions change with SSRI treatment and that some of these changes are independent of clinical treatment response.

CSF monoamines, age and impulsivity in wild grivet monkeys (Cercopithecus aethiops aethiops).

Brain monoaminergic activity has been associated with behaviors, such as impulsive risk-taking, that tend to peak during adolescence in humans and nonhuman primates. This study was designed to assess natural variation in monoamine neurotransmitter metabolism in relation to age and behavioral impulsivity in grivet monkeys (Cercopithecus aethiops aethiops) living in their native habitat and subject to natural ecological pressures. Cisternal cerebrospinal fluid, collected from 22 animals living in the Awash National Park, Ethiopia, was assayed for the major metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MHPG). Concentrations of HVA declined significantly from one year of age to older adulthood. Further, a significant curvilinear relationship was identified between age and the 5-HIAA/HVA ratio, with the trough coinciding with the period of adolescence. Finally, behavioral impulsivity, as measured by re-entering baited traps a second time after the animal had already been captured and sampled for CSF, was related to lower levels of MHPG. The results suggest that normal variation in central monoaminergic activity may have functional consequences in wild populations.

Cerebrospinal fluid monoaminergic metabolites differ in wild anubis and hybrid (Anubis hamadryas) baboons: possible relationships to life history and behavior.

The article reports monoaminergic metabolite [homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)], values from the cerebrospinal fluid (CSF) of 27 wild baboons (Papio hamadryas) aged 40 to 140 months. Animals were either anubis, or anubis with hamadryas admixture; males of the latter subspecies generally have a reduced tendency to disperse from their natal groups. Overall, the values and interrelationships among the CSF monoamine metabolites resembled data reported from closely related, captive-housed animals. For example, age was significantly correlated with HVA concentrations (r = -60, p < .05), but not with the other metabolites. Notably, males characterized by hamadryas admixture had significantly higher concentrations of HVA, 5-HIAA, and MHPG (p < .05, respectively), a result possibly driven by differences in serotonergic activity. These data provide initial evidence that variation in central monoaminergic activity, as indicated by CSF monoamine metabolite concentrations, may reflect differences in behavior and life history that have taxonomic and, perhaps, evolutionary significance.

Moral development and psychopathological interference in conscience functioning among adolescents after trauma.

OBJECTIVES: To compare moral development and psychopathological interference with conscience functioning (PI) among adolescents exposed to different degrees of earthquake-related trauma and to investigate the relationship of moral development and PI to exposure to trauma, severity of posttraumatic stress disorder (PTSD) symptoms, postearthquake adversities, and extent of loss of nuclear family members. METHOD: Adolescents (N = 193) from 2 cities at different distances from the epicenter were evaluated. The Stilwell Structured Conscience Interview was used to assess moral development and PI. Structured self-report instruments were used to obtain ratings of severity of earthquake-related trauma, posttraumatic stress symptoms, and postearthquake adversities. RESULTS: Adolescents in the city near the epicenter manifested advanced moral development as compared with their counterparts in the less affected city. Concomitantly, they endorsed responses indicating PI. Levels of PI were significantly correlated with severity of PTSD symptoms. CONCLUSION: In the aftermath of a catastrophic natural disaster, children assume greater responsibilities and confront a multitude of morally challenging interpersonal situations which may result in an advancement of their moral development. Yet, at the same time, PTSD symptoms and negative schematizations of self and others may give rise to disturbances in conscience functioning. The findings suggest that therapeutic consideration should be given to assisting children in integrating the horror of their traumatic experiences and the harshness of posttrauma adversities into an adaptive schema of good and evil in themselves and the world.

Apolipoprotein E genotype and noncognitive symptoms in Alzheimer's disease.

BACKGROUND: The apolipoprotein E (ApoE) epsilon 4 allele confers significant risk for Alzheimer's disease and is associated with a greater amyloid burden in the brain. Future treatments may target molecular mechanisms associated with this allele, and it is important to define any phenotypic characteristics that correspond to this genotype. We sought to clarify the relationship between ApoE status and noncognitive symptoms in Alzheimer's disease patients. METHODS: Possible and probable Alzheimer's disease patients from a clinical trial (n = 605) were assessed with the 10-item Neuropsychiatric Inventory cross-sectionally prior to treatment, and their ApoE genotype was determined. Among the population studied, the following numbers with specific genotypes were studied: 23-2/3, 17-2/4, 209-3/3, 288-3/4, 68-4/4. RESULTS: When correlations were controlled for the patient's level of cognitive impairment, there was no relationship between epsilon 4 dose and any of the 10 noncognitive symptoms assessed, including psychosis, mood changes, and personality alterations. CONCLUSIONS: Among patients with comparable disease severity, the epsilon 4 allele does not confer additional psychiatric morbidity.

Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine.

Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ventrolateral (VLPFC) prefrontal cortical activity mediate the depressed state. Pre- to post-treatment studies indicate that these abnormalities normalize with successful treatment. We performed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of interest (ROIs) for this analysis were drawn by a rater blind to subject identity on the magnetic resonance image of each subject and transferred onto their coregistered PET scans. We hypothesized that DLPFC metabolism would increase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cortex (OFC), and the inferior frontal gyrus (IFG)] would decrease with successful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scale of > 50% and a Clinical Global Improvement Scale rating of 'much' or 'very much' improved. By these criteria, nine of the subjects were classified as treatment responders. These responders had significantly greater decreases in normalized VLPFC and OFC metabolism than did non-responders. There were no significant effects of treatment response on change in the DLPFC or IFG in this sample. However, there was a positive correlation between change in HAM-D scores and change in normalized IFG and VLPFC metabolism. There were no significant interactions with laterality. On pre-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implicate ventral prefrontal-subcortical brain circuitry in the mediation of response to serotonin reuptake inhibitors in MDD.

Apathy is not depression.

If depression is associated with apathy, then they should be expressed together in different dementia syndromes and should co-occur at varying levels of disease severity. The authors performed a cross-sectional comparison of neuropsychiatric symptoms in 30 Alzheimer's disease, 28 frontotemporal dementia, 40 Parkinson's disease, 34 Huntington's disease, and 22 progressive supranuclear palsy patients, using a standardized rating scale (the Neuropsychiatric Inventory). Apathy did not correlate with depression in the combined sample; apathy (r = -0.40, P < 0.0001), but not depression, correlated with lower cognitive function as measured by the Mini-Mental State Examination. The relationship of apathy to depression also varied across diagnostic groups. Apathy is a specific neuropsychiatric syndrome that is distinct from depression. Distinguishing these two syndromes has therapeutic implications.

Midline cerebral morphometry distinguishes frontotemporal dementia and Alzheimer's disease.

We investigated and contrasted midline cerebral structures in frontotemporal dementia (FTD) and Alzheimer's disease (AD). FTD and AD may be difficult to distinguish clinically. FTD typically affects frontal and anterior temporal regions, whereas AD tends to involve more posterior temporal and parietal areas. We hypothesized that disease-specific cerebral alterations would be differentially reflected in corresponding regions of the corpus callosum (CC), pericallosal CSF space (PCS), or their ratio (CC:PCS). Regions-of-interest (ROIs) from midsagittal MRIs in 17 AD, 16 FTD, and 12 elderly control (EC) subjects were analyzed. ROIs were divided into four regions using an anatomic landmark-based computer algorithm and were adjusted for head size variation. FTD subjects had a much smaller anterior CC region and significantly larger PCS area, particularly in anterior regions. AD and EC subjects did not differ significantly in any total or regional ROI measure. Total and anterior CC:PCS ratios were markedly lower in FTD patients. Across groups, total CC:PCS correlated significantly with midsagittal cerebral area and was similarly associated with Mini-Mental State Examination score. Anterior CC (AD) and PCS (FTD) regions exhibited disease-specific relationships to these variables. A discriminant model using two ROI variables correctly classified 91% of AD and FTD patients, comparing favorably with blind clinical MRI diagnostic ratings. Midline cerebral structural alterations reflect differential patterns of cerebral degeneration in AD and FTD, yielding morphometric indices that may facilitate the study of brain-behavior relationships and differential diagnosis of dementia.