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Biomedical subjects

D Yurgelun-Todd

Publications and source records attributed to D Yurgelun-Todd.

At least 19 recordsLinked to original sources
PubMed2006

Psychopathology factors in first-episode affective and non-affective psychotic disorders.

BACKGROUND: Since the onset, prevalence, and course of specific psychopathological features rarely have been analyzed simultaneously from the start of dissimilar psychotic illnesses, we compared symptom-clusters in first-episode DSM-IV affective and non-affective psychotic disorders. METHODS: Subjects (N=377) from the McLean-Harvard First Episode Project hospitalized for first-lifetime primary psychotic illnesses were followed prospectively for 2 years to verify stable DSM-IV diagnoses. We ascertained initial symptoms from baseline SCID and clinical assessments, applying AMDP and Bonn psychopathology schemes systematically to describe a broad range of features. Final consensus diagnoses were based on intake and follow-up SCID assessments, family interviews, and medical records. Factor-analytic methods defined first-episode symptom-clusters (Factors), and multiple-regression modeling related identified factors to initial DSM-IV diagnoses and to later categories (affective, non-affective, or schizoaffective disorders). RESULTS: Psychopathological features were accommodated by four factors: I represented mania with psychosis; II a mixed depressive-agitated state; III an excited-hallucinatory-delusional state; IV a disorganized-catatonic-autistic state. Each factor was associated with characteristic prodromal symptoms. Factors I and III associated with DSM-IV mania, II with major depression or bipolar mixed-state, III negatively with delusional disorder, IV with major depression and negatively with mania. Factors I and II predicted later affective diagnoses; absence of Factor I features predicted non-affective diagnoses, and no Factor predicted later schizoaffective diagnoses. CONCLUSION: The findings contribute to descriptive categorizations of psychopathology from onset of dissimilar psychotic illnesses. This approach was effective in identifying and subtyping affective psychotic disorders early in their clinical evolution, but non-affective and schizoaffective conditions appear to be more complex and unstable.

Adult↗
PubMed2003

Attributes of long-term heavy cannabis users: a case-control study.

BACKGROUND: Although cannabis is the most widely used illicit drug in the United States, few recent American studies have examined the attributes of long-term heavy cannabis users. METHOD: Using a case-control design, we obtained psychological and demographic measures on 108 individuals, age 30-55, who had smoked cannabis a mean of 18000 times and a minimum of 5000 times in their lives. We compared these heavy users to 72 age-matched control subjects who had smoked at least once, but no more than 50 times in their lives. RESULTS: We found no significant differences between the two groups on reported levels of income and education in their families of origin. However, the heavy users themselves reported significantly lower educational attainment (P < 0.001) and income (P = 0.003) than the controls, even after adjustment for a large number of potentially confounding variables. When asked to rate the subjective effects of cannabis on their cognition, memory, career, social life, physical health and mental health, large majorities of heavy users (66-90%) reported a 'negative effect'. On several measures of quality of life, heavy users also reported significantly lower levels of satisfaction than controls. CONCLUSION: Both objective and self-report measures suggest numerous negative features associated with long-term heavy cannabis use. Thus, it seems important to understand why heavy users continue to smoke regularly for years, despite acknowledging these negative effects. Such an understanding may guide the development of strategies to treat cannabis dependence.

Adult↗
PubMed2001

Neuropsychological performance in long-term cannabis users.

BACKGROUND: Although cannabis is the most widely used illicit drug in the United States, its long-term cognitive effects remain inadequately studied. METHODS: We recruited individuals aged 30 to 55 years in 3 groups: (1) 63 current heavy users who had smoked cannabis at least 5000 times in their lives and who were smoking daily at study entry; (2) 45 former heavy users who had also smoked at least 5000 times but fewer than 12 times in the last 3 months; and (3) 72 control subjects who had smoked no more than 50 times in their lives. Subjects underwent a 28-day washout from cannabis use, monitored by observed urine samples. On days 0, 1, 7, and 28, we administered a neuropsychological test battery to assess general intellectual function, abstraction ability, sustained attention, verbal fluency, and ability to learn and recall new verbal and visuospatial information. Test results were analyzed by repeated-measures regression analysis, adjusting for potentially confounding variables. RESULTS: At days 0, 1, and 7, current heavy users scored significantly below control subjects on recall of word lists, and this deficit was associated with users' urinary 11-nor-9-carboxy-Delta9-tetrahydrocannabinol concentrations at study entry. By day 28, however, there were virtually no significant differences among the groups on any of the test results, and no significant associations between cumulative lifetime cannabis use and test scores. CONCLUSION: Some cognitive deficits appear detectable at least 7 days after heavy cannabis use but appear reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use.

Adolescent↗
PubMed2001

Residual neuropsychologic effects of cannabis.

Acute intoxication with cannabis clearly produces cognitive impairment, but it is less clear how long cognitive deficits persist after an individual stops regular cannabis use. Numerous methodologic difficulties confront investigators in the field attempting to assess the residual neuropsychologic effects of cannabis among heavy users, and these must be understood to properly evaluate available studies. At present, it appears safe to conclude that deficits in attention and memory persist for at least several days after discontinuing regular heavy cannabis use. Some of these deficits may be caused or exacerbated by withdrawal effects from the abrupt discontinuation of cannabis; these effects typically peak after 3 to 7 days of abstinence. It is less clear, however, whether heavy cannabis use can cause neurotoxicity that persists long after discontinuation of use. It seems likely that such long-term effects, if they exist, are subtle and not clinically disabling--at least in the majority of cases.

Attention↗
PubMed2001

Prefrontal gray matter volume reduction in first episode schizophrenia.

Functional measures have consistently shown prefrontal abnormalities in schizophrenia. However, structural magnetic resonance imaging (MRI) findings of prefrontal volume reduction have been less consistent. In this study, we evaluated prefrontal gray matter volume in first episode (first hospitalized) patients diagnosed with schizophrenia, compared with first episode patients diagnosed with affective psychosis and normal comparison subjects, to determine the presence in and specificity of prefrontal abnormalities to schizophrenia. Prefrontal gray and white matter volumes were measured from first episode patients with schizophrenia (n = 17), and from gender and parental socio-economic status-matched subjects with affective (mainly manic) psychosis (n = 17) and normal comparison subjects (n = 17), age-matched within a narrow age range (18--29 years). Total (left and right) prefrontal gray matter volume was significantly reduced in first episode schizophrenia compared with first episode affective psychosis and comparison subjects. Follow-up analyses indicated significant left prefrontal gray matter volume reduction and trend level reduction on the right. Schizophrenia patients showed 9.2% reduction on the left and 7.7% reduction on the right compared with comparison subjects. White matter volumes did not differ among groups. These data suggest that prefrontal cortical gray matter volume reduction is selectively present at first hospitalization in schizophrenia but not affective psychosis.

Adolescent↗
PubMed2001

Permutation testing made practical for functional magnetic resonance image analysis.

We describe an efficient algorithm for the step-down permutation test, applied to the analysis of functional magnetic resonance images. The algorithm's time bound is nearly linear, making it feasible as an interactive tool. Results of the permutation test algorithm applied to data from a cognitive activation paradigm are compared with those of a standard parametric test corrected for multiple comparisons. The permutation test identifies more weakly activated voxels than the parametric test, always activates a superset of the voxels activated by this parametric method, almost always yields significance levels greater than or equal to those produced by the parametric method, and tends to enlarge activated clusters rather than adding isolated voxels. Our implementation of the permutation test is freely available as part of a widely distributed software package for analysis of functional brain images.

Algorithms↗
PubMed2000

Impaired verbal memory is associated with impaired motor performance in schizophrenia: relationship to brain structure.

Deficient ability to take advantage of predictable elements in the performance of cognitive tasks has been proposed as an underlying factor for a number of deviances in schizophrenia. In a schizophrenic sample (n=39), we propose and test the view that certain memory and motor anomalies arise because of a compromise in the capacity to take advantage of the redundant (predictable) features of cognitive tasks. Results demonstrate a relationship between reduced capacity to take advantage of predictable features of two different cognitive processing tasks, one verbal memory, and the other motor. Poorer verbal recall on high-redundancy word lists was associated with a reduced ability to produce synchronous finger tapping in response to a high redundancy auditory stimulus, and inversely correlated with formal thought disorder ratings. These relationships, we suggest, reflect a specific and common schizophrenic deficit in the use of redundancies, not attributable to a generalized deficiency in performance. Structural imaging evidence from a subsample of these subjects (n=16) implicates frontal areas as the locus of this cognitive impairment.

Adult↗
PubMed2000

Planum temporale and Heschl gyrus volume reduction in schizophrenia: a magnetic resonance imaging study of first-episode patients.

BACKGROUND: Magnetic resonance imaging studies in schizophrenia have revealed abnormalities in temporal lobe structures, including the superior temporal gyrus. More specifically, abnormalities have been reported in the posterior superior temporal gyrus, which includes the Heschl gyrus and planum temporale, the latter being an important substrate for language. However, the specificity of the Heschl gyrus and planum temporale structural abnormalities to schizophrenia vs affective psychosis, and the possible confounding roles of chronic morbidity and neuroleptic treatment, remain unclear. METHODS: Magnetic resonance images were acquired using a 1.5-T magnet from 20 first-episode (at first hospitalization) patients with schizophrenia (mean age, 27.3 years), 24 first-episode patients with manic psychosis (mean age, 23.6 years), and 22 controls (mean age, 24.5 years). There was no significant difference in age for the 3 groups. All brain images were uniformly aligned and then reformatted and resampled to yield isotropic voxels. RESULTS: Gray matter volume of the left planum temporale differed among the 3 groups. The patients with schizophrenia had significantly smaller left planum temporale volume than controls (20.0%) and patients with mania (20.0%). Heschl gyrus gray matter volume (left and right) was also reduced in patients with schizophrenia compared with controls (13.1%) and patients with bipolar mania (16.8%). CONCLUSIONS: Compared with controls and patients with bipolar manic psychosis, patients with first-episode schizophrenia showed left planum temporale gray matter volume reduction and bilateral Heschl gyrus gray matter volume reduction. These findings are similar to those reported in patients with chronic schizophrenia and suggest that such abnormalities are present at first episode and are specific to schizophrenia.

Adolescent↗
PubMed2000

Biological aspects of the link between smoking and depression.

A link between smoking and depressive symptoms has been described in the literature for over a decade. The neurotransmitter systems affected by cigarette smoke mirror the neurotransmitter pathways thought to be involved in the biological mechanisms of depression. Cigarette smoke contains several psychoactive chemicals; nicotine is the best studied among these and is widely accepted to be the addictive substance in tobacco. Nicotine binds to nicotinic receptors in the brain, augmenting the release of numerous neurotransmitters, including dopamine, serotonin, norepinephrine, acetylcholine, gamma-aminobutyric acid, and glutamate. Cigarette smoke has other psychoactive properties apart from nicotinic receptor stimulation. For example, it inhibits monoamine oxidase (the enzyme responsible for breaking down the biogenic amine neurotransmitters norepinephrine, serotonin, and dopamine) in the brain. Various antidepressants act through modulation of the biogenic amine neurotransmitter pathways. That the neural substrates modified by both smoking and antidepressant drugs overlap has relevance to smoking cessation. The use of antidepressants as adjuvants to smoking-cessation treatment can enhance cessation success rates. Understanding the neurobiological mechanisms underlying the association between smoking and depression may improve physicians' ability to assist smokers in their efforts to quit and will contribute to a more thorough comprehension of both the biology of addiction and the etiology of depression.

Affect↗
PubMed1999

Subgenual cingulate cortex volume in first-episode psychosis.

OBJECTIVE: Gray matter volume and glucose utilization have been reported to be reduced in the left subgenual cingulate of subjects with familial bipolar or unipolar depression. It is unclear whether these findings are secondary to recurrent illness or are part of a familial/genetic syndrome. The authors' goal was to clarify these findings. METHOD: Volumetric analyses were performed by using magnetic resonance imaging in 41 patients experiencing their first episode of affective disorder or schizophrenia and in 20 normal comparison subjects. RESULTS: The left subgenual cingulate volume of the patients with affective disorder who had a family history of affective disorder was smaller than that of patients with affective disorder with no family history of the illness and the normal comparison subjects. Patients with schizophrenia did not differ from comparison subjects in left subgenual cingulate volume. CONCLUSIONS: Left subgenual cingulate abnormalities are present at first hospitalization for psychotic affective disorder in patients who have a family history of affective disorder.

Adult↗
PubMed1998

A quantitative magnetic resonance imaging study of caudate and lenticular nucleus gray matter volume in primary unipolar major depression: relationship to treatment response and clinical severity.

The authors investigated whether there were differences in caudate and lenticular nucleus volumes in depressed patients relative to comparison subjects, and whether differences in basal ganglia volume were associated with treatment response to fluoxetine. Brain magnetic resonance images were obtained from 38 unipolar depressed patients and 20 matched comparison subjects. Patients were divided into groups of 'responders' and 'non-responders' based on change in the 17-item Hamilton Depression Rating Scale (HDRS) score after a 10-week open trial of fluoxetine, 20 mg/day. There were no group mean differences in caudate and lenticular nucleus volumes between patients and comparison subjects. Female treatment responders tended to have larger caudate nucleus volumes than male 'responders', and also larger right caudate nucleus volumes than their female 'non-responder' counterparts. Baseline HDRS scores correlated negatively with left caudate nucleus volume in depressed patients. Thus, in mild to moderately depressed patients, we were unable to find differences in caudate and lenticular nucleus-gray matter volumes relative to comparison subjects. One possible reason is that caudate nucleus-gray matter volume and severity of depression are inversely correlated, suggesting that severity of depression may be an important covariate when comparing caudate volumes in depressed patients and control subjects.

Adult↗
PubMed1998

Lower left temporal lobe MRI volumes in patients with first-episode schizophrenia compared with psychotic patients with first-episode affective disorder and normal subjects.

OBJECTIVE: Magnetic resonance imaging (MRI) studies of schizophrenic patients have revealed structural brain abnormalities, with low volumes of gray matter in the left posterior superior temporal gyrus and in medial temporal lobe structures. However, the specificity to schizophrenia and the roles of chronic morbidity and neuroleptic treatment in these abnormalities remain unclear. METHOD: Magnetic resonance (1.5-T) scans were obtained from 33 patients with first-episode psychosis and 18 age-matched normal comparison subjects, all right-handed. Sixteen of the patients were diagnosed with affective disorder and 17 with schizophrenia. RESULTS: Quantitative volumetric analysis showed that the patients with first-episode schizophrenia had significantly smaller gray matter volume in the left posterior superior temporal gyrus than did the patients with first-episode affective psychosis or the comparison subjects, with a significant left-less-than-right asymmetry. The schizophrenic patients also showed a smaller gray matter volume of the left posterior amygdala-hippocampal complex than the comparison subjects. Both the patients with schizophrenia and those with affective psychosis had significant left-less-than-right asymmetry of the posterior amygdala-hippocampal complex. CONCLUSIONS: These findings suggest that temporal lobe abnormalities are present at the first hospitalization for schizophrenia and that low volume of the left posterior superior temporal gyrus gray matter is specific to schizophrenia compared with affective disorder.

Adolescent↗
PubMed1998

MRI study of cavum septi pellucidi in schizophrenia, affective disorder, and schizotypal personality disorder.

OBJECTIVE: A cavum between the septi pellucidi may reflect neurodevelopmental anomalies in midline structures of the brain. The authors examined cavum septi pellucidi in subjects with schizophrenia, affective disorder, and schizotypal personality disorder and in normal subjects. METHOD: Thirty schizophrenic patients (15 chronic, 15 first-episode), 16 patients with affective disorder (first-episode), 21 patients with schizotypal personality disorder, and 46 normal subjects were evaluated with magnetic resonance imaging. Cavum septi pellucidi was assessed by counting the number of 1.5-mm slices containing cavum septi pellucidi. RESULTS: The presence or absence of cavum septi pellucidi did not differentiate among groups. However, the prevalence of abnormal cavum septi pellucidi (i.e., cavum septi pellucidi contained on four or more slices) was 30.4% for schizophrenic patients (36.4% for chronic, 25.0% for first-episode), 20.0% for patients with affective disorder, 18.8% for patients with schizotypal personality disorder, and 10.3% for normal subjects. When the authors used the Nopoulos et al. criteria for rating cavum septi pellucidi, which omitted borderline cases with cavum septi pellucidi on three slices, the prevalence of abnormal cavum septi pellucidi increased to 35.0% for schizophrenia (40.0% for chronic, 30.0% for first-episode), 25.0% for affective disorder, 27.3% for schizotypal personality disorder, and 13.0% for normal subjects. There was a statistically significant difference in ratings between schizophrenic and normal subjects. CONCLUSIONS: The results suggest that alterations in midline structures during the course of neurodevelopment may play a role in the pathogenesis of schizophrenia.

Adult↗
PubMed1997

Evidence for a sex-specific residual effect of cannabis on visuospatial memory.

BACKGROUND: In an exploratory study, we used a novel computerized battery of neuropsychological tests of attention to assess residual cognitive impairment in marijuana users. METHODS: We compared 25 college students who were heavy marijuana smokers (who had smoked a median of 29 days in the last 30 days) with 30 students who were light smokers (who had smoked a median of 1 day in the last 30 days). All subjects were tested after a supervised period of abstinence from marijuana and other drugs lasting at least 19 h. RESULTS: Differences between the overall groups of heavy and light smokers did not reach statistical significance on the four subtests of attention administered. However, upon examining data for the two sexes separately, marked and significant differences were found between heavy- and light-smoking women on the subtest examining visuospatial memory. On this test, subjects were required to examine a 6 x 6 'checkerboard' of squares in which certain squares were shaded. The shaded squares were then erased and the subject was required to indicate with the mouse which squares had formerly been shaded. Increasing numbers of shaded squares were presented at each trial. The heavy-smoking women remembered significantly fewer squares on this test, and they made significantly more errors than the light-smoking women. These differences persisted despite different methods of analysis and consideration for possible confounding variables. CONCLUSIONS: This observation suggests that it may be important to study the residual effects of marijuana on men and women separately-particularly since women have been greatly underrepresented in previous studies in this area.

Adolescent↗
PubMed1996

MRI brain abnormalities in chronic schizophrenia: one process or more?

It has been suggested that schizophrenia is primarily a prefrontal-temporal-limbic circuitry disorder. Further, it has been argued that primary neurologic vulnerability to the illness is established only during early stages of brain development and is not progressive. We tested the hypothesis of whether brain volume losses in prefrontal and temporal-limbic regions have occurred either before or after brain growth was hypothesized to be complete in schizophrenia. Nineteen chronic schizophrenic patients and 19 age- and sex-matched normal controls underwent magnetic resonance imaging (MRI). All scans were segmented into gray and white matter and cerebrospinal fluid (CSF) compartments for the frontal and temporal lobes and posterior cerebral hemispheres. Multivariate analysis of variance was used to analyze absolute intracranial cerebrum and subregion volumes, i.e., gray, white and CSF, absolute tissue (i.e., gray plus white) volumes, and tissue to intracranial volume (TCV) ratios. Patients showed significant intracranial volume reductions only in the frontal lobes but highly significantly lower TCV ratios (i.e., greater relative tissue loss) in all three major regions. It is suggested that the observed decreases in frontal intracranial volumes reflect a pathologic process in schizophrenia that impacted the frontal regions before brain growth was complete. We hypothesize that the generalized lower patient TCV ratios are attributable to a process that affected the whole cerebrum over a time period after brain volume had reached its maximum levels.

Adult↗
PubMed1996

The residual cognitive effects of heavy marijuana use in college students.

OBJECTIVE: To assess whether frequent marijuana use is associated with residual neuropsychological effects. DESIGN: Single-blind comparison of regular users vs infrequent users of marijuana. PARTICIPANTS: Two samples of college undergraduates: 65 heavy users, who had smoked marijuana a median of 29 days in the last 30 days (range, 22 to 30 days) and who also displayed cannabinoids in their urine, and 64 light users, who had smoked a median of 1 day in the last 30 days (range, 0 to 9 days) and who displayed no urinary cannabinoids. INTERVENTION: Subjects arrived at 2 PM on day 1 of their study visit, then remained at our center overnight under supervision. Neuropsychological tests were administered to all subjects starting at 9 AM on day 2. Thus, all subjects were abstinent from marijuana and other drugs for a minimum of 19 hours before testing. MAIN OUTCOME MEASURES: Subjects received a battery of standard neuropsychological tests to assess general intellectual functioning, abstraction ability, sustained attention, verbal fluency, and ability to learn and recall new verbal and visuospatial information. RESULTS: Heavy users displayed significantly greater impairment than light users on attention/executive functions, as evidenced particularly by greater perseverations on card sorting and reduced learning of word lists. These differences remained after controlling for potential confounding variables, such as estimated levels of premorbid cognitive functioning, and for use of alcohol and other substances in the two groups. CONCLUSIONS: Heavy marijuana use is associated with residual neuropsychological effects even after a day of supervised abstinence from the drug. However, the question remains open as to whether this impairment is due to a residue of drug in the brain, a withdrawal effect from the drug, or a frank neurotoxic effect of the drug. from marijuana

Adult↗
PubMed1996

Impaired attention in depressive states: a non-specific deficit?

Although cognitive research on attention has advanced significantly in recent years, these advances have produced few specific hypotheses regarding the attentional impairment seen in depression, and few experiments designed to test them. We review the limited neuropsychological literature on impaired attention in depressive states, with emphasis on areas where the findings of modern cognitive research might be applied in the future to design more sophisticated tests of attentional impairment. At present, it is not possible to determine whether the attentional deficits seen in depression are specific to this disorder, or whether they represent a final common pathway of impaired cognition seen in many different mental and organic deficit states, such as schizophrenia and dementias.

Anxiety↗