Biomedical subjects

Todd Lencz

Publications and source records attributed to Todd Lencz.

33 records · Page 2Linked to original sources

PubMed2005

Volume reduction in prefrontal gray matter in unsuccessful criminal psychopaths.

BACKGROUND: Although studies of neurologic patients have suggested that prefrontal structural impairments may predispose to sociopathy, it is unknown whether there is a relationship between psychopathy and prefrontal volume in individuals from the community and whether any prefrontal structural impairment is specific to "unsuccessful" (caught) psychopaths as opposed to "successful" (uncaught) psychopaths. This study tests the hypothesis that psychopathy is associated with a reduction in prefrontal gray volume but that this abnormality is specific to unsuccessful psychopaths. METHOD: Prefrontal gray and white matter volumes were assessed using structural magnetic resonance imaging (MRI) in 16 unsuccessful psychopaths, 13 successful psychopaths, and 23 control subjects. RESULTS: Higher total as well as subfactor psychopathy scores (arrogant/deceptive, affective, and impulsive/unstable) were all associated with low prefrontal gray volume. Unsuccessful psychopaths, but not successful psychopaths, had a 22.3% reduction in prefrontal gray matter volume compared with control subjects. CONCLUSIONS: These results demonstrating for the first time a prefrontal structural deficit in community psychopaths provide partial support for a prefrontal theory of psychopathy but highlight an important difference between successful and unsuccessful psychopaths.

Adult↗

PubMed2005

Prospective study of adolescents with subsyndromal psychosis: characteristics and outcome.

OBJECTIVE: The aim of this study was to examine the characteristics and outcome of adolescents with psychotic disorder not otherwise specified (PsyNOS) and brief psychotic disorder (BrPsy), two neglected subsyndromal diagnostic entities. METHODS: As part of an ongoing, naturalistic study investigating adolescents considered to be prodromal for schizophrenia, 29 youngsters (mean age, 16.2 +/- 2.7 years) with PsyNOS or BrPsy were identified as theoretically at highest risk for schizophrenia and followed for over 6 (mean, 22.8 +/- 19.4) months. RESULTS: Contrary to our expectations, only 7 of the 26 individuals (27.0%) with follow-up data developed schizophrenia or schizoaffective disorder, and only 2 subjects (7.7%) retained their diagnosis of BrPsy/PsyNOS. The most frequent other diagnoses at follow-up were mood disorders (34.6%), personality disorders (11.5%), and obsessive-compulsive disorder (7.7%). Regarding severity of outcome, 38.5% of the patients progressed to a syndromal psychotic disorder, 23.1% continued to have attenuated positive symptoms, and 38.4% improved to having attenuated negative symptoms only, or no positive or negative symptoms. BrPsy was associated with lower maximum levels of negative symptoms (p = 0.02) and higher likelihood of symptom remission (p = 0.02). CONCLUSIONS: This study indicates that psychotic symptoms not fulfilling criteria for schizophrenia or a psychotic mood disorder are unreliable predictors of a syndromal psychotic disorder outcome at 2 years. Long-term studies of PsyNOS and BrPsy are needed to clarify where these disorders fall in the developmental course of schizophrenia.

Adolescent↗

PubMed2005

White matter abnormalities in early-onset schizophrenia: a voxel-based diffusion tensor imaging study.

OBJECTIVE: To investigate abnormalities in the structural integrity of brain white matter as suggested by diffusion tensor imaging in adolescents with early-onset schizophrenia (onset of psychosis by age 18). METHOD: Twenty-six patients with schizophrenia and 34 age- and gender-matched healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Fractional anisotropy maps were compared between groups in the white matter using a voxelwise analysis after intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy values in the left anterior cingulate region in close proximity to the caudate nucleus (95% confidence interval of schizophrenic-healthy: -66 to -20). Using regression analysis, the rate of change in fractional anisotropy differed significantly between groups in this region across the age span examined (10-20 years), after adjusting for group differences in premorbid intellectual capacity and parental socioeconomic status. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These data suggest that early-onset schizophrenia is associated with a disruption in the structural integrity of white matter tracts in the anterior cingulate region. These structural abnormalities may contribute to the deficits in motivation, attention, memory, and higher executive functions in adolescents with schizophrenia.

Adolescent↗

PubMed2005

Prefrontal white matter in pathological liars.

BACKGROUND: Studies have shown increased bilateral activation in the prefrontal cortex when normal individuals lie, but there have been no structural imaging studies of deceitful individuals. AIMS: To assess whether deceitful individuals show structural abnormalities in prefrontal grey and white matter volume. METHOD: Prefrontal grey and white matter volumes were assessed using structural magnetic resonance imaging in 12 individuals who pathologically lie, cheat and deceive ('liars'),16 antisocial controls and 21 normal controls. RESULTS: Liars showed a 22-26% increase in prefrontal white matter and a 36-42% reduction in prefrontal grey/white ratios compared with both antisocial controls and normal controls. CONCLUSIONS: These findings provide the first evidence of a structural brain deficitinliars, they implicate the prefrontal cortex as an important (but not sole) component in the neural circuitry underlying lying and provide an initial neurobiological correlate of a deceitful personality.

Adult↗

PubMed2004

Nonspecific and attenuated negative symptoms in patients at clinical high-risk for schizophrenia.

BACKGROUND: Retrospective studies have shown that nonspecific psychopathology and negative symptoms, including social isolation and academic dysfunction, tend to precede onset of psychosis. The present report describes the baseline psychopathology of subjects in the Hillside Recognition and Prevention (RAP) Program, and presents an operationalized classification algorithm for the prospective study of both positive and negative symptoms of clinical high-risk (CHR) for schizophrenia. METHODS: Eighty-two adolescent and young adult patients were characterized using semi-structured interviews of both a parent informant and the patient. The Scale of Prodromal Symptoms (SOPS) was utilized to derive a three-part classification scheme: CHR- subjects (n=20) were defined as having at least one attenuated negative symptom with no positive symptoms; CHR+ subjects (n=42) were defined as having one or more attenuated positive symptoms without psychosis; schizophrenia-like psychosis (SLP) subjects (n=20) were defined as having a psychotic symptom, but without meeting criterion A, B, or C of DSM-IV schizophrenia. RESULTS: Social isolation was the most common presenting symptom. The three RAP subgroups did not significantly differ in levels of attenuated negative and disorganized symptoms, despite the fact that these were not required for inclusion in the CHR+ and SLP groups. Common co-morbid diagnoses included major depression, attention deficit hyperactivity disorder, avoidant personality disorder, and Cluster A personality disorders. CONCLUSIONS: Negative symptoms and other nonspecific behavioral abnormalities represent clinically important phenomena in prodromal patients, and may provide insight into pathophysiologic mechanisms in schizophrenia and possible preventive interventions.

Adolescent↗

PubMed2004

Left middle temporal gyrus activation during a phonemic discrimination task.

There is considerable evidence that receptive language processing depends, at least in part, on cortical tissue in the temporal lobe. Few studies, however, have investigated the neural basis of phonemic discrimination while controlling for non-linguistic and attentional components. In this study nine healthy volunteers discriminated sets of phonemes and tones interspersed by rest periods in a block design paradigm while undergoing fMRI. A comparison of phonemic discrimination with tone discrimination revealed pure left lateralized superior and middle temporal gyrus activations. A comparison of phonemic discrimination with the rest blocks resulted in areas of activations encompassing the language and non-language components of the task. Our findings are consistent with prior reports demonstrating the involvement of the superior and middle temporal gyrus in phonemic discrimination and stronger left temporal lobe activation during speech compared to non-speech sounds. This study also demonstrates the advantage of tone discrimination control blocks as opposed to conventional rest periods to isolate the pure language component of phonemic discrimination.

Adult↗

PubMed2004

Hippocampal structural asymmetry in unsuccessful psychopaths.

BACKGROUND: Structural and functional hippocampal abnormalities have been previously reported in institutionalized psychopathic and aggressive populations. This study assessed whether prior findings of a right greater than left (R > L) functional asymmetry in caught violent offenders generalize to the structural domain in unsuccessful, caught psychopaths. METHODS: Left and right hippocampal volumes were assessed using structural magnetic resonance imaging (MRI) in 23 control subjects, 16 unsuccessful psychopaths, and 12 successful (uncaught) community psychopaths and transformed into standardized space. RESULTS: Unsuccessful psychopaths showed an exaggerated structural hippocampal asymmetry (R > L) relative both to successful psychopaths and control subjects (p <.007) that was localized to the anterior region. This effect could not be explained by environmental and diagnostic confounds and constitutes the first brain imaging analysis of successful and unsuccessful psychopaths. CONCLUSIONS: Atypical anterior hippocampal asymmetries in unsuccessful psychopaths may reflect an underlying neurodevelopmental abnormality that disrupts hippocampal-prefrontal circuitry, resulting in affect dysregulation, poor contextual fear conditioning, and insensitivity to cues predicting capture.

Adult↗

PubMed2003

Corpus callosum abnormalities in psychopathic antisocial individuals.

CONTEXT: Psychopathic antisocial individuals have previously been characterized by abnormal interhemispheric processing and callosal functioning, but there have been no studies on the structural characteristics of the corpus callosum in this group. OBJECTIVES: To assess whether (1) psychopathic individuals with antisocial personality disorder show structural and functional impairments in the corpus callosum, (2) group differences are mirrored by correlations between dimensional measures of callosal structure and psychopathy, (3) callosal abnormalities are associated with affective deficits, and (4) callosal abnormalities are independent of psychosocial deficits. DESIGN: Case-control study. SETTING: Community sample. PARTICIPANTS: Fifteen men with antisocial personality disorder and high psychopathy scores and 25 matched controls, all from a larger sample of 83 community volunteers. MAIN OUTCOME MEASURES: Structural magnetic resonance imaging measures of the corpus callosum (volume estimate of callosal white matter, thickness, length, and genu and splenium area), functional callosal measures (2 divided visual field tasks), electrodermal and cardiovascular activity during a social stressor, personality measures of affective and interpersonal deficits, and verbal and spatial ability. RESULTS: Psychopathic antisocial individuals compared with controls showed a 22.6% increase in estimated callosal white matter volume (P<.001), a 6.9% increase in callosal length (P =.002), a 15.3% reduction in callosal thickness (P =.04), and increased functional interhemispheric connectivity (P =.02). Correlational analyses in the larger unselected sample confirmed the association between antisocial personality and callosal structural abnormalities. Larger callosal volumes were associated with affective and interpersonal deficits, low autonomic stress reactivity, and low spatial ability. Callosal abnormalities were independent of psychosocial deficits. CONCLUSIONS: Corpus callosum abnormalities in psychopathic antisocial individuals may reflect atypical neurodevelopmental processes involving an arrest of early axonal pruning or increased white matter myelination. These findings may help explain affective deficits and previous findings of abnormal interhemispheric transfer in psychopathic individuals.

Adult↗

PubMed2003

Impairments in perceptual competency and maintenance on a visual delayed match-to-sample test in first-episode schizophrenia.

BACKGROUND: Deficits in working memory (WM) have been reported in patients with schizophrenia, but WM is a complex construct dependent on several subprocesses, including input representation (perceptual competency) and holding stimuli on-line (maintenance). A visual delayed match-to-sample task (DMST) was developed to isolate perceptual competency from maintenance during delays. It was hypothesized that patients in the first episode of schizophrenia would exhibit dissociable deficits in both WM domains. METHODS: Performance on the DMST was assessed in 57 patients in the first episode of schizophrenia or schizoaffective disorder and 22 healthy comparison subjects. In phase 1 of the DMST, a complex visual stimulus (target) was followed immediately by a forced choice between 2 test stimuli, and item difficulty (differences between the test stimuli) was titrated until each subject achieved a consistent accuracy (80%-90%) in this no-delay condition. In phase 2, a delay of 4 or 8 seconds with a mask of randomly illuminated pixels was introduced between target and test stimuli; test stimuli were fixed in difficulty level based on phase 1 titration. Main outcome measures were mean item difficulty attained in the no-delay condition and mean accuracy in matching after delay. RESULTS: Compared with controls, patients attained a lower level of difficulty in the no-delay condition (P =.001) and significantly lower accuracy with delay (P =.002). CONCLUSIONS: Deficits in both domains of WM suggest abnormality in the posterior and prefrontal cortexes. These deficits can be observed in a task involving complex visual pattern stimuli using only a brief delay and are present even in unmedicated patients in the first episode of illness.

Adult↗

PubMed2003

Overview of the First Annual Workshop on the Schizophrenia Prodrome.

The First Annual Workshop of the Schizophrenia Prodrome was held in New York City in April 2002. This workshop was organized to address many of the unique methodological issues and controversies facing researchers interested in early intervention and prevention. It brought together representatives of most of the prodromal research groups active at that time as well as a number of consultants. This report summarizes the five major topics discussed throughout the workshop: (1) vulnerability and risk factors, (2) developmental issues, (3) neuroimaging and cognition, (4) alternative prevention strategies, and (5) clinical trials. The outcome of this workshop included consensus on several research issues, recognition that continued discussion and research was needed on many others, the emergence of a spirit of collaboration and collegiality among participants, and the very enthusiastic generation of the articles that make up this special issue of the Schizophrenia Bulletin. Two additional results were the decision to hold similar workshops in the future and the formation of the International Prodromal Research Network to foster international multisite collaborations.

Clinical Trials as Topic↗

PubMed2003

The schizophrenia prodrome revisited: a neurodevelopmental perspective.

Despite the widespread acceptance of the neurodevelopmental model of schizophrenia, its application to research concerned with the prodromal phase of illness is limited. Little recognition has been given to the concept of an enduring biological vulnerability to illness that may be responsive to early intervention. Rather, the focus of most prodromal studies is on emerging positive symptoms. The Recognition and Prevention (RAP) program follows the strategy of being equally concerned with the nonspecific symptoms reflecting the core of schizophrenia and those directly related to psychosis. Data were collected from 62 adolescents (mean age = 16.4 years) during the initial 3-year pilot phase of the RAP program (1998-2001). Subjects were divided into three clinical high-risk groups, characterized by (1) negative and nonspecific symptoms (e.g., social isolation, school failures), the earliest prodrome stage; (2) emerging attenuated positive symptoms of moderate intensity; and (3) severe attenuated (but subpsychotic) positive symptoms, considered most proximal to psychosis. Four risk factors, derived from the neurodevelopmental literature, were selected to reflect the vulnerability core: cognitive deficits, affective disturbances, social isolation, and school failure. All four domains were equally impaired across the three risk groups, supporting the presence of the underlying vulnerability core regardless of the magnitude of emerging positive symptoms. An observational pilot study was also conducted to identify the medications typically used to treat emerging positive symptoms. Antidepressants were used as frequently as antipsychotics to treat adolescents presenting with moderate attenuated positive symptoms. Regardless of type of medication, moderately symptomatic youngsters did quite well over the approximately 1-year followup period. By contrast, adolescents presenting with more severe (but nonpsychotic) attenuated symptoms were treated with antipsychotics, often in combination with other agents. Outcome for the more symptomatic youngsters was, however, more guarded, with nearly half (i.e., 47%) of the group converting to a schizophrenia spectrum psychotic disorder. Nonadherence to medication appeared to be a major risk factor in this group. We conclude that a neurodevelopmental model of schizophrenia is supported by our data and that a range of novel treatment strategies may be neuroprotective by directly affecting the disorder's vulnerability core.

Adolescent↗

PubMed2003

The assessment of "prodromal schizophrenia": unresolved issues and future directions.

Because of the novelty of research with clinical high risk ("prodromal") patients, many unresolved issues exist concerning how the prodromal state is defined and measured. Data are presented from the Recognition and Prevention (RAP) program at the Zucker Hillside Hospital to address several outstanding questions. Baseline attenuated positive symptoms were rated in 42 putatively prodromal patients in the RAP program using the Scale of Prodromal Symptoms (SOPS). Followup data of 6 months or more were available on 34 of these subjects; 9 of these (26.5%) developed psychotic disorders. Patients who developed psychosis had significantly higher SOPS positive symptom scores at baseline than those who did not. Various thresholds, using both total SOPS positive symptom scores and highest single item score, significantly predicted transition to psychosis, which calls into question appropriate cutoffs for the distinction between health, prodromal status, and psychosis. The SOPS positive symptom "conceptual disorganization" was found to be significantly related to disorganized behavior but not to other positive symptoms or to psychotic outcome, suggesting the importance of examining dimensions of psychopathology. The dimensional quantification of prodromal symptom severity may be an important direction for future studies of the assessment of at-risk states.

Adolescent↗

PubMed2003

Smaller anterior hippocampal formation volume in antipsychotic-naive patients with first-episode schizophrenia.

OBJECTIVE: The authors investigated volumetric alterations of the anterior hippocampal formation in patients experiencing a first episode of schizophrenia relative to healthy comparison subjects. METHOD: From contiguous 1.5-mm coronal magnetic resonance images, the hippocampal formation was divided into posterior and anterior segments, and the anterior hippocampal formation was separated from the amygdala. Volumes of the posterior and anterior hippocampal formation and amygdala were computed in 46 (31 male and 15 female) patients experiencing a first episode of schizophrenia and in 34 (21 male and 13 female) healthy comparison subjects. Twenty-four patients were antipsychotic naive at the time of the scan. RESULTS: Patients had significantly reduced total (right plus left) anterior hippocampal formation volume relative to healthy comparison subjects but did not differ in volumes of either the posterior hippocampal formation or amygdala. Similar findings were obtained when analyses were restricted to the antipsychotic-naive subgroup of patients. CONCLUSIONS: These findings suggest that volumetric abnormalities of the hippocampus-amygdala complex may be specific to the anterior hippocampal formation in patients experiencing a first episode of schizophrenia and are consistent with hypotheses regarding abnormal frontolimbic connectivity playing a role in the pathophysiology of the disorder.

Acute Disease↗

PubMed2002

The schizophrenia prodrome: treatment and high-risk perspectives.

Interest in the prodromal stage of schizophrenia-the stage directly preceding the onset of psychosis-has recently undergone a dramatic increase. To a great extent, this has resulted from the convergence of two very different research traditions. Many treatment researchers have moved from a concern with symptom control to an interest in prevention and view the prodrome as the optimal stage to begin intervention with anti-psychotics. High-risk researchers, who view the identification of accurate risk factors as necessarily preceding preventive programs, have begun to move from the premorbid to the prodromal phase as the most effective starting point. Thus, researchers in both traditions have targeted the schizophrenia prodrome as the most likely gateway to prevention. However, clashes between the two traditions in approaches, methodology and research goals have also led to considerable controversy. Such issues as how best to define the prodrome, what the actual risk for schizophrenia is among prodromal individuals, and what type of medication should be used remain largely unresolved. The Hillside Recognition and Prevention (RAP) Program has been designed to address many of these and related questions. Within a naturalistic treatment framework, the RAP program combines both high-risk and treatment research strategies. Preliminary findings from a 3-year RAP pilot study, for example, suggest that the prodrome is a developmentally complex phase of schizophrenia, that it consists of distinctly different subgroups and that novel anti-psychotics are clearly beneficial for some but not all individuals. Depending upon clinical characteristics and phase of the prodrome, anti-depressants also appear highly effective.

Antipsychotic Agents↗

PubMed2002

Prefrontal structural and functional deficits in schizotypal personality disorder.

Structural prefrontal deficits have been reported in patients with schizophrenia, but it is unclear if they are also found in patients with schizophrenia spectrum personality disorders. The hypothesis that a spectrum group will be characterized by prefrontal structural deficits was tested by assessing prefrontal gray and white volumes using magnetic resonance imaging in a community sample of 16 individuals with schizotypal/paranoid personality disorder, 27 comparisons, and 26 psychiatric controls. Frontal neurocognitive functioning was also assessed using the Wisconsin Card Sorting Test and the Continuous Performance Test. The spectrum group showed reduced prefrontal gray volumes and poorer frontal functioning compared to both other groups. Structural deficits were independent of functional deficits and together correctly classified 84.2 percent of subjects. Structural but not functional deficits were abolished after a strict control for antisocial personality was made. Results support the notion that frontal deficits may be centrally involved in the etiology of schizophrenia but also suggest that comorbid antisocial behavior may be one factor accounting for differences in prefrontal structural findings across studies.

Adult↗