Severe childhood trauma and clinical and neurocognitive features in schizotypal personality disorder.

OBJECTIVE: Literature suggests that childhood trauma increases vulnerability for schizophrenia-spectrum disorders, including schizotypal personality disorder (SPD). Yet, it remains unexplored whether childhood trauma predicts symptom load and the level of neurocognitive functioning in SPD. METHOD: We included 225 individuals with SPD and 127 healthy controls. Childhood trauma was evaluated using the Childhood Trauma Questionnaire, and schizotypal traits were assessed using the Schizotypal Personality Questionnaire. Standard neurocognitive assessments covered six cognitive domains. RESULTS: All types of reported childhood trauma were significantly associated with SPD, in a linear fashion. Severe sexual abuse showed the greatest magnitude of association with higher cognitive-perceptual load (e.g., ideas of reference, odd belief or magical thinking); severe emotional neglect was associated with interpersonal scores (e.g., excessive social anxiety, constricted affect) within the SPD group. SPD individuals who reported severe trauma showed worse cognitive functioning (i.e., working memory, verbal/visual learning and memory, as well as verbal fluency). CONCLUSIONS: Particular severe childhood trauma types were associated with higher cognitive-perceptual and interpersonal symptoms in SPD, along with worse cognitive functioning. These findings highlight the need for clinicians to enquire about childhood trauma in SPD patients, since unaddressed early adverse experiences may carry long-term negative consequences.

Gender differences and similarities in aggression, suicidal behaviour, and psychiatric comorbidity in borderline personality disorder.

OBJECTIVE: We examined gender differences and similarities in aggression, impulsivity, suicidal behaviour, and psychiatric comorbidity in men and women with borderline personality disorder (BPD) compared with healthy controls. METHOD: A community sample of 511 participants (healthy controls: 81 men and 82 women; BPD patients: 145 men and 203 women) were rigorously characterized using structured diagnostic interviews and symptom severity assessments. RESULTS: In comparison with women with BPD, men were less educated, had higher total Barratt Impulsivity Scale (BIS), BIS-motoric impulsiveness and BIS-non-planning impulsiveness subscale, total Buss-Perry Aggression Questionnaire (BPAQ), and BPAQ-physical aggression subscale scores. Men with BPD were more likely to have comorbid narcissistic, antisocial, paranoid, and schizotypal personality disorders, alcohol and substance use disorders but less likely to have dependent and obsessive-compulsive personality disorders compared to women with BPD. There was a trend toward higher maximum lethality of suicide attempts in men suicide attempters compared with women suicide attempters but no difference between men and women with regard to the proportion of suicide attempters or the number of suicide attempts. CONCLUSION: Men with BPD are more impaired and may be at higher risk of dying by suicide compared to women with BPD.

Realization of a resonant Fermi gas with a large effective range.

We have measured the interaction energy and three-body recombination rate for a two-component Fermi gas near a narrow Feshbach resonance and found both to be strongly energy dependent. Even for de Broglie wavelengths greatly exceeding the van der Waals length scale, the behavior of the interaction energy as a function of temperature cannot be described by atoms interacting via a contact potential. Rather, energy-dependent corrections beyond the scattering length approximation are required, indicating a resonance with an anomalously large effective range. For fields where the molecular state is above threshold, the rate of three-body recombination is enhanced by a sharp, two-body resonance arising from the closed-channel molecular state which can be magnetically tuned through the continuum. This narrow resonance can be used to study strongly correlated Fermi gases that simultaneously have a sizable effective range and a large scattering length.

Evidence for an excited-state Efimov trimer in a three-component Fermi gas.

We observe enhanced three-body recombination in a three-component ;{6}Li Fermi gas attributable to an excited Efimov trimer state intersecting the three-atom scattering threshold near 895 G. From measurements of the recombination rate we determine the Efimov parameters kappa_{*} and eta_{*} for the universal region above 600 G which includes three overlapping Feshbach resonances. The value of kappa_{*} also predicts the locations of loss features previously observed near 130 and 500 G [T. B. Ottenstein, Phys. Rev. Lett. 101, 203202 (2008)10.1103/PhysRevLett.101.203202; J. H. Huckans, Phys. Rev. Lett. 102, 165302 (2009)10.1103/PhysRevLett.102.165302] suggesting they are associated with a ground-state Efimov trimer near threshold. We also report on the realization of a degenerate three-component Fermi gas with approximate SU(3) symmetry.

Three-body recombination in a three-state Fermi gas with widely tunable interactions.

We investigate the stability of a three spin state mixture of ultracold fermionic 6Li atoms over a range of magnetic fields encompassing three Feshbach resonances. For most field values, we attribute decay of the atomic population to three-body processes involving one atom from each spin state and find that the three-body loss coefficient varies by over 4 orders of magnitude. We observe high stability when at least two of the three scattering lengths are small, rapid loss near the Feshbach resonances, and two unexpected resonant loss features. At our highest fields, where all pairwise scattering lengths are approaching a_{t}=-2140a_{0}, we measure a three-body loss coefficient L_{3} approximately 5x10;{-22} cm;{6}/s and a trend toward lower decay rates for higher fields indicating that future studies of color superfluidity and trion formation in a SU(3) symmetric Fermi gas may be feasible.

Positron emission tomography with deoxyglucose-F18 imaging of sleep.

Positron emission tomography with deoxyglucose-F18 was obtained during nighttime sleep in 36 normal volunteers, 12 studied in rapid eye movement sleep (REM period 2), 12 in nonREM sleep, and 12 while awake with eyes closed. Metabolic rate was higher throughout the cortex in REM than nonREM sleep, with differences most marked in the cingulate and frontal cortex, thalamus, and visual association areas. Whole-brain metabolic rates in the waking condition were intermediate between those in REM and nonREM sleep. Metabolism in the primary visual cortex and parts of the lateral temporal lobe was relatively constant in the REM/nonREM conditions. REM sleep did not differ from either the nonREM or waking conditions in hemispheric lateralization of metabolic activity. Compared with REM sleep, nonREM sleep was associated with significantly lower metabolic rates in the temporal and occipital regions, as well as the thalamus.

Striatal size and relative glucose metabolic rate in schizotypal personality disorder and schizophrenia.

BACKGROUND: Schizotypal personality disorder (SPD) shares social deficits and cognitive impairment with schizophrenia, but is not typically characterized by frank psychosis. Because striatal size and functional activity have both been shown to be associated with psychotic symptoms, we carried out the first study of SPD to assess the caudate and putamen for comparison with findings in schizophrenia. METHODS: Patients with SPD (n = 16), schizophrenic patients (n = 42), and age- and sex-matched normal control subjects (n = 47) were assessed with magnetic resonance imaging. All of the patients with SPD and subsamples of the schizophrenic patients (n = 27) and control subjects (n = 32) were also assessed with positron emission tomography using fluorodeoxyglucose F-18. RESULTS: The relative size of the putamen in controls was significantly larger than in patients with SPD and significantly smaller than in schizophrenic patients, while the relative size of the caudate was similar in all 3 groups. Compared with control values, relative glucose metabolic rate in the ventral putamen was significantly elevated in patients with SPD and reduced in schizophrenic patients. When subsamples of schizophrenic patients (n = 10) and patients with SPD (n = 10) both of whom never received medication were compared, this pattern was more marked, with the highest value for the putamen being found in patients with SPD for the ventral slice and the lowest value for the right dorsal putamen. CONCLUSIONS: Patients with SPD showed reduced volume and elevated relative glucose metabolic rate of the putamen compared with both schizophrenic patients and controls. These alterations in volume and activity may be related to the sparing of patients with SPD from frank psychosis.

Sensorimotor gating deficits and hypofrontality in schizophrenia.

Patients with schizophrenia exhibit (a) deficient sensorimotor gating as indexed by impaired prepulse inhibition (PPI) of the startle eyeblink reflex suggesting abnormal automatic information processing and (b) abnormal attentional modulation of PPI suggesting impaired controlled information processing. Here we test the hypothesis of deficient attentional modulation of PPI in schizophrenia as a defect in the interrelationship between frontal lobe functions of planning and executive action and posterior function of processing of sensory stimulation using positron emission tomography (PET). Consistent with the literature, our findings indicate that unmedicated schizophrenia patients exhibit lower frontal/occipital ratios (termed "hypofrontality") compared with healthy controls (n=15 in each group) during a standard tone-length-judgment (attention-to-prepulse) task. Moreover, better attentional modulation of PPI was associated with higher frontal/occipital ratios in the control, but not the patient group. These findings extend animal models to humans by demonstrating the importance of frontal and occipital lobe coordination in the modulation of PPI.

Thalamic activation during an attention-to-prepulse startle modification paradigm: a functional MRI study.

BACKGROUND: Prepulse inhibition (PPI) of the startle reflex reflects early stages of information processing and is modulated by selective attention. Animal models indicate medial frontal-thalamic circuitry is important in PPI modulation. We report data from the first functional magnetic resonance imaging (fMRI) study examining whether attending to or ignoring a prepulse differentially activates brain areas within this circuitry. METHODS: Ten healthy subjects received structural and functional MRI. During fMRI acquisition, subjects heard intermixed attended and ignored tones serving as prepulses to the startle stimulus. Regions of interest were traced on structural MRI and coregistered to fMRI images. RESULTS: Greater amplitude fMRI blood-oxygen-level-dependent response to attended than ignored PPI conditions occurred in the right thalamus, and bilaterally in the anterior and mediodorsal thalamic nuclei, whereas the startle-alone condition showed deactivation. In transitional medial cortex (Brodmann Area 32), which is involved in affective processing of noxious stimuli, the startle-alone condition elicited the greatest response, the attended-PPI condition showed the smallest response, and the ignored-PPI condition was intermediate. CONCLUSIONS: These findings extend animal models to humans by indicating thalamic involvement in the modulation of PPI. Further fMRI investigations may elucidate other key structures in the circuitry underlying normal and disordered modulation of PPI.

Attentional stages of information processing during a continuous performance test: a startle modification analysis.

This study of 31 college students employed the startle eye-blink modification (SEM) technique to index both early and later stages of attentional processing during a memory-load version of the Continuous Performance Test (CPT). Participants viewed a series of digits and pressed a button after the digit 7 of each 3-7 sequence. A startling noise burst was presented either 120 or 1,200 ms following three preselected prepulses: target (3), nontarget (non-3 and non-7 digits), or target plus distractor (3 and simultaneous tone distractor). Greater startle inhibition occurred 120 ms following target and target-plus-distractor prepulses compared with nontargets, indicating early selective attention. No difference was observed between SEM during target and target-plus-distractor prepulses, suggesting the distractor was effectively ignored. At 1,200 ms, the three prepulse types produced nondifferential inhibition, suggesting that modality-specific selective attention occurs in anticipation of the presentation of the next CPT prepulse. These findings indicate that SEM distinguishes between different early selective attention and later anticipatory attention subprocesses underlying the CPT.

Deformation-based morphometry and its relation to conventional volumetry of brain lateral ventricles in MRI.

Deformation-based morphometry (DBM) is a useful technique to detect morphological differences over the entire brain since it analyses positional differences between every voxel and a standard brain. In this report we compare DBM to semimanual tracing of brain ventricles in a population of 39 patients with schizophrenia. High-resolution T(1)-weighted magnetic resonance images were obtained and processed with DBM and interactive tracing software. We evaluate the validity of the DBM in two different approaches. First, we divide subjects into two groups based on the mean ventricular/brain ratios and compute statistical maps of displacement vectors and their spatial derivatives. This analysis demonstrates a striking consistency of the DBM and visual tracing results. We show that restricting the information about the deformation fields by computing the local Jacobian determinant (as a measure of volume change) provides evidence of the shape of ventricular deformation which is unavailable from ventricular volume measures alone. Second, we compute a mean measure of the Jacobian values over the entire ventricles and observe a correlation of r = 0.962 with visual tracing based ventricular/brain ratios. The results support the usefulness and validity of DBM for the local and global examination of brain morphology.

Temporal lobe volume determined by magnetic resonance imaging in schizotypal personality disorder and schizophrenia.

The volumes of the whole temporal lobe, the superior temporal gyrus and the corpus callosum were measured on magnetic resonance images from 13 patients with schizotypal personality disorder (SPD), 27 patients with schizophrenia, and 31 age- and sex-matched controls. Temporal lobe structures were traced on consecutive 1.2mm thick SPGR images. Both patient groups had smaller temporal lobes than normal volunteers, a difference that was more marked for the area outside the superior temporal gyrus than for the STG. Correcting for brain volume diminished differences between normal subjects and schizophrenia patients, but the differences between normal subjects and SPD patients remained. Normal volunteers and SPD patients showed significant correlations between the sagittal section area of the posterior portion of the corpus callosum, which carries temporal interhemispheric connections, and the white matter volume of the temporal lobe. While the sample size is modest, taken together, these results suggest that the psychopathological symptoms of SPD may be related to temporal gray matter loss with relatively intact white matter connectivity, while the cognitive and psychotic symptoms of schizophrenia may be related to temporal gray loss combined with disruption of normal patterns of white matter development.

Patterns of cortical activity and memory performance in Alzheimer's disease.

BACKGROUND: Declarative memory changes are the hallmark of Alzheimer's disease, although their functional neuroanatomy is not restricted to a single structure. Factor analysis provides statistical methods for evaluating patterns of cerebral changes in regional glucose uptake. METHODS: Thirty-three Alzheimer's patients and 33 age- and gender-matched control subjects were studied with magnetic resonance imaging and positron emission tomography with [(18)F] deoxyglucose. During the tracer-uptake period, subjects performed a serial verbal learning task. Cortical activity was measured in 32 regions of interest, four in each lobe on both hemispheres. RESULTS: Factor analysis with varimax rotation identified seven factors explaining 80% of the variance ("parietal cortex," "occipital cortex," "right temporo-prefrontal areas," "frontal cortex," "motor strip," "left temporal cortex," and "posterior temporal cortex"). Relative to control subjects, Alzheimer's patients showed significantly reduced values on the factors occipital cortex, right temporo-prefrontal areas, frontal cortex, and left temporal cortex. The factor temporo-prefrontal areas showed large differences between patients with good and poor performance, but little difference when control subjects were similarly divided. CONCLUSIONS: Findings suggest that Alzheimer's disease is characterized by altered patterns of cortical activity, rather than deficits in a single location, and emphasize the importance of right temporo-prefrontal circuitry for understanding memory deficits.

Magnetic resonance imaging of the thalamic mediodorsal nucleus and pulvinar in schizophrenia and schizotypal personality disorder.

BACKGROUND: The importance of neuronal interactions in development, the cortical dependence of many thalamic nuclei, and the phenomenon of transsynaptic degeneration suggest possible abnormalities in thalamic nuclei with connections to other brain regions implicated in schizophrenia. Because frontal and temporal lobe volumes are diminished in schizophrenia, volume loss could characterize their primary thalamic relay nuclei (mediodorsal nucleus [MDN] and pulvinar). METHODS: Tracers delineated the thalamus, MDN, and pulvinar on contiguous 1.2-mm magnetic resonance images in 12 schizophrenic patients, 12 with schizotypal personality disorder (SPD), and 12 normal control subjects. The MDN and pulvinar were rendered visible by means of a Sobel intensity-gradient filter. RESULTS: Pixel overlap for delineation of all structures by independent tracers was at least 80%; intraclass correlations were r = 0.78 for MDN and r = 0.83 for pulvinar. Pulvinar volume was smaller in schizophrenic (1.22 +/- 0.24 cm(3)) and SPD (1.20 +/- 0.23 cm(3)) patients than controls (1.37 +/- 0.25 cm(3)). Differences for MDN were not statistically significant; however, when expressed as percentage of total brain volume, pulvinar and MDN together were reduced in SPD (0.14%) and schizophrenic (0.15%) patients vs controls (0.16%). Reductions were more prominent in the left hemisphere, with MDN reduced only in the schizophrenic group, and pulvinar in both patient groups. Total thalamic volume did not differ among the 3 groups. CONCLUSIONS: Measurement of MDN and pulvinar in magnetic resonance images is feasible and reproducible. Schizophrenic and SPD patients have volume reduction in the pulvinar, but only schizophrenic patients show reduction relative to brain volume in MDN.

Feeling unreal: a PET study of depersonalization disorder.

OBJECTIVE: The goal of this study was to assess brain glucose metabolism and its relationship to dissociation measures and clinical symptoms in DSM-IV depersonalization disorder. METHOD: Positron emission tomography scans coregistered with magnetic resonance images of eight subjects with depersonalization disorder were compared to those of 24 healthy comparison subjects. The two groups did not differ in age, sex, education, performance on a baseline neuropsychological battery, or performance on a verbal learning task administered during [(18)F]fluorodeoxyglucose uptake. A cortical analysis by individual Brodmann's areas was performed. RESULTS: Compared to the healthy subjects, subjects with depersonalization disorder showed significantly lower metabolic activity in right Brodmann's areas 22 and 21 of the superior and middle temporal gyri and had significantly higher metabolism in parietal Brodmann's areas 7B and 39 and left occipital Brodmann's area 19. Dissociation and depersonalization scores among the subjects with depersonalization disorder were significantly positively correlated with metabolic activity in area 7B. CONCLUSIONS: Depersonalization appears to be associated with functional abnormalities along sequential hierarchical areas, secondary and cross-modal, of the sensory cortex (visual, auditory, and somatosensory), as well as areas responsible for an integrated body schema. These findings are in good agreement with the phenomenological conceptualization of depersonalization as a dissociation of perceptions as well as with the subjective symptoms of depersonalization disorder.

On the clinical and cognitive meaning of impaired sensorimotor gating in schizophrenia.

Schizophrenia patients have been shown to have a defective sensorimotor gating process as indexed by impaired prepulse inhibition of the startle eyeblink reflex. Moreover, we have previously reported that schizophrenia patients have dysfunctional attentional modulation of prepulse inhibition. The present experiment combined our previous sample of 14 schizophrenia outpatients and 12 demographically matched control subjects with a new sample of 10 outpatients and 6 control subjects. All participants performed a tone-length judgement task that involved attending to one pitch of tone (the attended prepulse) and ignoring another pitch of tone (the ignored prepulse). During this task the acoustic startle eyeblink reflex was electromyographically recorded from the orbicularis oculi muscle. The results replicated the finding of impaired attentional modulation of prepulse inhibition in the new sample of schizophrenia outpatients compared to demographically matched control subjects. Specifically, the new control group exhibited greater startle modification during the attended prepulse, whereas the new patient group failed to show this differential effect. In addition, impaired prepulse inhibition following the attended prepulse was significantly correlated with heightened delusions, conceptual disorganization, and suspiciousness as measured with the expanded Brief Psychiatric Rating Scale. These correlations were significant with prepulse inhibition to the attended prepulse but not with prepulse inhibition to the ignored prepulse. Impaired prepulse inhibition was not correlated with negative symptoms. All in all, the results support the hypothesis that impaired attentional modulation of startle prepulse inhibition reflects basic neurocognitive processes related to thought disorder in schizophrenia.

Hypofrontality in unmedicated schizophrenia patients studied with PET during performance of a serial verbal learning task.

Previous research indicates that verbal learning and memory deficits are among the most severe cognitive deficits observed in schizophrenia. However, the concomitant patterns of regional brain function associated with these deficits in schizophrenia are not well understood. The present study examined verbal-memory performance and simultaneous relative glucose metabolic rates (rGMR) with FDG PET in 20 unmedicated schizophrenia patients who met stringent memory-performance criteria and 32 age- and sex-matched normal volunteers. On a modified version of the California Verbal Learning Test, patients recalled fewer correct words using a semantic-clustering strategy and exhibited more intrusions compared with normal subjects. However, patients had higher serial-ordering strategy scores, indicating their use of a less efficient organizational strategy. Among patients, greater use of the serial-ordering strategy was associated with decreased rGMR in frontal cortex and increased rGMR in temporal cortex. Patients had lower rGMR primarily in frontal and temporal cortex, but not parietal and occipital lobe regions. Patients also exhibited hypofrontality (lower ratio of frontal to occipital rGMR) compared with normal subjects. Among the patients, more severe hypofrontality was associated with increased perseveration errors.

Shape and size of the corpus callosum in schizophrenia and schizotypal personality disorder.

The size and shape of the corpus callosum were assessed on sagittal section magnetic resonance images in 27 patients with schizophrenia, 13 patients with schizotypal personality disorder (SPD), and 30 healthy volunteers. High-resolution 1.2mm axial SPGR images were acquired and resectioned so that the sagittal plane passed through the anterior and posterior commissures and was parallel to the interhemispheric fissure. The corpus callosum and the whole brain were traced on midsagittal section slices of each brain, and the callosum was divided into 30 anteroposterior sectors. Pixel-by-pixel chi-square and thin-plate spline analyses were used to assess between-group shape differences. Size of the corpus callosum was smaller anteriorly in the genu of the corpus callosum and posteriorly in the splenium in schizophrenic patients than in normal controls. The genu of the corpus callosum was larger in SPD patients than in schizophrenic patients or normal controls. The posterior corpus callosum was largest in normal controls, smaller in SPD patients, and smallest in schizophrenic patients. Shape analysis was consistent with these size comparisons, and suggested a downward bowing of the corpus callosum in schizophrenic and SPD patients. SPD patients also had a region of the callosum just posterior to the genu that was narrower than in the other two groups. The decreases in corpus callosal size in schizophrenia varied directly with length of illness, perhaps indicative of a progressive process. The patient-control differences in callosal size and shape are consistent with a hypothesis of decreased connectivity between the left and the right hemispheres in schizophrenia and SPD.

Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum.

OBJECTIVE: In an exploration of the schizophrenia spectrum, the authors compared thalamic size, shape, and metabolic activity in unmedicated patients with schizophrenia and schizotypal personality disorder to findings in age- and sex-matched healthy control subjects. METHOD: Coregistered magnetic resonance imaging (MRI) and positron emission tomography scans were obtained in 27 schizophrenic patients, 13 patients with schizotypal personality disorder, and 32 control subjects who performed a serial verbal learning test during tracer uptake. After thalamus edges were outlined on 1.2-mm MRI scans, a radial warping program yielded significance probability mapping in three dimensions. RESULTS: Significance probability mapping (with resampling) identified an area in the region of the mediodorsal nucleus bilaterally with significantly lower relative metabolism in the schizophrenia group than in either the control or schizotypal personality disorder groups, which did not differ from each other. The three groups did not differ significantly in total thalamic volume in square millimeters or thalamic volume relative to brain volume. Shape analyses revealed that schizophrenic patients had significantly fewer pixels in the left anterior region, whereas patients with schizotypal personality disorder had significantly fewer pixels in the region of the right mediodorsal nucleus than did control subjects. CONCLUSIONS: Schizophrenic patients showed significant metabolism and shape differences from control subjects in selective subregions of the thalamus, whereas patients with schizotypal personality disorder showed only a difference in shape. Because the mediodorsal and anterior nuclei have different connections with limbic and prefrontal structures, the anterior thalamic shrinkage and mediodorsal metabolic and shape changes might relate to the different clinical pictures in schizotypal personality disorder and schizophrenia.

Visualizing fronto-striatal circuitry and neuroleptic effects in schizophrenia.

Disturbances in fronto-striatal circuitry have been postulated to be important in schizophrenia. Positron emission tomography typically shows decreased metabolic rates in these areas relative to other brain areas in schizophrenia. After treatment with typical neuroleptics, striatal metabolic rates are increased, but other brain areas tend not to show significant changes. Atypical neuroleptics less markedly affect striatal metabolic rates, but show wider cortical effects. In order to examine fronto-striatal circuitry, a technique for visualizing the correlations between metabolic rates in all brain areas was applied in 33 controls and 27 unmedicated schizophrenic patients. Correlation images revealed strong fronto-striatal connections in controls, but weak fronto-striatal links in schizophrenic patients. Changes in striatal circuits, also reflected in recent anatomical studies, may be important for understanding antipsychotic effects.