Network Structure of Childhood Trauma, Bodily Disturbances, and Schizotypy in Schizophrenia and Nonclinical Controls.

Background and Hypothesis: Exposure to childhood trauma has been linked to the development of psychosis and bodily self-disturbances, 2 hallmarks of schizophrenia (SZ). Prior work demonstrated that bodily disturbances serve as a bridge between childhood trauma and SZ symptomatology, but the diagnostic specificity of these connections remains unknown. This study uses network analysis to bridge this gap by comparing the interplays between childhood trauma, bodily self-disturbances, and schizotypy in clinical and general populations. Study Design: Networks were constructed to examine the relationships between schizotypy (Schizotypal Personality Questionnaire; SPQ), bodily self-disturbances (Perceptual Aberration Scale; PAS), and childhood trauma (Childhood Trauma Questionnaire, CTQ) in 152 people with SZ and 162 healthy comparison participants (HC). The Fused Graphical Lasso was used to jointly estimate the networks in the 2 groups and the structure and strength of the networks were compared. Node centrality and shortest paths between CTQ, PAS, and schizotypy were examined. Study Results: When comparing SZ and HC, the network of bodily self-disturbances, childhood trauma, and schizotypy were similarly structured, but the network was significantly stronger in SZ than HC. In both groups, bodily self-disturbances were on one of the shortest paths between childhood trauma to schizotypal experiences. Conclusions: Our findings revealed reliable associations between childhood trauma, bodily self-disturbance, and schizotypy, with bodily disturbances acting as a bridge from childhood trauma to schizotypy. The elevated strength of the SZ network indicates a more highly interconnected, and therefore reactive network in which exposure to childhood trauma can more easily activate bodily disturbances and schizotypy.

Interplay between childhood trauma, bodily self-disturbances, and clinical phenomena in schizophrenia spectrum disorders: A network analysis.

BACKGROUND: Bodily self-disturbances have long been considered central to schizophrenia. Exposure to childhood trauma has been linked to the development of both psychosis and bodily self-disturbances, yet little work has examined the role of bodily self-disturbances in the relationship between childhood trauma and schizophrenia symptomatology. This study uses network analysis to bridge this gap. METHODS: Networks were constructed to examine relationships between schizophrenia symptoms (Positive and Negative Symptom Scale; PANSS), bodily self-disturbances (Perceptual Aberration Scale; PAS), and self-reported exposure to childhood trauma (Childhood Trauma Questionnaire, Short-Form; CTQ-SF) in 152 people with a schizophrenia-spectrum disorder. Shortest path and bridge analyses were conducted to assess the role of bodily self-disturbances in linking childhood trauma to schizophrenia symptomatology. Three networks were constructed: 1) PAS, childhood trauma, and PANSS sub-scale composites (positive, negative, general); 2) PAS, childhood trauma, and positive symptoms, 3) PAS, childhood trauma, and distress symptoms. RESULTS: Shortest path analysis revealed that bodily self-disturbances were on the shortest path between childhood trauma and positive and general symptoms (Network 1), between trauma and hallucinations (Network 2), and between trauma and depression (Network 3). Bodily self-disturbances were also found to serve as a bridge between childhood trauma and positive symptoms of schizophrenia, particularly delusions and hallucinations. CONCLUSIONS: Using a novel, data-driven approach, we showed that bodily self-disturbances play a key role in linking childhood trauma to positive and co-morbid affective symptoms of schizophrenia. Threat experiences (i.e., abuse) specifically relate to bodily self-disturbances and psychotic symptoms.

Smaller anterior hippocampal subfields in the early stage of psychosis.

Hippocampal volume is smaller in schizophrenia, but it is unclear when in the illness the changes appear and whether specific regions (anterior, posterior) and subfields (CA1, CA2/3, dentate gyrus, subiculum) are affected. Here, we used a high-resolution T2-weighted sequence specialized for imaging hippocampal subfields to test the hypothesis that anterior CA1 volume is lower in early psychosis. We measured subfield volumes across hippocampal regions in a group of 90 individuals in the early stage of a non-affective psychotic disorder and 70 demographically similar healthy individuals. We observed smaller volume in the anterior CA1 and dentate gyrus subfields in the early psychosis group. Our findings support models that implicate anterior CA1 and dentate gyrus subfield deficits in the mechanism of psychosis.

Modulation of hippocampal activity in schizophrenia with levetiracetam: a randomized, double-blind, cross-over, placebo-controlled trial.

Hippocampal hyperactivity is a novel pharmacological target in the treatment of schizophrenia. We hypothesized that levetiracetam (LEV), a drug binding to the synaptic vesicle glycoprotein 2 A, normalizes hippocampal activity in persons with schizophrenia and can be measured using neuroimaging methods. Thirty healthy control participants and 30 patients with schizophrenia (28 treated with antipsychotic drugs), were randomly assigned to a double-blind, cross-over trial to receive a single administration of 500 mg oral LEV or placebo during two study visits. At each visit, we assessed hippocampal function using resting state fractional amplitude of low frequency fluctuations (fALFF), cerebral blood flow (CBF) with arterial spin labeling, and hippocampal blood-oxygen-level-dependent (BOLD) signal during a scene processing task. After placebo treatment, we found significant elevations in hippocampal fALFF in patients with schizophrenia, consistent with hippocampal hyperactivity. Additionally, hippocampal fALFF in patients with schizophrenia after LEV treatment did not significantly differ from healthy control participants receiving placebo, suggesting that LEV may normalize hippocampal hyperactivity. In contrast to our fALFF findings, we did not detect significant group differences or an effect of LEV treatment on hippocampal CBF. In the context of no significant group difference in BOLD signal, we found that hippocampal recruitment during scene processing is enhanced by LEV more significantly in schizophrenia. We conclude that pharmacological modulation of hippocampal hyperactivity in schizophrenia can be studied with some neuroimaging methods, but not others. Additional studies in different cohorts, employing alternate neuroimaging methods and study designs, are needed to establish levetiracetam as a treatment for schizophrenia.

Hippocampal Network Dysfunction in Early Psychosis: A 2-Year Longitudinal Study.

Background: Hippocampal abnormalities are among the most consistent findings in schizophrenia. Numerous studies have reported deficits in hippocampal volume, function, and connectivity in the chronic stage of illness. While hippocampal volume and function deficits are also present in the early stage of illness, there is mixed evidence of both higher and lower functional connectivity. Here, we use graph theory to test the hypothesis that hippocampal network connectivity is broadly lowered in early psychosis and progressively worsens over 2 years. Methods: We examined longitudinal resting-state functional connectivity in 140 participants (68 individuals in the early stage of psychosis, 72 demographically similar healthy control individuals). We used an anatomically driven approach to quantify hippocampal network connectivity at 2 levels: 1) a core hippocampal-medial temporal lobe cortex (MTLC) network; and 2) an extended hippocampal-cortical network. Group and time effects were tested in a linear mixed effects model. Results: Early psychosis patients showed elevated functional connectivity in the core hippocampal-MTLC network, but contrary to our hypothesis, did not show alterations within the broader hippocampal-cortical network. Hippocampal-MTLC network hyperconnectivity normalized longitudinally and predicted improvement in positive symptoms but was not associated with increasing illness duration. Conclusions: These results show abnormally elevated functional connectivity in a core hippocampal-MTLC network in early psychosis, suggesting that selectively increased hippocampal signaling within a localized cortical circuit may be a marker of the early stage of psychosis. Hippocampal-MTLC hyperconnectivity could have prognostic and therapeutic implications.

Cerebellar Effects on Abnormal Psychomotor Function Are Mediated by Processing Speed in Psychosis Spectrum.

Psychomotor disturbance has been identified as a key feature of psychotic disorders, with motor signs observed in upwards of 66% of unmedicated, first-episode patients. Aberrations in the cerebellum have been directly linked to sensorimotor processing deficits including processing speed, which may underly psychomotor disturbance in psychosis, though these brain-behavior-symptom relationships are unclear, in part due to within-diagnosis heterogeneity across these levels of analysis. In 339 psychosis patients (242 schizophrenia-spectrum, 97 bipolar with psychotic features) and 217 controls, we evaluated the relationship between cerebellar grey matter volume in the Yeo sensorimotor network and psychomotor disturbance (mannerisms and posturing, retardation, excitement of the Positive and Negative Syndrome Scale [PANSS]), as mediated by processing speed (assessed via the SCIP). Models included intracranial volume, age, sex, and chlorpromazine equivalents as covariates. We observed significant mediation by processing speed, with a small positive effect of the cerebellum on processing speed (ß = 0.172, p = 0.029, d = 0.24) and a medium negative effect of processing speed on psychomotor disturbance (ß = -0.254, p < 0.001, d = 0.60), with acceptable specificity and sensitivity suggesting this model is robust against unmeasured confounding. The current findings suggest a critical role of cerebellar circuitry in a well-established sensorimotor aberration in psychosis (processing speed) and the presentation of related psychomotor phenotypes within psychosis. Establishing such relationships is critical for intervention research, such as TMS. Future work will employ more dimensional measures of psychomotor disturbance and cognitive processes to capture normative and aberrant brain-behavior-symptom relationships and may also determine the magnitude of these relationships within subtypes of psychosis (e.g., disorganized behavior, catatonia).

Accurate Confidence and Bayesian Interval Estimation for Non-centrality Parameters and Effect Size Indices.

Reporting effect size index estimates with their confidence intervals (CIs) can be an excellent way to simultaneously communicate the strength and precision of the observed evidence. We recently proposed a robust effect size index (RESI) that is advantageous over common indices because it's widely applicable to different types of data. Here, we use statistical theory and simulations to develop and evaluate RESI estimators and confidence/credible intervals that rely on different covariance estimators. Our results show (1) counter to intuition, the randomness of covariates reduces coverage for Chi-squared and F CIs; (2) when the variance of the estimators is estimated, the non-central Chi-squared and F CIs using the parametric and robust RESI estimators fail to cover the true effect size at the nominal level. Using the robust estimator along with the proposed nonparametric bootstrap or Bayesian (credible) intervals provides valid inference for the RESI, even when model assumptions may be violated. This work forms a unified effect size reporting procedure, such that effect sizes with confidence/credible intervals can be easily reported in an analysis of variance (ANOVA) table format.

Anterior hippocampal dysfunction in early psychosis: a 2-year follow-up study.

BACKGROUND: Cross-sectional studies indicate that hippocampal function is abnormal across stages of psychosis. Neural theories of psychosis pathophysiology suggest that dysfunction worsens with illness stage. Here, we test the hypothesis that hippocampal function is impaired in the early stage of psychosis and declines further over the next 2 years. METHODS: We measured hippocampal function over 2 years using a scene processing task in 147 participants (76 individuals in the early stage of a non-affective psychotic disorder and 71 demographically similar healthy control individuals). Two-year follow-up was completed in 97 individuals (50 early psychosis, 47 healthy control). Voxelwise longitudinal analysis of activation in response to scenes was carried out within a hippocampal region of interest to test for group differences at baseline and a group by time interaction. RESULTS: At baseline, we observed lower anterior hippocampal activation in the early psychosis group relative to the healthy control group. Contrary to our hypothesis, hippocampal activation remained consistent and did not show the predicted decline over 2 years in the early psychosis group. Healthy controls showed a modest reduction in hippocampal activation after 2 years. CONCLUSIONS: The results of this study suggest that hippocampal dysfunction in early psychosis does not worsen over 2 years and highlight the need for longer-term longitudinal studies.

Increased amplitude of hippocampal low frequency fluctuations in early psychosis: A two-year follow-up study.

Neuroimaging studies have revealed hippocampal hyperactivity in schizophrenia. In the early stage of the illness, hyperactivity is present in the anterior hippocampus and is thought to spread to other regions as the illness progresses. However, there is limited evidence for changes in basal hippocampal function following the onset of psychosis. Resting state functional MRI signal amplitude may be a proxy measure for increased metabolism and disrupted oscillatory activity, both consequences of an excitation/inhibition imbalance underlying hippocampal hyperactivity. Here, we used fractional amplitude of low frequency fluctuations (fALFF) to test the hypothesis of progressive hippocampal hyperactivity in a two-year longitudinal case-control study. We found higher fALFF in the anterior and posterior hippocampus of individuals in the early stage of non-affective psychosis at study entry. Contrary to our hypothesis of progressive hippocampal dysfunction, we found evidence for normalization of fALFF over time in psychosis. Our findings support a model in which hippocampal fALFF is a marker of psychosis vulnerability or acute illness state rather than an enduring feature of the illness.

BNST and amygdala connectivity are altered during threat anticipation in schizophrenia.

In schizophrenia, impairments in affect are prominent and anxiety disorders are prevalent. Neuroimaging studies of fear and anxiety in schizophrenia have focused on the amygdala and show alterations in connectivity. Emerging evidence suggests that the bed nucleus of the stria terminalis (BNST) also plays a critical role in anxiety, especially during anticipation of an unpredictable threat; however, previous studies have not examined the BNST in schizophrenia. In the present study, we examined BNST function and connectivity in people with schizophrenia (n = 31; n = 15 with comorbid anxiety) and controls (n = 15) during anticipation of unpredictable and predictable threat. A secondary analysis tested for differences in activation and connectivity of the central nucleus of the amygdala (CeA), which has also been implicated in threat anticipation. Analyses tested for group differences in both activation and connectivity during anticipation of unpredictable threat and predictable threat (p < .05). Relative to controls, individuals with schizophrenia showed stronger BNST-middle temporal gyrus (MTG) connectivity during unpredictable threat anticipation and stronger BNST-MTG and BNST-dorsolateral prefrontal connectivity during predictable threat anticipation. Comparing subgroups of individuals with schizophrenia and a comorbid anxiety disorder (SZ+ANX) to those without an anxiety disorder (SZ-ANX) revealed broader patterns of altered connectivity. During unpredictable threat anticipation, the SZ+ANX group had stronger BNST connectivity with regions of the salience network (insula, dorsal anterior cingulate cortex). During predictable threat anticipation, the SZ+ANX group had stronger BNST connectivity with regions associated with fear processing (insula, extended amygdala, prefrontal cortex). A secondary CeA analysis revealed a different pattern; the SZ+ANX group had weaker CeA connectivity across multiple brain regions during threat anticipation compared to the SZ-ANX group. These findings provide novel evidence for altered functional connectivity during threat anticipation in schizophrenia, especially in individuals with comorbid anxiety.

Stable habituation deficits in the early stage of psychosis: a 2-year follow-up study.

Neural habituation, the decrease in brain response to repeated stimuli, is a fundamental, highly conserved mechanism that acts as an essential filter for our complex sensory environment. Convergent evidence indicates neural habituation is disrupted in both early and chronic stages of schizophrenia, with deficits co-occurring in brain regions that show inhibitory dysfunction. As inhibitory deficits have been proposed to contribute to the onset and progression of illness, habituation may be an important treatment target. However, a crucial first step is clarifying whether habituation deficits progress with illness. In the present study, we measured neural habituation in 138 participants (70 early psychosis patients (<2 years of illness), 68 healthy controls), with 108 participants assessed longitudinally at both baseline and 2-year follow-up. At follow-up, all early psychosis patients met criteria for a schizophrenia spectrum disorder (i.e., schizophreniform disorder, schizophrenia, schizoaffective disorder). Habituation slopes (i.e., rate of fMRI signal change) to repeated images were computed for the anterior hippocampus, occipital cortex, and the fusiform face area. Habituation slopes were entered into a linear mixed model to test for effects of group and time by region. We found that early psychosis patients showed habituation deficits relative to healthy control participants across brain regions, and that these deficits were maintained, but did not worsen, over two years. These results suggest a stable period of habituation deficits in the early stage of schizophrenia.

Relational Memory in the Early Stage of Psychosis: A 2-Year Follow-up Study.

BACKGROUND: Relational memory, the ability to bind information into complex memories, is moderately impaired in early psychosis and severely impaired in chronic schizophrenia, suggesting relational memory may worsen throughout the course of illness. METHODS: We examined relational memory in 66 early psychosis patients and 64 healthy control subjects, with 59 patients and 52 control subjects assessed longitudinally at baseline and 2-year follow-up. Relational memory was assessed with 2 complementary tasks, to test how individuals learn relationships between items (face-scene binding task) and make inferences about trained relationships (associative inference task). RESULTS: The early psychosis group showed impaired relational memory in both tasks relative to the healthy control group. The ability to learn relationships between items remained impaired in early psychosis patients, while the ability to make inferences about trained relationships improved, although never reaching the level of healthy control performance. Early psychosis patients who did not progress to schizophrenia at follow-up had better relational memory than patients who did. CONCLUSIONS: Relational memory impairments, some of which improve and are less severe in patients who do not progress to schizophrenia, are a target for intervention in early psychosis.

Visual-Tactile Spatial Multisensory Interaction in Adults With Autism and Schizophrenia.

Background: Individuals with autism spectrum disorder (ASD) and schizophrenia (SZ) exhibit multisensory processing difficulties and social impairments, with growing evidence that the former contributes to the latter. However, this work has largely reported on separate cohorts, introducing method variance as a barrier to drawing broad conclusions across studies. Further, very few studies have addressed touch, resulting in sparse knowledge about how these two clinical groups may integrate somatic information with other senses. Methods: In this study, we compared adults with ASD (n = 29), SZ (n = 24), and typical developmental histories (TD, n = 37) on two tasks requiring visual-tactile spatial multisensory processing. In the first task (crossmodal congruency), participants judged the location of a tactile stimulus in the presence or absence of simultaneous visual input that was either spatially congruent or incongruent, with poorer performance for incongruence an index of spatial multisensory interaction. In the second task, participants reacted to touch in the presence or absence of dynamic visual stimuli that appeared to approach or recede from the body. Within a certain radius around the body, defined as peripersonal space (PPS), an approaching visual or auditory stimulus reliably speeds reaction times (RT) to touch; outside of this radius, in extrapersonal space (EPS), there is no multisensory effect. PPS can be defined both by its size (radius) and slope (sharpness of the PPS-EPS boundary). Clinical measures were administered to explore relations with visual-tactile processing. Results: Neither clinical group differed from controls on the crossmodal congruency task. The ASD group had significantly smaller and more sharply-defined PPSs compared to the other two groups. Small PPS size was related to social symptom severity across groups, but was largely driven by the TD group, without significant effects in either clinical group. Conclusions: These results suggest that: (1) spatially static visual-tactile facilitation is intact in adults with ASD and SZ, (2) spatially dynamic visual-tactile facilitation impacting perception of the body boundary is affected in ASD but not SZ, and (3) body boundary perception is related to social-emotional function, but not in a way that maps on to clinical status.

Relational memory in the early stage of psychotic bipolar disorder.

Relational memory is impaired in psychotic disorders. In non-affective psychotic disorders, relational memory deficits are present in the early stage of illness and become more pronounced in the chronic stage. Previous studies have demonstrated cognitive deficits in early-stage psychotic bipolar disorder, but it is unclear whether relational memory is impaired. We examined relational memory using a face-scene binding task in early-stage psychotic bipolar disorder patients (n = 33) and compared their performance with healthy control (n = 40) and early-stage non-affective psychosis participants (n = 40). During training, participants learned to associate faces with background scenes. During testing, participants viewed a scene overlaid by three faces and were asked to recall the matching face. Relational memory was assessed indirectly using eye movements and explicitly using forced-choice recognition. Preferential viewing of the matching face, as captured by overall proportion of viewing and viewing across time, was significantly lower in psychotic bipolar disorder than in the healthy control group. However, preferential viewing of the matching face in psychotic bipolar disorder was significantly better than in non-affective psychosis. These findings provide novel evidence that relational memory in patients with early-stage psychotic bipolar disorder is intermediate between healthy control and early-stage non-affective psychosis subjects.

Hippocampal volume in early psychosis: a 2-year longitudinal study.

Cross-sectional studies suggest that hippocampal volume declines across stages of psychosis. In contrast, longitudinal studies indicate that hippocampal volume is stable in the critical period following illness onset. How can these seemingly disparate sets of findings be resolved? In the present study, we examine two previously unexplored reasons for this discrepancy. First, only specific subregions of the hippocampus may change during the early stage of psychosis. Second, there is diagnostic heterogeneity in the early stage of psychosis and cross-sectional analysis does not permit examination of illness trajectory. Some early stage individuals will have persistent illness leading to a diagnosis of schizophrenia, whereas in others, psychosis will remit. Hippocampal volume may be reduced only in individuals who will ultimately be diagnosed with schizophrenia. We acquired longitudinal structural MRI data from 63 early psychosis and 63 healthy control participants, with up to 4 time points per participant collected over 2 years. Subfield volumes were measured in the anterior and posterior hippocampus using automated segmentation specialized for longitudinal analysis. We observed a volume deficit in early psychosis participants compared to healthy controls that was most pronounced in the anterior hippocampus, but this deficit did not change over 2 years. Importantly, we found that anterior cornu ammonis volume is smaller at baseline in individuals who were diagnosed with schizophrenia at follow-up, but normal in those who maintained a diagnosis of schizophreniform disorder over 2 years. Smaller hippocampal volume is not diagnostic of psychosis, but is instead prognostic of clinical outcome.

Habituation during encoding: A new approach to the evaluation of memory deficits in schizophrenia.

BACKGROUND: Memory is significantly impaired in schizophrenia. However, memory measures are often complex and confounded by additional impairments such as motivation and task comprehension, which can affect behavioral performance and obscure neural function during memory tasks. Neural signatures of memory encoding that are robust to potential confounds may shed additional light on neural deficits contributing to memory impairment in schizophrenia. METHODS: Here, we investigate a potential neural signature of memory-habituation-and its relationship with healthy and impaired memory function. To limit potential confounds, we used a passive depth of encoding memory task designed to elicit neural responses associated with memory encoding while limiting other cognitive demands. To determine whether habituation during encoding was predictive of intact memory processing, we first compared neural habituation over repeated encoding exposures with subsequent explicit memory in healthy individuals. We then tested whether a similar relationship existed in patients with schizophrenia. RESULTS: Explicit memory performance was impaired in patients with schizophrenia relative to healthy control subjects. In healthy participants, more habituation over repeated exposures during encoding was associated with greater repetition-related increases in accuracy during testing. However, in patients with schizophrenia, better performance was associated with less habituation, or a more sustained neural response during encoding. CONCLUSIONS: These results suggest that sustained neural activity is required for normal repetition-related improvements in memory performance in schizophrenia, in line with a neural inefficiency model. Habituation may serve as a valuable index of neural processes that underlie behavioral memory performance.

Evidence for inhibited temperament as a transdiagnostic factor across mood and psychotic disorders.

BACKGROUND: The conceptualization of risk for psychiatric illness is moving from risk factors for specific psychiatric disorders to factors that confer risk for multiple disorders. One potential transdiagnostic risk factor is inhibited temperament, a trait characterized by a fearful or avoidant response to novelty. Inhibited temperament is an established risk factor for anxiety disorders, and evidence suggests inhibited temperament is elevated in schizophrenia, bipolar disorder, and major depressive disorder. METHODS: In the current study, we tested the hypothesis that inhibited temperament is a transdiagnostic factor in 490 participants including individuals with schizophrenia (n=184), psychotic bipolar disorder (n=61), major depression disorder (n=53), or no disorders (n=192). Participants completed assessments of temperament, personality, clinical symptoms, cognition, and functioning. An ANOVA was used to test for group differences in inhibited temperament scores. Regressions were used to test whether inhibited temperament scores were associated with the current measures and whether the associations were similar across disorders. RESULTS: Inhibited temperament was similarly elevated in all patient groups compared to controls. Inhibited temperament was similarly associated with anxiety, depression, negative affect, and quality of life across patient groups. Inhibited temperament was not associated with cognition or functional impairment. LIMITATION: Although the inhibited temperament measure is commonly used, it is a retrospective self-report which may be susceptible to biases. CONCLUSIONS: The current study provides evidence that inhibited temperament is a transdiagnostic factor impacting affective systems across mood and psychotic disorders. Inhibited patients may especially benefit from treatments that specifically target anxiety and depression.

Cognitive motor impairments and brain structure in schizophrenia spectrum disorder patients with a history of catatonia.

There is growing interest in understanding the behavioral and neural mechanisms of catatonia. Here, we examine cognition and brain structure in schizophrenia spectrum disorder (SSD) patients with a history of catatonia. A total of 172 subjects were selected from a data repository; these included SSD patients with (n = 43) and without (n = 43) a history of catatonia and healthy control subjects (n = 86). Cognitive functioning was assessed using the Screen for Cognitive Impairment in Psychiatry (SCIP) and brain structure was assessed using voxel-based morphometry (VBM) in the CAT12 toolbox. SSD patients with a history of catatonia showed worse performance on tests of verbal fluency and processing speed compared to SSD patients without such a history, even after controlling for current antipsychotic and benzodiazepine use. No differences were found between patients with and without a history of catatonia in terms of brain structure. Both patient groups combined showed significantly smaller grey matter volumes compared to healthy control subjects in brain regions consistent with prior studies, including the anterior cingulate, insular, temporal, and medial frontal cortices. The results highlight a cognitive-motor impairment in SSD patients with a history of catatonia. Challenges and limitations of examining brain structure in patients with a history of catatonia are discussed.

Hyperactivity and Reduced Activation of Anterior Hippocampus in Early Psychosis.

OBJECTIVE: In schizophrenia, the anterior hippocampus is hyperactive and shows reduced task-related recruitment, but the relationship between these two findings is unclear. The authors tested the hypothesis that hyperactivity impairs recruitment of the anterior hippocampus during scene processing. METHODS: Functional MRI data from 45 early-psychosis patients and 35 demographically matched healthy control subjects were analyzed using a block-design 1-back scene-processing task. Hippocampal activation in response to scenes and faces compared with scrambled images was measured. In a subset of 20 early-psychosis patients and 31 healthy control subjects, baseline hippocampal activity using cerebral blood volume (CBV) mapping was measured. Correlation analyses were used to examine the association between baseline hippocampal activity and task-related hippocampal activation. RESULTS: Activation of the anterior hippocampus was significantly reduced and CBV in the anterior hippocampus was significantly increased in the early stages of psychosis. Increased CBV in early-psychosis patients was inversely correlated with task-related activation during scene processing in the anterior hippocampus. CONCLUSIONS: Anterior hippocampal hyperactivity in early-psychosis patients appears to limit effective recruitment of this region during task performance. These findings provide novel support for the anterior hippocampus as a therapeutic target in the treatment of cognitive deficits in psychosis.