Improving the prospective prediction of a near-term suicide attempt in veterans at risk for suicide, using a go/no-go task.

BACKGROUND: Neurocognitive testing may advance the goal of predicting near-term suicide risk. The current study examined whether performance on a Go/No-go (GNG) task, and computational modeling to extract latent cognitive variables, could enhance prediction of suicide attempts within next 90 days, among individuals at high-risk for suicide. METHOD: 136 Veterans at high-risk for suicide previously completed a computer-based GNG task requiring rapid responding (Go) to target stimuli, while withholding responses (No-go) to infrequent foil stimuli; behavioral variables included false alarms to foils (failure to inhibit) and missed responses to targets. We conducted a secondary analysis of these data, with outcomes defined as actual suicide attempt (ASA), other suicide-related event (OtherSE) such as interrupted/aborted attempt or preparatory behavior, or neither (noSE), within 90-days after GNG testing, to examine whether GNG variables could improve ASA prediction over standard clinical variables. A computational model (linear ballistic accumulator, LBA) was also applied, to elucidate cognitive mechanisms underlying group differences. RESULTS: On GNG, increased miss rate selectively predicted ASA, while increased false alarm rate predicted OtherSE (without ASA) within the 90-day follow-up window. In LBA modeling, ASA (but not OtherSE) was associated with decreases in decisional efficiency to targets, suggesting differences in the evidence accumulation process were specifically associated with upcoming ASA. CONCLUSIONS: These findings suggest that GNG may improve prediction of near-term suicide risk, with distinct behavioral patterns in those who will attempt suicide within the next 90 days. Computational modeling suggests qualitative differences in cognition in individuals at near-term risk of suicide attempt.

Fluorodeoxyglucose positron emission tomography scans in patients with alcohol use disorder.

BACKGROUND: Diminished uptake of fluorodeoxyglucose (FDG) has been observed in patients with alcohol use disorder (AUD) but little statistical contrast of the regional brain deficits has been undertaken. This study examined prefrontal cortex inter-regional Brodmann area differences to delineate patterns associated with behavioral, neurotransmitter, and general toxicity hypotheses of cerebral involvement in AUD. METHODS: We obtained data from FDG positron emission tomography (PET) and anatomical magnetic resonance imaging (MRI) for 87 patients with AUD and 41 age- and sex-matched healthy volunteers. Patients were alcohol dependent and had negative breathalyzer tests at the time of imaging. They were assessed with the Beck Depression Inventory, Alcohol Urge Questionnaire, Obsessive Compulsive Drinking Scale, Spielberger State/Trait Anxiety Scale, Buss-Durkee Hostility Inventory, and the Drinker Inventory of Consequences (DrInC). PET images were co-registered to MRI and both voxel × voxel statistical mapping and stereotaxic regions of interest were obtained. RESULTS: Compared with healthy volunteers, patients with AUD had lower relative metabolic rates in the frontal, temporal, and parietal lobes, localizable most prominently to the dorsolateral and nearly all orbital prefrontal cortex, superior temporal gyrus, and inferior parietal lobule. In contrast, metabolic rates in the medial orbitofrontal and anterior cingulate cortex, and the subcortical structures (thalamus, cerebellum, ventral striatum, and the dorsal raphe nucleus) in patients were significantly greater. The severity of alcohol-related consequences as assessed by the DrInC scale was most highly associated with lower metabolism in the caudate, dorsolateral prefrontal, frontopolar, and anteroposterior cingulate cortex. CONCLUSIONS: Despite widespread metabolic abnormalities, decreases in AUD were most marked in frontal executive areas, consistent with diminished impulse control, and increases were most prominent in the striatum and cingulate areas, consistent with a suppressed reward system.

The MATRICS consensus cognitive battery for the assessment of cognitive impairment in schizotypal personality disorder.

Cognitive deficits are a core impairment across the range of schizophrenia (SZ) spectrum disorders, including schizotypal personality disorder (SPD). The MATRICS Consensus Cognitive Battery (MCCB) was developed to be a robust, specific, and valid cognitive assessment battery to assess cognition in clinical trials for treating cognitive impairments in SZ. Despite the similarity of cognitive impairments shown in SPD and SZ and the clear relevance of uniform assessment across a diagnostic spectrum, the MCCB has yet to be validated in SPD. As such, this is the first study to evaluate the sensitivity of the MCCB for the assessment of cognitive function in individuals with SPD. Participants were 30 individuals with SPD and 54 healthy controls (HC) assessed with the MCCB and supplemental neurocognitive assessments (Trails B, DOT test, Paced Auditory Serial Addition Test (PASAT), AX Continuous Performance Task (AX-CPT), and N-back). Individuals with SPD performed worse than HC participants on all MCCB subtests, as well as on converging supplemental tasks including Trails B, DOT test, PASAT, AX-CPT, and N-back. These results indicate that the MCCB was sensitive to cognitive impairment in SPD compared to controls. SPD participants demonstrate impairments similar to data of SZ participants within the literature, although to a slightly lesser degree of severity. Taken together, these results highlight the generalizability of using the MCCB across SZ spectrum diagnostic groups to assess cognition. Such findings allow for further comparison across disorders, greater understanding of the cognitive characteristics in the spectrum, and use of uniform assessment within cognitive intervention research.

Multi-modal risk factors differentiate suicide attempters from ideators in military veterans with major depressive disorder.

BACKGROUND: The suicide rate for United States military veterans is 1.5× higher than that of non-veterans. To meaningfully advance suicide prevention efforts, research is needed to delineate factors that differentiate veterans with suicide attempt/s, particularly in high-risk groups, e.g., major depressive disorder (MDD), from those with suicidal ideation (no history of attempt/s). The current study aimed to identify clinical, neurocognitive, and neuroimaging variables that differentiate suicide-severity groups in veterans with MDD. METHODS: Sixty-eight veterans with a DSM-5 diagnosis of MDD, including those with no ideation or suicide attempt (N = 21; MDD-SI/SA), ideation-only (N = 17; MDD + SI), and one-or-more suicide attempts (N = 30; MDD + SA; aborted, interrupted, actual attempts), participated in this study. Participants underwent a structured diagnostic interview, neurocognitive assessment, and 3 T-structural/diffusion tensor magnetic-resonance-imaging (MRI). Multinomial logistic regression models were conducted to identify variables that differentiated groups with respect to the severity of suicidal behavior. RESULTS: Relative to veterans with MDD-SI/SA, those with MDD + SA had significantly higher left cingulum fractional anisotropy, decreased attentional control on emotional-Stroop, and faster response time with intact accuracy on Go/No-Go. Relative to MDD + SI, MDD + SA had higher left cingulum fractional anisotropy and faster response time with intact accuracy on Go/No-Go. LIMITATIONS: Findings are based on retrospective, cross-sectional data and cannot identify causal relationships. Also, a healthy control group was not included given the study's focus on differentiating suicide profiles in MDD. CONCLUSIONS: This study suggests that MRI and neurocognition differentiate veterans with MDD along the suicide-risk spectrum and could inform suicide-risk stratification and prevention efforts in veterans and other vulnerable populations.

Training in Cognitive Reappraisal Normalizes Whole-Brain Indices of Emotion Regulation in Borderline Personality Disorder.

BACKGROUND: Borderline personality disorder (BPD) is the prototypical disorder of emotion dysregulation. We have previously shown that patients with BPD are impaired in their capacity to engage cognitive reappraisal, a frequently employed adaptive emotion regulation strategy. METHODS: Here, we report on the efficacy of longitudinal training in cognitive reappraisal to enhance emotion regulation in patients with BPD. Specifically, the training targeted psychological distancing, a reappraisal tactic whereby negative stimuli are viewed dispassionately as though experienced by an objective, impartial observer. At each of 5 sessions over 2 weeks, 22 participants with BPD (14 female) and 22 healthy control participants (13 female) received training in psychological distancing and then completed a widely used picture-based reappraisal task. Self-reported negative affect ratings and functional magnetic resonance imaging data were acquired at the first and fifth sessions. In addition to behavioral analyses, we performed whole-brain pattern expression analyses using independently defined patterns for negative affect and cognitive reappraisal implementation for each session. RESULTS: Patients with BPD showed a decrease in negative affect pattern expression following reappraisal training, reflecting a normalization in neural activity. However, they did not show significant change in behavioral self-reports. CONCLUSIONS: To our knowledge, this study represents the first longitudinal functional magnetic resonance imaging examination of task-based cognitive reappraisal training. Using a brief, proof-of-concept design, the results suggest a potential role for reappraisal training in the treatment of patients with BPD.

Neural correlates of impulsivity in bipolar disorder: A systematic review and clinical implications.

Impulsivity is a common feature of bipolar disorder (BD) with ramifications for functional impairment and premature mortality. This PRISMA-guided systematic review aims to integrate findings on the neurocircuitry associated with impulsivity in BD. We searched for functional neuroimaging studies that examined rapid-response impulsivity and choice impulsivity using the Go/No-Go Task, Stop-Signal Task, and Delay Discounting Task. Findings from 33 studies were synthesized with an emphasis on the effect of mood state of the sample and affective salience of the task. Results suggest trait-like brain activation abnormalities in regions implicated in impulsivity that persist across mood states. During rapid-response inhibition, BD exhibit under-activation of key frontal, insular, parietal, cingulate, and thalamic regions, but over-activation of these regions when the task involves emotional stimuli. Delay discounting tasks with functional neuroimaging in BD are lacking, but hyperactivity of orbitofrontal and striatal regions associated with reward hypersensitivity may be related to difficulty delaying gratification. We propose a working model of neurocircuitry dysfunction underlying behavioral impulsivity in BD. Clinical implications and future directions are discussed.

Association of interleukin-6 with suicidal ideation in veterans: a longitudinal perspective.

Introduction: Studies showing associations between inflammation in suicide are typically cross-sectional. Present study investigated how cytokine levels track with suicidal ideation and severity longitudinally. Methods: Veterans with a diagnosis of major depressive disorder (MDD) with or without suicide attempt history (MDD/SA n = 38, MDD/NS n = 41) and non-psychiatric non-attempter controls (HC n = 33) were recruited, MDD/SA and HC groups were followed longitudinally at 3 months and 6 months. Blood plasma was collected and processed using Luminex Immunology Multiplex technology. Results: Significant differences in depression severity (BDI) and suicidal ideation severity (SSI) were observed across all groups at study entry, wherein MDD/SA group had the highest scores followed by MDD/NS and HC, respectively. Cytokines IL-1ß, IL-4, TNF-α, IFN-γ, and IL-6 were examined at study entry and longitudinally, with IL6 levels differing significantly across the groups (p = 0.0123) at study entry. Significant differences in changes in cytokine levels between depressed attempters and the control group were detected for IL-6 (interaction F1,91.77 = 5.58, p = 0.0203) and TNF-α (F1,101.73 = 4.69, p = 0.0327). However, only depressed attempters showed a significant change, in IL-6 and TNF-α levels, decreasing over time [IL-6: b = -0.04, 95% CI = (-0.08, -0.01), p = 0.0245 and TNF-α: b = -0.02, 95% CI = (-0.04, -0.01), p = 0.0196]. Although IL-6 levels were not predictive of suicidal ideation presence [OR = 1.34, 95% CI = (0.77, 2.33), p = 0.3067], IL-6 levels were significantly associated with suicidal ideation severity (b = 0.19, p = 0.0422). Discussion: IL-6 was not associated with presence of suicidal ideation. IL-6 however, was associated with severity of ideation, suggesting that IL-6 may be useful in clinical practice, as an objective marker of heightened suicide risk.

Clinical features of individuals with schizotypal personality disorder with and without suicidal ideation.

This study compared demographic and clinical features in a sample of 384 participants: healthy controls (HC; n = 166) and individuals with schizotypal personality disorder (SPD) with (n = 50) and without (n = 168) suicidal ideation (SI) to examine specific risk factors for suicidality in SPD. Compared to the non-SI group, the SI group showed significantly greater severity of depression, aggression, impulsivity, affective lability, schizotypal features, poorer social adjustment, and had fewer social contacts. Individuals in the SI group were also more likely to have a history of a suicide attempt and comorbid borderline personality disorder in comparison to the non-SI group. Logistic regression analysis indicated that severity of depression and the number of social contacts drove the difference between the SI and non-SI groups. Compared with both SPD subgroups, the HC group was significantly less depressed, aggressive, impulsive, affectively labile, had fewer schizotypal features, was better socially adjusted, and had more social contacts. This study indicates that overall, the SI group is a more severely impaired group of individuals with SPD compared to the non-SI group. Better educating medical professionals about the diagnosis and management of SPD and its associations with suicidality is warranted.

The structure of antagonism: A hierarchical model of self- and interview-rated psychopathology.

Recent initiatives in the empirically based classification of psychopathology, namely, the Hierarchical Taxonomy of Psychopathology (HiTOP), have made significant strides in addressing the limitations of traditional taxonomies (i.e., Diagnostic and Statistical Manual of Mental Disorders, International Classification of Diseases). The current study aimed to extend this work by helping to clarify the lower order structure of an understudied dimension of psychopathology-antagonism (i.e., HiTOP antagonistic externalizing spectrum)-a core feature of many externalizing disorders and related to important outcomes such as interpersonal problems, childhood conduct problems, and incarceration. We examined the hierarchical structure of several measures of antagonistic externalizing features across both self-report and clinical interview ratings for 2,279 community participants with a diverse range of personality pathology (~75% with a personality disorder) and antagonistic behaviors (~30% with intermittent explosive disorder). Exploratory structural equation modeling was used to account for the shared variance between variables within self-report and interview methods. Results revealed an optimal lower order structure consisting of six factors labeled Antisociality, Anger, Hostility, Narcissism, Mistrust, and Attention Seeking. Factor scores yielded expected relations with self-report and interview ratings of psychopathology, personality, and childhood trauma. Implications for future research in classification and treatment of psychopathology are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Emergence of Language Related to Self-experience and Agency in Autobiographical Narratives of Individuals With Schizophrenia.

BACKGROUND AND HYPOTHESIS: Disturbances in self-experience are a central feature of schizophrenia and its study can enhance phenomenological understanding and inform mechanisms underlying clinical symptoms. Self-experience involves the sense of self-presence, of being the subject of one's own experiences and agent of one's own actions, and of being distinct from others. Self-experience is traditionally assessed by manual rating of interviews; however, natural language processing (NLP) offers automated approach that can augment manual ratings by rapid and reliable analysis of text. STUDY DESIGN: We elicited autobiographical narratives from 167 patients with schizophrenia or schizoaffective disorder (SZ) and 90 healthy controls (HC), amounting to 490 000 words and 26 000 sentences. We used NLP techniques to examine transcripts for language related to self-experience, machine learning to validate group differences in language, and canonical correlation analysis to examine the relationship between language and symptoms. STUDY RESULTS: Topics related to self-experience and agency emerged as significantly more expressed in SZ than HC (P < 10-13) and were decoupled from similarly emerging features such as emotional tone, semantic coherence, and concepts related to burden. Further validation on hold-out data showed that a classifier trained on these features achieved patient-control discrimination with AUC = 0.80 (P < 10-5). Canonical correlation analysis revealed significant relationships between self-experience and agency language features and clinical symptoms. CONCLUSIONS: Notably, the self-experience and agency topics emerged without any explicit probing by the interviewer and can be algorithmically detected even though they involve higher-order metacognitive processes. These findings illustrate the utility of NLP methods to examine phenomenological aspects of schizophrenia.

Smaller rostral cingulate volume and psychosocial correlates in veterans at risk for suicide.

Suicide research/clinical work remain in dire need of effective tools that can better predict suicidal behavior. A growing body of literature has started to focus on the role that neuroimaging may play in helping explain the path towards suicide. Specifically, structural alterations of rostral anterior cingulate cortex (rost-ACC) may represent a biological marker and/or indicator of suicide risk in Major Depressive Disorder (MDD). Furthermore, the construct of "grit," defined as perseverance for goal-attainment and shown to be associated with suicidality, is modulated by rost-ACC. The aim was to examine relationships among rost-ACC gray matter volume, grit, and suicidality in U.S. Military Veterans. Participants were age-and-sex-matched Veterans with MDD: with suicide attempt (MDD+SA:n = 23) and without (MDD-SA:n = 37). Groups did not differ in depression symptomatology. Participants underwent diagnostic interview, clinical symptom assessment, and 3T-MRI-scan. A Group (SA-vs.-No-SA) x Cingulate-region (rostral-caudal-posterior) x Hemisphere (left-right) mixed-model-multivariate-ANOVA was conducted. Left-rost-ACC was significantly smaller in MDD+SA, Group x Cingulate-region x Hemisphere-interaction. Lower grit and less left-rost-ACC gray matter each predicted suicide attempt history, but grit level was a more robust predictor of SA. Both structural alterations of rost-ACC and grit level represent potentially valuable tools for suicide risk assessment.

Serotonin transporter availability in physically aggressive personality disordered patients: associations with trait and state aggression, and response to fluoxetine.

RATIONALE: Characterizing the neuroanatomical basis of serotonergic abnormalities in severe, chronic, impulsive aggression will allow for rational treatment selection, development of novel therapeutics, and biomarkers to identify at-risk individuals. OBJECTIVES: The aim of this study is to identify associations between regional serotonin transporter (5-HTT) availability and trait and state aggression, as well as response to the anti-aggressive effects of fluoxetine. METHODS: We examined 5-HTT availability using positron emission tomography (PET) imaging with [11C]DASB in personality disordered patients with current physical intermittent explosive disorder (IED; n = 18), and healthy comparison participants (HC; n = 11), in the anterior cingulate cortex (ACC), amygdala (AMY), ventral striatum (VST), and midbrain (MID). After PET imaging, IED patients were treated with fluoxetine 20 mg daily (n = 9) or placebo (n = 6) for 12 weeks. Trait and state aggression, trait callousness, and childhood trauma were assessed. RESULTS: In IED patients, trait aggression was positively associated with [11C]DASB binding in the ACC and VST; covarying for trait callousness and childhood trauma enhanced these correlations. Baseline state aggression was positively correlated with ACC [11C]DASB in IED patients. Greater baseline VST [11C]DASB binding predicted greater decreases in state aggression with fluoxetine treatment. CONCLUSIONS: Consistent with prior reports, ACC 5-HTT is related to trait aggression, and adjusting for factors related to proactive (callousness) and reactive (childhood trauma) aggression subtypes further resolves this relationship. Novel findings of the study include a better understanding of the association between regional 5-HTT availability and state aggression, and the involvement of VST 5-HTT with trait aggression, and with the anti-aggressive effects of fluoxetine.

A review of structural MRI and diffusion tensor imaging in schizotypal personality disorder.

Individuals with schizotypal personality disorder (SPD) share genetic, phenomenologic, and cognitive abnormalities with people diagnosed with schizophrenia. To date, 15 structural MRI studies of the brain have examined size, and 3 diffusion tensor imaging studies have examined white matter connectivity in SPD. Overall, both types of structural neuroimaging modalities have shown temporal lobe abnormalities similar to those observed in schizophrenia, while frontal lobe regions appear to show more sparing. This intriguing pattern suggests that frontal lobe sparing may suppress psychosis, which is consistent with the idea of a possible neuroprotective factor. In this paper, we review these 18 studies and discuss whether individuals with SPD who both resemble and differ from schizophrenia patients in their phenomenology, share some or all of the structural brain imaging characteristics of schizophrenia. We attempt to group the MRI abnormalities in SPD into three patterns: 1) a spectrum of severity-abnormalities are similar to those observed in schizophrenia but not so severe; 2) a spectrum of region-abnormalities affecting some, but not all, brain regions affected in schizophrenia; and 3) a spectrum of compensation-abnormalities reflecting greater-than-normal white matter volume, possibly serving as a buffer or compensatory mechanism protecting the individual with SPD from the frank psychosis observed in schizophrenia.

A Pilot Randomized Control Trial of a Dyadic Safety Planning Intervention: Safe Actions for Families to Encourage Recovery (SAFER).

A recent systematic review on family and suicide prevention efforts identified a lack of family-based safety planning interventions for adults. To address this gap, The Safe Actions for Families to Encourage Recovery (SAFER) intervention was created. SAFER is a novel, manualized, 4- session, family-based treatment intervention that provides the tools and structure to support family involvement in Safety Planning Intervention (SPI) for Veterans at moderate risk for suicide. The SAFER intervention includes the use of psychoeducation, communication skills training, and development of a Veteran, and a complementary supporting partner, SPI. This Stage II (2aii) randomized clinical trial (RCT) evaluated the preliminary efficacy of this innovative and much-needed approach. Thirty-nine Veterans and an associated supporting partner were randomized to receive either SAFER or currently mandated (i.e., standard) individual Safety Planning Intervention (I-SPI). Veterans in the SAFER condition as compared to I-SPI exhibited significant monthly decrements in suicide ideation as measured by the Columbia Suicide Severity Rating Scale (B=-0.37; p=.032). Moreover, a treatment-by-time interaction emerged when predicting improvements in Veteran suicide-related coping (B=0.08; p=.028) and supporting partner support of Veteran's coping efforts (B=0.17; p=.032). However, the treatment effect for Veteran coping was not significant in dyadic analyses (B=0.07; p=.151) after controlling for the partner's support (B=0.16; p=.009). Self-reported appraisals of relational factors and self-efficacy were not impacted by condition for either Veterans or supporting partners. This initial efficacy pilot trial suggests that a brief dyad-based SPI has the potential to improve Veteran suicide symptoms and help family members support the Veteran's coping efforts. However more intensive family work may be required for changes in self-perceptions of burdensomeness, belongingness, and caregiver perceptions of the Veteran as a burden. Nonetheless, SAFER's discussion and disclosure about suicide symptoms facilitated more robust development of SPI for the Veteran and their accompanying supporting partner.

Arrest history and psychopathology among veterans at risk for suicide.

While preliminary evidence suggests an association between legal involvement and suicide risk among veterans, no research to date has explored the prevalence and/or correlates of legal involvement among veterans at high risk for suicide. The current study examined the relation of suicide attempt, suicidal ideation, and psychopathology to history of criminal arrest in a sample of 286 veterans at risk for suicide. Results indicated approximately half (47%) of at-risk veterans had a history of arrest. Inconsistent with hypotheses, arrest history was not associated with history of suicide attempt, current suicidal ideation, or severity of psychopathological symptoms. Arrest history was, however, associated with diagnoses of substance use disorder and antisocial personality disorder in this high-suicide risk sample. Further, likelihood of an antisocial personality disorder diagnosis was associated with higher frequency of past arrests. Taken together, results indicate that many veterans at risk for suicide have a history of arrest, and at-risk veterans with such history likely have a specific pattern of psychopathology, including antisocial personality traits and substance use. As such, legal status and history of justice involvement may be important considerations when assessing suicide risk and management of this high-risk population. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Hyperreactivity and Impaired Habituation of Startle Amplitude During Unpleasant Pictures in Borderline but Not Schizotypal Personality Disorder: Quantifying Emotion Dysregulation.

BACKGROUND: Borderline personality disorder (BPD) is characterized by greater intensity of reactions to unpleasant emotional cues and a slower-than-normal return of these responses to baseline. Habituation is defined as decreased response to repeated stimulation. Affect-modulated startle (AMS), a translational psychophysiological approach, is mediated by the amygdala and used to study emotion processing in both humans and animals. This is the first study to examine the specificity of habituation anomalies in BPD during passive emotional and neutral picture processing. METHODS: A total of 90 participants were studied: patients with BPD (n = 35), patients with schizotypal personality disorder (n = 26; included as a psychopathological comparison group), and healthy control subjects (n = 29). Participants received rigorous clinical assessments, and patients were unmedicated. AMS was examined during a series of intermixed unpleasant, neutral, and pleasant pictures. RESULTS: Compared with the other groups, patients with BPD showed greater overall AMS during unpleasant pictures and prolonged habituation of startle amplitude during unpleasant pictures from early to later trials. The groups did not differ in AMS during neutral or pleasant pictures or self-reported picture valence. Among the patients with BPD, prolonged habituation to unpleasant pictures was associated with greater symptom severity and suicidal/self-harming behavior. CONCLUSIONS: These findings 1) indicate that abnormal processing of and habituation to unpleasant pictures is observed in BPD but not schizotypal personality disorder, suggesting that these deficits are not simply characteristics of personality disorders in general; 2) are consistent with studies showing deficient amygdala habituation to unpleasant pictures in BPD; and 3) have significant implications for clinical assessment and treatment of BPD, e.g., alternative therapies for BPD such as gradual exposure to unpleasant emotional stimuli or amygdala neurofeedback may aid habituation deficits.

Cingulate and hippocampal subregion abnormalities in combat-exposed veterans with PTSD.

BACKGROUND: The hippocampus and cingulate gyrus are strongly interconnected brain regions that have been implicated in the neurobiology of post-traumatic stress disorder (PTSD). These brain structures are comprised of functionally distinct subregions that may contribute to the expression of PTSD symptoms or associated cardio-metabolic markers, but have not been well investigated in prior studies. METHODS: Two divisions of the cingulate cortex (i.e., rostral and caudal) and 11 hippocampal subregions were investigated in 22 male combat-exposed veterans with PTSD and 22 male trauma-exposed veteran controls (TC). Cardio-metabolic measures included cholesterol, body mass index, and mean arterial pressure. RESULTS: Individuals with PTSD had less caudal cingulate area compared to TC even after controlling for caudal cingulate thickness. Total hippocampus volume was lower in PTSD compared to TC, accounted for by differences in CA1-CA4, granule cell layer of the dentate gyrus, molecular layer, and subiculum. Individuals with PTSD had higher mean arterial pressure compared to TC, which correlated with hippocampus volume only in the PTSD group. LIMITATIONS: Sample size, cross-sectional analysis, no control for medications and findings limited to males. CONCLUSIONS: These data demonstrate preferential involvement of caudal cingulate area (vs. thickness) and hippocampus subregions in PTSD. The inverse association between hippocampus volume and mean arterial pressure may contribute to accelerated aging known to be associated with PTSD.

Frontotemporal thalamic connectivity in schizophrenia and schizotypal personality disorder.

Schizotypal personality disorder (SPD) resembles schizophrenia, but with attenuated brain abnormalities and the absence of psychosis. The thalamus is integral for processing and transmitting information across cortical regions and widely implicated in the neurobiology of schizophrenia. Comparing thalamic connectivity in SPD and schizophrenia could reveal an intermediate schizophrenia-spectrum phenotype to elucidate neurobiological risk and protective factors in psychosis. We used rsfMRI to investigate functional connectivity between the mediodorsal nucleus (MDN) and pulvinar, and their connectivity with frontal and temporal cortical regions, respectively in 43 healthy controls (HCs), and individuals in the schizophrenia-spectrum including 45 psychotropic drug-free individuals with SPD, and 20 individuals with schizophrenia-related disorders [(schizophrenia (n = 10), schizoaffective disorder (n = 8), schizophreniform disorder (n = 1) and psychosis NOS (n = 1)]. Individuals with SPD had greater functional connectivity between the MDN and pulvinar compared to individuals with schizophrenia. Thalamo-frontal (i.e., between the MDN and rostral middle frontal cortex) connectivity was comparable in SPD and HCs; in SPD greater connectivity was associated with less symptom severity. Individuals with schizophrenia had less thalamo-frontal connectivity and thalamo-temporal (i.e., pulvinar to the transverse temporal cortex) connectivity compared with HCs. Thalamo-frontal functional connectivity may be comparable in SPD and HCs, but abnormal in schizophrenia, and that this may be protective against psychosis in SPD.

Cingulate and temporal lobe fractional anisotropy in schizotypal personality disorder.

BACKGROUND: Consistent with the clinical picture of milder symptomatology in schizotypal personality disorder (SPD) than schizophrenia, morphological studies indicate SPD abnormalities in temporal lobe regions but to a much lesser extent in prefrontal regions implicated in schizophrenia. Lower fractional anisotropy (FA), a measure of white-matter integrity within prefrontal, temporal, and cingulate regions has been reported in schizophrenia but has been little studied in SPD. AIMS: The study aim was to examine temporal and prefrontal white matter FA in 30 neuroleptic-naïve SPD patients and 35 matched healthy controls (HCs). We hypothesized that compared with HCs, SPD patients would exhibit lower FA in temporal lobe and anterior cingulum regions but relative sparing in prefrontal regions. METHOD: We acquired diffusion tensor imaging (DTI) in all participants and examined FA in the white matter underlying Brodmann areas (BAs) in dorsolateral prefrontal (BAs 44, 45, and 46), temporal lobe (BAs 22, 21, and 20), and cingulum (BAs 25, 24, 31, 23, and 29) regions with a series of analyses using multivariate analysis of variance. RESULTS: Compared with HCs, the SPD group had significantly lower FA in the left temporal lobe but not prefrontal regions. In the cingulum, FA was lower in the SPD group in the posterior regions (BAs 31 and 23), higher in the anterior (BA 25) regions and lower overall in the right but not the left cingulum. Among the SPD group, lower FA in the cingulum was associated with more severe negative symptoms (e.g., odd speech). CONCLUSIONS: Similar to schizophrenia, our results indicate cingulum-temporal lobe FA abnormalities in SPD and suggest that cingulum abnormalities are associated with negative symptoms.