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Objective: To (a) compare the size of the dorsal and ventral striatum (caudate and putamen) in a large sample of antipsychotic-naïve individuals with schizotypal personality disorder (SPD) and healthy control participants; (b) examine symptom correlates of striatal size in SPD.Methods: The left and right caudate and putamen were hand-traced on structural MRI at five dorsal to ventral slice levels in 76 SPD and 148 healthy control participants. A Group×Region (caudate, putamen)×Slice (1-5: ventral, 2, 3, 4, dorsal)×Hemisphere (left, right) mixed-model MANOVA was conducted on size relative to whole brain.Results: Primary results showed that compared with the controls, the SPD group showed (a) larger bilateral putamen size overall and this enlargement was more pronounced at the most ventral and dorsal levels; in contrast, there were no between-group differences in caudate volume; (b) larger bilateral size of the striatum ventrally, averaged across the caudate and putamen. Among the SPD group, larger striatal size ventrally, particularly in the left hemisphere was associated with less severe paranoid symptoms.Conclusions: Striatal size is abnormal in SPD and resembles that of patients with schizophrenia who respond well to antipsychotic treatment. The results suggest that striatal size may be an important endophenotype to consider when developing new pharmacological treatments and when studying factors mitigating psychosis. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

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., (Published by Elsevier Inc.)

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., Competing Interests: Declaration of competing interest Dr. Harvey has received consulting fees or travel reimbursements from Alkermes, Bio Excel, Boehringer Ingelheim, Karuna Pharma, Merck Pharma, Minerva Pharma, and Sunovion (DSP) Pharma in the past year. He receives royalties from the Brief Assessment of Cognition in Schizophrenia (Owned by WCG Endpoint Solutions, Inc. and contained in the MCCB). He is chief scientific officer of i-Function, Inc. and Scientific Consultant to EMA Wellness, Inc. Dr. Perez-Rodriguez has received consulting fees from Alkermes and Neurocrine Biosciences., (Copyright © 2024. Published by Elsevier B.V.)

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-1β, 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 F 1,91.77  = 5.58, p  = 0.0203) and TNF-α ( F 1,101.73  = 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, Wilson, Alter, Ge, Hazlett, Goodman, Yehuda, Galfalvy and Haghighi.)

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.

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).

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., Competing Interests: Declaration of Competing Interest None, (Published by Elsevier B.V.)

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., (Published by Elsevier Ltd.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

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 [ 11 C]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 [ 11 C]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 [ 11 C]DASB in IED patients. Greater baseline VST [ 11 C]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., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

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., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (Published by Elsevier B.V.)

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., (© 2022 by the Research Society on Alcoholism.)

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., (Published by Elsevier B.V.)

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).

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.

Suicide is currently among the leading causes of death among individuals with schizophrenia. Reducing mortality from suicide remains a major clinical challenge in the care of veterans with schizophrenia. There is a need to increase our understanding of what elevates suicide risk in veterans with schizophrenia as a first step towards the future development of suicide prevention interventions. This study compared demographic and clinical features of military veterans with schizophrenia with vs. without suicidality to determine specific risk factors for suicidality. The sample consisted of two groups of veterans with schizophrenia: suicide ideators and/or attempters (SIA) and individuals without a history of suicidal ideation or attempts (no-SIA). Participants were interviewed using the Structured Clinical Interview for DSM-5 Axis I disorders (SCID-I), Positive and Negative Syndrome Scale for Schizophrenia (PANSS), Hamilton Depression Rating Scale (HDRS), and Schizotypal Personality Questionnaire (SPQ). In bivariate analyses, the PANSS-Positive Symptom scores, PANSS-General Psychopathology scores, HDRS total score, HDRS-Paranoid symptoms item score, and SPQ total scores were higher among SIA compared with no-SIA patients. In this unique clinical sample of veterans with schizophrenia, SIA patients were more likely to have mood disorders, post-traumatic stress disorder (PTSD), and/or alcohol use disorder in comparison to the no-SIA group. Logistic regression analysis indicated that the HDRS total score and presence/absence of comorbid mood disorder drive the difference between the groups. These results indicate that suicide risk assessment in veterans with schizophrenia should include identifying individuals with comorbid mood disorders/symptoms, PTSD, alcohol use disorder, marked positive symptoms, and schizotypal features., (Published by Elsevier Ltd.)

Self-harming behavior (SB) is one of the diagnostic criteria for borderline personality disorder (BPD). However, it is not exhibited by all individuals with BPD. Furthermore, studies examining the neural correlates of SB in BPD are lacking. Given research showing that BPD patients have difficulty habituating to affective stimuli, this study investigated whether anomalous amygdala activation is specific to BPD patients with SB. The authors used fMRI to compare amygdala activation in BPD patients with SB ( n = 15) to BPD patients without SB ( n = 18) and healthy controls ( n = 32) during a task involving pleasant, neutral, and unpleasant pictures, presented twice. BPD patients with SB demonstrated greater amygdala activity during the second presentation of unpleasant pictures. Results highlight neurobiological differences in BPD patients with and without SB and suggest that anomalous amygdala habituation to unpleasant stimuli may be related to SB.

In 2008, the Department of Veterans Affairs mandated that clinicians oversee the construction of a Suicide Safety Plan for every patient who is identified as "high risk" for suicide. While the Suicide Safety Plan is a mandated "best practice," there are currently no recommended guidelines for its augmentation in a group setting. To address this gap, a novel group intervention, "Project Life Force," (PLF; a 10-session manualized psychotherapy), was developed and piloted. Results indicate high feasibility and acceptability. Exploratory analysis revealed statistically significant decreases in suicidal thoughts/behaviors, depression, and hopelessness. Feedback from Veterans and PLF therapists is also discussed. Despite some limitations (e.g. small sample size) exploratory results suggest that PLF may be a promising treatment for Veterans with suicidal symptomology.

Introduction: Growing evidence suggests emotion reactivity-sensitivity and intensity of emotional experience-may represent a diathesis for suicide risk. However, our understanding of its ability to differentiate risk for suicidal ideation (SI) from suicide attempt (SA) is limited., Method: This study compares Veterans with SI (n = 81) to Veterans with SA (n = 177) history on factors relevant to emotion reactivity to determine which variable(s) best differentiate groups. Variables examined are multimodal: (a) self-report: childhood trauma, combat exposure; (b) clinician-assessed: non-suicidal self-injury (NSSI), structured diagnostic interview of psychopathology; and (c) psychophysiological: affect-modulated startle (AMS; proxy for amygdala reactivity and emotion reactivity) to unpleasant pictures was examined in a subset (n = 90)., Results: SA history was independently predicted by NSSI history, MDD, PTSD, and SUD diagnosis. Childhood trauma and combat exposure did not differentiate groups. The composite risk index demonstrated good accuracy (AUC=0.71, sensitivity=0.90, specificity=0.49). Only AMS independently predicted SA history when added to the model and accuracy was improved (AUC=0.82, sensitivity=0.85, specificity=0.56)., Conclusion: NSSI history, MDD, PTSD, and SUD diagnosis may be salient risk factors for this population. However, emotion reactivity is a more parsimonious predictor of SA history among Veterans suggesting it is an important treatment target among Veterans with SI., (© Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Sleep dysregulation is prevalent among veterans and is associated with increased risk of suicidal ideation and behaviors. A confluence of risk factors have been identified to date that contribute to increase risk for suicidal behavior. How these risk factors including childhood trauma, comorbid psychopathology, impulsivity, and hostility together with sleep disturbance contribute to suicide risk remains an open question. These factors have never been examined simultaneously in a unified mediation model, as investigated in the present study, to determine their relative contribution to suicide risk., Methods: Veterans (N = 105) were recruited across 3-groups, including Major Depressive Disorder (MDD) with/without a history of a suicide attempt (n = 35 and n = 37, respectively), and non-psychiatric controls, who had no history of mental illness or suicidal behavior (n = 33). The participants were assessed using validated self-report assessments with in-depth phenotyping for relevant risk factors associated with suicidal behavior including childhood adversity, depression severity, impulsivity, hostility, and sleep quality. These factors were included in mediation models using path analysis., Results: Across all subjects including those with MDD and non-psychiatric controls, mediation analysis showed that higher levels of childhood trauma had an indirect effect on poor sleep quality (p = 0.001). This effect was orthogonal, being independently mediated by both MDD psychopathology (p = 0.003), and higher traits of impulsivity (p = 0.001) and hostility (p = 0.015). Amongst MDD veterans, childhood trauma was directly associated with increased suicide risk (p = 0.034), irrespective of their severity of depression, or their degree of hostility and impulsivity., Limitations: include use of self-report data, and the inability to establish causal inferences with cross-sectional design., Conclusion: Childhood adversity as a significant pre-deployment risk factor for disturbed sleep and elevated suicide risk, potentially important for incorporation in clinical practice for suicide., (Published by Elsevier Ltd.)

Long-standing theories of borderline personality disorder (BPD) suggest that symptoms develop at least in part from childhood adversity. Emotion dysregulation may meaningfully mediate these effects. The current study examined three factors related to emotion dysregulation-alexithymia, affective lability, and impulsivity-as potential mediators of the relation between childhood adversity and BPD diagnosis in 101 individuals with BPD and 95 healthy controls. Path analysis compared three distinct models informed by the literature. Results supported a complex mediation model wherein (a) alexithymia partially mediated the relation of childhood adversity to affective lability and impulsivity; (b) affective lability mediated the relation of childhood adversity to BPD diagnosis; and (c) affective lability and impulsivity mediated the relation of alexithymia to BPD diagnosis. Findings suggest that affective lability and alexithymia are key to understanding the relationship between childhood adversity and BPD. Interventions specifically targeting affective lability, impulsivity, and alexithymia may be particularly useful for this population.

Rationale: Previous research has suggested that schizotypal personality disorder (SPD), a condition that shares clinical and cognitive features with schizophrenia, may be associated with elevated striatal dopamine functioning; however, there are no published studies of dopamine release within subregions of the striatum in SPD., Objectives: To characterize dopamine release capacity in striatal subregions and its relation to clinical and cognitive features in SPD., Methods: We used positron emission tomography with [ 11 C]raclopride and an amphetamine challenge to measure dopamine D2-receptor availability (binding potential, BP ND ), and its percent change post-amphetamine (∆BP ND ) to index amphetamine-induced dopamine release, in subregions of the striatum in 16 SPD and 16 healthy control participants. SPD participants were evaluated with measures of schizotypal symptom severity and working memory., Results: There were no significant group differences in BP ND or ∆BP ND in any striatal subregion or whole striatum. Among SPD participants, cognitive-perceptual symptoms were associated at trend level with ∆BP ND in the ventral striatum, and disorganized symptoms were significantly negatively related to ∆BP ND in several striatal subregions., Conclusions: In contrast to previous findings, SPD was not associated with elevated striatal dopamine release. However, in SPD, there was a moderate positive association between ventral striatal dopamine release and severity of cognitive-perceptual symptoms, and negative associations between striatal dopamine release and severity of disorganized symptoms. Future larger scale investigations that allow for the separate examination of subgroups of participants based on clinical presentation will be valuable in further elucidating striatal DA functioning in SPD.

Neuroimaging may predict response to cognitive remediation therapy and social skills training (CRT + SST) in schizophrenia. Identifying biological predictors of response is crucial for treatment decision making given not all patients respond to such interventions. Nineteen veterans with schizophrenia enrolled in an 8-week trial of CRT + SST. Ten participants completed diffusion tensor imaging (DTI) at baseline. Baseline fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and overall average FA predicted improvements in visual-spatial working memory, and social cognition, respectively. Neuroimaging may be useful in identifying therapeutic targets in schizophrenia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Despite considerable phenomentological differences between borderline personality disorder (BPD) and schizotypal personality disorder (SPD), research increasingly provides evidence that some BPD symptoms overlap with SPD symptoms (e.g., disturbed cognitions). We examined the cingulate, a brain region implicated in the pathophysiology of both disorders, to determine similarities/differences between the groups, and similarities/differences from healthy controls (HC's). 3T structural and diffusion tensor magnetic resonance imaging scans were acquired in BPD (n = 27), SPD (n = 32), HC's (n = 34). Results revealed that BPD patients exhibited significantly lower FA in posterior cingulate white matter compared to HC's (p = 0.04), but SPD patients did not., (Published by Elsevier B.V.)

This is a selective review of the work of Buchsbaum and colleagues. It revisits and pays tribute to four decades of publications employing positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) to examine the neurobiology of schizophrenia-spectrum disorders (including schizotypal personality disorder (SPD) and schizophrenia). Beginning with a landmark FDG-PET study in 1982 reporting hypofrontality in unmedicated schizophrenia patients, Buchsbaum and colleagues published high-impact work on regional glucose metabolic rate (GMR) abnormalities in the spectrum. Several key discoveries were made, including the delineation of schizophrenia-spectrum abnormalities in frontal and temporal lobe, cingulate, thalamus, and striatal regions using three-dimensional mapping with coregistered MRI and PET. These findings indicated that SPD patients have less marked frontal lobe and striatal dysfunction compared with schizophrenia patients, possibly mitigating frank psychosis. Additionally, these investigations were among the first to conduct early seed-based functional connectivity analyses with FDG-PET, showing aberrant cortical-subcortical circuitry and, in particular, revealing a thalamocortical circuitry abnormality in schizophrenia. Finally, pioneering work employing the first double-blind randomized antipsychotic (haloperidol) vs. placebo FDG-PET study design in schizophrenia indicated that GMR in the striatum, more than in any other region, was related to clinical response., (Copyright © 2019. Published by Elsevier B.V.)

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Given the common use of self-report questionnaires to assess schizotypy in personality pathology and schizophrenia research, it is important to determine the concordance between self-report and clinician ratings. 250 individuals with schizotypal personality disorder (SPD) and 116 community controls (CTR) were assessed on schizotypal traits using a clinical interview, the Structured Interview for DSM-IV Personality disorders (SIDP), and a self-report questionnaire, the Schizotypal Personality Questionnaire (SPQ). Ordinal logistic regressions examined concordance between self-reported and clinician-rated scores in CTR and SPD separately. Analyses of variance examined how the SPQ performed on differentiating between CTR with low schizotypy, CTR with high schizotypy, and SPD. For both CTR and SPD, higher SPQ subscale scores were significantly associated with higher clinician ratings on the respective SIDP items for the Ideas of Reference, Magical Thinking, Unusual Perceptual Experience, Suspiciousness, and Social Anxiety items, but not the Odd Speech or Limited Affect items. Higher SPQ subscale scores for Odd Behavior and Lack of Close Friends were significantly associated with the clinician-rated SIDP item scores in CTR but not SPD. CTR with low schizotypy scored lower on all SPQ subscales than CTR with high schizotypy, who did not differ from SPD. Self-report ratings are concordant with clinician ratings for positive schizotypal traits, whereas certain disorganization and interpersonal traits are not, particularly for individuals with SPD. The SPQ can differentiate between high and low schizotypy controls, but not between high schizotypy controls and individuals with SPD. Assessment of schizotypal traits should include both self-report questionnaires and clinician ratings., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Impaired cognition is a hallmark of schizophrenia spectrum disorders, including schizotypal personality disorder, and it is the best predictor of functional outcome. Cognitive remediation therapy has demonstrated efficacy for improving cognition, augmenting other rehabilitation efforts in schizophrenia, and effecting gains in real-world functioning. Pharmacological augmentation of cognitive remediation has been attempted, but the effects of augmentation on combined therapies, such as cognitive remediation and social skills training, have not been studied., Methods: Twenty-eight participants with schizotypal personality disorder enrolled in an 8-week, randomized, double-blind, placebo-controlled trial of guanfacine plus cognitive remediation and social skills training (15 guanfacine, 13 placebo). Cognition was assessed with the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB), social cognition with the Movie for the Assessment of Social Cognition (MASC), and functional capacity with the University of California San Diego Performance-Based Skills Assessment (UPSA)., Results: A statistically significant pre- versus posttreatment effect was observed for MCCB speed of processing, verbal learning, and visual learning and UPSA total score. A significant time-by-medication (guanfacine, placebo) interaction was observed for MCCB reasoning and problem solving and UPSA total score; the time-by-treatment interaction approached significance for MASC hypomentalizing errors., Conclusions: Both guanfacine and cognitive remediation plus social skills training were well tolerated, with no side effects or dropouts. Participants treated with cognitive remediation, social skills training, and guanfacine demonstrated statistically significant improvements in reasoning and problem solving, as well as in functional capacity and possibly social cognition, compared with those treated with cognitive remediation, social skills training, and placebo. Cognitive remediation plus social skills training may be an appropriate intervention for individuals with schizotypal personality disorder, and guanfacine appears to be a promising pharmaceutical augmentation to this psychosocial intervention.

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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This is a selective review of the work of Buchsbaum and colleagues. It revisits and pays tribute to four decades of publications employing positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) to examine the neurobiology of schizophrenia-spectrum disorders (including schizotypal personality disorder (SPD) and schizophrenia). Beginning with a landmark FDG-PET study in 1982 reporting hypofrontality in unmedicated schizophrenia patients, Buchsbaum and colleagues published high-impact work on regional glucose metabolic rate (GMR) abnormalities in the spectrum. Several key discoveries were made, including the delineation of schizophrenia-spectrum abnormalities in frontal and temporal lobe, cingulate, thalamus, and striatal regions using three-dimensional mapping with coregistered MRI and PET. These findings indicated that SPD patients have less marked frontal lobe and striatal dysfunction compared with schizophrenia patients, possibly mitigating frank psychosis. Additionally, these investigations were among the first to conduct early seed-based functional connectivity analyses with FDG-PET, showing aberrant cortical-subcortical circuitry and, in particular, revealing a thalamocortical circuitry abnormality in schizophrenia. Finally, pioneering work employing the first double-blind randomized antipsychotic (haloperidol) vs. placebo FDG-PET study design in schizophrenia indicated that GMR in the striatum, more than in any other region, was related to clinical response., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Both autism spectrum disorder (ASD) and schizophrenia are often characterized as disorders of white matter integrity. Multimodal investigations have reported elevated metabolic rates, cerebral perfusion and basal activity in various white matter regions in schizophrenia, but none of these functions has previously been studied in ASD. We used 18 fluorodeoxyglucose positron emission tomography to compare white matter metabolic rates in subjects with ASD (n = 25) to those with schizophrenia (n = 41) and healthy controls (n = 55) across a wide range of stereotaxically placed regions-of-interest. Both subjects with ASD and schizophrenia showed increased metabolic rates across the white matter regions assessed, including internal capsule, corpus callosum, and white matter in the frontal and temporal lobes. These increases were more pronounced, more widespread and more asymmetrical in subjects with ASD than in those with schizophrenia. The highest metabolic increases in both disorders were seen in the prefrontal white matter and anterior limb of the internal capsule. Compared to normal controls, differences in gray matter metabolism were less prominent and differences in adjacent white matter metabolism were more prominent in subjects with ASD than in those with schizophrenia. Autism spectrum disorder and schizophrenia are associated with heightened metabolic activity throughout the white matter. Unlike in the gray matter, the vector of white matter metabolic abnormalities appears to be similar in ASD and schizophrenia, may reflect inefficient functional connectivity with compensatory hypermetabolism, and may be a common feature of neurodevelopmental disorders.

Abnormalities in temporal and frontal cortical volume, white matter tract integrity, and hemispheric asymmetry have been implicated in schizophrenia-spectrum disorders. Schizotypal personality disorder can provide insight into vulnerability and protective factors in these disorders without the confounds associated with chronic psychosis. However, multimodal imaging and asymmetry studies in SPD are sparse. Thirty-seven individuals with SPD and 29 healthy controls (HC) received clinical interviews and 3T magnetic resonance T1-weighted and diffusion tensor imaging scans. Mixed ANOVAs were performed on gray matter volumes of the lateral temporal regions involved in auditory and language processing and dorsolateral prefrontal cortex involved in executive functioning, as well as fractional anisotropy (FA) of prominent white matter tracts that connect frontal and temporal lobes. In the temporal lobe regions, there were no group differences in volume, but SPD had reduced right>left middle temporal gyrus volume asymmetry compared to HC and lacked the right>left asymmetry in the inferior temporal gyrus volume seen in HC. In the frontal regions, there were no differences between groups on volume or asymmetry. In the white matter tracts, SPD had reduced FA in the left sagittal stratum and superior longitudinal fasciculus, and increased right>left asymmetry in sagittal stratum FA compared to HC. In the SPD group, lower left superior longitudinal fasciculus FA was associated with greater severity of disorganization symptoms. Findings suggest that abnormities in structure and asymmetry of temporal regions and frontotemporal white matter tract integrity are implicated in SPD pathology., (Published by Elsevier B.V.)

Schizotypy captures the underlying genetic vulnerability to schizophrenia. However, the genetic underpinnings of schizotypy remain unexplored. The authors examined the relationship between single nucleotide poly-morphisms (SNPs) and schizotypy. A sample of 137 subjects (43 healthy controls, 34 subjects with schizotypal personality disorder [SPD], 32 with borderline personality disorder, and 25 with other personality disorders) completed the Schizotypal Personality Questionnaire (SPQ). Subjects were genotyped using a custom array chip. Principal component analysis was used to cluster SPQ variables. Linear regression tested for associations between dimensional schizotypy and SNPs. Logistic regression tested for associations between SNPs and SPD diagnosis. There were significant associations between the minor alleles of three SNPs within the glycine receptor alpha 1 subunit (GLRA1) and the disorganized schizotypy dimension, even after Bonferroni correction. There were no significant associations between any SNPs and the categorical SPD diagnosis. Glycine receptor pathways may have an impact on dimensional traits of psychosis.

Several models have been proposed to account for observed overlaps in clinical features and genetic predisposition between schizophrenia and autism spectrum disorder. This study assessed similarities and differences in topological patterns and vectors of glucose metabolism in both disorders in reference to these models. Co-registered 18 fluorodeoxyglucose PET and MRI scans were obtained in 41 schizophrenia, 25 ASD, and 55 healthy control subjects. AFNI was used to map cortical and subcortical regions of interest. Metabolic rates were compared between three diagnostic groups using univariate and multivariate repeated-measures ANOVA. Compared to controls, metabolic rates in schizophrenia subjects were decreased in the frontal lobe, anterior cingulate, superior temporal gyrus, amygdala and medial thalamic nuclei; rates were increased in the occipital cortex, hippocampus, basal ganglia and lateral thalamic nuclei. In ASD subjects metabolic rates were decreased in the parietal lobe, frontal premotor and eye-fields areas, and amygdala; rates were increased in the posterior cingulate, occipital cortex, hippocampus and basal ganglia. In relation to controls, subjects with ASD and schizophrenia showed opposite changes in metabolic rates in the primary motor and somatosensory cortex, anterior cingulate and hypothalamus; similar changes were found in prefrontal and occipital cortices, inferior parietal lobule, amygdala, hippocampus, and basal ganglia. Schizophrenia and ASD appear to be associated with a similar pattern of metabolic abnormalities in the social brain. Divergent maladaptive trade-offs, as postulated by the diametrical hypothesis of their evolutionary relationship, may involve a more circumscribed set of anterior cingulate, motor and somatosensory regions and the specific cognitive functions they subserve.

Autism spectrum disorders and schizophrenia have been variously characterized as separate nosological entities with overlapping deficits in social cognition or diametrical extremes of a phenotypic continuum. This study aimed to determine how these models apply to comparative morphometric data. MRI scans of the brain were obtained in 49 subjects with schizophrenia, 20 subjects with autism and 39 healthy controls. Images were parcellated into 40 Brodmann areas and entered into repeated-measures ANOVA for between-group comparison of global and localized gray and white matter volumes. A pattern of lower gray mater volumes and greater white matter volumes was found in subjects with schizophrenia in comparison to subjects with autism. For both gray and white matter, this pattern was most pronounced in regions associated with motor-premotor and anterior frontal cortex, anterior cingulate, fusiform, superior and middle temporal gyri. Patient groups tended to diverge from healthy controls in opposite directions, with greater-than-normal gray matter volumes and lower-than-normal white matter volumes in subjects with autism and reversed patterns in subjects with schizophrenia. White matter reductions in subjects with autism were seen in posterior frontal lobe and along the cingulate arch. Normal hemispheric asymmetry in the temporal lobe was effaced in subjects with autism and schizophrenia, especially in the latter. Nearly identical distribution of changes and diametrically divergent volumetry suggest that autism and schizophrenia may occupy opposite extremes of the same cognitive continuum.

A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype., (Copyright © 2017. Published by Elsevier B.V.)

The long-term effects of blast exposure are a major health concern for combat veterans returning from the recent conflicts in Iraq and Afghanistan. We used an optimized diffusion tensor imaging tractography algorithm to assess white matter (WM) fractional anisotropy (FA) in blast-exposed Iraq and Afghanistan veterans ( n  = 40) scanned on average 3.7 years after deployment/trauma exposure. Veterans diagnosed with a blast-related mild traumatic brain injury (mTBI) were compared to combat veterans with blast exposure but no TBI diagnosis. Blast exposure was associated with decreased FA in several WM tracts. However, total blast exposure did not correlate well with neuropsychological testing performance and there were no differences in FA based on mTBI diagnosis. Yet, veterans with mTBI performed worse on every neurocognitive test administered. Multiple linear regression across all blast-exposed veterans using a six-factor prediction model indicated that the amount of blast exposure accounted for 11-15% of the variability in composite FA scores such that as blast exposure increased, FA decreased. Education accounted for 10% of the variability in composite FA scores and 25-32% of FA variability in the right cingulum, such that as level of education increased, FA increased. Total blast exposure, age, and education were significant predictors of FA in the left cingulum. We did not find any effect of post-traumatic stress disorder on cognition or composite FA. In summary, our findings suggest that greater total blast exposure is a contributing factor to poor WM integrity. While FA was not associated with neurocognitive performance, we hypothesize that FA changes in the cingulum in veterans with multiple combat exposures and no head trauma prior to deployment may represent a marker of vulnerability for future deficits. Future work needs to examine this longitudinally.

Patients with borderline personality disorder (BPD) are at high risk for suicidal behavior. However, many BPD patients do not engage in suicidal behavior. In this study, we compared clinical features of BPD patients with or without a history of suicide attempts and healthy volunteers. Compared with healthy volunteers, both BPD groups had higher Affective Lability Scale (ALS), ALS - Depression-Anxiety Subscale, Barratt Impulsivity Scale (BIS), and Lifetime History of Aggression (LHA) scores and were more likely to have a history of temper tantrums. BPD suicide attempters had higher ALS, ALS - Depression-Anxiety Subscale and LHA scores and were more likely to have a history of non-suicidal self-injury or temper tantrums compared to BPD non-attempters. Also, BPD suicide attempters were more likely to have a history of comorbid major depressive disorder and less likely to have comorbid narcissistic personality disorder (NPD) in comparison to BPD non-attempters. About 50% of study participants in each BPD group had a history of comorbid substance use disorder (SUD). Our study indicates that BPD patients with a history of suicide attempt are more aggressive, affectively dysregulated and less narcissistic than BPD suicide non-attempters., (Published by Elsevier Ireland Ltd.)

Objective: Despite advances in suicide prevention implemented throughout the US Department of Veterans Affairs (VA) including the hiring of Suicide Prevention Coordinators (SPCs) at every VA hospital, enhanced monitoring, and the availability of 24-hour crisis hotline services, suicide by veterans remains a critical problem affecting 20 veterans daily. Few empirically based treatment strategies for suicide prevention for postdeployment military personnel exist. This study aimed to test whether dialectical behavior therapy (DBT), one of the few psychosocial treatments with proven efficacy in diminishing suicidal behavior in individuals with personality disorder, can be applied to veterans irrespective of personality diagnosis., Methods: From January 2010 to December 2014, 91 nonpsychotic veterans at high risk for suicide (61 men, 30 women) were randomly assigned to a 6-month treatment trial at a veterans' medical center comparing standard DBT to treatment as usual (TAU) and followed for 6 months after trial completion. Primary outcome was suicide attempts, measured with the Columbia-Suicide Severity Rating Scale, and secondary outcomes were suicide ideation, depression, hopelessness, and anxiety. There were no exclusions pertaining to substance abuse, homelessness, or medical comorbidity., Results: Both DBT and TAU resulted in improvements in suicidal ideation, depression, and anxiety during the course of the 6-month treatment trial that did not differ between treatment arms. Survival analyses for suicide attempts and hospitalizations did not differ between treatment arms. However, DBT subjects utilized significantly more individual mental health services than TAU subjects (28.5 ± 19.6 vs 14.7 ± 10.9, F₁,₇₇ = 11.60, P = .001)., Conclusions: This study is the first to examine 6-month DBT in a mostly male, veteran population. Increased mental health treatment service delivery, which included enhanced monitoring, outreach, and availability of a designated SPC, did not yield statistically significant differences in outcome for veterans at risk for suicide in TAU as compared to the DBT treatment arm. However, both treatments had difficulty with initial engagement post-hospitalization. Future studies examining possible sex differences and strategies to boost retention in difficult-to-engage, homeless, and substance-abusing populations are indicated., Trial Registration: ClinicalTrials.gov identifier: NCT02462694., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Unlabelled: Recent studies demonstrate that veterans exhibit higher suicide risk compared with the general U.S., Population: A prior suicide attempt is a well-documented predictor of suicide death. Despite increased attention to clinical risk factors of suicide and efforts to develop psychosocial interventions to reduce suicide risk, the underlying biological factors that confer this risk are not well understood. This study examined affect-modulated startle (AMS) during a series of intermixed unpleasant, neutral, and pleasant pictures in a sample of 108 demographically-matched veterans at low (passive ideators: n = 26) and high risk (active ideators: n = 29; single attempters: n = 28; and multiple attempters: n = 25) for suicide based on the Columbia Suicide Severity Rating Scale. An exploratory aim involved a longitudinal component in a subset of the high-risk sample that went on to participate in a randomized 6-month clinical trial. We investigated whether baseline AMS predicts a subsequent suicide attempt at 12-month follow-up. Compared with the other three groups, multiple attempters showed greater startle potentiation during unpleasant pictures and deficient overall startle habituation from early to later trials. The groups did not differ in startle during neutral or pleasant pictures, or self-reported picture valence. Greater startle during unpleasant pictures was associated with greater emotion dysregulation as measured by the Difficulties in Emotion Regulation Scale and a future suicide attempt assessed prospectively at 12-month follow-up. These findings suggest that startle potentiation during unpleasant pictures in multiple-suicide attempters is a promising psychophysiological biomarker of suicide risk and underscore the clinical importance of targeting emotion dysregulation in the treatment of patients at-risk for suicide., (© 2016 Society for Psychophysiological Research. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Gender is an important variable in the study of mental health because of the actual and perceived differences between men and women. Relatively little is known how males and females differ in their manifestations of antisocial personality disorder (ASPD). Demographic and clinical features of 323 participants with ASPD were assessed and recorded. Women had fewer episodes of antisocial behavior involving or not involving police, higher scores on the Childhood Trauma Questionnaire (CTQ) and on Emotional Abuse and Sexual Abuse subscales of the CTQ compared to men. CTQ scores positively correlated with the number of episodes of antisocial behavior involving police in men but not in women. The percentage of patients with comorbid borderline and histrionic personality disorders was higher and the percentage of participants with cocaine use disorder was lower among women compared to men. Comorbid alcohol use disorder was frequent in both groups, while a higher percentage of women had comorbid mood disorders compared to men. Logistic regression analysis demonstrates that CTQ scores, histrionic personality disorder, and antisocial behavior involving the police drive the difference between the groups. Our findings indicate that treatment of individuals with ASPD should focus on the management of comorbid psychiatric disorders., (Published by Elsevier Ireland Ltd.)

The corpus callosum has been implicated as a region of dysfunctional connectivity in schizophrenia, but the association between age and callosal pathology is unclear. Magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI) were performed on adults (n=34) and adolescents (n=17) with schizophrenia and adult (n=33) and adolescent (n=15) age- and sex-matched healthy controls. The corpus callosum was manually traced on each participant׳s MRI, and the DTI scan was co-registered to the MRI. The corpus callosum was divided into five anteroposterior segments. Area and anisotropy were calculated for each segment. Both patient groups demonstrated reduced callosal anisotropy; however, the adolescents exhibited reductions mostly in anterior regions while the reductions were more prominent in posterior regions of the adults. The adolescent patients showed greater decreases in absolute area as compared with the adult patients, particularly in the anterior segments. However, the adults showed greater reductions when area was considered relative to whole brain white matter volume. Our results suggest that the initial stages of the illness are characterized by deficiencies in frontal connections, and the chronic phase is characterized by deficits in the posterior corpus callosum; or, alternatively, adolescent-onset schizophrenia may represent a different or more severe form of the illness., (Published by Elsevier Ireland Ltd.)

Background: DSM-5 places schizophrenia on a continuum from severe, chronic schizophrenia to the attenuated schizophrenia-like traits of schizotypal personality disorder (SPD), the prototypic schizophrenia-related personality disorder. SPD shares common genetic and neurobiological substrates with schizophrenia, including information processing abnormalities, although they are less marked. This is the first study to directly compare the P50 evoked electroencephalographic response-a measure of sensory gating and a neurophysiological endophenotype-between schizophrenia-spectrum groups. Two hypotheses were tested: (1) Compared with healthy controls (HCs), schizophrenia patients show reduced P50 suppression and SPD patients resemble schizophrenia but exhibit less marked deficits; and (2) Deficient P50 suppression in SPD is associated with greater clinical symptom severity., Methods: P50 was assessed in 32 schizophrenia-spectrum disorder patients (12 SPD, 20 schizophrenia patients) and 25 demographically-matched HCs. The standard conditioning (C)-testing (T) paradigm was used and P50 suppression was quantified using the T-C difference and the T/C ratio., Results: All P50 measures showed a linear, stepwise pattern with the SPD group intermediate between the HC and schizophrenia groups. Compared with HCs, both patient groups had lower conditioning and T-C difference values. Among the SPD group, greater clinical symptom severity was associated with greater conditioning-response amplitude deficits., Conclusion: These findings: (1) are novel in showing that P50 deficits in SPD resemble those observed in schizophrenia, albeit less marked; (2) support the concept that the phenomenological link between SPD and schizophrenia lies in shared neurocognitive/neurophysiological pathologies; and (3) provide evidence that P50 is a neurophysiological endophenotype for schizophrenia-spectrum disorders., (Published by Elsevier B.V.)