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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.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.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.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.

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.

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.

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-18fluorodeoxyglucose (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.

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.

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.

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

Research suggests many shared clinical features across individuals with Schizotypal Personality Disorder (SPD) and Borderline Personality Disorder (BPD), including problems with attention/ executive functioning and mood. Therefore, aspects of these areas of functioning were compared in SPD and BPD to better characterize their respective difficulties. BPD, SPD, and healthy control (HC) participants were administered measures of cognitive and mood functioning. Compared with healthy controls, SPD patients performed significantly worse on aspects of the Delayed-Matching- to-Sample task, a measure of short-term visual memory abilities; however, the individuals with BPD did not differ from healthy controls. Neither of the patient groups differed from HC’s on measures of processing speed or planning. With regard to mood functioning, the BPD group exhibited significantly higher levels of affective disturbance (e.g., sadness, fear, anger) compared with the SPD patients and HCs. Overall, findings suggest different patterns of fronto-subcortical weakness in each patient group. While SPD patients exhibited relative weakness with short-term memory, BPD patient performance on such measures did not reveal relative weakness compared with HCs but did implicate problems with mood.