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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. • Impulsivity is a common feature of bipolar disorder (BD). • Key brain regions involved in inhibition are underactivated in BD. • Brain regions involved in inhibition are overactivated when emotional stimuli are involved. • Brain activation abnormalities in BD during inhibition are trait-like across mood states. • Findings are consistent with disruptions in fronto-striatal-thalamic regions that are associated with symptoms of BD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Traumatic brain injury may impact impulsivity, increasing risk of suicide attempt. • Veterans with history of mild TBI showed more choice impulsivity. • However, less choice impulsivity may relate to more lethal suicide attempts. • Neither mild TBI nor suicide history related to motor impulsivity. Traumatic brain injury is associated with increased risk for suicide, but the underlying mechanisms remain poorly understood. One candidate mechanism is impulsivity, which includes both choice impulsivity (e.g., preference for smaller, immediate rewards) and motor impulsivity (inability to inhibit prepotent motor responding). We evaluated these facets of impulsivity in Veterans classified according to their history of mild TBI (mTBI) and/or prior suicide attempt. 99 Veterans were classified as having no mTBI or suicide attempt (control, n = 35), mTBI but no suicide attempt (mTBI, n = 42), or mTBI and prior attempt (mTBI+SA, n = 22). A computerized temporal discounting task (Monetary Choice Questionnaire) assessed choice impulsivity and a Go/No-go task assessed motor impulsivity. On temporal discounting, the control group showed less choice impulsivity than the mTBI group. Temporal discounting was not associated with suicide attempt history. However, among the mTBI+SA group, those with high-lethality suicide attempts showed less choice impulsivity than those with low-lethality attempts. No group differences emerged on the Go/No-go task. The findings are consistent with choice impulsivity as a potential pathway by which mTBI affects risk for suicide. The finding that high-lethality attempts were associated with greater willingness to wait for reward supports the emerging view of heterogeneous underlying pathways to suicide risk, with distinct phenotypes that implicate different therapeutic options. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. We obtained FDG positron emission tomography on 87 patients with Alcohol Use Disorder (AUD) and 41 age‐and sex‐matched healthy volunteers. Patients with AUD had reduced relative metabolic rates in the dorsolateral frontal cortex and elevated rates in the medial orbitofrontal, cingulate cortex, and subcortical structures (thalamus, ventral striatum). 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. [ABSTRACT FROM AUTHOR]

Abstract: It has been proposed that schizophrenia results partly from altered brain connectivity. The anterior cingulate cortex in particular has been demonstrated to be affected in schizophrenia, with studies reporting reduced volume, altered neuronal arrangement, decreased anisotropy in diffusion tensor images, and hypometabolism. We used a 3T Siemens scanner to acquire structural and diffusion tensor imaging in age-and sex-matched groups of 41 adults with chronic schizophrenia, 6 adults with recent-onset schizophrenia, and 38 healthy control subjects. We manually traced the anterior and posterior cingulate gyri on all subjects and then compared the volume and anisotropy across groups for the left and right anterior and posterior cingulate gyri. The anterior cingulate gyrus was divided axially into six equal segments, and the posterior cingulate gyrus into two segments. Volume was calculated for the anterior and posterior gyri, and average anisotropy was then calculated for each individual segment, looking separately at gray and white matter. We found decreased overall relative left and right gray matter volume in the anterior cingulate gyrus in persons with schizophrenia compared with healthy controls. Additionally, in both gray and white matter of the cingulate, we found that recent-onset patients had the highest anisotropy, chronic patients had the lowest, and controls were intermediate. These results provide additional evidence for the presence of both white and gray matter abnormalities in the cingulate gyrus, which has been implicated in schizophrenia. [Copyright &y& Elsevier]

Objetivo: Cada día hay más pruebas que demuestran que los circuitos del lóbulo frontal, cuerpo estriado, lóbulo temporal y cerebelo estàn alterados en los individuos con esquizofrenia, lo que sugiere que debería investigarse la actividad metabólica de la sustancia blanca que conecta estas áreas. Método: los autores obtuvieron tomografías por emisión de positrones (PET) con [18F] fluorodesoxiglucosa e imágenes de resonancia magnética (RM) ponderadas en T1 emparejadas de 170 individuos. Los participantes fueron 103 voluntarios normales y 67 pacientes con esquizofrenia (n = 61) o trastorno esquizoafectivo (n = 6) no tratados. Las imágenes se corregistraron y se trasladaron al espacio estándar para generar un mapa de su significación probabilística. Resultados: Comparados con los voluntarios normales, los pacientes presentaron mayores índices metabólicos relativos en la sustancia blanca frontal, el cuerpo calloso, el fascículo longitudinal superior y el núcleo de sustancia blanca del lóbulo temporal. El aumento de la actividad de la sustancia blanca fue más pronunciado en el centro de los grandes tractos de sustancia blanca, especialmente en las partes frontales del cerebro y en la cápsula interna. Este aumento en la sustancia blanca no pareció deberse por completo a cambios en las proporciones sustancia gris/sustancia blanca del cerebro, a un sesgo del índice metabólico del cerebro completo ni a un exceso de movimientos cefálicos de los pacientes, aunque estas posibilidades no pueden descartarse sin realizar determinaciones de la glucosa absoluta. Los pacientes también presentaron un metabolismo relativo de la glucosa significativamente menor en los lóbulos frontal y temporal, el núcleo caudado, la circunvolución cingular y el núcleo dorsomedial del tálamo frente a los voluntarios normales, en concordancia con estudios previos. Conclusiones: En las comparaciones entre pacientes esquizofrénicos no tratados y voluntarios normales, es evidente la existencia de aumentos metabólicos relativos en la sustancia blanca de los pacientes esquizofrénicos, así como de reducciones en la sustancia gris. Una ineficiencia de los circuitos cerebrales, defectos de la sustancia blanca que dan lugar a una mayor necesidad energética y alteraciones de la densidad de empaquetado de los axones son posibles explicaciones de este hallazgo de un mayor metabolismo relativo en la sustancia blanca en la esquizofrenia. [ABSTRACT FROM AUTHOR]

Background: The cingulate gyrus, which is involved in affect, attention, memory and higher executive functions, has been implicated as a dysfunctional region in schizophrenia. Postmortem studies report cytoarchitectural changes in the anterior cingulate gyrus (ACG) and functioning imaging studies show correlations between the degree of hypometabolism of the anterior cingulate and clinical symptoms in schizophrenia. Methods: Unmedicated patients with schizophrenia (n=27) and schizotypal personality disorder (SPD) (n=13), as well as sex- and age-matched control subjects (n=32), were studied with (18)F-fluorodeoxyglucose positron emission tomography (PET) scans and magnetic resonance imaging (MRI). As a control over mental activity, all subjects performed a verbal working memory task during the PET protocol. The cingulate gyrus was first outlined on the MRI scans and, after coregistration, the coordinates were applied to the PET scans to yield a three-dimensional metabolic map of the cingulate gyrus for each subject. A statistical resampling method was used to analyze the metabolic differences between groups. Results: Compared with controls, patients with schizophrenia had lower relative glucose metabolic rates in the left anterior cingulate and the right posterior cingulate gyrus (PCG) assessed by 3-D significance probability mapping. SPD patients had higher glucose metabolic rates (GMRs) in the left posterior cingulate than did controls. Furthermore, volumetric measurement with MRI showed the left anterior cingulate and Brodmann area 24' to be smaller in schizophrenic patients than controls. Conclusions: Compared with controls, patients with schizophrenia have metabolic and volumetric reductions in a cingulate gyrus area that is related to higher executive functions. Schizotypal patients rely more on sensory association areas to perform a cognitive task than do controls and seem to be a group that is partially distinct in its physiological and functional characteristics. [ABSTRACT FROM AUTHOR]

In an exploration of the schizophrenia spectrum, we compared cortical metabolic rates in unmedicated patients with schizophrenia and schizotypal personality disorder (SPD) with findings in age- and sex-matched normal volunteers. Coregistered magnetic resonance imaging (MRI) and positron emission tomography (PET) scans were obtained in 27 schizophrenic, 13 SPD, and 32 normal volunteers who performed a serial verbal learning test during tracer uptake. A template of Brodmann areas derived from a whole brain histological section atlas was used to analyze PET findings. Significantly lower metabolic rates were found in prefrontal areas 44–46 in schizophrenic patients than in normal volunteers. SPD patients did not differ from normal volunteers in most lateral frontal regions, but they had values intermediate between those of normal volunteers and schizophrenic patients in lateral temporal regions. SPD patients showed higher than normal metabolic rates in both medial frontal and medial temporal areas. Metabolic rates in Brodmann area 10 were distinctly higher in SPD patients than in either normal volunteers or schizophrenic patients. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. include use of self-report data, and the inability to establish causal inferences with cross-sectional design. 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. • Childhood trauma contributes to increased risk of sleep disturbance exacerbated by military service • The effect of childhood trauma on sleep disturbance is mediated by depression psychopathology, impulsivity, and hostility • Evaluation of childhood trauma as a pre-deployment risk factor for suicide needs to be incorporated in suicide prevention [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [11C]raclopride and an amphetamine challenge to measure dopamine D2-receptor availability (binding potential, BPND), and its percent change post-amphetamine (∆BPND) 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 BPND or ∆BPND in any striatal subregion or whole striatum. Among SPD participants, cognitive-perceptual symptoms were associated at trend level with ∆BPND in the ventral striatum, and disorganized symptoms were significantly negatively related to ∆BPND 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. [ABSTRACT FROM AUTHOR]

• Compared with healthy controls, patients with borderline personality disorder had significantly lower white matter fractional anisotropy in a segment of the posterior cingulate (approximately BA 23). • Cingulate white matter volume was significantly smaller in patients with borderline personality disorder compared with healthy controls. • Cingulate white matter volume was significantly smaller in patients with schizotypal personality disorder compared with healthy controls. • These findings in regions of the cingulate involved in error monitoring provide support for the use of clinical interventions in BPD that help promote self-monitoring, new learning, and the motivation to make adaptive change in cognition and behavior. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• The SI SPD group has greater impairment compared with the non-SI SPD group. • Depression and social networking drive the difference between SI and non-SI groups. • Both SI and non-SI SPD groups are impaired in comparison to the HC group. 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. [ABSTRACT FROM AUTHOR]

• Depressed Veterans with suicide attempt history exhibit smaller rostral anterior cingulate. • Less left rostral anterior cingulate cortex gray matter volume predicts suicide attempt history. • Lower levels of grit in depressed US Veterans predicts to suicide attempt history. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective Siever and Davis' (1991) psychobiological framework of borderline personality disorder (BPD) identifies affective instability (AI) as a core dimension characterized by prolonged and intense emotional reactivity. Recently, deficient amygdala habituation, defined as a change in response to repeated relative to novel unpleasant pictures within a session, has emerged as a biological correlate of AI in BPD. Dialectical behavior therapy (DBT), an evidence-based treatment, targets AI by teaching emotion-regulation skills. This study tested the hypothesis that BPD patients would exhibit decreased amygdala activation and improved habituation, as well as improved emotion regulation with standard 12-month DBT. Methods Event-related fMRI was obtained pre- and post-12-months of standard-DBT in unmedicated BPD patients. Healthy controls (HCs) were studied as a benchmark for normal amygdala activity and change over time (n = 11 per diagnostic-group). During each scan, participants viewed an intermixed series of unpleasant, neutral and pleasant pictures presented twice (novel, repeat). Change in emotion regulation was measured with the Difficulty in Emotion Regulation (DERS) scale. Results fMRI results showed the predicted Group × Time interaction: compared with HCs, BPD patients exhibited decreased amygdala activation with treatment. This post-treatment amygdala reduction in BPD was observed for all three pictures types, but particularly marked in the left hemisphere and during repeated-emotional pictures. Emotion regulation measured with the DERS significantly improved with DBT in BPD patients. Improved amygdala habituation to repeated-unpleasant pictures in patients was associated with improved overall emotional regulation measured by the DERS (total score and emotion regulation strategy use subscale). Conclusion These findings have promising treatment implications and support the notion that DBT targets amygdala hyperactivity-part of the disturbed neural circuitry underlying emotional dysregulation in BPD. Future work includes examining how DBT-induced amygdala changes interact with frontal-lobe regions implicated in emotion regulation. [ABSTRACT FROM AUTHOR]

• We examined connectivity of the mediodorsal nucleus (MDN) and pulvinar. • Groups included schizophrenia, schizotypal personality disorder (SPD) and controls. • Frontal to MDN functional connectivity was comparable in SPD and controls. • In SPD greater connectivity was associated with less symptom severity. • This pattern may be protective against psychosis in SPD. 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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Borderline personality disorder (BPD) often presents during adolescence. Early detection and intervention decreases its subsequent severity. However, little is known about early predictors and biological underpinnings of BPD. The observed abnormal functional connectivity among brain regions in BPD led to studies of white matter, as the neural substrate of connectivity. However, diffusion tensor imaging (DTI) studies in adult BPD have been inconclusive, and, as yet, there are no published DTI studies in borderline adolescents. Methods: We conducted DTI tractography in 38 BPD patients (14-adolescents, 24-adults) and 32 healthy controls (13-adolescents, 19-adults). Results: We found bilateral tract-specific decreased fractional anisotropy (FA) in inferior longitudinal fasciculus (ILF) in BPD adolescents compared to adolescent controls. ILF FA was significantly higher in adolescent controls compared to BPD adolescents, BPD adults and adult controls (Wilks F(3,57) = 3.55, p < 0.02). Follow-up voxelwise TBSS analysis demonstrated lower FA in BPD adolescents compared to adolescent controls also in uncinate and occipitofrontal fasciculi. Discussion: FA generally develops along an inverted U-shape curve, increasing through adolescence, and slowly decreasing in adulthood. Our findings suggest that, in adolescent BPD, this normal developmental “peak” in FA, which is seen in healthy controls, is not achieved. This suggests a possible neural substrate for the previously reported OFC-amygdala disconnect in adults with BPD. It raises the possibility that a white matter tract abnormality in BPD present in adolescence may not be appreciable in adulthood, but a functional abnormality in the coordination among brain regions persists. Our finding represents a possible biological marker to identify those at risk for developing BPD. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia ( n = 64) and healthy controls ( n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule. [ABSTRACT FROM AUTHOR]

Abstract: Sertindole, a 2nd generation antipsychotic with low movement disorder side effects, was compared with haloperidol in a 6-week crossover study. Fifteen patients with schizophrenia (mean age=42.6, range=22–59, 11 men and 4 women) received sertindole (12–24mg) or haloperidol (4–16mg) for 6weeks and then received a FDG-PET scan and an anatomical MRI. Patients were then crossed to the other treatment and received a second set of scans at week 12. Dose was adjusted by a physician blind to the medication type. Brodmann areas were identified stereotaxically using individual MRI templates applied to the coregistered FDG-PET image. Sertindole administration was associated with higher dorsolateral prefrontal cortex metabolic rates than haloperidol and lower orbitofrontal metabolic rates than haloperidol. This effect was greatest for gray matter of the dorsolateral Brodmann areas 8, 9, 10, 44, 45, and 46. Patients were further contrasted with an approximately age and sex-matched group of 33 unmedicated patients with schizophrenia and with a group of 55 normal volunteers. Sertindole administration was associated with greater change toward normal values and away from the values found in the unmedicated comparison group for dorsolateral prefrontal cortex gray matter and white matter underlying medial prefrontal and cingulate cortex. These results are consistent with the low motor side-effect profile of sertindole, greater improvement on prefrontal cognitive tasks with sertindole than haloperidol, and with the tendency of 2nd generation antipsychotic drugs to have greater frontal activation than haloperidol. [Copyright &y& Elsevier]

Abstract: Background: Decreased callosal size and anisotropy have been described in schizophrenia patients but their longitudinal progression remains poorly understood. Methods: We performed diffusion-tensor and structural magnetic resonance imaging at baseline and at follow-up four years later in 49 chronic schizophrenia patients and 16 healthy comparison subjects. Schizophrenia patients were subdivided into good-outcome (n =23) and poor-outcome (n =26) groups. Baseline-to-follow-up changes in size, shape, position and fractional anisotropy of the corpus callosum, divided into five sagittal sections and five rostro-caudal segments, were assessed. Results: At baseline scan and in comparison to healthy subjects, schizophrenia patients displayed 1) smaller callosal size, 2) lower average anisotropy in all sagittal sections except the midline, and 3) more dorsal average coordinate position. During the four years after the baseline scan, patients with schizophrenia exhibited a more pronounced decline in absolute size of the corpus callosum than healthy comparison subjects. As compared with the good-outcome group, the corpus callosum in poor-outcome patients at baseline was of smaller size and lower average anisotropy, more elongated and posteriorly positioned. During the follow-up interval, poor-outcome patients displayed a more pronounced decline in size but less pronounced decline in anisotropy of the corpus callosum than patients with good outcomes. Conclusions: Differences in callosal size between schizophrenia patients and healthy subjects seen at baseline continue to widen in the chronic phase of the illness, especially in patients with poor functional outcome. Baseline differences in callosal anisotropy among patients with different outcomes, however, diminish over time. [Copyright &y& Elsevier]

Abstract: Findings of white matter pathology as indicated by diffusion tensor anisotropy values in schizophrenia are well established, but the differences in this measure between the onset of the disease and the chronic state are not well known. To investigate the differences between these states in the progression of the disease of schizophrenia we acquired 1.5 T diffusion tensor anisotropy images on 35 adult patients with schizophrenia and schizoaffective disorder, 23 adolescents having their first psychotic episode, and age and sex matched controls (33 adults and 15 adolescents). Regions of interest in major cortical white matter tracts chosen as salient to the prefrontal executive deficit in schizophrenia were assessed using stereotaxic coordinates from the Talairach and Tournoux atlas. Regions of each tract along anterior–posterior and/or inferior–superior directions in both hemispheres were evaluated in multiway ANOVA. Tracts between the frontal lobe and other brain regions, but not temporal, occipital and interhemispheric tracts, showed a differential aging pattern in normals and patients indicating that the white matter pathology in these regions is not stable between the onset and the chronic state in schizophrenia. This suggests that tracts involved in the connectivity of the temporal lobe white matter deficits were already well in place in adolescent patients, while frontal lobe pathology continues to develop from adolescence to adulthood. [Copyright &y& Elsevier]

Abstract: Preliminary data suggest an association of posterior cortical gray matter reduction with poor outcome in schizophrenia. We made a systematic MRI assessment of regional gray and white matter volumes, parcellated into 40 Brodmann’s areas, in 104 patients with schizophrenia (51 with good outcomes, 53 with poor outcomes) and 41 normal comparison subjects, and investigated correlations of regional morphometry with outcome and severity of the illness. Schizophrenia patients displayed differential reductions in frontal and to a lesser degree temporal gray matter volumes in both hemispheres, most pronounced in the frontal pole and lateral temporal cortex. White matter volumes in schizophrenia patients were bilaterally increased, primarily in the frontal, parietal, and isolated temporal regions, with volume reductions confined to anterior cingulate gyrus. In patients with schizophrenia as a group, higher illness severity was associated with reduced temporal gray matter volumes and expanded frontal white matter volumes in both hemispheres. In comparison to good-outcome group, patients with poor outcomes had lower temporal, occipital, and to a lesser degree parietal gray matter volumes in both hemispheres and temporal, parietal, occipital, and posterior cingulate white matter volumes in the right hemisphere. While gray matter deficits in the granular cortex were observed in all schizophrenia patients, agranular cortical deficits in the left hemisphere were peculiar to patients with poor outcomes. These results provide support for frontotemporal gray matter reduction and frontoparietal white matter expansion in schizophrenia. Poor outcome is associated with more posterior distribution (posteriorization) of both gray and white matter changes, and with preferential impairment in the unimodal visual and paralimbic cortical regions. [Copyright &y& Elsevier]

Abstract: We acquired Positron emission tomography with 18-F-deoxyglucose (FDG-PET) and anatomical MRI in 30 never-previously medicated psychotic adolescents (ages 13–20). (FDG-PET) was obtained at baseline and after 8–9 weeks of a randomized double-blind trial of either olanzapine or haloperidol. Neuropsychological tests of executive function were also obtained. Patients carried out the serial verbal learning task, a modification of the California Verbal Learning Test, during the uptake of the FDG. PET scans were coregistered with spoiled gradient MRI (TR=24, TE=5, flip angle 40°, slice thickness 1.2 mm, field of view 230 mm) for accurate anatomical identification of regions of interest traced on the MRI. Twenty-two of the thirty patients completed the second PET and clinical evaluation. Individuals treated with olanzapine increased relative metabolic rates in the frontal lobe more than the occipital lobe while patients treated with haloperidol failed to increase frontal metabolic rates and did not show an anteroposterior gradient in medication response. Haloperidol increased striatal metabolic rate more than olanzapine. Both drugs increased thalamic metabolic rates and this increase was significantly larger in younger (age 13–15) than older (16–21) patients. [Copyright &y& Elsevier]

Background: Prior voxelwise studies of white matter anisotropy found widespread reductions involving all major fiber tracts of the schizophrenic brain. We set out to confirm these exploratory findings and evaluate their relation to illness severity using a hypothesis-driven region-of-interest approach.Methods: 104 schizophrenia patients (51 with good outcomes, 53 with poor outcomes) and 41 matched comparison subjects participated in the study. Regions of interest were selected on the basis of published voxelwise findings and placed within major fiber tracts using Talairach's stereotaxic coordinates.Results: Fractional anisotropy reductions in schizophrenia patients were confirmed in the left cingulum, anterior thalamic radiation, fronto-occipital and inferior longitudinal fasciculi, as well as bilaterally in the corpus callosum, anterior and posterior limbs of internal capsule, superior longitudinal fasciculus, optic radiation, and frontotemporal extrafascicular white matter. Anisotropy reductions were more extensive in patients with poor outcomes ("Kraepelinian"), particularly in the posterior corpus callosum, fronto-occipital fasciculus, left optic radiation and frontotemporal white matter. Lower anisotropy in the right hemisphere tracts was associated with more prominent positive symptomatology, whereas negative symptoms were inversely associated with anisotropy values in both hemispheres.Conclusions: These results support a global neural disconnectivity in schizophrenia patients, which is more severe in those with poor clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Alignment of white matter axons as inferred from diffusion tensor imaging has indicated changes in schizophrenia in frontal and frontotemporal white matter. Methods: Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired in 64 patients with schizophrenia and 55 normal volunteers. Anatomical images were acquired with a magnetization prepared rapid gradient echo sequence, and diffusion tensor images used a pulsed gradient spin-echo acquisition. Images were aligned and warped to a standard brain, and anisotropy in normal volunteers and patients was compared using significance probability mapping. Results: Patients showed widespread areas of reduced anisotropy, including the frontal white matter, the corpus callosum, and the frontal longitudinal fasciculus. Conclusions: These findings, which are consistent with earlier reports of frontal decreases in anisotropy, demonstrate that the effects are most prominent in frontal and callosal areas and are particularly widespread in frontal white matter regions. [Copyright &y& Elsevier]

Abstract: Methods based on the analysis of metabolic and volumetric interregional correlations have been used in neuroimaging research, yet metabolic and volumetric interregional correlations for identical regions of interest have never been compared in the same group of subjects. Magnetic resonance and [18F]-fluorodeoxyglucose positron emission tomography brain images were acquired in 59 healthy subject. Correlation matrices for relative glucose metabolic rates during a verbal learning task and for relative gray matter volumes were compiled between the manually traced mediodorsal, centromedian, and pulvinar nuclei of the thalamus and 39 cortical Brodmann''s areas. Metabolic correlations between the cortex and these thalamic nuclei followed the known patterns of anatomical connectivity in non-human primates. Intercorrelations of the mediodorsal nucleus were widespread with the prefrontal cortex (9 out of 10 Brodmann''s areas in the left hemisphere) and temporal lobe (10 out of 11 Brodmann''s areas in the left hemisphere) while the pulvinar correlated only with the parietal and occipital cortical areas. Different correlation patterns were observed for the regional gray matter volumes whereby only the pulvinar yielded extensive cortical intercorrelations, primarily with the occipital, parietal, anterior cingulate, and orbitofrontal areas in the right hemisphere. Metabolic thalamocortical correlations were much more extensive for the mediodorsal and centromedian nuclei whereas structural correlations were more extensive for the pulvinar. Therefore, metabolic and volumetric correlational methods are sensitive to different aspects of interregional relations in the brain and their comparison in the same group of subjects may render complementary and only partially overlapping connectivity information. [Copyright &y& Elsevier]

Objective: Disparate white matter fractional anisotropy (FA) findings have been reported in patients with schizophrenia in recent years. This may in part reflect heterogeneity of subjects in the studies, including differences in outcome and severity of the illness. We examined whether there is a relationship between white matter FA and outcome in patients with schizophrenia. Method: Diffusion-tensor images were obtained in 41 normal subjects and 104 patients with schizophrenia, divided into good-outcome (n=51) and poor-outcome (Kraepelinian; n=53) subtypes based on their ability for self-care. White matter FA and its relationship to regional tissue volumes were evaluated across 40 individual Brodmann's areas using a semi-automated parcellation technique. Results: Overall white matter FA was lower in schizophrenia patients than normal subjects, with regional reductions in widespread temporoparietal and selected prefrontal white matter regions. In schizophrenia patients, lower regional white matter FA was associated with lower regional gray matter volumes. In comparison to normal subjects, overall white matter FA was reduced in patients with poor outcomes in both hemispheres, but to a lesser extent and only in the right hemisphere in good-outcome patients. Lower regional FA was associated with larger regional white matter volumes in good-outcome group. Conclusions: Global FA reductions implicate white matter as tissue type in the pathophysiology of schizophrenia. In contrast to poor outcome, good outcome in schizophrenia patients may be associated with less extensive FA reductions, higher FA in regional frontal and cingulate white matter, and correlated increases in regional white matter volumes, particularly in the left hemisphere. [ABSTRACT FROM AUTHOR]

Background: Previous studies indicated that schizophrenia patients have reduced frontal volumes in comparison with normal, but among schizophrenics, reduced volumes of the posterior (temporal, parietal and occipital) cortex were associated with poor outcome. We examined whether this pattern is seen within the anteroposterior arch of the cingulate gyrus. Methods: MR images were acquired in 37 schizophrenia patients (Kraepelinian, n = 13; non-Kraepelinian, n = 24) and 37 controls, and CSF, gray and white matter volumes in individual Brodmann's areas (BA) of the cingulate arch (areas 25, 24, 23, 31, 30, 29) were assessed and examined in relation to outcome. Results: Schizophrenia patients had significant gray matter reductions in the absolute (mm(3)) volume of Brodmann's area 24 in anterior cingulate and, when corrected for brain size, in the whole cingulate and retrosplenial (areas 29-30) cortex. White matter volumes were increased in right posterior cingulate (area 31). Schizophrenia patients also showed abnormal lateralization of white matter volumes in retrosplenial cortex (area 30) and had lower correlations between frontal and anterior cingulate regions than controls. Poor-outcome subgroup exhibited significant bilateral gray matter deficits in posterior cingulate and retrosplenial cortices compared to good-outcome patients, while no white matter increases in these areas were seen. Conclusions: Poor outcome was associated with gray matter deficits in posterior cingulate while compensatory white matter increases in dorsal posterior regions may be related to better outcome. Possible consequences of this may include thought disorder, disturbance of consciousness, treatment resistance, and cognitive decline indicative of a dementing process as a superimposed or inherent part of this schizophrenia subtype. [ABSTRACT FROM AUTHOR]

The size of the thalamus was assessed in 106 patients with schizophrenia and 42 normal controls using high-resolution magnetic resonance imaging. The thalamus was traced at five axial levels proportionately spaced from dorsal to ventral directions. Patients with schizophrenia had significantly smaller thalamic areas at more ventral levels. Thalamic size was positively associated with frontal lobe and temporal lobe size. The effects were most marked in the patients with poorer clinical outcome (i.e., “Kraepelinian” patients). These findings are consistent with post-mortem and MRI measurement suggesting reduction in volume of the pulvinar, which occupies a large proportion of the ventral thalamus and which has prominent connections to the temporal lobe. [Copyright &y& Elsevier]

• Veterans with schizophrenia were highly engaged in this CRT + SST trial, with excellent attendance across cohorts. • Following CRT + SST, participants demonstrated significant improvement in reasoning and problem solving, verbal learning, and social cognition. • Baseline FA in the SLF predicted improvements in visual-spatial working memory while overall baseline FA predicted improvements in social cognition. • Results support the concept that determining the neurobiology underlying individual differences in treatment response is important for precision medicine in psychiatry. 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. [ABSTRACT FROM AUTHOR]

Background: The etiology of schizophrenia involves both biological and environmental risk factors. Studying childhood trauma in disorders along the schizophrenia spectrum, including schizotypal personality disorder (SPD), can inform early risk and protective factors for psychosis. However, no study has directly compared childhood trauma between SPD and schizophrenia., Study Design: One hundred twenty-four participants (schizophrenia/schizoaffective disorder [SZ] n = 45, SPD n = 32, and healthy controls [HCs] n = 47) matched on age and gender were assessed for different types of childhood abuse and neglect as well as clinical symptoms. Kruskal-Wallis H-tests examined group differences in childhood trauma severity and logistic regression modeled childhood trauma types that were associated with an SZ vs SPD diagnosis., Study Results: SZ and SPD had greater severity than HC on total trauma score and all types of childhood trauma assessed (all P-values < .05). SZ and SPD only differed on childhood sexual abuse, which was greater in SZ (P = .039). Childhood sexual abuse (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.02-1.27, P = .02) and emotional abuse (OR = 0.82, 95% CI = 0.71-0.95, P = .01) were independent predictors of an SZ vs SPD diagnosis. Sensitivity analysis indicated that a cutoff at mild sexual abuse was significant in predicting SZ vs SPD when compared with none/minimal sexual abuse. In SZ, greater sexual abuse was associated with positive schizotypal traits and in SPD, greater emotional abuse was associated with depressive symptoms., Conclusions: Findings suggest that childhood sexual and emotional abuse may be important factors that influence illness trajectory across the severity of disorders on schizophrenia spectrum. These findings have implications for understanding disease mechanisms and early prevention., (Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2024.)

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.)