Borderline Personality Disorder and Psychosis: A Case Managed by Transference-Focused Psychotherapy.

Transient stress-related paranoia is the descriptive definition of psychotic phenomena associated with borderline personality disorder. Although psychotic symptoms usually do not qualify patients for a separate diagnosis in the psychotic spectrum, statistical probabilities predict the co-occurrence of cases with comorbid borderline personality disorder and major psychotic disorder. This article presents three perspectives on a complex case of borderline personality disorder and psychotic disorder: one from a medication prescribing psychiatrist who is a transference-focused psychotherapist responsible for care, one from the anonymous patient, and one from a specialist in psychotic disorder. A discussion of clinical implications concludes this multidimensional presentation of borderline personality disorder and psychosis.

Computational analysis of spoken language in acute psychosis and mania.

OBJECTIVES: This study aimed to (1) determine the feasibility of collecting behavioral data from participants hospitalized with acute psychosis and (2) begin to evaluate the clinical information that can be computationally derived from such data. METHODS: Behavioral data was collected across 99 sessions from 38 participants recruited from an inpatient psychiatric unit. Each session started with a semi-structured interview modeled on a typical "clinical rounds" encounter and included administration of the Positive and Negative Syndrome Scale (PANSS). ANALYSIS: We quantified aspects of participants' verbal behavior during the interview using lexical, coherence, and disfluency features. We then used two complementary approaches to explore our second objective. The first approach used predictive models to estimate participants' PANSS scores from their language features. Our second approach used inferential models to quantify the relationships between individual language features and symptom measures. RESULTS: Our predictive models showed promise but lacked sufficient data to achieve clinically useful accuracy. Our inferential models identified statistically significant relationships between numerous language features and symptom domains. CONCLUSION: Our interview recording procedures were well-tolerated and produced adequate data for transcription and analysis. The results of our inferential modeling suggest that automatic measurements of expressive language contain signals highly relevant to the assessment of psychosis. These findings establish the potential of measuring language during a clinical interview in a naturalistic setting and generate specific hypotheses that can be tested in future studies. This, in turn, will lead to more accurate modeling and better understanding of the relationships between expressive language and psychosis.

What can we learn about brain donors? Use of clinical information in human postmortem brain research.

Postmortem studies on the human brain reside at the core of investigations on neurologic and psychiatric disorders. Ground-breaking advances continue to be made on the pathologic basis of many of these disorders, at molecular, cellular, and neural connectivity levels. In parallel, there is increasing emphasis on improving methods to extract relevant demographic and clinical information about brain donors and, importantly, translate it into measures that can reliably and effectively be incorporated in the design and data analysis of postmortem human investigations. Here, we review the main source of information typically available to brain banks and provide examples on how this information can be processed. In particular, we discuss approaches to establish primary and secondary diagnoses, estimate exposure to therapeutic treatment and substance abuse, assess agonal status, and use time of death as a proxy in investigations on circadian rhythms. Although far from exhaustive, these considerations are intended as a contribution to ongoing efforts from tissue banks and investigators aimed at establishing robust, well-validated methods for collecting and standardizing information about brain donors, further strengthening the scientific rigor of human postmortem studies.

Split-brain phenomena in anterior communicating artery aneurysm rupture: A case report.

In 1976, a patient with an anterior communicating artery aneurysm (ACoAA) rupture (diagnosed on angiography) and sub-arachnoid hemorrhage (SAH) underwent serial neuropsychological testing revealing a classical anterior cerebral artery (ACA) spasm picture with severe anterograde amnesia of Korsakoff's type and dysexecutive syndrome. In addition, the patient demonstrated impaired hemispheric interaction with alien hand syndrome, dyscopia-dysgraphia, complete left ear neglect, and other, more complex, split-brain phenomena. He was evaluated by A. R. Luria in 1976. Following surgery the patient demonstrated gradual improvement.

Prescription stimulant use is associated with earlier onset of psychosis.

A childhood history of attention deficit hyperactivity disorder (ADHD) is common in psychotic disorders, yet prescription stimulants may interact adversely with the physiology of these disorders. Specifically, exposure to stimulants leads to long-term increases in dopamine release. We therefore hypothesized that individuals with psychotic disorders previously exposed to prescription stimulants will have an earlier onset of psychosis. Age of onset of psychosis (AOP) was compared in individuals with and without prior exposure to prescription stimulants while controlling for potential confounding factors. In a sample of 205 patients recruited from an inpatient psychiatric unit, 40% (n = 82) reported use of stimulants prior to the onset of psychosis. Most participants were prescribed stimulants during childhood or adolescence for a diagnosis of ADHD. AOP was significantly earlier in those exposed to stimulants (20.5 vs. 24.6 years stimulants vs. no stimulants, p < 0.001). After controlling for gender, IQ, educational attainment, lifetime history of a cannabis use disorder or other drugs of abuse, and family history of a first-degree relative with psychosis, the association between stimulant exposure and earlier AOP remained significant. There was a significant gender × stimulant interaction with a greater reduction in AOP for females, whereas the smaller effect of stimulant use on AOP in males did not reach statistical significance. In conclusion, individuals with psychotic disorders exposed to prescription stimulants had an earlier onset of psychosis, and this relationship did not appear to be mediated by IQ or cannabis.

Positive association between plasma amylin and cognition in a homebound elderly population.

Our recent study reported that amylin, a pancreatic peptide that readily crosses the blood-brain barrier, improves learning and memory in Alzheimer's disease mouse models. However, the relationship between peripheral amylin and cognition in humans is unknown. In this follow-up study, using a cross-sectional, homebound elderly population, improvement in cognitive function with increasing quartiles of plasma amylin was suggested by positive association with verbal memory (p = 0.0002) and visuoconstruction tasks (p = 0.004), and inverse association with timed measures of attention (p < 0.0001) and executive function (p = 0.04). After adjusting for demographic information, apolipoprotein E4 allele, diabetes, stroke, kidney function, and lipid profile, log10 of plasma amylin remained associated with these cognitive domains. In contrast, plasma amyloid-ß peptide was not associated with these specific cognitive domains. Our study suggests that peripheral amylin may be protective for cognitive decline, especially in the domains affected by Alzheimer's disease.

Association between amylin and amyloid-ß peptides in plasma in the context of apolipoprotein E4 allele.

Amylin, a pancreatic peptide that readily crosses the blood brain barrier (BBB), and amyloid-beta peptide (Aß), the main component of amyloid plaques and a major component of Alzheimer's disease (AD) pathology in the brain, share several features. These include having similar ß-sheet secondary structures, binding to the same receptor, and being degraded by the same protease. Thus, amylin may be associated with Aß, but the nature of their relationship remains unclear. In this study, we used human samples to study the relationship between plasma amylin and Aß in the context of the apolipoprotein E alleles (ApoE). We found that concentrations of Aß1-42 (P<0.0001) and Aß1-40 (P<0.0001) increased with each quartile increase of amylin. Using multivariate regression analysis, the study sample showed that plasma amylin was associated with Aß1-42 (ß = +0.149, SE = 0.025, P<0.0001) and Aß1-40 (ß = +0.034, SE = 0.016, P = 0.04) as an outcome after adjusting for age, gender, ethnicity, ApoE4, BMI, diabetes, stroke, kidney function and lipid profile. This positive association between amylin and Aß1-42 in plasma was found regardless of the ApoE genotype. In contrast, the relationship between amylin and Aß1-40 in plasma seen in ApoE4 non-carriers disappeared in the presence of ApoE4. Using AD mouse models, our recent study demonstrates that intraperitoneal (i.p.) injection of synthetic amylin enhances the removal of Aß from the brain into blood, thus resulting in increased blood levels of both amylin and Aß. The positive association between amylin and Aß, especially Aß1-42, in human blood samples is probably relevant to the findings in the AD mouse models. The presence of ApoE4 may attenuate amylin's capacity to remove Aß, especially Aß1-40, from the AD brain.

The relationship between plasma amyloid-ß peptides and the medial temporal lobe in the homebound elderly.

BACKGROUND: The ratio of high amyloid-ß peptide40 (Aß40) and low Aß42 in plasma predicts the risk of Alzheimer's disease (AD) and is associated with episodic recall in depression. We thus examined the relationship between plasma Aß levels and brain volumes. METHODS: Homebound elders (N = 352) who had undergone brain MRI were used. Plasma Aß1-40 and Aß1-42 were measured by ELISA. Volumes of medial temporal regions, including the amygdala and hippocampus, were manually measured. RESULTS: Amygdala volume was associated with log(10) of plasma Aß1-42 (ß = +0.19, SE = 0.07, p = 0.005) after adjusting for AD, infarcts, white matter hyperintensities and demographics. In the absence of dementia, decreasing quartiles of plasma Aß1-42 (Mean + SD ml: Q4 = 4.1 ± 0.8; Q3 = 3.9 ± 0.7; Q2 = 3.6 ± 0.8 and Q1 = 3.7 ± 0.8, p = 0.01) and increasing quartiles of plasma Aß1-40/1-42 ratio were associated with smaller amygdala volume. Those depressed subjects with a high plasma Aß1-40/1-42 ratio had smaller amygdala (Mean + SD ml: 3.3 ± 0.8 vs. 3.6 ± 0.8, p = 0.04) and total brain volume (Mean + SD liter: 0.95 ± 0.07 vs. 1.04 ± 0.12, p = 0.005), and had a higher rate of MCI (67 vs. 36%, p = 0.02) than those with a low plasma Aß1-40/1-42 ratio. CONCLUSIONS: The combination of low plasma Aß1-42 concentration and atrophy of the medial temporal lobe structures, which regulates mood and cognition, may represent a biomarker for a prodromal stage of AD.

Depression and glycemic intake in the homebound elderly.

BACKGROUND: Depression is associated with an increase in the incidence of type 2 diabetes, but the mechanism is unclear. We aimed to study the relationship between depression and glycemic intake in the elderly, and examine whether antidepressant use modified this relationship. DESIGN, SETTING AND PARTICIPANTS: We evaluated 976 homebound elders in a cross-sectional study. Depression was defined by having a Center for Epidemiological Studies Depression (CES-D) score ≥16. Antidepressant use was documented. Glycemic index (GI), Glycemic load (GL), and fasting blood insulin levels were measured. RESULTS: Depressed elders had slightly higher GI (Mean±SD: 55.8±3.8 vs. 55.1±3.7, P=0.003) and higher insulin levels (Median: 84.0 vs. 74.4pmol/ml, P=0.05) than non-depressed elders. Depressed elders receiving antidepressants, primarily selective serotonin reuptake inhibitors (SSRI), had lower GI (Mean±SD: 55.1±4.7 vs. 56.2±3.4, P=0.002) and GL (Median: 170.3 vs. 6826.3, P=0.03) than those not taking antidepressants. After adjusting for potential confounding variables, GI remained positively associated with depression (ß=+0.65, SE=0.28, P=0.02); the logarithm of GL was positively associated with depression (ß=+0.33, SE=0.17, P=0.05) and negatively associated with antidepressant use (ß=-0.54, SE=0.18, P=0.003). CONCLUSIONS: Prospective studies are needed to examine whether high glycemic intake is a mediating factor between late life depression and the risk of type 2 diabetes.

Depression and plasma amyloid beta peptides in the elderly with and without the apolipoprotein E4 allele.

Depression associated with low plasma amyloid-beta peptide 42 (Abeta42) leading to a high ratio of Abeta40/Abeta42, a biomarker of Alzheimer disease (AD), may represent a unique depression subtype. The relationship between low plasma Abeta42 in depression and the major risk factor of AD, apolipoprotein E4 (ApoE4), is unknown. With the goal of clarifying this relationship, we analyzed 1060 homebound elders with ApoE characterization and depression status in a cross-sectional study. Plasma Abeta40 and Abeta42 were measured, and cognition were evaluated. In the absence of the ApoE4 allele, depressed subjects had lower plasma Abeta42 [median (Q1, Q3): 17.1 (11.6, 27.8) vs. 20.2 (12.9, 32.9) pg/mL, P=0.006], a higher Abeta40/Abeta42 ratio [median (Q1, Q3): 7.1 (4.6, 11.3) vs. 6.9 (3.4, 9.7), P=0.03], and lower cognitive function (mean+/-SD of Mini-Mental State Examination: 24.5+/-3.1 vs. 25.5+/-3.3, P<0.0001) than those without depression. In contrast, these relationships were not observed in the presence of ApoE4. Instead, regardless the depression status ApoE4 carriers had lower plasma Abeta42 and a higher Abeta40/Abeta42 ratio than non-ApoE4 carriers. Using multivariate logistic regression, it was found that depression was not associated with ApoE4 allele, but with the interaction between plasma Abeta42 and ApoE4 (odds ratio=3.94, 95% confidence interval=1.50, 10.33, P=0.005), denoting low plasma Abeta42 in the absence of ApoE4. Both ApoE4 carriers and non-ApoE4 carriers with depression had lower Abeta42 and a higher Abeta40/Abeta42 ratio in plasma compared with non-ApoE4 carriers without depression in the homebound elderly. As a combination of low plasma Abeta42 and high plasma Abeta40 has been shown to increase the risk of AD in 2 large cohort studies, amyloid-associated depression shown in this study may suggest a risk factor of AD in the absence of ApoE4.

Homocysteine and B vitamins relate to brain volume and white-matter changes in geriatric patients with psychiatric disorders.

OBJECTIVE: There is a growing literature on the relationship between low serum B-vitamins, elevated homocysteine, and cognitive impairment; however, few studies have examined radiological markers of associated neuropathology in geropsychiatry inpatients. The authors examined the relationship of homocysteine, folate, and vitamin B12 with magnetic resonance imaging (MRI) markers of neuropathology. METHODS: In this archival study, authors reviewed the MRIs and medical records of 34 inpatients in a geriatric psychiatry unit. Patients were selected if folate, B12, and/or homocysteine levels had been assessed and if the appropriate clinical MRIs were performed (19 men; mean age, 75 years). Patients with schizophrenia or current substance dependence were excluded. The relationships between MRI volume measures, white-matter hyperintensity (WMH) grade, and serum concentrations of folate, B12, and homocysteine were analyzed, using age-adjusted Pearson correlations. RESULTS: Homocysteine was related to WMH grade, but not brain-volume measures. Folate was associated with hippocampus and amygdala, and negatively associated with WMH. B12 level was not statistically associated with any brain measure. CONCLUSIONS: Elevated homocysteine and low folate were associated with radiological markers of neuropathology. Since no patient had clinically deficient folate, it may be important to rethink what defines functionally significant micronutrient deficiency and explore what this means in different age- and health-status groups. Larger samples will be needed to assess interactions between homocysteine, micronutrients, and other neuropathology risk factors.