Dorsolateral prefrontal cortex and hippocampus sustain impulsivity and aggressiveness in borderline personality disorder.

BACKGROUND: Borderline Personality Disorder (BPD) patients are characterized by increased levels of aggressivity and reduction of impulse control, which are behavioural dimensions mainly sustained by hippocampus and dorsolateral prefrontal cortex (DLPFC). In this study we aimed at investigating whether hippocampus and DLPFC anatomy may sustain impulsive and aggressive behaviours in BPD. METHODS: Fifteen DSM-IV BPD patients (11 females, 4 males) and fifteen 1:1 matched healthy controls (11 females, 4 males) were studied with a 1.5T magnetic resonance imaging (MRI) and underwent a psychopathological assessment in order to measure the severity of aggressive and impulsive traits. RESULTS: Right hippocampal volumes were significantly reduced in BPD patients compared to healthy subjects (p=0.027), particularly in those with a history of childhood abuse (p=0.01). Moreover, in patients but not in controls, right hippocampal volumes significantly inversely correlated with aggressiveness and DLPFC grey matter volumes significantly inversely associated with impulsiveness (p<0.05). CONCLUSIONS: Our results provide evidence that hippocampus and DLPFC play a separate and unique role in sustaining the control of impulse and aggressive behaviours in BPD patients.

Autism and genius: is there a link? The involvement of central brain loops and hypotheses for functional testing.

Mental processing is the product of the huge number of synaptic interactions that occur in the brain. It is easier to understand how brain functions can deteriorate than how they might be boosted. Lying at the border between the humanities, cognitive science and neurophysiology, some mental diseases offer new angles on this problematic issue. Despite their social deficits, autistic subjects can display unexpected and extraordinary skills in numerous fields, including music, the arts, calculation and memory. The advanced skills found in a subgroup of people with autism may be explained by their special mental functioning, in particular by their weak central coherence, one of the pivotal characteristics of the disorder. As a result of the increasing interest in autistic talent, there has recently emerged a tendency to screen any eccentric artist or scientist for traits of the autistic spectrum. Following this trend, we analyze the eccentricity of the popular pianist Glenn Gould and briefly discuss the major functional hypotheses on autistic hyperfunctioning, advancing proposals for functional testing. In particular, the potential involvement of rhythm-entrained systems and cerebro-cerebellar loops opens up new perspectives for the investigation of autistic disorders and brain hyperfunctioning.

Laterality effect on emotional faces processing: ALE meta-analysis of evidence.

Recognizing emotion from facial expressions draws on diverse psychological processes implemented in a large array of neural structures. Two major theories of cerebral lateralization of emotional perception have been proposed: (i) the Right-Hemisphere Hypothesis (RHH) and (ii) the Valence-Specific Hypothesis (VSH). To test these lateralization models we conducted a large voxel-based meta-analysis of current functional magnetic resonance imaging (fMRI) studies employing emotional faces paradigms in healthy volunteers. Two independent researchers conducted separate comprehensive PUBMED (1990-May 2008) searches to find all functional magnetic resonance imaging studies using a variant of the emotional faces paradigm in healthy subjects. Out of the 551 originally identified studies, 105 studies met inclusion criteria. The overall database consisted of 1785 brain coordinates which yield an overall sample of 1600 healthy subjects. We found no support for the hypothesis of overall right-lateralization of emotional processing. Conversely, across all emotional conditions the parahippocampal gyrus and amygdala, fusiform gyrus, lingual gyrus, precuneus, inferior and middle occipital gyrus, posterior cingulated, middle temporal gyrus, inferior frontal and superior frontal gyri were activated bilaterally (p=0.001). There was a valence-specific lateralization of brain response during negative emotions processing in the left amygdala (p=0.001). Significant interactions between the approach and avoidance dimensions and prefrontal response were observed (p=0.001).

Cognitive memory control in borderline personality disorder patients.

BACKGROUND: It has been demonstrated that the mechanism of cognitive memory control in humans is sustained by the hippocampus and prefrontal cortices, which have been found to be structurally and functionally abnormal in borderline personality disorder (BPD). We investigated whether the memory control mechanism is affected in BPD. METHOD: Nineteen Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV BPD patients and 19 matched healthy controls (HC) performed a specific think/no-think paradigm exploring the capacity of remembering and suppressing pair of words previously learned. After the think-no think phase, the second member of each word pair has to be remembered either when subjects are presented with the cue word showed at the beginning of the test (Same Probe Test; SPT) or when they are presented with an extra-list categorical word (Independent Probe Test; IPT). We evaluated the effect of suppression and of retrieval activity on later retention of words. RESULTS: Both on the SPT and on the IPT, HC showed the expected improvement of memory retrieval on to-be-remembered words, unlike BPD patients. On the SPT, HC, but not BPD patients, correctly recalled significantly more words among remembered words (RW) than among suppressed words (SW). Similarly to HC, subjects with BPD without a history of childhood abuse showed a significantly higher percentage of correctly recalled words among RW than among SW. CONCLUSIONS: The mechanism of active retrieval of memories and of improvement through repetition is impaired in BPD, particularly in those who experienced traumatic experiences. This impairment might play an important role, possibly resulting in the emergence of unwanted memories and dissociative symptoms.

Heart rate variability, training variation and performance in elite swimmers.

The aim of the present study was to investigate the relationships between heart rate variability (HRV) changes and both training variations and performances in elite swimmers. A secondary purpose was to measure catecholamine urinary excretion in elite swimmers to validate the HRV indices of sympathetic activity during training. Thirteen swimmers (4 females and 9 males) were tested before and after 4 weeks of intense training (IT) and 3 weeks of reduced training (RT). At the end of each period, the swimmers participated in an official competition of their best event. Individual performances were expressed as percentage of the previous season's best performance. Spectral analysis was used to investigate RR interval variability. HRV indices failed to show any significant changes between the study periods (p>0.05). Pre-IT HF was correlated with performance (r=0.45; p=0.05) and HFnu (r=0.59; p<0.05) during RT. On the other hand, once RT was completed, HFnu was correlated positively to performance (r=0.81; p<0.01) and negatively to fatigue (r=- 0.63; p<0.03). Conversely, the indices of sympathetic activity, i.e., LFnu and LF/HF ratio were inversely related to performance (both r=- 0.81; p<0.01); total fatigue score was correlated to the changes in HFnu (r=- 0.63; p<0.03) and in the LF/HF ratio (r=0.58; p<0.05). Changes in the adrenaline/noradrenaline ratio over the follow-up period were related to the changes in the LF/HF ratio (r=0.45; p<0.03). In highly trained swimmers coping well with a training program, including 4 weeks of IT followed by 3 weeks of RT, HRV indices were unaltered. On the other hand, after the 3 weeks of RT, HFnu was positively related to performance and inversely related to the fatigue score. Thus, elevated initial HF levels could be important in the parasympathetic activity increases during taper and, hence, in swimming performance improvement.

24-hr urinary catecholamine excretion, training and performance in elite swimmers.

The aim of the present study was to investigate the effects of training variations on 24-hr urinary noradrenaline (NA) and adrenaline (Ad) levels and the adrenaline/noradrenaline (Ad/NA) ratio to search for a possible relationship between catecholamine excretion, training, and performance in highly trained swimmers. Fourteen swimmers (5 female and 9 male) were tested after 4 weeks of intense training (IT), 3 weeks of reduced training (RT), and 5 weeks of low training (LT). At the end of each period, the swimmers performed their best event at an official competition. Individual performances were expressed as percentage of the previous season's best performance. The changes in NA levels after 4 weeks of IT were negatively related to changes in training volume (r=-0.70, p<0.01) and total training load (r=-0.68, p<0.02). NA levels measured at the end of IT were positively related to changes in performance after three weeks of RT (r=0.77, p<0.01). The percentage changes in performance between RT and LT were related to NA levels at the end of RT (r=0.60; p<0.04). Ad/NA ratios and Ad were related to performance (r=0.58, p<0.01; r=52, p<0.01; respectively). The differences in Ad/NA ratios and Ad between two consecutive competitions were related to the differences in performance (r=0.59, p<0.01; r=0.49, p<0.01; respectively). 24-hr NA and the Ad/NA excretion ratio were related to both training variations and performance. Thus, 24-hr NA levels and Ad/NA ratio may provide useful markers for monitoring training stress in elite swimmers.

Clinical outcome and olanzapine plasma levels in acute schizophrenia.

PURPOSE: This open label study was performed to evaluate the relationship between the plasma concentration of olanzapine and the response in acute schizophrenic inpatients. MATERIAL AND METHODS: A total of 54 inpatients, 38 males and 16 females, age ranging from 18 to 75 years, affected by Schizophrenia (DSM IV criteria) during an exacerbation phase were included in the study. Olanzapine (OLZ) was started at a dose of 5-20 mg/day and was increased to a mean dose of 15.27 mg +/-5.53 S.D. Patients were evaluated at baseline, and after 2 weeks, by using BPRS, PANNS, HRS-D, EPSE, and ACS. RESULTS: BPRS and total PANSS showed a statistically significant improvement at the end of the study. Olanzapine plasma levels (PL) ranged from 5 to 120 ng/ml (mean 33.15 ng/ml +/- 28.28 S.D.) and showed a positive correlation with OLZ dosage. A significant curvilinear correlation between OLZ PL and clinical improvement (BPRS, PANSS and HRS-D percent of amelioration) was observed. CONCLUSION: Olanzapine plasma level determination seems to be a useful tool in optimizing acute treatment particularly for more problematic cases.

GABAergic dysfunction in mood disorders.

The authors review the available literature on the preclinical and clinical studies involving GABAergic neurotransmission in mood disorders. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter present almost exclusively in the central nervous system (CNS), distributed across almost all brain regions, and expressed in interneurons modulating local circuits. The role of GABAergic dysfunction in mood disorders was first proposed 20 years ago. Preclinical studies have suggested that GABA levels may be decreased in animal models of depression, and clinical studies reported low plasma and CSF GABA levels in mood disorder patients. Also, antidepressants, mood stabilizers, electroconvulsive therapy, and GABA agonists have been shown to reverse the depression-like behavior in animal models and to be effective in unipolar and bipolar patients by increasing brain GABAergic activity. The hypothesis of reduced GABAergic activity in mood disorders may complement the monoaminergic and serotonergic theories, proposing that the balance between multiple neurotransmitter systems may be altered in these disorders. However, low GABAergic cortical function may probably be a feature of a subset of mood disorder patients, representing a genetic susceptibility. In this paper, we discuss the status of GABAergic hypothesis of mood disorders and suggest possible directions for future preclinical and clinical research in this area.

Clozapine-treated subjects with treatment-resistant schizophrenia: a systematic review of experimental and observational studies.

Randomized clinical trials have limitations because they focus on small samples of highly selected patients. Observational studies, which follow large cohorts of typical patients receiving pharmacological treatments, should overcome some of these trial limitations and provide information that cannot be generated with clinical trials. The present study aimed to compare experimental and observational studies of clozapine-treated subjects with treatment-resistant schizophrenia. A systematic review of experimental and observational studies evaluating clozapine-treated subjects in treatment-resistant schizophrenia was carried out. We identified 50 studies that met the inclusion criteria. Less than one-third of clinical trials enrolled more than 50 patients compared to 44% of prospective and nearly 90% of retrospective studies. In addition, 78% of prospective and 89% of retrospective observational studies lasted more than 12 weeks, while the majority of trials lasted less than 8 weeks. Most clinical trials defined treatment-resistant schizophrenia according to Kane's criteria, while the majority of observational studies adopted implicit criteria. In comparison with clinical trials, observational studies provided a higher weighted mean rate of clozapine-responders and a lower weighted mean rate of clozapine-dropouts. This literature survey suggests that the role of observational studies in the evaluation of medicines should be reconsidered. A new generation of observational studies should be developed to provide evidence on patient outcome in typical settings and under real-world circumstances, and on variables which may affect outcome.

Mortality in psychiatric patients 5 to 21 years after hospital admission in Italy.

BACKGROUND: Mental disorders have an increased mortality risk. However, most data have been provided by few countries, some mental disorders have received little attention, long-term studies of large samples are scarce, and insufficient control for confounding variables has lead to artefactual inconsistencies across studies. The aims of this study were: to quantify the mortality risk in psychiatric patients 5 to 21 years after hospital admission and to investigate temporal trends in mortality risk and predictive factors associated with mortality. METHOD: All patients admitted to an in-patient psychiatric unit in Italy between 1978 and 1994 were included and vital status and death causes were determined up to 21 years after admission. The observed number of deaths in the sample was compared with the expected number of deaths in the general population. Cox proportional hazard models were fitted to identify predictors of mortality. RESULTS: Mortality from natural and unnatural causes was higher than expected across all mental disorders. Standardized mortality risk was higher in males (SMR = 4.55; 95% CI 4.17-4.97) than in females (SMR = 3.43; 95% CI 3.07-3.83). Individuals aged less than 40 years were at higher risk in both sexes. The first several years following admission were characterized by a faster decline in survival. Several demographic and clinical factors were predictors of mortality. CONCLUSIONS: Mortality is high in individuals with mental disorders. Prevention of unnatural death causes is an important goal though insufficient to abate excess mortality, since natural death causes account for it to a larger extent.

Perspectives on the use of anticonvulsants in the treatment of bipolar disorder.

The authors reviewed the available literature on the efficacy of carbamazepine, valproate, and other newer anticonvulsants for the treatment of bipolar disorder. A comprehensive Medline search was conducted, and all uncontrolled and controlled reports on anticonvulsants used for the treatment of bipolar patients were identified. Carbamazepine and valproate have been shown to be effective in the acute treatment of bipolar disorder, and are the first-choice treatments for lithium-refractory patients. While the efficacy of these drugs in the acute treatment of the illness has been satisfactorily documented, double-blind randomized studies are still necessary to evaluate the long-term effectiveness of both anticonvulsants. Patients on a mixed state and rapid cyclers seem to respond better to valproate and carbamazepine than to lithium. The preliminary data evaluating the efficacy of newer anticonvulsants, such as gabapentin, lamotrigine, and topiramate in bipolar patients is still limited, but some of the available findings are promising, and these new agents may represent appropriate third choices for refractory bipolar individuals. Double-blind, controlled studies with the newer anticonvulsants are still largely unavailable, and it will be necessary to evaluate their acute and prophylactic mood-stabilizing effects. The prospects for future therapeutic advances in this area are also discussed.

Stapes surgery and psychiatric complications.

Changes in auditory perception can cause disturbances in development and personality. This phenomenon has been studied in particular in children hearing loss or in progressive or sudden hearing loss in the adult. We present the case of a patient with psychobehavioural alterations after restoration of hearing following a small fenestra stapedectomy for bilateral otosclerosis with moderate-severe hearing impairment. The diagnosis, physiopathology and medicolegal implications are discussed.

Predictive factors of death in primary lung cancer patients on admission to the intensive care unit.

OBJECTIVE: To assess the lung cancer patient's prognosis in the intensive care unit with early predictive factors of death. DESIGN: Retrospective study from July 1986 to February 1996. SETTING: Medical intensive care unit at a university hospital. PATIENTS: Fifty-seven patients with primary lung cancer admitted to our medical intensive care unit (MICU). MEASUREMENTS AND RESULTS: Data collection included demographic data (age, sex, underlying diseases, MICU admitting diagnosis) and evaluation of tumor (pathologic subtypes, metastases, lung cancer staging, treatment options). Three indexes were calculated for each patient: Karnofsky performance status, Simplified Acute Physiology Score (SAPS) II, and multisystem organ failure score (ODIN score). Mortality was high in the MICU: 66% of patients died during their MICU stay, and hospital mortality reached 75%. In multivariate analysis, acute pulmonary disease and Karnofsky performance status < 70 were associated with a poor MICU and post-MICU prognosis. For the survivors, long-term survival after MICU discharge depended exclusively on the severity of the lung cancer. CONCLUSIONS: We confirmed the high mortality rate of lung cancer patients admitted to the MICU. Two predictive factors of death in MICU were identified: performance status < 70 and acute pulmonary disease.

[Effects of anesthetic agents on arterial reactivity]. / Effets des agents anesthésiques sur la vasomotricité artérielle.

OBJECTIVE: To review the effects of halogenated and intravenous anaesthetics on arterial vasoreactivity. DATA SOURCE: Articles were obtained from a MEDLINE review (search terms: 'vascular smooth muscle, endothelium' used separately or associated with following anaesthetic agents: 'halothane, isoflurane, enflurane, desflurane, sevoflurane, thiopentone, propofol, ketamine, etomidate'. Other sources included review articles and textbooks. STUDY SELECTION AND DATA EXTRACTION: All experimental studies published since 1975 were analysed and pertinent data extracted. DATA SYNTHESIS: Within the vascular wall, arterial vasoreactivity involves the endothelium and the vascular smooth muscle. In vivo, arterial vasoreactivity is regulated by neuronal, hormonal, and metabolic factors. In vitro, the direct action of anaesthetic agents on the vessel can be studied in the absence of such factors. In vitro studies with arterial rings have shown that inhalational anaesthetics directly decrease endothelium-independent contraction induced by various pharmacological agents. This direct effect of anaesthetics results from a decrease in intracellular calcium, mainly caused by an inhibition of transsarcoplasmic calcium influx. Volatile anaesthetics decrease endothelium-dependent vasorelaxation at a site(s) within the nitric oxide (NO) signalling pathway, located downstream from the NO-related receptors and upstream from guanylyl cyclase. They may also decrease endothelium-independent vasorelaxation by inhibiting NO activation of guanylate cyclase. Intravenous anaesthetics, such as propofol, barbiturates, ketamine and etomidate also decrease vasoconstriction by various degrees. Propofol is the most potent inhibitor of vasoconstriction and thiopental the least one. All these IV anaesthetics have been shown to inhibit in some circumstances both endothelium-dependent and -independent vasorelaxation. Further studies are required to enable a better understanding of the mechanism and the site of action of these vascular effects of anaesthetics. For example, the investigation of the effects of anaesthetic agents on vascular reactivity in diseases associated with endothelial dysfunction may indirectly provide insight into the role of endothelium.

Medication errors at the administration stage in an intensive care unit.

OBJECTIVE: To assess the type, frequency and potential clinical significance of medication-administration errors. DESIGN: Prospective study using the observation technique as described by the American Society of HealthSystem Pharmacists but eliminating the disguised aspect. SETTING: Medical intensive care unit (ICU) in a university hospital. PATIENTS AND PARTICIPANTS: 2009 medication administration interventions by nurses. INTERVENTIONS: Pharmacist-performed observation of preparation and administration of medication by nurses, comparison with the original medical order and comparison with the data available in the literature. MEASUREMENTS AND RESULTS: 132 (6.6% of 2009 observed events) errors were detected. Their distribution is as follows: 41 dose errors, 29 wrong rate, 24 wrong preparation technique, 19 physicochemical incompatibility, 10 wrong administration technique and 9 wrong time errors. No fatal errors were observed, but 26 of 132 errors were potentially life-threatening and 55 potentially significant. CONCLUSION: According to this first observation-based study of medication administration errors in a European ICU, these errors were due to deficiencies in the overall organisation of the hospital medication track, in patient follow-up and in staff training.

Effects of propofol on vascular reactivity in isolated aortae from normotensive and spontaneously hypertensive rats.

We have investigated the effects of propofol 50 mumol litre-1 on contractile and relaxant responses in experimental hypertension and assessed endothelial modulation of these responses. Propofol attenuated norepinephrine-induced contraction of endothelium-intact and endothelium-denuded rings from both Wistar Tokyo (WKY) and spontaneously hypertensive rats (SHR). The effect was significantly greater in endothelium-intact aortae from SHR than in those from WKY rats. Propofol markedly attenuated AVP-induced contraction in aortae from both WKY and SHR. Propofol attenuation of norepinephrine contraction was also observed in rings from both SHR and WKY rats incubated with L-NAME. Propofol attenuation of norepinephrine contraction was suppressed by indomethacin in aortae from SHR but not in those from WKY rats. These results suggest that: (1) propofol attenuated vascular contraction of isolated aortae from SHR in part by a mechanism dependent on events distal to the receptor site (norepinephrine, arginine vasopressin); (2) the effect of propofol on contraction in SHR, observed in the presence of nitric oxide synthase inhibitors but not cyclooxygenase inhibitors, was consistent with either propofol induction of vasodilating cyclooxygenase metabolites from the endothelium or propofol inhibition of vasoconstricting cyclooxygenase metabolites.

Gastrocolic vein. Definition and report of two cases of avulsion.

The gastrocolic v. or Henle's gastrocolic trunk was described in 1868 [9]. We suggest defining this vein as the confluence of the right gastroepiploic and right upper colic vv. We report two original cases of avulsion of the gastrocolic v. occurring during a blunt abdominal trauma. The aim of this paper is a description, based on the literature, of the anatomy of the gastrocolic v. in order to precise the lesional mechanism. The gastrocolic v. is present in 70% of individuals. It is short (less than 25 mm) but of major calibre (3 to 10 mm). The gastrocolic v. is situated close beneath the root of the transverse mesocolon, and travels along the anterior surface of the head of the pancreas. Anatomic variations are detailed and a meta-analysis of interpretable studies was made. Both the supra- and infra-mesocolic surgical approaches are described. The radiologic and surgical importance of the gastrocolic v. is discussed. The lesional mechanism in both our cases of injury of the gastrocolic v. is explained.