Does operational diagnosis of schizophrenia significantly impact intellectual deficits in psychotic disorders?

BACKGROUND: Evidence suggests that, as a group, patients with schizophrenia have intellectual deficits that may precede the manifestation of psychotic symptoms; however, how successfully intelligence tests are able to discriminate schizophrenia from other psychotic disorders has yet to be investigated in detail. METHODS: Using Wechsler Adult Intelligence Scale-Revised (WAIS-R) data for 55 inpatients with schizophrenia and 28 inpatients with non-schizophrenic psychotic disorders (NSPD) (schizophreniform disorder, brief psychotic disorder, delusional disorder, psychotic disorder due to a general medical condition, and psychotic disorders not otherwise specified), intelligence performance was compared between schizophrenia and NSPD and among different subtypes of schizophrenia. RESULTS: There were no significant differences in intelligence quotient (IQ), verbal IQ (VIQ) and performance IQ (PIQ) discrepancy, and subtest scores of WAIS-R between the patients with schizophrenia and those with NSPD. These diagnostic groups were not discriminated well by any WAIS-R variables. Schizophrenia patients with prominent negative symptoms, on the other hand, had a significantly larger IQ discrepancy (VIQ > PIQ) than those without prominent negative symptoms and NSPD patients. Intelligence performance in schizophrenia did not differ with respect to diagnostic subtypes and longitudinal courses. CONCLUSIONS: The current study failed to show diagnostic usefulness of WAIS-R in discriminating schizophrenia and other psychoses. A diagnosis of schizophrenia does not significantly impact intellectual deficits in psychotic disorders.

Parietal white matter abnormalities in obsessive-compulsive disorder: a magnetic resonance spectroscopy study at 3-Tesla.

OBJECTIVE: To identify a neurochemical basis for the hypothesis that an aberrant cortico-subcortical circuit underlies obsessive-compulsive disorder (OCD). The white matter was also investigated because of recent research which suggests the altered connectivity of axons. METHOD: Using 3-Tesla magnetic resonance spectroscopy, the relative concentrations of N-acetylaspartate (NAA) and choline-containing compounds (Cho) to creatine/phosphocreatine (Cr) were measured in the anterior cingulate, basal ganglia, thalamus, frontal and parietal white matter of 12 OCD patients, and 32 control subjects. RESULTS: The mean concentration of Cho/Cr was significantly higher in the patients than in the controls, but only in the parietal white matter, while no significant group differences in NAA/Cr were observed in any of the brain regions. Parietal Cho/Cr correlated positively with the severity of OCD symptoms. CONCLUSION: This finding provides indirect evidence for the parietal white matter involvement in OCD, thus suggesting a change in the phospholipids of myelinated axons and/or glia cells.

The neurotoxic lipopeptide kalkitoxin interacts with voltage-sensitive sodium channels in cerebellar granule neurons.

The marine neurotoxin kalkitoxin, a thiazoline-containing lipid derived from the pantropical marine cyanobacterium Lyngbya majuscula, was assayed for interaction with the tetrodotoxin-sensitive, voltage-sensitive sodium channel (TTX-VSSC) in cerebellar granule neuron cultures (CGN). The naturally occurring isomer of kalkitoxin (KTx-7) blocked veratridine-induced (30 microM) neurotoxicity in a concentration-dependent manner (EC50 22.7 nM [9.5-53.9 nM, 95% confidence interval {CI}]) in CGN. Kalkitoxin was a potent inhibitor (EC50 26.1 nM [12.3-55.0 nM, 95% CI]) of the elevation of intracellular Ca2+ concentration [Ca2+](i) that accompanies exposure of CGN to veratridine. To further explore the potential interaction of KTx-7 with TTX-VSSC, we assessed the influence of KTX-7 on the binding of [3H]batrachotoxin ([3H]BTX) to neurotoxin site 2 on the TTX-VSSC. Although kalkitoxin was without effect on the basal binding of [3H]BTX to intact cerebellar granule neurons, in the presence of the positive allosteric modulator, deltamethrin, [3H]BTX binding was inhibited by KTx-7 in a concentration-dependent manner (11.9 nM [IC50=3.8-37.2 nM, 95% CI]). These results provide both direct and functional evidence for an interaction of kalkitoxin with the neuronal TTX-VSSC.

Bile duct schwannoma developed in the remnant choledochal cyst-a case associated with total agenesis of the dorsal pancreas.

A 59-year-old Japanese woman was referred to our hospital due to upper abdominal pain. At the age of 44, she was diagnosed with a congenital choledochal cyst, Todani's type Ic. She then underwent bypass operation with end-to-side choledochojejunostomy with Roux-en-Y technique as well as cholecystectomy. Magnetic resonance cholangiopancreatography revealed an 'oval' shaped cystic lesion with a maximal diameter of 25 mm, which had been 'spindle' shaped with a maximal diameter of 18 mm, 15 years ago. It also showed an anomalous pancreaticobiliary ductal union. In addition, a complete absence of the dorsal primordia of pancreas was revealed by magnetic resonance image and computed tomography scan. The patient underwent the surgical exploration for the resection of the 'oval' shaped cystic lesion. Haematoxylin and eosin staining of the thin section of the resected cyst showed a compact spindle cell pattern which was compatible with schwannoma, Antoni type A, which was confirmed by immunocytochemical technique. We present a very interesting case showing choledochal cyst, anomalous pancreaticobiliary ductal union, total agenesis of the dorsal pancreas and late-development of bile duct schwannoma in the remnant choledochal cyst.

Adult-onset leukoencephalopathy with vanishing white matter with a missense mutation in EIF2B5.

We report of a woman aged 52 years born to consanguineous parents and seeking treatment for progressive dementia and delusion. Neurologic examination revealed dementia and emotional instability, indifference, and confabulation. There was also mild spasticity of the bilateral lower limbs. MRI revealed diffuse white matter hyperintensity on T2-weighted images accompanied by hypointense areas on fluid-attenuated inversion recovery images. A homozygous missense mutation was identified in EIF2B5.

Characterization of the preferred stereochemistry for the neuropharmacologic actions of antillatoxin.

Antillatoxin is a potent ichthyotoxin and cytotoxin previously discovered from the marine cyanobacterium Lyngbya majuscula. Ensuing studies of its mechanism of action showed it to activate the mammalian voltage-gated sodium channel at a pharmacological site that is distinct from any previously described. The structure of antillatoxin, initially formulated from spectroscopic information, was subsequently corrected at one stereocenter (C-4) as a result of synthesis of four different antillatoxin stereoisomers (all possible C-4 and C-5 diastereomers). In the current study these four stereoisomers, (4R,5R)-, (4S,5R)-, (4S,5S)-, and (4R,5S)-antillatoxin, were characterized in five different biological assay systems: ichthyotoxicity to goldfish, microphysiometry using cerebellar granule cells (CGCs), lactose dehydrogenase efflux from CGCs, monitoring of intracellular Ca(2+) concentrations in CGCs, and cytotoxicity to Neuro 2a cells. Across these various biological measures there was great consistency in that the natural antillatoxin (the 4R,5R-isomer) was greater than 25-fold more potent than any of the other stereoisomers. Detailed NMR studies provided a number of torsion and distance constraints that were modeled using the MM2 force field to yield predicted solution structures of the four antillatoxin stereoisomers. The macrocycle and side chain of natural (4R,5R)-antillatoxin present an overall "L-shaped" topology with an accumulation of polar substituents on the external surface of the macrocycle and a hydrogen bond between N(H)-7' and the C(O)-1 carbonyl. The decreased potency of the three non-naturally occurring antillatoxin stereoisomers is certainly a result of their dramatically altered overall molecular topologies.

Smallest Todani's type II choledochal cyst.

A choledochal cyst is defined as an isolated or combined congenital dilation of the extra hepatic or intrahepatic biliary tree. Todani and colleagues proposed the five types of congenital choledochal cysts which have gained widespread acceptance. Type II choledochal cyst, a diverticulum of common bile duct, is rarest, and most reported cases of Type II were as large as several centimeters in size. We herein report the case of a small Type II choledochal cyst which was resected at pancreatoduodenectomy for carcinoma of the papilla of Vater. A 58-year-old Japanese male was referred to our hospital for the evaluation of jaundice. Preoperative cholangiogram via the percutaneous transhepatic biliary drainage tube revealed a complete obstruction at the narrow terminal segment. Furthermore, a small diverticular protrusion was demonstrated on the lower part of the common bile duct. The resected specimen showed a 2.2 x 1.7 x 1.2 cm carcinoma of the major papilla, and a deep, 2 mm in diameter and 5 mm in depth, depression on the posterior wall of the common bile duct. The anomalous pancreatobiliary duct was not seen. The deep depression was confirmed microscopically to penetrate the fibromuscular layer of the common bile duct and diagnosed as a Todani's Type II choledochal cyst. To our knowledge, the current case is the smallest Type II choledochal cyst which was completely resected.

Differential judgement of static facial expressions of emotions in three cultures.

Judging facial expressions of emotions has important clinical value in the assessment of psychiatric patients. Judging facial emotional expressions in foreign patients however, is not always easy. Controversy has existed in previous reports on cultural differences in identifying static facial expressions of emotions. While it has been argued that emotional expressions on the face are universally recognized, experimental data obtained were not necessarily totally supportive. Using the data reported in the literature, our previous pilot study showed that the Japanese interpreted many emotional expressions differently from USA viewers of the same emotions. In order to explore such discrepancies further, we conducted the same experiments on Chinese subjects residing in Beijing. The data showed that, similar to the Japanese viewers, Chinese viewers also judged many static facial emotional expressions differently from USA viewers. The combined results of the Chinese and the Japanese experiments suggest a major cross-cultural difference between American and Asian viewers in identifying some static facial emotional expressions, particularly when the posed emotion has negative connotations. The results have important implications for cross-cultural communications when facial emotional expressions are presented as static images.

Antillatoxin is a marine cyanobacterial toxin that potently activates voltage-gated sodium channels.

Antillatoxin (ATX) is a lipopeptide derived from the pantropical marine cyanobacterium Lyngbya majuscula. ATX is neurotoxic in primary cultures of rat cerebellar granule cells, and this neuronal death is prevented by either N-methyl-d-aspartate (NMDA) receptor antagonists or tetrodotoxin. To further explore the potential interaction of ATX with voltage-gated sodium channels, we assessed the influence of tetrodotoxin on ATX-induced Ca2+ influx in cerebellar granule cells. The rapid increase in intracellular Ca2+ produced by ATX (100 nM) was antagonized in a concentration-dependent manner by tetrodotoxin. Additional, more direct, evidence for an interaction with voltage-gated sodium channels was derived from the ATX-induced allosteric enhancement of [3H]batrachotoxin binding to neurotoxin site 2 of the alpha subunit of the sodium channel. ATX, moreover, produced a strong synergistic stimulation of [3H]batrachotoxin binding in combination with brevetoxin, which is a ligand for neurotoxin site 5 on the voltage-gated sodium channel. Positive allosteric interactions were not observed between ATX and either alpha-scorpion toxin or the pyrethroid deltamethrin. That ATX interaction with voltage-gated sodium channels produces a gain of function was demonstrated by the concentration-dependent and tetrodotoxin-sensitive stimulation of 22Na+ influx in cerebellar granule cells exposed to ATX. Together these results demonstrate that the lipopeptide ATX is an activator of voltage-gated sodium channels. The neurotoxic actions of ATX therefore resemble those of brevetoxins that produce neural insult through depolarization-evoked Na+ load, glutamate release, relief of Mg2+ block of NMDA receptors, and Ca2+ influx.

Frontal lobe membrane phospholipid metabolism and ventricle to brain ratio in schizophrenia: preliminary 31P-MRS and CT studies.

A number of studies employing in vivo phosphorous-31 magnetic resonance spectroscopy (31P-MRS) have demonstrated altered measurements of frontal phospholipid and high energy phosphorus metabolism in schizophrenia. Enlargement of both the cerebroventricular system and the cortical sulci also has been reported as the most consistent pathological finding in schizophrenia by several investigators. To our knowledge, however, only two studies have simultaneously examined structural and functional aspects of the biological substrate of schizophrenia in the same patients. Moreover, they may have failed to find a significant correlation between these variables because of small sample sizes. The possible relationship between frontal lobe membrane phospholipid metabolism and ventricle-to-brain ratio (VBR) in patients with schizophrenia was investigated. In 31 schizophrenic patients, frontal lobe membrane phospholipid metabolism was measured by 31P-MRS, and VBR was measured by computed tomography (CT). Stepwise multiple regression analysis disclosed that VBR positively correlated only with increased phosphodiester (PDE) level (beta = 0.381, p = 0.0345), but with no other metabolites. This finding may provide evidence for an association between structural brain abnormality and altered frontal lobe membrane metabolism in schizophrenic patients, although the p-value of the finding is not high.

Asymmetric total synthesis of (-)-mycothiazole.

[structure: see text] In this Letter we describe the first total synthesis of mycothiazole, a polyketide thiazole from a marine sponge. Key steps include our CMD oxidation for the conversion of thiazolidine 11 to thiazole 12 and the Nagao acetate aldol reaction of 5 with aldehyde 4 to construct the chiral secondary alcohol. The skipped diene was constructed by the standard Stille coupling, and the conjugated diene was synthesized by lithium(I)- and copper(I)-mediated Stille coupling.

Serum cholesterol levels and panic symptoms in patients with panic disorder: a preliminary study.

BACKGROUND: Although some previous research has focused on the relationship between panic disorder (PD) and a high total cholesterol (TC) level, it is still controversial. Recently, researchers have reported the heterogeneity of clinical symptoms in PD and the complexity of the correlations found among them. Therefore, the controversy on the TC level in PD may be due to the existence of clinical subgroups in PD. It is important to ascertain whether or not an elevated TC level in patients with PD is associated with specific panic symptoms. METHODS: In 104 drug-free patients with PD, we examined the relationship between TC level and each of several panic symptoms occurring at the time of panic attacks (PAs), which included anticipatory anxiety, agoraphobia, and 13 panic symptoms based on the DSM-III-R. RESULTS: Stepwise regression analysis revealed a significant effect of the presence of the symptom 'fear of dying' on TC levels. Patients with a fear of dying had a significantly higher TC level than those without it. LIMITATIONS: The relatively small sample size may limit the generalizability of our findings. DISCUSSION: These data suggest that TC level may be associated with panic symptoms in patients with PD.

Altered brain energy metabolism in lithium-resistant bipolar disorder detected by photic stimulated 31P-MR spectroscopy.

BACKGROUND: Previous 31P-MRS (magnetic resonance spectroscopy) studies suggested altered brain energy metabolism in bipolar disorder. This study characterized brain energy metabolism in lithium-resistant bipolar disorder using the photic-stimulation paradigm. METHODS: Subjects were 19 patients with DSM-IV bipolar disorder (nine responders and 10 nonresponders, 13 with bipolar I and six with bipolar II) in the euthymic state and 25 healthy volunteers. Energy metabolism in the occipital region was examined by 31P-MRS during photic stimulation (PS). Six 31P-MR spectra were obtained, one was before PS (Pre), two during 12 min of PS (PS1, PS2), and three after the PS (Post 1, Post 2, Post 3). RESULTS: Significant effect of diagnosis (lithium-responsive bipolar disorder, lithium-resistant bipolar disorder, and control) was found for the phosphocreatine peak area ratio during the course of the photic stimulation (P < 0.05 by repeated measures ANOVA). The phosphocreatine peak area ratio was significantly decreased at Post 1 and Post 2 compared with Pre in lithium-resistant bipolar patients (P = 0.01 and P = 0.01 by Dunnett's multiple comparison). CONCLUSIONS: The finding that phosphocreatine decreased after photic stimulation may be compatible with mitochondrial dysfunction. It is possible that mitochondrial function is impaired in lithium-resistant bipolar disorder.

Total synthesis of the antiviral marine natural product (-)-hennoxazole A.

[structure:see text] The marine natural product hennoxazole A was synthesized by a convergent approach. The diastereoselective Mukaiyama aldol reaction with beta-alkoxy aldehyde was used to construct the tetrahydropyran segment, and the preparation of the nonconjugated triene moiety was accomplished via S(N)2 displacement of allylic bromide with vinyllithium and Takai's iodoolefination followed by palladium-catalyzed cross coupling with MeMgBr. The final steps involve an amide coupling using DEPC and oxazole synthesis via a oxidation/cyclodehydration process.

Cloning two genes for nicotianamine aminotransferase, a critical enzyme in iron acquisition (Strategy II) in graminaceous plants.

Nicotianamine aminotransferase (NAAT), the key enzyme involved in the biosynthesis of mugineic acid family phytosiderophores (MAs), catalyzes the amino transfer of nicotianamine (NA). MAs are found only in graminaceous plants, although NA has been detected in every plant so far investigated. Therefore, this amino transfer reaction is the first step in the unique biosynthesis of MAs that has evolved in graminaceous plants. NAAT activity is dramatically induced by Fe deficiency and suppressed by Fe resupply. Based on the protein sequence of NAAT purified from Fe-deficient barley (Hordeum vulgare) roots, two distinct cDNA clones encoding NAAT, naat-A and naat-B, were identified. Their deduced amino acid sequences were homologous to several aminotransferases, and shared consensus sequences for the pyridoxal phosphate-binding site lysine residue and its surrounding residues. The expression of both naat-A and naat-B is increased in Fe-deficient barley roots, while naat-B has a low level of constitutive expression in Fe-sufficient barley roots. No detectable mRNA from either naat-A or naat-B was present in the leaves of either Fe-deficient or Fe-sufficient barley. One genomic clone with a tandem array of naat-B and naat-A in this order was identified. naat-B and naat-A each have six introns at the same locations. The isolation of NAAT genes will pave the way to understanding the mechanism of the response to Fe in graminaceous plants, and may lead to the development of cultivars tolerant to Fe deficiency that can grow in calcareous soils.

Quantitative proton magnetic resonance spectroscopy of the bilateral frontal lobes in patients with bipolar disorder.

BACKGROUND: Using 31P and 1H magnetic resonance spectroscopy (MRS) we previously reported that phosphocreatine was decreased in the left frontal lobe and choline-containing compounds were increased in the basal ganglia in the depressive state in patients with bipolar disorder. We applied quantitative 1H-MRS for further characterization of biochemical alteration in the frontal lobes of bipolar patients. METHODS: Twenty-three bipolar patients and 20 normal controls were examined by 1H-MRS with a 1.5T MR system. All patients were examined in the euthymic state, and eight patients were also examined in the depressive state. Volumes of interest of 2.5 x 2.5 x 2.5 cm were selected in the left and right frontal lobes. Absolute concentrations of N-acetyl-1-aspartate, creatine plus phosphocreatine, and choline-containing compounds were calculated from each metabolite peak. RESULTS: Creatine concentration in the left frontal lobe in bipolar patients in the depressive state was significantly lower than that in the euthymic state. Creatine concentration in the right frontal lobe in the male patients was significantly higher than that in the female patients and a similar trend was also found in the control subjects. CONCLUSIONS: We found a state-dependent change of creatine metabolism in the left frontal lobe of bipolar patients. The present results are compatible with our previous report of decreased phosphocreatine measured by 31P-MRS in the left frontal lobe in bipolar disorder. We also found an effect of gender on the creatine concentration. There may be a gender difference in creatine transport function into the brain.

Binding of [3H]U-101958 to sigma1 receptor-like sites in human cerebellum and neuroblastoma cells.

1-Benzyl-4-[N-(3-isopropoxy-2-pyridinyl)-N-methyl]-amino-piperidine ([3H]U-101958), a dopamine D4 receptor ligand, was found to bind to a large sigma1 receptor-like component in human cerebellum and SK-N-MC neuroblastoma cells with high affinity (2-4 nM Kd). By contrast, binding to dopamine D4 receptors represented 10% or less of the sigma1 receptor-like site. Considering that U-101958 has been characterized as either a dopamine D4 receptor agonist or antagonist, depending on the system under study, the observation that U-101958 also binds to sigma1 receptor-like sites is important for accurate interpretation of the pharmacological actions of this compound. [3H]U-101958 may be a useful radioligand for sigma1 rather than dopamine D4 receptor sites.

Relationship of energy metabolism detected by 31P-MRS in the human brain with mental fatigue.

To search for a possible relationship between brain energy metabolism and mental fatiguability, 10 normal volunteers were examined by 31P-MRS (phosphorus-31 magnetic resonance spectroscopy) in the occipital cortex during photic stimulation (PS), and Uchida-Kraepelin test (UKT), a standardized serial calculation task, was used for measurement of intraindividual characteristics of mental fatigue in these subjects. More decrease of phosphocreatine measured by 31P-MRS during the PS was significantly associated with more effects of rest assessed by UKT (r = -0.86, p <0.005). More decrease in pH after PS was associated with steeper decline of performance (r = 0.78, p <0.01). These findings suggest that characteristics of brain energy metabolism in an individual may relate to intrinsic patterns of mental fatigability.

Conformational change of ascidiacyclamide caused by asymmetric modification for an isoleucine residue: structural analyses of [Gly], [Leu], and [Phe]ascidiacyclamides by x-ray diffraction and NMR spectroscopy.

Ascidiacyclamide, a cytotoxic cyclic peptide from tunicate, is composed of unusual amino acids and has a repeated sequence, c[-thiazole-D-Val-oxazoline-L-Ile-]2 ([Ile]ASC). The symmetric chemical structure has been assumed to be correlated with the cytotoxicity, and it is reasonable to consider that the disturbance of its structure from the C2 symmetry results in the changes of conformation and activity. In order to quantitatively estimate the molecular conformation-activity relationship, an isoleucine residue was substituted by Gly, Leu, or Phe to disturb the C2 symmetry. The conformations of three derivatives were examined by nmr spectroscopy and the crystal structure of [Leu]ASC was also analyzed by x-ray diffraction method. The 1H-nmr experiments and the constrained molecular dynamics simulations showed the twisted "figure 8" conformers for [Gly] and [Phe]ASCs and the "square" conformer for [Leu]ASC in the DMSO solution. The x-ray crystal analysis of [Leu]ASC also revealed the square form similar to the solution structure. On the other hand, their cytotoxic activities were measured using L1210 leukemia cells and were related with the bulkiness and/or hydrophobicity of the side chain of the substituted amino acid; [Phe] > or = [Ile] > [Leu] >> [Gly]ASCs. As an attempt to consider the correlation between the activity and conformer, the accessible surface area (ASA) was calculated for each derivative to estimate the size or bulkiness of its conformation. Although the ASAs of nmr structures were not directly related to the type of conformer (figure 8 or square form), it was an important probe to consider the cytotoxicity of each derivative.

Misinterpretation of facial expression: a cross-cultural study.

Accurately recognizing facial emotional expressions is important in psychiatrist-versus-patient interactions. This might be difficult when the physician and patients are from different cultures. More than two decades of research on facial expressions have documented the universality of the emotions of anger, contempt, disgust, fear, happiness, sadness, and surprise. In contrast, some research data supported the concept that there are significant cultural differences in the judgment of emotion. In this pilot study, the recognition of emotional facial expressions in 123 Japanese subjects was evaluated using the Japanese and Caucasian Facial Expression of Emotion (JACFEE) photos. The results indicated that Japanese subjects experienced difficulties in recognizing some emotional facial expressions and misunderstood others as depicted by the posers, when compared to previous studies using American subjects. Interestingly, the sex and cultural background of the poser did not appear to influence the accuracy of recognition. The data suggest that in this young Japanese sample, judgment of certain emotional facial expressions was significantly different from the Americans. Further exploration in this area is warranted due to its importance in cross-cultural clinician-patient interactions.