Factor structure of symptoms in functional psychoses

Global ratings from the Scale for the Assessment of Positive Symptoms and Scale for the Assessment of Negative Symptoms were subjected to principal-component analysis (PCA) in 80 schizophrenia patients, 76 patients with schizophreniform disorder, 80 patients with schizoaffective and mood disorders, and 78 patients with delusional, brief reactive, and atypical psychoses. The resulting factors were correlated with depressive, manic, and catatonic syndromes, and subjected to a multivariate analysis of variance across DSM-III-R diagnoses. PCAs revealed that psychosis, disorganization, and negative factors were also present in each of the nonschizophrenic groups. The disorganization factor tended to be related to the manic syndrome, and the negative factor to depressive and catatonic syndromes. Overall, the three factors had little diagnostic relevance in functional psychoses, although the negative factor was relatively more characteristic of schizophrenia. The data suggest that positive, negative, and disorganization factors are not specific to schizophrenia; this is consistent with a dimensional view of psychopathology in functional psychoses.     

A highly polymorphic microsatellite marker located within the choroideremia gene

Although serotonergic dysregulation is a leading pathogenetic hypothesis for obsessive-compulsive disorder (OCD), some evidence also suggests a possible dysregulation of the dopaminergic system in this disorder. Therefore, individual differences in deoxyribonucleic acid (DNA) coding for dopamine receptor proteins might contribute to the genetic background of this disorder. Previously we reported a null mutation in exon 1 of the dopamine D4 receptor gene. The variant type is characterized by a 13 bp deletion and is predicted to code for a truncated, non-functional receptor. We assessed the frequency of this polymorphism in 157 OCD patients, 196 schizophrenics, 111 bipolars and 162 healthy controls of Italian descent. Our findings do not implicate a role for this mutation in conferring a susceptibility to OCD and confirm previous negative results regarding its involvement in schizophrenia and bipolar disorder.     

Follow-up and family study of postpartum psychoses. Part I: Overview

A group of 119 patients suffering from a severe psychiatric postpartum disorder who were admitted for the first time in their life to a psychiatric hospital has been investigated. The onset of illness occurred within 3 months following delivery. The patients represented 92% of the total sample fulfilling the inclusion criteria. A follow-up investigation was performed after a mean of 21 years (range 2-35 years). Of the patients 66% had nonpuerperal psychotic episodes in later life. The diagnosis, taking into account the long-term course, was affective psychosis in 57%, schizoaffective psychosis in 18%, schizophreniform psychosis in 12%, brief reactive psychosis in 4% and schizophrenia in 9%. A bipolar psychosis was found in 31%. The relation of unipolar to bipolar psychoses corresponded to that in a control group of affectively ill women without puerperal onset. The frequency of a manic syndrome in bipolar psychoses at the index episode was the same as in nonpuerperal episodes, which does not suggest a mania-provoking pathoplastic effect of the puerperium. The comparison with female nonpuerperal controls matched for age and diagnosis revealed evidence of a better long-term course in the index patients. The risk of a puerperal relapse for further pregnancies was 35%. The global morbidity risk for functional psychoses in first-degree relatives was 11%, with affective psychoses representing the majority of secondary cases (6.8%). The index patients showed a nonsignificant lower morbidity risk in relatives than a control group of psychotically ill women without puerperal onset. The major aetiological factor found for postpartum psychoses is the relation of these disorders to functional psychoses. There is strong evidence that the postpartum period tends to provoke affective psychoses and other nonschizophrenic psychoses, but not, or only to a lesser degree, narrowly defined schizophrenias. The liability to puerperal decompensations suggests some common pathophysiological mechanism, the nature of which remains unknown.     

Buckling of cylinders may cause prolonged penile pain after prosthesis implantation: a case control study using magnetic resonance imaging of the penis

The evidence for a significant genetic contribution to the functional psychoses (schizophrenia and bipolar disorder) is now well established. However, in both cases, the non-mendelian mode of inheritance has made the identification of susceptibility loci particularly challenging. The neuropeptide cholecystokinin (CCK) is present both in the gut and the CNS. Studies of CCK-like immunoreactivity and CCK mRNA levels in human brains have revealed high concentrations in numerous loci and shown colocalisation of CCK with, for example, dopamine and tyrosine hydroxylase. Furthermore, antagonists of CCK-B receptors, which are found most frequently in the brain, inhibit the activity of brain dopamine neurons. Such findings suggest that, with respect to neuropsychiatric disorders, CCK is a suitable candidate for analysis using methods to detect gene variations which have the potential to affect protein structure or expression. In the present study, mutation analyses were carried out on the human CCK gene. Linked polymorphisms were found in the promoter region and in intron 1 close to the 3' mRNA splice acceptor site. However, the allele frequencies of these polymorphisms in samples of individuals affected with either schizophrenia (n=117) or bipolar disorder (n=124) did not differ from those of control subjects (n=234), suggesting that these variations do not confer a predisposition to either of the functional psychoses.     

Sources of diagnostic uncertainty for chronically psychotic cocaine abusers

OBJECTIVE: This study determined the sources and frequency of diagnostic uncertainty for patients with chronic psychosis and active cocaine abuse or dependence and assessed the usefulness of prospective follow-up in clarifying diagnosis. METHODS: A total of 165 male patients with chronic psychoses and cocaine abuse or dependence on inpatient units of a Veterans Affairs medical center were evaluated using the Structured Clinical Interview for DSM-III-R (SCID-R), urine tests, hospital records, and interviews with collateral sources. An algorithm allowing key SCID-R items and diagnostic criteria to be designated as provisionally met or uncertain was applied, resulting in a provisional diagnosis and a list of alternate diagnoses. The assessment was repeated 18 months later in an attempt to resolve diagnostic uncertainty. RESULTS: In 30 cases (18 percent), initial assessment produced a definitive diagnosis, including 21 cases of schizophrenia, six of schizoaffective disorder, and three of psychostimulant-induced psychotic disorder. In the other 135 cases, a definitive diagnosis could not be reached because of one or more sources of diagnostic uncertainty, including insufficient periods of abstinence (78 percent), poor memory (24 percent), and inconsistent reporting (20 percent). Reassessment at 18 months led to definitive diagnoses in 12 additional cases. CONCLUSIONS: It was frequently difficult to distinguish schizophrenia from chronic substance-induced psychoses. Rather than concluding prematurely that psychotic symptoms are, or are not, substance induced, clinicians should initiate treatment of both psychosis and the substance use disorder in uncertain cases. The persistence or resolution of psychosis during abstinence and additional history from the stabilized patient or collateral sources may clarify the diagnosis.     

Intraocular gene transfer of ciliary neurotrophic factor prevents death and increases responsiveness of rod photoreceptors in the retinal degeneration slow mouse

Several mutations causing both photoreceptor degeneration and malfunction have been identified in humans and animals. Although intraocular injection of trophic factors has been shown to reduce photoreceptor death in a few conditions of rapid photoreceptor loss, it is unclear whether long-term beneficial changes in functional properties of affected photoreceptors can be obtained by treatment with these factors. The rds/rds mouse is a spontaneous mutant bearing a null mutation in the rds/peripherin gene, which is linked to many forms of dominant retinal degenerations in humans. Here, we report that intraocular adenovirus-mediated gene transfer of ciliary neurotrophic factor (CNTF) in this mutant reduces photoreceptor loss, causes a significant increase in the length of photoreceptor segments, and results in a redistribution and an increase in the retinal content of the photopigment rhodopsin. These effects are accompanied by a significant increase in the amplitude of the a- and b-waves of the scotopic electroretinogram. These results suggest that continuous administration of CNTF could potentially be useful for the treatment of some forms of retinal degeneration.     

Increased overall antibiotic susceptibility in Staphylococcus aureus femAB null mutants

The staphylococcal pentaglycine side chain of the peptidoglycan is reduced to one glycine in femAB null mutants. This is associated with increased susceptibility to methicillin and to a whole range of unrelated antibiotics as well. Genetic evidence suggests that femAB null mutants are only viable because of a compensatory mutation in an unlinked site.     

Elevation of CSF somatostatin concentrations in mania

OBJECTIVE: The aim of this study was to compare levels of CSF somatostatin (somatotropin release-inhibiting factor) in drug-free patients with different major psychiatric disorders. METHOD: CSF somatostatin concentrations were measured in 66 drug-free inpatients with Research Diagnostic Criteria diagnoses of schizophrenia, major depressive disorder, manic disorder, or schizoaffective disorder. RESULTS: In comparison with both the patients with schizophrenia and the patients with schizoaffective disorder, the manic patients had markedly elevated CSF somatostatin concentrations. The depressed patients had significantly higher levels than the schizophrenic patients. CONCLUSIONS: Mania is associated with relatively higher CSF somatostatin concentrations.     

Searching for the psychometric boundaries of schizophrenia: Evidence from the New York High-Risk Study.

We offer a heuristic approach for using psychometric indicators to resolve questions in the classification of schizophrenia and elucidation of its clinical and genetic boundaries. A combination of signs derived from the Minnesota Multiphasic Personality Inventory (MMPI) was used to provide evidence for the accuracy of parental phenotypic assessments and the determination of risk for schizophrenia in children in the New York High-Risk Study. The MMPI indicators were useful in discriminating schizophrenia defined by the Research Diagnostic Criteria (RDC) from psychotic and nonpsychotic affective illness and normality, with moderately high to high predictive power, specificity, and sensitivity. Kappa calculations showed a high rate of chance-corrected diagnostic agreement for schizophrenia between the RDC and the MMPI. The data provide tentative support for the allocation of schizoaffective cases to one of two syndromic clusters related to either schizophrenia or affective illness. An exploratory attempt was made to demarcate schizophrenia as a discrete disorder separated by qualitative psychometric boundaries. The imprecision of the current psychiatric nosology may lead to difficulties in resolving distinctions between the functional psychoses, and we propose that use of both psychometric data and fixed diagnostic criteria can lead to a more valid definition of schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Isolated fourth nerve palsy from midbrain hemorrhage: case report

There is accumulating evidence for the efficacy of lamotrigine in the treatment of bipolar disorder, including bipolar depression, both as monotherapy and in combination with sodium valproate. We present the cases of 3 female patients admitted to our hospital with the diagnosis of schizoaffective disorder who were treated with lamotrigine. While dosages up to 200 mg/day, resulting in serum concentrations of less than 5 mg/l, were only partially effective, 400 mg/day (with serum concentrations >10 mg/l) led to considerable mood stability, with complete remission from paranoid symptoms. We suggest that lamotrigine might be helpful in the treatment of schizoaffective disorder, probably with serum concentrations of more than 5 mg/l.     

CSF neurotensin concentrations and antipsychotic treatment in schizophrenia and schizoaffective disorder

OBJECTIVE: The relationship between CSF neurotensin concentrations and measures of psychopathology in patients with schizophrenia or schizoaffective disorder was examined before and after treatment with antipsychotic drugs. METHOD: CSF neurotensin concentrations were measured in 42 drug-free patients with schizophrenia or schizoaffective disorder. For 18 of these patients, CSF neurotensin was measure again after 4 weeks of antipsychotic treatment. RESULTS: Significantly higher levels of pretreatment psychopathology were observed in the patients with the lowest CSF neurotensin concentrations. Furthermore, improvements in overall psychopathology and, particularly, negative symptoms were correlated with increases in CSF neurotensin concentrations during treatment. CONCLUSIONS: These findings provide further evidence for a role of neurotensin the pathophysiology of psychosis and in the mechanism of action of antipsychotic drugs.     

Affective and social-behavioral correlates of physical and social anhedonia in schizophrenia.

The association between scales measuring physical and social anhedonia, self-reports of affective response to emotion-eliciting films, and role play measures of social skill was evaluated in patients with schizophrenia, schizoaffective disorder, and bipolar affective disorder. It was hypothesized that patients with schizophrenia would report significantly greater anhedonia than the bipolar patients and that higher scores on the anhedonia scales (AHSs) would be related to attenuated reports of the experience of positive affect and poorer social skill. Patients with schizophrenia and schizoaffective disorder did not differ in ratings of anhedonia, but both groups had higher physical and social AHSs than did bipolar patients. Higher scores on the physical AHS, but not the social AHS, were related to attenuated reports of positive affect following viewing of affect-eliciting films in schizophrenia-schizoaffective disorder patients. Neither AHS was related to role play measures of social skill performance for any patient group. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus

A peripheral membrane protein that is interactive with lymphocytic choriomeningitis virus (LCMV) was purified from cells permissive to infection. Tryptic peptides from this protein were determined to be alpha-dystroglycan (alpha-DG). Several strains of LCMV and other arenaviruses, including Lassa fever virus (LFV), Oliveros, and Mobala, bound to purified alpha-DG protein. Soluble alpha-DG blocked both LCMV and LFV infection. Cells bearing a null mutation of the gene encoding DG were resistant to LCMV infection, and reconstitution of DG expression in null mutant cells restored susceptibility to LCMV infection. Thus, alpha-DG is a cellular receptor for both LCMV and LFV.     

Occurrence and clinical correlates of psychiatric comorbidity in patients with psychotic disorders

BACKGROUND: The aim of this study was to explore patterns and clinical correlates of psychiatric comorbidity in patients with schizophrenia spectrum disorders and mood spectrum disorders with psychotic features. METHOD: Ninety-six consecutively hospitalized patients with current psychotic symptoms were recruited and included in this study. Index episode psychotic diagnosis and psychiatric comorbidity were assessed using the Structured Clinical Interview for DSM-III-R-Patient Version (SCID-P). Psychopathology was assessed by the SCID-P, Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, and Hopkins Symptom Checklist. Awareness of illness was assessed with the Scale to Assess Unawareness of Mental Disorders. RESULTS: The total lifetime prevalence of psychiatric comorbidity in the entire cohort was 57.3% (58.1% in schizophrenia spectrum disorders and 56.9% in mood spectrum psychoses). Overall, panic disorder (24%), obsessive-compulsive disorder (24%), social phobia (17.7%), substance abuse (11.5%), alcohol abuse (10.4%), and simple phobia (7.3%) were the most frequent comorbidities. Within the group of mood spectrum disorders, negative symptoms were found to be more frequent among patients with psychiatric comorbidity than among those without comorbidity, while such a difference was not detected within the group of schizophrenia spectrum disorders. Social phobia, substance abuse disorder, and panic disorder comorbidity showed the greatest association with psychotic features. An association between earlier age at first hospitalization and comorbidity was found only in patients with unipolar psychotic depression. Patient self-reported psychopathology was more severe in schizophrenia spectrum patients with comorbidity than in those without, while such a difference was less pronounced in mood spectrum psychoses. CONCLUSION: These findings suggest that psychiatric comorbidity is a relevant phenomenon in psychoses and is likely to negatively affect the phenomenology of psychotic illness. Further studies in larger psychotic populations are needed to gain more insight into the clinical and therapeutic implications of psychiatric comorbidity in psychoses.     

Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa

Desmosomes are highly organized intercellular adhesive junctions that are particularly prominent in epidermis and other tissues experiencing mechanical stress. Desmoplakin, a constitutive component of the desmosomal plaque, is the most abundant protein present in such junctions and plays a critical role in linking the intermediate filament network to the plasma membrane in these tissues. Here we report the first mutation in the gene encoding desmoplakin. The identified mutation, resulting in a null allele and haploinsufficiency, was observed in genomic DNA from a kindred with the dominantly inherited skin disorder, striate palmoplantar keratoderma. Affected individuals had a linear pattern of skin thickening on the fingers and palms and circumscribed areas of skin thickening on the soles. Affected skin demonstrated loosening of intercellular connections, disruption of desmosome-keratin intermediate filament interactions and a proportion of rudimentary desmosomal structures. The disorder mapped to chromosome 6p21 with a maximum lod score of 10.67. The mutation was a heterozygous C-->T transition in exon 4 of the desmoplakin gene and predicted a premature termination codon in the N-terminal region of the peptide. This is the first reported mutation of desmo-plakin and also the first inherited skin disorder in which haploinsufficiency of a structural component has been implicated. It identifies dosage of desmoplakin as critical in maintaining epidermal integrity.     

Morphologic basis of psychoses associated with vascular and senile pathology

The paper deals with a study of 100 patients diagnosed as combined senile and vascular psychoses. It is marked that in classical cases of such combinations the disorder has 3 stages. On the first stage there is a predominance of vascular pathology. After 60 years of age (the second stage) the senile sumptomatology disguises many symptoms of vascular lesions. The third stage is characterized by a vascular catastrophe. In many cases of combined psychoses there may be complications of other somatic pathology and mainly of lung and liver disorders.     

Mutation in the mismatch repair gene Msh6 causes cancer susceptibility

Mice carrying a null mutation in the mismatch repair gene Msh6 were generated by gene targeting. Cells that were homozygous for the mutation did not produce any detectable MSH6 protein, and extracts prepared from these cells were defective for repair of single nucleotide mismatches. Repair of 1, 2, and 4 nucleotide insertion/deletion mismatches was unaffected. Mice that were homozygous for the mutation had a reduced life span. The mice developed a spectrum of tumors, the most predominant of which were gastrointestinal tumors and B- as well as T-cell lymphomas. The tumors did not show any microsatellite instability. We conclude that MSH6 mutations, like those in some other members of the family of mismatch repair genes, lead to cancer susceptibility, and germline mutations in this gene may be associated with a cancer predisposition syndrome that does not show microsatellite instability.     

Nutritional status and serum lipids of a rural population in Northeast Thailand--an example of health transition

The authors retrospectively evaluated the etiology and clinical findings of patients with first manifestations of psychotic symptoms after the age of 65. Nearly 10% of over 1,700 consecutive geriatric patients admitted to an acute inpatient psychogeriatric unit had late-life onset psychotic symptoms. About three-fourths of these were women, usually in their seventies. Dementia of the Alzheimer's type was the most common cause of psychosis arising in late life, followed by major depression, medical/toxic causes, delirium, bipolar disorder, delusional disorder, schizophrenia, and schizoaffective disorder. Clinical manifestations consisted mostly of delusions and hallucinations.     

Release of ciliary neurotrophic factor from cultured astrocytes and its modulation by cytokines

CNTF rescues various types of lesioned neurons in vivo, and it needs to be released from astrocytes into the extracellular space to have the effect. However, direct evidence for CNTF release has not been unequivocally demonstrated. We hypothesized that the rapid sequestration by CNTF receptor present on cultured astrocytes might be the cause of the inability to detect CNTF released into astrocyte-conditioned medium (ACM). Therefore, we measured CNTF immunoreactivity in medium conditioned by astrocytes treated with phosphatidylinositol-specific phospholipase C (PI-PLC) which was used to prevent released CNTF from binding to the CNTF receptor, since PI-PLC cleaves glycosyl-phosphatidylinositol anchor of CNTFR alpha, the unique component involved in CNTF binding. CNTF was not detectable in untreated ACM, but was detectable in PI-PLC-treated ACM. These results together with the evidence that PI-PLC treatment did not have a toxic effect on astrocytes prove the fact that CNTF can be released from astrocytes without cell lysis. Subsequently, the effect of cytokines such as IL-1 beta, TNF-alpha, and EGF on CNTF release was examined. These cytokines increased CNTF protein levels in ACMs without increasing CNTF protein levels in astrocyte-extracts, indicating that they enhanced CNTF release from astrocytes.