Resting state functional magnetic resonance imaging reveals distinct brain activity in heavy cannabis users - a multi-voxel pattern analysis.

Chronic cannabis use can cause cognitive, perceptual and personality alterations, which are believed to be associated with regional brain changes and possible changes in connectivity between functional regions. This study aims to identify the changes from resting state functional magnetic resonance imaging scans. A two-level multi-voxel pattern analysis was proposed to classify male cannabis users from normal controls. The first level analysis works on a voxel basis and identifies clusters for the input of a second level analysis, which works on the functional connectivity between these regions. We found distinct clusters for male cannabis users in the middle frontal gyrus, precentral gyrus, superior frontal gyrus, posterior cingulate cortex, cerebellum and some other regions. Based on the functional connectivity of these clusters, a high overall accuracy rate of 84-88% in classification accuracy was achieved. High correlations were also found between the overall classification accuracy and Barrett Barrett Impulsiveness Scale factor scores of attention and motor. Our result suggests regional differences in the brains of male cannabis users that span from the cerebellum to the prefrontal cortex, which are associated with differences in functional connectivity.

Propranolol for the treatment of infantile haemangiomas: our experience with 44 patients.

Propranolol is an effective, safe treatment for complicated infantile haemangiomas (IH). We evaluated all patients (n = 44) with IH treated with propranolol in our department. Of the 44 patients who were begun on propranolol therapy, 26 patients have completed the treatment to date and all had a good response. The mean duration of treatment was 45.7 weeks. Four patients developed rebound growth of their IH, which responded to the reintroduction of propranolol. Two patients with PHACES (posterior fossa malformations, haemangiomas, arterial anomalies, coarctation of the aorta/cardiac abnormalities, eye anomalies and sternal defects/supraumbilical raphe) syndrome were treated with lower than standard doses, because of concern about possible cerebrovascular compromise. Adverse effects were minor in most patients. Three patients discontinued propranolol because of vomiting, wheeze, and hypoglycaemia, respectively. Our duration of treatment was longer than that of other series, and may be due to our group having higher rates of hypotension, recorded in 27.3% of patients, precluding an increase in propranolol dose. Our experience supports that propranolol is an effective first-line agent for complicated IH.

Rings in the neonate.

Neonatal lupus erythematosus (NLE) is an uncommon disease of the neonate. It is believed to be caused by the transplacental passage of maternal autoantibodies to the ribonucleoproteins (Ro/SSA, La/SSB or rarely U RNP) as these are almost invariably present in NLE sera. The most common clinical manifestations include cutaneous lupus lesions and congenital complete heart block. Hepatobiliary and haematologic abnormalities are reported less frequently. We describe a patient with cutaneous NLE to illustrate and raise awareness of the characteristic annular eruption of this condition. We also emphasize the need for thorough investigation for concomitant organ involvement and for maternal education regarding risk in future pregnancies.

Steady state and induced auditory gamma deficits in schizophrenia.

Steady state auditory evoked potentials (SSAEPs) in the electroencephalogram (EEG) and magnetoencephalogram (MEG) have been reported to be reduced in schizophrenia, most consistently to frequencies in the gamma range (40 Hz and greater). The current study evaluated the specificity of this deficit over a broad range of stimulus frequencies and harmonics, the relationship between phase locking and signal power, and whether induced 40 Hz activity was also affected. SSAEPs to amplitude modulated tones from 5 to 50 Hz were obtained from subjects with schizophrenia (SZ) and healthy control subjects in 5 Hz steps. Time-frequency spectral analysis was used to differentiate EEG activity synchronized in phase across trials using Phase Locking Factor (PLF) and Mean Power (MP) change from baseline activity. In the SSAEP frequency response condition, patients with SZ showed broad band reductions in both PLF and MP. In addition, the control subjects showed a more pronounced increase in PLF with increases in power compared to SZ subjects. A noise pulse embedded in 40 Hz stimuli resulted in a transient reduction of PLF and MP at 40 Hz in control subjects, while SZ showed diminished overall PLF. Finally, induced gamma (around 40 Hz) response to unmodulated tone stimuli was also reduced in SZ, indicating that disturbances in this oscillatory activity are not confined to SSAEPs. In summary, SZ subjects show impaired oscillatory responses in the gamma range across a wide variety of experimental conditions. Reduction of PLF along with reduced MP may reflect abnormalities in the auditory cortical circuits, such as a reduction in pyramidal cell volume, spine density and alterations in GABAergic neurons.

Calciphylaxis in a patient with normal renal function: response to treatment with sodium thiosulfate.

Calciphylaxis is a rare, life-threatening cause of skin necrosis. The condition is primarily reported in patients with end-stage renal disease, and is associated with significant morbidity and mortality. Treatment has mainly been empirical. We report a case of calciphylaxis in a patient with normal renal function and hypoparathyroidism, who responded to treatment with sodium thiosulfate. To our knowledge, this is the first reported case of the use of sodium thiosulfate to treat calciphylaxis in a patient with normal renal function.

Tinea capitis in a paediatric population.

Tinea capitis is an increasing problem in Europe. The pattern of infection is changing with an increase in pathogenic anthropophilic dermatophytes particularly Trichophyton tonsurans. We aimed to determine the frequency of tinea capitis in a paediatric population attending dermatology outpatients and examine the clinical spectrum of disease. A retrospective analysis was performed of all laboratory proven tinea capitis cases presenting to the dermatology outpatient department at The Children's University Hospital, Temple Street over an 18-month period (1st January 2004 to 30th of June 2005 inclusive). Sixty-two children had tinea capitis of whom 53 (85.5%) were of African descent. Thirty-five (56%) were male and 27 female (44%). The average age at presentation was 4.02 years (age range 1-163 months) with five cases occurring in children less than one year of age. The most common pathogen was the anthropophilic dermatophyte Trichophyton tonsurans, accounting for 47 (75.8%) of all cases of tinea capitis. Eight (12.9%) were secondary to Microsporum ferrigineum, 2 (3.2%) secondary to Trichophyton violaceum, both Trichophyton soudanese and Trichophyton verruosum accounted for 1.6% each. The zoophilic organism Microsporum canis was diagnosed in 3 cases (4.8%). Presenting signs included scaling of the scalp (35.47%), scaling of the scalp and alopecia (53.24%), and alopecia and kerion (11.29%/o). The duration of symptoms was recorded in 52 patients with the average duration 8.38 months (range 0.5-72 months). In 20 cases an associated skin involvement on other areas of the body was recorded. All patients at diagnosis were either on no, suboptimal or inappropriate treatment. The prevalence of tinea capitis is increasing in this hospital based cohort. The main pathogen is now Trichophyton tonsurans. Children of African descent are at increased risk of infection. The diagnosis is poorly recognized and needs to be highlighted as a public health issue. There is a need for community based prevalence studies.

Thyroid autoimmunity in chronic urticaria.

BACKGROUND: Chronic urticaria (CU) is an autoimmune process in some patients. An association between CU and autoimmune thyroid disease has also previously been proposed. Our group has identified functionally significant histamine-releasing autoantibodies in one subset of CU patients (subset 1), predicted by positive autologous intradermal serum tests and positive histamine release from donor basophil leucocytes in vitro. Sera from a second subset of patients (subset 2), all of whom had positive autologous intradermal serum tests, failed to release histamine from donor basophils. A final disease subset (subset 3) has no identifiable skin reactivity (negative autologous serum skin test) or in vitro histamine releasing activity. OBJECTIVES: In order to examine further the possible relationships between thyroid autoimmunity, thyroid dysfunction and CU, we have examined thyroid autoantibodies and thyroid-stimulating hormone (TSH) levels (an indirect measure of thyroid dysfunction) in the three CU subsets. PATIENTS/METHODS: We studied 182 patients (69% female), of whom 90 had a positive autologous intradermal serum test. RESULTS: Eighteen skin test-positive and four skin test-negative patients had thyroid microsomal antibodies (TMA). TSH outside the normal range was found in 13 skin test-positive and one skin test-negative patient. These findings represent clustering of TMA positivity [risk ratio (RR) 4.06, 95% confidence interval (CI) 1.56-10.6] and of abnormal thyroid function (RR 15.5, CI 2.07-11.6) among the skin test-positive patients. However, in the overall study group an elevated TSH was present in seven patients (3.8%, CI 1.6-7.8) comparable to the 5% expected prevalence in the community. Thyroglobulin antibodies (TGA) were present in two of 182 patients. CONCLUSIONS: There were significant differences between skin test-positive and skin test-negative patients with regard to autoimmune thyroid disease. Evidence for autoimmune thyroid disease and abnormal thyroid function was largely found among the skin test-positive patients, supporting the theory of an autoimmune aetiology in this group.

Eyeblink conditioning deficits indicate timing and cerebellar abnormalities in schizophrenia.

Accumulating evidence indicates that individuals with schizophrenia manifest abnormalities in structures (cerebellum and basal ganglia) and neurotransmitter systems (dopamine) linked to internal-timing processes. A single-cue tone delay eyeblink conditioning paradigm comprised of 100 learning and 50 extinction trials was used to examine cerebellar timing circuits in 13 medicated patients with schizophrenia and 13 age- and sex-matched controls. Patients with schizophrenia showed impaired learning of the conditioned response compared to controls and also greater within-subject variability in the timing of their responses. These findings are consistent with models of schizophrenia in which timing deficits underlie information-processing abnormalities and clinical features of the disorder.

Auditory event-related potential abnormalities in bipolar disorder and schizophrenia.

Auditory P300 latency prolongation or amplitude reduction has been reported in patients affected by bipolar disorder and in schizophrenia. The purpose of this study was to test whether the auditory P300 and earlier event-related potential (ERP) components elicited during an auditory discrimination task could differentiate between these two disorders. Thirteen patients with manic or mixed bipolar disorder, 12 patients with schizophrenia, and 24 control subjects were evaluated. None of the subjects had a history of alcohol or substance abuse or dependence. ERPs were elicited during an auditory discrimination task in which a subject pressed a key to infrequent 1500 Hz tones interspersed amid a series of 1000 Hz tones. The amplitude and latency of N100 and P200 were measured from ERPs to non-target tones, and N200 and P300 were measured from ERPs to target tones. N100, P200 and N200 amplitudes were reduced in schizophrenia patients, but not in bipolar patients. Both bipolar disorder and schizophrenia patients showed reduced P300 amplitude and prolonged P300 latency. Amplitude reduction in the early ERP components implicates auditory processing deficits in schizophrenia. Both groups showed reductions in P300 amplitude, suggesting a disturbance of the temporal-parietal generators of this component. Prolonged P300 latency is consistent with impaired attentional processing in schizophrenia and symptomatic bipolar disorder patients.

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study.

The present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial-temporal lobe regions - two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal-prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.

Psychological features in persons at risk for familial Alzheimer's disease.

Persons at risk for inherited neurodegenerative diseases may experience symptoms of anxiety and depression because of concern over the possibility of developing the disease in the future. The purpose of this study was to assess psychological and emotional symptoms in persons at the age of risk for developing early-onset familial Alzheimer's disease (FAD). Their responses on a psychiatric rating scale (SCL-90-R) were compared with four groups: patients with mild FAD; head injury patients; patients with clinically diagnosed depression; and healthy control subjects. Mean scores of the at-risk FAD group were not statistically different than those of the controls. In contrast, the head injury and depressed groups had significantly elevated scores across the clinical scales. These results suggest that depression and anxiety are not prominent features in persons at genetic risk for early-onset familial Alzheimer's disease. Similar results have been found in studies of persons at risk for developing Huntington's disease, another autosomal dominant neurodegenerative disease.

The P3 auditory event-related brain potential indexes major personality traits.

BACKGROUND: The amplitude of the auditory P3 event-related potential is reduced in patients with axes I and II disorders. Data regarding P3 amplitude and normal personality traits in healthy individuals have been inconsistent, however, although more extreme variants of dimensional traits such as neuroticism and extraversion are associated with psychiatric morbidity. METHODS: Male subjects (n = 18) recruited from the community completed the NEO Five-Factor Inventory, which consists of five scales: Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness. P3 potentials were generated using an auditory discrimination paradigm to which a third, novel stimulus was added. Partial least squares analysis, a multivariate statistical procedure, was used to test the relationship, in both stimulus conditions, between P3 amplitude at six electrode sites and the five personality dimensions. RESULTS: P3 amplitude across conditions and sites was positively related to Extraversion, Openness, Agreeableness, and Conscientiousness and negatively related to Neuroticism. CONCLUSIONS: Previous studies have shown that both reduced P3 amplitude and a high Neuroticism/low Extraversion-Openness-Agreeableness-Conscientiousness trait pattern are associated with the presence of, and risk for, substantial psychiatric morbidity. Our results suggest that processes indexed by auditory P3 amplitude are related to these broad personality dimensions in healthy individuals.

Randomized double-blind study of cyclosporin in chronic 'idiopathic' urticaria.

BACKGROUND: Histamine-releasing activity (HRA) is detectable in up to 50% of patients with chronic ordinary urticaria. OBJECTIVES: To determine the effect of cyclosporin on clinical features and HRA in patients with chronic urticaria. METHODS: Thirty patients with severe unremitting disease, responding poorly to antihistamines and showing a positive autologous serum skin test (ASST) as a marker of HRA, were randomized to 4 mg kg-1 daily of cyclosporin (Sandimmun, n = 20) or placebo (n = 10) for 4 weeks. Non-responders were offered open-label cyclosporin for 4 weeks. All were followed for up to 20 weeks or until clinical relapse; all took cetirizine 20 mg daily throughout the study. The primary measure of efficacy was a daily urticaria activity score (UAS) of weal numbers and itch (maximum score 42 per week). A positive response was defined as a reduction to < 25% of baseline weekly UAS and relapse as a return to > 75%. The effect of cyclosporin on serum HRA was assessed by in vitro basophil histamine release assays and ASSTs before and after treatment. RESULTS: Twenty-nine patients (19 active, 10 controls) completed the randomized trial medication. Eight of 19 on active treatment but none on placebo had responded at 4 weeks (P < 0.05). Three others on active drug met the criterion for response at 2 weeks but not at 4 weeks. Mean reduction in UAS between weeks 0 and 4 was 12.7 (95% confidence interval, CI 6.6-18.8) for active and 2.3 (95% CI - 3.3-7.9) for placebo (P = 0.005). Seventeen non-responders (seven randomized to active and 10 to placebo) chose open-label cyclosporin and 11 responded after 4 weeks. Six of the eight randomized active drug responders relapsed within 6 weeks. Of the 19 responders to randomized and open-label cyclosporin, five (26%) had not relapsed by the study end-point. Mean in vitro serum HRA fell from 36% (95% CI 22-49%) to 5% (95% CI 1-8%) after cyclosporin treatment (n = 11, P < 0.0001). The ASST response to post-treatment serum was also reduced (P < 0.05). CONCLUSIONS: This study shows that cyclosporin is effective for chronic urticaria and provides further evidence for a role of histamine-releasing autoantibodies in the pathogenesis of this chronic 'idiopathic' disease.

Event-related potentials elicited during a context-free homograph task in normal versus schizophrenic subjects.

Thought disorder in schizophrenia may involve abnormal semantic activation or faulty working memory maintenance. Event-related potentials (ERPs) were recorded while sentences reading "THE NOUN WAS ADJECTIVE/VERB" were presented to 34 schizophrenic and 34 control subjects. Some nouns were homographs with dominant and subordinate meanings. Their sentence ending presented information crucial for interpretation (e.g., The bank was [closed, steep]). Greatest N400 activity to subordinate homograph-meaning sentence endings in schizophrenia would reflect a semantic bias to strong associates. N400 to all endings would reflect faulty verbal working memory maintenance. Schizophrenic subjects showed N400 activity to all endings, suggesting problems in contextual maintenance independent of content, but slightly greater N400 activity to subordinate endings that correlated with the severity of psychosis. Future research should help determine whether a semantic activation bias in schizophrenia toward strong associates is reflected in ERP activity or whether this effect is overshadowed by faulty verbal working memory maintenance of context.

Visual perception and working memory in schizotypal personality disorder.

OBJECTIVE: Patients affected by schizophrenia show deficits in both visual perception and working memory. The authors tested early-stage vision and working memory in subjects with schizotypal personality disorder, which has been biologically associated with schizophrenia. METHOD: Eleven subjects who met DSM-III-R criteria for schizotypal personality disorder and 12 normal comparison subjects were evaluated. Performance thresholds were obtained for tests of visual discrimination and working memory. Both form and trajectory processing were evaluated for each task. RESULTS: Subjects with schizotypal personality disorder showed intact discrimination of form and trajectory but were impaired on working memory tasks. CONCLUSIONS: These data suggest that subjects with schizotypal personality disorder, unlike patients affected by schizophrenia, have relatively intact visual perception. Subjects with schizotypal personality disorder do show specific deficits on tasks of comparable difficulty when working memory demands are imposed. Schizotypal personality disorder may be associated with a more specific visual processing deficit than schizophrenia, possibly reflecting disruption of frontal lobe systems subserving visual working memory operations.

Personality traits in schizophrenia: comparison with a community sample.

The objective of this study was to compare personality trait profiles in patients with schizophrenia and healthy controls. Male outpatients with schizophrenia (N = 24) and a male nonpsychiatric community sample (N = 46) completed the NEO-FFI personality questionnaire. Multivariate analyses were used to compare mean scale scores and scale profiles for each group. The overall personality profile of clinically stable patients with schizophrenia differed significantly from that of a community sample. On individual scales, patients scored significantly higher on neuroticism and significantly lower on conscientiousness. These results confirm and extend those of previous studies that used normative data for comparison and a much longer version of the same personality questionnaire. Prospective studies of populations at risk are needed to determine whether group differences reflect a premorbid diathesis for schizophrenia or a secondary effect of serious mental illness.

Gamma frequency-range abnormalities to auditory stimulation in schizophrenia.

BACKGROUND: Basic science studies at the neuronal systems level have indicated that gamma-range (30-50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing gamma-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization. METHODS: Synchronization of the electroencephalogram (EEG) to different rates (20-40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation. RESULTS: Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train. CONCLUSIONS: These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks.

Identification of neural circuits underlying P300 abnormalities in schizophrenia.

Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.