The effect of five day dosing with THCV on THC-induced cognitive, psychological and physiological effects in healthy male human volunteers: A placebo-controlled, double-blind, crossover pilot trial.

Rationale: Cannabis is mostly grown under illegal and unregulated circumstances, which seems to favour a product increasingly high in its main cannabinoid ∆-9-tetrahydrocannabinol (THC). ∆-9-tetrahydrocannabivarin (THCV) is a relatively untested cannabinoid which is said to be a cannabinoid receptor neutral antagonist, and may inhibit the effects of THC.

Objectives: To explore the safety and tolerability of repeated THCV administration and its effects on symptoms normally induced by THC in a sample of healthy volunteers.

A screen for genes expressed in the olfactory organs of Drosophila melanogaster identifies genes involved in olfactory behaviour.

Background: For insects the sense of smell and associated olfactory-driven behaviours are essential for survival. Insects detect odorants with families of olfactory receptor proteins that are very different to those of mammals, and there are likely to be other unique genes and genetic pathways involved in the function and development of the insect olfactory system.

Methodology/principal Findings: We have performed a genetic screen of a set of 505 Drosophila melanogaster gene trap insertion lines to identify novel genes expressed in the adult olfactory organs.

Chemical communication in insects: the peripheral odour coding system of Drosophila melanogaster.

Animals use their chemosensory systems to detect and discriminate among chemical cues in the environment. Remarkable progress has recently been made in our knowledge of the molecular and cellular basis of chemosensory perception in insects, based largely on studies in the vinegar fly Drosophila melanogaster. This progress has been possible due to the identification of gene families for olfactory receptors, the use of electro-physiological recording techniques on sensory neurons, the manifold of genetic manipulations that are available in this species and insights from several insect model systems.

Disruption of frontal θ coherence by Δ9-tetrahydrocannabinol is associated with positive psychotic symptoms.

The main ingredient in cannabis, Δ(9)-tetrahydrocannabinol (THC), can elicit acute psychotic reactions in healthy individuals and precipitate relapse in schizophrenic patients. However, the neural mechanism of this is unknown. We tested the hypothesis that THC psychopathology is related to changes in electroencephalography (EEG) power or inter-regional coherence.

Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology.

Delta-9-tetrahydrocannabinol (Delta-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Delta-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Delta-9-THC.

Psychosis and autism: magnetic resonance imaging study of brain anatomy.

Background: Autism-spectrum disorder is increasingly recognised, with recent studies estimating that 1% of children in South London are affected. However, the biology of comorbid mental health problems in people with autism-spectrum disorder is poorly understood.

Aims: To investigate the brain anatomy of people with autism-spectrum disorder with and without psychosis.

Event-related potential correlates of paranormal ideation and unusual experiences.

Separate dimensions of schizotypy have been differentially associated with electrophysiological measures of brain function, and further shown to be modified by sex/gender. We investigated event-related potential (ERP) correlates of two subdimensions of positive schizotypy, paranormal ideation (PI) and unusual experiences (UEs). Seventy-two individuals with no psychiatric diagnosis (men=36) completed self-report measures of UE and PI and performed an auditory oddball task.

Selective pressures on Drosophila chemosensory receptor genes.

The evolution and patterns of selection of genes encoding 10 Drosophila odorant receptors (Or) and the sex pheromone receptor Gr68a were investigated by comparing orthologous sequences across five to eight ecologically diverse species of Drosophila. Using maximum likelihood estimates of dN/dS ratios we show that all 11 genes sampled are under purifying selection, indicating functional constraint. Four of these genes (Or33c, Or42a, Or85e, and Gr68a) may be under positive selection, and if so, there is good evidence that 12 specific amino acid sites may be under positive selection.

Modulation of neural response to happy and sad faces by acute tryptophan depletion.

Background: Central serotonin (5HT) plays a major role in emotional processing. We used functional neuroimaging (fMRI) to investigate the effects of experimental manipulation of central 5HT levels on the regional neural response to happy and sad facial expressions.

Methods: Ten healthy participants (eight men and two women) were scanned during an implicit emotional processing task after receiving a tryptophan-free (acute tryptophan depletion, ATD) or a balanced amino acid drink in a double-blind design.

Facial emotion processing in criminal psychopathy. Preliminary functional magnetic resonance imaging study.

Background: It has been suggested that people with psychopathic disorders lack empathy because they have deficits in processing distress cues (e.g. fearful facial expressions).

Effect of acute tryptophan depletion on pre-frontal engagement.

Background: Serotonin is known to modulate cognitive functioning and has been implicated in the cognitive deficits associated with affective disorders. The present study examined regional brain activation during two tasks that are known to engage the pre-frontal cortex and are performed poorly by patients with depression and bipolar disorder. We tested the hypothesis that acute tryptophan depletion (ATD) would attenuate pre-frontal activation during both tasks.

Event-related potential correlates of depression, insight and negative symptoms in males with recent-onset psychosis.

Objective: The neurobiology of clinical characteristics -in particular depression, insight and negative symptoms- in recent-onset psychosis (ROP) was studied using event-related potentials (ERPs).

Methods: Twenty right-handed ROP men and 20 controls completed an auditory-oddball task. ROP men had minimum exposure to antipsychotic medication.

Tryptophan depletion reduces right inferior prefrontal activation during response inhibition in fast, event-related fMRI.

Rationale And Objective: In animal and human studies, the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) has been implicated in mediating impulsiveness and aggression. To test the hypothesis that 5-HT modulates neuro-cognitive brain activation during inhibitory control, we examined the effect of acute tryptophan depletion (ATD), a dietary challenge, which has been shown to decrease 5-HT synthesis in the brain, on functional brain activation during a go/no-go task.

Methods: Nine healthy, right-handed volunteers performed a rapid, event-related go/no-go task in two functional magnetic resonance imaging (fMRI) scanning sessions, 5 h after either a tryptophan-free or a balanced amino acid drink in a double-blind, sham depletion-controlled, counterbalanced, crossover design.

Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer's disease.

We performed an affected sib-pair (ASP) linkage analysis to test for the effects of age at onset (AAO), rate of decline (ROD), and Apolipoprotein E (APOE) genotype on linkage to late-onset Alzheimer's disease (AD) in a sample comprising 428 sib-pairs. We observed linkage of mean AAO to chromosome 21 in the whole sample (max LOD = 2.57).

Variation in the urokinase-plasminogen activator gene does not explain the chromosome 10 linkage signal for late onset AD.

Linkage studies indicate that the same region of chromosome 10 contains a risk locus for late onset Alzheimer disease (LOAD) and a QTL for plasma Abeta42 levels suggesting that a single locus may influence risk for AD by elevating plasma Abeta42 [Ertekin-Taner et al., 2000; Myers et al., 2000].

Full genome screen for Alzheimer disease: stage II analysis.

We performed a two-stage genome screen to search for novel risk factors for late-onset Alzheimer disease (AD). The first stage involved genotyping 292 affected sibling pairs using 237 markers spaced at approximately 20 cM intervals throughout the genome. In the second stage, we genotyped 451 affected sibling pairs (ASPs) with an additional 91 markers, in the 16 regions where the multipoint LOD score was greater than 1 in stage I.

Familial influence on variation in age of onset and behavioural phenotype in Alzheimer's disease.

Background: Alzheimer's disease manifests considerable heterogeneity, the cause of which is unknown.

Aims: To determine the familial (genotypic) influence on phenomenology (phenotype) in Alzheimer's disease.

Method: Affected sibling pairs with Alzheimer's disease were assessed for a range of cognitive and non-cognitive symptoms.

Susceptibility locus for Alzheimer's disease on chromosome 10.

The apolipoprotein E (APOE) gene is the only genetic risk factor that has so far been linked to risk for late-onset Alzheimer's disease (LOAD). However, 50 percent of Alzheimer's disease cases do not carry an APOE4 allele, suggesting that other risk factors must exist. We performed a two-stage genome-wide screen in sibling pairs with LOAD to detect other susceptibility loci.

A pilot study of sibling resemblance in later life.

Objective: Behavioural genetic studies of later life are strictly limited. We carried out a community-based pilot study of sibling resemblance with the primary aims of establishing the feasibility of such work in this population and estimating genetic influence on depression and its risk factors.

Methodology: Data were collected on surviving siblings of individuals interviewed in previous phases of an epidemiological study of the elderly (the Gospel Oak survey); scales relevant to the investigation of late life depression and its risk factors were utilized.

No association between the alpha-2 macroglobulin I1000V polymorphism and Alzheimer's disease.

Recent reports have suggested that variability in the alpha2-macroglobulin gene is a genetic risk factor for Alzheimer's disease. Here we have both tested a common polymorphism in the gene (I1000V) for association with the disease in a four-site case control study design, and tested the locus for linkage in a large series of sibpairs afflicted with late onset disease. Our results fail to show an association between this polymorphism and disease.

An unusual case of pica.

Pica is the persistent, culturally and developmentally inappropriate ingestion of non-nutritive substances (DSM-IV). AB is a 75-year-old lady with a 40-year history of schizophrenia and a 20-year history of pica who, at emergency laparotomy, had 175.32 Pounds of loose change in her stomach.