Riccardo A. Paoli

The C9ORF72 hexanucleotide repeat expansion is a rare cause of schizophrenia

A hexanucleotide repeat expansions in the first intron of C9ORF72 has been shown to be responsible for a high number of familial cases of amyotrophic lateral sclerosis and/or frontotemporal lobar degeneration. The same mutation has been described in a patient with bipolar disorder, but up to now, not in patients suffering from schizophrenia. We determined the frequency of the C9ORF72 hexanucleotide repeat expansions in a population of 298 patients with schizophrenia or schizoaffective disorder. The pathogenic repeat expansion was detected in 2 patients (0.67%). Both of them presented with auditory hallucinations and had comorbid alcohol abuse. In addition, a positive family history for psychiatric and/or neurodegenerative diseases was present. The repeat expansion in the C9ORF72 gene is a rare, but possible, cause of schizophrenic spectrum disorders. We cannot rule out however whether the number of repeats influence the phenotype.

Progranulin gene variability influences the risk for bipolar I disorder, but not bipolar II disorder.

OBJECTIVE Recent data have shown that genetic variability in the progranulin (GRN) gene may contribute to the susceptibility to developing bipolar disorder (BD). However, in regard to patients with BD, no information is available on the role of genetic variability and plasma progranulin levels in different types of this disorder. METHODS In this study, we performed an association analysis of GRN in an Italian population consisting of 134 patients with BD and 232 controls to evaluate progranulin plasma levels. RESULTS The presence of the polymorphic variant of the rs5848 single nucleotide polymorphism is protective for the development of bipolar I disorder (BD-I) (odds ratio = 0.55, 95% confidence interval: 0.33-0.93; p = 0.024) but not bipolar II disorder (BD-II) (p > 0.05). In addition, plasma progranulin levels are significantly decreased in BD [mean ± standard deviation (SD) 112 ± 35 versus 183 ± 93 ng/mL in controls; p < 0.001]. CONCLUSIONS Regarding the influence of GRN variability on BD susceptibility, the predisposing genetic background differs between BD-I and BD-II, possibly implying that pathogenic mechanisms differ between the two subtypes of BD.

The impact of psychosis on brain anatomy in bipolar disorder: A structural MRI study

BACKGROUND Bipolar disorder (BD) is a major psychiatric illness characterized by heterogeneous symptoms including psychotic features. Up until now, neuroimaging studies investigating cerebral morphology in patients with BD have underestimated the potential impact of psychosis on brain anatomy in BD patients. In this regard, psychotic and non-psychotic BD may represent biologically different subtypes of the disorder, being possibly associated with specific cerebral features. METHODS In the present study, magnetic resonance imaging (MRI) at 3T was used to identify the neuroanatomical correlates of psychosis in an International sample of BD patients. A large sample of structural MRI data from healthy subjects (HC) and BD patients was collected across two research centers. Voxel based morphometry was used to compare gray matter (GM) volume among psychotic and non-psychotic BD patients and HC. RESULTS We found specific structural alterations in the two patient groups, more extended in the psychotic sample. Psychotic patients showed GM volume deficits in left frontal cortex compared to HC, and in right temporo-parietal cortex compared to both HC and non-psychotic patients (p < 0.001, > 100 voxels). Psychotic patients also exhibited enhanced age-related GM volume deficits in a set of subcortical and cortical regions. LIMITATIONS The integration of multiple datasets may have affected the results. CONCLUSIONS Overall, our results confirm the importance of classifying BD based on psychosis. The knowledge of the neuronal bases of psychotic symptomatology in BD can provide a more comprehensive picture of the determinants of BD, in the light of the continuum characteristic of major psychoses.

The metabolic basis of cognitive insight in psychosis: A positron emission tomography study

The purpose of this study was to investigate the relationship between cognitive insight and cerebral metabolism in patients suffering from psychosis. The Beck Cognitive Insight Scale (BCIS) was administered to 63 patients with psychosis undergoing Positron Emission Tomography investigation. The sample was divided into two groups considering the BCIS score. Data were analyzed using Statistical Parametric Mapping. Results: patients with low insight, compared to those with high insight, showed decreased metabolism in the right fusiform gyrus, left precuneus, superior temporal gyrus and insula bilaterally, as well as increased metabolism in the left orbito-frontal gyrus (all p<0.005). Our results suggest that reduced posterior (occipito-temporo-insulo-parietal) and increased anterior (orbitofrontal) cerebral metabolism may sustain low cognitive insight in psychosis.

The combination of pharmacogenetic and pharmacokinetic analyses to optimize clomipramine dosing in major depression: a case report

Polymorphisms in cytochrome P450 2D6 and 2C19 can lead to interindividual differences in drug plasma concentrations, affecting clomipramine efficacy. Pharmacokinetic and pharmacogenetic analyses may improve drug therapy.

I38 A clinical based synopsis of available psychopharmacological treatment in huntington’s disease

Background The clinical manifestations of Huntington’s disease (HD) also include psychiatric disturbances, as well as motor and cognitive disorders. Estimated rates for lifetime prevalence of psychiatric disorders among HD patients vary between 33% and 76%. Tetrabenazine is considered the first line treatment for motor disturbances in absences of some psychiatric contraindication (suicide risk). The current literature on the psychopharmacological treatment lack of a large randomised controlled trial, however many small case series are available. Aims We present a review of the literature describing treatments of psychiatric manifestation in HD, focusing on specific disturbances and the role of polytherapy. Methods A search in the main database sources (Medline, Isi Web of Knowledge and Medscape) has been performed in order to obtain a comprehensive evaluation of available psychopharmacological treatment in HD. Results Antidepressants like selective serotonin and serotonin norepinephrine reuptake inhibitors improve depression and are also used in obsessive-compulsive symptoms in HD patients. Mood stabiliser (Valproic Acid or Lamotrigine), alone or in combination with other drugs, are used in pathological mood swings and irritability. Atypical antipsychotics (Risperdidone, Olanzapine and Aripiprazole) were used in psychotic symptoms, and for managing agitation also in place of Tetrabenazine, with reduction of pathological movement. Conclusions Psychiatric symptoms in HD seem to respond well to psychopharmacological treatment. It is important to recognise psychiatric aspects and tailoring specific treatment, not only for psychopathology treatment with improvement of mood, ideation and quality of life of patients and prevention of serious complications how suicidality, but even for better managing neurological symptoms in HD.

Reversible Valproate Induced Pisa Syndrome and Parkinsonism in a Neuro-Oncology Patient with Depression and Epilepsy

Neurological and psychiatric conditions frequently overlap in neuro-oncology. This overlapping negatively affects patients’ quality of life and decreases the ability of providers to manage specific symptoms by therapy modulation, especially when psychopharmacotherapy needs to be prescribed. We describe here a patient with recurrent brain tumor, symptomatic epilepsy and depression who developed Pisa syndrome and parkinsonism after several months of valproic acid use. An accurate recognition of symptoms and treatment side effect allowed an appropriate clinical approach so as to rapidly improve both movement disorder and depression without increasing the risk of developing seizure. This has improved the autonomy and quality of life in a patient with poor prognosis.

1103 – Obesity, psychopathology and neuropsychology: clinical and therapeutic considerations

Introduction Experimental evidence indicates that patients with severe mental illness such as schizophrenia or mood disorders have a higher incidence of overweight and obesity (Daumit et al., 2003). Objectives This review describes the neuropsychological functioning and therapeutical approaches (psychotherapeutic, pharmacological, surgical) in obese patients with psychiatric disorders. Aims To provide suggestions for good clinical practice in obese subjects with psychopathology, based on data found in the literature. Methods MEDLINE and PubMed databases (1962-2012) were searched for English-language articles. Results Most of the literature says that the best treatment for these patients should use an integrated approach, starting from an assessment of the psychological and cognitive resources to set up a more effective and personalized therapeutic path. Conclusions Obese patients who have psychiatric disorders represent a population that requires specific treatment measures; in fact, the development, the maintenance and the outcome of the problem of weight are influenced not only by physical and life style factors, but also by specific factors related to psychopathology, neuropsycology, and side effects of certain drugs.