Uneven focal shoe deterioration in Tourette syndrome.

A 31-year-old single man (AB) sought neuropsychiatric consultation for treatment-resistant motor and vocal tics. He described himself expressing a total of 24 different tics, mainly facial twitches (eye blinking, raising eyebrows, mouth opening, lips licking, stereotyped grimacing) and inappropriate utterances (grunting, throat clearing, sniffing), since the age of 7. There appeared to be no family history of tic disorder. He reported occasional utterance of swear words in contextually inappropriate situations (coprolalia), and the urge to copy other people’s movements (echopraxia). Other tic-associated symptoms included self-injurious behaviours and forced touching of objects. A.B. met both DSM-IV-tr and ICD-10 criteria for Tourette syndrome, and also DSM-IV-tr criteria for attention deficit hyperactivity disorder (combined type) in childhood

Acute weight gain, gender, and therapeutic response to antipsychotics in the treatment of patients with schizophrenia

BACKGROUND: Previous research indicated that women are more vulnerable than men to adverse psychological consequences of weight gain. Other research has suggested that weight gain experienced during antipsychotic therapy may also psychologically impact women more negatively. This study assessed the impact of acute treatment-emergent weight gain on clinical and functional outcomes of patients with schizophrenia by patient gender and antipsychotic treatment (olanzapine or haloperidol). METHODS: Data were drawn from the acute phase (first 6-weeks) of a double-blind randomized clinical trial of olanzapine versus haloperidol in the treatment of 1296 men and 700 women with schizophrenia-spectrum disorders. The associations between weight change and change in core schizophrenia symptoms, depressive symptoms, and functional status were examined post-hoc for men and women and for each medication group. Core schizophrenia symptoms (positive and negative) were measured with the Brief Psychiatric Rating Scale (BPRS), depressive symptoms with the BPRS Anxiety/Depression Scale and the Montgomery-Asberg Depression Rating Scale, and functional status with the mental and physical component scores on the Medical Outcome Survey-Short Form 36. Statistical analysis included methods that controlled for treatment duration. RESULTS: Weight gain during 6-week treatment with olanzapine and haloperidol was significantly associated with improvements in core schizophrenia symptoms, depressive symptoms, mental functioning, and physical functioning for men and women alike. The conditional probability of clinical response (20% reduction in core schizophrenia symptom), given a clinically significant weight gain (at least 7% of baseline weight), showed that about half of the patients who lost weight responded to treatment, whereas three-quarters of the patients who had a clinically significant weight gain responded to treatment. The positive associations between therapeutic response and weight gain were similar for the olanzapine and haloperidol treatment groups. Improved outcomes were, however, more pronounced for the olanzapine-treated patients, and more olanzapine-treated patients gained weight. CONCLUSIONS: The findings of significant relationships between treatment-emergent weight gain and improvements in clinical and functional status at 6-weeks suggest that patients who have greater treatment-emergent weight gain are more likely to benefit from treatment with olanzapine or haloperidol regardless of gender

Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication

Rationale: Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. Objectives: We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor M3 (CHRM3) receptor genes for an association with body mass index (BMI) and glycated hemoglobin (HbA1c). Methods: We included 430 Caucasian patients with a non-affective psychotic disorder using antipsychotics for at least 3 months. Primary endpoints of the study were cross-sectionally measured BMI and HbA1c; secondary endpoints were obesity and hyperglycaemia. Two single-nucleotide polymorphisms (SNPs) in the HRH1 gene, rs346074 and rs346070, and one SNP in the CHRM3 gene, rs3738435, were genotyped. Our primary hypothesis in this study was an interaction between genotype on BMI and antipsychotic affinity for the H1 and M3 receptor. Results: A significant association of interaction between haplotype rs346074-rs346070 and BMI (p value 0.025) and obesity (p value 0.005) in patients using high-H1 affinity antipsychotics versus patients using low-H1 affinity antipsychotics was found. There was no association of CHRM3 gene variant rs3738435 with BMI, and we observed no association with HbA1c or hyperglycaemia in any of the variants. Conclusions: This study, for the first time, demonstrates a significant association between HRH1 variants and BMI in patients with a psychotic disorder using antipsychotics. In future, genotyping of HRH1 variants may help predicting weight gain in patients using antipsychotics

Reducing weight gain in people with schizophrenia, schizoaffective disorder, and first episode psychosis: describing the process of developing the STructured lifestyle Education for People With SchizophrEnia (STEPWISE) intervention

Background Obesity is twice as common in people with schizophrenia as the general population and associated with significantly worsened psychiatric and physical health. Despite National Institute for Health and Care Excellence guidelines for the management of psychosis recommending that mental health services offer lifestyle programmes to people with schizophrenia to improve physical health, this is not currently occurring. The aim of the STEPWISE research programme was to develop a lifestyle intervention addressing obesity and preventing weight gain in people with schizophrenia, schizoaffective disorder, or first episode psychosis taking antipsychotic medication, through an approach and fundamental principles drawn from existing diabetes and diabetes prevention interventions. This paper describes the often under-reported process of developing such an intervention from first principles. Methods Following an extensive literature review, an iterative cycle of development with input from people with schizophrenia, mental healthcare professionals, facilitators, and other stakeholders, a new weight management intervention for the target group was developed. A set of four core weekly sessions was piloted in Sheffield, followed at 3-monthly intervals by three booster sessions and telephone support contact once every 2 weeks, to form an intervention lasting 12 months. Facilitators were provided with a 4-day training package to support delivery of the intervention. Results This paper reports the process of development, including challenges and how these were addressed. It describes how user input influenced the structure, topics, and approach of the intervention. The outcome of this process was a feasible and acceptable lifestyle intervention to support people with schizophrenia, schizoaffective disorder, or first episode psychosis to manage their weight. This pilot provided opportunities for refinement of the intervention and facilitator training prior to testing in a multi-centre randomised controlled trial. Key findings from the pilot were linked to accessibility, focus, uptake, and retention, which influenced session length, travel arrangements, refreshment, breaks, and supporting tools to incentivise participants. Conclusions The STEPWISE intervention has been evaluated in a randomised controlled trial in 10 mental health trusts in England, and the results will be published in the British Journal of Psychiatry and the NIHR Journals Library

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain