LSD-induced changes in the functional connectivity of distinct thalamic nuclei.

The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging studies. However, a detailed analysis of LSD effects on nuclei-resolved thalamocortical connectivity is still missing. Here, in a group of healthy volunteers, we evaluated whether LSD intake alters the thalamocortical coupling in a nucleus-specific manner. Structural and resting-state functional Magnetic Resonance Imaging (MRI) data were acquired in a placebo-controlled study on subjects exposed to acute LSD administration. Structural MRI was used to parcel the thalamus into its constituent nuclei based on individual anatomy. Nucleus-specific changes of resting-state functional MRI (rs-fMRI) connectivity were mapped using a seed-based approach. LSD intake selectively increased the thalamocortical functional connectivity (FC) of the ventral complex, pulvinar, and non-specific nuclei. Functional coupling was increased between these nuclei and sensory cortices that include the somatosensory and auditory networks. The ventral and pulvinar nuclei also exhibited increased FC with parts of the associative cortex that are dense in serotonin type 2A receptors. These areas are hyperactive and hyper-connected upon LSD intake. At subcortical levels, LSD increased the functional coupling among the thalamus's ventral, pulvinar, and non-specific nuclei, but decreased the striatal-thalamic connectivity. These findings unravel some LSD effects on the modulation of subcortical-cortical circuits and associated behavioral outputs.

Lurasidone use in Cannabis-Induced Psychosis: A Novel Therapeutic Strategy and Clinical Considerations in Four Cases Report.

BACKGROUND: Lurasidone is an atypical antipsychotic approved for the acute and maintenance treatment of schizophrenia. Recently, lurasidone was also extended FDA approval for adults with major depressive episodes associated with bipolar I disorder (bipolar depression), as either a monotherapy or as adjunctive therapy with lithium or valproate. The use of low doses of atypical antipsychotics is an essential component of early intervention in psychosis, but little has yet been studied on first episode cannabis-induced psychosis. For its particular performance and tolerability, lurasidone is becoming an important option for the treatment of first-episode psychosis in youth. Case presentation four patients experiencing first cannabis-induced psychotic episode were treated with lurasidone. In all patients, there was an improvement in the clinical picture of psychosis. The recovery was positive, not only with the remission of positive and negative symptoms, but also regarding disruptive behaviour, with the return of functioning. All the patients were treated with lurasidone, with a target dose of 74-128 mg/day. No significant side effects were reported. CONCLUSION: There are non-controlled studies for the use of lurasidone in first episode psychosis cannabis induced. These findings suggest that lurasidone is an atypical antipsychotic beneficial in this clinical picture. Treatment with medium-high doses of lurasidone could be effective and tolerable in this phase of the disorder. Randomized control trials with longer follow-up are recommended to confirm these positive results.

Body-environment integration: Temporal processing of tactile and auditory inputs along the schizophrenia continuum.

According to the dimensional approach to psychosis, there is a continuum from low schizotypy to schizophrenia patients. The temporal aspect of sensory processing seems to be compromised across such continuum, as suggested by different studies separately investigating unisensory or multisensory domains. Most of these studies have so far focused primarily on the temporal processing of visual and auditory stimuli, either in schizotypy or schizophrenia, while leaving the tactile domain and the integration of touch with other senses mostly unexplored. Given the relevance of body-related perceptual abnormalities for psychosis proneness, we aimed at filling this gap in the literature across two studies. We asked participants with increasing levels of schizotypy (study 1) and schizophrenia patients (study 2) to perform three simultaneity judgement tasks: a unimodal tactile task, a unimodal auditory task and a bimodal audio-tactile task. Each task allowed estimating a simultaneity range (SR), as a proxy of the individual tolerance to asynchronies in the tactile, auditory and audio-tactile domains, respectively. Results showed larger SRs as the level of schizotypy increases. Specifically, the linear effect of schizotypy levels on the audio-tactile task was stronger than on the auditory task, which in turn was greater than the effect on the tactile task (study 1). Differently, schizophrenia patients showed larger SRs than controls in all the three tasks (study 2). The current study is the first empirical investigation across the continuum from low schizotypy to schizophrenia of the tolerance to asynchronies in the processing of external (auditory) and body-related (tactile) inputs.

The use of supplements and performance and image enhancing drugs in fitness settings: A exploratory cross-sectional investigation in the United Kingdom.

OBJECTIVE: The strive for perfection is prevalent in the fitness industry. This study aimed to explore the use of products to enhance performance alongside exposure to exercise addiction, appearance anxiety and self-esteem in fitness settings. METHODS: An online survey was prepared and piloted before wider dissemination in fitness clubs via snowballing and selected mailing lists. A list of commonly used products, including Performance and Image Enhancing Drugs (PIEDs) was provided. Exercise addiction (Exercise Addiction Inventory; EAI), anxiety levels (Appearance Anxiety Inventory; AAI) and their self-esteem (Rosenberg's Self-Esteem Scale; RSE) were also measured. RESULTS: 377 questionnaires were completed. A significant number of participants declared the use products either to lose weight (16%) or to reach their fitness goals (41%). The Internet played a major role in both the supply of information and the provision of the enhancement products (33.7%) and side effects were reported (10.5%). Only a limited number of participants sought a medical opinion about taking products (5.1%). EAI scores were high (m=20.02 ± 4.1), AAI (m=15.98 ± 4.8) showed an intermediate level of anxiety, while self-esteem was low (RSE m=12.59 ± 2.2). CONCLUSION: This pilot study identified the emergence of a new drug trend in fitness settings and showed a potential relationship to exercise addiction, anxiety disorders and low self-esteem. The Internet played a crucial role in disseminating often untested products, including PIEDs without medical supervision and unwanted side-effects were reported. More studies in the field are required in order to safeguard public health and inform policy making.

Following "the Roots" of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries.

The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of Mitragyna speciosa Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.

Novel psychoactive substances in young adults with and without psychiatric comorbidities.

OBJECTIVE: Comorbidities between psychiatric diseases and consumption of traditional substances of abuse (alcohol, cannabis, opioids, and cocaine) are common. Nevertheless, there is no data regarding the use of novel psychoactive substances (NPS) in the psychiatric population. The purpose of this multicentre survey is to investigate the consumption of a wide variety of psychoactive substances in a young psychiatric sample and in a paired sample of healthy subjects. METHODS: A questionnaire has been administered, in different Italian cities, to 206 psychiatric patients aged 18 to 26 years and to a sample of 2615 healthy subjects matched for sex, gender, and living status. RESULTS: Alcohol consumption was more frequent in the healthy young population compared to age-matched subjects suffering from mental illness (79.5% versus 70.7%; P < 0.003). Conversely, cocaine and NPS use was significantly more common in the psychiatric population (cocaine 8.7% versus 4.6%; P = 0.002) (NPS 9.8% versus 3%; P < 0.001). CONCLUSIONS: The use of novel psychoactive substances in a young psychiatric population appears to be a frequent phenomenon, probably still underestimated. Therefore, careful and constant monitoring and accurate evaluations of possible clinical effects related to their use are necessary.

Plasma levels of n-3 fatty acids in bipolar patients: deficit restricted to DHA.

Epidemiological studies suggest that n-3 polyunsaturated fatty acid (n-3 FA) deficiency is a risk factor for bipolar disorders (BDs). The aim of this study was to determine whether such a deficit does exist in patients with BD and to characterize the overall plasma fatty acid (FA) profile in these patients. Using gas chromatography/mass spectrometry, we measured fasting plasma levels of 15 FAs in 42 patients diagnosed with BD according to DSM-IV criteria and in 57 age- and gender-matched healthy controls. Plasma docosahexaenoic acid (DHA) levels were significantly decreased in bipolar patients (p < 0.001 versus healthy controls). Compared with controls, patients had higher plasma levels of all other FAs, including arachidonic acid (AA, p < 0.001), alpha-linolenic acid (ALA, p < 0.001), and eicosapentaenoic acid (EPA) (p < 0.001). Although in the present study we observed significant DHA deficits in the plasma of bipolar patients our findings do not support the therapeutic use of ALA and/or EPA supplementation. DHA may provide a basis for possible pharmacological intervention in psychiatric disorders at the level of second messengers linked to the phosphatidylinositol cycle. Finally, measurement of FA levels in plasma seems to be more reliable and reproducible than assays of erythrocyte FA content.

Impact of an 18-month, NHS-based, treatment exposure for heroin dependence: results from the London Area Treat 2000 Study.

We set out to examine the impact of treatment for heroin dependence on drug use, injecting behavior, health problems, criminality, and physical and mental health over 18 months among heroin-dependent Londoners. A total of 100 heroin users were recruited for this longitudinal prospective cohort study with repeated measures (T0 as baseline, T1 after 9 months, and T2 after 18 months). The psychiatric evaluation and assessment of drug abuse levels were determined by the CIDI and the EuropASI. Additional evaluations included the WHO-DAS II for disability assessment and the UCLA-SSI for social support. The number of days of heroin use in the 30 days previous to each single assessment significantly reduced over time (p < .001). Similar reduction levels were observed for cocaine (p < .05), benzodiazepines (p < .001), and polydrug abuse (p < .001), but not for cannabis and alcohol. The number of injecting occasions reduced in parallel, with increase in days in work and reduction of money spent for drug acquisition activities and money obtained from criminal/illegal activities. The number of subjects experiencing suicidal ideation reduced over time (p < .05). In line with previous suggestions, significant reductions in drug use, criminality, psychopathology, and injecting behavior following treatment exposure for heroin dependence were observed. It is, however, of concern that alcohol and cannabis misuse levels remained unchanged.

Anhedonia and substance dependence: clinical correlates and treatment options.

Anhedonia is a condition in which the capacity of experiencing pleasure is totally or partially lost, and it refers to both a state symptom in various psychiatric disorders and a personality trait. It has a putative neural substrate, originating in the dopaminergic mesolimbic and mesocortical reward circuit. Anhedonia frequently occurs in mood disorders, as a negative symptom in schizophrenia, and in substance use disorders. In particular, we focus our attention on the relationships occurring between anhedonia and substance use disorders, as highlighted by many studies. Several authors suggested that anhedonia is an important factor involved in relapse as well as in the transition from recreational use to excessive drug intake. In particular, anhedonia has been found to be a frequent feature in alcoholics and addicted patients during acute and chronic withdrawal as well as in cocaine, stimulant, and cannabis abusers. Furthermore, in subjects with a substance dependence disorder, there is a significant correlation between anhedonia, craving, intensity of withdrawal symptoms, and psychosocial and personality characteristics. Therefore treating anhedonia in detoxified alcohol-dependent subjects could be critical in terms of relapse prevention strategies, given its strong relationship with craving.

Prefrontal-thalamic-cerebellar gray matter networks and executive functioning in schizophrenia.

OBJECTIVE: Poor executive functioning is a core deficit in schizophrenia and has been linked to frontal lobe alterations. We aimed to identify (1) prefrontal cerebral areas in which decreased volume is linked to executive dysfunction in schizophrenia; and (2) areas throughout the brain that are volumetrically related to the prefrontal area identified in the first analysis, thus detecting more extended volumetric networks associated with executive functioning. METHOD: Fifty-three outpatients with schizophrenia and 62 healthy controls, matched for age, gender and handedness, were recruited. High-resolution images were acquired on a 1.5 tesla scanner and regional gray and white matter volumes were analyzed by voxel-based morphometry within SPM5 (statistical parametric mapping, University College London, UK). Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST). RESULTS: Twenty-one patients with poor executive functioning showed reduced dorsolateral prefrontal and anterior cingulate gray matter volume as compared to 30 patients with high WCST performance, with a maximum effect in the left dorsolateral prefrontal cortex. Left dorsolateral prefrontal gray matter volume predicted WCST performance after controlling for possible confounding effects of global cognitive functioning, verbal attention span, negative symptoms, illness duration and education. In this area, both patient groups had less gray matter than healthy controls. Left dorsolateral prefrontal gray matter volume was positively related to dorsal prefrontal, anterior cingulate and parietal gray matter volume; and negatively related to thalamic, cerebellar, pontine and right parahippocampal gray matter volume. CONCLUSIONS: Volumetric alterations in prefrontal-thalamic-cerebellar gray matter networks may lead to executive dysfunction in schizophrenia.