Orally disintegrating olanzapine induces less weight gain in adolescents than standard oral tablets

We compared the changes in weight (kg) and body mass index (BMI) (kg/m²) in 52 hospitalized adolescents between baseline and after 12 weeks of monotherapy with either (i) olanzapine (OLZ) orally disintegrating tablets (ODT) (N = 16; 16.6 mg/day ± 4.4 [SD]), or (ii) OLZ standard oral tablets (SOT) (N = 10; 18.0 mg/day ± 4.2), or (iii) risperidone (N = 26; 2.8 mg/day ± 1.2). Significantly greater increases in mean weight and BMI were observed in the patients treated with OLZ SOT (8.9 ± 5.1 [SD] kg; 1.9 ± 0.6 kg/m², respectively) than in those with ODT (3.0 ± 2.1 kg; 1.1 ± 0.8 kg/m²). Similarly, OLZ ODT treatment was associated with significantly greater increases in weight and BMI than risperidone (1.0 ± 1.8 kg; 0.4 ± 0.7 kg/m²). These findings suggest that adolescents gain less weight with OLZ ODT than OLZ SOT, possibly because the former formulation shortens the time of interaction with digestive serotonin receptors mediating satiety.     

Multiplexed neurochemical signaling by neurons of the ventral tegmental area

The ventral tegmental area (VTA) is an evolutionarily conserved structure that has roles in reward-seeking, safety-seeking, learning, motivation, and neuropsychiatric disorders such as addiction and depression. The involvement of the VTA in these various behaviors and disorders is paralleled by its diverse signaling mechanisms. Here we review recent advances in our understanding of neuronal diversity in the VTA with a focus on cell phenotypes that participate in ‘multiplexed’ neurotransmission involving distinct signaling mechanisms. First, we describe the cellular diversity within the VTA, including neurons capable of transmitting dopamine, glutamate or GABA as well as neurons capable of multiplexing combinations of these neurotransmitters. Next, we describe the complex synaptic architecture used by VTA neurons in order to accommodate the transmission of multiple transmitters. We specifically cover recent findings showing that VTA multiplexed neurotransmission may be mediated by either the segregation of dopamine and glutamate into distinct microdomains within a single axon or by the integration of glutamate and GABA into a single axon terminal. In addition, we discuss our current understanding of the functional role that these multiplexed signaling pathways have in the lateral habenula and the nucleus accumbens. Finally, we consider the putative roles of VTA multiplexed neurotransmission in synaptic plasticity and discuss how changes in VTA multiplexed neurons may relate to various psychopathologies including drug addiction and depression.     

Comparison of chemokines (CCL-5 and SDF-1), chemokine receptors (CCR-5 and CXCR-4) and IL-6 levels in patients with different severities of depression

BackgroundDepression can be perceived as a psychoneuroimmunological disorder in which cytokines affecting the body's neurochemical and neuroendocrine functions play an important role. Among cytokines, chemokines participating in activation of the inflammatory response are considered to be crucial.Methods160 men and women were enrolled in the study. 120 of them were diagnosed with various types of depression. The mean age was 45.2 ± 4.5 years (range: 19–47 years). The control group consisted of 40 healthy individuals. The average age in this group was 42.4 ± 4.1 years. Plasma levels of chemokines and their receptors (CCL-5 – RANTES and CXCR-5, SDF-1 and CXCR-4), as well as of IL-6, were assessed by ELISA.ResultsThere was an increase in SDF-1 and CCL-5 levels in women and men with different severities of depression, versus the control group. Also, an increase in the IL-6 levels, CXCR4 and CCR-5 receptors was observed in both women and men with all types of depression. Levels of SDF-1 and CCL-5 chemokines, as well as of CCR-5 and CXCR4 chemokine receptors, were higher in women than in men.ConclusionsThe results of this study indicate the need for assessment of CCL-5 and SDF-1 chemokines levels, as they are likely markers of developing depression. Early measurement of these chemokines levels may be helpful in choosing the best pharmacotherapy.     

Altered gut microbiota and mucosal immunity in patients with schizophrenia

Evidence shows that gut microbiota may play important roles in schizophrenia pathogenesis via the “gut-brain” axis, but the mechanisms remain unclear. Here, eighty-four patients with schizophrenia and 84 sex- and age-matched healthy controls were enrolled. Shotgun metagenomic sequencing and 16S rRNA sequencing were performed, and the gut microbiota-associated epitopes (MEs) were predicted, which, together with IgA content, were used to determine the gut microbiota composition associated with gut immune status. Patients with schizophrenia had significantly reduced gut microbiota richnesses compared with those of the healthy controls, and the gut microbiota compositions clearly distinguished the patients with schizophrenia from the healthy controls. Based on two-stage metagenomic-wide association studies, nineteen gut microbiota taxonomies were associated with schizophrenia, and the microbial dysbiosis (MD) index was calculated based on the abundance of differential taxonomies. We found that MD index was positively correlated with MEs diversity and gut IgA levels, and negatively correlated with gut microbiota richness. Glutamate synthase (GOGAT) was more active in the guts of patients with schizophrenia than in those of healthy controls, and high GOGAT activity was associated with altered gut microbiota taxonomies associated with gut IgA levels. Our results may imply a role of the microbiome in the etiology of schizophrenia and contribute to the development of microbiome targeted interventions for schizophrenia.     

Endocannabinoid mechanism in amphetamine-type stimulant use disorders: A short review

Recent evidence shows that the endocannabinoid system is involved in amphetamine-type stimulants (ATS) use disorders. To elucidate the role of the endocannabinoid system in ATS addiction, we reviewed results of studies using cannabinoid receptor agonists, antagonists as well as knockout model. The endocannabinoid system seems to play a role in reinstatement and relapse of ATS addiction and ATS-induced psychiatric symptoms. The molecular mechanisms of this system remains unclear, the association with dopamine system in nucleus accumbens is most likely involved. However, the function of the endocannabinoid system in anxiety and anti-anxiety effects induced by ATS is more complicated. These findings suggest that the endocannabinoid system may play an important role in the mechanism of ATS addiction and provide new idea for treating ATS addiction.     

Test-retest reliability of duration-related and frequency-related mismatch negativity

Objectives–Mismatch negativity (MMN) has been demonstrated as a potential biomarker for pre-attentive processing and prognosis in patients with psychosis. However, previous studies mainly evaluated the reliability of MMN across only two repeated sessions, which is inadequate to draw a convincing conclusion. The current study aimed to assess multi-session test-retest reliability in duration-related MMN (dMMN) and frequency-related MMN (fMMN).Methods–We recorded four repeated sessions of electroencephalography (EEG) from 16 healthy participants in an oddball task. MMNs were extracted and their reliability was evaluated by intra-class coefficient (ICC). We also analyzed the correlation between fMMN and dMMN.Results–Both dMMN and fMMN amplitudes exhibited good test-retest reliability, and fMMN had better reliability (average ICC = 0.7279) than dMMN (average ICC = 0.6974). Moreover, dMMN and fMMN showed more than moderate linear correlation in amplitudes (r = 0.598, CI: [0.100, 0.857]).Conclusion–Both the duration- and frequency-related MMN amplitudes were highly reliable across four-session experiments. These results provide further evidence for the potential utility of MMNs as biomarkers in research into brain function, and prognosis in psychotic illness.     

Prolactin serum levels correlate with inflammatory status in drug-naïve first-episode schizophrenia

Objectives. The present study was to examine the relationship between serum levels of prolactin and the inflammatory status in drug-naïve, first-episode schizophrenia patients with normal weight. Methods. Patients with normal weight, drug-naïve, first-episode schizophrenia and healthy controls were enrolled in the study. Serum levels of prolactin (PRL) were measured using electrical chemiluminescence immunoassay. Serum levels of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Results. Sixty patients with normal weight, drug-naïve, first-episode schizophrenia and 60 healthy controls were enrolled. The schizophrenia group had higher serum levels of PRL, IL-1β, IL-6 and TNF-α compared with the control group. There was a gender difference of hyperprolactinemia in schizophrenia group. There were positive relationships between serum levels of PRL and serum levels of IL-1β, IL-6 and TNF-α within the schizophrenia group. Within the schizophrenia group, TNF-α was the strongest predictor among the three cytokines for serum levels of prolactin after controlling for gender, age, education, smoking status and disease duration. Conclusions. Patients with normal weight, drug-naïve, first-episode schizophrenia present elevated serum levels of PRL, which might be related to the up-regulated inflammatory status in this patient population.     

The association between Parkinson’s disease and Sexual dysfunction: Clinical correlation and therapeutic implications

Sexual function which comprises of desire, arousal, orgasm and satisfaction and pain, involves coordinated physiologic responses from multiple different pathways. Sexual dysfunction (SD) occurs when these domains of the sexual response cycle are affected. SD is a common but under-recognized non-motor feature in Parkinson’s disease (PD), a common age-related neurodegenerative disorder. SD significantly affects the quality of life of PD patients and their partners. Advanced age, gender, hormone deficiency, neuropsychiatric and medical comorbidities contribute to SD in PD. Possible potential pathological mechanisms include vasculogenic, endocrinologic, neurogenic and psychogenic factors. Various therapeutic interventions, both pharmacological and non-pharmacological modalities have been suggested to improve SD in PD. However, erectile dysfunction (ED) is the only SD with evidence-based treatment available. Non-pharmacological therapies are also offering promising evidence in the improvement of SD. A multidisciplinary approach in the assessment, investigation, and treatment is needed to address the real life complex issues (gender and comorbidities, neurobiological, vasoactive, hormonal as well as psychosocial aspects). Future clinical studies with validated and standardized methods in assessing SD as well as experimental models will be necessary for better insight into the pathophysiology. This would facilitate appropriate therapy and improve sexual rehabilitation in PD patients.