Journal of molecular psychiatry最新文献

Background: Traumatic stress does not only increase the risk for posttraumatic stress disorder (PTSD), but is also associated with adverse secondary physical health outcomes. Despite increasing efforts, we only begin to understand the underlying biomolecular processes. The hypothesis-free assessment of a wide range of metabolites (termed metabolite profiling) might contribute to the discovery of biological pathways underlying PTSD.

Methods: Here, we present the results of the first metabolite profiling study in PTSD, which investigated peripheral blood serum samples of 20 PTSD patients and 18 controls. We performed liquid chromatography (LC) coupled to Quadrupole/Time-Of-Flight (QTOF) mass spectrometry. Two complementary statistical approaches were used to identify metabolites associated with PTSD status including univariate analyses and Partial Least Squares Discriminant Analysis (PLS-DA).

Results: Thirteen metabolites displayed significant changes in PTSD, including four glycerophospholipids, and one metabolite involved in endocannabinoid signaling. A biomarker panel of 19 metabolites classifies PTSD with 85% accuracy, while classification accuracy from the glycerophospholipid with the highest differentiating ability already reached 82%.

Conclusions: This study illustrates the feasibility and utility of metabolite profiling for PTSD and suggests lipid-derived and endocannabinoid signaling as potential biological pathways involved in trauma-associated pathophysiology.

Background: Sleep hygiene is a core component for psychological treatments of insomnia and essential for maintaining a satisfactory sleep. Our study aimed to measure the sleep hygiene awareness and the self-reported quality of sleep among three age groups (young adults, adults and middle-aged adults) and to determine their relation. We also measured their relation with diurnal preference.

Methods: Using an online questionnaire, we surveyed six hundred fifty two participants, recruited nationwide from the community and from the students in three main cities in Romania.

Results: Sleep hygiene awareness was moderate on the whole and significantly worse in young adults (compared to the other age groups) and in those complaining of poor sleep (compared to those with good sleep). Sleep quality was average and linked positively with diurnal preference (the more evening oriented, the poorer the sleep). Diurnal preference was not found to play a role regarding sleep hygiene awareness.

Conclusions: Our results suggest that better sleep hygiene awareness does not necessarily guarantee better sleep quality and that it may actually be an indicator of dissatisfaction with the obtained sleep.

Background: The etiology of schizophrenia is not precisely known; however, mitochondrial function and cerebral energy metabolism abnormalities were determined to be possible factors associated with the etiology of schizophrenia. Impaired mitochondrial function negatively affects neuronal plasticity, and can cause cognitive deficits and behavioral abnormalities observed during the clinical course of schizophrenia. The present study aimed to investigate the relationship between the clinical features of schizophrenia, and mitochondrial complex activation, based on measurement of mRNA levels in the NDUFV1, NDUFV2, NDUFS1, and UQCR10 genes involved in the peripheral mitochondrial complex.

Methods: The study included 138 schizophrenia patients and 42 healthy controls. The schizophrenia group was divided into a chronic schizophrenia subgroup (n = 84) and a first-episode schizophrenia subgroup (n = 54). The symptoms profile and severity of disorder were evaluated using the Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), and Brief Psychiatric Rating Scale (BPRS).

Results: The level of mRNA expression of NDUFV1, NDUFV2, and NDUFS1 was significantly higher in the schizophrenia group than in the control group. The mRNA level of NDUFV2 was positively correlated with BPRS and SAPS scores in the first-episode schizophrenia subgroup.

Conclusion: The findings showed that there was a positive correlation between gene mRNA levels and psychotic symptomatology, especially positive symptoms. Our results suggest that mRNA levels of the NDUFV1, NUDFV2, and NDUFS1 genes of complex I of the mitochondrial electron transport chain might become a possible peripheral marker for the diagnosis of schizophrenia.

Objectives: Since the elimination of items associated with Sluggish Cognitive Tempo (SCT) during the transition from DSM-III to DSM-IV from the diagnostic criteria of Attention-deficit Hyperactivity Disorder (ADHD), interest in SCT and its associated cognitive as well as emotional and social consequences is on the increase. The current review discusses recent findings on SCT in clinical as well as community based ADHD populations. The focus is further on clinical correlates of SCT in populations different from ADHD, SCT's genetic background, SCT's association with internalizing and other behavioral comorbidities, as well as SCT's association with social functioning and its treatment efficacy.

Method: A systematic review of empirical studies on SCT in ADHD and other pathologies in PsycInfo, SocIndex, Web of Science and PubMed using the key terms "Sluggish Cognitive Tempo", "Cognitive Tempo", "Sluggish Tempo" was performed. Thirty-two out of 63 studies met inclusion criteria and are discussed in the current review.

Results/conclusion: From the current literature, it can be concluded that SCT is a psychometrically valid construct with additive value in the clinical field of ADHD, oppositional defiant disorder (ODD), internalizing disorders and neuro-rehabilitation. The taxonomy of SCT has been shown to be far from consistent across studies; however, the impact of SCT on individuals' functioning (e.g., academic achievement, social interactions) seems remarkable. SCT has been shown to share some of the genes with ADHD, however, related most strongly to non-shared environmental factors. Future research should focus on the identification of adequate SCT measurement to promote symptom tailored treatment and increase studies on SCT in populations different from ADHD.

Irritable bowel syndrome (IBS) is a functional syndrome characterized by chronic abdominal pain accompanied by altered bowel habits. Although generally considered a functional disorder, there is now substantial evidence that IBS is associated with a poor quality of life and significant negative impact on work and social domains. Neuroimaging studies documented changes in the prefrontal cortex, ventro-lateral and posterior parietal cortex and thalami, and implicate alteration of brain circuits involved in attention, emotion and pain modulation. Emerging data reveals the interaction between psychiatric disorders including generalized anxiety disorder, panic disorder, major depressive disorder, bipolar disorder, and schizophrenia and IBS, which suggests that this association should not be ignored when developing strategies for screening and treatment. Psychological, social and genetic factors appear to be important in the development of IBS symptomatology through several mechanisms: alteration of HPA axis modulation, enhanced perception of visceral stimuli or psychological vulnerability. Elucidating the molecular mechanisms of IBS with or without psychiatric comorbidities is crucial for elucidating the pathophysiology and for the identification of new therapeutical targets in IBS.

Modern molecular psychiatry benefits immensely from the scientific and technological advances of general neuroscience (including genetics, epigenetics, and proteomics). This "progress" of molecular psychiatry, however, will be to a degree "unbalanced" and "epiphytic" should the development of the corresponding theoretical frameworks and conceptualization tools that allow contextualization of the individual neuroscientific findings within the specific perspective of mental health care issues be neglected. The General Psychopathology, published by Karl Jaspers in 1913, is considered a groundbreaking work in psychiatric literature, having established psychopathology as a space of critical methodological self-reflection, and delineating a scientific methodology specific to psychiatry. With the advance of neurobiology and molecular neuroscience and its adoption in psychiatric research, however, a growing alienation between current research-oriented neuropsychiatry and the classical psychopathological literature is evident. Further, consensus-based international classification criteria, although useful for providing an internationally accepted system of reliable psychiatric diagnostic categories, further contribute to a neglect of genuinely autonomous thought on psychopathology. Nevertheless, many of the unsolved theoretical problems of psychiatry, including those in the areas of nosology, anthropology, ethics, epistemology and methodology, might be fruitfully addressed by a re-examination of classic texts, such as Jaspers's General Psychopathology, and their further development and adaptation for 21st century psychiatry.

Currently, neuropsychological impairment among HIV+ patients on antiretroviral therapy leads to a reduction in the quality of life and it is an important challenge due to the high prevalence of HIV-associated neurocognitive disorders and its concomitant consequences in relation to morbidity and mortality- including those HIV+ patients with adequate immunological and virological status. The fact that the virus is established in CNS in the early stages and its persistence within the CNS can help us to understand HIV-related brain injury even when highly active antiretroviral therapy is effective. The rising interest in HIV associated neurocognitive disorders has let to development new diagnostic tools, improvement of the neuropsychological tests, and the use of new biomarkers and new neuroimaging techniques that can help the diagnosis. Standardization and homogenization of neurocognitive tests as well as normalizing and simplification of easily accessible tools that can identify patients with increased risk of cognitive impairment represent an urgent requirement. Future efforts should also focus on diagnostic keys and searching for useful strategies in order to decrease HIV neurotoxicity within the CNS.

Background: Autism spectrum disorder (ASD) is heritable and neurodevelopmental with unknown causes. The serotonergic and oxytocinergic systems are of interest in autism for several reasons: (i) Both systems are implicated in social behavior, and abnormal levels of serotonin and oxytocin have been found in people with ASD; (ii) treatment with selective serotonin reuptake inhibitors and oxytocin can yield improvements; and (iii) previous association studies have linked the serotonin transporter (SERT; SLC6A4), serotonin receptor 2A (HTR2A), and oxytocin receptor (OXTR) genes with ASD. We examined their association with high functioning autism (HFA) including siblings and their interaction.

Methods: In this association study with HFA children (IQ > 80), siblings, and controls, participants were genotyped for four single nucleotide polymorphisms (SNPs) in OXTR (rs2301261, rs53576, rs2254298, rs2268494) and one in HTR2A (rs6311) as well as the triallelic HTTLPR (SERT polymorphism).

Results: We identified a nominal significant association with HFA for the HTTLPR s allele (consisting of S and LG alleles) (p = .040; odds ratio (OR) = 1.697, 95% CI 1.191-2.204)). Four polymorphisms (HTTLPR, HTR2A rs6311, OXTR rs2254298 and rs53576) in combination conferred nominal significant risk for HFA with a genetic score of ≥4 (OR = 2.09, 95% CI 1.05-4.18, p = .037). The resulting area under the receiver operating characteristic curve was 0.595 (p = .033).

Conclusions: Our findings, combined with those of previous reports, indicate that ASD, in particular HFA, is polygenetic rather than monogenetic and involves the serotonergic and oxytocin pathways, probably in combination with other factors.

Background: The neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT3) could play a role in addictive behavior. Interactions between BDNF and dopamine transmission influence the alcohol intake. It has been hypothesized that extensive alcohol consumption leads to diminished circulating BDNF levels and impaired BDNF-mediated protective mechanisms. What is more, alcohol dependency causes changes in lipid metabolism which in turn may influence the neurotrophin system.

Methods: In this study, we tested the hypothesis that alcohol withdrawal increases the serum levels of BDNF in alcoholic patients and investigated correlations between serum BDNF and NT3 and alcohol in breath as well as with the body-mass-index (BMI), lipoprotein profiles and lifestyle factors in 110 male in-patients diagnosed with alcohol addiction on the first day after admission and at discharge.

Results: The intoxication level (alcohol in breath at admission) was significantly correlated with liver enzymes and BDNF concentrations (R = .28; p = .004). Patients with positive breath-alcohol test at admission had about 9 times higher NT3 levels and higher liver enzyme concentration levels than nonintoxicated subjects. Alcohol intoxicated patients with pathological aspartate aminase (ASAT) levels had even higher NT3 level (F = 5.41; p = .022). The concentration of NT3 was positively associated with the (BMI) (admission R = .36; p = .004; discharge R = .33; p = .001), and the obese patients had 3 to 5 times higher NT3 concentration than the others. Low-density lipoprotein (LDL) concentration levels were found to positively correlate with NT3 concentration levels (admission R = .025; p = .015 discharge R = .24; p = .23).

Conclusion: Other than expected, the levels of NT3 and to a lesser extent BDNF levels, were found to be significantly increased in acute alcohol abuse. Alcohol deprivation did not significantly change the serum neurotrophin levels at admission. NT3 levels were positively correlated with the BMI and LDL levels. Because of expected difference between genders, we recommend investigating these correlations further in patients of both genders.

Background: The dopamine (DA) hypothesis of schizophrenia proposes the mental illness is caused by excessive transmission of dopamine in selected brain regions. Multiple lines of evidence, including blockage of dopamine receptors by antipsychotic drugs that are used to treat schizophrenia, support the hypothesis. However, the dopamine D2 receptor (DRD2) blockade cannot explain some important aspects of the therapeutic effect of antipsychotic drugs. In this study, we hypothesized that antipsychotic drugs could affect the transcription of genes in the DA pathway by altering their epigenetic profile.

Methods: To test this hypothesis, we examined the effect of olanzapine, a commonly used atypical antipsychotic drug, on the DNA methylation status of genes from DA neurotransmission in the brain and liver of rats. Genomic DNA isolated from hippocampus, cerebellum, and liver of olanzapine treated (n = 2) and control (n = 2) rats were analyzed using rat specific methylation arrays.

Results: Our results show that olanzapine causes methylation changes in genes encoding for DA receptors (dopamine D1 receptor, dopamine D2 receptor and dopamine D5 receptor), a DA transporter (solute carrier family 18 member 2), a DA synthesis (differential display clone 8), and a DA metabolism (catechol-O-methyltransferase). We assessed a total of 40 genes in the DA pathway and found 19 to be differentially methylated between olanzapine treated and control rats. Most (17/19) genes showed an increase in methylation, in their promoter regions with in silico analysis strongly indicating a functional potential to suppress transcription in the brain.

Conclusion: Our results suggest that chronic olanzapine may reduce DA activity by altering gene methylation. It may also explain the delayed therapeutic effect of antipsychotics, which occurs despite rapid dopamine blockade. Furthermore, given the common nature of epigenetic variation, this lends insight into the differential therapeutic response of psychotic patients who display adequate blockage of dopamine receptors.