Acta Neuropsychiatrica最新文献

Background: Peripheral gene expression of several molecular pathways has been studied in major depressive disorder (MDD) with promising results. We sought to investigate some of these genes in a treatment-free Latino sample of Mexican descent.

Material and methods: The sample consisted of 50 MDD treatment-free cases and 50 sex and age-matched controls. Gene expression of candidate genes of neuroplasticity (BDNF, p11, and VGF), inflammation (IL1A, IL1B, IL4, IL6, IL7, IL8, IL10, MIF, and TNFA), the canonical Wnt signaling pathway (TCF7L2, APC, and GSK3B), and mTOR, was compared in cases and controls. RNA was obtained from blood samples. We used bivariate analyses to compare subjects versus control mean mRNA quantification of target genes and lineal regression modelling to test for effects of age and body mass index on gene expression.

Results: Most subjects were female (66%) with a mean age of 26.7 (SD 7.9) years. Only GSK3B was differentially expressed between cases and controls at a statistically significant level (p = 0.048). TCF7L-2 showed the highest number of correlations with MDD-related traits, yet these were modest in size.

Discussion: GSK3B encodes a moderator of the canonical Wnt signaling pathway. It has a role in neuroplasticity, neuroprotection, depression, and other psychiatric phenotypes. We found that adding population diversity has the potential to elicit distinct peripheral gene expression markers in MDD and MDD-related traits. However, our results should only be considered as hypothesis-generating research that merits further replication in larger cohorts of similar ancestry.

Objective: Accumulating evidence from preclinical and clinical studies indicates that prenatal exposure to stress impairs the development of the offspring brain and facilitates the emergence of mental illness. This study aims to describe the impact of prenatal restraint stress on cognition and exploration to an unfamiliar environment at adulthood in an outbred strain of mice.

Methods: Late pregnant mice were exposed to restraint stress and adult offspring (60 days of age) behaviours were assessed in the object recognition task and open field test.

Findings: Prenatal stress (PNS) impaired new object recognition in male and female mice. Importantly, the learning deficits in female PNS mice were linked to their estrous cycle. Actually, PNS females in metestrus/diestrus but not in proestrus/estrus phases displayed recognition deficits compared to controls. Concerning locomotion in an unfamiliar environment, male but not female PNS mice displayed significant increase, but showed no differences in the distance travelled within the centre zone of the arena.

Conclusion: Present findings support the view that maternal restraint-stress during late pregnancy impairs recognition memory in both male and female offspring, and in females, this cognitive deficit is dependent on the estrous cycle phase. Ultimately, these data reinforce that PNS is an aetiological component of psychiatric disorders associated with memory deficits.

Objective: Abnormalities in neurotransmission via N-methyl-D-aspartic acid receptor (NMDAR) play a role in the pathophysiology of neuropsychiatric disorders. The impact of repetitive transcranial magnetic stimulation (rTMS) on NMDAR-related amino acids remains unknown. We aim to investigate the effects of rTMS on NMDAR-related amino acids in serum of post-stroke patients.

Methods: Ninety-five consecutive post-stroke patients with upper limb hemiparesis were recruited. In 27 patients, the Beck Depression Inventory (BDI) score was 10 or higher. Twelve depressed patients underwent rehabilitation in combination with rTMS and 15 non-depressed patients underwent rehabilitation only without rTMS for 14 days. 1 Hz rTMS was applied to the primary motor area in the non-lesional hemisphere. BDI was conducted before and after treatment. Serum glutamine, glutamate, glycine, L-serine, and D-serine levels were measured before and after treatment.

Results: There were no differences between depressed patients and non-depressed patients in clinical characteristics, levels of the five amino acids in serum, and the ratio of amino acids. However, in 27 depressed patients there was a significant correlation between levels of glutamate in serum and BDI (ρ=0.428、p=0.026). BDI decreased significantly in depressed patients after treatment with or without rTMS. D-serine decreased in the rehabilitation with rTMS group, but increased in the rehabilitation without rTMS group. L-serine increased in the rehabilitation with rTMS group, but decreased in the rehabilitation without rTMS group.

Conclusions: The results suggest that rTMS can modulate NMDAR-related amino acids in blood, producing beneficial effects.

Objective: Gene-environment (GxE) interactions may comprise an important part of the aetiology of depression, and childhood maltreatment (CM), a significant stressor, has consistently been linked to depression. Hence, in this systematic review, we aimed to investigate the interaction between hypothalamus-pituitary-adrenal axis (HPA-axis) genes and CM in depression.

Methods: We conducted a literature search using the Pubmed, Embase, and PsychINFO databases in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We included studies investigating GxE interactions between HPA-axis genes [Angiotensin Converting Enzyme (ACE), Arginine Vasopressin (AVP), Corticotrophin Releasing Hormone (CRH), Corticotrophin Releasing Hormone Receptor 1 (CRHR1), Corticotrophin Releasing Hormone Receptor 2 (CRHR2), FK506 binding protein (FKBP5), Nuclear Receptor subfamily 3 group C member 1 (NR3C1), Nuclear Receptor subfamily 3 group C member 2 (NR3C2)] and CM in depression.

Results: The literature search identified 159 potentially relevant studies. Following screening, 138 of these were excluded. Thus, 21 studies, investigating a total of 51 single nucleotide polymorphisms, were included in the final study. The most prevalent genes in the current study were CRHR1 and FKBP5. Significant GxE interactions were reported in seven of eight studies for CRHR1:rs110402 and CM, and in five of eight studies for FKBP5:rs1360780 and CM. In summary, our results suggest possible GxE interactions between CRHR1, FKBP5, NR3C1, and NR3C2 and CM, respectively. For the remaining genes, no relevant literature emerged.

Conclusions: We find that genetic variation in four HPA-axis genes may influence the effects of CM in depression.

Objective: To investigate the association of prenatal alcohol exposure (PAE) and early neurodevelopment in the first 2 years of life, adjusting for maternal socio-demographic and psychosocial factors, in the Drakenstein Child Health Study (DCHS), a South African birth cohort study.

Methods: The DCHS comprises a population-based birth cohort of 1143 children, of which a subsample completed the Bayley Scales of Infant Development-III (BSID-III) at 6 (n = 260) and 24 months of age (n = 734). A subset of alcohol-exposed and -unexposed children was included in this analysis at age 6 (n = 52 exposed; n = 104 unexposed) and 24 months (n = 92 exposed; n = 184 unexposed). Multiple hierarchical regression was used to explore the associations of PAE with motor and language development.

Results: PAE was significantly associated with decreased gross motor [odds ratio (OR) = 0.16, 95% confidence interval (CI) = 0.06-0.44, p = 0.001] or fine motor (OR = 0.16, 95% CI = 0.06-0.46, p = 0.001) functioning after adjusting for maternal socio-demographic and psychosocial factors at 6 months of age only. No significant effects were found in either receptive or expressive communication and cognitive outcomes at either time points.

Conclusion: PAE has potentially important consequences for motor development in the first 2 years of life, a period during which the most rapid growth and maturation occur. These findings highlight the importance of identifying high-risk families in order to provide preventive interventions, particularly in antenatal clinics and early intervention services.

Cannabinoid signalling modulates several aspects of brain function, including the generation and survival of neurons during embryonic and adult periods. The present review intended to summarise evidence supporting a role for the endocannabinoid system on the control of neurogenesis and neurogenesis-dependent functions. Studies reporting participation of cannabinoids on the regulation of any step of neurogenesis and the effects of cannabinoid compounds on animal models possessing neurogenesis-dependent features were selected from Medline. Qualitative evaluation of the selected studies indicated that activation of cannabinoid receptors may change neurogenesis in embryonic or adult nervous systems alongside rescue of phenotypes in animal models of different psychiatric and neurological disorders. The text offers an overview on the effects of cannabinoids on central nervous system development and the possible links with psychiatric and neurological disorders such as anxiety, depression, schizophrenia, brain ischaemia/stroke and Alzheimer's disease. An understanding of the mechanisms by which cannabinoid signalling influences developmental and adult neurogenesis will help foster the development of new therapeutic strategies for neurodevelopmental, psychiatric and neurological disorders.

Objective: To evaluate brexpiprazole adjunctive to antidepressant therapies (ADTs) as maintenance treatment in patients with major depressive disorder with inadequate response to ADT, utilising a novel study design.

Methods: The study comprised an 8-week prospective treatment period with open-label ADT with double-blind placebo treatment and a 24-week randomised treatment period. Investigators and patients were blinded to treatment periods, randomisation criteria, and timing of randomisation. Patients with early response to open-label ADT were withdrawn at Week 6. Patients fulfilling criteria for inadequate response were randomised to ADT+brexpiprazole 1-3 mg/day, or ADT+placebo. The primary endpoint was full remission: Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤10 and ≥50% decrease from randomisation (i.e. baseline) in MADRS total score for at least 8 consecutive weeks.

Results: The primary efficacy analysis failed to show a statistically significant difference between the proportions of patients on ADT+brexpiprazole (21.4%) and ADT+placebo (24.9%) achieving full remission; odds ratio: 0.83; p=0.2641. The secondary endpoint of change from baseline to Week 6 in MADRS total score showed no difference between ADT+brexpiprazole and ADT+placebo (-0.4; p=0.3259). The most frequent treatment-emergent adverse event (TEAE) in patients receiving ADT+brexpiprazole was weight increased (9.5% vs. 5.0% in ADT+placebo). The incidence of TEAEs leading to withdrawal in the randomised treatment period was 6.3% in the ADT+brexpiprazole group and 3.4% in the ADT+placebo group.

Conclusion: Adjunctive brexpiprazole did not differentiate from ADT+placebo on the primary endpoint of full remission. A number of design elements in this previously untried study design may have contributed to the study result. Brexpiprazole was well tolerated.

Objective: Prior studies suggest that a dysregulation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is involved in the pathophysiology of major depression. We aimed to elucidate changes in cortical GABA content in relation to depression and electroconvulsive therapy (ECT) using magnetic resonance spectroscopy (MRS).

Methods: In total, 11 patients with major depression or depressive episode of bipolar disorder (mean pre-ECT Ham-17 of 26) and 11 healthy subjects were recruited. GABA was quantified using short-TE MRS in prefrontal and occipital cortex. Other neurometabolites such as glutathione (GSH), N-acetylaspartate (NAA) and glutamate (Glu) were secondary outcome measures.

Results: No significant differences in GABA/Cr levels were observed between patients at baseline and healthy subjects in prefrontal cortex, t(20)=0.089, p=0.93 or occipital cortex t(21)=0.37, p=0.72. All patients improved on Ham-17 (mean post-ECT Ham-17 of 9). No significant difference was found in GABA, Glu, glutamine, choline or GSH between pre- and post-ECT values. However, we observed a significant decrease in NAA levels following ECT t(22)=3.89, p=0.0038, and a significant correlation between the NAA decline and the number of ECT sessions p=0.035.

Conclusions: Our study does not support prior studies arguing for GABA as a key factor in the treatment effect of ECT on major depression. The reduction in NAA levels following ECT could be due to neuronal loss or a transient dysfunction in prefrontal cortex. As no long-term follow-up scan was performed, it is unknown whether NAA levels will normalise over time.

Objective: To explore the correlations between observer ratings and instrumental parameters across domains of psychomotor functioning in depression.

Method: In total, 73 patients with major depressive disorder underwent extensive psychomotor and clinical testing. Psychomotor functioning was assessed with (i) an observer-rated scale (the CORE measure) and also objectively with (ii) 24-h actigraphy, and (iii) a fine motor drawing task.

Results: Observer ratings of retardation correlated with instrumental assessments of fine and gross motor functioning. In contrast, observer ratings of agitation did not correlate with observer ratings of retardation or with the instrumental measures. These associations were partly influenced by age and, to a lesser extent, by depression severity.

Conclusion: Psychomotor disturbance is a complex concept with different manifestations in depressed patients. Although observer ratings of retardation correspond well with instrumental measures of the motor domains, objective measurement of agitation and other aspects of psychomotor disturbance require further research.