Clinical and biological correlates of optical coherence tomography findings in schizophrenia.

There is a growing body of evidence indicating retinal layer thinning in schizophrenia. However, neuropathological processes underlying these retinal structural changes and its clinical correlates are yet to be known. Here, we aim to investigate the clinical and biological correlates of OCT findings in schizophrenia. 50 schizophrenia patients and 40 healthy controls were recruited. Retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and macular and choroidal thicknesses were recorded. A comprehensive battery of neuropsychological tests was applied. Fasting glucose, triglycerides and HDL-cholesterol levels, TNF-α, IL-1ß and IL-6 levels were measured. Right IPL was significantly thinner in patients than the controls after controlling for various confounders (F = 5.42, p = .02). Higher IL-6, IL-1ß, and TNF-α levels were associated with decreased left macular thickness (r = - 0.26, p = .027, r = - 0.30, p = 0.012, and r = - 0.24, p = .046, respectively) and higher IL-6 was associated with thinning of right IPL (r = - 0.27, p = 0.023) and left choroid (r = - 0.23, p = .044) in the overall sample. Thinning of right IPL and left macula were also associated with worse executive functioning (r = 0.37, p = 0.004 and r = 0.33, p = 0.009) and attention (r = 0.31, p = 0.018 and r = 0.30, p = 0.025). In patients with schizophrenia, IPL thinning was associated with increased BMI (r = - 0.44, p = 0.009) and decreased HDL levels (r = 0.43, p = 0.021). Decreased TNF-α level was related to IPL thinning, especially in the left eye (r = 0.40, p = 0.022). These findings support the hypothesis that OCT might provide the opportunity to establish an accessible and non-invasive probe of brain pathology in schizophrenia and related disorders. However, future studies investigating retinal structural changes as a biological marker for schizophrenia should also consider the metabolic state of the subjects.

Evidence for an association of serum melatonin concentrations with recognition and circadian preferences in patients with schizophrenia.

Melatonin, a neuro-differentiation factor, may play a role in the neurodevelopmental origins of schizophrenia. Cognitive impairment and decreased melatonin are reported in schizophrenia; however, the relationship between them remains unclear. We hypothesised that patients with schizophrenia would have lower concentrations of circulating melatonin than healthy controls and that melatonin levels would be associated with cognitive impairment. This study included 47 patients with schizophrenia and 40 healthy controls (HC). Serum melatonin concentrations were measured using the enzyme-linked immunosorbent assay. Positive and Negative Syndrome Scales (PANSS), The Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI), the Stroop and Oktem verbal memory processes (VMPT) tests were applied. Patients with schizophrenia had lower levels of melatonin compared to the HC group (p = 0.016), also after controlling for age, sex, and body mass index (BMI) (p = 0.024). In patients with schizophrenia, melatonin concentrations were associated with higher BMI (rho = 0.34, p = 0.01) and lower MEQ score (rho = -0.29, p = 0.035). The patient sample was split into low and high melatonin categories by using the median melatonin concentration in HC as the cut-off. Patients in the low melatonin group had poorer performance in VMPT-Recognition (p = 0.026) and Stroop-Colour Error (p = 0.032). Notwithstanding its limitations, the findings of this exploratory study suggest that decreased serum melatonin concentrations observed in schizophrenia might also be associated with cognitive impairment and circadian preferences. Future studies are required to investigate the role of melatonergic pathways in patients with schizophrenia.

Clinical evaluation of biological rhythm domains in patients with major depression.

OBJECTIVE: Sleep, physical activity, and social domains of biological rhythm disruptions may have specific effects on the symptom cluster and severity of depression. However, there is a lack of structured clinical evaluation to specify the domains of biological rhythms in patients with depression. METHODS: Ninety drug-naïve subjects with depression and 91 matched healthy controls were recruited for the study. The severity of depression was examined with the Hamilton Rating Scale for Depression (HRSD), while biological rhythm was evaluated using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). RESULTS: Patients with depression showed significantly greater biological rhythm disturbances than healthy controls in all domains of BRIAN (sleep, activity, social, and eating). BRIAN-Total correlated positively with HRSD-Total and HRSD-Total without sleep cluster. The sleep and activity domains correlated significantly with HRSD-Total score. Additionally, the sleep, activity, and social domains correlated significantly with HRSD-Total without the sleep cluster score. Regression analysis revealed the activity (ß = 0.476, t = 5.07, p<0.001) and sleep (ß = 0.209, t = 2.056, p = 0.043) domains may predict HRSD-Total score. CONCLUSION: Consideration of biological rhythm domains in clinical examination and focusing on the sleep and activity domains may hold promise for the management of depression.

Insomnia Might Influence the Thickness of Choroid, Retinal Nerve Fiber and Inner Plexiform Layer.

Sleep may play a fundamental role in retinal regulation and the degree of retinal variables. However, no clinical study has investigated optical coherence tomography (OCT) parameters in patients with primary insomnia. All participants were evaluated with the insomnia severity index (ISI) and the Pittsburgh sleep quality index (PSQI). The retinal nerve fiber layer (RNFL), ganglion cell layer (GC), inner plexiform layer (IPL), macula and choroidal (CH) thickness were compared between 52 drug-naïve patients with primary insomnia and 45 age-gender-BMI-smoke status matched healthy controls (HC). The patients with primary insomnia differed from the HC regarding RNFL-Global (p = 0.024) and RNFL-Nasal inferior (p = 0.010); IPL-Temporal (p < 0.001), IPL-Nasal (p < 0.001); CH-Global (p < 0.001), CH-Temporal (p = 0.004), CH-Nasal (p < 0.001), and CH-Fovea (p = 0.019). ISI correlated with RNFL-Global and RNFL-Nasal inferior. The regression analysis revealed that ISI was the significant predictor for the thickness of RNFL- Nasal inferior (p = 0.020), RNFL-Global (p = 0.031), and CH-Nasal (p = 0.035) in patients with primary insomnia. Sleep disorders are seen commonly in patients with psychiatric, including ocular diseases. Adjusting the effect of insomnia can help to clarify the consistency in findings of OCT.

Reduced regulatory T cells with increased proinflammatory response in patients with schizophrenia.

AIM: To investigate whether circulating T cells including regulatory T cells (Treg) and derived cytokines contribute to the immune imbalance observed in schizophrenia. METHODS: Forty patients with schizophrenia and 40 age, sex, body mass index, education, and smoking status-matched healthy controls (HC) are included in the study. We stained cells with anti-CD14, anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-CD20, and anti-CD16/56. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with the human FoxP3 kit containing anti-CD4/anti-CD25 and intracellular anti-Foxp3. PBMCs were cultured for 72 h and stimulated with anti-CD3/anti-CD28. Cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, and IL-17A) were measured from the culture supernatant and plasma using the Th1/Th2/Th17 cytokine bead array kit. RESULTS: In comparison with HC, Treg percentages in schizophrenia were higher (1.17 ± 0.63 vs 0.81 ± 0.53, P = 0.005) in unstimulated but lower in the stimulated condition (0.73 ± 0.69 vs 0.97 ± 0.55, P = 0.011). Activated T cell percentages were higher in schizophrenia than HC in unstimulated (2.22 ± 0.78 vs 1.64 ± 0.89, P = 0.001) and stimulated (2.25 ± 1.01 vs 1.72 ± 1.00, P = 0.010) conditions. The culture supernatant levels of IL-6 (7505.17 ± 5170.07 vs 1787.81 ± 1363.32, P < 0.001), IL-17A (191.73 ± 212.49 vs 46.43 ± 23.99, P < 0.001), TNF-α (1557 ± 1059.69 vs 426.57 ± 174.62, P = 0.023), and IFN-γ (3204.13 ± 1397.06 vs 447.79 ± 270.13, P < 0.001); and plasma levels of IL-6 (3.83 ± 3.41vs 1.89 ± 1.14, P = 0.003) and IL-17A (1.20 ± 0.84 vs 0.83 ± 0.53, P = 0.033) were higher in patients with schizophrenia than HC. CONCLUSION: Our explorative study shows reduced level of Foxp3 expressing Treg in a stimulated condition with induced levels of proinflammatory cytokines in patients with schizophrenia.

Prenatal ethanol intoxication and maternal intubation stress alter cell survival and apoptosis in the postnatal development of rat hippocampus.

It is well known that the fetal ethanol exposure and prenatal stress may have adverse effects on brain development. Interestingly, some morphological and functional recovery from their teratogenic effects that take place during brain maturation. However, mechanisms that underlie this recovery are not fully elucidated. The aim of this study was to examine whether the postnatal attenuation of fetal alcohol - and maternal stress­induced morphological and functional deficits correlates with compensatory changes in the expression/activation of the brain proteins involved in inflammation, cell survival and apoptosis. In this project, we investigated the hippocampus which belongs to the brain regions most susceptible to the adverse effects of prenatal ethanol exposure. Pregnant rat dams were administered ethanol (A) or isocaloric glucose solution (IC) by a gastric intubation during gestational days 7-20. The pure control group received ad libitum laboratory chow and water with no other treatment. The hippocampi of fetal-ethanol and control pups were examined at the postnatal day (PD)1, PD10, PD30 and PD60. Moderate fetal-ethanol exposure and prenatal intubation stress caused a significant increase in molecular factors relating to inflammation (iNOS) and cell survival/apoptosis pathways (PTEN, GSK-3 and ERK) at birth, with a rapid compensation from these developmental deficits upon removal of alcohol at PD10. Indeed, an increase in ERK1/2 and JNK1/2 activation at PD30 was observed with ethanol consumption. It indicates that the recovery process in A and IC brains started soon after the birth upon the ethanol and stressor withdrawal and continued until the adulthood.

Clinical evaluation of biological rhythm domains in patients with major depression

Objective: Sleep, physical activity, and social domains of biological rhythm disruptions may have specific effects on the symptom cluster and severity of depression. However, there is a lack of structured clinical evaluation to specify the domains of biological rhythms in patients with depression. Methods: Ninety drug-naïve subjects with depression and 91 matched healthy controls were recruited for the study. The severity of depression was examined with the Hamilton Rating Scale for Depression (HRSD), while biological rhythm was evaluated using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). Results: Patients with depression showed significantly greater biological rhythm disturbances than healthy controls in all domains of BRIAN (sleep, activity, social, and eating). BRIAN-Total correlated positively with HRSD-Total and HRSD-Total without sleep cluster. The sleep and activity domains correlated significantly with HRSD-Total score. Additionally, the sleep, activity, and social domains correlated significantly with HRSD-Total without the sleep cluster score. Regression analysis revealed the activity (β = 0.476, t = 5.07, p<0.001) and sleep (β = 0.209, t = 2.056, p = 0.043) domains may predict HRSD-Total score. Conclusion: Consideration of biological rhythm domains in clinical examination and focusing on the sleep and activity domains may hold promise for the management of depression.