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• The depressed adolescents with NSSI have executive dysfunction. • The executive dysfunction is associated with the abnormal NAA metabolism in the right thalamus and ACC. • The abnormal NAA/Cr ratio may distinguish between NSSI adolescents and those without NSSI adolescents. H protons magnetic resonance spectroscopy (1H-MRS) has been used to detect the biochemical metabolism changes and the mechanism of executive dysfunction in major depressive disorder (MDD). While, finding information associated with non-suicidal self-injury (NSSI) among adolescents with MDD is challenging. The present study aimed to examine the executive function and biochemical metabolism alterations, as well as to elucidate their associations in depressed adolescents with NSSI. A total of 86 adolescents with MDD (40 with NSSI, and 46 without NSSI) and 28 healthy controls were recruited in the current study. The executive function was assessed by Digital symbol test (DST), Wisconsin Card Sorting Test (WCST), Trail Making Test, part B (TMT-B), and Verbal fluency (VF). Bilateral metabolite levels of the prefrontal cortex (PFC), anterior cingulated cortex (ACC), lenticular nucleus (LN) of basal ganglia and thalamus were obtained by 1H-MRS at 3.0 T, and then the ratios of N-acetyl aspartate (NAA) and choline-containing compounds (Cho) to creatine (Cr) were determined, respectively. Finally, association analysis was conducted to investigate their relationships. The depressed adolescents with NSSI showed significantly lower VF scores than those without NSSI and healthy controls. We also found significantly higher NAA/Cr ratios in the right thalamus, while significantly lower Cho/Cr ratios in the right thalamus of NSSI group than the MDD without NSSI group and healthy controls. And NSSI group also showed lower NAA/Cr ratio in the right LN than the MDD without NSSI group. For MDD with NSSI, the NAA/Cr ratios of the left thalamus were positively correlated with the time of TMTB and the Cho/Cr ratios of the left ACC were positively correlated with the VF scores. Depressed adolescents with NSSI may have executive dysfunction and NAA and Cho metabolism abnormalities in the thalamus. And the NAA/Cr ratios of the right LN could distinguish NSSI from depressed adolescents. Further, the executive dysfunction may be associated with the abnormal NAA metabolism in the left thalamus and ACC. [ABSTRACT FROM AUTHOR]

It is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. In individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N -acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. Our findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC. • Serum levels of Cu and CER decreased in men with MDD, while the Cu/Zn ratio increased in women with MDD. • In males with MDD, a gender-specific decrease in the NAA/PCr + Cr ratio was noted in the left ACC. • The Cu/Zn ratio and Fe levels in male MDD patients are associated with changes in neurometabolism in the ACC. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) and insomnia have been linked to deficiencies in cognitive performance. However, the underlying mechanism of cognitive impairment in MDD patients with insomnia symptoms (IS) remains unclear. This study aimed to explore the effects of IS in patients with MDD by comparing cognitive function indices among those with IS, those without insomnia symptoms (NIS), and healthy controls (HCs). In addition, we assessed whether the dysfunction of central nervous system (CNS) is one of the important pathophysiologic mechanisms of IS in patients with MDD by comparing the biochemical metabolism ratios in the anterior cingulate cortex (ACC). Fifty-five MDD with IS, 39 MDD without IS, and 47 demographically matched HCs underwent the MATRICS Consensus Cognitive Battery (MCCB) assessment and proton magnetic resonance spectroscopy (1H-MRS). MCCB cognitive scores and biochemical metabolism in ACC were assessed and compared between groups. Compared to the HCs group, IS and NIS groups scored significantly lower in seven MCCB cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning problem solving and social cognition). IS group showed a lower speed of processing and lower Cho/Cr ratio in the left ACC vs. NIS group and HCs. Also, in IS group, the Cho/Cr ratio in the left ACC was positively correlated with the composite T -score. Patients with comorbidity of MDD with IS may exhibit more common MCCB cognitive impairments than those without IS, particularly speed of processing. Also, dysfunction of ACC may underlie the neural substrate of cognitive impairment in MDD with IS. • Major depressive disorder with insomnia symptoms suffered more common MCCB cognitive impairments and neuro dysfunction. • Using proton magnetic resonance spectroscopy to assess brain biochemical metabolism. • MDD patients with insomnia symptoms exhibited lower Cho/Cr ratio in left ACC. • Brain biochemical metabolism changes in ACC were correlated with cognitive function impairments in MDD with insomnia symptoms. [ABSTRACT FROM AUTHOR]

Background: Brain biochemical abnormalities have been associated with major depressive disorder (MDD) and cognitive impairments. However, the cognitive performance and neurometabolic alterations of MDD patients accompanied by gastrointestinal (GI) symptoms remain to be elucidated. We aimed to reveal the features and correlation between cognitive impairments and brain biochemical abnormalities of depressed patients with GI symptoms.Methods: Fifty MDD patients with GI symptoms (GI group), 46 patients without GI symptoms (NGI group) and 50 demographically matched healthy controls (HCs) underwent Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) assessments. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to obtain ratios of N-acetyl aspartate to creatine (NAA/Cr) and choline-containing compounds to creatine (Cho/Cr) in the thalamus, putamen and anterior cingulate cortex (ACC). Finally, association analysis was conducted to investigate the relationships of these measurements.Results: Compared to HCs, participants in both the GI and NGI groups had significantly reduced performance in the six MCCB cognitive domains (all p < 0.05), except for reasoning and problem solving. Higher Cho/Cr ratios in the right thalamus (p < 0.05) and lower NAA/Cr ratios in the left putamen (p < 0.05) were found in the NGI group than in the GI group. The severity of GI symptoms was negatively correlated with Cho/Cr ratios in the right ACC (r = -0.288, p = 0.037). In addition, the T-scores of visual learning were negatively correlated with NAA/Cr ratios in the right ACC (r = -0.443, p = 0.001) and right thalamus (r = -0.335, p = 0.015).Conclusion: Our findings suggest that MDD patients with GI symptoms may exhibit greater neurometabolic alternations than those without GI symptoms, while both show similar cognitive dysfunction. In addition, neurometabolic alterations in the ACC and thalamus may underlie the neural basis of GI symptoms and cognitive impairment in MDD. [ABSTRACT FROM AUTHOR]

Background. Middle-aged (45-59 years old) patients with major depressive disorder (MDD) have a predilection for dementia and cognitive disorders (CDs); however, the characteristics and mechanisms of CDs in these patients remain unclear. There are also known connections between thyroid-stimulating hormone (TSH), brain biochemical metabolism, and cognitive function (CF); however, there is scanty of information about these connections in middle-aged MDD patients. Methods. Cognitive assessment was performed on 30 first-episode, untreated middle-aged patients with MDD and 30 well-matched healthy controls (HCs) using the MATRICS Consensus Cognitive Battery (MCCB). N-acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in the prefrontal cortex (PFC) and cerebellum were also obtained via proton magnetic resonance spectroscopy (1H-MRS), and the TSH level was measured by chemiluminescence analysis. Results. MDD patients presented significantly lower processing speed, working memory, verbal learning, reasoning problem-solving, visual learning, and composite cognition scores than controls, with a statistically lower NAA/Cr ratio in the right cerebellum. Age was positively related to reasoning problem-solving in the MDD group (r = 0.6249 , p = 0.0220). Education also showed a positive association with visual learning, social cognition, and composite cognition. The 24-item Hamilton Depression Rating Scale (HDRS-24) score was negatively related to all domains of CF. TSH levels were markedly decreased in the MDD group, and a positive connection was determined between the NAA/Cr ratio in the right PFC and the TSH level. Conclusions. Middle-aged MDD patients have multidimensional CDs. There are changes in PFC and cerebellar biochemical metabolism in middle-aged patients with MDD, which may be related to CDs or altered TSH levels. [ABSTRACT FROM AUTHOR]

Background: Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) both showed cognitive impairment, and the altered neurometabolic may associate with cognitive impairment. However, there are limited comparative working memory (WM) and neuroimaging studies on these two disorders. Therefore, we investigated the characteristics of WM and neurometabolic changes in patients with OCD and MDD.Methods: A total of 64 unmedicated patients (32 OCD and 32 MDD), and 33 healthy controls (HC) were included to conduct WM assessment comprising Digit Span Test (DST), 2-back task and Stroop Color and Word Test (SCWT). Additionally, all subjects underwent protons magnetic resonance spectroscopy (1H-MRS) to collect neurometabolic ratios of N-acetyl aspartate (NAA) and choline-containing compounds (Cho) to creatine (Cr) in the prefrontal cortex (PFC) and lentiform nucleus (LN). Finally, differential and correlation analysis were conducted to investigate their characteristics and relationships.Results: Compared with HC, both OCD and MDD patients exhibited a lower accuracy rate in the 2-back task, and only MDD patients performed worse in DST scores and longer reaction times in SCWT (all p < 0.05). Both OCD and MDD patients had lower NAA/Cr ratios in bilateral PFC (all p < 0.05). And the decreased NAA/Cr ratios in right PFC were positively correlated to DST scores in MDD group (r = 0.518, p = 0.003).Conclusions: Both OCD and MDD showed WM impairment and neurometabolic alterations in PFC. Besides, MDD performed more severe and broader WM impairment compared to OCD. Moreover, the dysfunction of PFC may underlie the neural basis of WM impairment in MDD. [ABSTRACT FROM AUTHOR]

Background: Studies show that disturbances of the fronto-striato-thalamic-cerebellar circuit could be correlated to facial emotion processing (FEP) biases in major depressive disorder (MDD). Nevertheless, the underlying mechanism of natural metabolism-emotion relationships in adolescent MDD remains unclear.Methods: Thirty-seven adolescent patients with MDD and 30 healthy controls completed FEP tasks using the Chinese Facial Affective Picture System (CAFPS). Proton magnetic resonance spectroscopy (1H-MRS) was also used to obtain ratios of N-acetylaspartate (NAA) /creatine (Cr) and choline (Cho) /Cr ratios in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), putamen, thalamus and cerebellum. Correlations between abnormal neurometabolic ratios and FEP were also computed.Results: Compared with the control group, the MDD group had significantly lower accuracy and perception intensity of happiness, and significantly higher accuracy of disgust and perception intensity of sad and fearful faces in FEP tasks. Compared to healthy controls, adolescent patients with MDD showed significantly lower NAA/Cr ratios in the left PFC, higher NAA/Cr ratios in the right thalamus, and higher Cho/Cr ratios in the right putamen, although there were no significant differences in metabolites in the ACC and cerebellum between two groups. In the MDD group, NAA/Cr ratios of the right thalamus were negatively correlated with happy reaction time and positively correlated with sad, anger, and fear intensity; Cho/Cr ratios in the right putamen were positively correlated with fear reaction time.Conclusions: Our findings suggest that FEP bias may exist in adolescents with MDD, while the impairment of FEP may be associated with abnormal metabolites in the fronto-striato-thalamic circuit. [ABSTRACT FROM AUTHOR]

Aimin Luo,3 Shunkai Lai,1 Tingting He,4 Yuchong Luo,2 Ying Wang,5 Yiliang Zhang,1 Shiyi Shen,4 Hui Huang,4 Shenglin Wen,2 Yanbin Jia11Department of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, People's Republic of China; 2Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, People's Republic of China; 3Department of Psychology, Guangdong Sanjiu Brain Hospital, Guangzhou, Guangdong Province, People's Republic of China; 4School of Management, Jinan University, Guangzhou, Guangdong Province, People's Republic of China; 5Medical Imaging Center, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, People's Republic of China*These authors contributed equally to this workCorrespondence: Yanbin JiaDepartment of Psychiatry, First Affiliated Hospital, Jinan University, Guangzhou, People's Republic of ChinaTel +86 13392489168Fax +86 020-38688888Email [email protected] Purpose: This study aimed to investigate the mechanism of working memory (WM) impairment in drug-naive obsessive-compulsive disorder (OCD) by using neuropsychological tests and proton magnetic resonance spectroscopy (1H-MRS). Patients and Methods: A total of 55 patients with drug-naive OCD and 55 healthy controls (HCs) were recruited for this study. The working memory (WM) was evaluated using the digit span test (DST), visual space memory test (VSMT), and the 2-back task and stroop color word test (SCWT). The bilateral metabolite levels of the prefrontal cortex (PFC) were evaluated by 1H-MRS, then determined the ratios of N-acetyl aspartate (NAA), choline-containing compounds (Cho), and myo-inositol (MI) to creatine (Cr). The independent sample t-test was used to analyse the differences in WM performance and neurometabolite ratios. Multivariate linear regression analysis was performed to screen the influential factors of WM, with an introduction level of 0.05 and a rejection level of 0.10. Results: 1) Patients with OCD performed significantly worse on DST (score), VSMT (score), 2-back task (accuracy rate), SCWT (execution time) when compared with HCs. 2) NAA/Cr and Cho/Cr in the left PFC (lPFC) and MI/Cr ratios in the bilateral PFC of OCD patients were significantly lower when compared to HCs. 3) For OCD patients, the NAA/Cr ratio in the lPFC was negatively correlated with the score of DST (forwards), the Cho/Cr ratio in the lPFC was positively correlated with the accuracy rate of 2-back task, and the MI/Cr ratio in the right PFC (rPFC) was positively correlated with the score of DST (forwards) and the accuracy rate of VSMT. We also found that the compulsive symptoms showed a positive correlation with MI/Cr ratio of the rPFC. Conclusion: Drug-naive OCD patients have demonstrated WM impairments, including phonological loop, visual-spatial sketchpad and central executive system, and the WM impairments might be associated with hypometabolism in the PFC, especially the lPFC. [ABSTRACT FROM AUTHOR]

The underlying mechanism of cognitive impairment in bipolar II depression (BD II) remains unclear. Studies show disturbances of the hypothalamus-pituitary-thyroid (HPT) axis are suspected of correlating to brain neurometabolic alterations and cognitive deficits in psychiatric disorders. While, the nature of their inter-relationships in BD II depression remain enigmatic. 106 patients with unmedicated BD II depression and 100 healthy controls underwent cognitive function assessment using Trail Making Test, Part-A (TMT-A), Digit Symbol Substitution Test (DSST), and Semantic Verbal Fluency testing (SVF). Of those, 69 patients and 53 healthy controls had serum thyroid hormone levels measured including free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4) and thyroid-stimulating hormone (TSH). Additionally, 79 of the patients and 76 of the healthy controls underwent proton magnetic resonance spectroscopy (H-MRS) to obtain ratios of N -acetyl aspartate to creatine (NAA/Cr) and choline-containing compounds to creatine (Cho/Cr) in the prefrontal cortex (PFC), anterior cingulate cortex (ACC) and thalamus. Finally, association and multiple regression analysis were conducted to investigate their inter-relationships. Patients with BD II depression showed significantly lower DSST and verbal fluency scores and longer completion time of TMT-A than did healthy controls. The FT3, TT3, and TSH levels of the BD cohort significantly decreased, while their FT4 levels increased. We also found significantly lower NAA/Cr ratios in the PFC and higher NAA/Cr ratios in the left thalamus of patients with BD II depression than in healthy controls. Furthermore, association analysis showed that increased FT4 negatively correlated to DSST and SVF, while increased FT4 correlation significantly with increasing TSH and DSST. Multiple regression analyses revealed relationships between TSH and NAA in the left PFC and the left thalamus, while correlating to SVF testing within the BD II depression cohort. Our results demonstrate coinciding thyroid hormone abnormalities, cognitive dysfunction, and neurometabolic alterations of the PFC-thalamic circuitry occur in an early course of BD II depression. Further understanding of the interaction between thyroid-stimulating hormone and NAA/Cr of PFC-thalamic circuitry may shed light on the etiology of associated cognitive impairment. • A significantly negative correlation of FT4 to DSST and to SVF, along with a significantly positive correlation of TSH to DSST in patients with BD II depression. • The FT4 levels had a significantly inverse association with NAA/Cr ratios in the left PWM and a significantly positive correlation of TSH levels to NAA/Cr ratios in the left PWM and left thalamus of BD II depression. • The interaction of abnormal thyroid hormones levels and NAA/Cr neurometabolic disruption of the PWM and the thalamus may impact cognitive function in patients with BD II depression. [ABSTRACT FROM AUTHOR]

Objectives: Evidence of the relationship between neurometabolic changes in the cortico-striato-cerebellar (CSC) circuit and bipolar disorder (BD) is still limited. To elucidate the pathogenesis of BD, we investigated the underlying neurometabolic changes and their effect on CSC lateralization circuits in unmedicated patients with bipolar II depression.Methods: Forty unmedicated participants with bipolar II depression and forty healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS). We obtained bilateral metabolic ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in the prefrontal white matter (PWM), anterior cingulate cortex (ACC), basal ganglia (BG) and the cerebellum. Metabolic ratios were characterized using a laterality index (LI) for left-right asymmetry.Results: Overall, aberrant lateralization in the CSC circuit was characteristic in patients with bipolar II depression. Patients with bipolar II depression showed significantly lower NAA/Cr ratios in the left PWM, right ACC, left BG and left cerebellum when compared with the healthy controls. For bipolar II depression, we found lower NAA/Cr LI in the PWM, BG, and cerebellum, higher NAA/Cr LI in the ACC, and higher Cho/Cr LI in the BG and cerebellum when compared to the standard value (1.0). For healthy controls, we found lower NAA/Cr LI only in the BG and higher Cho/Cr LI in the cerebellum when compared to 1.0.Limitations: As a cross-sectional study with a small sample size, progressive changes and complex metabolic interactions with treatment were not observed.Conclusions: Our findings suggest that abnormal biochemical metabolism with aberrant lateralization in the CSC circuit may be an underlying pathophysiology of bipolar II depression. [ABSTRACT FROM AUTHOR]