Common neural deficits across reward functions in major depression: a meta-analysis of fMRI studies.

Major depressive disorder (MDD) is characterized by deficient reward functions in the brain. However, existing findings on functional alterations during reward anticipation, reward processing, and learning among MDD patients are inconsistent, and it was unclear whether a common reward system implicated in multiple reward functions is altered in MDD. Here we meta-analyzed 18 past studies that compared brain reward functions between adult MDD patients (N = 477, mean age = 26.50 years, female = 59.40%) and healthy controls (N = 506, mean age = 28.11 years, females = 55.58%), and particularly examined group differences across multiple reward functions. Jack-knife sensitivity and subgroup meta-analyses were conducted to test robustness of findings across patient comorbidity, task paradigm, and reward nature. Meta-regression analyses assessed the moderating effect of patient symptom severity and anhedonia scores. We found during reward anticipation, MDD patients showed lower activities in the lateral prefrontal-thalamus circuitry. During reward processing, patients displayed reduced activities in the right striatum and prefrontal cortex, but increased activities in the left temporal cortex. During reward learning, patients showed reduced activity in the lateral prefrontal-thalamic-striatal circuitry and the right parahippocampal-occipital circuitry but higher activities in bilateral cerebellum and the left visual cortex. MDD patients showed decreased activity in the right thalamus during both reward anticipation and learning, and in the right caudate during both reward processing and learning. Larger functional changes in MDD were observed among patients with more severe symptoms and higher anhedonia levels. The thalamic-striatal circuitry functional alterations could be the key neural mechanism underlying MDD patients overarching reward function deficiencies.

CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor.

BACKGROUND: Genetic risks may predispose individuals to major mood disorders differently. This study investigated the gene polymorphisms of previously reported candidate genes for major depressive disorder (MDD) and bipolar disorder (BPD) in the Han Chinese population. METHODS: Twenty loci of 13 candidate genes were detected by MALDI-TOF mass spectrometry in 439 patients with MDD, 600 patients with BPD, and 464 healthy controls. The distribution of genotypes in alleles, Hardy-Weinberg equilibrium, and genetic association were analyzed using the PLINK software. The linkage of disequilibrium and haplotype analyses were performed using the Haploview software. RESULTS: Out of the 20 loci analyzed, CYP2C19-rs4986893, ABCB1-rs1045642, and SCN2A-rs17183814 passed Bonferroni correction; their statistical powers were > 55%. The minor allele frequencies (MAF) of CYP2C19-rs4986893 in the MDD group (0.0547) and BPD group (0.0533) were higher than that of the control group (0.0259, P < 0.05), leading to the odds ratios (ORs) of MDD (2.178) and BPD (2.122), respectively. In contrast, the lower MAFs of ABCB1-rs1045642 were observed in both MDD (0.3599, OR = 0.726) and BPD (0.3700, OR = 0.758) groups than controls (0.4364, P < 0.05). The MDD group had a higher MAF of SCN2A-rs17183814 than controls (0.1743 vs. 0.1207, OR = 1.538, P < 0.05). Moreover, a G-A haplotype composed by CYP2C19-rs4986893 and -rs4244285 was associated with BPD (OR = 1.361, P < 0.01), and the A-G haplotype increased the risks to both MDD (OR = 2.306, P < 0.01) and BPD (OR = 2.332, P < 0.001). The CYP2C19 intermediate metabolizer and poor metabolizer (IM&PM) status was related to the raised risk of both MDD (OR = 1.547, P < 0.01) and BPD (OR = 1.808, P < 0.001). CONCLUSION: Our data indicate that the impaired CYP2C19 metabolism caused by the haplotypes integrated by CYP2C19 alleles might confer the risk to MDD and BPD, whereas the ABCB1-rs1045642 T allele serves as a protective factor.

A novel technology for in vivo detection of cell type-specific neural connection with AQP1-encoding rAAV2-retro vector and metal-free MRI.

A mammalian brain contains numerous neurons with distinct cell types for complex neural circuits. Virus-based circuit tracing tools are powerful in tracking the interaction among the different brain regions. However, detecting brain-wide neural networks in vivo remains challenging since most viral tracing systems rely on postmortem optical imaging. We developed a novel approach that enables in vivo detection of brain-wide neural connections based on metal-free magnetic resonance imaging (MRI). The recombinant adeno-associated virus (rAAV) with retrograde ability, the rAAV2-retro, encoding the human water channel aquaporin 1 (AQP1) MRI reporter gene was generated to label neural connections. The mouse was micro-injected with the virus at the Caudate Putamen (CPU) region and subjected to detection with Diffusion-weighted MRI (DWI). The prominent structure of the CPU-connected network was clearly defined. In combination with a Cre-loxP system, rAAV2-retro expressing Cre-dependent AQP1 provides a CPU-connected network of specific type neurons. Here, we established a sensitive, metal-free MRI-based strategy for in vivo detection of cell type-specific neural connections in the whole brain, which could visualize the dynamic changes of neural networks in rodents and potentially in non-human primates.

Chronic stress-induced depression requires the recruitment of peripheral Th17 cells into the brain.

BACKGROUND: Depression is a recurrent and devastating mental disease that is highly prevalent worldwide. Prolonged exposure to stressful events or a stressful environment is detrimental to mental health. In recent years, an inflammatory hypothesis has been implicated in the pathogenesis of stress-induced depression. However, less attention has been given to the initial phases, when a series of stress reactions and immune responses are initiated. Peripheral CD4+ T cells have been reported as the major contributors to the occurrence of mental disorders. Chronic stress exposure-evoked release of cytokines can promote the differentiation of peripheral CD4+ cells into various phenotypes. Among them, Th17 cells have attracted much attention due to their high pathogenic potential in central nervous system (CNS) diseases. Thus, we intended to determine the crucial role of CD4+ Th17 cells in the development of specific subtypes of depression and unravel the underpinnings of their pathogenetic effect. METHODS: In the present research, a daily 6-h restraint stress paradigm was employed in rats for 28 successive days to mimic the repeated mild and predictable, but inevitable environmental stress in our daily lives. Then, depressive-like symptoms, brain-blood barrier (BBB) permeability, neuroinflammation, and the differentiation and functional changes of CD4+ cells were investigated. RESULTS: We noticed that restrained rats showed significant depressive-like symptoms, concomitant BBB disruption and neuroinflammation in the dorsal striatum (DS). We further observed a time-dependent increase in thymus- and spleen-derived naïve CD4+ T cells, as well as the aggregation of inflammatory Th17 cells in the DS during the period of chronic restraint stress (CRS) exposure. Moreover, increased Th17-derived cytokines in the brain can further impair the BBB integrity, thus allowing more immune cells and cytokines to gain easy access to the CNS. Our findings suggested that, through a complex cascade of events, peripheral immune responses were propagated to the CNS, and gradually exacerbated depressive-like symptoms. Furthermore, inhibiting the differentiation and function of CD4+ T cells with SR1001 in the early stages of CRS exposure ameliorated CRS-induced depressive-like behaviour and the inflammatory response. CONCLUSIONS: Our data demonstrated that inflammatory Th17 cells were pivotal in accelerating the onset and exacerbation of depressive symptoms in CRS-exposed rats. This subtype of CD4+ T cells may be a promising therapeutic target for the early treatment of stress-induced depression.

Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis.

IMPORTANCE: COVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome. OBJECTIVE: To quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome. DATA SOURCES: Systematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists. STUDY SELECTION: Primary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected. DATA EXTRACTION & SYNTHESIS: Two reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model. MAIN OUTCOMES & MEASURES: The co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome. RESULTS: The literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I2 = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I2 = 98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals. CONCLUSIONS & RELEVANCE: A significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena. STUDY REGISTRATION: PROSPERO (CRD42021256965).

Effectiveness of intravenous ketamine in mood disorder patients with a history of neurostimulation.

BACKGROUND: Patients unsuccessfully treated by neurostimulation may represent a highly intractable subgroup of depression. While the efficacy of intravenous (IV) ketamine has been established in patients with treatment-resistant depression (TRD), there is an interest to evaluate its effectiveness in a subpopulation with a history of neurostimulation. METHODS: This retrospective, posthoc analysis compared the effects of four infusions of IV ketamine in 135 (x̄ = 44 ± 15.4 years of age) neurostimulation-naïve patients to 103 (x̄ = 47 ± 13.9 years of age) patients with a history of neurostimulation. The primary outcome evaluated changes in depression severity, measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16). Secondary outcomes evaluated suicidal ideation (SI), anxiety severity, measured by the Generalized Anxiety Disorder 7-Item (GAD-7), and consummatory anhedonia, measured by the Snaith-Hamilton Pleasure Scale (SHAPS). RESULTS: Following four infusions, both cohorts reported a significant reduction in QIDS-SR16 Total Score (F (4, 648) = 73.4, P < .001), SI (F (4, 642) = 28.6, P < .001), GAD-7 (F (2, 265) = 53.8, P < .001), and SHAPS (F (2, 302) = 45.9, P < .001). No between-group differences emerged. Overall, the neurostimulation-naïve group had a mean reduction in QIDS-SR16 Total Score of 6.4 (standard deviation [SD] = 5.3), whereas the history of neurostimulation patients reported a 4.3 (SD = 5.3) point reduction. CONCLUSION: IV ketamine was effective in reducing symptoms of depression, SI, anxiety, and anhedonia in both cohorts in this large, well-characterized community-based sample of adults with TRD.

Safety, Tolerability, and Real-World Effectiveness of Intravenous Ketamine in Older Adults With Treatment-Resistant Depression: A Case Series.

OBJECTIVE: To evaluate the safety, tolerability, and effectiveness of repeated doses of intravenous (IV) ketamine in older adults (i.e., ≥60 years of age) with treatment-resistant depression. METHOD: In this case series, fifty-three older adults (Mage = 67, SD = 6; 57% female [n = 30]) received 4 IV ketamine infusions, administered over 1-2 weeks. Effectiveness of IV ketamine was measured using the Quick Inventory for Depressive Symptomatology-Self Report 16 (QIDS-SR16) approximately 2 days after infusions 1-3, and 1-2 weeks after infusion 4. Safety was measured as hemodynamic changes before, during, immediately after, and 20 minutes after each infusion. Tolerability was assessed via systematic reporting of treatment-emergent adverse events during and after each infusion, in addition to symptoms of dissociation measured using the Clinician Administered Dissociative States Scale. Partial response (25%-50% symptomatic improvement from baseline), response (≥50% symptomatic improvement from baseline), clinically significant improvements (≥25% symptomatic improvement from baseline), and remission rates (QIDS-SR16 ≤5) were also calculated. RESULTS: Participants reported significant decreases in depressive symptoms (i.e., as measured by the QIDS-SR16) with repeated ketamine infusions (F(4, 92) = 7.412, p <0.001). The mean QIDS-SR16 score was 17.12 (SD = 5.33) at baseline and decreased to 12.52 (SD = 5.79) following 4 infusions. After 4 infusions, 31% (n = 8) of participants partially responded to IV ketamine, 27% (n = 7) responded, 58% (n = 15) experienced clinically significant improvements, and 10% (n = 3) met remission criteria. Thirty-six participants (69%) experienced treatment-emergent hypertension during at least 1 infusion, and 10 (19%) required intervention with an antihypertensive. Drowsiness was the most commonly reported adverse event (50% of infusions; n = 73). CONCLUSION: Ketamine was associated with transient treatment-emergent hypertension. Response and remission rates were comparable to those reported in general adult samples. Findings are limited by the open-label, chart review nature of this study.

AdipoRon Treatment Induces a Dose-Dependent Response in Adult Hippocampal Neurogenesis.

AdipoRon, an adiponectin receptor agonist, elicits similar antidiabetic, anti-atherogenic, and anti-inflammatory effects on mouse models as adiponectin does. Since AdipoRon can cross the blood-brain barrier, its chronic effects on regulating hippocampal function are yet to be examined. This study investigated whether AdipoRon treatment promotes hippocampal neurogenesis and spatial recognition memory in a dose-dependent manner. Adolescent male C57BL/6J mice received continuous treatment of either 20 mg/kg (low dose) or 50 mg/kg (high dose) AdipoRon or vehicle intraperitoneally for 14 days, followed by the open field test to examine anxiety and locomotor activity, and the Y maze test to examine hippocampal-dependent spatial recognition memory. Immunopositive cell markers of neural progenitor cells, immature neurons, and newborn cells in the hippocampal dentate gyrus were quantified. Immunosorbent assays were used to measure the serum levels of factors that can regulate hippocampal neurogenesis, including adiponectin, brain-derived neurotrophic factor (BDNF), and corticosterone. Our results showed that 20 mg/kg AdipoRon treatment significantly promoted hippocampal cell proliferation and increased serum levels of adiponectin and BDNF, though there were no effects on spatial recognition memory and locomotor activity. On the contrary, 50 mg/kg AdipoRon treatment impaired spatial recognition memory, suppressed cell proliferation, neuronal differentiation, and cell survival associated with reduced serum levels of BDNF and adiponectin. The results suggest that a low-dose AdipoRon treatment promotes hippocampal cell proliferation, while a high-dose AdipoRon treatment is detrimental to the hippocampus function.

Inflammation, brain structure and cognition interrelations among individuals with differential risks for bipolar disorder.

Neuro-inflammation might impact on clinical manifestations and cognition function via changing the volumes of key brain structures such as the anterior cingulate cortex (ACC) in bipolar disorder (BD). In this study, we investigated the interrelations among interleukin (IL)-6 cytokine level, grey matter (GM) volume of the anterior cingulated cortex (ACC), and attention function among offspring of parents diagnosed with BD. The offspring were categorized as being either asymptomatic or symptomatic based on whether they manifested pre-defined sub-threshold mood symptoms. We found that the symptomatic offspring showed significantly higher serum levels of IL-6 than the asymptomatic offspring (F(1, 59) = 67.65, p < 0.001). On the brain level, we obtained significant interactive effect of group and IL6 level on the ACC GM (PFWE = 0.017). Specifically, the GM volume of the rostral ACC was negatively associated with the levels of IL-6 in the asymptomatic offspring (PFWE = 0.021), but not the symptomatic offspring (PFWE > 0.05). Mediation analyses revealed that the GM volume of the rostral ACC significantly mediated the negative association between the IL-6 levels and attention performance in the asymptomatic offspring (bootstrapping Confidence Interval (CI) = -6.0432 to -0.0731) but not the symptomatic offspring (bootstrapping CI = -0.3197 to 1.3423). Our data suggest that the asymptomatic and symptomatic bipolar offspring may exhibit different neurocognitive-inflammatory profiles, which could be further validated as viable biosignatures for BD risk and resilience.

The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder.

OBJECTIVE: To determine the effectiveness of intravenous (IV) ketamine on anxiety, irritability, agitation, and suicidality, in adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD). METHOD: Adults (N = 201) with treatment-resistant MDD or BD received repeat-dose IV ketamine treatment at a community-based clinic. Mixed features were measured using symptoms of anxiety, irritability, and agitation (AIA), as measured by the Generalized Anxiety Disorder-7 (GAD-7) scale. The Quick Inventory for Depressive Symptomatology Self-Report-16 (QIDS-SR16 ) was used to measure overall treatment response, and the QIDS-SR16 suicidal ideation (SI) item was used to measure change in SI symptoms with ketamine treatment. The anxiety, irritability, and agitation items on the GAD-7 were used to assess effectiveness of IV ketamine in treating symptoms of mixed features. RESULTS: In this retrospective analysis, 113 participants met AIA criteria. Participants with AIA experienced a significantly greater reduction in overall depressive symptoms (F(1, 558) = 9.49, P = .002), SI (F(1, 558) = 3.103, P = .079), anxiety (F(1, 198) = 5.52, P = .007), irritability (F(1, 198) = 28.35, P < .001), and agitation as measured by "trouble relaxing" (F(1, 198) = 6.70, P = .010) from baseline compared to the non-AIA group, regardless of number of treatments received. CONCLUSIONS: Our preliminary results suggest that IV ketamine is effective in rapidly treating AIA and SI in adults with treatment-resistant mood disorders. This observation suggests that IV ketamine could be considered a treatment alternative for adults with MDD or BD presenting with mixed features.

Aberrant brain structural-functional connectivity coupling in euthymic bipolar disorder.

Aberrant structural (diffusion tensor imaging [DTI]) and resting-state functional magnetic resonance imagining connectivity are core features of bipolar disorder. However, few studies have explored the integrity agreement between structural and functional connectivity (SC-FC) in bipolar disorder. We examine SC connectivity coupling index whether could potentially provide additional clinical predictive value for bipolar disorder spectrum disorders besides the intramodality network measures. By examining the structural (DTI) and resting-state functional network properties, as well as their coupling index, among 57 euthymic bipolar disorder patients (age 13-28 years, 18 females) and 42 age- and gender-matched healthy controls (age 13-28 years, 16 females), we found that compared to controls, bipolar disorder patients showed increased structural rich-club connectivity as well as decreased functional modularity. Importantly, the coupling strength between structural and functional connectome was decreased in patients compared to controls, which emerged as the most powerful feature discriminating the two groups. Our findings suggest that structural-functional coupling strength could serve as a valuable biological trait-like feature for bipolar disorder over and above the intramodality network measures. Such measure can have important clinical implications for early identification of bipolar disorder individuals, and inform strategies for prevention of bipolar disorder onset and relapse.

Association between cognitive function and performance on effort based decision making in patients with major depressive disorder treated with Vortioxetine.

BACKGROUND: It is well established that deficits in motivation, reward, and cognition are common during and in between syndromal episodes of depression as part of Major Depressive Disorder (MDD). Informed by evidence indicating functional and structural interconnectivity between cognitive and reward brain circuits, we preliminarily evaluate the association between measures of cognitive performance and reward/motivation. METHODS: This is a post-hoc analysis of a primary study (i.e. the THINC-it sensitivity to change study). Adults (18-65 years of age) meeting DSM-5 criteria for MDD, single-episode or recurrent confirmed by M.I.N.I. with moderate severity or greater (i.e. Montgomery Asberg Depression Rating Scale ≥20). All eligible subjects received vortioxetine 10-20 mg open-label for 8 weeks. The Effort Expenditure Reward Task (EEfRT) was the principal measure of motivation and reward. We directly compare the effects of cognitive measures and depressive symptoms on effort-based decision-making using the THINC-it composite score and MADRS total score. RESULTS: Twenty-one participants with MDD (Mean age = 38.47, SD = 12.85) and 20 healthy volunteers (Mean age = 41.50, SD = 14.21) completed the optional EEfRT task. Amongst individuals with MDD, performance in processing speed, executive function (i.e. Trails B) and overall composite cognitive score was positively associated with the proportion of hard-task choices in the high reward condition (i.e. greater reward valuation). Across both groups, a greater probability (χ2 = 1.137) and magnitude of reward (χ2 = 0.045) was associated with increased effort (i.e. choosing the hard task more frequently). Using fully factored GEE models, we observed a positive association between performance on the Trails test (ß = 2.223, SE = 0.928, p = 0.017) as well as the composite score (ß = 0.978, SE = 0.0.459, p = 0.033), and greater effort for high rewards. In addition, it was observed that a positive association (i.e. greater effort for reward in higher probability) was observed with depressive symptoms and overall cognitive measures. CONCLUSION: Herein, we observed that an association exists between overall cognitive function, notably processing speed and executive function and reward function. Specifically, a greater effort for hard task rewards (using the EEfRT task) was manifested in individuals exhibiting higher levels of cognitive performance in a well-characterized sample of MDD treated with Vortioxetine.

Obesity and frontal-striatal brain structures in offspring of individuals with bipolar disorder: Results from the global mood and brain science initiative.

OBJECTIVES: To compare frontal-striatal brain volumes between offspring of individuals with bipolar disorder (BD) and healthy controls; to investigate the associations of body mass index (BMI) and age with brain volumes; and to assess the moderating effects of BMI and age on the relationship between risk status and structural brain differences. METHODS: We cross-sectionally assessed structural regional and global brain volumes using magnetic resonance imaging and BMI among 53 BD offspring subjects, stratified by risk status, and 23 non-BD offspring controls (aged 8-28 years). Analyses of variance and covariance and linear regression analyses were conducted to investigate the associations between BMI and measures of brain volume, as well as the interaction effects between age, BMI, and risk status on brain volumes. RESULTS: After adjusting for age, sex, and intracranial volume, higher BD risk status was associated with lower bilateral cerebellar cortical and right pars orbitalis volumes. Higher BMI was significantly associated with greater brain volumes in frontal and subcortical structures. A significant interaction effect between BMI and risk status was observed in right middle frontal volume. The moderating effect of BMI on brain volume was most robustly observed among subjects aged 14-19 years and less robustly observed among those aged 20-28 years; BMI and brain volumes were negatively correlated among subjects aged 8-13 years. CONCLUSIONS: Alterations in brain structures in individuals at risk for BD may be moderated by BMI. Obesity among individuals with a family history of BD may confer additional risk, particularly in mid-adolescence.

Adverse effects of obesity on cognitive functions in individuals at ultra high risk for bipolar disorder: Results from the global mood and brain science initiative.

BACKGROUND: The burden of illness associated with bipolar disorder (BD) warrants early pre-emption/prevention. Prediction models limited to psychiatric phenomenology have insufficient predictive power. Herein, we aimed to evaluate whether the presence of overweight/obesity is associated with greater cognitive decline in individuals at high risk (HR) or ultra high risk (UHR) for BD. METHODS: We conducted a retrospective analysis to investigate the moderational role of body mass index (BMI) on measures of cognitive function. Subjects between the ages of 8 and 28 years with a positive family history of BD were compared to age-matched controls with a negative family history of BD. Subjects with at least one biological parent with bipolar I/II disorder were further stratified into UHR or HR status by the presence or absence, respectively, of subthreshold hypomanic, major depressive, attenuated psychotic, and/or attention-deficit/hyperactivity disorder symptoms. RESULTS: A total of 36 individuals at HR for BD, 33 individuals at UHR for BD, and 48 age-matched controls were included in the analysis. Higher BMI was significantly associated with lower performance on measures of processing speed (i.e. Brief Assessment of Cognition in Schizophrenia-symbol coding: r=-.186, P=.047) and attention/vigilance (i.e. Continuous Performance Test-Identical Pairs: r=-.257, P=.006). There were trends for negative correlations between BMI and measures of working memory (i.e. Wechsler Memory Scale-III Spatial Span: r=-0.177, P=.059) and overall cognitive function (i.e. Measurement and Treatment Research to Improve Cognition in Schizophrenia composite score: r=-.157, P=.097). Negative associations between BMI and cognitive performance were significantly stronger in the UHR group than in the HR group, when compared to controls. CONCLUSIONS: Individuals at varying degrees of risk for BD exhibit greater cognitive impairment as a function of co-existing overweight/obesity. Prediction models for BD may be substantively informed by including information related to overweight/obesity and, perhaps, other general medical conditions that share pathology with BD. Our findings herein, as well as the salutary effects of bariatric surgery on measures of cognitive function in obese populations, provide the rationale for hypothesizing that mitigating excess weight in individuals at elevated risk for BD may forestall or prevent declaration of illness.

Neuropsychological performance of patients with soft bipolar spectrum disorders.

OBJECTIVES: There is much evidence that shows that a substantial number of individuals with DSM-IV-defined unipolar depression (UP) manifest hypomanic sub-syndrome and bipolar diathesis. Other definitions have conceptualized the term soft bipolar spectrum (SBP) for these individuals. Little is known about the cognitive profiles of individuals with SBP. We hypothesized that they are representative of individuals with bipolar II disorder and are different from that of 'strict' UP. METHODS: Consecutive referrals suffering major depressive episodes were categorically assigned to groups of either bipolar I disorder (n = 98), bipolar II disorder (n = 138), or UP (n = 300). Based on the SBP criteria by Akiskal and Pinto (17), patients with UP were subdivided into 81 SBP and 219 strict UP. We administered self- and clinician-administered scales to evaluate affective temperaments, and neuropsychological tests to assess seven cognitive domains. RESULTS: Patients with SBP performed significantly better than strict UP patients in the domains of processing speed (p = 0.002), visual-spatial memory (p = 0.017), and verbal working memory (p = 0.017). Compared to patients with bipolar I disorder, patients with SBP were significantly better in set shifting (p < 0.001) and visual-spatial memory (p = 0.042). Patients with SBP performed similarly to patients with bipolar II disorder in all of the cognitive domains tested (p > 0.05). There was a group × cognitive domain interaction effect between bipolar I disorder, bipolar II disorder, SBP, and strict UP groups [Pillai's F = 2.231, df = (18,1437), p = 0.002]. CONCLUSIONS: Our data suggest that patients with SBP differ from patients with UP not only in external validators (e.g., family history of bipolar disorder) and hypomanic symptoms, but also in neuropsychological performance and that the profiles of cognitive functioning were different across bipolar I disorder and 'bipolar II spectrum' that subsumes bipolar II disorder and SBP.

Effects of frequent assessments on the severity of suicidal thoughts: an ecological momentary assessment study.

Objective: In recent years, there has been a significant increase in research using ecological momentary assessment (EMA) to explore suicidal thoughts and behaviors (STBs). Meanwhile, concerns have been raised regarding the potential impacts of frequent and intense STBs assessments on the study participants. Methods: From November 2021 to June 2023, a total of 83 adolescent and young adult outpatients (Mage = 21.0, SDage = 6.3, 71.1% female), who were diagnosed with mood disorders, were recruited from three psychiatric clinics in China. Smartphone-based EMA was used to measure suicidal thoughts three times per day at randomly selected times. We examined the change of suicidal thoughts in each measurement and within 1 day to evaluate potential adverse effects using Bayesian multilevel models. Results: The 3,105 effective surveys were nested in 83 participants (median follow-up days: 14 days). The results of two-level models indicated that suicidal thoughts decreased during the monitoring period. However, this effect varied among different individuals in the two-level model. Conclusion: Our findings did not support the notion that repeated assessment of suicidal thoughts is iatrogenic, but future research should continue to investigate the impact of frequent assessment on suicidal thoughts, taking into account individual differences and utilizing larger sample sizes.

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression: a randomized controlled study.

JOURNAL/nrgr/04.03/01300535-202409000-00036/figure1/v/2024-01-16T170235Z/r/image-tiff Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses. Moreover, anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms. Lycium barbarum polysaccharide (LBP), derived from Goji berries, exhibits notable antioxidative and anti-inflammatory properties. In our recent double-blinded randomized placebo-controlled trial, we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression. It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines. In the double-blinded randomized controlled trial, we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group. In the LBP group, adolescents were given 300 mg/d LBP. A 6-week follow up was completed by 24 adolescents, comprising 14 adolescents from the LBP group (15.36 ± 2.06 years, 3 men and 11 women) and 10 adolescents from the placebo group (14.9 ± 1.6 years, 2 men and 8 women). Our results showed that after 6 weeks of treatment, the interleukin-17A level in the LBP group was lower than that in the placebo group. Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors, which were associated with the improvement in depressive symptoms. These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level, thereby exerting an antidepressant effect.

A preliminary study on brain developmental features of bipolar disorder familial risk and subthreshold symptoms.

BACKGROUND: Risk for Bipolar disorder (BD) is increased among individuals with family history or subthreshold mood symptoms. However, the brain structural developments associated with these BD risks remained unknown. METHODS: This longitudinal cohort study examined the brain grey matter volume (GMV) developmental features of familial and symptomatic risks for BD, and their associations with participants' global function levels. We recruited unaffected BD offspring with (N=26, age=14.9±2.9 years, 14 females) or without (N=35, age=15.3±2.7 years, 19 females) subthreshold manic or depressive symptoms, and unaffected non-BD offspring with (N=49, age=14.5±2.2 years, 30 females) or without (N=68, age=15.0±2.3 years, 37 females) symptoms. The offspring had no mood disorder diagnosis prior to the study. The average follow-up duration was 2.63±1.63 years. RESULTS: We found at baseline, significant interactive effects of familial risk and subthreshold symptoms indicated the symptomatic offspring exhibited markedly large GMV in the brain affective and cognitive circuitries. During follow-up, the combined group of BD offspring (symptomatic and non-symptomatic) displayed accelerated GMV decrease than BD non-offspring, in the hippocampus and anterior cingulate cortex. In contrast, the combined group of symptomatic participants (offspring and non-offspring) displayed slower GMV decrease than non-symptomatic participants, in the ventromedial prefrontal cortex. Larger GMV at baseline, and accelerated GMV decrease during follow-up, prospectively and longitudinally predicted positive global function changes. All results survived multiple-testing correction. CONCLUSIONS: These findings indicated that familial and symptomatic risks of BD are associated with distinct brain structural developments, and unraveled key brain developmental features of particularly vulnerable high-risk individuals to subsequent functional deterioration.

The validity and reliability of the Chinese version of the biological rhythms interview of assessment in neuropsychiatry in the community: a large Chinese college student population.

Objective: To test the psychometric properties of the Chinese version of the biological rhythms interview of assessment in neuropsychiatry (C-BRIAN) in a group of young adults with and without depressive symptoms. Methods: Three hundred and seventy-eight university students were recruited as participants. Based on the scores from Center for Epidemiological Survey Depression Scale (CES-D), students were divided into the depressed group and healthy group. Explorative factor analysis was applied to assess the construct validity of the C-BRIAN. The Pittsburgh Sleep Quality Index (PSQI) and CES-D were compared with the C-BRIAN to test the convergent validity. The internal consistency of the C-BRIAN was also examined. Results: Three factors were extracted (activities, eating patterns, and sleep factors) explaining 63.9% of the total variance. The internal consistencies were very good with a coefficient of 0.94 (overall) and 0.89-0.91 for three factors. The domains of activities, eating patterns, and sleep were moderately correlated with PSQI (r=0.579) and CES-D (r=0.559) (ps<0.01). Conclusion: Our findings suggest that C-BRIAN has good validity and reliability which can be used to assess the biological rhythm in the young adult population with depressive symptoms. C-BRIAN would be a reliable tool to detect depressive symptoms for timely prevention and intervention in the community.