Depression is one of the most frequent psychiatric symptoms observed in people during the development of Alzheimer's disease (AD). We hypothesized that genetic factors conferring risk of depression might affect AD development. In this study, we screened 31 genes, which were located in 19 risk loci for major depressive disorder (MDD) identified by two recent large genome-wide association studies (GWAS), in AD patients at the genomic and transcriptomic levels. Association analysis of common variants was performed by using summary statistics of the International Genomics of Alzheimer's Project (IGAP), and association analysis of rare variants was conducted by sequencing the entire coding region of the 31 MDD risk genes in 107 Han Chinese patients with early-onset and/or familial AD. We also quantified the mRNA expression alterations of these MDD risk genes in brain tissues of AD patients and AD mouse models, followed by protein-protein interaction network prediction to show their potential effects in AD pathways. We found that common and rare variants of L3MBTL2 were significantly associated with AD. mRNA expression levels of 18 MDD risk genes, in particular SORCS3 and OAT, were differentially expressed in AD brain tissues. 13 MDD risk genes were predicted to physically interact with core AD genes. The involvement of HACE1, NEGR1, and SLC6A15 in AD was supported by convergent lines of evidence. Taken together, our results showed that MDD risk genes might play an active role in AD pathology and supported the notion that depression might be the "common cold" of psychiatry.

Anhedonia and amotivation, the hallmarks of negative symptoms in schizophrenia, are believed to be due to “emotion–behavior decoupling,” a failure in translating pleasure experience into appropriate goal‐directed behavior. A number of studies have reported that long‐term institutionalized schizophrenia patients suffer from more severe negative symptoms than community‐dwelling patients, but few studies have investigated pleasure experience and motivational behavior in schizophrenia patients who have experienced long‐term institutionalization. In this study, we recruited 26 long‐term institutionalized schizophrenia patients, 27 community‐dwelling schizophrenia patients, and 27 healthy controls. Participants were administered two specific computer‐based tasks to assess anhedonia and amotivation. The Anticipatory and Consummatory Pleasure (ACP) Task was used to measure emotion–behavior decoupling and the Effort‐Expenditure for Rewards Task (EEfRT) was used to measure amotivation related to rewards. Findings from the ACP Task showed that compared with healthy controls, the coupling between emotion experience and motivated behavior was significantly weaker in both clinical groups, suggesting that emotion–behavior decoupling could be a stable trait in schizophrenia patients. In the EEfRT, compared with both community‐dwelling patients and healthy controls, institutionalized patients with schizophrenia failed to expend more effort to gain potential rewards even when reward probability increased. These findings further reveal the underlying mechanism of anhedonia and amotivation and their potential relationships with long‐term institutionalization in patients with schizophrenia.

Anhedonia is considered as one of the five dimensions of negative symptoms and mainly refers to the reduction of the capacity of feeling pleasure. Increasing evidence suggests that anhedonia in schizophrenia may be partly explained by cognitive impairment. However, the associations between specific cognitive impairment and anhedonia are not fully investigated. The purpose of this study was to examine anticipatory anhedonia, consummatory anhedonia, and their cognitive associations in schizophrenia. A total number of 100 patients with schizophrenia and 67 healthy volunteers were recruited. The clinical symptoms of schizophrenia were assessed. Anticipatory pleasure, consummatory pleasure, and cognitive functions of each participant were measured. Multiple linear regression analysis was performed to investigate the influencing factors of anhedonia in schizophrenia. The results showed no significant differences in sex, age, education year, body mass index (BMI), and marital status between the schizophrenia group and healthy control group (all P > 0.05). Both anticipatory and consummatory pleasure in the schizophrenia group were significantly lower than those in the healthy control group (all P < 0.05). Immediate memory, visual spanning, language, attention, and delayed memory were significantly poorer in the schizophrenia group (all P < 0.05). The results showed that language deficit is an independent risk factor for anticipatory anhedonia (B' = 0.265, P = 0.008, 95% CI: 0.038-0.244), while delayed memory deficit is an independent risk factor for consummatory anhedonia (B' = 0.391, P < 0.001, 95% CI:0.085-0.237). To the best of our knowledge, this is the first study that reported the specific cognitive associations of anhedonia in schizophrenia. The findings have added new evidence on the influencing factors of anhedonia and provided clues for the associations between clinical manifestations of schizophrenia.

BackgroundMotivational deficit is a common feature of negative symptoms in patients with schizophrenia. Patients with schizophrenia are impaired in goal-directed behaviour and effort allocation decision-making to pursue a potential reward. On the other hand, limited work has suggested that schizophrenia patients who experienced long-term social deprivation showed more severe negative symptoms. However, it is not yet fully clear the long-lasting impact of long-term social deprivation on motivation in these patients. The current study aimed to investigate the effect of long-term social deprivation on effort allocation pattern in patients with schizophrenia.MethodsWe recruited 21 patients with schizophrenia institutionalized for more than 15 years and 20 patients with schizophrenia dwelling in the community and 24 healthy controls for this study. We administered the Effort-Expenditure for Rewards Task (EEfRT) to capture reward-based motivational salience, which requires participants make decision to choose a hard or easy task based on reward probability and magnitude. Moreover, a set of self-reported checklists including the Chapman Psychosis Proneness Scales, the Temporal Experience of Pleasure Scale, the Anticipatory and Consummatory Interpersonal Pleasure Scale and the Emotional Expressivity Scale were also administered to all the participants. For patients with schizophrenia, they also received rating score on the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS).ResultsInstitutionalized patients had exhibited significantly more prominent negative symptoms, especially in alogia subscale, attention subscale, and a trend of statistical significance in anhedonia subscale of SANSS. The two clinical groups did not differ in positive symptoms subscale and general psychopathology symptoms subscale of PANSS. Findings from one-way ANOVA analysis showed that both institutionalized patients and community-dwelling patients with schizophrenia did not differ from healthy controls in experiential pleasure and emotion expression. For performance in the EEFRT, amotivation was only observed in institutionalized patients with schizophrenia, they were significantly less likely to expend effort to pursue a potential reward than healthy controls in both medium (50%) probability and high (80%) probability level. Hence, as the reward probability increased, unlike healthy controls, institutionalized patients could not increase their hard task choices.DiscussionInstitutionalized patients with schizophrenia exhibited significantly more motivational deficits than healthy controls, and such impairment was not observed in community-dwelling patients. However, both institutionalized patients and community-dwelling patients with schizophrenia showed no deficits in self-reported scales measuring pleasure experience and expression. These findings further revealed that long-term social deprivation may be a vital contributor to severe motivation deficits of patients with schizophrenia.