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Neuropsychological deficits are present across various cognitive domains in major depressive disorder (MDD). However, a consistent and specific profile of neuropsychological abnormalities has not yet been established.
We assessed cognition in 170 patients with non-psychotic MDD using the Brief Assessment of Cognition in Schizophrenia and the scores were compared with those of 42 patients with schizophrenia as a reference for severity of cognitive impairment. Hierarchical cluster analysis was conducted to determine whether there are discrete neurocognitive subgroups in MDD. We then compared the subgroups in terms of several clinical factors and social functioning.
Three distinct neurocognitive subgroups were found: (1) a mild impairment subgroup with near-normative performance and mild dysfunction in motor speed; (2) a selective impairment subgroup, which exhibited preserved working memory and executive function, but moderate to severe deficits in verbal memory, motor speed, verbal fluency, and attention/information processing speed; and (3) a global impairment subgroup with moderate to severe deficits across all neurocognitive domains, comparable with deficits in schizophrenia. The global impairment subgroup was characterized by lower pre-morbid intelligence quotient (IQ). Moreover, a significant difference between groups was observed in premorbid IQ (p = 0.003), antidepressant dose (p = 0.043), antipsychotic dose (p = 0.013), or anxiolytic dose (p < 0.001).
These results suggest the presence of multiple neurocognitive subgroups in non-psychotic MDD with unique profiles, one of which exhibits deficits comparable to those of schizophrenia. The results of the present study may help guide future efforts to target these disabling symptoms using different treatments.
Obesity is a risk factor for psychiatric diseases. Recently, a number of single nucleotide polymorphisms (SNPs) have been shown to be related to body mass index (BMI). In this study, we investigated the association of BMI-related SNPs with psychiatric diseases and one of their endophenotypes, memory performance, in a Japanese population.
The subjects were 1624 patients with one of three psychiatric diseases (799 patients with major depressive disorder, 594 with schizophrenia, and 231 with bipolar disorder) and 1189 healthy controls. Memory performance was assessed using the Wechsler Memory Scale – Revised (WMS-R). Genomic DNA was prepared from venous blood and used to genotype 23 BMI-related SNPs using the TaqMan 5′-exonuclease allelic discrimination assay. We then analysed the relationships between the SNPs and psychiatric disease and various subscales of the WMS-R.
Three SNPs (rs11142387, rs12597579, and rs6548238) showed significant differences in the genotype or allele frequency between patients with any psychiatric diseases and controls. Furthermore, six SNPs (rs11142387, rs12597579, rs2815752, rs2074356, rs4776970, and rs2287019) showed significant differences in at least one subscale of the WMS-R depending on the genotypes of the healthy controls. Interestingly, rs11142387 near the Kruppel-like factor 9 (KLF9) was significantly associated with psychiatric disease and poor memory function.
We identified three and six BMI-related SNPs associated with psychiatric disease and memory performance, respectively. In particular, carrying the A allele of rs11142387 near KLF9 was found to be associated with psychiatric disease and poor memory performance, which warrants further investigations.
l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial.
Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years). l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS).
HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration.
Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.
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