mPFC-rTMS for patients with insomnia disorder using resting-state functional magnetic resonance imaging: a protocol for a randomized controlled trial.

BACKGROUND: Insomnia is the most common sleep disorder. Repetitive transcranial magnetic stimulation (rTMS) is safe and effective for insomnia disorder (ID). Convergent evidence show that the medial prefrontal cortex (mPFC) may be involved in the regulation of sleep and awakening at the cortical level and may serve as a potential target of rTMS in the treatment of ID. The purpose of this clinical trial is to study the efficacy of mPFC-rTMS in the treatment ID and explore the neural mechanism using resting-state functional magnetic resonance imaging (fMRI). METHODS AND DESIGN: This will be a parallel-group randomized, patient- and assessor-blinded trial. The study will recruit 60 ID patients assigned to a real mPFC-rTMS group or a sham mPFC-rTMS group. The allocation ratio is 1:1, with 30 subjects in each group. Interventions will be administered five times per week over a 4-week period, with an 8-week follow-up period. All participants will undergo neuropsychological and fMRI evaluations. The primary outcome measure of this study is the change scores of the Pittsburgh Sleep Quality Index (PSQI). The secondary outcome measures include the fMRI measurements, the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), a sleep diary, and a polysomnography. Assessment of all parameters will be performed at baseline, post-treatment, and during follow-up. DISCUSSION: It is expected that the study results will provide strong evidence of the effectiveness and the neural mechanism by which mPFC-rTMS improves sleep quality in ID patients. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR2100054154. Registered on 10 December 2021.

Age at onset of recurrent major depression in Han Chinese women - a replication study.

BACKGROUND: The relationship between age at onset (AAO) and major depression (MD) has been studied in US, European and Chinese populations. However, larger sample studies are needed to replicate and extend earlier findings. METHODS: We re-examined the relationship between AAO and the clinical features of recurrent MD in Han Chinese women by analyzing the phase I (N=1848), phase II (N=4169) and total combined data (N=6017) from the CONVERGE project. Linear, logistic, multiple linear and multinomial logistic regression models were used to determine the association of AAO with continuous, binary and categorical variables. RESULTS: The effect size of the association between AAO and clinical features of MD was quite similar in the phase I and phase II samples. These results confirmed that MD patients with earlier AAO tended to suffer more severe, recurrent and chronic illness and cases of MD with earlier AAO showed increased neuroticism, greater family history and psychiatric comorbidity. In addition, we showed that earlier AAO of MD in Han Chinese women was associated with premenstrual symptoms, postnatal depression, a highly authoritarian or cold childhood parental rearing style and a reduced probability for having melancholia. LIMITATIONS: Data were collected retrospectively through interview and recall bias may have affected the results. CONCLUSIONS: MD with earlier AAO in Han Chinese women shows a distinct set of clinical features which are similar to those reported in Western populations.

The prevalence, clinical correlates and structure of phobic fears in Han Chinese women with recurrent major depression.

BACKGROUND: Phobic fears are common in the general population and among individuals with major depression (MD). We know little about the prevalence, clinical correlates, and structure of phobic fears in Chinese women with MD. METHODS: We assessed 22 phobic fears in 6017 Han Chinese women with MD. We used exploratory factor analysis to examine the structure of these phobic fears. We examined the relationship between individual phobic fears and the severity of MD, neuroticism, comorbid panic disorder, generalized anxiety disorder and dysthymia using logistic regression models. RESULTS: The frequency of phobic fears ranged from 3.0% (eating in public) to 36.0% (snakes). Phobic fears were significantly associated with more severe MD, high neuroticism, and co-morbid panic disorder, generalized anxiety disorder and dysthymia. Our factor analysis suggested four underlying subgroups of phobic fears which differed in their clinical correlates, severity and patterns of comorbidity. LIMITATIONS: Data were collected retrospectively through interview and recall bias may have affected the results. CONCLUSIONS: Phobic fears are correlated with comorbid MD and more severe MD. These phobic fears clearly subdivide into four subgroups that differ meaningfully from each other.

Clinical features of patients with dysthymia in a large cohort of Han Chinese women with recurrent major depression.

BACKGROUND: Dysthymia is a form of chronic mild depression that has a complex relationship with major depressive disorder (MDD). Here we investigate the role of environmental risk factors, including stressful life events and parenting style, in patients with both MDD and dysthymia. We ask whether these risk factors act in the same way in MDD with and without dysthymia. RESULTS: We examined the clinical features in 5,950 Han Chinese women with MDD between 30-60 years of age across China. We confirmed earlier results by replicating prior analyses in 3,950 new MDD cases. There were no significant differences between the two data sets. We identified sixteen stressful life events that significantly increase the risk of dysthymia, given the presence of MDD. Low parental warmth, from either mother or father, increases the risk of dysthymia. Highly threatening but short-lived threats (such as rape) are more specific for MDD than dysthymia. While for MDD more severe life events show the largest odds ratio versus controls, this was not seen for cases of MDD with or without dysthymia. CONCLUSIONS: There are increased rates of stressful life events in MDD with dysthymia, but the impact of life events on susceptibility to dysthymia with MDD differs from that seen for MDD alone. The pattern does not fit a simple dose-response relationship, suggesting that there are moderating factors involved in the relationship between environmental precipitants and the onset of dysthymia. It is possible that severe life events in childhood events index a general susceptibility to chronic depression, rather than acting specifically as risk factors for dysthymia.

Clinical predictors of familial depression in Han Chinese women.

BACKGROUND: A number of clinical features potentially reflect an individual's familial vulnerability to major depression (MD), including early age at onset, recurrence, impairment, episode duration, and the number and pattern of depressive symptoms. However, these results are drawn from studies that have exclusively examined individuals from a European ethnic background. We investigated which clinical features of depressive illness index familial vulnerability in Han Chinese females with MD. METHODS: We used lifetime MD and associated clinical features assessed at personal interview in 1,970 Han Chinese women with DSM-IV MD between 30-60 years of age. Odds Ratios were calculated by logistic regression. RESULTS: Individuals with a high familial risk for MD are characterized by severe episodes of MD without known precipitants (such as stress life events) and are less likely to feel irritable/angry or anxious/nervous. CONCLUSIONS: The association between family history of MD and the lack of a precipitating stressor, traditionally a characteristic of endogenous or biological depression, may reflect the association seen in other samples between recurrent MD and a positive family history. The symptomatic associations we have seen may reflect a familial predisposition to other dimensions of psychopathology, such as externalizing disorders or anxiety states.

Examining the relationship between lifetime stressful life events and the onset of major depression in Chinese women.

BACKGROUND: In European and US studies, patients with major depressive disorder (MDD) report more stressful life events (SLEs) than controls, but this relationship has rarely been studied in Chinese populations. METHODS: Sixteen lifetime SLEs were assessed at interview in two groups of Han Chinese women: 1970 clinically ascertained with recurrent MDD and 2597 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression. RESULTS: 60% of controls and 72% of cases reported at least one lifetime SLE. Fourteen of the sixteen SLEs occurred significantly more frequently in those with MDD (median odds ratio of 1.6). The three SLEs most strongly associated with risk for MDD (OR>3.0) preceded the onset of MDD the majority of the time: rape (82%), physical abuse (100%) and serious neglect (99%). LIMITATIONS: Our results may apply to females only. SLEs were rated retrospectively and are subject to biases in recollection. We did not assess contextual information for each life event. CONCLUSIONS: More severe SLEs are more strongly associated with MDD. These results support the involvement of psychosocial adversity in the etiology of MDD in China.