Treatment resistant depression in elderly.

Treatment refractory depression (TRD) in the elderly is a common psychiatric disorder with high comorbidity and mortality. Older adults with TRD often have complicated comorbidities and several predisposing risk factors, which may lead to neuropsychiatric dysfunction and poor response to treatment. Several hypotheses suggest the underlying mechanisms, including vascular, immunological, senescence, or abnormal protein deposition. Treatment strategies for TRD include optimization of current medication dose, augmentation, switching to an alternative agent or class, and combination of different antidepressant classes, as well as nonpharmacological adjuvant interventions such as biophysical stimulation and psychotherapy. In summary, treatment recommendations for TRD in the elderly favor a multimodal approach, combining pharmacological and nonpharmacological treatments.

Posttraumatic stress disorder and the risk of erectile dysfunction: a nationwide cohort study in Taiwan : PTSD and erectile dysfunction.

BACKGROUND: This study aimed to investigate the association between posttraumatic stress disorder and the risk of developing erectile dysfunction. METHODS: In this population-based retrospective cohort study, we used Taiwan's National Health Insurance Research Database to analyze patients who were newly diagnosed with posttraumatic stress disorder (PTSD) between 2000 and 2013, with a 1:3 ratio by age and index year matched with patients in a non-PTSD comparison group, for the risk of erectile dysfunction. RESULTS: In total, 5 out of 1079 patients in the PTSD group developed erectile dysfunction, and 3 out of 3237 patients in the non-PTSD group (47.58 vs. 9.03 per 100,000 per person-year) developed erectile dysfunction. The Kaplan-Meier analysis showed that the PTSD cohort had a significantly higher risk of erectile dysfunction (log-rank, p < 0.001). The Cox regression analysis revealed that the study subjects were more likely to develop an injury (hazard ratio: 12.898, 95% confidence intervals = 2.453-67.811, p = 0.003) after adjusting for age, monthly income, urbanization level, geographic region, and comorbidities. Psychotropic medications used by the patients with PTSD were not associated with the risk of erectile dysfunction. CONCLUSIONS: Patients who suffered from PTSD had a higher risk of developing erectile dysfunction.

Potential Negative Effects of Dextromethorphan as an Add-On Therapy to Methylphenidate in Children With ADHD.

Objectives: Methylphenidate (MPH) is highly effective in controlling the symptoms of attention-deficit/hyperactivity disorder (ADHD), but some children with ADHD either do not respond to, or do not tolerate, treatment. Dextromethorphan (DM) is a neuroprotective agent which has been used in the treatment of neuropsychiatric disorders. This clinical trial had examined the effect of DM on the use of MPH in the children with ADHD. Methods: This randomized double-blind clinical trial had evaluated 44 male outpatients, aged between 6 and 12 years, with a diagnosis of ADHD. The study subjects were randomly assigned into one of the two groups: receiving MPH alone (15-60 mg per day) or MPH plus DM (30-60 mg per day) for 8 weeks. Assessments, comprising the Chinese version of the Child Behavior Checklist (CBCL-C) scale and the Swanson, Nolan and Pelham Questionnaire (SNAP)-IV rating tests conducted by parents and the serum cytokines measured by microarray and enzyme-linked immunosorband assay (ELISA), were compared between groups at baseline and at 8 weeks after the medication was started. Results: There were a significant decrease at the mean scores of both CBCL-C and SNAP-IV scales after 8 weeks of treatment, but no significant differences between MPH and MPH+DM groups. Compared with the MPH-only group, the mean scores of some psychometric parameters reported on the CBCL-C and SNAP-IV scales regarding time effects as well as the attention problems on the CBCL-C scale regarding group effect were significantly higher in the DM+MPH group. Although there were no significant differences in the levels of various serum cytokines between groups, the subjects in the DM-MPH group had relatively fewer and lower levels of adverse effects. Significant interactions were found between the withdrawn/depression item reported on the CBCL-C scale and tumor necrosis factor α (ခTNF-α) (p = 0.027), as well as between thought problems item on the CBCL-C and TNF-α (p = 0.028) in subjects who had received DM+MPH treatment. Conclusion: Following the trial, DM+MPH was not superior to MPH alone for the treatment of children with ADHD, yet DM may potentially have negative effects on ADHD symptoms when combined with MPH. Clinical Trial Registration: Clinicaltrials.gov, trial number: NCT01787136.

Effects of oxytocin on prosocial behavior and the associated profiles of oxytocinergic and corticotropin-releasing hormone receptors in a rodent model of posttraumatic stress disorder.

BACKGROUND: Traumatic experience may lead to various psychological sequelae including the unforgettable trauma-associated memory as seen in posttraumatic stress disorder (PTSD), with a mechanism of impaired fear extinction due to biological imbalance among hypothalamic-pituitary-adrenal (HPA) axis and fear circuit areas such as medial prefrontal cortex (mPFC), hippocampus, and amygdala. Recently the impaired sociability seen in PTSD patients received great attention and the involvement of oxytocin (OXT) mediation is worth being investigated. This study examined whether the trauma-altered prosocial behavior can be modulated by OXT manipulation and its relationship with corticotropin-releasing hormone (CRH) signaling. METHODS: Male rats previously exposed to a single prolonged stress (SPS) were evaluated for their performance in social choice test (SCT) and novel object recognition test (NORT) following the introduction of intranasal oxytocin (OXT) and OXT receptor antagonist atosiban (ASB). OXT receptors (OXTR) and CRH receptors (CRHR1, CRHR2) were quantified in both protein and mRNA levels in medial prefrontal cortex (mPFC), hippocampus, and amygdala. RESULTS: SPS reduced inclination of rats staying at the sociable place with performing less prosocial contacts. OXT can amend the deficit but this effect was blocked by ASB. Expression of OXTR became reduced following SPS in mPFC and amygdala, the latter exhibited higher therapeutic specificity to OXT. Expression of CRHR1 appeared more sensitive than CRHR2 to SPS, higher CRHR1 protein levels were found in mPFC and amygdala. CONCLUSION: Psychological trauma-impaired sociability is highly associated with OXT signaling pathway. Intranasal OXT restored both the SPS-impaired prosocial contacts and the SPS-reduced OXTR expressions in mPFC and amygdala. OXT may have therapeutic potential to treat PTSD patients with impaired social behaviors.

Effects of Oxytocin on Fear Memory and Neuroinflammation in a Rodent Model of Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a trauma-induced mental disorder characterized by fear extinction abnormalities, which involve biological dysfunctions among fear circuit areas in the brain. Oxytocin (OXT) is a neuropeptide that regulates sexual reproduction and social interaction and has recently earned specific attention due to its role in adjusting neurobiological and behavioral correlates of PTSD; however, the mechanism by which this is achieved remains unclear. The present study aimed to examine whether the effects of OXT on traumatic stress-induced abnormalities of fear extinction (specifically induced by single prolonged stress (SPS), an animal model of PTSD) are associated with pro-inflammatory cytokines. Seven days after SPS, rats received intranasal OXT 40 min before a cue-dependent Pavlovian fear conditioning-extinction test in which rats' freezing degree was used to reflect the outcome of fear extinction. We also measured mRNA expression of IL-1ß, IFN-γ, and TNF-α in the medial prefrontal cortex (mPFC), hippocampus, and amygdala at the end of the study, together with plasma oxytocin, corticosterone, IL-1ß, IFN-γ, and TNF-α, to reflect the central and peripheral changes of stress-related hormones and cytokines after SPS. Our results suggested that intranasal OXT effectively amends the SPS-impaired behavior of fear extinction retrieval. Moreover, it neurochemically reverses the SPS increase in pro-inflammatory cytokines; thus, IL-1ß and IFN-γ can be further blocked by the OXT antagonist atosiban (ASB) in the hippocampus. Peripheral profiles revealed a similar response pattern to SPS of OXT and corticosterone (CORT), and the SPS-induced increase in plasma levels of IL-1ß and TNF-α could be reduced by OXT. The present study suggests potential therapeutic effects of OXT in both behavioral and neuroinflammatory profiles of PTSD.

Predictors of Nicotine Dependence in Adolescents: Symptoms of Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) have been associated with the use of cigarettes, but little is known about the impact of the subthreshold symptoms of BD or ADHD on the course of nicotine dependence. Identifying the links is essential for elucidating the pathway and supporting the development of nicotine prevention strategies for adolescents. METHODS: Participants (n = 3322) aged 15-17 years completed the Chinese version of the ADHD Self-Report Scale and the Mood Disorder Questionnaire. The modified Fagerström Tolerance Questionnaire was completed to measure their nicotine use or dependence. Mediation analyses were performed to explore the relationship of two predictors. RESULTS: The prevalence rates of cigarette smoking and nicotine dependence in this study were 14.4% and 2.3%, respectively. Male gender (odds ratio [OR] 2.30; 95% confidence interval [CI] 1.60-3.30), subclinical symptoms of ADHD (OR 1.34; 95% CI 1.04-1.71), clinical symptoms of ADHD (OR 1.69; 95% CI 1.08-2.66), and symptoms of BD (OR 1.59; 95% CI1.09 to 2.32) were associated with nicotine use. Male gender (OR 4.60; 95% CI 1.41-14.98) and symptoms of BD (OR 6.14; 95% CI 3.37-11.18), but not symptoms of ADHD, were associated with nicotine dependence. In mediation analyses, we found that the effect of ADHD symptoms was no longer significant after controlling for symptoms of BD, and the mediation ratio (PM) was 0.39. CONCLUSIONS: Our findings suggest that mood disturbances other than symptoms of ADHD are more likely to be a key predictor of nicotine dependence among adolescents. The conclusions may improve our understanding of the course of nicotine dependence and help to promote potential health policy for nicotine control among youths.

Evidence for the indirect effects of perceived public stigma on psychosocial outcomes: The mediating role of self-stigma.

This study examined the possible mediating role of self-stigma in the relationship between perceived public stigma and psychosocial outcomes and how this mechanism may be contingent on illness severity in a non-Western (Chinese) sample. A total of 251 participants, namely 151 psychiatric outpatients with psychotic disorders and 100 psychiatric outpatients without psychotic disorders, completed a questionnaire on stigma and psychosocial outcomes that covered topics such as self-esteem, depressive symptoms, and subjective quality of life (QoL). Using a cross-sectional design, ordinary least squares regression and bootstrapping mediation analyses were used to test whether self-stigma mediated the relationship between perceived public stigma and psychosocial outcomes and whether this mediating process was moderated by diagnostic status. The results indicated that self-stigma mediated the effect of perceived public stigma on psychosocial outcomes such as self-esteem, depressive symptoms, and subjective QoL among both patients with psychotic disorders and those without psychotic disorders after controlling for demographic and clinical characteristics. Further, moderated mediation analyses revealed that the indirect effect of perceived public stigma on psychosocial outcomes were not moderated by the status of psychotic diagnoses. Self-stigma might be an essential and tractable target for interventions aimed at breaking the vicious cycle of discrimination and stigmatization toward people with mental illness regardless of their diagnoses.

Protective Effects of Quetiapine on Metabolic and Inflammatory Abnormalities in Schizophrenic Patients during Exacerbated Stage.

Inflammation has been considered important in the pathogenesis of schizophrenia. Increasing evidence reveals that patients with schizophrenia have abnormal expression of cytokines, which are related to development of metabolic abnormalities. Metabolic abnormality has become a critical issue, though its longitudinal relationship with the disorder, such as the antipsychotics influence, is unclear. We aimed to investigate whether abnormalities of metabolic parameters and cytokine levels in acute exacerbated schizophrenic patients existed, and whether intervention of antipsychotic could help. The present study analyzed peripheral cytokines and metabolic/hemodynamic parameters in healthy controls and acute exacerbated schizophrenic patients hospitalized for three weeks under the unique treatment of quetiapine, a well-known second-generation antipsychotic. Our results showed that patients with schizophrenia were predisposed to metabolic abnormalities in acute exacerbation, including body mass index (BMI) and waist circumference (WC). The patients were also prone to dysglycemia, lower high-density lipoprotein cholesterol (HDL-c) levels, and higher blood pressure with concomitant of elevation of interleukin (IL)-2, IL-6 and IL-10 in which IL-6 was associated with BMI. After quetiapine treatment, IL-2, IL-6 and IL-10 remained higher than the controls, but IL-10 was significantly decreased in follow-up comparison. Glycemic-related indexes, HDL-c and IL-10 levels were significantly changed by variance analysis. Results of the present study imply that acute exacerbated schizophrenic patients with metabolism abnormalities may involve disruption of expression of cytokines, and that quetiapine may have therapeutic effects. Nonetheless, metabolism parameters of patients undergoing treatment with quetiapine should be closely monitored.

Sensorimotor gating deficits are inheritable in an isolation-rearing paradigm in rats.

Early life experience is a key etiological factor of neuropsychiatric dysfunctions and is associated with developmental origins. Impaired prepulse inhibition (PPI) following an acoustic startle response is acknowledged as a cardinal characteristic in socially deprived weanling rats, which has been employed to investigate the underlying mechanisms of sensorimotor gating abnormalities in certain mental disorders, including schizophrenia. Because impaired PPI is a postnatal malfunction, it is interesting to examine whether it can be passed to the next generation. Isolation-rearing (IR) rats had been socially deprived since weaning, which mated with social rearing rats. Next, the offspring of IR rats were reared in a normal social environment. Locomotion, PPI, monoamines, and genes in schizophrenia-relevant brain areas [medial prefrontal cortex (mPFC) and hippocampus] were later measured. To this end, we observed that the next generation of IR offspring rats appeared with impaired PPI in which the PPI deficit can be observed as early as three weeks after birth. The third generation also exhibited lower levels of dopamine and serotonin in the mPFC and hippocampus; however, higher levels of both monoamines were measured in the striatum. Finally, Slc1a2 was more highly expressed in the mPFC of the third generation male rats. The present study demonstrates a transgenerational inheritance of IR-induced character and may help to elucidate the underlying pathoetiology of schizophrenia.

New onset somnambulism associated with different dosage of mirtazapine: a case report.

Somnambulism consists of variously complex behaviors that may result in harm to self or to others. Many different medications have been reported to induce somnambulism, and a few of them are newer antidepressants. A 40-year-old woman with history of major depression who experienced new onset somnambulism for successive 3 nights, whereas the antidepressant mirtazapine was increased from 30 to 45 mg/d. The notable and complex sleepwalking symptoms terminated dramatically on the first night after withdrawal of mirtazapine. There is clearly a cause-and-effect relationship between the treatment of higher-dosage mirtazapine and development of somnambulism. It might be related to the different affinities to 5-hydroxytryptamine 2 (5-HT(2)) and H(1) receptors at different dosages of mirtazapine, which explain the patient experiencing sleepwalking episodes exclusively at higher doses of mirtazapine. Clinical physicians should be aware of this adverse effect and taper or discontinue the regimen if sleepwalking develops.