ObjectiveGender differences, including younger age of onset and greater premorbid deficits in men, have been reported in adult-onset schizophrenia. This study comprehensively evaluated gender differences in childhood-onset schizophrenia (COS), a rare variant of the disorder.MethodDemographic, premorbid, clinical, familial, and cognitive characteristics, presence of chromosomal abnormalities, and brain magnetic resonance imaging cortical volumes were evaluated in 133 patients with COS. Cortical analyses included age- and gender-matched healthy volunteers (n = 124).ResultsMales with COS (n = 72) had a slightly but significantly younger age of onset than females with COS (mean age 9.51 ± 2.28 versus 10.29 ± 1.63 years, t131 = 2.21, p = .03), higher verbal IQ scores (83.00 ± 15.97 versus 75.58 ± 15.10, t89 = 2.24, p = .03), and higher rates of comorbid pervasive developmental disorder (28.17% versus 6.90%, χ21 = 9.54, p < .01) and attention-deficit/hyperactivity disorder (43.86% versus 21.43%, χ21 = 5.40, p = .02). There were no significant gender differences across other demographic, IQ, or clinical measurements, frequency of chromosomal abnormalities, family clinical measurements, premorbid functioning, or in gender-by-disorder interactions for magnetic resonance imaging brain measurements.ConclusionThe present comprehensive examination found few remarkable gender differences in COS. Although less striking than that seen in adult-onset schizophrenia, males with COS had a younger age of onset. Attention-deficit/hyperactivity disorder and pervasive developmental disorder rates were high in COS overall, suggesting greater neurodevelopmental vulnerability in COS. However, the gender ratios of these comorbidities in COS mirror those of the general populations, indicating that these gender differences might be unrelated to COS. Gender differences, including younger age of onset and greater premorbid deficits in men, have been reported in adult-onset schizophrenia. This study comprehensively evaluated gender differences in childhood-onset schizophrenia (COS), a rare variant of the disorder. Demographic, premorbid, clinical, familial, and cognitive characteristics, presence of chromosomal abnormalities, and brain magnetic resonance imaging cortical volumes were evaluated in 133 patients with COS. Cortical analyses included age- and gender-matched healthy volunteers (n = 124). Males with COS (n = 72) had a slightly but significantly younger age of onset than females with COS (mean age 9.51 ± 2.28 versus 10.29 ± 1.63 years, t131 = 2.21, p = .03), higher verbal IQ scores (83.00 ± 15.97 versus 75.58 ± 15.10, t89 = 2.24, p = .03), and higher rates of comorbid pervasive developmental disorder (28.17% versus 6.90%, χ21 = 9.54, p < .01) and attention-deficit/hyperactivity disorder (43.86% versus 21.43%, χ21 = 5.40, p = .02). There were no significant gender differences across other demographic, IQ, or clinical measurements, frequency of chromosomal abnormalities, family clinical measurements, premorbid functioning, or in gender-by-disorder interactions for magnetic resonance imaging brain measurements. The present comprehensive examination found few remarkable gender differences in COS. Although less striking than that seen in adult-onset schizophrenia, males with COS had a younger age of onset. Attention-deficit/hyperactivity disorder and pervasive developmental disorder rates were high in COS overall, suggesting greater neurodevelopmental vulnerability in COS. However, the gender ratios of these comorbidities in COS mirror those of the general populations, indicating that these gender differences might be unrelated to COS.
Approximately one third of individuals with major depressive disorder have treatment-resistant depression (TRD). Glutamatergic modulators such as the N-methyl-d-aspartate receptor antagonist ketamine have rapid and robust antidepressant effects, but their use has been limited by accessibility and route of administration. This open-label pilot study assessed the adjunctive antidepressant efficacy of dextromethorphan/quinidine (DM/Q) in TRD.Inpatients with TRD (n = 17, 40.8 ± 12.3 years; 9 females/8 males) received adjunctive open-label DM/Q (20 mg/10 mg) up to 3 times daily. The study had no set endpoint; participants were followed until they discontinued DM/Q or were discharged. Montgomery-Asberg Depression Rating Scale (MADRS) scores were obtained at baseline (before DM/Q administration) and regularly during hospitalization. Full response was defined as a ≥50% reduction in baseline MADRS score, partial response as a 25% to 50% decrease in baseline MADRS score, and nonresponse as a <25% reduction or an increase in baseline MADRS score.The 17 inpatients received open-label DM/Q for 5.1 ± 2.7 weeks. Forty-seven percent of participants responded to DM/Q-12% achieved a full response and 35% achieved a partial response. The largest MADRS difference observed at any time point was -6.4 ± 8.4 (-21.0% ± 29.9%), and the MADRS difference observed at time of DM/Q discontinuation or hospital discharge was -4.8 ± 8.4 (-15.9% ± 29.7%). Twenty-four percent of participants experienced a nonserious adverse event; none experienced a serious adverse event.In this open-label pilot study, 47% of participants responded to adjunctive DM/Q, which was well tolerated. Larger placebo-controlled trials are needed to determine the real-world efficacy of DM/Q.
Background: Large geographic health disparities have been well-documented within the U.S. Although approximately 60 million Americans-or roughly 20% of the total U.S. population—live in rural areas, rural residents may be less likely to participate in health research, including mental health research, due to multiple barriers. This retrospective analysis evaluated the urbanity and rurality of inpatient research participants and potential research participants over a five-year period at the Experimental Therapeutics and Pathophysiology Branch (ETPB), NIMH-NIH (Bethesda, Maryland), which conducts experimental medicine and neurobiological research in mood disorders.Methods: Participant and potential participant zip codes were converted to Rural Urban Commuting Area (RUCA) codes (1-3 urban, 4-10 rural). These results were compared with each other and with U.S. population data.Results: The analysis included 184 research participants and 2836 potential research participants; the former were admitted to an in-person research unit and the latter were screened by phone or online. ETPB research participants had an urban residence rate of 92.3% and a rural residence rate of 7%. Potential ETPB research participants had an urban residence rate of 90.5% and a rural residence rate of 8.6%. In comparison, the U.S. urban residence rate is 80% and the rural rate is 20%.Conclusion: At the ETPB, both research participants with mood disorders who were admitted to an in-person research unit and potential research participants who were screened online or by phone were under-represented relative to participants from urban areas. Further study of research recruitment barriers in rural areas of the U.S is needed.
Schizophrenia is increasingly recognized as a neurodevelopmental disorder with altered connectivity among brain networks. In the current study we examined large-scale network interactions in childhood-onset schizophrenia, a severe form of the disease with salient genetic and neurobiological abnormalities. Using a data-driven analysis of resting-state functional magnetic resonance imaging fluctuations, we characterized data from 19 patients with schizophrenia and 26 typically developing controls, group matched for age, sex, handedness, and magnitude of head motion during scanning. This approach identified 26 regions with decreased functional correlations in schizophrenia compared to controls. These regions were found to organize into two function-related networks, the first with regions associated with social and higher-level cognitive processing, and the second with regions involved in somatosensory and motor processing. Analyses of across- and within-network regional interactions revealed pronounced across-network decreases in functional connectivity in the schizophrenia group, as well as a set of across-network relationships with overall negative coupling indicating competitive or opponent network dynamics. Critically, across-network decreases in functional connectivity in schizophrenia predicted the severity of positive symptoms in the disorder, such as hallucinations and delusions. By contrast, decreases in functional connectivity within the social-cognitive network of regions predicted the severity of negative symptoms, such as impoverished speech and flattened affect. These results point toward the role that abnormal integration of sensorimotor and social-cognitive processing may play in the pathophysiology and symptomatology of schizophrenia.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
