Individual Differences in Hemispheric Emotional Valence by Computerized Test Correlate with Lateralized Differences in Nucleus Accumbens, Hippocampal and Amygdala Volumes.

Purpose: Conventional theories of hemispheric emotional valence (HEV) postulate fixed hemispheric differences in emotional processing. Schiffer's dual brain psychology proposes that there are prominent individual differences with a substantial subset showing a reversed laterality pattern. He further proposed that hemispheric differences were more akin to differences in personality than in emotional processing. This theory is supported by findings that unilateral treatments, such as transcranial magnetic stimulation, are effective if they accurately target individual differences in laterality. The aim of this paper was to assess if a computer test of hemispheric emotional valence (CTHEV) could effectively identify individual differences in HEV and to ascertain if these individual differences were associated with underlying differences in brain structure and connectivity. Patients and Methods: The CTHEV was administered to 50 (18 male/32 female) right-handed participants, aged 18-19 years, enrolled in a study assessing the neurobiological effects of childhood maltreatment. Based on a literature review, we determined whether CTHEV correlated with lateralized volumes of the nucleus accumbens, amygdala, hippocampus, and subgenual anterior cingulate as well as volume of the corpus callosum. Results: CTHEV scores correlated with laterality indices of the nucleus accumbens (p = 0.00016), amygdala (p = 0.0138) and hippocampus (p = 0.031). A positive left hemispheric valence was associated with a larger left-sided nucleus accumbens and hippocampus and a smaller left amygdala. We identified four eigenvector network centrality DTI measures that predict CTHEV, most notably the left amygdala, and found that CTHEV results correlated with total and segment-specific corpus callosal volumes. Conclusion: Individual differences in HEV can be readily assessed by computer test and correlate with differences in brain structure and connectivity that could provide a mechanistic understanding. These findings provide further support for a revised understanding of HEV and provide a tool that could be used to guide lateralized brain treatments.

Clinical experience using intranasal ketamine in the longitudinal treatment of juvenile bipolar disorder with fear of harm phenotype.

OBJECTIVES: Fear of Harm (FOH) is a pediatric onset phenotype of bipolar disorder (BD) characterized by BD plus treatment resistance, separation anxiety, aggressive obsessions, parasomnias, and thermal dysregulation. Intranasal ketamine (InK) in 12 youths with BD-FOH produced marked improvement during a two-week trial. Here we report on the open effectiveness and safety of InK in maintenance treatment of BD-FOH from the private practice of one author. METHODS: As part of a chart review, patients 18 years or older and parents of younger children responded to a clinical effectiveness and safety survey. Effectiveness was assessed from analysis of responses to 49 questions on symptomatology plus qualitative content analyses of written reports and chart review. Adverse events (AEs) were analyzed by frequency, duration and severity. Peak InK doses ranged from 20 to 360mg per administration. RESULTS: Surveys were completed on 45 patients treated with InK for 3 months to 6.5 years. Almost all patients were "much" to "very much" improved clinically and in ratings of social function and academic performance. Significant reductions were reported in all symptom categories. There were 13 reports of persistent AEs, none of which resulted in discontinuation. Acute emergence reactions were sporadically observed in up to 75%, but were mild and of brief duration. LIMITATIONS: Retrospective review from a single practice without placebo control with potential for response and recall bias. CONCLUSIONS: InK every 3-4 days at sub-anesthetic doses appeared to be a beneficial and well-tolerated treatment. Use of InK may be considered as a tertiary alternative in treatment refractory cases. Randomized control trials are warranted.

Does sleep disruption mediate the effects of childhood maltreatment on brain structure?

Background: Childhood maltreatment is associated with alterations in morphology of stress susceptible brain regions. Maltreatment is also known to markedly increase risk for psychopathology and to have an enduring disruptive effect on sleep. Objective: To determine whether abnormalities in sleep continuity have effects on brain morphometry and to evaluate the extent to which sleep impairments mediate the effects of maltreatment on brain structure. Method: Maltreatment and Abuse Chronology of Exposure (MACE) scale ratings, actigraph-assessed sleep and 3T MRI were obtained on N = 37 18-19-year-old participants recruited from the community (N = 34 with neuroimaging). Results: Fourteen participants had no history of maltreatment while N = 23 were exposed, on average, to 4.7 types of maltreatment. Multiplicity of maltreatment was strongly associated with reduced sleep efficiency, increased wake after sleep onset time and number/duration of awakenings, which were independent of effects of maltreatment on depression and anxiety. The most important predictors of impaired sleep were exposure to parental non-verbal emotional abuse at 9-10 years of age. Reduced sleep efficiency correlated with reduced grey matter volume in hippocampus including CA1 subfield, molecular layer and dentate gyrus as well as inferior frontal gyrus and insula. Sleep mediated 39-46% of the effects of maltreatment on volume of hippocampal structures and inferior frontal gyrus. Conclusions: Actigraph-assessed sleep is disrupted in maltreated late teens and mediates a significant portion of the effects of maltreatment on hippocampal volume. Studies are needed to assess whether efforts to enhance sleep in maltreated children can pre-empt or ameliorate neurobiological consequences of maltreatment.

Objetivo: determinar si las anomalías en la continuidad del sueño tienen efectos sobre la morfometría cerebral y evaluar en qué medida las alteraciones del sueño intervienen en los efectos del maltrato sobre la estructura del cerebro. Método: Se obtuvieron las puntuaciones de la Escala de cronología de la exposición al maltrato y al abuso (MACE, por sus siglas en inglés), sueño evaluado por actigraph y 3T MRI en N = 37 participantes de 18-19 años reclutados en la comunidad (N = 34 con neuroimagen). Resultados: Catorce participantes no tenían antecedentes de malos tratos mientras que N = 23 habían estado expuestos, de media, a 4.7 tipos de maltrato. La multiplicidad de los malos tratos se asoció fuertemente con una menor eficiencia del sueño, tiempo mayor de vigilia después de la hora de inicio del sueño y el número / duración de despertares, que fueron independientes de los efectos del maltrato sobre la depresión y la ansiedad. Los predictores más importantes de problemas de sueño fueron la exposición al abuso emocional no verbal de los padres a los 9-10 años de edad. La reducción de la eficiencia del sueño se correlacionó con la reducción del volumen de la materia gris en el hipocampo, incluido el subcampo CA1, la capa molecular y la circunvolución dentada, así como la circunvolución frontal inferior y la ínsula. El sueño mediaba en el 39-46% de los efectos del maltrato sobre el volumen de las estructuras del hipocampo y la circunvolución frontal inferior. Conclusiones: el sueño evaluado por Actigraph se ve alterado en adolescentes mayores maltratados y media en una parte importante de los efectos del maltrato sobre el volumen del hipocampo. Se necesitan estudios para evaluar si los esfuerzos para mejorar el sueño en los niños maltratados pueden adelantar o mejorar las consecuencias neurobiológicas del maltrato.