Department of Psychiatry

This resource document discusses the use of seclusion or restraint for purposes of mental health intervention in correctional facilities. Correctional mental health standards essentially state that seclusion or restraint, when used for health care purposes, should be implemented in a manner consistent with current community practice. The community practice was significantly impacted and revised during July 1999, after the Health Care Financing Administration defined rules for the use of seclusion and restraint in facilities that participate in Medicare and Medicaid. Since few correctional facilities are Medicare or Medicaid participants, these rules had little impact on the use of seclusion or restraint for mental health care purposes in correctional systems. Consequently, many correctional health care systems have not developed policies, procedures, or practices that are consistent with current community practice. This document provides guidance in remedying such problems, with a f...

Conversion therapies are any treatments, including individual talk therapy, behavioral (e.g. aversive stimuli), group therapy or milieu (e.g. "retreats or inpatient treatments" relying on all of the above methods) treatments, which attempt to change an individual's sexual orientation from homosexual to heterosexual. However these practices have been repudiated by major mental health organizations because of increasing evidence that they are ineffective and may cause harm to patients and their families who fail to change. At present, California, New Jersey, Oregon, Illinois, Washington, DC, and the Canadian Province of Ontario have passed legislation banning conversion therapy for minors and an increasing number of US States are considering similar bans. In April 2015, the Obama administration also called for a ban on conversion therapies for minors. The growing trend toward banning conversion therapies creates challenges for licensing boards and ethics committees, most...

Religion and spirituality have been associated in many studies with an impact on mental and physical health. However, the relationship between religious faith and transgender identities is not well studied. To understand this relationship, the LGBT Committee of the Group for the Advancement of Psychiatry undertook a qualitative analysis. Participants in this study are a subset of a larger project investigating the role of religion and spirituality among all members of the LGBTQ community. The larger study invited input on LGBTQ identity and faith using an announcement posted by the "Dear Abby" column, published in hundreds of newspapers around the globe. Of the 86 participants in the study, eight responses were examined by participants who identified as transgender. Qualitative analysis of these survey results revealed the following themes: awareness of gender identity and development, mental health, God's creation and spirit, fear of rejection, ambivalent acceptance, self-sacrifice for community, reconciliation with faith. Themes of both faith identity and gender identity were prevalent. Aspects of dual-identity development were painful and conflictual, but other aspects offered comfort, acceptance, and joy. When a participant's family and community showed even partial acceptance of their transgender identity, greater resilience and integration resulted.

Background: Apathy is a prominent feature of geriatric depression that predicts poor clinical outcomes and hinders depression treatment. Yet little is known about the neurobiology and treatment of apathy in late-life depression. This study examined apathy prevalence in a clinical sample of depressed elderly, response of apathy to selective serotonin reuptake inhibitor (SSRI) treatment, and neuroanatomical correlates that distinguished responders from non-responders and healthy controls. Methods: Participants included 45 non-demented, elderly with major depression and 43 elderly comparison individuals. After a 2-week single-blind placebo period, depressed participants received escitalopram 10 mg daily for 12 weeks. The Apathy Evaluation Scale (AES) and 24-item Hamilton Depression Rating Scale (HDRS) were administered at baseline and 12 weeks. MRI scans were acquired at baseline for concurrent structural and diffusion tensor imaging of anterior cingulate gray matter and associated white matter tracts. Results: 35.5% of depressed patients suffered from apathy. This declined to 15.6% (po 0.1) following treatment, but 43% of initial sufferers continued to report significant apathy. Improvement of apathy with SSRI was independent of change in depression but correlated with larger left posterior subgenual cingulate volumes and greater fractional anisotropy of left uncinate fasciculi. Limitations: Modest sample size, no placebo control, post-hoc secondary analysis, use of 1.5T MRI scanner Conclusions: While prevalent in geriatric depression, apathy is separable from depression with regards to medication response. Structural abnormalities of the posterior subgenual cingulate and uncinate fasciculus may perpetuate apathetic states by interfering with prefrontal cortical recruitment of limbic activity essential to motivated behavior.

Estrogens (E) and progestins regulate synaptogenesis in the CA1 region of the dorsal hippocampus during the estrous cycle of the female rat, and the functional consequences include changes in neurotransmission and memory. Synapse formation has been demonstrated by using the Golgi technique, dye filling of cells, electron microscopy, and radioimmunocytochemistry.

Objectives: The aims of this study were to examine: (1) the relationship between apathy and disability in late-life depression, and (2) the functional significance of improvement in apathy following escitalopram treatment in terms of its relationship
to disability. Methods: Subjects were 71 non-demented elderly with non-psychotic major depression. After a 2-week single-blind placebo period, subjects who had Hamilton Depression Rating Scale (HDRS) greater than or equal to18 received escitalopram 10 mg daily for 12 weeks. Apathy and disability were assessed with the Apathy Evaluation Scale (AES) and the World Health Organization Disability Assessment Scale II (WHODAS),
respectively. These measures and the HDRS were administered at baseline and again following 12 weeks of treatment. Results: At baseline, 38% of depressed subjects had significant apathy (AES >36.5). Severity of apathy at baseline significantly correlated
with severity of disability. In a multivariate regression model, baseline severity of apathy, but not the overall depressive syndrome (HDRS), significantly correlated with baseline disability. Following escitalopram treatment, improvement in apathy
significantly correlated with improvement in disability measures, while change in the rest of the depressive syndrome did not. The overall change in apathy and disability in response to escitalopram treatment was significant but small. Conclusions:
Apathy is common in late-life depression and is associated with disability above and beyond the influence of other depressive symptoms. Given the strong relationship between apathy and disability, understanding the neurobiology of apathy and
developing treatments for apathy may improve the functional outcomes of late-life depression.

Electrical synapses are formed by gap junctions and permit electrical coupling, which shapes the synchrony of neuronal ensembles. Here, we provide a direct demonstration of receptor-mediated strengthening of electrical coupling in mammalian brain. Electrical coupling in the inferior olive of rats was strengthened by activation of NMDA-type glutamate receptors (NMDARs), which were found at synaptic loci and at extrasynaptic loci 20-100 nm proximal to gap junctions. Electrical coupling was strengthened by pharmacological and synaptic activation of NMDARs, whereas costimulation of ionotropic non-NMDAR glutamate receptors transiently antagonized the effect of NMDAR activation. NMDAR-dependent strengthening (1) occurred despite increased input conductance, (2) induced Ca 2+ -influx microdomains near dendritic spines, (3) required activation of the Ca 2+ /calmodulin-dependent protein-kinase II, (4) was restricted to neurons that were weakly coupled, and (5) thus strengthened coupling, mainly between nonadjacent neurons. This provided a mechanism to expand the synchronization of rhythmic membrane potential oscillations by chemical neurotransmitter input.

Estradiol (E) mediates increased synaptogenesis in the hippocampal CA1 stratum radiatum (sr) and enhances memory in young and some aged female rats, depending on dose and age. Young females rats express more estrogen receptor α (ERα) immunolabeling in CA1sr spine synapse complexes than aged rats and ERα regulation is E sensitive in young but not aged rats. The current study examined whether estrogen receptor β (ERβ) expression in spine synapse complexes may be altered by age or E treatment. Young (3-4 months) and aged (22-23 months) female rats were ovariectomized 7 days prior to implantation of silastic capsules containing either vehicle (cholesterol) or E (10% in cholesterol) for 2 days. ERβ immunoreactivity (ir) in CA1sr was quantitatively analyzed using post-embedding electron microscopy. ERβ-ir was more prominent postsynaptically than presynaptically and both age and E treatment affected its synaptic distribution. While age decreased the spine synaptic complex localization of ERβ-ir (i.e., within 60 nm of the pre-and post-synaptic membranes), E treatment increased synaptic ERβ in both young and aged rats. In addition, the E treatment, but not age, increased dendritic shaft labeling. This data demonstrates that like ERα the levels of ERβ-ir decrease in CA1 axospinous synapses with age, however, unlike ERα the levels of ERβ-ir increase in these synapses in both young and aged rats in response to E. This suggests that synaptic ERβ may be a more responsive target to E, particularly in aged females.

The ovarian hormone estrogen increases the axospinous synapse density in the hippocampal CA1 region of young female rats but fails to do so in aged rats. This estrogen-mediated alteration of spine synapse structures suggests the coincident requirement for the structural reorganization of the underlying actin cytoskeleton network. Actin reorganization is known to require the deactivation of Cofilin, an actin depolymerization factor. Cofilin is deactivated by LIM Kinase (LIMK), and LIMK activity is modulated by the phosphorylation of specific residues. We have previously demonstrated that estrogen is able to increase phosphorylated LIMK (pLIMK) immunoreactivity (IR) in the hippocampus in vivo and that this estrogen-stimulated pLIMK-IR is decreased in the aged brain. Because Cofilin phosphorylation allows for actin filament elongation and spine synapse growth, we sought to determine if estrogen acts through Cofilin and if such estrogen action requires the observed LIMK activity. Using both hippocampal neurons and the NG108-15 neuroblastoma cell line, we demonstrate here that estrogen stimulates the phosphorylation of Cofilin in vitro. Furthermore, this estrogen action on Cofilin requires LIMK. Lastly, while initiating the phosphorylation of LIMK and Cofilin, estrogen can also stimulate the formation of filopodial extensions, an early step in the formation of nascent spines, demonstrating that estrogen can alter the actin-dependent neuronal morphology. This linkage of estrogen communication to Cofilin via LIMK provides the functionality to the age-sensitive pLIMK-IR that we have observed in vivo.

The experiments strongly suggested that the reason why Purkinje cells die so easily after global brain ischemia relates to deficiencies in aldolase C and EAAT4 that allow them to survive pathologically intense synaptic input from the inferior olive after the restoration of blood flow. This conclusion is based on: (a) the remarkably tight correspondence between the regional absence of aldolase C and EAAT4 in Purkinje cells and the patterned loss of Purkinje cells after a bout of global brain ischemia; (b) the necessity of the olivocerebellar pathway for the ischemic death of Purkinje cells; and (c) the build-up of pathologically synchronous and high-frequency burst activity within the inferior olive during recovery from ischemia. Indeed, the correspondence between the absence of aldolase C and EAAT4 to sensitivity to ischemia could be demonstrated for zones of Purkinje cells as small as two neurons. A second finding was that Purkinje cells are not uniformly sensitive to transient isc...

The diagnosis and treatment of latelife depression is often complicated by its clinical context. As a rule, late-life depression afflicts medically ill, disabled persons living under chronic stress and/or isolation. Symptoms and signs of medical illnesses and behavioral limitations from disability are often difficult to distinguish from depressive symptomatology. Underreporting of depressed mood and other psychological symptoms is common by older adults and contributes to underdiagnosis of depression. Many antide-pressant drugs and some psychotherapies have been found more efficacious than their respective comparison conditions. However, each of these treatments helps less than half of depressed older adults, necessitating a treatment strategy in which failure or intolerance of each treatment step informs the next. Clinical subpopulations of late-life depressionpsychotic depression, dysthymic disorder, depression associated with an adverse life event, treatment-resistant depression, and residual symptoms of depressionrequire special attention.

Executive functions are control mechanisms that regulate aspects of cognition and emotion. Impairments in executive functioning are prominent following disruption to frontolimbic connections involved in mood regulation. Executive dysfunction is common in older adults with major depression and is associated with poor course of illness and worse clin-Kevin J. Manning, PhD, is a Clinical Neuropsychology Fellow, Weill

Objective: Apathy is prevalent in late-life depression and predicts poor response to antidepressants, chronicity of depression, disability, and greater burden to caregivers. However, little is known about its neurobiology. Salience processing provides motivational context to stimuli. The aim of this study was to examine the salience network (SN) resting-state functional connectivity (rsFC) pattern in elderly depressed subjects with and without apathy. Methods: Resting-state functional MRI data were collected from 16 non-demented, non-MCI, elderly depressed subjects and 10 normal elderly subjects who were psychotropic-free for at least 2 weeks. The depressed group included 7 elderly, depressed subjects with high comorbid apathy and 9 with low apathy. We analyzed the rsFC patterns of the right anterior insular cortex (rAI), a primary node of the SN. Results: Relative to non-apathetic depressed elderly, depressed elderly subjects with high apathy had decreased rsFC of the rAI to dorsal anterior cingulate and to subcortical/limbic components of the SN. Depressed elderly subjects with high apathy also exhibited increased rsFC of the rAI to right dorsolateral prefrontal cortex and right posterior cingulate cortex when compared to non-apathetic depressed elderly. Conclusions: Elderly depressed subjects with high apathy display decreased intrinsic rsFC of the SN and an altered pattern of SN rsFC to the right DLPFC node of the central executive network when compared to elderly non-apathetic depressed and normal, elderly subjects. These results suggest a unique biological signature of the apathy of late-life depression and may implicate a role for the rAI and SN in motivated behavior.

Electrical synapses are formed by gap junctions and permit electrical coupling, which shapes the synchrony of neuronal ensembles. Here, we provide a direct demonstration of receptor-mediated strengthening of electrical coupling in mammalian brain. Electrical coupling in the inferior olive of rats was strengthened by activation of NMDA-type glutamate receptors (NMDARs), which were found at synaptic loci and at extrasynaptic loci 20-100 nm proximal to gap junctions. Electrical coupling was strengthened by pharmacological and synaptic activation of NMDARs, whereas costimulation of ionotropic non-NMDAR glutamate receptors transiently antagonized the effect of NMDAR activation. NMDAR-dependent strengthening (1) occurred despite increased input conductance, (2) induced Ca 2+-influx microdomains near dendritic spines, (3) required activation of the Ca 2+ /calmodulin-dependent protein-kinase II, (4) was restricted to neurons that were weakly coupled, and (5) thus strengthened coupling, mainly between nonadjacent neurons. This provided a mechanism to expand the synchronization of rhythmic membrane potential oscillations by chemical neurotransmitter input.