Access to Psychotherapy Notes: Review of Legal Standards for Mental Health Clinicians.

Patients' access to their psychotherapy records may be assumed to be well protected; however, the matter is intricately regulated. In fact, the statutes and rights pertaining to patient access to psychotherapy notes vary across states. Taken together, federal and state laws indirectly and inconsistently delineate lawful access-as well as clinical exceptions to providing access-to psychotherapy notes. Federal law defers to state laws when the latter afford individuals greater access to their notes. Both federal and individual state levels vary in providing for possible conditions under which access may be restricted. Right of access to psychotherapy notes is a matter of importance for all mental health clinicians in the United States. Awareness and integration of pertinent laws and regulations allow clinicians to manage such matters without a negative impact on their clinical care. Further consideration of how clinical practice interacts with other dimensions of health care administration (clinical, ethical, and legal) may serve to enhance the integrity of a clinician's work and the ability to adapt to difficult clinical circumstances with confidence.

Death of the suicide law: A changing standard of liability for clinicians.

High rates of suicide continue to plague the modern world, with clinicians, researchers, and policymakers working urgently to ameliorate what has been recognized as a worldwide public health crisis. Under American Law, individuals- including health care providers, could generally not be held liable for causing the suicide of another person. This article presents a review of suicide law in the United States in the context of a recent civil case in which a physician with expertise in mental health was sued for the death of an ex-partner who committed suicide in his home. Historical events and landmark legal cases spanning the 15th century to now are examined and presented as a narrative review to inform society and mental health clinicians a-like towards interpreting the changing medical-legal landscape. As modern advances in science continue to discern the critical biopsychosocial factors that contribute to the act of suicide, there is an inevitably growing concern that suicide may no longer be an incomprehensible nor irrational event as has been assumed for centuries. Thus, it may be considered that individual with expertise and qualification to treat a group of individuals at higher risk of suicide (severe mental illness) may be subject to a different standard than the average individual. This article seeks to present a complex matter where no simple or broad-sweeping conclusions can yet be drawn, however remains a critically important matter for mental health clinicians.

International perspective on physician knowledge, attitude and practices related to medical cannabis.

Background: The trends of recreational use of cannabis and use of cannabis for medical indications (i.e. "medical cannabis") have grown in recent years. Despite that, there is still limited scientific evidence to guide clinical decision-making and the strength of evidence for the medical use of cannabis is currently considered to be low. In contrast, there's growing evidence for negative health outcomes related to use of cannabis. In this rapidly shifting landscape, the role of physician's attitudes regarding the therapeutic value of cannabis has become essential. This study aimed to characterize knowledge/experience, attitudes, and potential predictors of clinical practice regarding medical cannabis. Methods: We conducted a cross-sectional survey of physicians from 17 countries between 2016-2018. The survey comprised of 28 questions designed to explore physician knowledge, attitude, and practices regarding the use of medical cannabis. Descriptive statistics were used to examine willingness to recommend medical cannabis for medical and psychiatric indications, followed by regression analysis to identify predictors of physician willingness to recommend medical cannabis. Results: A total of 323 physicians responded to the survey. Mean age was 35.4± 9.5 years, with 10.04 ±8.6 years of clinical experience. 53 percent of physicians were women. Clinical experience with medical cannabis was overall limited (51.4% noted never having recommended medical cannabis; 33% noted inadequate knowledge regarding medical cannabis). Overall willingness to recommend medical cannabis was highest for chemotherapy-induced nausea, refractory chronic neuropathic pain, and spasticity in amyotropic lateral sclerosis (ALS). Conclusion: This international study examining knowledge, attitudes and practices related to medical cannabis among physicians revealed that there are significant gaps in domain-specific knowledge related to medical cannabis. There is wide variability in willingness to recommend medical cannabis that is not consistent with the current strength of evidence. This study thus highlights the need for greater education related to domain-specific knowledge about medical cannabis.

Hypothalamic-pituitary-adrenal and autonomic response to psychological stress in abstinent alcohol use disorder individuals with and without depressive symptomatology.

BACKGROUND: Stress and depression have each been associated with relapse risk. In clinical practice, chronic alcohol use is often accompanied by poor emotional and self-regulatory processes. Tonic and phasic changes in stress responsivity impact an individual's relapse risk to alcohol. A further complicating factor is the pervasive coexistence of depressive symptoms in those with Alcohol Use Disorder (AUD), where the contribution of depressive symptomatology to these processes is not well understood. Individuals with AUD (AD) (21 with and 12 without sub-clinical depressive symptoms) and 37 social drinking controls (16 with and 21 without sub-clinical depressive symptoms) as part of a more extensive study (Fox et al., 2019). All participants were exposed to two 5-min personalized guided imagery conditions (stress and neutral) in a randomized and counterbalanced order across consecutive days. Alcohol craving, negative mood, Stroop performance, and plasma measures (cortisol, adrenocorticotrophic hormone, and salivary alpha-amylase) were collected before and after imagery exposure. RESULTS: Elevations in autonomic response (heart rate) to imagery (stress and neutral) were observed as a function of drinking (in both depressed and non-depressed individuals with alcohol use disorder compared with depressed and non-depressed social drinkers). Conversely, suppressed cortisol following stress was observed as a function of depressive symptomatology across both drinking groups. Individuals with comorbid AD and depressive symptoms demonstrated attenuated Adrenocorticotropic Hormone and poor Stroop performance compared with the other groups, indicating an interactive effect between drinking and depression on pituitary and inhibitory systems. CONCLUSION: Sub-clinical depressive pathophysiology may be distinct from drinking severity and may alter relapse-related stress adaptations during protracted abstinence from alcohol.

The Relationship Between Cannabinoids and Neural Oscillations: How Cannabis Disrupts Sensation, Perception, and Cognition.

Disruptions in neural oscillations are believed to be one critical mechanism by which cannabinoids, such as delta-9-tetrahyrdrocannabinol (THC; the primary psychoactive constituent of cannabis), perturbs brain function. Here we briefly review the role of synchronized neural activity, particularly in the gamma (30-80 Hz) and theta (4-7 Hz) frequency range, in sensation, perception, and cognition. This is followed by a review of clinical studies utilizing electroencephalography (EEG) which have demonstrated that both chronic and acute cannabinoid exposure disrupts neural oscillations in humans. We also offer a hypothetical framework through which endocannabinoids modulate neural synchrony at the network level. This also includes speculation on how both chronic and acute cannabinoids disrupt functionally relevant neural oscillations by altering the fine tuning of oscillations and the inhibitory/excitatory balance of neural circuits. Finally, we highlight important clinical implications of such oscillatory disruptions, such as the potential relationship between cannabis use, altered neural synchrony, and disruptions in sensation, perception, and cognition, which are perturbed in disorders such as schizophrenia.

Relationships Between Telomere Length, Plasma Glucagon-like Peptide 1, and Insulin in Early-Life Stress-Exposed Nonhuman Primates.

Background: Early-life stress is associated with alterations in telomere length, a marker of accumulated stress and aging, and a risk factor for psychiatric disorders. Nonhuman primate maternal variable foraging demand (VFD) is a validated early-life stress model, resulting in anxiety- and depressive-like symptoms in offspring. Previous studies reported increased plasma glucagon-like peptide 1 (pGLP-1) along with insulin resistance in this model. We investigated whether VFD rearing related to adult telomere length and to these neuroendocrine markers. Methods: Adult leukocyte telomere length was measured in VFD-reared (12 males, 13 females) and non-VFD-reared (9 males, 26 females) bonnet macaques. Associations between adult telomere length and adolescent fasting pGLP-1 or insulin resistance in VFD-reared versus non-VFD-reared groups were examined using regression modeling, controlling for sex, weight, and age. Results: VFD subjects had relatively longer telomeres than non-VFD subjects (p = .017), and females relatively longer than males (p = .0004). Telomere length was positively associated with pGLP-1 (p = .0009) and with reduced insulin sensitivity (p < .0001) in both sexes, but not as a function of rearing group. Conclusions: Unexpectedly, VFD was associated with longer adult telomere length. Insulin resistance may lead to higher pGLP-1 levels in adolescence, which could protect telomere length in VFD offspring as adults. Associations between adult telomere length and adolescent insulin resistance and high pGLP-1 may reflect an adaptive, compensatory response after early-life stress exposure.

Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder.

There is considerable interest in the therapeutic potential of psychedelic drugs. Dimethyltryptamine (DMT) is a potent, rapid-onset, and short-acting psychedelic drug that has not yet been independently tested for the treatment of depression. The safety, tolerability, and efficacy of intravenous DMT were investigated in treatment-resistant individuals with major depressive disorder (MDD) and healthy controls (HC) in an open-label, fixed-order, dose-escalation (0.1 mg/kg followed by 0.3 mg/kg) exploratory phase 1 study that was conducted in a typical hospital setting with strategic psychoeducation/support, but minimal psychotherapy. Tolerability, safety, cardiovascular function, abuse liability, psychedelic, and psychotomimetic effects, mood, and anxiety were assessed at each dosing session. In addition, depression was measured using the HAMD-17 in MDD participants 1 day after each dosing session. DMT was tolerated by both HC (n = 3) and MDD participants (n = 7) studied; there were no dropouts. HAMD-17 scores decreased significantly (p = 0.017) compared to baseline in MDD participants the day after receiving 0.3 mg/kg DMT (mean difference -4.5 points, 95% CI: -7.80 to -1.20, Hedge's g = 0.75). Adverse events were mostly mild with one self-limited serious event. DMT increased blood pressure, heart rate, anxiety, psychedelic effects, and psychotomimetic effects, which resolved within 20-30 min of injection. There were no dose-related differences in measures of drug reinforcement and abuse liability. In this small exploratory pilot study, intravenous DMT at doses of 0.1 and 0.3 mg/kg was mostly safe and tolerated and may have next-day (rapid) antidepressant effects in patients with treatment-resistant MDD. Further rigorous trials are warranted to replicate these findings and to determine the durability of antidepressant effects.

Early Life Stress and the Fate of Kynurenine Pathway Metabolites.

Early life stress (ELS) precedes alterations to neuro-immune activation, which may mediate an increased risk for stress-related psychiatric disorders, potentially through alterations of central kynurenine pathway (KP) metabolites, the latter being relatively unexplored. We hypothesized that ELS in a non-human primate model would lead to a reduction of neuroprotective and increases of neurotoxic KP metabolites. Twelve adult female bonnet macaques reared under conditions of maternal variable foraging demand (VFD) were compared to 27 age- and weight-matched non-VFD-exposed female controls. Baseline behavioral observations of social affiliation were taken over a 12-week period followed by the first cerebrospinal fluid (CSF) sample. Subjects were then either exposed to a 12-week repeated separation paradigm (RSP) or assigned to a "no-RSP" condition followed by a second CSF. We used high-performance liquid chromatography for kynurenine (KYN), tryptophan, 5-hydroxyindoleacetic acid, kynurenic acid (KYNA), and anthranilic acid (ANTH) as a proxy for quinolinic acid determination. At baseline, social affiliation scores were reduced in VFD-reared versus control subjects. CSF log KYNA and log KYNA/KYN ratio were lower in VFD-reared versus control subjects. CSF log KYNA/KYN was positively correlated with CSF log ANTH in VFD only (r = 0.82). Controlling for log KYNA/KYN, log ANTH was elevated in VFD-reared subjects versus controls. CSF log KYNA/KYN obtained post-RSP was positively correlated with mean social affiliation scores during RSP, specifically in VFD. ELS is associated with a reduced neuroprotective and increased neurotoxic pathway products. That the two contrasting processes are paradoxically correlated following ELS suggests a cross-talk between two opposing KP enzymatic systems.

Developmental Antecedents of Adult Macaque Neurogenesis: Early-Life Adversity, 5-HTTLPR Polymorphisms, and Adolescent Hippocampal Volume.

INTRODUCTION: Attenuated adult hippocampal neurogenesis may manifest in affective symptomatology and/or resistance to antidepressant treatment. While early-life adversity and the short variant ('s') of the serotonin transporter gene's long polymorphic region (5-HTTLPR) are suggested as interacting risk factors for affective disorders, no studies have examined whether their superposed risk effectuates neurogenic changes into adulthood. Similarly, it is not established whether reduced hippocampal volume in adolescence, variously identified as a marker and antecedent of affective disorders, anticipates diminished adult neurogenesis. We investigate these potential developmental precursors of neurogenic alterations using a bonnet macaque model. METHODS: Twenty-five male infant bonnet macaques were randomized to stressed [variable foraging demand (VFD)] or normative [low foraging demand (LFD)] rearing protocols and genotyped for 5-HTTLPR polymorphisms. Adolescent MRI brain scans (mean age 4.2y) were available for 14 subjects. Adult-born neurons were detected post-mortem (mean age 8.6y) via immunohistochemistry targeting the microtubule protein doublecortin (DCX). Models were adjusted for age and weight. RESULTS: A putative vulnerability group (VG) of VFD-reared 's'-carriers (all 's/l') exhibited reduced neurogenesis compared to non-VG subjects. Neurogenesis levels were positively predicted by ipsilateral hippocampal volume normalized for total brain volume, but not by contralateral or raw hippocampal volume. LIMITATIONS: No 's'-carriers were identified in LFD-reared subjects, precluding a 2×2 factorial analysis. CONCLUSION: The 's' allele (with adverse rearing) and low adolescent hippocampal volume portend a neurogenic deficit in adult macaques, suggesting persistent alterations in hippocampal plasticity may contribute to these developmental factors' affective risk in humans.

The Law and Practice of Off-Label Prescribing and Physician Promotion.

Prescription of medications for off-label indications is an increasingly common practice; recent events highlight such prescribing as one of the cornerstones of evolving clinical treatment. Clinicians are afforded substantial deference in prescribing practices and other treatments falling within the realm of the actual practice of medicine, including prescribing for off-label indications. Yet clinicians are not necessarily free to promote a medication for the same off-label indication they may have just prescribed for a patient. While trends in jurisprudence appear to be favoring clinicians' freedom to promote prescription medication for any use, in a majority of jurisdictions, the U.S. government can still bring considerable weight to bear on clinicians promoting off-label uses of prescription medications. We review the relevant laws and regulations pertaining to off-label prescription and promotion, as well as the possible legal consequences. The regulations pertaining to physician and pharmaceutical manufacturers regarding off-label drug use are complex. Suggestions are provided to help physicians better navigate the medical-legal landscape when prescribing or promoting medications for off-label use. Physician mindfulness to pertinent legal precedents will allow them to prescribe and promote medications with a higher level of critical reasoning to optimize care and reduce risk.

Involvement of Innate and Adaptive Immune Systems Alterations in the Pathophysiology and Treatment of Depression.

Major depressive disorder (MDD) is a prevalent and debilitating disorder, often fatal. Treatment options are few and often do not provide immediate relief to the patients. The increasing involvement of inflammation in the pathology of MDD has provided new potential therapeutic avenues. Cytokine levels are elevated in the blood and cerebrospinal fluid of MDD patients whereas immune cells often exhibit an immunosuppressed phenotype in MDD patients. Blocking cytokine actions in patients exhibiting MDD show some antidepressant efficacy. However, the role of cytokines, and the immune response in MDD patients remain to be determined. We reviewed here the roles of the innate and adaptive immune systems in MDD, as well as potential mechanisms whereby the immune response might be regulated in MDD.

Defective Inflammatory Pathways in Never-Treated Depressed Patients Are Associated with Poor Treatment Response.

Inflammation has been involved in the pathophysiology and treatment response of major depressive disorder (MDD). Plasma cytokine profiles of 171 treatment-naive MDD patients (none of the MDD patients received an adequate trial of antidepressants or evidence-based psychotherapy) and 64 healthy controls (HCs) were obtained. MDD patients exhibited elevated concentrations of 18 anti- and proinflammatory markers and decreased concentrations of 6 cytokines. Increased inflammasome protein expression was observed in MDD patients, indicative of an activated inflammatory response. The plasma of MDD patients was immunosuppressive on healthy donor peripheral blood mononuclear cells, inducing reduced activation of monocytes/dendritic cells and B cells and reduced T cell memory. Comparison between 33 non-responders and 71 responders at baseline and 12 weeks revealed that after treatment, anti-inflammatory cytokine levels increase in both groups, whereas 5 proinflammatory cytokine levels were stabilized in responders, but continued to increase in non-responders. MDD patients exhibit remodeling of their inflammatory landscape.

Early Life Stress, Mood, and Anxiety Disorders.

Early life stress has been shown to exert profound short- and long-term effects on human physiology both in the central nervous system and peripherally. Early life stress has demonstrated clear association with many psychiatric disorders including major depression, posttraumatic stress disorder, and bipolar disorder. The Diagnostic and Statistics Manuel of Mental Disorders (DSM) diagnostic categorical system has served as a necessary framework for clinical service, delivery, and research, however has not been completely matching the neurobiological research perspective. Early life stress presents a complex dynamic featuring a wide spectrum of physiologic alterations: from epigenetic alterations, inflammatory changes, to dysregulation of the hypothalamic pituitary axis and has further added to the challenge of identifying biomarkers associated with psychiatric disorders. The National Institute of Mental Health's proposed Research Domain Criteria initiative incorporates a dimensional approach to assess discrete domains and constructs of behavioral function that are subserved by identifiable neural circuits. The current neurobiology of early life stress is reviewed in accordance with dimensional organization of Research Domain Criteria matrix and how the findings as a whole fit within the Research Domain Criteria frameworks.

Adult glucocorticoid receptor mRNA expression volatility in response to an acute stressor and juvenile CSF corticotropin-releasing factor: A pilot neurodevelopmental study.

INTRODUCTION: Early life stress (ELS) has been shown to play a role in establishing persistent maladaptive HPA axis modifications that may contribute to the pathogenesis of mood and anxiety disorders. Central glucocorticoid receptor (GR) messenger RNA (mRNA) expression may facilitate (mal)adaptive responsivity to ELS. The role of adult monocytic GR mRNA expression, a putative CNS proxy, during acute stress exposure was explored as well as the ELS marker, juvenile cerebrospinal fluid (CSF) corticotropin-releasing factor. METHODS: Six adult macaques (three of which were exposed to variable foraging demand, a form of ELS) underwent acute restraint. Baseline GR expression and plasma cortisol concentrations were separately measured followed by subsequent measurements following stress completion (t=0min, 4h, 5 days and 7 days). Juvenile CSF CRF concentrations were available in five subjects to determine their developmental association with GR expression in response to stress. RESULTS: As expected acute restraint stress produced a significant increase in plasma cortisol concentrations most robustly observed at 4h post-stress time point. There was a significant juvenile CSF CRF concentration x time interaction in predicting adult GR mRNA expression in response to stress (partial η2=0.80). During acute stress juvenile CRF concentrations negatively predicted GR expression and during recovery, "flipped" to positively predict expression. Juvenile CSF CRF concentrations positively correlated with the volatility of adult GR mRNA expression. CONCLUSIONS: During acute stress, relatively high CSF CRF concentrations are associated with relatively rapid reductions in GR expression. Return to an ambient post-stress state was characterized by a direct relationship, consistent with increased HPA axis restraint in high CRF subjects. An ELS-associated allostatic adaptation suggests relative elevations of juvenile CSF CRF concentration set the stage for a relative hyper-volatility of adult GR mRNA expression in response to acute stress with potential long-term implications for HPA axis regulation.