What Does "Least Restrictive" or "Less Restrictive" Mean in Mental Health Law? Contradictions and Confusion in the Case of Queensland, Australia.

Most legal systems in the West allow for involuntary treatment of mental illness, usually on the basis that without such treatment the person would be a danger to themselves or others. While historically the mental health law jurisdiction has been a protective one, it has become increasingly influenced by civil rights and international human rights law, which privilege the value of autonomy and the right to personal liberty.In this regard, an important principle that has developed is that decisions about treatment for mental illness must be the "least restrictive alternative" available. This may mean, for example, that a person is supported to make a decision on treatment for their mental illness, according to evolving practices of "supported decision-making," so that their legal capacity is still recognized. If involuntary treatment is required, the "least restrictive" approach demands that the liberty and integrity of the person be respected to the greatest extent possible.The Mental Health Act 2016 (Qld) ("MHAQ") prescribes that decision-making on non-consensual treatment should preferably be done according to what it calls the "less restrictive way." However, the "less restrictive way" is defined as decision-making by patients under advance directives, and also by substitute decision-makers, including by attorneys or guardians not appointed by the patient, usually a family member. The MHAQ states that these arrangements are distinguished from and prioritized over what it calls "involuntary treatment and care," where the decision for non-consensual treatment is made by the treating team.However, we argue that these arrangements are not in fact "less restrictive" of the person's autonomy, but are less accountable forms of decision-making. Decision-making by treating teams under involuntary treatment provisions is subject to higher levels of transparency and accountability. In Australian states these decisions are reviewed regularly by a specially constituted, independent mental health tribunal. By contrast, treatment decisions made under the "less restrictive way" are not even defined as constituting involuntary treatment, and are outside the scope of the tribunal's review.In the case of decision-making by advance directive, we acknowledge that this is widely considered to be "less restrictive" of a person's right to legal capacity and autonomy. However, in these cases, the patient may actually be refusing treatment at the time the advance directive is relied upon. This raises serious questions as to whether such "voluntary" admissions and treatment should not be subject to the same oversight and accountability as involuntary ones. Patients have a right to less restrictive forms of decision-making, but when deprived of their liberty, they also have a right to adequate safeguards established by law.The term "less restrictive" in the MHAQ is largely misplaced and misleading. In the case of advance directives, it deflects attention from the potentially restrictive nature of the treatment and the lack of accountability. Even more problematically, the privileging of private substitute decision-making under the less restrictive way ignores the real risk of abuse and undue influence within the personal and family sphere. We argue that the "less restrictive way" under the MHAQ is a step backwards for the rights of patients, in that it shifts power to family on the risky assumption that decision-making by these less supervised individuals is more likely to uphold human rights. We believe that this reflects a pre-feminist assumption that the informal, family, private sphere is nearly always safe. This is a contentious assumption, which nevertheless underpins much unproblematized thinking and advocacy on supported decision-making. This issue also highlights the need for further elucidation and discussion on what least restrictive means in the context of involuntary treatment for mental illness.

The long noncoding RNA FEDORA is a cell type- and sex-specific regulator of depression.

Women suffer from depression at twice the rate of men, but the underlying molecular mechanisms are poorly understood. Here, we identify marked baseline sex differences in the expression of long noncoding RNAs (lncRNAs), a class of regulatory transcripts, in human postmortem brain tissue that are profoundly lost in depression. One such human lncRNA, RP11-298D21.1 (which we termed FEDORA), is enriched in oligodendrocytes and neurons and up-regulated in the prefrontal cortex (PFC) of depressed females only. We found that virally expressing FEDORA selectively either in neurons or in oligodendrocytes of PFC promoted depression-like behavioral abnormalities in female mice only, changes associated with cell type-specific regulation of synaptic properties, myelin thickness, and gene expression. We also found that blood FEDORA levels have diagnostic implications for depressed women and are associated with clinical response to ketamine. These findings demonstrate the important role played by lncRNAs, and FEDORA in particular, in shaping the sex-specific landscape of the brain and contributing to sex differences in depression.

Sex-Specific Role for SLIT1 in Regulating Stress Susceptibility.

BACKGROUND: Major depressive disorder is a pervasive and debilitating syndrome characterized by mood disturbances, anhedonia, and alterations in cognition. While the prevalence of major depressive disorder is twice as high for women as men, little is known about the molecular mechanisms that drive sex differences in depression susceptibility. METHODS: We discovered that SLIT1, a secreted protein essential for axonal navigation and molecular guidance during development, is downregulated in the adult ventromedial prefrontal cortex (vmPFC) of women with depression compared with healthy control subjects, but not in men with depression. This sex-specific downregulation of Slit1 was also observed in the vmPFC of mice exposed to chronic variable stress. To identify a causal, sex-specific role for SLIT1 in depression-related behavioral abnormalities, we performed knockdown (KD) of Slit1 expression in the vmPFC of male and female mice. RESULTS: When combined with stress exposure, vmPFC Slit1 KD reflected the human condition by inducing a sex-specific increase in anxiety- and depression-related behaviors. Furthermore, we found that vmPFC Slit1 KD decreased the dendritic arborization of vmPFC pyramidal neurons and decreased the excitability of the neurons in female mice, effects not observed in males. RNA sequencing analysis of the vmPFC after Slit1 KD in female mice revealed an augmented transcriptional stress signature. CONCLUSIONS: Together, our findings establish a crucial role for SLIT1 in regulating neurophysiological and transcriptional responses to stress within the female vmPFC and provide mechanistic insight into novel signaling pathways and molecular factors influencing sex differences in depression susceptibility.

Sex-Specific Role for the Long Non-coding RNA LINC00473 in Depression.

Depression is a common disorder that affects women at twice the rate of men. Here, we report that long non-coding RNAs (lncRNAs), a recently discovered class of regulatory transcripts, represent about one-third of the differentially expressed genes in the brains of depressed humans and display complex region- and sex-specific patterns of regulation. We identified the primate-specific, neuronal-enriched gene LINC00473 as downregulated in prefrontal cortex (PFC) of depressed females but not males. Using viral-mediated gene transfer to express LINC00473 in adult mouse PFC neurons, we mirrored the human sex-specific phenotype by inducing stress resilience solely in female mice. This sex-specific phenotype was accompanied by changes in synaptic function and gene expression selectively in female mice and, along with studies of human neuron-like cells in culture, implicates LINC00473 as a CREB effector. Together, our studies identify LINC00473 as a female-specific driver of stress resilience that is aberrant in female depression.