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Science careers and mental health

Science’s hyper-competitive environment and its ‘publish or perish’ culture can breed anxiety and depression. Nature's latest global graduate survey, published in October 2017, showed 12% of all respondents had sought help for anxiety or depression caused by their PhD studies. And an international study published in Nature Biotechnology in March 2018 provided compelling evidence of a mental health crisis in graduate education with nearly 40% of respondents showing signs of moderate to severe depression. Our online resource aims to highlight this important issue and provides support and advice, not only to scientists struggling with poor mental health but also their colleagues, mentors, and supervisors.

Image: Sébastien Thibault

Articles

Nature’s survey of more than 6,000 graduate students reveals the turbulent nature of doctoral research.

Career Feature | | Nature

The medical programmes we see in our training as physician-scientists are becoming more progressive and supportive of students. Here’s what academia can learn from them, say Yoo Jung Kim and Erik Faber.

Career Column | | Nature

Confronting loss can give rise to difficult career choices, says Summer Praetorius.

Career Column | | Nature

How a study on the high rate of anxiety and depression in PhD students is helping to erase the stigma around mental-health issues.

Career Q&A | | Nature

In the face of routine rejection, many scientists must learn to cope with the insidious beast that is impostor syndrome.

Feature | | Nature

Research

The lateral habenula (LHb) is a region of the brain that is associated with aversion and other negative emotions. Hailan Hu and colleagues present a pair of papers in this week's issue on the role of burst firing in LHb neurons in depression in rats. First, they show that ketamine, a drug that can be used as an antidepressant, blocks LHb neuron bursting activity, and that both NMDAR and low-voltage-sensitive T-type calcium channels (T-VSCCs) are required for the drug to be effective. In the second study, the authors identify a potential mechanism for regulating this bursting behaviour that could represent a new therapeutic target. Levels of an astroglial potassium channel, Kir4.1, covary with the degree of membrane hyperpolarization and bursting activity of LHb neurons, as well as depression-related behaviours in various rodent models. The team suggest that blocking LHb neuron bursting activity could revive reward centres in the brain and elevate mood, and provide a model framework for developing rapid-acting antidepressants.

Article | | Nature

The lateral habenula (LHb) is a region of the brain that is associated with aversion and other negative emotions. Hailan Hu and colleagues present a pair of papers in this week's issue on the role of burst firing in LHb neurons in depression in rats. First, they show that ketamine, a drug that can be used as an antidepressant, blocks LHb neuron bursting activity, and that both NMDAR and low-voltage-sensitive T-type calcium channels (T-VSCCs) are required for the drug to be effective. In the second study, the authors identify a potential mechanism for regulating this bursting behaviour that could represent a new therapeutic target. Levels of an astroglial potassium channel, Kir4.1, covary with the degree of membrane hyperpolarization and bursting activity of LHb neurons, as well as depression-related behaviours in various rodent models. The team suggest that blocking LHb neuron bursting activity could revive reward centres in the brain and elevate mood, and provide a model framework for developing rapid-acting antidepressants.

Article | | Nature

The strongest genetic association found in schizophrenia is its association to genetic markers across the major histocompatibility complex (MHC) locus, first described in three Nature papers in 2009. The association signal at the MHC is extremely complex. Here Steven McCarroll and colleagues report a dissection of the MHC association to schizophrenia. They find a strong contribution from many structurally diverse alleles of the complement component 4 (C4) genes. The linkage was higher for C4 alleles that promoted greater expression of C4A, measured in the brain tissues of adult post-mortem donors with or without schizophrenia. The authors suggest that C4 may work with other components of the classical complement cascade to promote synaptic pruning, and demonstrate that C4 mediates synaptic refinement in a mouse model.

Article | | Nature

Salvos of neuronal activity in the brain’s lateral habenula, regulated by astrocyte cells, drive depression-like behaviours in rodents. The finding might help us to understand one antidepressant and to develop more.

News & Views | | Nature

The NMDAR antagonist ketamine has rapid and sustained antidepressant effects; this has prompted a search for alternative NMDAR antagonists that have the same antidepressant properties but lack the undesirable side effects of ketamine. Todd Gould and colleagues now show that the metabolism of (R,S)-ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant activity, and that the (2R,6R)-HNK enantiomer exerts rapid and sustained antidepressant actions in mice. These effects are NMDAR-independent but require AMPAR activation. Importantly, (2R,6R)-HNK lacks the side effects associated with ketamine. These findings suggest new options for the development of novel rapid-acting antidepressants.

Article | | Nature

Lithium is widely used as a mood stabilizer in bipolar disorder, but not all patients respond favourably. In this paper, Fred Gage and colleagues generated hippocampal dentate gyrus-like neurons from induced pluripotent stem cells (iPSCs) obtained from lithium-responsive and lithium-non-responsive patients with bipolar disorder in order to assess differences in cellular phenotypes. They found mitochondrial abnormalities and hyperexcitability in young iPSC-derived neurons from bipolar disorder patients. Hyperexcitability was reversed by lithium treatment only in neurons derived from lithium-responsive individuals. This suggests that hyperexcitability may be an early endophenotype of bipolar disorder and that iPSC models may be useful for the development of new therapies.

Letter | | Nature

Autism spectrum disorder (ASD) is associated with brain overgrowth, but it has been unclear how this relates to behavioural symptoms. In a longitudinal neuroimaging study of young children at high familial risk of autism, Heather Hazlett and colleagues now show that high-risk children who receive a diagnosis of ASD at 24 months of age had an increased cortical growth rate at 6–12 months. Early overgrowth in high-risk children is associated with social impairments at 24 months, and imaging data obtained at 6 and 12 months can predict an ASD diagnosis at 24 months in high-risk children. These findings indicate that differences in the developmental trajectory towards ASD emerge as early as the first year of life.

Letter | | Nature

D2 dopamine receptors are the principal targets for antipsychotic drugs for the treatment of schizophrenia, and offer possibilities for treating depression and Parkinson's disease. However, molecular-level understanding of these receptors is limited, and many available drugs cause serious side-effects as a result of activity at other dopamine receptors. Here, Bryan Roth and colleagues report the crystal structure of the D2 receptor in complex with the antipsychotic drug risperidone. This structure shows an unusual binding mode of the drug, distinct from those observed in the related D3 and D4 receptors, whereby a hydrophobic patch formed by a tryptophan residue regulates the entry and exit of the drug. Mutation at this position reduces the drug residence time, which is believed to be related to side-effects of common antipsychotics. This work hints at ways to develop safer antipsychotic drugs that are selective for D2.

Letter | | Nature

The discovery in 1936 that rats respond to various damaging stimuli with a general response that involves alarm, resistance and exhaustion launched the discipline of stress research.

News & Views | | Nature

Books