“Border line Persnality Disorder: Needed attention equally as bipolar disorder”

Borderline personality disorder  & Bipolar disorder both are disabling and life-threatening conditions. The serotonin system and the HPA (stress) axis are predominantly affected in both. However, the deterioration of psychiatric and physical health caused by borderline personality disorder rivals that of bipolar disorder, according to Mark Zimmerman, M.D., a researcher at Rhode Island Hospital. His research was published online in the British Journal of Psychiatry on 25th april 2015. “The level of psychosocial morbidity and suicidality associated with border line personality disorder is as great, or greater, than that experienced by patients with bipolar disorder,” said Zimmerman, director of outpatient psychiatry at Rhode Island Hospital and director of the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project. Thus, from the perspective of mental health improvement,  detection and treatment of Borderline personality disorder is equally important as diagnosing and treating bipolar disorders. Like bipolar patients, persons with Borderline personality disorder are likely to also suffer from depression, anxiety disorders, eating disorders and suicidal behaviors. These co-occurring mental illnesses may have symptoms that overlap with both disorders make it tricky recognize in patients.

Bipolar disorder is a widely researched, well-publicized, well-funded topic. By contrast, Border line personality disorder is seldom discussed and it is not included in the Global Burden of Disease study, a comprehensive registry that quantifies diseases by cost, mortality, geography, risk and other factors.

The cause of borderline personality disorder is complex with both psychologically and
neurobiologically. Genetic factors and adverse childhood experiences (e.g. attachment trauma, emotional neglect) may cause emotional dysregulation and heightened impulsivity leading to dysfunctional behaviours and psychosocial
deficits, which again could reinforce emotional dysregulation and impulsivity.There might be the chance that undiagnosed or unrecognized borderline personality disorder may lead to bipolar disorder and worsens the mental health of person. Therefore, unrecognized Border line Persnality Disorder needs attention in the field of neuroscience research.

Psychosocial morbidity associated with bipolar disorder and borderline personality disorder in psychiatric out-patients: comparative study.
Mark Zimmerman, William Ellison, Theresa A. Morgan, Diane Young, Iwona Chelminski, Kristy Dalrymple

T- Cells can produce Neurotransmitters: A bridge between Adaptive Immunity and Brain Function?

Apart from the conventional role of T cell in immunity, their presence in the nervous system has provided a glimpse to interaction between immunology and neurology. Adaptive immunity has been less studied which plays a significant role in brain function. T cells appear to be significant in a) learning and memory and b) Decrease of pro-inflammatory response not only through cytokines production but also by regulation of neurotransmitter release. It has been reported that stimulation of vagus nerve activates the spleenic nerve which activates CD4+ T cells to release acetylcholine. That certain populations of memory T cells have capacity to produce acetylcholine is certainly an interesting finding which could pave way for reciprocal interaction between the neural and immune system. In 2011, it was proved that T cells not only possess Choline Acetyl Transferase (ChaT) but also express α7 nAchR which interact with TCR. Interaction of α7 nAchR with TCR activates TCR/CD 3 complex reported to be involved in the process of Long Term Potentiation (LTP) critical for memory formation. Moreover, T cell–derived IL-4 has been shown to play a dual role in the maintenance of cognitive function and also antagonize the deleterious effects of pro inflammatory cytokines on astrocytes and neurons in brain. Various studies have demonstrated that T cells could decrease inflammation through separately through their dopamine D1, D5 receptors via D1R/D5R-cAMP-PKA-CREB signaling pathway and as well as via acetylcholine α7 nAchR leading to finally suppress of IL-12 and IL 10 production. Presence of T cells though noted in CSF has been noticed but how they migrate in and out of CSF is not clear. Here we would like to elaborate upon possible interaction between neurotransmitters and T cell interaction to mediate critical functions of learning, memory formation and modulation of pro-inflammatory response.

Neurosteroids: A missing link between GABArgic inhibition seizures and stress

The nervous system is a well-known target for the endocrine effects of hormonal steroids coming from peripheral steroidogenic glands. However, the nervous system is also controlled in a paracrine and autocrine manner by steroids directly synthesized by neurons and glial cells, named neurosteroids. E.E. Baulieu introduced the term ‘‘neurosteroid’’ in 1981 to designate steroids, which are synthesized de novo in the brain via the classic mevalonate pathway to cholesterol and independently of plasma levels. Neuroactive steroids  are capable of modifying neural activities by affecting neurotransmitter receptor binding and regulating response to hypothalamo-pituitary-adrenocortical (HPA) axis.

Stress induces a physiological response which is mediated by the HPA axis. CRH is released from the hypothalamus and acts in the pituitary to signal the release of adrenocorticotropic hormone (ACTH), which triggers the release of cortisol from the adrenal gland in humans (corticosterone in mice). The HPA axis is regulated by inputs from numerous different brain regions, involving multiple neurotransmitter systems, as well as the feedback of steroid hormones acting on mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) These inputs impinge on CRH neurons in the paraventricular nucleus (PVN), which mediate the output of the HPA axis. Indeed, in severely depressed patients, emotional arousal, cognitive abnormality and vulnerability to psychotic episodes are linked to a hyperactive HPA axis and high level of circulating glucocorticoids, which returns to normal after antidepressant treatment.  Although CRH neurons receive a wide variety of inputs from diverse brain regions, their activity is ultimately regulated by GABAergic inhibition. A role for GABA in HPA axis regulation has been well established.

The GABAA receptor is the main target of action of neuroactive steroids. GABAA receptors are hetero pentameric GABA-gated chloride channels: they are involved in fast inhibitory neurotransmission. Composition of the five subunits determines the functional and pharmacological properties of GABAA receptors. The best known and most widely distributed form in the CNS consists of two alphas, two betas, and a third subunit, which together constitute the chloride ion channel. Site-specific binding of the GABAA receptor, in subunit beta, determines the opening of the ion channel and chloride influx. The increase in negative charge leads to a hyperpolarization of the membrane, making it less susceptible to excitation. The activation of GABAA receptors prevents a potential short circuit in the depolarization induced by excitatory neurotransmitters.

The neuroactive steroids increase the flow of chloride ions from GABAA receptors, by increasing both the frequency and duration of the opening of the ion channel.  Due to the increased probability of opening of the chloride channel of the GABAA receptor, neuroactive steroids increase a massive influx of the ion and potentiate inhibitory GABAergic transmission. A short, regulatory loop linking neuroactivesteroids’ effects to GABA actions might exist.

Allopregnanolone and other similar neurosteroids act as positive allosteric modulators and direct activators of GABAA receptors. Given the emerging understanding of the role of neurosteroids as autocrine modulators of neuronal excitability, the question arises as to whether endogenous neurosteroids regulate seizure susceptibility. Because in epilepsy inhibitory activity of GABA is inhibited. Lawrence et al. provide important new evidence that the availability of neurosteroids does indeed critically influence the propensity for seizures. These investigators used epileptic female rats that had experienced prolonged bout of status epilepticus induced by lithium– pilocarpine treatment. The epileptic animals exhibited about six seizures per day, each lasting approximately a minute. However, when neurosteroids were withdrawn, using the neurosteroid synthesis inhibitor finasteride, an enormous (more than ten-fold) increase in seizure frequency was observed. In contrast, finasteride—a selective inhibitor of 5α-reductase, the first and rate-limiting enzymatic step in the synthesis of neurosteroids from their steroid hormone precursors (e.g., progesterone)—did not induce seizures in normal animals. Similarly, there is no evidence that finasteride causes seizures in humans who do not have epilepsy.


Lawrence et al. conducted a final experiment in ovariectomized epileptic animals that had low serum progesterone levels maintained by subcutaneous implantation of a progesterone pellet. Unexpectedly, these animals also exhibited a huge (25-fold) increase in seizure frequency following finasteride treatment. Unfortunately, the authors did not study animals in which peripheral progesterone was completely eliminated. Nevertheless, the results of this last experiment suggest that the exacerbation of seizures that occurs following finasteride treatment is due to the inhibition of brain neurosteroid synthesis and is not caused by suppression of the conversion of peripheral (ovarian) progesterone to allopregnanolone. This important conclusion focuses attention squarely on brain neurosteroids as critical regulators of seizures in epilepsy. Clearly, more needs to be learned about the role of locally synthesized neurosteroids in epileptic brain circuits. It can be concluded that potential of neurosteroids may prove as a novel treatment approach for seizures.