Hypothalamic-pituitary-adrenal axis hyperactivity is normalized after successful intermittent theta-burst stimulation in resistant depressed patients.

The present pilot study assessed the effects of multi-session intermittent theta-burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex in 17 treatment resistant depressed inpatients (TRDs) showing cortisol non-suppression to the overnight dexamethasone suppression test (DST) at baseline (i.e., maximum post-DST cortisol [CORmax] level > 130 nmol/L). After 20 iTBS sessions, the DST was repeated in all TRDs. At baseline, post-DST CORmax levels were higher in TRDs compared to healthy control subjects (HCs; n = 17) (p < 0.0001). After 20 iTBS sessions, post-DST CORmax levels decreased from baseline (p < 0.03) and were comparable to HCs. Decreases in post-DST CORmax levels were related to decreases in 17-item Hamilton Depression Rating Scale (HAMD-17) scores (ρ = 0.53; p < 0.03). At endpoint, 10 TRDs showed DST normalization (among them 7 were responders [i.e., HAMD-17 total score > 50% decrease from baseline]), and 7 did not normalize their DST (among them 6 were non-responders) (p < 0.05). Our results suggest that successful iTBS treatment may restore normal glucocorticoid receptor feedback inhibition at the pituitary level.

Systematic Review of the Apomorphine Challenge Test in the Assessment of Dopaminergic Activity in Schizophrenia.

So far, neuroendocrine studies conducted in schizophrenic patients have yielded conflicting results. Many of these discrepancies may be explained by the diversity of factors that influence the hormonal levels (at baseline and in response to pharmacological stimuli), the heterogeneity of the populations studied, the absence of standardization of test challenges and the confounding and long-lasting effects of previous treatments. Numerous studies have used apomorphine (APO) in the evaluation of dopaminergic (DA) function in schizophrenic patients. APO, a direct acting DA receptor agonist, decreases prolactin (PRL) and stimulates growth hormone (GH), adrenocorticotropic hormone (ACTH) and cortisol secretion. Therefore, the magnitude of hormonal responses to APO is an indirect assessment of the functionality of DA receptors at the hypothalamic-pituitary level. This review provides an update on the applications of the APO test in schizophrenia in clinical, pathophysiological and therapeutic fields.

Hypothalamic-prolactin axis regulation in major depressed patients with suicidal behavior.

BACKGROUND: So far, little is known about the control of hypothalamic-prolactin axis activity by dopamine (DA) and thyrotropin-releasing hormone (TRH) in depressed patients with suicidal behavior disorder (SBD). METHODS: We evaluated prolactin (PRL) responses to apomorphine (APO; a DA direct receptor agonist) and 0800 h and 2300 h protirelin (TRH) tests in 50 medication-free euthyroid DSM-5 major depressed inpatients with SBD (either current [n = 22], or in early remission [n = 28]); and 18 healthy hospitalized controls (HCs). RESULTS: Baseline (BL) PRL levels were comparable across the three diagnostic groups. SBDs in early remission did not differ from HCs regarding PRL suppression to APO (PRLs), PRL stimulation to 0800 h and 2300 h TRH tests (∆PRL), and ∆∆PRL values (difference between 2300 h-∆PRL and 0800 h-∆PRL values). Current SBDs showed lower PRLs and ∆∆PRL values than HCs and SBDs in early remission. Further analyses revealed that current SBDs with a history of violent and high-lethality suicide attempts were more likely to exhibit co-occurrence of low ∆∆PRL and PRLS values. CONCLUSIONS: Our results suggest that regulation of the hypothalamic-PRL axis is impaired in some depressed patients with current SBD, particularly those who have made serious suicide attempts. Considering the limitations of our study, our findings support the hypothesis that decreased pituitary D2 receptor functionality (possibly adaptive to increased tuberoinfundibular DAergic neuronal activity) together with decreased hypothalamic TRH drive might be a biosignature for high-lethality violent suicide attempts.

Dopamine Function and Hypothalamic-Pituitary-Thyroid Axis Activity in Major Depressed Patients with Suicidal Behavior.

Involvement of the dopaminergic (DA) and hypothalamic-pituitary-thyroid (HPT) systems in suicidal behavior is still poorly understood. We assessed multihormonal responses to apomorphine (APO; a short acting DA receptor agonist) and 8 AM and 11 PM protirelin (TRH) tests in 30 medication-free DSM-5 euthyroid major depressed inpatients with suicidal behavior disorder (SBD) (current, n = 14; in early remission, n = 16) and 18 healthy hospitalized control subjects (HCs). Compared to HCs, responses to APO and TRH tests were unaltered in SBDs in early remission. However, current SBDs exhibited increased APO-induced growth hormone (GH) and adrenocorticotropin (ACTH) stimulation, and reduced 11 PM thyrotropin (TSH) and ∆∆TSH values (difference between 11 PM and 8 AM TRH-TSH responses). In current SBDs, the association between high APO-GH concentrations and low ∆∆TSH values was more common in recent suicide attempters than in past suicide attempters. These preliminary results suggest that co-occurring alterations in the DA and HPT systems (i.e., DA receptor hyperresponsiveness associated with decreased hypothalamic TRH drive) may contribute to the pathophysiology of suicidal behavior. Conversely, normalization of DA and TRH functions might reflect a process of recovery from suicidality. Thus, our findings suggest that drugs targeting the DAergic and TRH systems could be relevant in suicide prevention.

Neuroendocrine Assessment of Dopaminergic Function during Antidepressant Treatment in Major Depressed Patients.

The effects of antidepressants on dopamine (DA) receptor sensitivity in the mesolimbic-hypothalamic system have yielded contradictory results. The postsynaptic DA receptor function was evaluated by the cortisol response to apomorphine (APO; 0.75 mg SC) in 16 drug-free DSM-5 major depressed inpatients and 18 healthy hospitalized control (HC) subjects. Cortisol response to the dexamethasone suppression test (DST) was also measured. After two and four weeks of antidepressant treatment (ADT), the DST and APO test were repeated in all patients. Cortisol response to APO (∆COR) was not influenced by the hypothalamic-pituitary-adrenal (HPA) axis activity, as assessed by the DST. Pre-treatment ∆COR values did not differ significantly between patients and HCs. During ADT, ∆COR values were lower than in HCs at week 2 and 4. After four weeks of treatment, among the eight patients who had blunted ∆COR values, seven were subsequent remitters, while among the eight patients who had normal ∆COR values, seven were non-remitters. Considering the limitations of our study, the results suggest that following chronic ADT, the desensitization of postsynaptic DA receptors connected with the regulation of the HPA axis at the hypothalamic level is associated with clinical remission. These results could reflect increased DA levels in the mesolimbic pathway.

Thyroid axis activity and dopamine function in depression.

BACKGROUND: Several lines of evidence suggest alterations in both hypothalamic-pituitary-thyroid (HPT) axis and dopamine (DA) function in depressed patients. However, the functional relationships between HPT and DA systems have not been well defined. METHODS: We examined thyrotropin (TSH) response to 0800 h and 2300 h protirelin (TRH) challenges, and adrenocorticotropic hormone (ACTH), cortisol and growth hormone (GH) responses to apomorphine (APO, a DA receptor agonist), in 58 drug-free DSM-IV major depressed inpatients without a suicidal behavior, and 22 healthy hospitalized controls. RESULTS: Compared with controls, patients showed 1) lower basal serum 2300 h-TSH, 2300 h-∆TSH, and ∆∆TSH (difference between 2300 h-∆TSH and 0800 h-∆TSH) levels, and 2) lower cortisol response to APO (∆COR). A negative relationship between ∆∆TSH values and hormonal responses to APO was observed in the depressed group, but not in the control group. When patients were classified on the basis of their ∆∆TSH status, patients with reduced ∆∆TSH values (< 2.5 mU/L) showed hormonal APO responses comparable to those of controls. Patients with normal ∆∆TSH values exhibited lower ∆ACTH, ∆COR, and ∆GH values than patients with reduced ∆∆TSH values and controls. CONCLUSION: Taken together, these results suggest that hypothalamic DA function is unaltered in depressed patients with HPT dysregulation (i.e., increased hypothalamic TRH drive leading to altered TRH receptor chronesthesy on pituitary thyrotrophs). Conversely, hypothalamic DA-receptor function is decreased in patients with normal HPT axis activity. These findings are discussed in the context of the role of TRH as a homeostatic neuromodulator in depression.

First-Dose Methylphenidate-Induced Changes in the Anti-Saccade Task Performance and Outcome in Adults with Attention-Deficit/Hyperactivity Disorder.

Objective: We examined whether the anti-saccade task (AST) performance after the first methylphenidate (MPH) dose could be associated with subsequent clinical outcome in adults with attention-deficit/hyperactivity disorder (ADHD). Methods: Ninety-seven drug-naive DSM-5 ADHD adults participated in this study. The AST parameters were measured at baseline, after the first MPH-dose (10 mg orally), and 6 months after chronic MPH treatment. Results were compared with those of 50 healthy control (HC) subjects. Results: At baseline, ADHDs showed longer saccadic reaction times and more direction errors than HCs (both p < 0.00001). Acute and chronic MPH administration resulted in normalization of the AST performances. Multivariate regression analysis after adjusting for age, sex, weight, and severity of symptoms at baseline, revealed that a low percentage of direction errors after the first MPH-dose (i.e., ≤10%) could predict remission at month 6 (OR: 5.84; 95% CI: 2.00-17.11; p = 0.001). Conclusions: Our findings indicate that: (1) impairments of motor planning and response inhibition in adults with ADHD are improved with MPH, and (2) a low direction error percentage after the first MPH-dose may be an independent predictor of remission.ClinicalTrials.gov identifier: NCT03411434.

Are the thyroid and adrenal system alterations linked in depression?

BACKGROUND: Disturbances in the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes have been frequently found in major depression. Given that glucocorticoids may inhibit thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) secretion, it has been hypothesized that hypercortisolemia could lead to HPT axis abnormalities. So far, data on interactions between the HPA and HPT axes in depression remain inconclusive. METHODS: In order to investigate this issue, we examined circadian rhythms of serum TSH and cortisol (sampled at 4 -hly intervals throughout a 24 -h span), TSH responses to 0800 h and 2300 h protirelin (TRH) tests and cortisol response to dexamethasone suppression test (DST) in 145 unmedicated inpatients meeting DSM-IV criteria for major depressive disorder (MDDs) and 25 healthy hospitalized control subjects (HCs). RESULTS: The secretion of TSH and cortisol exhibited a significant circadian rhythm both in HCs and MDDs. However, compared to HCs, MDDs showed: 1) reduced TSH mesor and amplitude values; 2) blunted 2300 h-ΔTSH and ΔΔTSH values (i.e. differences between 2300 h and 0800 h TRH-TSH responses); and 3) increased cortisol mesor and post-DST cortisol values. DST nonsuppresssors (n = 40, 27 %) showed higher cortisol mesor than DST suppressors (n = 105, 73 %). There was no difference between DST suppressors and nonsuppressors in their TSH circadian parameters and TRH-TSH responses. In addition, cortisol values (circadian and post-DST) were not related to TRH test responses. CONCLUSION: Our results do not confirm a key role for hypercortisolemia in the HPT axis dysregulation in depression.

Dopaminergic, Noradrenergic, Adrenal, and Thyroid Abnormalities in Psychotic and Affective Disorders.

BACKGROUND: This study aimed to assess hypothalamic-pituitary dopaminergic (DA), noradrenergic (NA), thyroid (HPT), and adrenal (HPA) activity in schizophrenia, in schizoaffective disorder, and in bipolar disorder. METHOD: We investigated a combined approach of hormone responses to (1) apomorphine (APO), a short-acting DA receptor agonist which decreases prolactin secretion (PRL), and stimulates secretion of growth hormone (GH), adrenocorticotropin (ACTH), and cortisol; (2) clonidine (CLO), an alpha 2-adrenoceptor agonist which stimulates GH secretion; (3) 8 AM and 11 PM protirelin (TRH) which stimulates thyrotropin (TSH) secretion; and (4) dexamethasone which suppresses cortisol secretion, in 13 hospitalized healthy male controls and 39 untreated male inpatients: 13 with DSM-IV paranoid schizophrenia, 13 with DSM-IV schizoaffective disorder (bipolar subtype, depressed at the time of the study), and 13 with DSM-IV bipolar disorder (depressed). RESULTS: Compared to controls, paranoid schizophrenic patients showed (1) lower APO-induced ACTH and cortisol stimulation, and (2) higher post-dexamethasone cortisol values. Compared to controls, schizoaffective and bipolar patients showed (1) lower ΔΔTSH values (i.e., difference between 11 PM and 8 AM TRH-TSH responses), (2) lower APO-induced PRL suppression, (3) lower CLO-induced GH stimulation, and (4) higher post-dexamethasone cortisol values. CONCLUSIONS: Although results must be interpreted with caution because of the small sample, this preliminary study suggests that depressed bipolar and schizoaffective patients share common biological dysregulations, distinct from that of paranoid schizophrenic patients. From a pathophysiological viewpoint, paranoid schizophrenic patients can be characterized by hyposensitivity of the hypothalamic DA receptors (possibly resulting from an increase in presynaptic DA release) associated with increased HPA axis activity, while depressed bipolar and schizoaffective patients can be characterized by hyposensitivity of the pituitary TRH and DA-D2 receptors (possibly linked to the activation of the hypothalamic TRH and tuberoinfundibular DA neurons, respectively), together with subsensitive postsynaptic α2-adrenoreceptors at the hypothalamic level (possibly secondary to an erratic release of NA) and increased HPA axis activity.

A New Dataset of People Flow in an Industrial Site with UWB and Motion Capture Systems.

Improving performance and safety conditions in industrial sites remains a key objective for most companies. Currently, the main goal is to be able to dynamically locate both people and goods on the site. Security and access regulation to restricted areas are often ensured by doors or badge barriers and those have several issues when faced with people being in places they are not supposed to be in or even tools of objects being used incorrectly. In addition to this, a growing use of new devices requires precise information about their location in the environment such as mobile robots or drones. Therefore, it is becoming essential to have the tools to dynamically manage these flows of people and goods. Ultra-wide-band and motion capture solutions will be used to quickly identify people who may be in unauthorized areas or performing tasks which they have been uninstructed to do. In addition to the dynamic tracking of people, this also overcomes some issues associated with moving objects or tools around the production floor. We offer a new set of data that provides precise information on worker movement. This dataset can be used to develop new metrics regarding worker efficiency and safety.

Differences in multihormonal responses to the dopamine agonist apomorphine between unipolar and bipolar depressed patients.

BACKGROUND: A large number of studies suggest that dopaminergic function may be impaired in depressed patients, particularly in bipolar patients. The dopamine D2/D1 agonist apomorphine (APO) can be useful in the evaluation of dopaminergic function. However, most studies show conflicting results in APO test responses when evaluating unipolar and bipolar depressed patients. Thus, the objective of this study was to apply the APO test to assess whether hypothalamic-pituitary dopaminergic function is altered in unipolar and bipolar depression. METHODS: We evaluated multihormonal responses to APO test (0.75 mg subcutaneous) in 134 drug-free DSM-IV major depressed inpatients (54 with bipolar depression [BD] and 80 with unipolar depression [UD]), compared with 36 healthy controls (HCs). We also examined the cortisol response to the dexamethasone suppression test (DST, 1 mg orally) in all subjects. RESULTS: No significant differences in prolactin (PRL), cortisol, adrenocorticotropin (ACTH) or growth hormone (GH) baseline values were found across the three groups. ACTH/cortisol and GH responses to APO were also comparable. BD patients showed lower PRL suppression to APO than did UD patients and HCs (both p < 0.00001). Although responses to DST were comparable between UD and BD patients, the former exhibited higher post-DST cortisol levels than did HCs (p < 0.05). CONCLUSIONS: Our results suggest that BD patients, unlike UD patients, have altered post-synaptic D2 receptor sensitivity at the pituitary level. This alteration does not seem secondary to hypercortisolemia. These findings, if confirmed by other studies with larger samples, may support the use of dopamine agents in BD patients treatment.

Relationship between chronobiological thyrotropin and prolactin responses to protirelin (TRH) and suicidal behavior in depressed patients.

BACKGROUND: So far, investigations of the relationships between suicidality and the activity of the thyrotropic and lactotropic axes are scarce and have yielded conflicting results. METHODS: We studied the thyrotropin (TSH) and prolactin (PRL) responses to 0800h and 2300h protirelin (TRH) stimulation tests, carried out on the same day, in 122 euthyroid DSM-5 major depressed inpatients with suicidal behavior disorder (SBD) (either current [n=71], or in early remission [n=51]); and 50 healthy hospitalized controls. RESULTS: Baseline TSH and PRL measurements did not differ across the 3 groups. In SBDs in early remission, the TSH and PRL responses to TRH tests (expressed as the maximum increment above baseline value after TRH [Δ]) were indistinguishable from controls. Current SBDs showed (1) lower 2300h-ΔTSH and lower ΔΔTSH values (differences between 2300h-ΔTSH and 0800h-ΔTSH) than controls and SBDs in early remission; and (2) lower baseline free thyroxine (FT4B) levels than controls. In the current SBD group, ΔΔPRL values (differences between 2300h-ΔPRL and 0800h-ΔPRL) were correlated negatively with lethality. Moreover, in current SBDs (1) violent suicide attempters (n=15) showed lower FT4B levels, lower TSH-TRH responses (both at 0800h and 2300h), and lower ΔΔTSH and ΔΔPRL values than controls, while (2) non-violent suicide attempters (n=56) showed lower ΔΔTSH values than controls and higher TSH-TRH responses (both at 0800h and 2300h) than violent suicide attempters. CONCLUSIONS: Our results suggest that central TRH secretion is not altered in depressed patients with SBD in early remission. The findings that current SBDs exhibit both decreased FT4B levels and decreased evening TSH responses (and consequently, decreased ΔΔTSH values) support the hypothesis that hypothalamic TRH drive is reduced-leading to an impaired TSH resynthesis in the pituitary during the day after the morning TRH challenge. In violent suicide attempters, the marked abnormalities of TRH test responses might indicate a greatest reduction in hypothalamic TRH drive. These results further strengthen the possibility that a deficit in central TRH function may play a key role in the pathogenesis of suicidal behavior.

Chronobiological hypothalamic-pituitary-thyroid axis status and antidepressant outcome in major depression.

BACKGROUND: We previously demonstrated that the difference between 2300h and 0800h TSH response to protirelin (TRH) tests on the same day (ΔΔTSH test) is an improved measure in detecting hypothalamic-pituitary-thyroid (HPT) axis dysregulation in depression. This chronobiological index (1) is reduced in about three quarters of major depressed inpatients, and (2) is normalized after successful antidepressant treatment. In the present study, we examined whether early changes in HPT axis activity during the first 2 weeks of antidepressant treatment could be associated with subsequent outcome. METHODS: The ΔΔTSH test was performed in 50 drug-free DSM-IV euthyroid major depressed inpatients and 50 hospitalized controls. After 2 weeks of antidepressant treatment the ΔΔTSH test was repeated in all inpatients. Antidepressant response was evaluated after 6 weeks of treatment. RESULTS: At baseline, ΔΔTSH values were significantly lower in patients compared to controls and 38 patients (76%) showed reduced ΔΔTSH values (i.e., <2.5mU/L). After 2 weeks of antidepressant treatment, 20 patients showed ΔΔTSH normalization (among them 18 were subsequent remitters), while 18 patients did not normalize their ΔΔTSH (among them 15 were non-remitters) (p<0.00001). Among the 12 patients who had normal ΔΔTSH values at baseline, 8 out 9 who had still normal values after 2 weeks of treatment were remitters, while the 3 with worsening HPT axis function (i.e., reduced ΔΔTSH value after 2 weeks of treatment) were non-remitters (p<0.02). A logistic regression analysis revealed that ΔΔTSH levels after 2 weeks of treatment could predict the probability of remission (odds ratio [OR]=2.11, 95% confidence interval [CI]=1.31-3.41). CONCLUSIONS: Our results suggest that after 2 weeks of antidepressant treatment: (1) chronobiological restoration of the HPT axis activity precedes clinical remission, and (2) alteration of the HPT axis is associated with treatment resistance.

What future for neuroendocrinology in psychiatry?

In psychiatry, neuroendocrine techniques were initially considered a potential "window into the brain" by indirectly marking central nervous system limbic dysfunction. At present this conception has evolved, owing to significant progress over the last decades demonstrating direct involvement of neuropeptides and neurohormones in psychiatric diseases. In a synchronic perspective, neuroendocrine investigations evaluate a functional status at a given moment in the evolution of the disease, which results from both etiopathogenic processes and compensatory homeostatic mechanisms. These vital physiological changes appear to be potential targets for novel hormonally based pharmacotherapies. However, in the past few years, the interest for the study of neuroendocrine dysregulations in psychiatric patients has declined. In order to better understand this relative disinterest, this article will attempt to shed light on strengths and limitations of the neuroendocrine approaches in psychiatry. It is necessary to bear in mind that the usefulness of these techniques in the clinical, pathophysiological and therapeutic fields depends largely on the selectivity of stimuli and the appropriateness of the methodologies used. Owing to the complexity of the clinical phenomena, multifactorial approaches (combining several neuroendocrine challenge tests to imaging, immunological, neurophysiological, neurochemical and/or genetic techniques) are to be privileged in psychiatric investigations. Despite the inherent limitations of these approaches, due to their technical and ethical constraints, the neuroendocrine strategy can inform modern clinical practice and lead to new breakthroughs in future science and practice.

Prolactin and thyroid hormone levels are associated with suicide attempts in psychiatric patients.

The aim of this study is to evaluate biological factors associated with recent suicidal attempts in a naturalistic sample. A total of 439 patients suffering from major depression disorder (MDD), bipolar disorder (BD) and psychotic disorders (schizophrenia, schizoaffective disorder and psychosis not otherwise specified), who were consecutively assessed in the Emergency Department of an Italian Hospital (January 2008-December 2009), were included. In the whole sample, suicide attempters and non-attempters differed with regard to free triiodothyronine (FT3) and prolactin values only. A univariate general linear model indicated significant effects of sex (F(1;379)=9.29; P=0.002), suicidal status (F(1;379)=4.49; P=0.04) and the interaction between sex and suicidal status (F(1;379)=5.17; P=0.02) on prolactin levels. A multinomial logistic regression model indicated that suicidal attempters were 2.27 times (odds ratio (OR)=0.44; 95% confidence interval (95%CI): 0.23/0.82; P=0.01) less likely to have higher FT3 values than non-attempters; while prolactin values failed to reach statistical significance (OR=0.99; 95%CI: 0.98/1.00; P=0.051). Both prolactin and thyroid hormones may be involved in a complex compensatory mechanism to correct reduced central serotonin activity. Further studies may help in understanding how these findings can be used by clinicians in assessing suicide risk.

Bases neurobiológicas de vulnerabilidad psiquiátrica a lo largo de las etapas de la vida hormonal de la mujer / Neurobiological bases of psychiatric vulnerability through the female hormonal stages

Women are about twice more likely than men to suffer from depression, it has been hypothesized that reproductive events (i.e., premenstrual, pre and postpartum, menopausal transition) may represent vulnerability periods for depression, in part because of a heightened sensitivity to intense hormonal fluctuations. 1) Most women report physical or emotional symptoms premenstrually, some being severe enough to be diagnosed as premenstrual dysphoric disorder (PMDD); some recent studies suggest that PMDD is biologically different from major depression; 2) While pregnancy does not increase the risk for depression, women with a past history of depression are at risk for recurrent episodes or relapse if antidepressant medications are discontinued; 3) Hormonal changes during the postpartum period may trigger symptoms of postpartum depression; 4) Almost half of perimenopausal women are clinically depressed, and over a third experience their first episode of depression in the perimenopausal period. The increase in major depressive episodes during this period has been linked to erratic gonadal hormonal changes.

Las mujeres poseen alrededor del doble de posibilidades que los hombres de sufrir depresión. Se ha planteado como hipótesis que los eventos reproductivos (ej. premenstrual, pre y postparto, transición menopáusica) pueden representar periodos de vulnerabilidad para la depresión, en parte, debido a la elevada sensibilidad a las intensas fluctuaciones hormonales. 1) La mayoría de las mujeres informan síntomas físicos o emocionales premenstruales, siendo algunos suficientemente severos para ser diagnosticados como trastorno disfórico premenstrual (TDPM); algunos estudios recientes sugieren que el TDPM es biológicamente diferente de la depresión mayor; 2) Mientras que el embarazo no aumenta el riesgo para la depresión, las mujeres con una historia pasada de depresión están en riesgo para episodios recurrentes o recaída si se discontinúan los medicamentos antidepresivos; 3) Los cambios hormonales durante el período del postparto pueden gatillar síntomas de depresión postparto; 4) Casi la mitad de las mujeres perimenopáusicas están clínicamente deprimidas y sobre un tercio experimenta su primer episodio de depresión en el período perimenopáusico. El aumento de los episodios depresivos mayores durante este período se ha relacionado con cambios erráticos de las hormonas gonadales.

Neurobiología del estrés / Neurobiology of stress

Classically stress is defined as a threatening of homeostasis to which the organism, in order to survive, responds with a large number ofadaptative responses implicating the activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Acute stress response involves several brain regions (e.g. prefrontal cortex, amygdala, hippocampus, hypothalamus) where sex differences have been evidenced both in structure and function; limbic andforebrain regions are extremely sensitive to hormones released during stress, especially glucocorticoids. Chronic stress, on the other hand, causes adaptive plasticity in the brain, in which local neurotransmitters as well as systemic hormones interact to produce structural as well as functional changes. Stress-induced structural/functional changes in brain regions may contribute to the development of psychiatric disorders such as depression and post-traumatic stress disorder. It is suggested that gonadal hormone influences provide complex contributions to sex differences in vulnerabilities to stress-related diseases.

Clásicamente el estrés se define como una amenaza a la homeostasis, frente a la cual el organismo, para sobrevivir, reacciona con un gran número de respuestas adaptativas que implican la activación del sistema nervioso simpático y el eje hipotalámico-pituitario-adrenal. La respuesta al estrés agudo incluye varias regiones cerebrales (ej. cortex prefrontal, amígdala, hipocampo, hipotálamo) donde se han evidenciado las diferencias sexuales, tanto en la estructura como en la función; las regiones límbicas y cerebrales anteriores son extremadamente sensibles a las hormonas liberadas durante el estrés, especialmente los glucocorticoides. Por otra parte, el estrés crónico causa plasticidad adaptativa en el cerebro, en el cual los neurotransmisores locales, como también las hormonas sistémicas, interactúan para producir cambios estructurales y funcionales. Los cambios estructurales/funcionales en las regiones cerebrales inducidos por el estrés pueden contribuir al desarrollo de desórdenes psiquiátricos, tales como depresión y trastorno por estrés postraumático. Se ha sugerido que las influencias de la hormona gonadal proporcionan complejas contribuciones a las diferencias sexuales en las vulnerabilidades a las enfermedades relacionadas con el estrés.

Thyroid axis activity and suicidal behavior in depressed patients.

The aim of this study was to investigate the relationship between suicidal behavior and hypothalamic-pituitary thyroid (HPT) axis activity in depressed patients. The serum levels of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were evaluated before and after 0800 and 2300 h thyrotropin-releasing hormone (TRH) challenges, on the same day, in 95 medication-free DSM-IV euthyroid major depressed inpatients and 44 healthy hospitalized controls. Compared to controls: (1) patients with a positive suicide history (PSH; n=53) showed lower basal FT4 (at 0800 h: p<0.005; at 2300 h: p<0.03), but normal FT3 levels, while patients with a negative suicide history (NSH; n=42) showed normal FT4 and FT3 levels; (2) TSH responses to TRH (DeltaTSH) were blunted in NSHs (at 0800 h: p<0.03; at 2300 h: p<0.00001), but not in PSHs; (3) both NSHs and PSHs showed lower DeltaDeltaTSH values (differences between 2300 h-DeltaTSH and 0800 h-DeltaTSH) (p<0.000001 and p<0.003, respectively). Compared to NSHs, basal FT4 levels were reduced in PSHs (at 0800 h: p<0.002; at 2300h: p<0.006). HPT parameters were not significantly different between recent suicide attempters (n=32) and past suicide attempters (n=21). However, compared to controls, recent suicide attempters showed lower 2300 h-DeltaTSH (p<0.04) and DeltaDeltaTSH (p<0.002) values, and lower basal FT4 values (at 0800 h: p<0.006; at 2300 h: p<0.02). Our results, obtained in a large sample of depressed inpatients, indicate that various degrees of HPT axis dysregulation are associated with the history of suicide.