Confused Sex Orientation

Sexual orientation refers to an individual’s personal and social identity involving behaviors, ideas, and/or emotions concerning sexuality. The ultimate causes and mechanisms of sexual orientation development in humans remain unclear and many theories are speculative and controversial. However, advances in neuroscience explain and illustrate characteristics linked to sexual orientation.

Developmental neurobiology

Many theories concerning the development of sexual orientation involve fetal neural development, with proposed models illustrating prenatal hormone exposure, maternal immunity, and developmental instability. Other proposed factors include genetic control of sexual orientation. No conclusive evidence has been shown that environmental or learned effects are responsible for the development of non-typical sexual orientation.

Prenatal androgen model

Sexual dimorphisms in the brain and behavior among vertebrates are accounted for the by the influence of gonadal steroidal androgens as demonstrated in animal models over the past few decades. The prenatal androgen model of homosexuality describes the neuro-developmental effects of fetal exposure to these hormones. Homosexual men are exposed to high androgen levels early in development, explaining their tendency to be less right-handed and by extension the hyper-masculinized traits observed. It is currently argued that temporal and local variations in androgen exposure to a fetus’s developing brain is a factor in the pathways determining homosexuality. Recent research has been performed to find somatic markers for prenatal hormonal exposure which have been found to show variation based on sexual orientation in healthy adult individuals.

Other evidence supporting the role of testosterone and prenatal hormones in sexual orientation development include observations of male subjects with cloacal exstrophy who were sex-assigned as female during birth only later to declare themselves male. This supports the theory that the prenatal testosterone surge is crucial for gender identity development. Additionally, females whose mothers were exposed to diethylstilbestrol (DES) during pregnancy show higher rates of bi- and homosexuality.

2D:4D digit ratio

The best, non-invasive, marker of prenatal hormone exposure is the digit ratio of the second and fourth finger lengths (2D:4D ratio), a known sexually dimorphic measure (males showing lower ratios than females). Patients with androgen over-exposure (such as in congenital adrenal hyperplasia) show lower 2D:4D ratios, providing evidence linking prenatal androgen exposure as key to this feature. XY individuals with androgen insensitivity syndrome due to a dysfunctional gene for the androgen receptor present as women and have feminine digit ratios, as would be predicted if androgenic hormones affect digit ratios. This finding also demonstrates that the sex difference in digit ratio is unrelated to the Y chromosome per se.

Additionally, the 2D:4D ratio has been shown to be affected by variation in the androgen receptor gene in men. The ratio of testosterone to estrogen in amniotic fluid has also been found to be negatively correlated with the 2D:4D ratio.Independent studies that homosexual women have masculinized (lower) digit ratios, and homosexual men show either hyper-masculinized or feminized ratios. These findings reinforce the prenatal androgen model - abnormal prenatal hormone exposure is related to the development of human homosexuality.

Auditory evoked potentials

Studies of the central nervous system processing of auditory sensation, aspects of which has been linked to prenatal androgen exposure, to click-stimuli have shown that homosexual women have masculinized responses while homosexual men have hyper-masculinized responses.

Fraternal birth order effect

Studies show that homosexual men have higher numbers of older male siblings. This finding led to the development of the fraternal birth order effect theory of homosexuality, stating that a mother becomes progressively immunized to successive male children, leading to increased chances of homosexuality in later male children. The mechanism involves the mother producing increasing anti-male antibodies to male-specific antigens expressed in male fetuses. These antibodies are thought to block the full masculinization of the fetal brain by “binding to and inactivating male-specific molecules located on the surface of fetal brain cells” thus preventing the morphogenesis of masculinized sexual preferences. Estimations that there is a 33% increase in chances of homosexuality in a male child with each older male sibling. A BBC study reported that the fraternal birth order effect does not apply to left-handed homosexual males. Support for this theory is given by data that the effect holds true only for biological brothers and the chances of male homosexuality is not increased by the number of older stepbrothers or adoptive siblings. This theory does not apply to the development of female homosexuality.

Developmental instability and handedness

The chances of being left-handed may be increased in homosexual populations. In comparison with a heterosexual sample, a 2000 meta-analysis of earlier studies  showed that homosexual men have approximately one-third (34%) higher odds of being left-handed while homosexual women have almost twice (91%) higher odds of being so. It has been proposed that non-right-handedness (including ambidexterity) is related to homosexuality through developmental instability. Developmental instability refers to the level of vulnerability to environmental and genetic stresses and perturbations during development.
However, as the effect is not particularly strong, the results remain disputed, even though several studies appear to show a relationship.

Structural differences

Postmortem and imaging studies over the past two decades have revealed structural differences in both global structures and sexually-related brain structures between heterosexual and homosexual subjects.

Hypothalamus

The hypothalamus is known to be involved in sex differences in reproductive behavior, mediating responses in menstrual cycles in women and specifically the anterior hypothalamus of the brain helps regulate male-typical sexual behavior. Recently, the hypothalamus has been linked to gender identity and sexual orientation.
The hypothalamus is also linked to sexual orientation through findings that show that activity of aromatase, an important enzyme converting androgens to estrogens, is high in the preoptic hypothalamic region of mammals during the pre- and neonatal periods. This activity is linked to sexual differentiation and may be a basis in structural and functional sexual differences playing a role in mediating the sexual orientation development due to prenatal hormonal exposure.

The suprachiasmatic nucleus (SCN) of the anterior hypothalamus has also been found to relate to sexual orientation, with homosexual men having twice as large of a vasopressin-containing subnucleus of the SCN than heterosexuals. This might be a neurological explanation for the finding that homosexual men arise and retire earlier each day than heterosexuals, as it is known that the SCN is involved in modulating human circadian rhythms. Analogously, in a rat model study, it was found that male rats treated with an aromatase inhibitor showed a partner preference for females when tested in the late dark phase but showed homosexual mating preferences when tested in the early dark phase, implicating the involvement of the SCN in sexual orientation in other species.

Cerebral asymmetry

The size of the brain’s hemispheres is a sexually dimorphic trait in which men tend to show asymmetry in the volumes of their hemispheres while women show volumetric symmetry. A recent volumetric MRI study that homosexuals showed sex-atypical symmetry: homosexual men showed hemispheric volumes to be symmetric similar to heterosexual women and homosexual women showed asymmetry in hemispheric volumes as heterosexual men do. These findings demonstrate a global neurological difference in brain structures showing sex-atypical characteristics associated with sexual orientation.

Anterior commissure

The anterior commissure, a bundle of white matter fibers connecting the 2 cerebral hemispheres, was found to be larger in homosexual men and heterosexual women than in heterosexual men. This finding provides a possible anatomical basis for higher inter-hemispheric functional connections in homosexuals explaining why homosexual men and heterosexual women show language circuit functional symmetry in out performing heterosexual men in verbal tests.

Functional differences

Neural processing in response to specific stimuli and sexually-biased cognitive tasks have been found to be correlated with an individual’s sexual orientation.

Response to pheromones

Two proposed human pheromones; the progesterone derivative 4 (AND) and an estrogen-like steroid estra have been shown to have sexual orientation specific responses in activating the neural circuits of the anterior hypothalamus in homosexual and heterosexual subjects. Anterior hypothalamus is involved in processing reproductive functions and recent evidence suggests it helps integrate hormonal and sensory cues involved in sexual behavior and sexual preference.

Recent functional neuro-imaging experiments have shown that the presentation of AND, found in male sweat, as an olfactory stimuli produced normal olfactory responses in heterosexual men and homosexual women, while activating the anterior hypothalamus in homosexual men and heterosexual women. The proposed pheromone EST, found in the urine of pregnant women, produces normal olfactory activation in homosexual men and heterosexual women while homosexual women and heterosexual men demonstrated sexually-related hypothalamic responses.

Homosexual men showed the same sexually-related functional responses to these stimuli as heterosexual women and homosexual women responded like heterosexual men. This research conducted by Berglund and Savicoverall that AND and EST induce “sex-specific effects on the autonomic nervous system” and that the stimuli elicited a response pathway that was dependent on the subject’s sexual orientation rather than phenotypic sex.

Functional cerebral asymmetry

Differences in neural processing and cognitive tasks have been found in relation to sexual orientation. In cerebral lateralization / sexual orientation; prenatal hormonal events would lead to functional cerebral asymmetries related to sexual orientation.

Certain cognitive tasks are known to be sexually dimorphic. The better verbal ability of women is associated with reduced lateralization of language tasks while the male advantage in spatial reasoning corresponds to marked cerebral lateralization. Sexual orientation effects in some of these tasks have been found in recent studies.

In the Vincent Mechanical Diagrams test, a dot detection divided field measure of functional cerebral asymmetry, homosexual men performed the same as heterosexual women with both scoring lower than heterosexual men displaying less asymmetry. Additionally, homosexual men display higher verbal performance IQ scores on subtests of the Wecshler Adult Intelligence Scale, in concordance with female testing patterns. On several other tests, including a male-biased targeted throwing task and a female-biased Purdue pegboard test, the performance of homosexual men and heterosexual women showed no statistical difference from each other, while both significantly differed from heterosexual men.

Additionally, reduced asymmetry was found in a magnetoencephelographic study in which MEG-based source location estimates of an auditory evoked signal is found to be hemispherically symmetric in heterosexual women and homosexual men, while asymmetric in heterosexual men.

Response to visual sexual stimuli

A recent functional magnetic resonance imaging study has demonstrated that upon viewing of both heterosexual and homosexual erotic visual stimuli, only those images corresponding to the subject’s sexual orientation produced hypothalamic activation patterns associated with sexual arousal. The response of heterosexuals viewing heterosexual adult videos showed the same pattern of sexual arousing neural processing as homosexuals viewing same-sex adult videos, while the viewing of the opposite orientation’s images did not elicit the same response

Remember, sex is fun, there are no norms in sexuality, each and every one can express his sex life the way he or she feels it suits him or her. Science (OMS) do not consider homosexuality or bisexuality as pathology. Unfortunately Sex in general is still a taboo nearly all around the planet.

 All Genders Unsatisfied Sex Life

Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm.

To maximize the benefits of medications and behavioural techniques in the management of sexual dysfunction it is important to have a comprehensive approach to the problem, A thorough sexual history and assessment of general health and other sexual problems (if any) are very important. Assessing (performance) anxiety, guilt (associated with masturbation in many Indian men), stress and worry are integral to the optimal management of sexual dysfunction. When a sexual problem is managed inappropriately or sub-optimally, it is very likely that the condition will subside immediately but re-emerge after a while. When this cycle continues, it strongly reinforces failure that eventually make clients not to access any help and suffer it all their life. So, it is important to get a thorough assessment from professionals and therapists who are qualified to manage sexual problems. Internet-based information is good for gaining knowledge about sexual functioning and sexual problem but not for self-diagnosis and/or self-management.

Categories

Sexual dysfunction disorders may be classified into four categories: sexual desire disorders, arousal disorders, orgasm disorders and pain disorders.

Sexual desire disorders

Sexual desire disorders or decreased libido are characterised by a lack or absence for some period of time of sexual desire or libido for sexual activity or of sexual fantasies. The condition ranges from a general lack of sexual desire to a lack of sexual desire for the current partner. The condition may have started after a period of normal sexual functioning or the person may always have had no/low sexual desire.

The causes vary considerably, but include a possible decrease in the production of normal estrogen in women or testosterone in both men and women. Other causes may be aging, fatigue, pregnancy, medications (such as the SSRIs) or psychiatric conditions, such as depression and anxiety. Loss of libido from SSRIs usually reverses after SSRIs are discontinued, but in some cases it does not. This has been called PSSD; however, this is not a classification that would be found in any current medical text. While a number of causes for low sexual desire are often cited, only some of these have ever been the object of empirical research. Many rely entirely on the impressions of therapists.

Sexual arousal disorders

Sexual arousal disorders were previously known as frigidity in women and impotence in men, though these have now been replaced with less judgmental terms. Impotence is now known as erectile dysfunction, and frigidity has been replaced with a number of terms describing specific problems with, for example, desire or arousal.

For both men and women, these conditions can manifest themselves as an aversion to, and avoidance of, sexual contact with a partner. In men, there may be partial or complete failure to attain or maintain an erection, or a lack of sexual excitement and pleasure in sexual activity.

There may be medical causes to these disorders, such as decreased blood flow or lack of vaginal lubrication. Chronic disease can also contribute, as well as the nature of the relationship between the partners. Unlike disorders of orgasm, as the success of Viagra (sildenafil citrate) attests, most erectile disorders in men are primarily physical conditions.

Erectile dysfunction

Erectile dysfunction or impotence is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis. There are various underlying causes, such as damage to the nervi erigentes which prevents or delays erection, or diabetes, which simply decreases blood flow to the tissue in the penis, many of which are medically reversible.

The causes of erectile dysfunction may be psychological or physical. Psychological impotence can often be helped by almost anything that the patient believes in; there is a very strong placebo effect. Physical damage is much more severe. One leading physical cause of ED is continual or severe damage taken to the nervi erigentes. These nerves course beside the prostate arising from the sacral plexus and can be damaged in prostatic and colo-rectal surgeries.

Due to its embarrassing nature and the shame felt by sufferers, the subject was taboo for a long time, and is the subject of many urban legends. Folk remedies have long been advocated, with some being advertised widely since the 1930s. The introduction of perhaps the first pharmacologically effective remedy for impotence, sildenafil name Viagra), in the 1990s caused a wave of public attention, propelled in part by the news-worthiness of stories about it and heavy advertising.

The Latin term impotentia coeundi describes simple inability to insert the penis into the vagina. It is now mostly replaced by more precise terms.

Orgasm disorders

Orgasm disorders are persistent delays or absence of orgasm following a normal sexual excitement phase. The disorder can have physical, psychological, or pharmacological origins. SSRI antidepressants are a common pharmaceutical culprit, as they can delay orgasm or eliminate it entirely.

Sexual pain disorders

Sexual pain disorders affect women almost exclusively and are known as dyspareunia (painful intercourse) or vaginismus (an involuntary spasm of the muscles of the vaginal wall that interferes with intercourse).

Dyspareunia may be caused by insufficient lubrication (vaginal dryness) in women. Poor lubrication may result from insufficient excitement and stimulation, or from hormonal changes caused by menopause, pregnancy, or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sex.

It is unclear exactly what causes vaginismus, but it is thought that past sexual trauma (such as rape or abuse) may play a role. Another female sexual pain disorder is called vulvodynia or vulvar vestibulitis. In this condition, women experience burning pain during sex which seems to be related to problems with the skin in the vulvar and vaginal areas. The cause is unknown.

Uncommon sexual disorders in men

Erectile dysfunction from vascular disease is usually seen only amongst elderly individuals who have atherosclerosis. Vascular disease is common in individuals who have diabetes, peripheral vascular disease, hypertension and those who smoke. Any time blood flow to the penis is impaired, erectile dysfunction is the end result.

Hormone deficiency is a relatively rare cause of erectile dysfunction. In individuals with testicular failure like klinefelter's syndrome, or those who have had radiation therapy, chemotherapy or childhood exposure to mumps virus, the testes may fail and not produce testosterone. Other hormonal causes of erectile failure include brain tumors, hyperthyroidism, hypothyroidism or disorders of the adrenal gland.

Structural abnormalities of the penis like Peyronie's disease can make sexual intercourse difficult. The disease is characterized by thick fibrous bands in the penis which leads to a deformed-looking penis.

Drugs are also a cause of erectile dysfunction. Individuals who take drugs to lower blood pressure, uses antipsychotics, antidepressants, sedatives, narcotics, antacids or alcohol can have problems with sexual function and loss of libido.

Priapism is a painful erection that occurs for several hours and occurs in the absence of sexual stimulation. This condition develops when blood gets trapped in the penis and is unable to drain out. If the condition is not promptly treated, it can lead to severe scarring and permanent loss of erectile function. The disorder occurs in young men and children. Individuals with sickle-cell disease and those who abuse certain medications can often develop this disorder.

Causes

There are many factors which may result in a person experiencing a sexual dysfunction. These may result from emotional or physical causes.

Sexual dysfunction may arise from emotional factors, including interpersonal or psychological problems. Interpersonal problems may arise from marital or relationship problems, or from a lack of trust and open communication between partners, and psychological problems may be the result of depression, sexual fears or guilt, past sexual trauma, sexual disorders, among others.

Sexual dysfunction is especially common among people who have anxiety disorders. Ordinary anxiousness can obviously cause erectile dysfunction in men without psychiatric problems, but clinically diagnosable disorders such as panic disorder commonly cause avoidance of intercourse and premature ejaculation. Pain during intercourse is often a comorbidity of anxiety disorders among women.

Sexual activity may also be impacted by physical factors. These would include use of drugs, such as alcohol, nicotine, narcotics, stimulants, antihypertensives, antihistamines, and some psychotherapeutic drugs. For women, almost any physiological change that affects the reproductive system-premenstrual syndrome, pregnancy, postpartum, menopause can have an adverse effect on libido. Injuries to the back may also impact sexual activity, as would problems with an enlarged prostate gland, problems with blood supply, nerve damage (as in spinal cord injuries).

Disease, such as diabetic neuropathy, multiple sclerosis, tumors, and, rarely, tertiary syphilis may also impact on the activity, as would failure of various organ systems (such as the heart and lungs), endocrine disorders (thyroid, pituitary, or adrenal gland problems), hormonal deficiencies (low testosterone, estrogen, or androgens), and some birth defects.

Symptoms

Psychological sexual disorders

The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders lists the following psychological sexual disorders:

•    Hypoactive sexual desire disorder (see also asexuality, which is not classified as a disorder)
•    Bestiality

•    Sexual aversion disorder (avoidance of or lack of desire for sexual intercourse)
•    Female sexual arousal disorder (failure of normal lubricating arousal response)
•    Male erectile disorder

•    Female orgasmic disorder (see Anorgasmia)

•    Male orgasmic disorder (see Anorgasmia)

•    Premature ejaculation

•    Dyspareunia

•    Vaginismus

•    Paraphilias

•    PTSD due to genital mutilation or childhood sexual abuse

•    Anhedonia

•    Gender identity disorder

•    Dysphoria

•    Premenstrual syndrome

Other sexual problems

•    Sexual dissatisfaction (non-specific)

•    Lack of sexual desire

•    Anorgasmia

•    Impotence

•    Sexually transmitted diseases

•    Delay or absence of ejaculation, despite adequate stimulation

•    Inability to control timing of ejaculation

•    Inability to relax vaginal muscles enough to allow intercourse

•    Inadequate vaginal lubrication preceding and during intercourse

•    Burning pain on the vulva or in the vagina with contact to those areas

•    Unhappiness or confusion related to sexual orientation

•    Transsexual and transgender people may have sexual problems

        (before or after   surgery), though actually being transgendered or transsexual is not

       a sexual problem in itself.

•    Persistent sexual arousal syndrome

•    Post SSRI Sexual Dysfunction

•    Sexual addiction

•    Hypersexuality

•    All forms of Female genital cutting

Other related problems

•    Pedophilia

•    Necrophilia

•    Zoophilia

•    Infertility

•    Paraphilia

Treatment for males

Since in many men the cause of sexual dysfunction is related to anxiety about performance, psychotherapy can help. Situational anxiety arises from an earlier bad incident or lack of experience. This anxiety often leads to development of fear towards sexual activity and avoidance. In return evading leads to a cycle of increased anxiety and desensitization of the penis. In some cases, erectile dysfunction may be due to marital disharmony. Marriage counseling sessions are recommended in this situation.

Lifestyle changes such as discontinuing smoking, drug or alcohol abuse can also help in some types of erectile dysfunction.

 Trauma Fixation

Posttraumatic stress disorder(PTSD) is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma. This event may involve the threat of death to oneself or to someone else, or to one's own or someone else's physical, sexual, or psychological integrity, overwhelming the individual's ability to cope. As an effect of psychological trauma, PTSD is less frequent and more enduring than the more commonly seen acute stress response. Diagnostic symptoms for PTSD include re-experiencing the original trauma(s) through flashbacks or nightmares, avoidance of stimuli associated with the trauma, and increased arousal - such as difficulty falling or staying asleep, anger, and hypervigilance. Formal diagnostic criteria (both DSM-IV-TR and ICD-10) require that the symptoms last more than one month and cause significant impairment in social, occupational, or other important areas of functioning.

Classification

Post-traumatic stress disorder is classified as an anxiety disorder, characterized by aversive anxiety-related experiences, behaviors, and physiological responses that develop after exposure to a psychologically traumatic event (sometimes months after). Its features persist for longer than 30 days, which distinguishes it from the briefer acute stress disorder. These persisting posttraumatic stress symptoms cause significant disruptions of one or more important areas of life function. It has three sub-forms: acute, chronic, and delayed-onset.

Causes

Psychological trauma

PTSD is believed to be caused by either physical trauma or psychological trauma, or more frequently a combination of both. According to Atkinson et al. (2000) PTSD is more likely to be caused by physical or psychological trauma caused by humans — such as rape, war, or terrorist attack — than by trauma caused by natural disasters. Possible sources of trauma include experiencing or witnessing childhood or adult physical, emotional or sexual abuse. In addition, experiencing or witnessing an event perceived as life-threatening such as physical assault, adult experiences of sexual assault, accidents, drug addiction, illnesses, medical complications, or employment in occupations exposed to war (such as soldiers) or disaster (such as emergency service workers).

Traumatic events that may cause PTSD symptoms to develop include violent assault, kidnapping, sexual assault, torture, being a hostage, prisoner of war or concentration camp victim, experiencing a disaster, violent automobile accidents or getting a diagnosis of a life-threatening illness. Children or adults may develop PTSD symptoms by experiencing bullying or mobbing. Approximately 25% of children exposed to family violence can experience PTSD. Preliminary research suggests that child abuse may interact with mutations in a stress-related gene to increase the risk of PTSD in adults.

Multiple studies show that parental PTSD and other posttraumatic disturbances in parental psychological functioning can, despite a traumatized parent's best efforts, interfere with their response to their child as well as their child's response to trauma. Parents with violence-related PTSD may, for example, inadvertently expose their children to developmentally inappropriate violent media due to their need to manage their own emotional deregulation. Clinical findingsthat a failure to provide adequate treatment to children after they suffer a traumatic experience, depending on their vulnerability and the severity of the trauma, will ultimately lead to PTSD symptoms in adulthood.

Evolutionary psychology

Evolutionary psychology views different types of fears and reactions caused by fears as adaptations that may have been useful in the ancestral environment in order to avoid or cope with various threats. Mammals generally display several defensive behaviors roughly dependent on how close the threat is: avoidance, vigilant immobility, withdrawal, aggressive defense, appeasement, and finally complete frozen immobility (the last possibly to confuse a predator's attack reflex or to simulate a dead and contaminated body). PTSD may correspond to and be caused by over-activation of such fear circuits. Thus, PTSD avoidance behaviors may correspond to mammal avoidance of and withdrawal from threats. Heightened memory of past threats may increase avoidance of similar situations in the future as well as be a prerequisite for analyzing the past threat and develop better defensive behaviors if the threat should reoccur. PTSD hyper-arousal may correspond to vigilant immobility and aggressive defense. Complex post-traumatic stress disorder (and phenomena such as the Stockholm syndrome) may in part correspond to the appeasement stage and possibly the frozen immobility stage.

There may be evolutionary explanations for differences in resilience to traumatic events. Thus, PTSD is rare following traumatic fire which may be explained by events such as forest fires long being part of the evolutionary history of mammals. On the other hand, PTSD is much more common following modern warfare, which may be explained by modern warfare being a new development and very unlike the quick inter-group raids that are argued to have characterized the paleolithic.

Neuroendocrinology

PTSD symptoms may result when a traumatic event causes an over-reactive adrenaline response, which creates deep neurological patterns in the brain. These patterns can persist long after the event that triggered the fear, making an individual hyper-responsive to future fearful situations.

PTSD displays biochemical changes in the brain and body that differ from other psychiatric disorders such as major depression. Individuals diagnosed with PTSD respond more strongly to a dexamethasone suppression test than individuals diagnosed with clinical depression.

In addition, most people with PTSD also show a low secretion of cortisol and high secretion of catecholamines in urine, with a norepinephrine/cortisol ratio consequently higher than comparable non-diagnosed individuals. This is in contrast to the normative fight-or-flight response, in which both catecholamine and cortisol levels are elevated after exposure to a stressor.

Brain catecholamine levels are high, and corticotropin-releasing factor (CRF) concentrations are high. Together, these findings suggest abnormality in the hypothalamic-pituitary-adrenal (HPA) axis.

Given the strong cortisol suppression to dexamethasone in PTSD, HPA axis abnormalities are likely predicated on strong negative feedback inhibition of cortisol, itself likely due to an increased sensitivity of glucocorticoid receptors. Some researchers have associated the response to stress in PTSD with long-term exposure to high levels of norepinephrine and low levels of cortisol, a pattern associated with improved learning in animals.

Translating this reaction to human conditions gives a pathophysiological explanation for PTSD by a maladaptive learning pathway to fear response through a hypersensitive, hyperreactive and hyperresponsive HPA axis.

Low cortisol levels may predispose individuals to PTSD: Following war trauma, Swedish soldiers serving in Bosnia and Herzegovina with low pre-service salivary cortisol levels had a higher risk of reacting with PTSD symptoms, following war trauma, than soldiers with normal pre-service levels. Because cortisol is normally important in restoring homeostasis after the stress response, it is thought that trauma survivors with low cortisol experience a poorly contained—that is, longer and more distressing—response, setting the stage for PTSD.

However, there is considerable controversy within the medical community regarding the neurobiology of PTSD. A review of existing studies on this subject showed no clear relationship between cortisol levels and PTSD. Only a slight majority have found a decrease in cortisol levels while others have found no effect or even an increase.

Neuroanatomy

Regions of the brain associated with stress and posttraumatic stress disorder.

Three areas of the brain whose function may be altered in PTSD have been identified: the prefrontal cortex, amygdala and hippocampus. Much of this research has utilised PTSD victims from the Vietnam War. For example, a prospective study using the Vietnam Head Injury Study showed that damage to the prefrontal cortex may actually be protective against later development of PTSD. In a study by Gurvits et al., combat veterans of the Vietnam War with PTSD showed a 20% reduction in the volume of their hippocampus compared with veterans who suffered no such symptoms. This finding could not be replicated in chronic PTSD patients traumatized at an air show plane crash in 1988 (Ramstein, Germany).

In human studies, the amygdala has been shown to be strongly involved in the formation of emotional memories, especially fear-related memories. Neuroimaging studies in humans have revealed both morphological and functional aspects of PTSD.

The amygdalocentric model of PTSD proposes that it is associated with hyperarousal of the amygdala and insufficient top-down control by the medial prefrontal cortex and the hippocampus particularly during extinction. This is consistent with an interpretation of PTSD as a syndrome of deficient extinction ability. A study at the European Neuroscience Institute-Goettingen (Germany) found that fear extinction-induced IGF2/IGFBP7 signaling promotes the survival of 17–19-day-old newborn hippocampal neurons. This suggests that therapeutic strategies that enhance IGF2 signaling and adult neurogenesis might be suitable to treat diseases linked to excessive fear memory such as PTSD. Further animal and clinical research into the amygdala and fear conditioning may suggest additional treatments for the condition.

Genetics

There is evidence that susceptibility to PTSD is hereditary. For twin pairs exposed to combat in Vietnam, having a monozygotic (identical) twin with PTSD was associated with an increased risk of the co-twin having PTSD compared to twins that were dizygotic (non-identical twins). Recently, it has been found that several single-nucleotide polymorphisms (SNPs) in FK506 binding protein 5 (FKBP5) interact with childhood trauma to predict severity of adult PTSD. These findings suggest that individuals with these SNPs who are abused as children are more susceptible to PTSD as adults.

This is particularly interesting given that FKBP5 SNPs have previously been associated with peritraumatic dissociation (that is, dissociation at the time of the trauma), which has itself been shown to be predictive of PTSD. Furthermore, FKBP5 may be less expressed in those with current PTSD.

Another recent study found a single SNP in a putative estrogen response element on ADCYAP1R1 (encodes pituitary adenylate cyclase-activating polypeptide type I receptor or PAC1) to predict PTSD diagnosis and symptoms in females. Incidentally, this SNP is also associated with fear discrimination. The study suggests that perturbations in the PACAP-PAC1 pathway are involved in abnormal stress responses underlying PTSD.

Risk factors

Although most people (50-90%) encounter trauma over a lifetime, only about 8% develop full PTSD. Vulnerability to PTSD presumably stems from an interaction of biological diathesis, early childhood developmental experiences, and trauma severity. Predictor models have consistently found that childhood trauma, chronic adversity, and familial stressors increase risk for PTSD as well as risk for biological markers of risk for PTSD after a traumatic event in adulthood. This effect of childhood trauma, which is not well understood, may be a marker for both traumatic experiences and attachment problems. Proximity to, duration of, and severity of the trauma also make an impact; and interpersonal traumas cause more problems than impersonal ones.

Military experience

Schnurr, Lunney, and Sengupta identified risk factors for the development of PTSD in Vietnam veterans. Among those are:

•    Hispanic ethnicity, coming from an unstable family, being punished severely during childhood, childhood asocial behavior and depression as pre-military factors
•    War-zone exposure, peritraumatic dissociation, depression as military factors
•    Recent stressful life events, post-Vietnam trauma and depression as post-military factors.

They also identified certain protective factors, such as:

•    Japanese-American ethnicity, high school degree or college education, older age at entry to war, higher socioeconomic status and a more positive paternal relationship as pre-military protective factors.

•    Social support at homecoming and current social support as post-military factors. Other research also indicates the protective effects of social support in averting PTSD or facilitating recovery if it develops.

There may also be an attitudinal component; for example, a soldier who believes that they will not sustain injuries may be more likely to develop symptoms of PTSD than one who anticipates the possibility, should either be wounded. Likewise, the later incidence of suicide among those injured in home fires above those injured in fires in the workplace suggests this possibility.

Foster care

In the Casey Family Northwest Alumni Study, conducted in conjunction with researchers from the Harvard Medical School in Oregon and Washington state, the rate of PTSD in adults who were in foster care for one year between the ages of 14-18 was found to be higher than that of combat veterans. Up to 25 percent of those in the study meet the diagnostic criteria for PTSD as compared to 12-13 percent of Iraq war veterans and 15 percent of Vietnam War veterans, and a rate of 4 percent in the general population. The recovery rate for foster home alumni was 28.2% as opposed to 47% in the general population.

Diagnosis

Criteria

The diagnostic criteria for PTSD, stipulated in the Diagnostic and Statistical Manual of Mental Disorders IV (Text Revision) (DSM-IV-TR), may be summarized as:

A: Exposure to a traumatic event

This must have involved both (a) loss of "physical integrity", or risk of serious injury or death, to self or others, and (b) a response to the event that involved intense fear, horror or helplessness (or in children, the response must involve disorganized or agitated behavior). (The DSM-IV-TR criterion differs substantially from the previous DSM-III-R stressor criterion, which specified the traumatic event should be of a type that would cause "significant symptoms of distress in almost anyone," and that the event was "outside the range of usual human experience.")

B: Persistent re-experiencing

One or more of these must be present in the victim: flashback memories, recurring distressing dreams, subjective re-experiencing of the traumatic event(s), or intense negative psychological or physiological response to any objective or subjective reminder of the traumatic event(s).

C: Persistent avoidance and emotional numbing

This involves a sufficient level of:

•    avoidance of stimuli associated with the trauma, such as certain thoughts or feelings, or talking about the event(s);

•    avoidance of behaviors, places, or people that might lead to distressing memories;
•    inability to recall major parts of the trauma(s), or decreased involvement in significant life activities;

•    decreased capacity (down to complete inability) to feel certain feelings;
•    an expectation that one's future will be somehow constrained in ways not normal to other people.

D: Persistent symptoms of increased arousal not present before

These are all physiological response issues, such as difficulty falling or staying asleep, or problems with anger, concentration, or hypervigilance.

E: Duration of symptoms for more than 1 month

If all other criteria are present, but 30 days have not elapsed, the individual is diagnosed with Acute stress disorder.

F: Significant impairment

The symptoms reported must lead to "clinically significant distress or impairment" of major domains of life activity, such as social relations, occupational activities, or other "important areas of functioning".

Assessment

Since the introduction of DSM-IV, the number of possible events which might be used to diagnose PTSD has increased; one study suggests that the increase is around 50%.Various scales exist to measure the severity and frequency of PTSD symptoms. Standardized screening tools such as Trauma Screening Questionnaire and PTSD Symptom Scale can be used to detect possible symptoms of posttraumatic stress disorder, and suggest the need for a formal diagnosis.

Research-based alternative symptom groups

Emerging factor analytic research suggests that PTSD symptoms group empirically into four clusters, not the three currently described in the Diagnostic and Statistical Manual of Mental Disorders. One model supported by this research divides the traditional avoidance symptoms into a cluster of numbing symptoms (such as loss of interest and feeling emotionally numb) and a cluster of behavioral avoidance symptoms (such as avoiding reminders of the trauma). An alternative model adds a fourth cluster of dysphoric symptoms. These include symptoms of emotional numbing, as well as anger, sleep disturbance, and difficulty concentrating.

DSM-5 proposed diagnostic criteria changes

In preparation for the May 2013 release of the DSM-5, the fifth version of the American Psychiatric Association's diagnostic manual, draft diagnostic criteria was released for public comment, followed by a two-year period of field testing. Proposed changes to the criteria (subject to ongoing review and research) include the following:
•    Criterion A (prior exposure to traumatic events) is more specifically stated, and evaluation of an individual's emotional response at the time (current criterion A2) is dropped.
•    Several items in Criterion B (intrusion symptoms) are rewritten to add or augment certain distinctions now considered important.

•    Special consideration is given to developmentally appropriate criteria for use with children and adolescents. This is especially evident in the restated Criterion B - intrusion symptoms. Development of age-specific criteria for diagnosis of PTSD is ongoing at this time.
•    Criterion C (avoidance and numbing) has been split into "C" and "D":

• -Criterion C (new version) now focuses solely on avoidance of behaviors or physical or temporal reminders of the traumatic experience(s). What were formerly two symptoms are now three, due to slight changes in descriptions.
• -New Criterion D focuses on negative alterations in cognition and mood associated with the traumatic event(s), and contains two new symptoms, one expanded symptom, and four largely unchanged symptoms specified in the previous criteria.
• -Criterion E (formerly "D"), which focuses on increased arousal and reactivity, contains one modestly revised, one entirely new, and four unchanged symptoms.
• -Criterion F (formerly "E") still requires duration of symptoms to have been at least one month.
• -Criterion G (formerly "F") stipulates symptom impact ("disturbance") in the same way as before.
• -The "acute" vs "delayed" distinction is dropped; the "delayed" specifier is considered appropriate if clinical symptom onset is no sooner than 6 months after the traumatic event(s).
• "Developmental trauma disorder", a proposed new diagnosis, was still under discussion at the time of the draft publication.

Management

Prevention and early intervention strategies

Modest benefits have been seen from early access to cognitive behavioral therapy, as well as from some medications such as propranolol. Critical incident stress management has been suggested as a means of preventing PTSD but subsequent studies suggest the likelihood of its producing iatrogenic outcomes. A review of multiple studies confirmed the finding of no benefit to trauma survivors from single-session early-response interventions, as well as a failure of blanket multiple-session prevention interventions to yield a benefit to all participants (some were even harmed).

Preventive Treatments

Psychological debriefing

The first form of preventive treatment is that of a psychological debriefing. Psychological debriefing is the most often used preventive measure. One of the main reasons for this is the relative ease with which this treatment can be given to individuals directly following an event. It consists of interviews that are meant to allow individuals to directly confront the event and share their feelings with the counselor and to help structure their memories of the event. However, while this form of therapy is the most often used it is actually the least effective. Studies have had mixed findings concerning psychological debriefings and have ranged from being of significant help to helping in the formation of PTSD in individuals who would otherwise have not developed PTSD. The greater number of studies tends to simply find that it is neither overly beneficial nor harmful.

Risk Targeted Interventions

Risk targeted interventions are those that attempt to mitigate specific formative information or events. It can target modeling normal behaviors, instruction on a task or giving information on the event. For example, rape victims were given an instruction video on the procedures for a forensic exam. Also included in the video was advice on how to identify and stop avoidance behavior and control anxiety. Finally, the individuals modeling the forensic exam were shown to be calm and relaxed. PTSD diagnosis for those who saw the video were thirty three percent less than for those who went through the standard forensic procedure.

Psychobiological Treatments

Psychobiological treatments have also found success, especially with cortisol. Psychobiological treatments target biological changes that occur after a traumatic event. They also attempt to chemically alter learning or memory formation. Cortisol treatments after a traumatic event have found success in mitigating later diagnosis of PTSD. As discussed earlier Cortisol is often lower in individuals who are at risk of PTSD after a traumatic event than their counterparts. By increasing cortisol levels to normal levels this has been shown to reduce arousal post event as well prevent GR upregulation.

Stepped Collaborative Care

Stepped collaborative care is where individuals who are at risk are monitored for symptoms. As symptoms of PTSD appear the level of care is increased to treat those symptoms.

Psychotherapeutic interventions

Many forms of psychotherapy have been advocated for trauma-related problems such as PTSD. Basic counseling practices common to many treatment responses for PTSD include education about the condition and provision of safety and support.

The psychotherapy programs with the strongest demonstrated efficacy include cognitive behavioral programs, variants of exposure therapy, stress inoculation training (SIT), variants of cognitive therapy (CT), eye movement desensitization and reprocessing (EMDR), and many combinations of these procedures.

EMDR or trauma-focused cognitive behavioral therapy (TFCBT) was recommended as first-line treatments for trauma victims in a 2007 review; however, "the evidence base [for EMDR] was not as strong as that for TFCBT ... Furthermore, there was limited evidence that TFCBT and EMDR were superior to supportive/non-directive treatments, hence it is highly unlikely that their effectiveness is due to non-specific factors such as attention." A meta-analytic comparison of EMDR and cognitive behavioral therapy found both protocols indistinguishable in terms of effectiveness in treating PTSD.

Behavioral and Cognitive Behavioral therapy

Cognitive behavioral therapy (CBT) seeks to change the way a trauma victim feels and acts by changing the patterns of thinking and/or behavior responsible for negative emotions. CBT have been proven to be an effective treatment for PTSD, and is currently considered the standard of care for PTSD by the United States Department of Defense. In CBT, individuals learn to identify thoughts that make them feel afraid or upset, and replace them with less distressing thoughts. The goal is to understand how certain thoughts about events cause PTSD-related stress.

Recent research on contextually based third-generation behavior therapies suggests that they may produce results comparable to some of the better validated therapies. Many of these therapy methods have a significant element of exposure, and have demonstrated success in treating the primary problems of PTSD and co-occurring depressive symptoms.

Exposure therapy is a type of cognitive behavioral therapy that involves assisting trauma survivors to re-experience distressing trauma-related memories and reminders in order to facilitate habituation and successful emotional processing of the trauma memory. Most exposure therapy programs include both imaginal confrontation with the traumatic memories and real-life exposure to trauma reminders; this therapy modality is well supported by clinical evidence. Indeed, the success of exposure-based therapies has raised the question of whether exposure is a necessary ingredient in the treatment of PTSD. Some organizations have endorsed the need for exposure. The US Department of Veterans Affairs has been actively training mental health treatment staff in prolonged exposure therapy and Cognitive Processing Therapy in an effort to better treat US Veterans with PTSD.

Eye movement desensitization and reprocessing

Eye movement desensitization and reprocessing (EMDR) is specifically targeted as a treatment for PTSD. Based on the evidence of controlled research, the American Psychiatric Association and the United States Department of Veterans Affairs and Department of Defense have placed EMDR in the highest category of effectiveness and research support in the treatment of trauma.

Interpersonal psychotherapy

Other approaches, particularly involving social supports, may also be important. An open trial of interpersonal psychotherapy reported high rates of remission from PTSD symptoms without using exposure. A current, NIMH-funded trial in New York City is now (and into 2013) comparing interpersonal psychotherapy, prolonged exposure therapy, and relaxation therapy.

Medication

A variety of medications has shown adjunctive benefit in reducing PTSD symptoms, but "there is no clear drug treatment for PTSD". Positive symptoms (re-experiencing, hypervigilance, increased arousal) generally respond better to medication than negative symptoms (avoidance, withdrawal), and it is recommended that any drug trial last for at least 6–8 weeks.

Symptom management:

Potentially useful medication classes

SSRIs (selective serotonin reuptake inhibitors). SSRIs are considered to be a first-line drug treatment. SSRIs for which there are data to support use include: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.

Among the anti-depressants described in this section, bupropion and venlafaxine have the lowest patient drop-out rates. Sertraline, fluoxetine, and nefazodone have a modestly higher drop-out rate (~15%), and the heterocyclics and paroxetine have the highest rates (~20%+).Where drop-out is caused or feared because of medication side-effects, it should be remembered that most patients do not experience such side-effects.

Alpha-adrenergic antagonists. Prazosin ("Minipress"), in a small study of combat veterans, has shown substantial benefit in relieving or reducing nightmares. Clonidine ("Catapres") can be helpful with startle, hyperarousal, and general autonomic hyperexcitability.

Anti-convulsants, mood stabilizers, anti-aggression agents. Carbamazepine ("Tegretol") has likely benefit in reducing arousal symptoms involving noxious affect, as well as mood or aggression. Topiramate ("Topamax") has been effective in achieving major reductions in flashbacks and nightmares, and no reduction of effect was seen over time. Zolpidem ("Ambien") has also proven useful in treating sleep disturbances.
Lamotrigine ("Lamictal") may be useful in reducing reexperiencing symptoms, as well as avoidance and emotional numbing. Valproic acid ("Depakene") and has shown reduction of symptoms of irritability, aggression, and impulsiveness, and in reducing flashbacks. Similarly, lithium carbonate has worked to control mood and aggressions (but not anxiety) symptoms. Buspirone ("BuSpar") has an effect similar to that of lithium, with the additional benefit of working to reduce hyperarousal symptoms.

Antipsychotics. Risperidone can be used to help with dissociation, mood issues, and aggression.

Atypical antidepressants. Nefazodone ("Serzone") can be effective with sleep disturbance symptoms, and with secondary depression, anxiety, and sexual dysfunction symptoms. Trazodone ("Desyrel") can also reduce or eliminate problems with disturbed sleep, and with anger and anxiety.

Beta blockers. Propranolol ("Inderal") has demonstrated possibilities in reducing hyperarousal symptoms, including sleep disturbances.

Benzodiazepines. These can be used with caution for short-term anxiety relief, hyperarousal, and sleep disturbance. While benzodiazepines can alleviate acute anxiety, there is no consistent evidence that they can stop the development of PTSD, or are at all effective in the treatment of posttraumatic stress disorder. Additionally benzodiazepines may reduce the effectiveness of psychotherapeutic interventions and there is some evidence that benzodiazepines may contribute to the development and chronification of PTSD. Other drawbacks include the risk of developing a benzodiazepine dependence and withdrawal syndrome; additionally individuals with PTSD are at an increased risk of abusing benzodiazepines.

Glucocorticoids. Additionally, post-stress high dose corticosterone administration was recently found to reduce 'PTSD-like' behaviors in a rat model of PTSD. In this study, corticosterone impaired memory performance, suggesting that it may reduce risk for PTSD by interfering with consolidation of traumatic memories. The neurodegenerative effects of the glucocorticoids, however, may prove this treatment counterproductive.

Heterocyclic / Tricyclic anti-depressants anti-depressants. Amitriptyline ("Elavil") has shown benefit for positive distress symptoms, and for avoidance, and Imipramine ("Tofranil") has shown benefit for intrusive symptoms.

Monoamine-oxidase inhibitors (MAOIs). Phenelzine ("Nardil") has for some time been observed to be effective with hyperarousal and depression, and is especially effective with nightmares.

Miscellaneous other medications. Clinical trials evaluating methylene-dioxy-methamphetamine (MDMA, "Ecstasy") in conjunction with psychotherapy are being conducted in Switzerland and Israel.

Symptom prevention: potentially useful medication classes

Some medications have shown benefit in preventing PTSD or reducing its incidence, when given in close proximity to a traumatic event. These medications include:

Alpha-adrenergic antagonists. Anecdotal report of success in using clonidine ("Catapres") to reduce traumatic stress symptoms suggests that it may have benefit in preventing PTSD.

Beta blockers. Propranolol ("Inderal"), similarly to clonidine, may be useful if there are significant symptoms of "over-arousal". These may inhibit the formation of traumatic memories by blocking adrenaline's effects on the amygdala.

Glucocorticoids. There is some evidence suggesting that administering glucocorticoids immediately after a traumatic experience may help prevent PTSD. Several studies have shown that individuals who receive high doses of hydrocortisone for treatment of septic shock, or following surgery, have a lower incidence and fewer symptoms of PTSD.

Opiates. In a retrospective analysis of combat injury field data for US troops in Iraq, it was found that those who received morphine in the early stages of their treatment had a significantly lower rate of subsequent PTSD, when compared with those who did not receive morphine at that time.

Medications by symptom group affected

Medications can affect one or more of the symptoms, in one or more of the three major symptom classes involved in diagnosing PTSD, which can be summarized in the following table:

class    Symptom    Medication

Reexperiencing

intrusive recall    amitriptyline; fluoxetine; imipramine; lamotrigine; sertraline   

intrusive reexperiencing    amitriptyline; fluoxetine; imipramine; nefazodone; sertraline

(women only); topiramate;

sleep disturbance, nightmares    benzodiazepines; carbamazepine; clonidine;

nefazodone; phenelzine; prazosin; topiramate; trazodone; zolpidem

dissociative recall risperidone

intense psychological distress (anger, anxiety) when exposed to reminders of traumatic event(s)    benzodiazepines; buspirone; carbamazepine; lithium (not for anxiety); nefazodone; trazodone

Avoidance

avoidance    amitriptyline; fluoxetine; lamotrigine; nefazodone; sertraline

feelings of detachment or estrangement from others    amitriptyline; risperidone
restricted range of affect (numbing)    amitriptyline; lamotrigine; sertraline (women only)

Hyperarousal

general hyperarousal    amitriptyline; nefazodone; phenelzine; sertraline (women only)

sleep disturbance, nightmares    benzodiazepines; carbamazepine; clonidine; nefazodone; phenelzine; trazodone; zolpidem

irritability, anger (and impulsiveness)    carbamazepine; nefazodone; valproic acid

anger    buspirone; fluoxetine; lithium; trazodone

aggression    risperidone

exaggerated startle response; general autonomic hyperexcitability    benzodiazepines;

buspirone; carbamazepine; clonidine; propranolol; valproic acid

Some medications can also help with symptoms which may occur secondary to PTSD.

Secondary symptom    Medication

depression    nefazodone; phenelzine

dream content distortions    nefazodone

relapse of symptoms    carbamazepine;

self-mutilation    clonidine; buprenorphine

sexual function reduction    nefazodone

sleep hours reduction    nefazodone

Medication and self-medication issues and risks with PTSD

Alcohol abuse and drug abuse commonly co-occur with PTSD. Recovery from posttraumatic stress disorder or other anxiety disorders may be hindered, or the condition worsened, by medication or substance overuse, abuse, or dependence; resolving these problems can bring about a marked improvement in an individual's mental health status and anxiety levels.

Benzodiazepines are risky in several ways. They can be especially addictive when PTSD is present, and this is especially true with the fast-acting ones. Dis-inhibition upon initiation of treatment is another risk with this medication class. Finally, termination of the drug can be especially difficult. Recovery from benzodiazepine abuse or dependence tends to take a lot longer than recovery from alcohol abuse or dependence, but people can regain their previous good health. PTSD symptoms may temporarily worsen however, during alcohol withdrawal or benzodiazepine withdrawal.

Yohimbine (not considered specifically appropriate for PTSD) increases arousal by increasing release of endogenous norepinephrine, and can worsen PTSD symptoms.