outbursts of laughter and/or crying. pba has a high prevalence rate with estimates of 1.5–2 million cases in the united states alone. multiple sclerosis multiple sclerosis is a chronic demyelinating disease in which the myelin sheaths of cells in the brain and spinal cord are irreparably damaged. symptoms of depression are very common in patients at all stages of the disease and may be exacerbated by medical treatments, notably interferon beta-1a. neurotoxicity various compounds have been shown to have neurotoxic effects many of which have been implicated as having a causal relationship in the development of depression. cigarette smoking there has been research which suggests a correlation between cigarette smoking and depression. the results of one recent study suggest that smoking cigarettes may have a direct causal effect on the development of depression. there have been various studies done showing a positive link between smoking, suicidal ideation and suicide attempts. in a study conducted among nurses, those smoking between 1-24 cigarettes per day had twice the suicide risk; 25 cigarettes or more, 4 times the suicide risk, than those who had never smoked. in a study of 300,000 male u.s. army soldiers, a definitive link between suicide and smoking was observed with those smoking over a pack a day having twice the suicide rate of non-smokers. link between smoking depression and suicide "current daily smoking, but not past smoking, predicted the subsequent occurrence of suicidal thoughts or attempt." "it would seem unwise, nevertheless, to rule out the possibility that smoking might be among the antecedent factors associated with the development of depression." "abstinence from cigarettes for prolonged periods may be associated with a decrease in depressive symptomatology." "the stress induction model of smoking suggests, however, that smoking causes stress and concomitant negative affect." medication various medications have been suspected of having a causal relation in the development of depression; this has been classified as "organic mood syndrome". some classes of medication such as those used to treat hypertension, have been recognized for decades as having a definitive relationship with the development of depression. monitoring of those taking medications which have shown a relationship with depression is often indicated, as well as the necessity of factoring in the use of such medications in the diagnostic process. topical tretinoin (retin-a); derived from vitamin a and used for various medical conditions such as in topical solutions used to treat acne vulgaris. although applied externally to the skin, it may enter the bloodstream and cross the blood brain barrier where it may have neurotoxic effects. interferons; proteins produced by the human body, three types have been identified alpha, beta and gamma. synthetic versions are utilized in various medications used to treat different medical conditions such as the use of interferon-alpha in cancer treatment and hepatitis c treatment. all three classes of interferons may cause depression and suicidal ideation. chronic exposure to organophosphates the neuropsychiatric effects of chronic organophosphate exposure include mood disorders, suicidal thinking and behaviour, cognitive impairment and chronic fatigue. neuropsychiatric bipolar disorder bipolar disorder is frequently misdiagnosed as major depression, and is thus treated with antidepressants alone which is not only not efficacious it is often contraindicated as it may exacerbate hypomania, mania, or cycling between moods. there is ongoing debate about whether this should be classified as a separate disorder because individuals diagnosed with major depression often experience some hypomanic symptoms, indicating a continuum between the two. nutritional deficiencies nutrition plays a key role in every facet of maintaining proper physical and psychological wellbeing. insufficient or inadequate nutrition can have a profound effect on mental health. the emerging field of nutritional neuroscience explores the various connections between diet, neurological functioning and mental health. vitamin b6: pyridoxal phosphate (plp), the active form of b6, is a cofactor in the dopamine serotonin pathway, a deficiency in vitamin b6 may cause depressive symptoms. folate (vitamin b9) – vitamin b12 cobalamin: low blood plasma and particularly red cell folate and diminished levels of vitamin b12 have been found in patients with depressive disorders. "e suggest that oral doses of both folic acid (800 μg/(mcg) daily) and vitamin b12 (1 mg daily) should be tried to improve treatment outcome in depression." long chain fatty acids: higher levels of omega-6 and lower levels of omega-3 fatty acids has been associated with depression and behavioral change. vitamin d deficiency is associated with depression sleep disorders insomnia: while the inability to fall asleep is often a symptom of depression, it can also in some instances serve as the trigger for developing a depressive disorder. it can be transient, acute or chronic. it can be a primary disorder or a co-morbid one. restless legs syndrome (rls), also known as wittmaack-ekbom's syndrome, is characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. it most commonly affects the legs, but can also affect the arms or torso, and even phantom limbs. restless leg syndrome has been associated with major depressive disorder. "adjusted odds ratio for diagnosis of major depressive disorder... suggested a strong association between restless legs syndrome and major depressive disorder and/or panic disorder." sleep apnea is a sleep disorder characterized by pauses in breathing during sleep. each episode, called an apnea, lasts long enough for one or more breaths to be missed; such episodes occur repeatedly throughout the sleep cycle. undiagnosed sleep apnea may cause or contribute to the severity of depression. circadian rhythm sleep disorders, of which few clinicians are aware, often go untreated or are treated inappropriately, as when misdiagnosed as either primary insomnia or as a psychiatric condition.