Suicide represents a deeply tragic outcome in clinical practice. While predicting suicide in individuals remains challenging due to its complex and multifactorial nature, a significant proportion, ranging from 30% to 70%, of suicides occur among patients receiving some form of treatment [1–3]. Gaining a deeper understanding of the interplay between biological, clinical, and situational factors contributing to suicide is crucial for clinicians. This knowledge empowers them to effectively recognize risk factors and implement timely clinical interventions aimed at mitigating suicide risk.
1. Diagnosis of Suicidal Behavior
Suicide can occur across the spectrum of psychiatric diagnoses. However, research consistently indicates a heightened prevalence of suicide in individuals with mood disorders, particularly major depressive disorder and bipolar disorder [4]. Numerous other psychiatric conditions also exhibit elevated suicide rates, including mixed drug abuse, alcohol and opioid abuse, eating disorders, schizophrenia, personality disorders, and even acute stress disorders [4, 5]. It is hypothesized that the underlying factors contributing to suicide may be mood depression, severe anxiety, and heightened trait impulsivity, which can manifest across various psychiatric disorders [6]. The increased risk of suicide is particularly pronounced in bipolar disorder [7]. Furthermore, the impact of early childhood abuse as a significant factor in elevated suicide risk has gained increasing recognition [8]. Child abuse is considered to be linked to both the early onset of mood disorders and the development of impulsivity [8].
2. Behavioral Traits and Suicide Risk
Recent studies focusing on suicidal behavior have highlighted the significance of behavioral traits that mediate suicide risk. Strong evidence supports the familial-genetic transmission of suicidal behavior, and a growing body of research points to specific behavioral traits as mediators of this risk [8–12].
Angry impulsivity has been consistently identified as a prominent risk factor for suicidal behavior [6, 8–12]. Impulsivity as a trait is observed across various diagnostic categories but shows a strong association with bipolar disorder, substance abuse, cluster B personality disorders, and a history of early childhood abuse [6, 9]. A study involving prisoners with a family history of suicide revealed elevated scores for neuroticism and hostility, in addition to impulsivity [13].
Suicide risk factors can be broadly categorized into chronic high-risk factors and immediate or acute high-risk factors. A prior suicide attempt stands out as the most frequently reported risk factor for suicide in numerous studies [4, 14]. While a history of suicide attempts is a significant indicator, it’s important to note that the actual suicide rate among individuals with prior attempts is approximately 5%–10%. A previous suicide attempt can be indicative of underlying impulsivity. However, relying solely on past suicidal behavior for risk assessment can be misleading. Isometsa and Lonnqvist [15] reported that in a large study of suicides, approximately 62% of male suicides and 38% of female suicides occurred on their first attempt.
Suicidal ideation, especially when coupled with a suicide plan, is widely recognized as a strong predictor of suicide risk. However, it is a common misconception that denying suicidal ideation or plans automatically indicates low risk. Isometsa et al.’s [16] study of 100 suicide cases where patients had seen their psychiatrist on the same day revealed that only 22% of those who committed suicide had reported suicidal thoughts during their last visit. Similarly, in a study of 76 inpatient suicides by Busch et al. [17], 76% of inpatients had nursing notes documenting their denial of suicidal ideation as the last communication before their suicide. It is a natural human tendency to assume that if a positive indicator suggests risk, a negative one implies low risk. However, this does not hold true for suicide. A patient at high risk might experience suicidal impulses shortly after denying suicidal intent or might be deliberately concealing their intentions to avoid intervention. Therefore, a denial of suicidal intent or plan should be considered a neutral factor, to be evaluated alongside the patient’s history, life circumstances, and current clinical status.
Angry impulsivity is a persistent chronic high suicide risk factor, which, when combined with specific situations [6, 8, 18–20], mood states, or anxiety, can trigger suicidal behavior. Other chronic risk factors include male gender, living alone, handgun ownership, and a history of significant chronic pain [21–24].
In suicide risk assessment, it is not uncommon for a patient to present as a chronic high risk for suicide but not be in acute risk at the time of evaluation. The presence of chronic risk factors may influence a clinician’s judgment regarding a patient’s current risk level. The term “high-risk group” acknowledges that while individual suicide prediction is not possible, certain risk factors can categorize a patient into a group with elevated risk, warranting management accordingly. While chronic risk factors can be valuable for actuarial prediction within groups, the patient’s clinical state and current life situation at the time of assessment, combined with chronic risk factor consideration, provide the most crucial information for clinicians to determine if a patient should be managed as being in an acute high-risk group for suicide.
The patient’s clinical state at the time of assessment, considered in the context of their recent clinical history and recent life stressors or losses, is paramount in determining risk group status and guiding treatment planning.
3. Clinical State and Imminent Risk
A thorough evaluation of a patient’s current clinical state and life situation is the most critical source of information to ascertain whether a patient is at high acute risk for suicide. Recent clinical worsening of depressive or anxiety symptoms is highly significant and necessitates a comprehensive suicide assessment. The presence of a mixed state, or mixed features where depressive symptoms coexist with manic or hypomanic features, is often associated with heightened activity, impulsivity, and severe anxiety/agitation, leading to increased suicidal behavior risk.
Critical events associated with high risk include recent psychiatric inpatient admission or discharge, with the risk remaining elevated for up to a year post-discharge [15, 25–27]. Recent experiences such as the loss of a loved one, divorce, major financial setbacks, job loss, a serious medical diagnosis (e.g., cancer diagnosis), or legal problems can precipitate a suicidal state, particularly in individuals with pre-existing depression or high impulsivity [5, 28–30]. Assessing a patient’s coping mechanisms in response to such “life blows” is crucial when these events have occurred.
A clinical state assessment should evaluate how the patient is managing life stress and whether negative traits like negative affect have recently intensified. Has the patient increased alcohol consumption, which can amplify angry impulsivity [25, 31]? Is the patient exhibiting increased comorbid anxiety, agitation, or substance abuse [25, 31]?
4. Comorbid Anxiety: Dysphoric Arousal and Suicide
The nature of “comorbid” anxiety in mood disorders remains under investigation. It’s unclear whether it represents a distinct comorbid anxiety disorder or is an intrinsic aspect of mood disorder symptomatology. Current diagnostic systems differentiate symptoms of mood disorders like major depression and bipolar depression from anxiety disorders. However, a study using the Schedule for Affective Disorders and Schizophrenia, Current (SADS-C), which rates symptom presence and severity in major depression, found moderate anxiety in 62% of patients and panic attacks in 29% [32]. Another study by Clayton et al. [33] examining over 300 patients with primary depression revealed a high prevalence of anxiety symptoms across a wide severity range. The frequency of anxiety onset after depression and depression in patients with pre-existing generalized anxiety disorder (GAD) raises questions about whether anxiety should be considered a core symptom criterion for major depression and bipolar depression, with or without mixed states.
In 1990, Fawcett et al. [25] conducted a prospective study of 13 suicides within the first year and 34 suicides over 10 years in a predominantly hospitalized sample of patients with major affective disorders (N = 954). While prior suicide attempts, suicidal ideation severity, and hopelessness severity were not significantly greater in the 13 first-year suicides compared to non-suicides, they were significantly associated with suicide over a 2- to 10-year period [25]. However, psychic anxiety and panic attack levels were significantly more severe or frequent at baseline in the 13 suicide patients compared to non-suicides. A subsequent study by Hall et al. [34] found elevated psychic anxiety levels in 90% of 100 patients hospitalized for suicide attempts, as measured by SADS-C psychic anxiety scores reflecting the month prior to the attempt.
In 2003, Busch et al. [17] reviewed 76 inpatient suicide cases. Chart reviews spanning the week before suicide revealed that 79% of cases showed severe anxiety and/or agitation for at least 3–7 days prior to suicide (despite 76% denying suicidal thoughts in their last communication with nursing staff) [17]. In 2007, Simon et al. [35] reviewed 32,000 bipolar disorder cases from managed care databases, finding that comorbid GAD diagnoses were associated with elevated suicide rates (odds ratio [OR] = 1.8) and suicide attempts (OR = 1.4). While comorbid substance abuse elevated suicide attempt rates, it did not increase suicide risk in this sample [35].
A 2008 study by Stordal et al. [36] involving 60,995 subjects in Norway, who self-rated monthly on the Hospital Anxiety and Depression scale from 1995 to 1997, showed that the 10,670 male and 3933 female suicides exhibited a simultaneous peak in depression and anxiety severity ratings during their suicide month (r = 0.72, p = .01), peaking in spring and early fall (p = .01). Finally, a study by Pfeiffer et al. [37] of over 887,000 veterans treated for depression demonstrated that suicide was significantly associated with comorbid diagnoses of GAD, anxiety disorder NOS, and panic disorder, but not PTSD or other anxiety disorders (OR = 1.8). Furthermore, a significant increase in suicide was linked to antianxiety medication use (OR = 1.8), with further elevation in patients on high-dose antianxiety medications (OR = 2.2). This suggests that anxiety severity, rather than specific anxiety disorder diagnoses, may be associated with suicide, as indicated in the Fawcett et al. [32] study.
While suicidality studies in bipolar patients versus completed suicide have not found prior suicide attempts associated with comorbid GAD, it is argued that suicide attempts and completed suicide are not entirely equivalent. These studies also did not measure anxiety severity at the time of attempts, only past history, thus not fully addressing the presented issues [37].
A recent cross-national study by Nock et al. [6] of suicide attempts in over 100,000 subjects found suicide linked to anxiety co-occurrence. Nock proposed that while depression is associated with suicidal thoughts, disorders characterized by anxiety and poor impulse control lead to suicidal behavior [6]. This was supported by Brown et al. [38] in personality and mood disorders, linked to low cerebrospinal fluid (CSF) 5-hydroxy indolacetic acid (5-HIAA) levels, indicating decreased brain serotonin turnover associated with impulsivity. Swann et al. [20] reported increased impulsivity with more frequent suicide attempts, and Taylor et al. [39] found increased anxiety leading to increased impulsivity in bipolar patients.
In 1965, Bunney and Fawcett [40] reported three suicide cases with elevated 24-hour urinary excretion of 17-hydroxycorticosteroids (a cortisol metabolite) in the days leading up to suicide (patients at NIMH). A subsequent paper detailed more cases [41]. Later, the dexamethasone suppression test, measuring hypophyseal pituitary adrenal (HPA) system overactivity, showed HPA overactivity in suicide patients [42–46]. Except for Sachar et al.’s [47] schizophrenic suicide patient with elevated 17-hydroxycorticoids exhibiting “ego disintegration” but no anxiety or dysphoric hyperarousal, these reports lacked anxiety findings. This raises the question of whether patients on the verge of suicide experience state anxiety or dysphoric hyperarousal, correlating with HPA axis overactivity.
Increased anxiety symptoms in major depression or bipolar disorder patients may be intrinsic to the primary mood disorder, not secondary to comorbid anxiety. It is hoped that DSM-V will include an anxiety severity dimension for all mood disorder diagnoses, highlighting anxiety’s significant role in mood disorder outcomes and emphasizing successful treatment of severe anxiety in these patients.
The STAR*D study reported that severe anxiety predicted poor antidepressant treatment response [48, 49]. Coryell and colleagues’ analyses [50, 51] demonstrated that elevated baseline anxiety severity predicts significantly longer depressive episodes in major mood disorder patients followed for 16–20 years.
Severe anxiety or dysphoric hyperarousal is a crucial clinical state variable to assess and address in suicide risk management. Increased impulsivity related to anxiety/arousal in response to negative events should also be considered and managed. While not universally present before suicide, inpatient suicide studies found it in 76% of cases [17]. The authors’ review of ∼100 outpatient suicide cases suggests severe anxiety/dysphoric hyperarousal in over half. Severe anxiety/dysphoric hyperarousal may be a common clinical indicator of imminent suicide risk. However, a subgroup of patients meticulously planning suicide may show no anxiety/hyperarousal signs, appearing calm and resolute, concealing their plans, making intervention very difficult.
5. Comorbid Substance Abuse and Suicide Risk
Another critical comorbid factor requiring assessment is increased substance abuse. Alcohol and other substance abuse are well-established risk factors for suicidal behavior [31]. The collaborative study found recent onset of moderate alcohol abuse in the weeks/days before suicide, suggesting self-treatment for untreated severe anxiety and insomnia. Alcohol and other substances’ disinhibiting effects are well-known, increasing impulsivity and impairing judgment, thereby elevating suicide risk.
Harris and Baraclough’s review [4] found elevated suicide rates in patients with mixed drug abuse, opioid abuse, and alcohol abuse. Increased abuse severity may indicate heightened suicidal behavior risk.
6. The Case for a Suicidal Behavior Diagnosis
Given that suicide/suicidal behavior occurs across psychiatric diagnoses, exhibits independent familial transmission with genetic risk, and is statistically predicted by prior suicidal behavior, the question arises: should suicidal behavior be a separate diagnostic category?
A suicidal behavior disorder diagnosis could enhance clinical focus on suicide prevention interventions for vulnerable patients. Current evidence suggests patients with suicidal behavior history receive inadequate pharmacologic treatment, similar to other depressed patients [52].
Significant scientific data supports a suicidal behavior diagnosis, including genetic transmission factors from twin studies, diagnosis-independent familial transmission, biological risk markers, and subsequent suicidal behavior prediction from past behavior [53].
However, concerns exist that this diagnosis could be stigmatizing and harm the doctor-patient relationship. Also, given that many suicides are first attempts [14], such a diagnosis might only modestly improve acute suicide risk assessment. Would a separate suicidal behavior disorder diagnosis improve clinical care for suicidal patients? Such a category could aid research in better detecting and treating acute suicide risk. Appropriate diagnostic criteria would need to be defined: prior suicide attempts, suicide plans/rehearsals, or immediate/chronic suicidal ideation?
From a clinical practice perspective, a major gap is the lack of clinical or biological markers to detect acute suicide risk in individuals. Given the difficulty in predicting individual behavior, this area of knowledge may always be limited. However, any information relevant to detecting acute high-risk states is valuable in suicide prevention efforts.
7. Summary and Conclusions
Suicide occurs across diagnoses, stemming from mood depression, hopelessness, severe anxiety, and increased impulsivity, often linked to early abuse histories and past suicidal behavior, and situational factors like symptom worsening, frequently in the context of major loss. Chronic risk factors like early childhood abuse, impulsivity, substance abuse history, living alone, and past suicide attempts are crucial to identify and consider. Acute risk factors such as severe anxiety, insomnia, increased impulsivity, symptom worsening, suicide plans/preparation, and recognition of major loss may allow for intervention before a lethal attempt. Biological trait factors like impulsivity, often related to early abuse, substance abuse, and changes in HPA, adrenergic response, and serotonin systems, appear across diagnoses. In the presence of mood depression, common across diagnoses and always in mood disorders, suicidal ideas can develop and translate into attempts when these factors are present, often triggered by adverse events or symptom exacerbation.
Further understanding of these pathways to suicide will enhance clinical knowledge for timely intervention and improve the capacity to prevent acute suicidal risk states in vulnerable individuals.
REFERENCES
1.Luoma JB, Martin CE, Oearson JL. Contact with mental health and primary care providers before suicide: A review of the evidence. Am J Psychiatry. 2002;159:908–916. [PMC free article: PMC5072576] [PubMed: 12042175]
2.Baraclough B, Bunch J, Nelson B, Sainsbury P. A hundred cases of suicide: Clinical aspects. Br J Psychiatry. 1974;125:355–373. [PubMed: 4425774]
3.Robins E. The Final Months. Oxford University Press; Oxford, U.K.: 1981. p. 47.
4.Harris EC, Baraclough B. Suicide as an outcome for mental disorders. A meta-analysis. Br J Psychiatry. 1997;170:205–228. [PubMed: 9229027]
5.Gradus JL, Qin P, Lincoln AK, Miller M, Lawler E, Sørensen HT, Lash TL. Acute stress reaction and completed suicide. Int J Epidemiol. 2010;39:1478–1484. [PubMed: 20624822]
6.Nock MK, Hwang I, Sampson N, Kessler RC, Angermeyer M, Beautrais A, Borges G, Bromet E, Bruffaerts R, de Girolamo G, de Graaf R, Florescu S, Gureje O, Haro JM, Hu C, Huang Y, Karam EG, Kawakami N, Kovess V, Levinson D, Posada-Villa J, Sagar R, Tomov T, Viana MC, Williams DR. Cross-national analysis of the associations among mental disorders and suicidal behavior: Findings from the WHO World Mental Health Surveys. PLoS Med. 2009;6:1–17. [PMC free article: PMC2717212] [PubMed: 19668361]
7.Baldessarini RJ, Pompili M, Tondo L. Suicide in bipolar disorder: Risks and management. CNS Spectr. 2006;11:466–471. [PubMed: 16816785]
8.Brent D. What family studies teach us about suicidal behavior: Implications for research, treatment, prevention. Eur Psychiatry. 2010;25:260–263. [PubMed: 20451355]
9.Baldessarini RJ, Hennen J. Genetics of suicide: An overview. Harv Rev Psychiatry. 2004;12:1–13. [PubMed: 14965851]
10.Roy A. Family history of suicide. Arch Gen Psychiatry. 1983;40:971–974. [PubMed: 6615160]
11.Mann JJ, Bortinger J, Oquendo MA, Currier D, Li S, Brent DA. Family history of suicidal behavior and mood disorders in probands with mood disorders. Am J Psychiatry. 2005;162:1672–1679. [PubMed: 16135627]
12.Roy A. Family history of suicide and impulsivity. Arch Suicide Res. 2006;10940:347–352. [PubMed: 16920685]
13.Sarchiapone M, Carli V, Janiri L, Marchetti M, Cesaro C, Roy A. Family history of suicide and personality. Arch Suicide Res. 2009;13:178–184. [PubMed: 19363754]
14.Coryell W, Young EA. Clinical predictors of suicide in primary major depressive disorder. J Clin Psychiatry. 2005;66:412–417. [PubMed: 15816781]
15.Isometsa ET, Lonnqvist JK. Suicide attempts preceding completed suicide. Br J Psychiatry. 1998;173:531–535. [PubMed: 9926085]
16.Isometsa ET, Heikkinen ME, Marttunen MJ, Henriksson MM, Aro HM, Lönnqvist JK. The last appointment before suicide: Is suicide intent communicated? Am J Psychiatry. 1995;152:919–922. [PubMed: 7755124]
17.Busch KA, Fawcett J, Jacobs D. Clinical correlates of inpatient suicide. J Clin Psychiatry. 2003;64:14–19. [PubMed: 12590618]
18.Zhang J, Wieczorek W, Conwell Y, Tu XM, Wu BY, Xiao S, Jia C. Characteristics of young rural Chinese suicides: A psychological autopsy study. Psychol Med. 2010;40:581–589. [PMC free article: PMC2996472] [PubMed: 19656428]
19.Dumais A, Lesage AD, Alda M, Rouleau G, Dumont M, Chawky N, Roy M, Mann JJ, Benkelfat C, Turecki G. Risk factors for suicide in major depression: A case control study of impulsive and aggressive behaviors in men. Am J Psychiatry. 2005;162:116–124. [PubMed: 16263852]
20.Swann AC, Dougherty DM, Pazzaglia PJ, Pham M, Steinberg JL, Moeller FG. Increased impulsivity associated with severity of suicide attempt history in patients with bipolar disorder. Am J Psychiatry. 2005;162:1680–1687. [PubMed: 16135628]
21.Ligen MA, Zivin K, Austin KL, Bohnert AS, Czyz EK, Valenstein M, Kilbourne AM. Severe pain predicts greater likelihood of subsequent suicide. Suicide Life Threat Behav. 2010;40:597–608. [PubMed: 21198328]
22.Lofman S, Rasanen P, Hakko H. Suicide among persons with back pain: A population-based study of 2310 suicide victims in Northern Finland. Spine. 2011;36:541–548. [PubMed: 21217427]
23.Scott KM, Hwang I, Chiu WT, Kessler RC, Sampson NA, Angermeyer M, Beautrais A, Borges G, Bruffaerts R, de Graaf R, Florescu S, Fukao A, Haro JM, Hu C, Kovess V, Levinson D, Posada-Villa J, Scocco P, Nock MK. Chronic physical conditions and their association with first onset of suicidal behavior in the world mental health surveys. Psychosom Med. 2010;72:712–719. [PubMed: 20498290]
24.Kessler RC, Borges G, Walters EE. Prevalence of risk factors for lifetime suicide attempts in the National Comorbidity Survey. Arch Gen Psychiatry. 1999;56:617–626. [PubMed: 10401507]
25.Fawcett J, Scheftner WA, Fogg L, Clark DC, Young MA, Hedeker D, Gibbons R. Time-related predictors of suicide in major affective disorder. Am J Psychiatry. 1990;147:1189–1194. [PubMed: 2104515]
26.Kan CK, Ho TP, Dong JY, Dunn EL. Risk factors for suicide in the immediate post-discharge period. Soc Psychiatry Psychiatr Epidemiol. 2007;42:208–214. [PubMed: 17268761]
27.Goldacre M, Seagroat V, Hawton K. Suicide after discharge from psychiatric inpatient care. Lancet. 1993;342:283–286. [PubMed: 8101307]
28.Peteet JR, Maytal G, Rokni K. Inimaginable loss: Contingent suicidal ideation in family members of oncology patients. Psychosomatics. 2010;51:166–170. [PubMed: 20332292]
29.Ahn E, Shin DW, Cho SI, Park S, Won YJ, Yun YH. Suicide rates and risk factors among Korean cancer patients, 1993–2005. Cancer Epidemiol Biomarkers Prev. 2010;19:2097–2105. [PubMed: 20696665]
30.Fang F, Keating NL, Mucci LA, Adami HO, Stampfer MJ, Valdimarsdóttir U, Fall K. Immediate risk of suicide and cardiovascular death after a prostate cancer diagnosis: Cohort study in the United States. J Natl Cancer Inst. 2010;102:307–314. [PubMed: 20124521]
31.Flensborg-Madsen T, Knop J, Mortensen EL, Becker U, Sher L, Grønbaek M. Alcohol use disorders increase the risk of completed suicide-irrespective of other psychiatric disorders. A longitudinal cohort study. Psychiatry Res. 2009;167:123–130. [PubMed: 19359047]
32.Fawcett J, Kravitz H. Anxiety syndromes and their relationship to depressive illness. J Clin Psychiatry. 1983;44:8–11. [PubMed: 6874657]
33.Clayton P, Grove WM, Coryell W. Follow-up and family study of anxious depression. Am J Psychiatry. 1991;148:1512–1517. [PubMed: 1928465]
34.Hall RC, Platt DE, Hall RC. Suicide risk assessment: A review of risk factors for suicide in 100 outpatients who make severe suicide attempts. Psychosomatics. 1999;40:18–27. [PubMed: 9989117]
35.Simon GE, Hunkeler E, Fireman B, Lee JY, Savarino J. Risk of suicide attempt and suicide death in patients treated for bipolar disorder. Bipolar Disord. 2007;9:526–530. [PubMed: 17680924]
36.Stordal E, Morken G, Mykletun A, Neckelmann D, Dahl AA. Monthly variation in rates of comorbid depression and anxiety in the general population at 63–65 degrees North: The HUNT study. J Affect Disord. 2008;106:273–278. [PubMed: 17707514]
37.Pfeiffer PN, Ganoczy D, Ilgen M, Zivin K, Valenstein M. Comorbid anxiety as a suicide risk factor among depressed veterans. Depress Anxiety. 2009;26:752–757. [PMC free article: PMC2935592] [PubMed: 19544314]
38.Brown GL, Ebert MH, Goyer PF, Jimerson DC, Klein WJ, Bunney WE, Goodwin FK. Aggression, suicide, and serotonin: Relationships to CSF amine metabolites. Am J Psychiatry. 1982;139:741–748. [PubMed: 6177256]
39.Taylor CT, Hirshfeld-Becker DR, Ostacher MJ, Chow CW, LeBeau RT, Pollack MH, Nierenberg AA, Simon NM. Anxiety is associated with impulsivity in bipolar disorder. J Anxiety Disord. 2008;22:868–876. [PubMed: 17936573]
40.Bunney WE Jr, Fawcett JA. Possibility of a biochemical test for suicidal potential: An analysis of endocrine findings prior to three suicides. Arch Gen Psychiatry. 1965;13:232–239. [PubMed: 14339278]
41.Bunney WE, Fawcett JA, Davis JM, Gifford S. Further evaluation of urinary 17-hydroxycortocosteroids in suicidal patients. Arch Gen Psychiatry. 1969;21:138–150. [PubMed: 5804011]
42.Coryell W, Schlesser MA. Suicide and the dexamethasone suppression test in unipolar depression. Am J Psychiatry. 1981;138:1120–1121. [PubMed: 7258395]
43.Targum SD, Rosen L, Capodanno AE. The dexamethasone suppression test in suicidal patients with unipolar depression. Am J Psychiatry. 1983;140:877–879. [PubMed: 6859303]
44.Yerevanian Bl, Olafsdottir H, Milanese E, Russotto J, Mallon P, Baciewicz G, Sagi E. Normalization of the dexamethasone suppression test at discharge from hospital. Its prognostic value. J Affect Disord. 1983;5:191–197. [PubMed: 6224831]
45.Jokinen J, Nordström AL, Nordström P. CSF 5-HIAA and DST non-suppressionorthogonal biologic risk factors for suicide in male mood disorder inpatients. Psychiatry Res. 2009;165:96–102. [PubMed: 19062105]
46.Coryell W, Schlesser M. Combined biological tests for suicide prediction. Psychiatry Res. 2007;150:187–191. [PMC free article: PMC1880882] [PubMed: 17289156]
47.Sachar EJ, Kanter SS, Buie D, Engle R, Mehlman R. Psychoendocrinology of ego disintegration. Am J Psychiatry. 1970;126:1067–1068. [PubMed: 5411360]
48.Fava M, Alpert JE, Carmin CN, Wisniewski SR, Trivedi MH, Biggs MM, Shores-Wilson K, Morgan D, Schwartz T, Balasubramani GK, Rush AJ. Clinical correlates and symptom patterns or anxious depression among patients with major depressive disorder in STAR*D. Psychol Med. 2004;34:1299–1308. [PubMed: 15697056]
49.Fava M, Rush AJ, Alpert JE, Carmin CN, Balasubramani GK, Wisniewski SR, Trivedi MH, Biggs MM, Shores-Wilson K. What clinical and symptom features and comorbid disorders characterize outpatients with anxious major depressive disorder: A replication and extension. Can J Psychiatry. 2006;51:823–835. [PubMed: 17195602]
50.Coryell W, Solomon DA, Fiedorowicz JG, Endicott J, Schettler PJ, Judd LL. Anxiety and outcome in bipolar disorder. Am J Psychiatry. 2009;166:1238–1243. [PMC free article: PMC3551283] [PubMed: 19797434]
51.Coryell W, Fiedorowicz JG, Solomon D, Leon AC, Rice JP, Keller MB. Effects of anxiety on the long-term course of depressive disorders. Br J Psychiatry. 2012;200:210–215. [PMC free article: PMC3290796] [PubMed: 21984801]
52.Oquendo MA, Kamali M, Ellis SP, Grunebaum MF, Malone KM, Brodsky BS, Sackeim HA, Mann JJ. Adequacy of antidepressant treatment after discharge and the occurrence of suicidal acts in major depression: A prospective study. Am J Psychiatry. 2002;159:1746–1751. [PubMed: 12359682]
53.Oquendo MA, Baca-Garcia E, Mann JJ, Giner J. Issues for DSM-V: Suicidal behavior as a separate diagnosis on a separate axis. Am J Psychiatry. 2008;165:1383–1384. [PMC free article: PMC3776420] [PubMed: 18981069]
