atypical depression


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(Updated 5/26/04)

Perugi G, Toni C, Travierso MC, Akiskal HS.
The role of cyclothymia in atypical depression: toward a data-based reconceptualization of the borderline-bipolar II connection.
J Affect Disord 2003 Jan;73(1-2):87-98
"OBJECTIVE: Recent data, including our own, indicate significant overlap between atypical depression and bipolar II. Furthermore, the affective fluctuations of patients with these disorders are difficult to separate, on clinical grounds, from cyclothymic temperamental and borderline personality disorders. The present analyses are part of an ongoing Pisa-San Diego investigation to examine whether interpersonal sensitivity, mood reactivity and cyclothymic mood swings constitute a common diathesis underlying the atypical depression-bipolar II-borderline personality constructs. METHOD: We examined in a semi-structured format 107 consecutive patients who met criteria for major depressive episode with DSM-IV atypical features. Patients were further evaluated on the basis of the Atypical Depression Diagnostic Scale (ADDS), the Hopkins Symptoms Check-list (HSCL-90), and the Hamilton Rating Scale for Depression (HRSD), coupled with its modified form for reverse vegetative features as well as Axis I and SCID-II evaluated Axis II comorbidity, and cyclothymic dispositions ('APA Review', American Psychiatric Press, Washington DC, 1992). RESULTS: Seventy-eight percent of atypical depressives met criteria for bipolar spectrum-principally bipolar II-disorder. Forty-five patients who met the criteria for cyclothymic temperament, compared with the 62 who did not, were indistinguishable on demographic, familial and clinical features, but were significantly higher in lifetime comorbidity for panic disorder with agoraphobia, alcohol abuse, bulimia nervosa, as well as borderline and dependent personality disorders. Cyclothymic atypical depressives also scored higher on the ADDS items of maximum reactivity of mood, interpersonal sensitivity, functional impairment, avoidance of relationships, other rejection avoidance, and on the interpersonal sensitivity, phobic anxiety, paranoid ideation and psychoticism of the HSCL-90 factors. The total number of cyclothymic traits was significantly correlated with 'maximum' reactivity of mood and interpersonal sensitivity. A significant correlation was also found between interpersonal sensitivity and 'usual' and 'maximum' reactivity of mood. LIMITATION: Correlational study. CONCLUSIONS: Mood lability and interpersonal sensitivity traits appear to be related by a cyclothymic temperamental diathesis which, in turn, appears to underlie the complex pattern of anxiety, mood and impulsive disorders which atypical depressive, bipolar II and borderline patients display clinically. We submit that conceptualizing these constructs as being related will make patients in this realm more accessible to pharmacological and psychological interventions geared to their common temperamental attributes. More generally, we submit that the construct of borderline personality disorder is better covered by more conventional diagnostic entities." [Abstract]

Benazzi F.
Should mood reactivity be included in the DSM-IV atypical features specifier?
Eur Arch Psychiatry Clin Neurosci 2002 Jun;252(3):135-40
"BACKGROUND: The definition of atypical depression is still an unsolved issue. DSM-IV atypical features specifier criteria always require mood reactivity, but why mood reactivity should be included is unclear. The study aim was to test whether mood reactivity should be included in DSM-IV atypical features specifier. METHODS: Consecutively, 164 unipolar and 241 "soft" bipolar II major depressive episode (MDE) outpatients were interviewed with the Structured Clinical Interview for DSM-IV. The DSM-IV criteria for atypical features specifier were strictly followed. Associations were tested by univariate logistic regression. RESULTS: MDE with atypical features was present in 41.4 % of patients. Bipolar II disorder was significantly more common in patients with atypical features. MDE with atypical features was significantly associated with bipolar II, female gender, lower age of onset, more axis I comorbidity, fewer psychotic features, and more depressive mixed states. In the whole sample, mood reactivity was significantly associated with all the atypical symptoms, apart from leaden paralysis, and all the other atypical symptoms were significantly associated with each other. In the bipolar II sub-sample, mood reactivity was associated with many, but not all, atypical symptoms, while in the unipolar sub-sample it was associated with no atypical symptom. Atypical symptoms were significantly more common in mood reactive than in non-mood reactive patients, apart from leaden paralysis. Bipolar II disorder and mood reactivity were strongly associated. CONCLUSIONS: Results may support the inclusion of mood reactivity in the DSM-IV atypical features specifier for bipolar II disorder, but not for unipolar depression." [Abstract]

Posternak MA, Zimmerman M.
Symptoms of atypical depression.
Psychiatry Res 2001 Nov 1;104(2):175-81
"Studies examining the demographic and clinical features of depressed patients who meet criteria for the atypical features subtype have often yielded conflicting results. The present study sought to evaluate the demographic and clinical correlates associated with each of the five symptoms (mood reactivity, hypersomnia, hyperphagia, leaden paralysis and rejection sensitivity) that constitute the DSM-IV criteria set of atypical depression. Symptom prevalence rates were determined for 661 psychiatric outpatients diagnosed with a major depressive disorder, and were analyzed as a function of age, sex, severity, and episode duration. We found that: (1) younger age was positively associated with hypersomnia and negatively associated with leaden paralysis, while middle age was positively associated with both hyperphagia and rejection sensitivity; (2) female sex was associated with all of the atypical symptoms except rejection sensitivity; (3) a greater severity of illness was positively associated with leaden paralysis and rejection sensitivity, and negatively associated with mood reactivity; and (4) a duration of illness of greater than 3 months was positively associated with hyperphagia, leaden paralysis, and rejection sensitivity. Thus, the five atypical features do not appear to be associated with the same clinical profiles." [Abstract]

Parker G, Roy K, Mitchell P, Wilhelm K, Malhi G, Hadzi-Pavlovic D.
Atypical depression: a reappraisal.
Am J Psychiatry 2002 Sep;159(9):1470-9
"OBJECTIVE: The study evaluated the DSM-IV definition of the atypical features specifier for a major depressive episode in major depressive disorder. METHOD: Nonpsychotic patients with major depressive disorder were assessed to determine if the DSM-IV model and decision rules for the atypical features specifier for a major depressive episode could be supported. RESULTS: The five clinical features of the DSM-IV atypical features specifier for a major depressive episode showed weak internal consistency, and the mandatory criterion A feature of mood reactivity did not show specificity in relation to any of the four criterion B accessory symptoms. The more severe the depression, the less likely the patient was to report criterion A and hence to meet criteria for the atypical features specifier. Remodeling the five features favored the personality style descriptor of interpersonal rejection sensitivity as an alternate primary feature. A reformulated model also suggested lifetime panic disorder and social phobia as higher-order determinants of atypical features in major depressive disorder. Additional analyses of criteria suggested that interpersonal rejection sensitivity and leaden paralysis had a phenomenological base in anxiety, that mood reactivity was linked with irritability, and that neither weight gain nor hypersomnia were clearly aligned with anxiety or depression, raising questions about their status as symptoms. CONCLUSIONS: The current definition and modeling of the DSM-IV atypical features specifier for a major depressive episode in major depressive disorder appears problematic. As suggested by earlier descriptions of atypical depression, certain expressions of anxiety may have primacy, and some clinical features associated with the DSM-IV model may be adaptive homeostatic responses rather than pathological symptoms." [Abstract]

Gold PW, Chrousos GP.
Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states.
Mol Psychiatry 2002;7(3):254-75
"Stress precipitates depression and alters its natural history. Major depression and the stress response share similar phenomena, mediators and circuitries. Thus, many of the features of major depression potentially reflect dysregulations of the stress response. The stress response itself consists of alterations in levels of anxiety, a loss of cognitive and affective flexibility, activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system, and inhibition of vegetative processes that are likely to impede survival during a life-threatening situation (eg sleep, sexual activity, and endocrine programs for growth and reproduction). Because depression is a heterogeneous illness, we studied two diagnostic subtypes, melancholic and atypical depression. In melancholia, the stress response seems hyperactive, and patients are anxious, dread the future, lose responsiveness to the environment, have insomnia, lose their appetite, and a diurnal variation with depression at its worst in the morning. They also have an activated CRH system and may have diminished activities of the growth hormone and reproductive axes. Patients with atypical depression present with a syndrome that seems the antithesis of melancholia. They are lethargic, fatigued, hyperphagic, hypersomnic, reactive to the environment, and show diurnal variation of depression that is at its best in the morning. In contrast to melancholia, we have advanced several lines of evidence of a down-regulated hypothalamic-pituitary adrenal axis and CRH deficiency in atypical depression, and our data show us that these are of central origin. Given the diversity of effects exerted by CRH and cortisol, the differences in melancholic and atypical depression suggest that studies of depression should examine each subtype separately. In the present paper, we shall first review the mediators and circuitries of the stress system to lay the groundwork for placing in context physiologic and structural alterations in depression that may occur as part of stress system dysfunction." [PDF]

Levitan RD, Vaccarino FJ, Brown GM, Kennedy SH.
Low-dose dexamethasone challenge in women with atypical major depression: pilot study.
J Psychiatry Neurosci 2002 Jan;27(1):47-51
"OBJECTIVE: To examine if atypical depression may be associated with hypersuppression of the hypothalamic-pituitary-adrenal (HPA) axis. METHOD: Eight women with atypical major depression and 11 controls with no history of psychiatric illness, matched on age and body mass index, were challenged with low-dose dexamethasone (0.25 mg and 0.50 mg in random order and 1 week apart). Dexamethasone was self administered at 11 pm, and plasma cortisol samples were drawn at 8 am and 3 pm on the following day. RESULTS: After the 0.50-mg dexamethasone challenge, mean suppression of morning cortisol was significantly greater in patients with atypical depression (91.9%, standard deviation [SD] 6.8%) than in the controls (78.3%, SD 10.7%; p < 0.01). CONCLUSION: These preliminary data add to the growing body of literature that suggests atypical depression, in contrast to classic melancholia, may be associated with exaggerated negative feedback regulation of the HPA axis." [Abstract]

McGinn LK, Asnis GM, Rubinson E.
Biological and clinical validation of atypical depression.
Psychiatry Res 1996 Mar 29;60(2-3):191-8
"Depressed patients with (a) mood reactivity alone (MR group), (b) mood reactivity plus one or more associated features (atypical depression, AD group), and (c) patients with neither mood reactivity nor atypical depression (non-MR/AD group) were compared on their cortisol response to 75 mg of desipramine (DMI), a relatively selective norepinephrine reuptake inhibitor. AD patients exhibited a significantly higher cortisol response to DMI compared with MR and non-MR/AD patients, suggesting that atypical depression may be associated with a less impaired norepinephrine system. MR and non-MR/AD patients did not differ, suggesting that mood reactivity alone is not associated with the biological profile observed in atypical depression. Results indicate that while mood reactivity may be necessary for the diagnosis of atypical depression, the additional presence of at least one associated symptom is required for a distinct biological profile. Our findings provide further biological validation of the concept of atypical depression." [Abstract]

Lam RW, Stewart JN.
The validity of atypical depression in DSM-IV.
Compr Psychiatry 1996 Nov-Dec;37(6):375-83
"Atypical depression has been included in the DSM-IV as an episode specifier of major depressive episodes and dysthymia. This report will review evidence for the clinical validity of atypical depression using operational criteria for the validation of clinical syndromes. English language articles between 1969 and March 1996 were found using a computerized and manual reference search and were selected according to the following criteria: (1) primary research, (2) definition of atypical depression, which includes depression and not anxiety alone, and (3) relevance of data for validation of atypical depression. Studies were evaluated on Kendall's six criteria for establishing clinical validity. There are supporting data for diagnostic validity of atypical depression in the criteria of clinical description and differential treatment response, with atypical depression having a superior response to monoamine oxidase (MAO) inhibitors compared to tricyclic antidepressants." [Abstract]

Kasckow JW, Baker D, Geracioti TD Jr.
Corticotropin-releasing hormone in depression and post-traumatic stress disorder.
Peptides 2001 May;22(5):845-51
"Corticotropin-releasing hormone (CRH) has been implicated in the regulation of a wide range of behaviors including arousal, motor function, feeding, and reproduction. Because depressed patients are often hypercortisolemic and intracerebroventricular administration of CRH to experimental animals produces a syndrome reminiscent of depression, dysregulation of this compound has been suggested to be involved in the pathogenesis of depressive and anxiety disorders. Studies of cerebrospinal fluid CRH levels and clinical neuroendocrine tests in patients with anxiety and affective disorders have supported this hypothesis. This review discusses these neuroendocrine findings in melancholic and atypical depression as well as post-traumatic stress disorder (PTSD). Overall, the data suggest that melancholic depression is characterized by hyperactive central CRH systems with overactivity of the pituitary-adrenal (HPA) axis. On the other hand, atypical depression is characterized by hypoactive central CRH systems and accompanying underactivity of the hypothalamic-pituitary-adrenal axis. Furthermore, the neuroendocrinology of PTSD appears to be unique, in that patients have hyperactive central CRH systems with underactivity of the pituitary-adrenal axis." [Abstract]

Tsigos C, Chrousos GP.
Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress.
J Psychosom Res 2002 Oct;53(4):865-71
"The stress system coordinates the adaptive responses of the organism to stressors of any kind.(1). The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic beta-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and beta-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T(4)) to triiodothyronine (T(3)), contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing "low turnover" osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LC/NE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli." [Abstract]

Davidson JR, Abraham K, Connor KM, McLeod MN.
Effectiveness of chromium in atypical depression: a placebo-controlled trial.
Biol Psychiatry 2003 Feb 1;53(3):261-4
"BACKGROUND: Chromium picolinate (CP) has been reported to benefit patients with symptoms of atypical depression. METHODS: A placebo-controlled, double-blind, pilot study of CP was conducted in 15 patients with DSM-IV major depressive disorder, atypical type. Patients received 600 micro g of CP or matching placebo (PBO) for 8 weeks. RESULTS: Seven (70%) CP and zero (0%) PBO patients met responder criteria (p =.02). Other outcomes were consistent with greater effect of CP. Three patients on CP failed to show any improvement. Chromium picolinate was well tolerated. CONCLUSIONS: Chromium picolinate shows promising antidepressant effects in atypical depression. Its mechanism of action may relate to 5HT2A downregulation, increased insulin sensitivity, or to other effects." [Abstract]

Bouwer C, Claassen J, Dinan TG, Nemeroff CB.
Prednisone augmentation in treatment-resistant depression with fatigue and hypocortisolaemia: a case series.
Depress Anxiety 2000;12(1):44-50
"Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis have long been implicated in major depression with hypercortisolaemia reported in typical depression and hypocortisolaemia in some studies of atypical depression. We report on the use of prednisone in treatment-resistant depressed patients with reduced plasma cortisol concentrations. Six patients with treatment-resistant major depression were found to complain of severe fatigue, consistent with major depression, atypical subtype, and to demonstrate low plasma cortisol levels. Prednisone 7.5 mg daily was added to the antidepressant regime. Five of six patients demonstrated significant improvement in depression on prednisone augmentation of antidepressant therapy. Although hypercortisolaemia has been implicated in some patients with depression, our findings suggest that hypocortisolaemia may also play a role in some subtypes of this disorder. In treatment-resistant depressed patients with fatigue and hypocortisolaemia, prednisone augmentation may be useful." [Abstract]

Anisman H, Ravindran AV, Griffiths J, Merali Z.
Endocrine and cytokine correlates of major depression and dysthymia with typical or atypical features.
Mol Psychiatry 1999 Mar;4(2):182-8
"Depression has been associated with both suppression and enhancement of various aspects of immune functioning. It was of interest to determine whether cytokine alterations associated with depression, including interleukin-1 (IL-1beta) and interleukin-2 (IL-2), were related to the neurovegetative symptom profile or to the chronicity of the illness. Circulating ACTH, cortisol, norepinephrine (NE) and epinephrine levels, and production of IL-1beta and IL-2 from mitogen-stimulated lymphocytes were assessed in classical major depression, atypical depression (ie, with reversed neurovegetative features), and dysthymia (chronic depression without comorbid major depression) with either typical or atypical profiles, as well as nondepressed control subjects. Among atypical depressives, plasma ACTH levels were elevated while cortisol was reduced relative to controls. Irrespective of neurovegetative profile, IL-1beta production was increased in dysthymic patients, and was highly correlated with age-of-onset and duration of illness. In contrast, IL-2 production was reduced in each of the groups, although less so among atypical major depressives. Moreover, IL-2 production in the depressive groups was directly related to plasma NE levels. While neither depressed mood per se nor neurovegetative features accounted for this effect, it seemed likely that chronicity of illness or age-of-onset were associated with cytokine alterations. Given that circulating cytokines influence neuroendocrine functioning, and may affect neurovegetative features, a role for interleukins may exist with respect to the pathophysiology of certain subtypes of depression." [Abstract]

Geracioti TD Jr, Loosen PT, Orth DN.
Low cerebrospinal fluid corticotropin-releasing hormone concentrations in eucortisolemic depression.
Biol Psychiatry 1997 Aug 1;42(3):165-74
"Hypersecretion of corticotropin-releasing hormone (CRH) and resulting hypercortisolism have been implicated in the pathogenesis of major depression. To test this CRH hypersecretion hypothesis, cerebrospinal fluid (CSF) was continuously withdrawn from 11:00 AM to 5:00 PM via an indwelling subarachnoid catheter (placed at 8:00 AM), and immunoreactive CRH concentrations were determined at 10-min intervals in 10 depressed patients, the majority of whom exhibited at least one "atypical" symptom, and in 15 normal volunteers. CSF CRH was low, plasma adrenocorticotropin (ACTH) tended to be low, and plasma cortisol was normal in the depressed patients. Also, tobacco smokers had lower CSF CRH than nonsmokers. CRH increased acutely in response to lumbar puncture, had a brief half-life, showed rapid variability in concentration over time, and displayed a diurnal concentration rhythm that was preserved in fasting individuals and in most depressed patients. CSF CRH did not correlate with plasma ACTH or cortisol; this and its rapidly fluctuating levels suggest a primarily extrahypothalamic origin of lumbar CSF CRH." [Abstract]

Young EA, Carlson NE, Brown MB.
Twenty-four-hour ACTH and cortisol pulsatility in depressed women.
Neuropsychopharmacology 2001 Aug;25(2):267-76
"Increased plasma cortisol in patients with major depression is a well documented finding, although it is present in only 25-30% of subjects with major depression. However, ACTH and cortisol are secreted in a pulsatile manner, so it is unclear if increased ACTH secretion occurs in depression and if there are changes in the pulsatile components of ACTH secretion. Ten-minute sampling for ACTH and cortisol was performed for 24 hr in 25 premenopausal depressed women, whose age and menstrual cycle day matched control women. As a group, the depressed women demonstrated a trend to increase cortisol secretion (p = 0.089). There was no difference in mean cortisol between the patient group as a whole (8.36 +/- 2.9 microg/dl) and those patients meeting criteria for atypical depression (8.38 +/- 1.9 microg/dl), but patients meeting criteria for endogenous showed increased cortisol (12.17 +/- 4 microg/dl) Mean ACTH was not significantly different between patients and controls. Pulse analyses revealed similar number of secretory events and similar amplitudes for cortisol secretory bursts in patients and controls. The baseline component area under the curve of cortisol secretion was increased at a trend level (p =.064) in depressed patients, and the baseline AUC for ACTH was significantly increased in depressed patients (p =.045). No differences were found in pulsatile components of ACTH secretion between patients and matched controls. Harmonic analyses indicated no significant differences between patients and controls on any detected rhythm for ACTH or cortisol. These data suggest that the pulsatile and circadian components of the HPA axis are normal in premenopausal depressed women and that only 24% of depressed women demonstrate hypercortisolemia." [Abstract]

McGrath PJ, Stewart JW, Harrison WM, Ocepek-Welikson K, Rabkin JG, Nunes EN, Wager SG, Tricamo E, Quitkin FM, Klein DF.
Predictive value of symptoms of atypical depression for differential drug treatment outcome.
J Clin Psychopharmacol 1992 Jun;12(3):197-202
"Data for 401 depressed outpatients with mood reactivity who participated in a randomized trial comparing placebo, imipramine, and phenelzine were analyzed for predictors of differential response by stepwise multiple regression techniques. Features of the Columbia criteria for atypical depression including oversleeping, overeating, severe anergy, and pathologic rejection sensitivity were each predictive of a poorer response to imipramine than to phenelzine only when compared to those patients with none of the features. These features were not additive in their contribution to differential outcome. Lack of endogenous features was not predictive of a differential drug treatment response. Compared with patients who have no symptoms of atypical depression, patients with any of the four features had an inferior imipramine response rather than a superior phenelzine response. These analyses indicate that the clear differential responsivity to medication treatment in atypical depression is not simply related to any one defining symptom and that further correlates of this apparent biological heterogeneity need to be explored." [Abstract]

Wager S, Robinson D, Goetz R, Nunes E, Gully R, Quitkin F.
Cholinergic REM sleep induction in atypical depression.
Biol Psychiatry 1990 Feb 15;27(4):441-6
"The arecoline REM induction test, a measurement of central cholinergic sensitivity, was performed in 10 patients with atypical depression. Arecoline induced REM sleep significantly more rapidly than placebo. Atypical depressives without evidence of anxiety, in particular those without panic attacks, had a more rapid REM induction response to arecoline than atypicals with anxiety symptoms. We compared our atypical depressives with normal controls and affectively ill patients studied in other laboratories. The rapid REM induction response observed in atypical depressives without anxiety was comparable to that seen in endogenous depressives and euthymic bipolars. Previous studies have demonstrated the presence of cholinergic supersensitivity in the latter two groups of patients. Our results suggest that atypical depressives may be distinguished in their response to arecoline based on their anxiety history, and that cholinergic supersensitivity is present in atypical depressives without anxiety. Additional studies with larger samples and simultaneously studied control groups are necessary to test these preliminary findings." [Abstract]

Quitkin FM, Rabkin JG, Stewart JW, McGrath PJ, Harrison W, Davies M, Goetz R, Puig-Antich J.
Sleep of atypical depressives.
J Affect Disord 1985 Jan-Feb;8(1):61-7
"Patients who met provincial criteria for atypical depression were contrasted with a group of patients who met RDC criteria for endogenous depression and a group of normal controls on a standard series of sleep variables. Atypical depressives were differentiated from normal controls by a shortened REMP latency. They did not, however, appear to have the sleep continuity disturbance exhibited by endogenous depressives. This preliminary work suggests that atypical depressives may have a unique pattern of sleep variables consisting of REM abnormalities without continuity disturbance. If this pattern is observed in additional studies, it would add to the validity of considering atypical depression a subtype of unipolar depressive illness." [Abstract]

Moller SE.
[Carbohydrates and depression]
Ugeskr Laeger 1989 Sep 4;151(36):2250-2
"In the past decade, several related behavioural disorders have been recognized which are characterized by disturbances of mood and appetite. Some authors have reported that a significant number of patients suffering from some of these diseases, i.e. subtypes of atypical depression or obesity, crave carbohydrates. It is suggested that the common neurobiological substrate for this symptom is disturbed function of central serotonin, which may play a role in the regulation of carbohydrate intake. Other authors have disputed hypothetical regulation of carbohydrate intake by serotonin and doubt the existence of true carbohydrate cravers. Evidence from basal and clinical studies of these topics is reported and discussed." [Abstract]

Bruder GE, Stewart JW, McGrath PJ, Ma GJ, Wexler BE, Quitkin FM.
Atypical depression: enhanced right hemispheric dominance for perceiving emotional chimeric faces.
J Abnorm Psychol 2002 Aug;111(3):446-54
"Two studies compared hemispatial bias for perceiving chimeric faces in patients having either atypical or typical depression and healthy controls. A total of 245 patients having major depressive disorder (MDD) or dysthymia (164 with atypical features) and 115 controls were tested on the Chimeric Faces Test. Atypical depression differed from typical depression and controls in showing abnormally large right hemisphere bias. This was present in patients having either MDD or dysthymia and was not related to anxiety, physical anhedonia, or vegetative symptoms. In contrast, patients having MDD with melancholia showed essentially no right hemisphere bias. This is further evidence that atypical depression is a biologically distinct subtype and underscores the importance of this diagnostic distinction for neurophysiologic studies." [Abstract]

Kendler KS, Eaves LJ, Walters EE, Neale MC, Heath AC, Kessler RC.
The identification and validation of distinct depressive syndromes in a population-based sample of female twins.
Arch Gen Psychiatry 1996 May;53(5):391-9
"BACKGROUND: Depression, a clinically heterogeneous syndrome, may also be etiologically heterogeneous. Using a prospective, epidemiologic, and genetically informative sample of adult female twins, we identify and validate a typology of depressive syndromes. METHODS: Latent class analysis was applied to 14 disaggregated DSM-III-R symptoms for major depression reported over the last year by members of 1029 female-female twin pairs. RESULTS: Seven classes were identified, of which 3 represented clinically significant depressive syndromes: (1) mild typical depression, (2) atypical depression, and (3) severe typical depression. Severe typical depression was characterized by comorbid anxiety and panic, long episodes, impairment, and help seeking. Atypical depression was similar in severity to mild typical depression, but was characterized by increased eating, hypersomnia, frequent, relatively short episodes, and a proclivity to obesity. Individuals with recurrent episodes tended to have the same syndrome on each occasion. The members of twin pairs concordant for depression had the same depressive syndrome more often than expected by chance and this resemblance was greater in monozygotic than in dizygotic pairs. CONCLUSION: In an epidemiologic sample of female twins, depression is not etiologically homogeneous, but is instead made up of several syndromes that are at least partially distinct from a clinical, longitudinal, and familial/genetic perspective." [Abstract]

Sullivan PF, Kessler RC, Kendler KS.
Latent class analysis of lifetime depressive symptoms in the national comorbidity survey.
Am J Psychiatry 1998 Oct;155(10):1398-406
"OBJECTIVE: Although clinical trials have documented the importance of identifying individuals with major depression with atypical features, there are fewer epidemiological data. In a prior report, the authors used latent class analysis (LCA) to identify a distinctive atypical depressive subtype; they sought to replicate that finding in the current study. METHOD: Using the National Comorbidity Survey data, the authors applied LCA to 14 DSM-III-R major depressive symptoms in the participants' lifetime worst episodes (N=2,836). Validators of class membership included depressive disorder characteristics, syndrome consequences, demography, comorbidity, personality/attitudes, and parental psychiatric history. RESULTS: The best-fitting LCA solution had six classes. Four were combinations of atypicality and severity: severe atypical, mild atypical, severe typical, and mild typical. Syndrome severity (severe atypical and typical versus mild atypical and typical classes) was associated with a pronounced pattern of more and longer episodes, worse syndrome consequences, increased psychiatric comorbidity, more deviant personality and attitudes, and parental alcohol/drug use disorder. Syndrome atypicality (severe and mild atypical versus severe and mild typical classes) was associated with decreased syndrome consequences, comorbid conduct disorder and social phobia, higher interpersonal dependency and lower self-esteem, and parental alcohol/drug use disorder. CONCLUSIONS: As in prior reports, the atypical subtype of depression can be identified in epidemiological samples and, like typical depression, exists in mild and severe variants. Atypical depressive subtypes were characterized by several distinctive features. However, the correspondence between epidemiologically derived typologies of atypical depression and DSM-IV major depression with atypical features is not yet known." [Abstract]

Benazzi F.
Can only reversed vegetative symptoms define atypical depression?
Eur Arch Psychiatry Clin Neurosci 2002 Dec;252(6):288-93
"BACKGROUND: The definition of atypical depression (AD) has recently seen a rebirth of studies, as the evidence supporting the current DSM-IV atypical features criteria is weak. Study aim was to compare a definition of AD requiring only oversleeping and overeating (reversed vegetative symptoms) to the DSM-IV AD definition (always requiring mood reactivity, plus overeating/weight gain, oversleeping, leaden paralysis, and interpersonal sensitivity [at least 2]). METHODS: Consecutive 202 major depressive disorder (MDD) and 281 bipolar II outpatients were interviewed, during a major depressive episode (MDE), with the Structured Clinical Interview for DSM-IV. The DSM-IV criteria for AD were compared to a new AD definition based only on oversleeping and overeating, which was the one often used in community studies. Associations were tested by univariate logistic regression. RESULTS: The frequency of DSM-IV AD was 42.8 %, and that of the new AD definition was 38.7 %. DSM-IV AD, and the new AD definition, had almost all the same significant associations: bipolar II, female gender, lower age, lower age of onset, axis I comorbidity, depressive mixed state, MDE symptoms lasting more than 2 years, and bipolar family history. DSM-IV AD was present in 86 % of the new AD definition sample. The new definition of AD was significantly associated with all the other DSM-IV AD symptoms not included in it. The new AD definition was strongly associated with DSM-IV AD (odds ratio = 17.8), and had sensitivity = 77.7 %, specificity = 90.5 %, positive predictive value = 86.1 %, negative predictive value = 84.4 %, and ROC area curve = 0.85, for predicting DSM-IV AD. CONCLUSIONS: Results support a simpler definition of AD, requiring only oversleeping and overeating, and support the similar AD definition previously used in community studies. This definition is easier and quicker to assess by clinicians than the DSM-IV definition (mood reactivity and interpersonal sensitivity are more difficult to assess). Some pharmacological studies support this new AD definition (by showing better response to MAOI than to TCA, as shown in DSM-IV AD)." [Abstract]

Benazzi F.
Testing DSM-IV definition of atypical depression.
Ann Clin Psychiatry. 2003 Mar;15(1):9-16.
"The definition of atypical depression (AD) has recently seen a rebirth of studies, as the evidence supporting DSM-IV atypical features criteria is weak. Study aim was to test the validity of DSM-IV definition of AD. Consecutive 202 major depressive disorder (MDD) and 281 bipolar II outpatients were interviewed, during a major depressive episode (MDE), with the Structured Clinical Interview for DSM-IV. The relationships of DSM-IV AD versus variables often reported to distinguish AD and non-AD (gender, age, onset, bipolar II, axis I comorbidity, MDE severity, residual MDE symptoms, depressive mixed state), and versus bipolar family history, were tested. Each DSM-IV AD symptom's relationship with the variables found significantly associated to DSM-IV AD was then tested, in order to assess the degree of concordance among all AD symptoms. Associations were tested by univariate logistic regression (STATA 7). Frequency of DSM-IV AD was 42.8%. DSM-IV AD was significantly more common in bipolar II versus MDD (53.7% vs. 27.7%, p = 0.0000). DSM-IV AD significant associations were the following: bipolar II, female gender, lower age, lower age of onset, residual MDE symptoms, axis I comorbidity, psychotic features, depressive mixed state, and bipolar family history. Testing associations of each DSM-IV AD symptom versus the variables found associated to DSM-IV AD showed high concordance. All AD symptoms were significantly associated with DSM-IV AD, and with most study variables. Results support the current DSM-IV definition of AD." [Abstract]

Benazzi F.
Is atypical depression a moderate severity depression? A 536-case study.
J Psychiatry Neurosci 1999 May;24(3):244-7
"OBJECTIVE: To determine if atypical depression is less common among outpatients with severe depression than among those with nonsevere depression. DESIGN: Case series. SETTING: Private practice. PATIENTS: Five hundred and thirty-six consecutive outpatients presenting for treatment of unipolar or bipolar II depression. OUTCOME MEASURES: Prevalence of atypical depression among patients with severe depression (Global Assessment of Functioning Scale [GAF] score of 50 or less) and nonsevere depression. RESULTS: There was no significant difference in the prevalence of atypical depression between patients with severe and nonsevere depression. CONCLUSIONS: Results do not support previous studies that atypical depression is usually of moderate severity. A rating scale like the GAF, which assesses both symptom severity and impairment of functioning, may give a more complete assessment of depression severity than a symptoms rating scale (used in previous studies), which does not cover atypical features and does not assess functioning." [Abstract]

Williamson DE, Birmaher B, Brent DA, Balach L, Dahl RE, Ryan ND.
Atypical symptoms of depression in a sample of depressed child and adolescent outpatients.
J Am Acad Child Adolesc Psychiatry 2000 Oct;39(10):1253-9
"OBJECTIVE: To examine the presence of symptoms of atypical depression among children and adolescents with a major depressive disorder (MDD). METHOD: One thousand forty-six youths (aged 6-19 years) meeting DSM-III-R criteria for MDD were included in the study. All subjects had presented at an outpatient clinic seeking treatment and were identified as having MDD via clinical interviews using the semistructured Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode (K-SADS-P) with the youngster themselves and a parent/guardian. A diagnosis of atypical depression was derived from the symptoms of depression assessed in the K-SADS-P and required the presence of mood reactivity and at least one the following symptoms: hypersomnia, increased appetite, weight gain, or psychomotor retardation (substituted for leaden paralysis). RESULTS: One hundred sixty-two (15.5%) of the depressed youths met criteria for atypical depression. The symptoms of atypical depression were found to correlate marginally, and the diagnosis of atypical depression had marginal construct validity for both children and adolescents. CONCLUSIONS: The findings from this large sample of depressed children and adolescents suggest that atypical features of depression occur in this age group. However, the diagnosis of atypical depression appears to have only marginal construct validity for both children and adolescents." [Abstract]

Benazzi F.
Psychomotor changes in melancholic and atypical depression: unipolar and bipolar-II subtypes.
Psychiatry Res 2002 Nov 15;112(3):211-20
"Psychomotor changes are reported to be 'nearly always present' in the melancholic subtype of major depressive episode (MDE) in DSM-IV-TR, and are believed by some researchers to be markers of melancholia. The aim of this study was to compare melancholic and atypical forms of MDE and to determine whether psychomotor changes are core features of melancholic MDE. The Structured Clinical Interview of DSM-IV was used to consecutively assess 107 unipolar and 164 bipolar-II MDE outpatients. The criteria used to define melancholic and atypical MDE followed DSM-IV-TR. Melancholic MDE was present in 17.7% of patients; atypical MDE, in 35.0%. The group of patients with melancholic MDE had the following differences from the atypical group: higher age, higher age at onset, fewer females, more unipolar cases, fewer bipolar-II cases, lower Global Assessment of Functioning scores, more MDE symptoms, and more psychotic features. Percentages of observable and marked psychomotor changes (agitation and retardation combined) did not differ significantly between the two groups, though the melancholic group tended to have more symptoms. Retardation was significantly more common in melancholic MDE, but its frequency was very low in both melancholic and atypical cases (12.5 vs. 0.0%). Logistic regression controlling for age, gender and illness duration had little effect on the findings, which suggests that psychomotor changes are not core features of melancholic MDE." [Abstract]

Perugi G, Akiskal HS, Lattanzi L, Cecconi D, Mastrocinque C, Patronelli A, Vignoli S, Bemi E.
The high prevalence of "soft" bipolar (II) features in atypical depression.
Compr Psychiatry 1998 Mar-Apr;39(2):63-71
"Seventy-two percent of 86 major depressive patients with atypical features as defined by the DSM-IV and evaluated systematically were found to meet our criteria for bipolar II and related "soft" bipolar disorders; nearly 60% had antecedent cyclothymic or hyperthymic temperaments. The family history for bipolar disorder validated these clinical findings. Even if we limit the diagnosis of bipolar II to the official DSM-IV threshold of 4 days of hypomania, 32.6% of atypical depressives in our sample would meet this conservative threshold, a rate that is three times higher than the estimates of bipolarity among atypical depressives in the literature. By definition, mood reactivity was present in all patients, while interpersonal sensitivity occurred in 94%. Lifetime comorbidity rates were as follows: social phobia 30%, body dysmorphic disorder 42%, obsessive-compulsive disorder 20%, and panic disorder (agoraphobia) 64%. Both cluster A (anxious personality) and cluster B (e.g., borderline and histrionic) personality disorders were highly prevalent. These data suggest that the "atypicality" of depression is favored by affective temperamental dysregulation and anxiety comorbidity, clinically manifesting in a mood disorder subtype that is preponderantly in the realm of bipolar II. In the present sample, only 28% were strictly unipolar and characterized by avoidant and social phobic features, without histrionic traits." [Abstract]

Benazzi F.
Is there a link between atypical and early-onset "unipolar" depression and bipolar II disorder?
Compr Psychiatry 2003 Mar-Apr;44(2):102-9
"The aim of the present study was to determine whether there is a link between "unipolar" depression with atypical features and early onset, and bipolar II disorder, using atypical features and early onset as markers of bipolarity. A total of 158 consecutive unipolar and 234 bipolar II major depressive episode (MDE) outpatients were interviewed using the Structured Clinical Interview for DSM-IV (SCID). Patients were divided into those with and without atypical features, and into those with and without early onset. Comparisons were made on variables reported to distinguish bipolar from unipolar: age of onset, recurrences, atypical features, depressive mixed state (MDE plus three or more concurrent hypomanic symptoms [DMX3]), and bipolar II family history. Compared to bipolar II patients, patients with atypical unipolar were not significantly different regarding age of onset, DMX3, recurrences, and bipolar II family history. Compared to non-atypical unipolar patients, atypical unipolar patients had a significantly different age of onset. Nonatypical unipolar patients, versus bipolar II patients, were significantly different regarding age of onset, recurrences, DMX3, and bipolar II family history. Early onset unipolar, versus bipolar II, were not significantly different regarding atypical features, recurrences, DMX3, and bipolar II family history. Later onset unipolar patients, versus bipolar II patients, were significantly different regarding atypical features, recurrences, DMX3, and bipolar II family history. These results support a link of atypical and early-onset "unipolar" depression with bipolar II disorder, and support Pages and Dunner's suggestion to combine bipolar II and recurrent unipolar into a single group." [Abstract]

Matza LS, Revicki DA, Davidson JR, Stewart JW.
Depression with atypical features in the National Comorbidity Survey: classification, description, and consequences.
Arch Gen Psychiatry. 2003 Aug;60(8):817-26.
"BACKGROUND: Atypical depression has been found to be distinct from other types of depression in terms of psychiatric symptom profile and treatment response. However, debate continues regarding its specific characteristics, impact, and diagnostic criteria. The current study was conducted to increase understanding of atypical depression diagnosed using only the reversed vegetative symptoms of hypersomnia and hyperphagia. METHODS: An atypical depression group (n = 304 [36.4% of the depressed sample; 39.0% when weighted to approximate the national population]) was identified within the US National Comorbidity Survey, which assessed psychiatric disorders among a nationally representative sample using the Composite International Diagnostic Interview. The atypical group was identified based on DSM-III-R criteria for a major depressive episode, in addition to atypical features of hypersomnia and hyperphagia. Comparison groups were those with nonatypical depression (n = 532) and individuals without a psychiatric disorder (n = 4071). RESULTS: Compared with nonatypical depression, atypical depression was associated with a greater percentage of women and an earlier age of onset. The atypical group also reported higher rates of most depressive symptoms, suicidal thoughts and attempts, psychiatric comorbidity (panic disorder, social phobia, and drug dependence), disability and restricted activity days, use of some health care services, paternal depression, and childhood neglect and sexual abuse (P<.05). Compared with people without psychiatric disorders, the atypical group reported higher rates of disability and restricted activity days, use of all mental health care services, parental depression, and childhood abuse (P<.001). CONCLUSIONS: This analysis of a nationally representative US sample suggests that overeating and oversleeping can be used to identify an atypical depression subgroup that is distinct from other depressed patients in terms of demographics, psychiatric comorbidities, and abuse history. Findings also suggest that atypical depression is associated with increased distress, suicidal ideation, and disability compared with nonatypical depression." [Abstract]

Derecho CN, Wetzler S, McGinn LK, Sanderson WC, Asnis GM.
Atypical depression among psychiatric inpatients: clinical features and personality traits.
J Affect Disord 1996 Jun 20;39(1):55-9
"OBJECTIVE: This study investigates the frequency and characteristics of Atypical Depression (AD) among depressed inpatients. METHOD: Twenty-one depressed inpatients received DSM-IV diagnoses, were rated on the Hamilton Depression Rating Scale (HAMD), and assessed for AD using the Atypical Depressive Disorder Scale. AD was defined as the presence of mood reactivity and two of four associated features: hyperphagia, hypersomnia, leaden paralysis, rejection sensitivity. Mood reactivity was defined as the ability to reach 50% of a non-depressed mood. All subjects completed the SCL-90, MCMI-II, and a suicide survey. RESULTS: Seven patients (33%) met criteria for AD. AD and non-AD patients did not differ in terms of severity of depression, history of suicide attempts, levels of clinical symptomatology, age of onset of depression, prior hospitalizations, and most personality characteristics. However, AD patients scored significantly higher than non-AD patients on the SCL-90 Interpersonal Sensitivity and MCMI-II Avoidant scales, and were more likely to be single. CONCLUSION: AD is fairly prevalent on an inpatient service, comparable to the frequency found in outpatient settings. AD is not a milder form of depression. The only differences between AD and non-AD patients reflect the personality trait of rejection sensitivity which is a defining feature of AD." [Abstract]

Posternak MA, Zimmerman M.
The prevalence of atypical features across mood, anxiety, and personality disorders.
Compr Psychiatry 2002 Jul-Aug;43(4):253-62
"This study examines and compares the prevalence rates of the atypical features subtype across each of the major mood, anxiety, and personality disorders (PDs). It also evaluates the impact that comorbid anxiety and PDs have on the likelihood that depressed patients will present with atypical symptoms. Eleven hundred thirty psychiatric outpatients were evaluated for the presence of atypical symptoms. All axis I diagnoses were made using the Structured Clinical Interview for DSM-IV (SCID). PDs were assessed in a subset of 530 patients using the Structured Interview for DSM-IV Personality Disorders (SIDP-IV). From a sample of 579 patients diagnosed with a current major depressive disorder, 22.5% met criteria for the atypical subtype. Prevalence rates were similar in bipolar and unipolar patients, although the pattern of symptoms was distinct. Prevalence rates were lower in patients with dysthymic disorder (12.5%), adjustment disorder with depressed mood (9.4%), and depression not otherwise specified (NOS) (7.9%). When major depression existed in the presence of a comorbid anxiety disorder, the likelihood of presenting with atypical features doubled. Nine percent of the patients diagnosed with an anxiety disorder (without a comorbid depressive disorder) met criteria for atypical features. Two of the four atypical symptoms, leaden paralysis and rejection sensitivity, were found to be especially prominent in nondepressed anxiety disorder patients. Of the 10 PDs listed in DSM-IV, only avoidant PD was associated with the atypical features subtype. In large part, this was accounted for by the high rate of rejection sensitivity in these patients. In conclusion, as many as one quarter of depressed patients who present for outpatient psychiatric treatment meet criteria for the atypical features subtype. There appears to be a strong association between anxiety and atypical depression, but the exact nature of this relationship needs to be further elucidated. It is unclear whether personality pathology is independently associated with the atypical features subtype." [Abstract]

Benazzi F.
Prevalence and clinical features of atypical depression in depressed outpatients: a 467-case study.
Psychiatry Res 1999 Jun 30;86(3):259-65
"The prevalence of DSM-IV atypical depression and differences between atypical versus non-atypical depression were investigated in 467 unipolar and bipolar depressed outpatients in private practice. Consecutive outpatients presenting for treatment of a major depressive episode were assessed with the Comprehensive Assessment of Symptoms and History following DSM-IV criteria, the Montgomery-Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale. The prevalence of atypical depression was 38.1%. Of the variables investigated (unipolar and bipolar diagnoses, age at onset, gender, psychosis, comorbidity, chronicity, duration of illness, recurrences, and severity), age at onset was significantly lower, and female gender, comorbidity, and bipolar II disorder were significantly more common in atypical than nonatypical depression. Comparisons between bipolar II atypical depression and unipolar atypical depression did not show significant differences, apart from age at onset. Findings suggest that there are important clinical differences between atypical and non-atypical depression in private practice outpatients." [Abstract]

Benazzi F.
Early-onset versus late-onset atypical depression: unipolar and bipolar II.
J Affect Disord 2000 Dec;61(1-2):95-9
"BACKGROUND: To find differences between early- and late-onset atypical depression (AD). METHODS: 211 unipolar/bipolar II AD outpatients, interviewed with DSM-IV Structured Clinical Interview and depression rating scales. Logistic regression was used. RESULTS: Early-onset AD was significantly associated with age, female gender, duration of illness, recurrences, chronicity, MADRS, bipolar II and unipolar. Early-onset bipolar II AD was significantly associated with age, female gender, duration of illness, recurrences and chronicity. Early-onset unipolar AD was significantly associated with age. Limitations: Age at onset recall bias, single interviewer, non-blind, cross-sectional assessment, bipolar II diagnosis reliability. CONCLUSIONS: Bipolar II AD is more likely to be chronic if early onset." [Abstract]

Benazzi F.
Atypical depression with hypomanic symptoms.
J Affect Disord 2001 Jul;65(2):179-83
"BACKGROUND: Depressive mixed states (major depressive episodes with some hypomanic symptoms) (DMS) are not classified in DSM-IV and are understudied. The aims of this study were to find the prevalence and clinical features of DMS in atypical depression. METHODS: A total of 87 bipolar II and unipolar depressed outpatients were interviewed within the DSM-IV Structured Clinical Interview. RESULTS: More than two hypomanic symptoms were present in 50.0% of the atypical and 20.3% of the non-atypical depression cases (P=0.006). DMS mainly included irritable mood, distractibility, racing thoughts, and increased talking. LIMITATIONS: There was a single interviewer, and it was a non-blind, cross-sectional assessment, with bipolar II reliability. CONCLUSIONS: Findings have treatment implications, as antidepressants may worsen DMS, and mood stabilizers may improve it." [Abstract]

Benazzi F.
Atypical depression in private practice depressed outpatients: a 203-case study.
Compr Psychiatry 1999 Jan-Feb;40(1):80-3
"The prevalence of DSM-IV atypical depression and comparisons between atypical and typical depression were studied in 203 consecutive unipolar and bipolar depressed outpatients presenting for treatment of depression in private practice. The prevalence of atypical depression was 31%. Of the variables investigated (unipolar/bipolar diagnosis, age at baseline/onset of first major depressive episode, gender, psychosis, comorbidity, chronicity, duration of illness, recurrence, and severity), a bipolar II diagnosis was significantly more common, the age at baseline and duration of illness were significantly lower, and the proportion of females and psychiatric comorbidity were significantly higher in atypical versus typical depression. Secondary analysis showed that bipolar II atypical depression had a significantly earlier age at baseline/onset and affected more females, but there were no other significant differences versus typical depression. The findings suggest important clinical differences between atypical and typical depression, and a bipolar II subtype may be separated from the broad category of atypical depression." [Abstract]

Angst J, Gamma A, Sellaro R, Zhang H, Merikangas K.
Toward validation of atypical depression in the community: results of the Zurich cohort study.
J Affect Disord 2002 Nov;72(2):125-38
"AIMS: This paper (1) examines the validity of the atypical subtype of depression in a community-based longitudinal cohort study, (2) presents estimates of the prevalence and sex differences of DSM-IV atypical depression and a newly more broadly defined atypical syndrome in the community and (3) compares the clinical correlates and treatment patterns of those with atypical depression with other depressives. METHODS: The Zurich cohort study is comprised of 591 subjects selected from a population-based cohort of young adults representative of the canton of Zurich in Switzerland, who were screened in 1978 with the Symptom Checklist 90-R [L.R. Derogatis (1977)] and followed prospectively with five interviews between 1979 and 1993. Atypical depression was defined on a spectrum ranging from atypical major to minor to atypical depressive symptoms alone. RESULTS: The rate of DSM-IV atypical major depressive episodes in this community is 4.8% and for major atypical depression syndrome is 7.3%. Whereas there was no marked sex difference for nonatypical features, there was a significant female preponderance for DSM-IV and broadly defined atypical depressive subtypes. Systematic investigation of the diagnostic criteria for atypical depression revealed that a nonhierarchical definition of atypical depression with respect to mood reactivity yielded as valid a syndromic definition as the current hierarchy based on mood reactivity as an essential feature. Very high comorbidity (odd ratios>2.0) was found with seasonality, bipolar II, social phobia, binge eating, neurasthenia and sociopathy. LIMITATIONS: Atypical depression was not defined a priori, its criteria were derived from two sections of the Zurich interview. CONCLUSIONS: Atypical depression has high population prevalence and substantial significance in terms of clinical severity, impairment, and service use. The intriguing finding that the sex difference in depression may be attributed to atypical features of depression will need further investigation. Overall, our data indicate that the atypical subtype of depression is a valid entity based on evidence from such traditional indicators of validity as inclusion criteria and indicators of course. However, there are some problems with discriminatory validity from other disorders. Although comorbidity with these disorders may in part reflect an operational artifact of symptom overlap, further work needs to be done in distinguishing atypical depression from bipolar II." [Abstract]

Posternak MA, Zimmerman M.
Lack of association between seasonality and psychopathology in psychiatric outpatients.
Psychiatry Res 2002 Nov 15;112(3):187-94
"There exists an extensive literature documenting the impact of seasonality on rates of depression, atypical depression, bulimia, and suicide. In the present report drawn from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we reviewed the results of 1500 diagnostic evaluations of patients who presented to our psychiatric outpatient practice between 1995 and 2001. We sought to determine whether seasonal fluctuations in psychopathology were discernible at the level of how patients present for psychiatric treatment. Contrary to our hypotheses, we did not find (1) higher rates of onset of major depressive disorder in the spring and fall, (2) higher rates of depressive symptoms or rates of atypical depression in the winter, (3) higher rates of bulimia in the winter, or (4) higher rates of suicidal ideation in the spring. We conclude from these results that the association between seasonality and psychopathology may not be discernible at the level of presentations to an outpatient psychiatric practice." [Abstract]

Tam EM, Lam RW, Robertson HA, Stewart JN, Yatham LN, Zis AP.
Atypical depressive symptoms in seasonal and non-seasonal mood disorders.
J Affect Disord 1997 Jun;44(1):39-44
"The authors examined the rates of atypical depression and prevalence of specific atypical symptoms in patients with seasonal versus non-seasonal depression. Fifty-three patients with seasonal affective disorder (SAD) were compared to 54 patients with non-seasonal major depressive disorder (MDD) using the atypical depression diagnostic scale (ADDS). SAD patients scored significantly higher than non-seasonal MDD patients in hyperphagia and hypersomnia, and significantly lower in interpersonal sensitivity and other rejection avoidance. There was no difference in the rate of ADDS diagnosis of atypical depression. Differences between atypical depression and SAD suggest that they are separate subtypes of depression with an overlapping symptom picture." [Abstract]

Stewart JW, Quitkin FM, Terman M, Terman JS.
Is seasonal affective disorder a variant of atypical depression? Differential response to light therapy.
Psychiatry Res 1990 Aug;33(2):121-8
"Similar symptomatology has been described for both seasonal affective disorder (SAD) and atypical depression. For example, hyperphagia, hypersomnia, and intense lethargy are common to both, suggesting that they might be subtypes of the same disorder. If SAD and atypical depression are different manifestations of the same underlying pathophysiology, treatment effective for one might also benefit the other. Bright artificial lights (2500 lux, 6-8 a.m. and p.m.) were significantly less effective in treating eight patients diagnosed as having atypical depression without a seasonal pattern than 25 SAD patients. Differential treatment outcome suggests that SAD and atypical depression are separate disorders." [Abstract]

Sullivan PF, Prescott CA, Kendler KS.
The subtypes of major depression in a twin registry.
J Affect Disord 2002 Apr;68(2-3):273-84
"OBJECTIVE: The subtypes of major depression (MD) remain incompletely understood. While there is consensus about the existence of MD with 'typical' vegetative features, further data are required to evaluate the existence of MD with atypical features. METHOD: Assessment of MD symptomatology in year prior to interview was available in 6846 individual twins from a population-based twin registry. The nine 'A' criteria for DSM-IV MD were unpacked so that the nature of sleep disturbance, appetite and weight changes, and motoric alterations were recorded. Latent class analysis was used to create an empirical typology of MD. RESULTS: Seven latent classes appeared to provide the best representation of the data. The most severe of these classes had interpretable profiles corresponding to typical MD, atypical MD, and 'minor' but seemingly important depressive states. These classes were generally more deviant than a comparison group for nearly all available validators. There tended to be a gradient with the typical class being most extreme, minor depressive classes the least extreme, and the atypical class having an intermediate position. CONCLUSIONS: Our findings support the existence of atypical depression as a phenomenological subtype of MD. Besides the differences in symptom patterns, there are many more similarities than differences across a range of external validators. Similar to other reports, we found evidence of the importance and morbidity of depressive symptomatology that does not meet the DSM-IV MD thresholds." [Abstract]

Agosti V, Stewart JW.
Atypical and non-atypical subtypes of depression: comparison of social functioning, symptoms, course of illness, co-morbidity and demographic features.
J Affect Disord 2001 Jun;65(1):75-9
"BACKGROUND: There are scant data regarding the demographic and psychosocial characteristics of outpatients with Atypical Depression (AD). METHODS: The demographic characteristics, rates of chronic dysphoria, baseline Symptom Check List Revised, and Social Adjustment Scale scores of 320 moderately depressed patients with and without AD were compared. RESULTS: ADs had a higher number of self-reported symptoms, greater impairments in functioning, and higher rates of chronic dysphoria and bipolar II than patients without Atypical Depression (NAD). LIMITATIONS: Variables used in this study were mostly cross-sectional, and the analyses were performed post-hoc. CONCLUSIONS: These data suggest ADs had a more pernicious course of illness than NADs, and that patients with AD were more symptomatic and dysfunctional at admission." [Abstract]

Derecho CN, Wetzler S, McGinn LK, Sanderson WC, Asnis GM.
Atypical depression among psychiatric inpatients: clinical features and personality traits.
J Affect Disord 1996 Jun 20;39(1):55-9
"OBJECTIVE: This study investigates the frequency and characteristics of Atypical Depression (AD) among depressed inpatients. METHOD: Twenty-one depressed inpatients received DSM-IV diagnoses, were rated on the Hamilton Depression Rating Scale (HAMD), and assessed for AD using the Atypical Depressive Disorder Scale. AD was defined as the presence of mood reactivity and two of four associated features: hyperphagia, hypersomnia, leaden paralysis, rejection sensitivity. Mood reactivity was defined as the ability to reach 50% of a non-depressed mood. All subjects completed the SCL-90, MCMI-II, and a suicide survey. RESULTS: Seven patients (33%) met criteria for AD. AD and non-AD patients did not differ in terms of severity of depression, history of suicide attempts, levels of clinical symptomatology, age of onset of depression, prior hospitalizations, and most personality characteristics. However, AD patients scored significantly higher than non-AD patients on the SCL-90 Interpersonal Sensitivity and MCMI-II Avoidant scales, and were more likely to be single. CONCLUSION: AD is fairly prevalent on an inpatient service, comparable to the frequency found in outpatient settings. AD is not a milder form of depression. The only differences between AD and non-AD patients reflect the personality trait of rejection sensitivity which is a defining feature of AD." [Abstract]

Alpert JE, Uebelacker LA, McLean NE, Nierenberg AA, Pava JA, Worthington JJ 3rd, Tedlow JR, Rosenbaum JF, Fava M.
Social phobia, avoidant personality disorder and atypical depression: co-occurrence and clinical implications.
Psychol Med 1997 May;27(3):627-33
"BACKGROUND: Increasing attention has been directed in recent years to the detection and treatment of psychiatric co-morbidity among depressed individuals. The overlap of social phobia (SP) and avoidant personality disorder (APD) has been well recognized and a relationship between these disorders and depression has been suggested. METHODS: The pattern and clinical implications of co-morbidity of SP and APD with major depressive disorder (MDD), diagnosed by DSM-III-R criteria, were studied among 243 out-patients presenting with depression. RESULTS: Overall, 26.7% of adults in our sample with MDD met criteria for SP and 28.4% for APD. Almost two-thirds of depressed adults meeting criteria for social phobia or avoidant personality disorder met criteria for both (SP+APD). Depressed adults who met criteria for both SP+APD exhibited a significantly higher proportion of atypical depression (54.8%) compared with those with neither SP nor APD (31.1%). Among depressed patients, the co-occurrence of SP with APD was also associated with an earlier age of onset of MDD, a greater number of comorbid Axis I diagnoses, and greater impairment of social adjustment and assertiveness. CONCLUSIONS: Results confirm the overlap of SP and APD in a depressed population and the high prevalence of these disorders in MDD. They suggest that depressed individuals with both SP and APD but not SP alone are at particularly high risk for atypical depression and for social dysfunction in excess of that caused by a current major depression." [Abstract]

Nierenberg AA, Phillips KA, Petersen TJ, Kelly KE, Alpert JE, Worthington JJ, Tedlow JR, Rosenbaum JF, Fava M.
Body dysmorphic disorder in outpatients with major depression.
J Affect Disord 2002 May;69(1-3):141-8
"BACKGROUND: Body dysmorphic disorder (BDD) is a distressing and impairing preoccupation with an imagined or slight defect in appearance, with depression as its most frequent comorbid condition. The purpose of this study was to evaluate the rate of BDD in a cohort of consecutive outpatients with typical and atypical major depressive disorder. METHODS: Three hundred and fifty consecutive outpatient subjects with major depression who entered an antidepressant treatment study were evaluated drug-free with the SCID-P, SCID-II, a diagnostic module for BDD, and other measures. Depressed subjects with comorbid BDD were compared to those without BDD with regard to demographics, course of depression, comorbid conditions, and other relevant variables. RESULTS: Twenty-eight (8.0%) subjects had a lifetime history of BDD and 23 (6.6%) had current BDD. Those with comorbid lifetime BDD had an earlier age of onset of depression and longer duration of the current episode, but not a greater number of depressive episodes or greater severity of depression. Subjects with and without BDD were similar with respect to age, gender, and marital status. There was a higher rate of lifetime and current BDD in subjects with atypical depression than in those with non-atypical depression (14.4% compared to 5.1%; chi(2)=6.63; P=0.01: 11.6% vs. 4.1%; chi(2)=7.02; P=0.02). Subjects with BDD also had higher rates of social phobia, any eating disorder, and any somatoform disorder but not obsessive compulsive disorder. They also had higher rates of avoidant, histrionic, and dependent personality disorders. LIMITATIONS: As we did not specifically examine bipolar spectrum conditions, the present study cannot address to what extent BDD is comorbid with Bipolar-II disorder. CONCLUSIONS: BDD is frequently comorbid with major depression, is associated with an earlier age of onset of depression and longer duration of depressive episodes, and is found more frequently with atypical than non-atypical depression." [Abstract]

Mannuzza S, Schneier FR, Chapman TF, Liebowitz MR, Klein DF, Fyer AJ.
Generalized social phobia. Reliability and validity.
Arch Gen Psychiatry 1995 Mar;52(3):230-7
"OBJECTIVE: To investigate the reliability and validity of DSM-III-R "generalized" social phobia by examining interrater agreement and comparing patients with generalized and "nongeneralized" social phobia on demographic characteristics, clinical variables, and familial social phobia. DESIGN: Two senior clinicians classified 129 patients attending an anxiety clinic as having DSM-III-R social phobia that is generalized (fears most social situations) or nongeneralized (less than most) based on independent narrative review. RESULTS: Good reliability was achieved (kappa = 0.69). Patients with generalized social phobia were more often single, had earlier onsets of social phobia, had more interactional fears, and had higher rates of atypical depression and alcoholism. Familial social phobia was more common among patients with generalized social phobia than patients with nongeneralized social phobia and controls, with no difference between the latter two groups. CONCLUSIONS: Generalized social phobia (1) can be distinguished reliably from nongeneralized social phobia, (2) is a valid subtype, and (3) may characterize a familial form of the disorder." [Abstract]

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Recent Atypical Depression Research

1) Silverstein B, Edwards T, Gamma A, Ajdacic-Gross V, Rossler W, Angst J
The role played by depression associated with somatic symptomatology in accounting for the gender difference in the prevalence of depression.
Soc Psychiatry Psychiatr Epidemiol. 2012 Jul 3;
PURPOSE: A variety of studies suggest the existence of a distinct phenotype of somatic depression, i.e., depression accompanied by significant somatic symptomatology. Previous research suggests that the gender difference in the prevalence of depression is primarily due to a difference in somatic depression. The aim of this study was to compare the gender difference in the prevalence of somatic depression and of depression not accompanied by significant somatic symptomatology (labelled "pure" depression) in two representative samples, the National Comorbidity Survey-Replication (NCS-R) and the Zurich Study. METHOD: The gender difference in lifetime somatic depression was compared to that of pure depression based on analyses weighted back to the general population in two representative samples. The NCS-R analyses involved a narrow definition of somatic depression with items from the DSM criteria for depression-appetite, sleep, and fatigue. The analysis of the Zurich study added headaches, body image issues, and breathing difficulties to the criteria and comparison to atypical depression. RESULTS: In both samples, the gender difference in depressive prevalence was due to a large difference in somatic depression with other phenotypes showing little or no gender difference. The gender differences were found to be due to the somatic symptoms rather than the number of symptoms and were much larger for somatic than for atypical depression. CONCLUSION: The gender difference in the prevalence of depression results from the higher prevalence among women of a specific phenotype, somatic depression. [PubMed Citation] [Order full text from Infotrieve]

2) Schellekens H, Finger BC, Dinan TG, Cryan JF
Ghrelin signalling and obesity: At the interface of stress, mood and food reward.
Pharmacol Ther. 2012 Sep;135(3):316-26.
The neuronal circuitry underlying the complex relationship between stress, mood and food intake are slowly being unravelled and several studies suggest a key role herein for the peripherally derived hormone, ghrelin. Evidence is accumulating linking obesity as an environmental risk factor to psychiatric disorders such as stress, anxiety and depression. Ghrelin is the only known orexigenic hormone from the periphery to stimulate food intake. Plasma ghrelin levels are enhanced under conditions of physiological stress and ghrelin has recently been suggested to play an important role in stress-induced food reward behaviour. In addition, chronic stress or atypical depression has often demonstrated to correlate with an increase in ingestion of caloric dense 'comfort foods' and have been implicated as one of the major contributor to the increased prevalence of obesity. Recent evidence suggests ghrelin as a critical factor at the interface of homeostatic control of appetite and reward circuitries, modulating the hedonic aspects of food intake. Therefore, the reward-related feeding of ghrelin may reveal itself as an important factor in the development of addiction to certain foods, similar to its involvement in the dependence to drugs of abuse, including alcohol. This review will highlight the accumulating evidence demonstrating the close interaction between food, mood and stress and the development of obesity. We consider the ghrelinergic system as an effective target for the development of successful anti-obesity pharmacotherapies, which not only affects appetite but also selectively modulates the rewarding properties of food and impact on psychological well-being in conditions of stress, anxiety and depression. [PubMed Citation] [Order full text from Infotrieve]

3) Culpepper L
The use of MAOIs in primary care.
J Clin Psychiatry. 2012 May;73(5):e19.
Once a mainstay of antidepressant treatment, monoamine oxidase inhibitors (MAOIs) have largely been abandoned in favor of medications with improved safety profiles. However, remission rates for patients with depression remain low, and primary care physicians continue to have patients who either do not respond or only partially respond to newer medications. MAOIs have proven efficacy for depression, particularly for patients with atypical depression, high levels of anxiety, anergic bipolar depression, and treatment-resistant depression. A transdermal delivery system has been developed for an MAOI that avoids the need for patients to follow dietary restrictions and has fewer metabolic and sexual side effects than some newer medications, which may make it particularly suited for use in primary care. [PubMed Citation] [Order full text from Infotrieve]

4) Nierenberg AA
Advancing the treatment of depression with personalized medicine.
J Clin Psychiatry. 2012 May;73(5):e17.
Personalized medicine holds the hope of increasing the likelihood that patients with depression will respond to treatment and achieve remission. Currently, insufficient evidence is available supporting personalizing variables. However, ongoing large individualized comparative effectiveness studies may provide detailed information in the future. Some of the features that have potential as personalizing variables that can help predict response to particular treatments, pending replication studies, include sex, hormonal status, atypical depression, childhood trauma, family history of mental illness, and certain biomarkers and genetic polymorphisms. [PubMed Citation] [Order full text from Infotrieve]

5) Levitan RD, Davis C, Kaplan AS, Arenovich T, Phillips DI, Ravindran AV
Obesity comorbidity in unipolar major depressive disorder: refining the core phenotype.
J Clin Psychiatry. 2012 May 15;
OBJECTIVE: While a significant body of research has demonstrated high comorbidity rates between depression and obesity, the vast majority of this work has considered depression as a unitary diagnosis. Given that increased appetite and weight gain are highly characteristic of the "atypical" subtype of depression, while classic depression is characterized by decreased appetite and weight loss, it would be important to examine whether increased obesity risk is consistent across the major vegetative subtypes of depression or is limited to the atypical subtype. METHOD: Using data from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we identified 5,092 US adults with past or current major depression based on DSM-IV-TR criteria and 1,500 gender-matched controls. Each depressed subject was designated as having classic, atypical, or undifferentiated depression based on core vegetative symptoms. Logistic regression models examined rates of current obesity (defined as a current body mass index [kg/m2] > 30) across the 3 depressive subgroups and nondepressed controls, adjusting for demographic differences. To limit the possible effect of current depressive symptoms on observed obesity rates, secondary analyses were completed in individuals with past depression only. RESULTS: Subjects with atypical depression had markedly elevated obesity rates compared to population controls and to other depressed subjects, with corresponding pairwise odds ratios consistently greater than 2.0 (P < .001). In contrast, obesity rates were not significantly different in subjects with classic depression and nondepressed controls. These results were manifest in individuals with either current or past depression and were independent of gender and age. CONCLUSIONS: While many individuals with classic depression will present with obesity due to the high prevalence of both disorders, only atypical depression is associated with an elevated risk of obesity relative to the population at large. Refining the target phenotype(s) for future work on depression and obesity might improve our understanding, prevention, and treatment of this complex clinical problem. [PubMed Citation] [Order full text from Infotrieve]

6) Avedisova AS, Marachev MP
[Clinical typology of atypical depression in bipolar and unipolar affective disorders].
Zh Nevrol Psikhiatr Im S S Korsakova. 2012;112(3 Pt 1):18-23.
Forty-six patients with the DSM-IV diagnosis of atypical depression have been examined using clinical-psychopathological and psychometric methods. Based on prevailing symptoms, three types of atypical depression have been singled out: atypical depression with mood reactivity, atypical depression with inverted autonomous symptoms and atypical depression with rejection sensitivity. Sociodemographic and clinical characteristics of each variant are presented and their representation in the structure of bipolar and unipolar depressive disorder is determined as well. [PubMed Citation] [Order full text from Infotrieve]

7) Maciukiewicz M, Czerski PM, Leszczynska-Rodziewicz A, Kapelski P, Szczepankiewicz A, Dmitrzak-Weglarz M, Skibinska M, Pawlak J, Hauser J, Karlowski WM
Analysis of OPCRIT results indicate the presence of a novel 'social functioning' domain and complex structure of other dimensions in the Wielkopolska (Poland) population.
Schizophr Res. 2012 Jul;138(2-3):223-32.
[PubMed Citation] [Order full text from Infotrieve]

8) O'Keane V, Frodl T, Dinan TG
A review of Atypical depression in relation to the course of depression and changes in HPA axis organization.
Psychoneuroendocrinology. 2012 Apr 10;
Depression is a clinically heterogenous condition defined by sub-types that can have diametrically opposed features, such as sleep and appetite. Within the same individual these features may change over time, and different symptom clusters may respond selectively to different treatments. It has been hypothesized that different pathophysiological processes may be operating in the different sub-types of depression and specifically that Melancholic depression may be associated with relative overactivity, and Atypical depression with relative hypoactivity, of the hypothalamic drive of the HPA axis. A consistent finding that emerges from the literature is that the experience of depression alters over the course of the illness with the features of Atypical depression dominating a more chronic clinical picture. This suggests that different stress states characterize the different profiles of depression as the illness becomes more chronic. There is evidence that the corticotropin-releasing hormone (CRH) control of HPA axis output is reduced in Atypical, compared to Melancholic, sub-types, but there is no convincing evidence that overall HPA activity, i.e., cortisol output, reduces. We suggest that there is a "switch" in the regulation of the HPA system from CRH to arginine vasopressin (AVP) control as stress becomes more sustained or repeated; resulting in an altered homeostasis within the HPA system. Cortisol, and the neuropeptides CRH and AVP, have different neurobiological, behavioural and experiental effects. The "switch" process should result in different neuropeptide/cortisol combinations and ratios and may explain the changing profile of depression over time. The heuristic merit in making a distinction between the different clinical states of depression will be discussed. [PubMed Citation] [Order full text from Infotrieve]

9) Brunault P, Jacobi D, Miknius V, Bourbao-Tournois C, Huten N, Gaillard P, Couet C, Camus V, Ballon N
High preoperative depression, phobic anxiety, and binge eating scores and low medium-term weight loss in sleeve gastrectomy obese patients: a preliminary cohort study.
Psychosomatics. 2012 Jul;53(4):363-70.
[PubMed Citation] [Order full text from Infotrieve]

10) Dauphinais DR, Rosenthal JZ, Terman M, DiFebo HM, Tuggle C, Rosenthal NE
Controlled trial of safety and efficacy of bright light therapy vs. negative air ions in patients with bipolar depression.
Psychiatry Res. 2012 Mar 30;196(1):57-61.
Treatment of bipolar disorder often results in patients taking several drugs in an attempt to alleviate residual depressive symptoms, which can lead to an accumulation of side effects. New treatments for bipolar depression that do not increase the side effect burden are needed. One nonpharmacological treatment with few side effects, bright light therapy, has been shown to be an effective therapy for seasonal affective disorder, yet has not been extensively studied for other forms of depression. Forty-four adults with bipolar disorder, depressed phase were randomized to treatment with bright light therapy, low-density or high-density negative ion generator for 8 weeks. The primary measure of efficacy was the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS). Adverse events were assessed using the Young Mania Rating Scale (YMRS) and Systematic Assessment for Treatment Emergent effects (SAFTEE). All outcome variables were statistically analyzed using a mixed model repeated measure analysis of variance (ANOVA). The results showed no statistically significant differences between groups in any outcome measures at study end point; adverse events, including switches into hypomania, were rare. Further research is needed to determine the efficacy of bright light therapy in this population. [PubMed Citation] [Order full text from Infotrieve]

11) Bech P, Stage KB, Larsen JK, Vestergaard P, Gram LF
The predictive validity of atypical neurovegetative depressive symptoms identified by the first principal component in the DUAG trial of moclobemide versus clomipramine.
J Affect Disord. 2012 Nov;140(3):253-259.
OBJECTIVE: To investigate to what extent the primary depression subtype atypical depression can predict differential outcome of the mono-amino-oxidase inhibitor (MAO-I) moclobemide and the tricyclic antidepressant clomipramine in the Danish University Antidepressant Group Study (DUAG). METHODS: In a randomised, double blind trial, a total of 117 patients with major depression were treated over 6weeks with either 400mg moclobemide or 150mg clomipramine. A baseline principal component analysis (PCA) was performed to identify atypical symptoms on the combined depression scales (Hamilton Depression Scale (HAM-D(17)) and the Quantitative Scale for Atypical Depression (QSAD)). The primary outcome scale was the subscale HAM-D(6) which contains the pure items of depression. RESULTS: PCA identified two items with loadings opposite to the other depression items within HAM-D(17) and QSAD, namely increased duration of sleep and increased appetite (atypical neurovegetative symptoms). Patients with a positive score at baseline on these items were classified as having atypical depression. In total 13 patients were classified as having atypical depression. Within this group of patients 8 received clomipramine and 5 patients received moclobemide. At endpoint the moclobemide treated patients had a significantly better response than the clomipramine treated (P=0.036), effect size 1.42, when using HAM-D(6) as outcome. However, in the 104 patients classified as having typical depression clomipramine was superior to moclobemide (P=0.034), effect size 0.47. LIMITATIONS: The number of patients with atypical neurovegetative symptoms was very small and no placebo arm was included. CONCLUSIONS: It is very important to screen for atypical depression (increased duration of sleep/increased appetite) in the acute therapy of patients with major depression. Our results add to the body of evidence that monoamine oxidase inhibitors are superior to tricyclic antidepressants in this sub-group of patients. [PubMed Citation] [Order full text from Infotrieve]

12) Murck H, Schüssler P, Steiger A
Renin-angiotensin-aldosterone system: the forgotten stress hormone system: relationship to depression and sleep.
Pharmacopsychiatry. 2012 May;45(3):83-95.
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13) Koić E, Strkalj-Ivezić S, Venus M, John N
[Excessive daytime sleepiness--as possible suicidal equivalent in people with depressive disorder].
Lijec Vjesn. 2011 Jul-Aug;133(7-8):263-8.
This paper presents the case of a patient suffering from atypical depression, with excessive daytime sleepiness, which was a suicidal equivalent. Patients who suffer from depression and sleep disorders can have an increased risk of suicidality, and to them should pay increased attention. Field of suicide as a means of resolving conflicts and unconscious mental escape from the reality of the obstacles, including sleep and daytime sleepiness, which may represent a form of "temporary suicide". The authors recommend that hypersomnia, daytime sleepiness in depressed patients and other sleep disorders should be treated as a potential risk factor for suicidal behavior. [PubMed Citation] [Order full text from Infotrieve]

14) Shibayama M
[Differential diagnosis between dissociative disorders and schizophrenia].
Seishin Shinkeigaku Zasshi. 2011;113(9):906-11.
The differential diagnosis of dissociative disorders includes many psychiatric disorders, such as schizophrenia, bipolar disorders (especially bipolar II disorder), depressive disorder (especially atypical depression), epilepsy, Asperger syndrome, and borderline personality disorder. The theme of this paper is the differential diagnosis between dissociative disorders and schizophrenia. Schneiderian first-rank symptoms in schizophrenia are common in dissociative disorders, especially in dissociative identity disorder (DID). Many DID patients have been misdiagnosed as schizophrenics and treated with neuroleptics. We compared and examined Schneiderian symptoms of schizophrenia and those of dissociative disorders from a structural viewpoint. In dissociative disorders, delusional perception and somatic passivity are not seen. "Lateness" and "Precedence of the Other" originated from the concept of "Pattern Reversal" (H. Yasunaga)" is characteristic of schizophrenia. It is important to check these basic structure of schizophrenia in subjective experiences in differential diagnosis between dissociative disorders and schizophrenia. [PubMed Citation] [Order full text from Infotrieve]

15) Bowens N, Heydendael W, Bhatnagar S, Jacobson L
Lack of elevations in glucocorticoids correlates with dysphoria-like behavior after repeated social defeat.
Physiol Behav. 2012 Feb 28;105(4):958-65.
Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis is often abnormal in depression and could hold clues for better treatment of this debilitating disease. However, it has been difficult to use HPA activity as a depression biomarker because both HPA hyperactivity and HPA hypoactivity have been reported in depression. Melancholic depression has typically been associated with HPA hyperactivity, while atypical depression has been linked with HPA hypoactivity. Many animal models of chronic stress recapitulate behavioral aberrations and elevated HPA activity that could represent a model for melancholic depression. However, there are no animal models that could be used to elucidate the etiology or treatment of atypical depression. We have used repeated social defeat in mice to test the hypothesis that this chronic stress would induce dysphoria-like behavior associated with HPA hypoactivity in a subset of subjects. Intruder mice were placed in the home cage of an aggressive resident mouse for 5 min/d for 30 days. The majority of intruder mice had elevated basal plasma corticosterone (High Morning Corticosterone, or HMC) and adrenal 11? hydroxylase mRNA levels relative to control mice that were handled daily. However, a subset of intruder mice (Low Morning Corticosterone; LMC) exhibited basal plasma corticosterone and 11? hydroxylase mRNA levels that were indistinguishable from control levels. Significant changes in emotional behavior only occurred in LMC mice, which exhibited anxiety-like increases in activity and defecation during tail suspension and anhedonia-like decreases in sucrose preference. Relative to HMC mice, LMC mice also showed increases in gene expression of mineralocorticoid receptor in CA2 hippocampus, consistent with the possibility that HPA activity in this group is constrained by increased sensitivity to glucocorticoid negative feedback. LMC mice also exhibited increased c-fos gene expression compared to HMC mice in the paraventricular hypothalamus and lateral septum suggesting that central pathways fail to habituate to chronic stress even though adrenocortical activity is not stimulated. We conclude that LMC mice showed adrenocortical hyporesponsiveness, which in combination with the behavioral abnormalities in this group may represent a model for the HPA hypoactivity associated with atypical depression. [PubMed Citation] [Order full text from Infotrieve]

16) Sachs-Ericsson N, Selby E, Corsentino E, Collins N, Sawyer K, Hames J, Arce D, Joiner T, Steffens DC
Depressed Older Patients With the Atypical Features of Interpersonal Rejection Sensitivity and Reversed-Vegetative Symptoms are Similar to Younger Atypical Patients.
Am J Geriatr Psychiatry. 2012 Jul;20(7):622-34.
[PubMed Citation] [Order full text from Infotrieve]

17) Farley S, Dumas S, El Mestikawy S, Giros B
Increased expression of the Vesicular Glutamate Transporter-1 (VGLUT1) in the prefrontal cortex correlates with differential vulnerability to chronic stress in various mouse strains: effects of fluoxetine and MK-801.
Neuropharmacology. 2012 Jan;62(1):503-17.
Major depression is a chronic psychiatric illness that is highly prevalent and disabling. The available medications are ineffective for many patients suggesting that differents molecular pathways could be specifically altered in the unresponsive patients. Recently, the glutamatergic system has emerged as a target in the research on depression and acute NMDA receptor blockade has been shown to produce strong antidepressant effects. We have studied the adaptations of four mice strains (C57BL/6, DBA/2, C3H and BALB/c) to a chronic unpredictable stress protocol, a widely used model of depression in rodents. BALB/c mice displayed strikingly different behavioral and neurochemical adaptations compared to the other strains tested, suggesting that different molecular pathways are involved in their specific vulnerability. They became hyperactive during the dark period, anhedonic-like and displayed no alterations in the tail suspension test (TST). After chronic stress, only the BALB/c displayed an increased frontocortical VGLUT1 expression which is suggestive of a dysregulation of their prefrontal glutamatergic system, and no BDNF mRNA alteration, although the acute stress modulation of this mRNA is similar to the other strains. Chronic administration of an antagonist of NMDA receptors, MK-801, induced antidepressant-like effects in the TST for stressed BALB/c, but was ineffective for the hyperactivity and anhedonia-like behavior, in contrast to fluoxetine. Chronic MK-801 was totally inactive on the behavior of stressed C57BL/6 mice. MK-801, but not fluoxetine, inhibited the VGLUT1 prefrontal increase in BALB/c. Fluoxetine increased VGLUT1 and BDNF mRNA expression in the hippocampus of the C57BL/6 but not in the BALB/c strain, suggesting a different reactivity in-between strain to both stress and antidepressant. Interestingly enough, the BDNF or VGLUT1 increase is not necessary to reverse the stress induced behavioral alterations in our experimental settings. This observation supports the conclusion that BDNF and VGLUT1 are depressive state markers, but not involved in its etiology. Finally, there is a substantial similarity between the phenotypes that are observed in the BALB/c mice and endogenous depression in humans, as well as between C57BL/6 mice and atypical depression. To have a better understanding of the variability of depression etiologies in human, and the implication of the glutamatergic system, it may be suggested that future animal studies in the mouse would systematically compare the two strains BALB/c and C57BL/6 for the identification of relevant biological mechanisms. This article is part of a special Issue entitled 'Anxiety and Depression'. [PubMed Citation] [Order full text from Infotrieve]

18) Blanco C, Vesga-López O, Stewart JW, Liu SM, Grant BF, Hasin DS
Epidemiology of major depression with atypical features: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
J Clin Psychiatry. 2012 Feb;73(2):224-32.
[PubMed Citation] [Order full text from Infotrieve]

19) Yoon HK, Kim YK, Lee HJ, Kwon DY, Kim L
Role of cytokines in atypical depression.
Nord J Psychiatry. 2012 Jun;66(3):183-8.
[PubMed Citation] [Order full text from Infotrieve]

20) Harald B, Gordon P
Meta-review of depressive subtyping models.
J Affect Disord. 2012 Jul;139(2):126-40.
[PubMed Citation] [Order full text from Infotrieve]