Cortisol secretion in prepubertal children with major depressive disorder. Episode and recovery

Plasma cortisol concentrations were measured every 20 minutes for 24 hours in a group of 45 rigorously assessed, drug-free, prepubertal children who met the unmodified Research Diagnostic Criteria for major depressive disorder (MDD), 20 children with nonaffective psychiatric disorders, and eight normal controls. All children were studied in a low-stress environment. There were no significant differences in plasma cortisol concentration among the three groups as measured by 24-hour mean, peak, nocturnal rise, or nadir values. Division of the MDD group into subgroups based on endogenicity, psychotic symptoms, and suicidality also failed to reveal significant differences for cortisol secretion. Hypersecretion of cortisol (defined as 2 SDs above the grand mean) was identified in only four children with depressive illness and one normal control. Following clinical recovery, 24 depressed children were restudied in a drug-free state and compared with themselves during the episode of illness and with both groups of controls. No significant differences in plasma cortisol concentrations were found. All four depressed hypersecretors were restudied after clinical recovery, and one showed persistence of hypersecretion. These results suggest that abnormalities of cortisol secretion occur infrequently in prepubertal children with major depression when they are studied in a nonstressful environment.     

Parent-child bonding and family functioning in depressed children and children at high risk and low risk for future depression

OBJECTIVE: To evaluate parent-child bonding and familial functioning in depressed children, children at high risk for depression, and low-risk controls. METHOD: Diagnoses of children and their relatives were obtained via structured interviews with all available informants. Depressed children (n = 54) received a diagnosis of current major depressive disorder (MDD). The high-risk children (n = 21) had no lifetime diagnoses of mood disorders, but at least one first-degree relative with a lifetime history of depression. The low-risk controls (n = 23) had no lifetime psychiatric disorders and no first-degree relative with a lifetime history of mood disorders. Parent-child bonding was evaluated with the child's report on the Parental Bonding Instrument (PBI). Familial functioning was evaluated with each parent answering the Family Assessment Device (FAD). RESULTS: Significant differences were found between the MDD and low-risk children on most parameters of the PBI and FAD. The children with MDD reported significantly elevated maternal overprotection, and their fathers scored significantly lower on the FAD scales of Behavioral Control and General Functioning, compared with the high-risk children. Mothers of high-risk children had significantly lower scores on the Roles and Affective Involvement dimensions of the FAD compared with mothers of low-risk children. Current maternal depression had a deleterious effect on the child's perception of maternal protection and paternal care, mother's report on all FAD scales, and father's report on most FAD scales, whether interacting with the child's depression or existing even if the child was not depressed. CONCLUSION: Maternal depression and its interaction with the child's depression appear to have negative consequences for parent-child bonding and family functioning.     

Clinical characteristics of depressive symptoms in children and adolescents with major depressive disorder

OBJECTIVE: Very few studies have compared the symptoms of major depressive disorder (MDD) and rates of comorbid psychiatric disorders between depressed children and adolescents. The aim of this study was to reproduce and extend these findings. METHOD: The Kiddie Schedule for Affective Disorders and Schizophrenia, present version (KSADS-P) was administered to parents (about their children) and in face-to-face interviews with 916 subjects aged 5.6 to 17.9 years with MDD (DSM criteria) (715 adolescents and 201 children; 348 male and 568 female). The subjects were consecutive referrals to an outpatient mood and anxiety disorders clinic. RESULTS: Depressed adolescents had significantly more hopelessness/helplessness, lack of energy/tiredness, hypersomnia, weight loss, and suicidality compared with children (p values < or = .001). In comparison with children, adolescents had significantly more substance abuse and less comorbid separation anxiety disorder and attention-deficit/hyperactivity disorder (p values < or = .001). Depressed female adolescents had significantly more suicidality than depressed male adolescents (p < or = .001). There were no other sex differences between males and females. The symptoms of depressed adolescents grouped into 3 factors (endogenous, negative cognitions/suicidality, and appetite/weight), whereas the symptoms in children grouped into 2 factors (endogenous/negative cognitions/suicidality and appetite/weight). CONCLUSIONS: These results provide further evidence for the continuity of MDD from childhood to adolescence.     

Families at high and low risk for depression: a 3-generation study

BACKGROUND: The familial nature of early-onset major depressive disorder (MDD) has been documented in numerous family studies of adults and is supported by studies of offspring of parents with MDD, for whom the risk is more than 3-fold. None of the published high-risk studies have gone beyond 2 generations, and few have a longitudinal design. We report results of an approximately 20-year follow-up of families at high and low risk for depression. The first 2 generations were interviewed 4 times during this period. The offspring from the second generation are now adults and have children of their own, the third generation of the original cohort. OBJECTIVE: To examine the familial aggregation of psychiatric disorders and functioning in grandchildren by their parents' and grandparents' depression status. DESIGN: Longitudinal, retrospective cohort, family study. PARTICIPANTS: One hundred sixty-one grandchildren and their parents and grandparents. MAIN OUTCOME MEASURES: Lifetime rate of psychiatric disorder and functioning in grandchildren, stratified by parental and by grandparental depression status, collected by clinicians blind to diagnoses of previous generations and to previous interviews. RESULTS: There were high rates of psychiatric disorders, particularly anxiety disorders, in the grandchildren with 2 generations of major depression, with 59.2% of these grandchildren (mean age, 12 years) already having a psychiatric disorder. The effect of parental depression on grandchildren's outcomes differed significantly with grandparental depression status. Among families with a depressed grandparent, increased risk of anxiety (relative risk, 5.17; 95% confidence interval, 1.4-18.7; P = .01) and increased risk of any disorder (relative risk, 5.52; 95% confidence interval, 2.0-15.4; P = .002) were observed in grandchildren with a depressed parent as compared with those with nondepressed parents. The severity of parental depression, as measured by impairment, significantly increased the rate of a mood disorder in these grandchildren (relative risk, 2.44; 95% confidence interval, 1.1-5.5; P = .03). In contrast, among grandchildren with nonfamilial depression, ie, depressed parents with no depressed grandparents, there was no significant effect of parental MDD on grandchildren diagnoses. However, parental MDD, regardless of whether families had a depressed grandparent, had a significant impact on the grandchildren's overall functioning. Potential confounding variables did not affect the strength of the association with parental and grandparental depression. CONCLUSIONS: The association between parental MDD and child diagnosis is moderated by grandparental MDD status. The rates of psychopathology are highest in grandchildren of parents and grandparents with a moderately to severely impairing depression. Anxiety disorders are the early sign of psychopathology in the young grandchildren. Early interventions in the offspring of 2 generations affected with moderately to severely impairing MDD seem warranted. This familial group may be the target for neuroimaging, genetic, and other biological studies.     

Prolactin response to thyrotropin-releasing hormone in schizoaffective depressed compared to depressed and schizophrenic men and healthy controls

Biological tests may help clarify the relationship of schizoaffective disorder to major depressive disorder (MDD) and schizophrenia (SCZ). Thyrotropin-releasing hormone (TRH), 500 micrograms, was administered intravenously to eight schizoaffective depressed (SD), ten SCZ, 23 MDD patients and 43 healthy controls (HC), all males, ages 20-66 years and drug-free. Research Diagnostic Criteria (RDC) were utilized for establishing diagnoses, Hamilton Rating Scale for Depression (HRSD) total scores were used for assessing depressive symptoms. There were no differences in dmax PRL (post-TRH prolactin peak minus baseline, mean +/- SD) amongst SD, SCZ and HC groups (27.3 +/- 5.2, 28.8 +/- 5.4 and 31.5 +/- 5.6 ng/ml respectively). Mean dmax PRL in MDD was significantly lower than each of the other three groups (17.1 +/- 2.2 ng/ml, P less than 0.05 for all). The essentially normal PRL response to TRH in SD, significantly different from MDD but similar to SCZ parallels our previous observations on the pattern of thyrotropin (TSH) response to TRH in the same diagnostic groups. These biological findings may be taken to indicate that schizoaffective disorder, depressed subtype, is closer to schizophrenia than to major depressive disorder. However, they cannot be considered definitive evidence to that effect since schizoaffective disorders are known to be quite heterogeneous, and since the utilized biological tests lack specificity.     

Multiple hormonal responses to morphine: relationship to diagnosis and dexamethasone suppression

Plasma cortisol, prolactin (PRL), growth hormone (GH), and thyroid stimulating hormone (TSH) responses to intravenous morphine (0.1 mg/kg body weight) were investigated in five healthy women and 22 female psychiatric inpatients (eight with major depression, 12 with schizophrenia and two with personality disorders) during a 120 min period. The results were also related to a subsequent dexamethasone suppression test (DST). Morphine caused a strong and progressive decline in plasma cortisol which was uniform in controls, depressed, and nondepressed patients. DST nonsuppressors had significantly higher cortisol levels during the entire period, but the same response to morphine. Morphine strongly stimulated PRL secretion, which was found to be significantly smaller in patients than in controls, but no difference was seen between depressed and nondepressed subjects. GH and TSH showed only minor and variable changes after morphine, with no overall significant differences. The data in this study do not support the assumption of a major alteration in opiate receptor responsivity either in depression or in DST nonsuppressor patients insofar as the regulation of the adrenal, thyroid, GH and PRL hormone secretion is concerned.     

Clinical differences between suicidal and nonsuicidal depressed children and adolescents

OBJECTIVE: To examine the clinical symptoms and comorbid psychiatric disorders of depressed children and adolescents with and without clinically significant suicidal ideation. METHOD: Children and adolescents aged 7 to 17 years with current DSM-III-R major depressive disorder (MDD) (N = 135) were recruited between January 1987 and April 2002. Current MDD symptoms and lifetime comorbid psychiatric disorders were assessed using either a combination of the Schedule for Affective Disorders and Schizophrenia for School Age Children-Epidemiologic and -Present Episode versions or the -Present Lifetime version. Thirty-two percent (N = 43) of the depressed subjects were classified as suicidal (at least suicidal ideation with a plan). RESULTS: Depressed suicidal youth presented with a more severe episode (p = .001) and a poorer functional status (p = .019), were more hopeless (p = .001), and presented more frequently with insomnia (p = .011). There was an interaction between suicide x sex x pubertal status for severity of MDD (p = .013), the presence of hopelessness (p < .001), poor functional status (p = .023), and comorbidity with a lifetime history of any disruptive behavior (p = .019). Among pre-pubertal depressed males, suicidal boys had significantly increased severity of MDD (p = .025) and poorer functional status (p = .044) than non-suicidal boys. Among postpubertal depressed females, suicidal girls were more frequently hopeless (p = .008) and presented an increased severity of MDD (p = .022) and more frequent lifetime history of any disruptive behavior (p = .03) when compared with nonsuicidal girls. CONCLUSION: There appears to be a sex difference for some clinical features, particularly hopelessness, among depressed suicidal children and adolescents. Whether hopelessness is a sex-specific characteristic of depressed suicidal children and adolescents requires further study.     

Physical health problems in depressed and nondepressed children and adolescents of parents with opiate dependence

The increased risk of physical health problems in adult depressed patients has been shown in numerous studies. A recent study of the offspring of depressed parents found similar associations. The purpose of this study is to examine the strength and specificity of the association between depression and physical health problems in children and adolescents whose parents are dependent upon opiates. The sample consisted of offspring ages 6-17 (mean age 11 years) of opiate addicts who had a history of major depressive disorder (MDD; n = 28); other mood disorders (n = 31); no history of mood disorders but other psychiatric disorders (n = 92); or no history of psychiatric disorder (n = 127). Detailed psychiatric assessment and medical history of the offspring by direct interview with the offspring and an informant were obtained blind to parental diagnosis. After controlling for possible confounders, there was an increased risk of dermatological disorders, headache, other neurological/neuromuscular disorders, bronchitis, other respiratory disorders and hospitalizations for nonsurgical procedures in offspring with MDD, as compared to nonpsychiatrically ill controls. The offspring with other mood disorders had a slightly elevated risk. Major depression in children and adolescents whose parents are dependent on opiates is associated with increased risk of physical health problems. This finding is consistent with other reports and the timing of the physical health problems requires further study.     

Children with prepubertal-onset major depressive disorder and anxiety grown up

BACKGROUND: The continuity in adulthood of major depressive disorder (MDD) first arising before puberty is largely unknown. This information could guide early treatment and clarify the appropriateness of including children with MDD in genetic studies. METHODS: Eighty-three subjects with onset of MDD, 44 subjects with anxiety disorder and no MDD, and 91 subjects with no evidence of past or current psychiatric disorders were assessed by two psychiatrists before puberty (Tanner stage < III) and were evaluated 10 to 15 years later as adults by an independent team without knowledge of the initial diagnosis. RESULTS: The clinical outcome of children with prepubertal-onset MDD in adulthood includes a high risk of suicide attempts (nearly 3-fold compared with normal controls and 2-fold compared with children with anxiety) and bipolar disorder. Compared with controls, both the children with MDD and those with anxiety went on to have increased risk of substance abuse and conduct disorder but not other disorders, increased use of longterm psychiatric and medical services, and overall impaired functioning. Children with prepubertal-onset MDD with a recurrence of MDD during follow-up had higher rates of MDD in their first-degree relatives. CONCLUSIONS: There is high morbidity in clinically referred children with prepubertal-onset MDD and anxiety, but continuity and specificity of MDD or anxiety disorder in adulthood is less clear. Caution is warranted in selecting clinically referred children with prepubertal-onset MDD for inclusion in genetic studies unless they have a family history of MDD and recurrence of MDD over time.     

Comorbidity in the interpretation of dexamethasone suppression test results in children: a review and report

The dexamethasone suppression test (DST) was administered as part of the initial clinical assessment to 83 children and adolescents who were consecutively referred for outpatient evaluation. All diagnoses were made clinically by a child psychiatrist according to DSM-III criteria. A weight-corrected dose of dexamethasone of 17 micrograms/kg was used. DSM-III diagnoses were made independent of DST results. Patients were stratified into four main diagnostic groups: major depressive disorder (MDD) (N = 27); attention deficit disorder with hyperactivity (ADDH) (N = 22); major depressive disorder plus attention deficit disorder with hyperactivity (MDD + ADDH) (N = 29); and psychiatric controls (PC) (N = 5). Rates of dexamethasone nonsuppression were found to be similarly elevated in children with MDD (29.6%), ADDH (22.7%), and MDD + ADDH (37.9%). All 5 psychiatric control patients had a normal postdexamethasone suppression (0%). A similar pattern of results emerged in a reexamination of the literature on available studies of DST in juveniles which revealed that children with major affective disorders, attention deficit disorder (ADDH), and anxiety disorders had comparable DST results that were significantly higher than the 5.6% rate found in normal controls. These findings provide further support for similarities in DST results between ADDH and MDD in outpatients. Although these results suggest a lack of specificity of the DST as a laboratory aid for the diagnosis of juvenile affective disorders, they are also consistent with findings indicating that the DST may be an index of clinical severity and other findings suggesting a possible association between ADDH and MDD. Despite its limitations, the DST may provide potentially useful clinical and research information regarding the pathophysiology of psychiatric disorders and in alerting clinicians to the presence of serious psychiatric disorders. The findings also stress the relevance of assessing comorbidity in interpreting DST results.     

A controlled family history study of prepubertal major depressive disorder

First-degree (N = 195) and second-degree (N = 785) adult relatives of prepubertal children with major depression (N = 48), children with nonaffective psychiatric disorders (N = 20), and normal children (N = 27) were assessed by the Family History-Research Diagnostic Criteria method (FH-RDC), except for the adult informant (usually the mother), who was directly interviewed. Compared with normal controls, prepubertal children with major depressive disorder (MDD) had significantly higher familial rates of psychiatric disorders in both first- and second-degree relatives, especially MDD, alcoholism, and "other" (mostly anxiety) diagnoses. Relatives of children in the nonaffective psychiatric control (PC) group had low rates of alcoholism, high rates of other (anxiety) disorder diagnoses, and intermediate rates of MDD (accounted for by those children with separation anxiety). This suggests that prepubertal onset of major depression may be especially likely in families with a high aggregation of affective disorders when these families also have a high prevalence of alcoholism, and that a proportion of children without affective disorder but with separation anxiety disorder in this study were at high risk for the development of affective illness later in life. These results support the validity of prepubertal-onset depressive illness as a diagnostic category, and are consistent with high familial rates of MDD and other psychiatric disorders found in family studies of adolescent and early-onset adult probands with major affective disorders, and with studies of the offspring of parents with major affective disorders. Within the child MDD group substantial heterogeneity was found. Low familial rates of MDD were associated with suicidality and comorbid conduct disorder in the child probands. The highest familial rates of MDD, approximately threefold those in the normal controls, and all the bipolar relatives, were found in the families of prepubertal probands with MDD who never had a concrete suicidal plan or act and who were without comorbid conduct disorder. A useful nosological continuum in which to classify prepubertal MDD may be to place at one end those patients with comorbid conduct disorder and at the other end those patients with manifestations related to bipolarity, including hypomania, mania, and psychotic subtype.     

Saliva cortisol and response to dexamethasone in children of depressed parents.

BACKGROUND: Major depression (MDD) is heritable, and children of depressed parents are at higher risk for the development of depression. However, depression in a parent might also act as a stressor leading to increased activation of neuroendocrine stress circuits. To address this question we examined saliva cortisol in children whose parents have a history of MDD. METHODS: We recruited 15 families with one parent with MDD (26 prepubertal children) and 16 control families without history of parental MDD (32 prepubertal children). All parents and children underwent Structured Clinical Interview for DSM-IV and Kiddie Schedule For Affective Disorders And Schizophrenia interviews, respectively. Families were asked to collect morning, afternoon, and bedtime saliva samples for 4 days for 2 weeks. At bedtime of the 3rd day, dexamethasone was administered. Two doses, standard and low, were used in each family. RESULTS: The majority of children demonstrated no psychiatric diagnosis. Children with MDD parents showed higher cortisol basally and higher cortisol after both 25 mg and 5 mg dexamethasone. However, this effect occurred predominantly in children whose parents were currently depressed. There were strong correlations for cortisol between parents and children (r = 52 in depressed; r = 499 in control). CONCLUSIONS: Elevated cortisol and impaired feedback seemed to reflect an environmental effect of MDD in a parent.     

Gender and the course of major depressive disorder through adolescence in clinically referred youngsters

OBJECTIVES: To determine whether there are gender differences among psychiatrically referred young patients in the presenting features and subsequent course of major depressive disorder (MDD) through adolescence. METHOD: The subjects were 92 participants in a longitudinal follow-up study that included repeated standardized psychiatric evaluations. Gender effects were examined on features of MDD as patients progressed from late childhood (mean age 11 years) to late adolescence (mean age 17 years). RESULTS: Salient features of MDD did not differ for girls versus boys, including age at MDD onset, recovery from the index episode, risk of a new episode, and rates of various comorbid disorders in the index and recurrent episodes. Rates of selected symptoms and severity of the depressive syndrome also were comparable for boys and girls throughout their development. CONCLUSIONS: Gender differences have been documented in epidemiological and community samples with respect to rates and correlates of depressed mood and some features of depressive disorders. However, the study of gender differences among clinically referred depressed youths has only recently gained momentum. The present findings complement existing reports suggesting a lack of compelling gender effects on salient presenting features and adolescent outcomes of MDD in clinically referred youths. Additional work is needed to determine whether gender effects are detectable on other clinical parameters of MDD during adolescence or further along in development.     

The clinical picture of depression in preschool children

OBJECTIVE: To investigate the clinical characteristics of depression in preschool children. METHOD: One hundred seventy-four subjects between the ages of 3.0 and 5.6 years were ascertained from community and clinical sites for a comprehensive assessment that included an age-appropriate psychiatric interview for parents. Modifications were made to the assessment of major depressive disorder (MDD) criteria so that age-appropriate manifestations of symptom states could be captured. Typical and "masked" symptoms of depression were investigated in three groups: depressed (who met all MDD criteria except duration criterion), those with nonaffective psychiatric disorders (who met criteria for attention-deficit/hyperactivity disorder and/or oppositional defiant disorder), and those who did not meet criteria for any psychiatric disorder. RESULTS: Depressed preschool children displayed "typical" symptoms and vegetative signs of depression more frequently than other nonaffective or "masked" symptoms. Anhedonia appeared to be a specific symptom and sadness/irritability appeared to be a sensitive symptom of preschool MDD. CONCLUSIONS: Clinicians should be alert to age-appropriate manifestations of typical MDD symptoms and vegetative signs when assessing preschool children for depression. "Masked" symptoms of depression occur in preschool children but do not predominate the clinical picture. Future studies specifically designed to investigate the specificity and sensitivity of the symptoms of preschool depression are now warranted.     

Decreased levels of serum brain-derived neurotrophic factor in both depressed and euthymic patients with unipolar depression and in euthymic patients with bipolar I and II disorders

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) has been proposed as a candidate molecule in the pathophysiology of major depressive disorder (MDD) and bipolar disorders (BD). Reduced levels of peripheral BDNF have been found in drug-free MDD patients, in drug-treated depressed or manic patients with BD type I (BD-I), but not in drug-treated euthymic BD-I individuals. No study has been done in patients with BD type II (BD-II). Moreover, the influence of Axis I psychiatric comorbidity on circulating BDNF in affective patients has never been evaluated. Therefore, in the present study, we aimed: (i) to confirm previous findings on peripheral BDNF in MDD and BD-I patients; (ii) to assess whether changes in circulating BDNF occur also in patients with BD-II; and (iii) to exclude the possibility that comorbid psychiatric disorders exerted an effect on BDNF levels in affective patients. METHODS: We measured serum BDNF concentrations by an enzyme-linked immunosorbent assay method in 85 subjects, including 24 euthymic patients with unipolar depression (UD), 17 euthymic patients with BD-I, 11 euthymic patients with BD-II, 11 UD patients with a current major depressive episode and 22 drug-free healthy controls. At the time of the study, 15 patients were drug-treated; the remaining ones were drug-free for at least four weeks. RESULTS: Compared to healthy controls, serum BDNF concentrations were significantly reduced in all the patient groups (F(4,80) = 3.840, p = 0.006) with no significant difference among them. Drug treatments and comorbid psychiatric disorders had no effect on lowered circulating BDNF levels in affective patients. CONCLUSIONS: Present results confirm previous independent findings of reduced circulating BDNF in patients with MDD and report, for the first time, decreased serum BDNF levels in euthymic patients with UD, BD-I and BD-II, independently from drug treatment status and concomitant Axis I psychiatric disorders.     

Sex-linked differences in cortisol, ACTH and prolactin responses to 5-hydroxy-tryptophan in healthy controls and minor and major depressed patients

Some researchers have found that the administration of 5-hydroxytryptophan (5-HTP) results in increased cortisol secretion in major depressives but not in healthy controls. Other authors observed gender-related differences in cortisol responses to 5-HTP in major depressives. In order to investigate the pituitary/adrenal responsivity to 5-HTP, the authors measured cortisol, adrenocorticotropic hormone (ACTH) and prolactin (PRL) in 30 healthy controls and in 90 depressed patients; the hormone levels were determined in baseline conditions and 60, 90 and 120 min after 125 mg L-5-HTP (orally, non-enteric coated). We found that healthy men had significantly higher cortisol responses to L-5-HTP than healthy women. In the major depressives with melancholia and/or psychotic features these differences were reversed: women exhibited significantly higher cortisol and PRL responses than men. In the female group the most severely depressed patients had increased cortisol and PRL responses to L-5-HTP. The amplitudes of the cortisol, ACTH and PRL responses to L-5-HTP were significantly and positively correlated. It was concluded that the central serotonergic regulation of ACTH and PRL is significantly different between the sexes and between healthy controls, minor depressives and severely depressed patients.     

Low birth weight and risk of affective disorders and selected medical illness in offspring at high and low risk for depression

Numerous studies have demonstrated that low birth weight (LBW) is associated with the development of medical conditions, such as hypertension and diabetes, and psychiatric disorders, such as depression. One possible mechanism through which LBW might increase risk for both medical and psychiatric disorders is by altering the biologic systems (such as the hypothalamic-pituitary-adrenal [HPA] axis function) that govern emotion regulation and physical reactivity. In this study, we conducted secondary data analyses in a longitudinal study originally designed to understand the intergenerational transmission of major depressive disorder (MDD). We examined the risk for both medical and psychiatric illnesses known to be influenced by HPA axis dysregulation in the context of parental depression. The study had 2 primary objectives: (1) to examine whether LBW increases the risk of selected adult illness that may be influenced by the HPA axis and (2) to examine whether the increased risk of illness varies by parental depression status. We conducted longitudinal assessments of 244 offspring of depressed and nondepressed parents for more than 20 years. Psychopathology and medical illness were assessed by direct interview conducted by clinicians blind to risk status and previous diagnosis. We examined the effect of BW in 3 categories: less than 2.5 kg (LBW), 2.5-3.5 kg, and more than 3.5 kg (reference group). Offspring with LBW had a significantly increased risk of MDD, anxiety disorders, phobia, suicidal ideation, impaired functioning, allergies, and hypertension compared to those with BW exceeding 3.5 kg. The association between LBW and depression was stronger among children of depressed parents than among children of nondepressed parents, with an interaction term (BW and parental depression status) significant for MDD (P = .05), suggesting that parental depression may augment the impact of LBW on offspring depression:     

The role of depression chronicity and recurrence on neurocognitive dysfunctions in HIV-infected adults

Research assessing whether major depressive disorders (MDD) impacts neurocognitive functions in HIV+ persons has yielded inconsistent results. However, none have considered the role of MDD remission, chronicity, and stability on treatment. Ninety-five HIV+ adults clinically stable on combined antiretroviral treatment completed a psychiatric interview, a depression scale, a neuropsychological, daily living, and cognitive complaints assessments at baseline and 18 months. Participants were screened for current (within 12 months of study entry) alcohol and/or substance use disorder. History of alcohol and/or substance abuse disorder prior to the 12 months entry screen and MDD treatments were recorded. Participants were grouped into two psychiatric nomenclatures: (1) lifetime: no MD episode (MDE), single MDE life-event treated and fully remitted, chronic MDD treated and stable, chronic MDD treated and unstable, and baseline untreated MDE; (2) recent: last 2 years MDE (yes or no). We found that lifetime and recent psychiatric history were more strongly associated with decreased in independence in daily living and cognitive complaints than with baseline neuropsychological performance. However, lack of full remission, instability on treatment in chronic MDD, and severity of symptoms in current MDE were factors in whether MDD impacted baseline neuropsychological performance. Depressive symptoms improved at follow-up in those with baseline moderate-severe symptoms, and MDD was not associated with neurocognitive change at 18 months. A history of alcohol and/or substance abuse disorder was significantly more frequent in those with treated and unstable chronic MDD but it was not associated with neuropsychological performance. MDD recurrence, chronicity profiles, and associated comorbidities are keys factors to understand any potential impact on neurocognitive abilities in HIV infection. More comprehensive consideration of these complex effects could serve at constructively updating the HAND diagnostic criteria.     

DSM-IV mental disorders and neurological complications in children and adolescents with human immunodeficiency virus type 1 infection (HIV-1).

AIM: - To study the types of psychiatric problem encountered in children infected with the human immunodeficiency virus (HIV) and their relationship to central nervous system disorder and the severity of infection. METHODS: - 17 HIV-infected children presenting with psychiatric problems were included. Mental disorders were evaluated according to DSM-IV criteria. Neurological disorders and progressive encephalopathy (presence or absence) diagnosis were evaluated by clinical and radiological examination. The severity of infection was assessed by the percentage of CD4 lymphocytes. RESULTS: - The most frequent diagnoses were major depression (MDD: 47%) and attention deficit hyperactivity disorder (ADHD: 29%). Major depression diagnosis was significantly associated with neuroimaging or clinical neurological abnormalities (p < 0.01). In contrast, no association was found between hyperactivity diagnosed according to DSM-IV criteria and central nervous system disorder. Percentage of CD4 lymphocytes were close to 0 for more than 80% of children presenting with psychiatric complications. CONCLUSION: - The very low % of CD4 lymphocytes of these children suggest that the appearance of a psychiatric complication should be regarded as a factor indicating severe HIV infection. Depressive disorders may be a clinical form of encephalopathy.     

Functional neuroanatomical substrates of altered reward processing in major depressive disorder revealed by a dopaminergic probe

CONTEXT: The pathophysiology of major depressive disorder (MDD) includes disturbances in several neuroanatomical substrates and neurotransmitter systems. The challenge is to elucidate the brain mechanisms of MDD behavioral symptoms, chiefly those of anhedonia. OBJECTIVES: To visualize the neuroanatomical substrates implicated in altered reward processing in MDD, using functional magnetic resonance imaging in combination with a dopaminergic probe (a 30-mg dose of oral dextroamphetamine sulfate) to stimulate the brain reward system; and to test the hypothesis that a hypersensitive response to dextroamphetamine in MDD involves the prefrontal cortex and the striatum. DESIGN AND INTERVENTIONS: Among subjects with MDD and healthy control subjects, functional magnetic resonance imaging data were collected before and after single-blind administration of dextroamphetamine. SETTING: Subjects were recruited through local newspaper advertisements and by word of mouth. PARTICIPANTS: Twelve depressed subjects (mean age, 34.83 years; male-female ratio, 6:6) met criteria for MDD according to the DSM-IV, were not taking antidepressants, and had no comorbid Axis I disorders. Twelve control subjects (mean age, 29.33 years; male-female ratio, 5:7) were healthy volunteers without a history of Axis I disorders. MAIN OUTCOME MEASURES: Functional magnetic resonance imaging blood oxygen level-dependent activation was measured during a controlled task, and dextroamphetamine-induced subjective effects were assessed using the Addiction Research Center Inventory. RESULTS: Subjects with MDD had a hypersensitive response to the rewarding effects of dextroamphetamine (2-fold increase; t(21) = 2.74, P = .01), with altered brain activation in the ventrolateral prefrontal cortex and the orbitofrontal cortex and the caudate and putamen (F(1,44) = 11.93, P = .001). CONCLUSION: Dopamine-related neuroanatomical substrates are involved in altered reward processing in MDD, shedding light on the neurobiology of the anhedonic symptoms in MDD and suggesting these substrates as future therapeutic targets.